https://www.explorationpub.com/Journals/ei Most Recent Articles : Exploration of Immunology. en-us Tue, 05 May 2026 13:44:49 GMT https://www.explorationpub.com/Journals/ei/Article/10031 Not applicable. Editorial Tue, 01 Dec 2020 00:00:00 GMT Dominique JCharron, ReemAl-Daccak, Tue, 01 Dec 2020 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10031 https://www.explorationpub.com/Journals/ei/Article/10032 Atopic dermatitis (AD) is characterized by skin barrier disruption, type 2 immune dysregulation, chronic pruritus, and abnormal colonization by Staphylococcus aureus (S. aureus). Tapinarof, an aryl hydrocarbon receptor modulator, has been demonstrated to attenuate the development of AD in clinical studies. Recently, we found that tapinarof upregulated the expression of filaggrin and loricrin, which are essential proteins in skin barrier functions. Paradoxically, tapinarof induced interleukin (IL)-24 secretion by normal human keratinocytes. IL-24 is produced by T helper 2 lymphocytes and keratinocytes following stimulation by type 2 cytokines, and IL-24 is upregulated in the skin of patients with AD. Furthermore, IL-24 contributes to skin barrier disruption and hyperplasia in AD, and it may exacerbate skin inflammatory responses, itch, and S. aureus infection. In this review, we summarized the current findings regarding the detrimental role of IL-24 in AD, thereby suggesting that co-treatment of tapinarof with therapeutics that block IL-24 signaling may represent a promising strategy for managing AD. Review Tue, 02 Mar 2021 00:00:00 GMT Yen HaiVu, MasutakaFurue, GakuTsuji, Tue, 02 Mar 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10032 https://www.explorationpub.com/Journals/ei/Article/10033 Aim: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019, a global pandemic. There is hence an urgent need for effective approaches to understand the mechanism of viral interaction with immune cells that lead to viral elimination and subsequent long-term immunity. The first, immediate response to the viral infection involves mobilization of native immunity and human leukocyte antigen (HLA) class I mechanisms to kill infected cells and eliminate the virus. The second line of defense involves the activation of HLA class II system for the production of antibodies against the virus which will add to the elimination of the virus and prevent future infections. In a previous study, investigated the relations between SARS-CoV-2 spike glycoprotein (S protein) and HLA class II alleles were investigaed; here report on the relations of the S protein and the open reading frame 1ab (ORF1ab) of SARS-CoV-2 to HLA class I alleles. Methods: An in silico sliding window approach was used to determine exhaustively the binding affinities of linear epitopes of 10 amino acid length (10-mers) to each of 61 common (global frequency ≥ 0.01) HLA class I molecules (17, 24 and 20 from gene loci A, B and C, respectively). A total of 8,354 epitopes were analyzed; 1,263 from the S protein and 7,091 from ORF1ab. Results: HLA-A genes were the most effective at binding SARS-CoV-2 epitopes for both spike and ORF1ab proteins. Good binding affinities were found for all three genes and were distributed throughout the length of the S protein and ORF1ab polyprotein sequence. Conclusions: Common HLA class I molecules, as a population, are very well suited to binding with high affinity to SARS-CoV-2 spike and ORF1ab proteins and hence should be effective in aiding the early elimination of the virus. Original Article Wed, 31 Mar 2021 00:00:00 GMT Spyros A.Charonis, Effie-PhotiniTsilibary, Apostolos P.Georgopoulos, Wed, 31 Mar 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10033 https://www.explorationpub.com/Journals/ei/Article/10034 Aim: Fragment crystallizable (Fc) glycans modulate Fc conformations and functions, and glycan may also regulate antigen recognition. In the antibody drug development, glycosylation patterns affect antibody drug characteristics and quality control. In order to provide a global feature of N-glycan interactions in response to antigen and Fc receptor bindings, the interactions among Fc N-glycans and N-glycans’ interaction with Fc CH2 and CH3 domains have been studied. Methods: Molecular dynamics simulations were used to generate conformation ensembles of free antibody, antibody-antigen complex, antibody-human Fc-gamma-receptor-I (hFcγRI) and antibody-antigen-hFcγRI, the hydrogen bonds and radial distance distribution involving N-glycans carbohydrate chains have been analyzed. Results: Two important interaction patterns have been observed. The first is the strong but non-specific interactions between two carbohydrate chains in free antibody. Secondly, it has been found that N-glycans carbohydrate chains can directly interact with CH3 domain in free antibody, and that the distance distribution between carbohydrate chains and CH3 domain clearly differentiate the free antibody, antibody-antigen complex, antibody-hFcγRI complex, and final antibody-antigen-hFcγRI complex. Conclusions: N-glycans partially acts as allosteric sensor and respond to antigen and hFcγRI binding. Original Article Tue, 20 Apr 2021 00:00:00 GMT BuyongMa, Tue, 20 Apr 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10034 https://www.explorationpub.com/Journals/ei/Article/10035 Interleukin (IL)-22 is produced from immune cells such as T helper (Th)22 cells, Th17/22 cells, and group 3 innate lymphoid cells. IL-22 signals via the IL-22 receptor 1 (IL-22R1) and the IL-10 receptor 2 (IL-10R2). As the IL-22R1/IL-10R2 heterodimer is preferentially expressed on border tissue between the host and the environment, IL-22 is believed to be involved in border defense. Epidermal keratinocytes are the first-line skin barrier and express IL-22R1/IL-10R2. IL-22 increases keratinocyte proliferation but inhibits differentiation. Aryl hydrocarbon receptor (AHR) is a chemical sensor and an essential transcription factor for IL-22 production. In addition, AHR also upregulates the production of barrier-related proteins such as filaggrin in keratinocytes, suggesting a pivotal role for the AHR-IL-22 axis in regulating the physiological skin barrier. Although IL-22 signatures are elevated in atopic dermatitis and psoriasis, their pathogenic and/or protective implications are not fully understood. Review Tue, 27 Apr 2021 00:00:00 GMT MasutakaFurue, MihokoFurue, Tue, 27 Apr 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10035 https://www.explorationpub.com/Journals/ei/Article/10036 Immunity is continuously evolving by evolutionary mechanisms shaped by pathogenic stimuli of different kinds. Man-made nanomaterials (NMs) have been developed in the last decades and represent a novel challenge for our immune system, especially when applied to medical science. Toxicological studies of such nanoparticles (NPs) revealed that size, shape, and surface chemistry are key parameters to understand their noxious effects on cellular mechanisms. Less is known on the immune reactions to NMs since prolonged exposure data are not so detailed as the results for acute administration. The importance of immunity to biocompatible NPs is underlined by their increasing use as drug or gene delivery carriers in common pharmaceutical preparations and vaccines. In the latter case, the immunomodulatory properties of NMs allow their use also as efficient adjuvants to enhance the innate immune response. In the current manuscript, the authors discuss the main concepts in this fast-growing field by restricting our view to NMs with consolidated application in biomedicine. Review Fri, 30 Apr 2021 00:00:00 GMT AnissaPisani, GiuseppeBardi, Fri, 30 Apr 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10036 https://www.explorationpub.com/Journals/ei/Article/10037 As the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is a new virus, the current knowledge on the immunopathogenesis of this newly emerged SARS-CoV-2 is beginning to unravel with intensive ongoing global research efforts. Although a plethora of new studies have been published in a short space of time describing how the virus causes disease and incurs insults on the host immune system and the underlying immunopathogenic mechanisms remain to be elucidated. Thus, the discussion in this review is based on the most current knowledge on the immunopathogenesis of SARS-CoV-2 that has emerged in the past 12 months. The main objective is to shed light on the most current concepts in immunopathological aspects of the lung, bloodstream, and brain caused by the SARS-CoV-2, which has led to the current pandemic resulting in > 100 million infections and > 2 million deaths, and ongoing. Review Thu, 01 Jul 2021 00:00:00 GMT NitinSaksena, Srinivasa ReddyBonam, MonicaMiranda-Saksena, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10037 https://www.explorationpub.com/Journals/ei/Article/10038 Arginase-1 (Arg1) and the inducible nitric oxide synthase 2 (NOS2) compete for the common substrate L-arginine, semi-essential amino acid, and central intestinal metabolite. Both enzymes exhibit various, sometimes opposing effects on immune responses, tissue regeneration, or microbial growth and replication. In sub-mucosal tissues of patients suffering from inflammatory bowel disease (IBD), similar as in experimental colitis, the expression and activity of both enzymes, Arg1 and NOS2 are more prominent than in respective controls. Accordingly, the metabolism of L-arginine is altered in IBD patients. Thus, L-arginine represents a promising medical target for clinical intervention in these devastating diseases. Previous studies primarily focused on the host side of L-arginine metabolism. Initial reports using Arg1 inhibitors generated conflicting results in murine colitis models. Subsequently, only the generation of conditional Arg1 knockout mice allowed reliable functional analyses of Arg1 and the L-arginine metabolism in the immune system. Utilizing cell-specific conditional Arg1 knockouts, we have recently reported that Arg1, surprisingly, hampered the resolution of experimental colitis due to the restriction of the intraluminal availability of L-arginine. Reduced levels of L-arginine restrained the compositional diversity of the intestinal microbiota and subsequently the mutual metabolism between the microbiota and the host. Thus, the intraluminal microbiota represents a potential therapeutic target for L-arginine metabolism aside from host-dependent L-arginine consumption. Review Thu, 01 Jul 2021 00:00:00 GMT BjörnNüse, JochenMattner, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10038 https://www.explorationpub.com/Journals/ei/Article/10039 Skin is the largest organ of the body having multifunctional activities. It has a dynamic cellular network with unique immunologic properties to maintain defensive actions, photoprotection, immune response, inflammation, tolerogenic capacity, wound healing, etc. The immune cells of the skin exhibit distinct properties. They can synthesize active vitamin D [1,24(OH)2D3] and express vitamin D receptors. Any difficulties in the cutaneous immune system cause skin diseases (psoriasis, vitiligo, atopic dermatitis, skin carcinoma, and others). Vitamin D is an essential factor, exhibits immunomodulatory effects by regulating dendritic cells’ maturation, lymphocytes’ functions, and cytokine production. More specifically, vitamin D acts as an immune balancing agent, inhibits the exaggeration of immunostimulation. This vitamin suppresses T-helper 1 and T-helper 17 cell formation decreases inflammatory cytokines release and promotes the maturation of regulatory T cells and interleukin 10 secretion. The deficiency of this vitamin promotes the occurrence of immunoreactive disorders. Administration of vitamin D or its analogs is the therapeutic choice for the treatment of several skin diseases. Review Thu, 01 Jul 2021 00:00:00 GMT SaptadipSamanta, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/10039 https://www.explorationpub.com/Journals/ei/Article/100310 Mesenchymal stromal cells (MSCs) are a mesodermal stem cell population, with known self-renewal and multilineage differentiation properties. In the last century, MSCs have been widely used in regenerative medicine and tissue engineering approaches. MSCs initially were isolated from bone marrow aspirates, but currently have been identified in a great number of tissues of the human body. Besides their utilization in regenerative medicine, MSCs possess significant immunoregulatory/immunosuppressive properties, through interaction with the cells of innate and adaptive immunity. MSCs can exert their immunomodulatory properties with either cell-cell contact or via paracrine secretion of molecules, such as cytokines, growth factors and chemokines. Of particular importance, the MSCs’ immunomodulatory properties are explored as promising therapeutic strategies in immune-related disorders, such as autoimmune diseases, graft versus host disease, cancer. MSCs may also have an additional impact on coronavirus disease-19 (COVID-19), by attenuating the severe symptoms of this disorder. Nowadays, a great number of clinical trials, of MSC-mediated therapies are evaluated for their therapeutic potential. In this review, the current knowledge on cellular and molecular mechanisms involved in MSC-mediated immunomodulation were highlighted. Also, the most important aspects, regarding their potential application in immune-related diseases, will be highlighted. The broad application of MSCs has emerged their role as key immunomodulatory players, therefore their utilization in many disease situations is full of possibilities for future clinical treatment. Review Thu, 01 Jul 2021 00:00:00 GMT PanagiotisMallis, EfstathiosMichalopoulos, TheofanisChatzistamatiou, Catherine StavropoulosGiokas, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100310 https://www.explorationpub.com/Journals/ei/Article/100311 Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 spread globally and creates an alarming situation. Following the SARS-CoV-2 paradigm, therapeutic efficacy is achieved via repurposing several antiviral, antibacterial, and antimalarial drugs. Innate and adaptive immune cells work close to combat infection through the intricate production of antibodies (Abs) and inflammatory cytokines. As an essential component of the immune system, Abs play an important role in eliminating viruses and maintaining homeostasis. B lymphocytes (B cells) are effector cells, stringent to produce neutralizing Abs to combat infection. After recognizing SARS-CoV-2 antigens by a surface receptor called B cell receptors (BCRs) on the plasma membrane, the BCRs transmembrane signal transduction and immune activation results in Ab production and development of immune memory. Thus, it ensures that plasma B cells can quickly start an intricate immune response to generate efficient protective Abs to clear the pathogen. Nevertheless, considering therapeutic challenges in the context of the new coronavirus pandemic, this review addresses the molecular mechanism of the immune activation and function of novel SARS-CoV-2 specific B cells in the production of SARS-CoV-2 specific Abs. Additionally, these studies highlighted the Ab-mediated pathogenesis, the intriguing role of nano-scale signaling subunits, non-structural proteins during COVID-19 infection, and structural insights of SARS-CoV-2 specific Abs. Review Wed, 01 Sep 2021 00:00:00 GMT KabeerHaneef, RabiaSaleem, Muhammad Saleem IqbalKhan, Olawale SamuelAdeyinka, SadeeqBanday, Muhammad UmerAsghar, Zia UrRahman, ZainabFatima, Wed, 01 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100311 https://www.explorationpub.com/Journals/ei/Article/100313 Head and neck squamous cell carcinoma (HNSCC) is a relatively widespread cancer with high mortality rates. Many patients with locally advanced disease are treated with combinations of surgery, radiation, and chemotherapy, while others are considered incurable and develop recurrent/metastatic (R/M) disease. Despite these treatment modalities, the 5-year survival rate of HNSCC has remained at 50% due to limited treatment options in patients with recurrent disease. Immunotherapy has been shown to induce durable responses in R/M patients, but only a minority of patients currently respond. A major hurdle in tumor immunotherapy is identifying the non-responders and markers to predict resistance in patients who at first responded to the therapy. In HNSCC patients, the tumor microenvironment (TME) assumes a vital role to either diminish or augment immune responses. There is an urgent need for extensive studies to be undertaken to better understand how tumor cells escape immune surveillance and resist immune attack. In this review, the impact of TME on the efficiency of immunotherapy, addressing the factors that mediate therapy resistance are highlighted. The composition of the TME encompassing the immunosuppressive cells including myeloid-derived suppressor cell (MDSC), regulatory T cells (Treg), mesenchymal stem cell (MSC), cancer-associated fibroblast (CAF), and tumor-associated macrophages (TAMs) and intrinsic factors like hypoxia, reactive oxygen species (ROS), extracellular matrix (ECM), angiogenesis, and epithelial-mesenchymal transition (EMT), how this debilitates immunosurveillance, and also discuss existing and potential strategies aimed at targeting these cellular and molecular TME components are reviewed. Understanding the interactions between the TME and immunotherapy is not only important in dissevering the mechanisms of action of immunosuppression but also offers scope for developing newer strategies to improve the competence of current immunotherapies. Review Wed, 01 Sep 2021 00:00:00 GMT Shalini K.Sureshbabu, Jueelee H.Godbole, AnandVaibhaw, Shubhada V.Chiplunkar, Wed, 01 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100313 https://www.explorationpub.com/Journals/ei/Article/100314 Understanding the interactions of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with humans is deeply grounded in immunology, from the diagnosis to pathogenesis, from the clinical presentations to the epidemiology, prevention, and treatment. However, the difficulty of capturing the complex and changeable array of immunological concepts and incorporating them into the strategies of control of the SARS-CoV-2 pandemic poses significant hindrances to establish optimal public health policies. The contribution of immunology to the control of the pandemic is to shed light on the features and mechanisms of the protective immunity elicited by SARS-CoV-2 infection and vaccines. Do they induce effective protective immunity? How? For how long? What is the effect of vaccination on individuals who were previously infected? To appropriately answer these questions, it is necessary to get rid of the outdated notion of a naïve, static, and closed immune system, which leads to misconceptions about susceptibility, specificity, immunological memory, and protective immunity. The present essay discusses these issues based on current immunological concepts. Review Wed, 01 Sep 2021 00:00:00 GMT EduardoTosta, Wed, 01 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100314 https://www.explorationpub.com/Journals/ei/Article/100312 Aim: The envelope protein of novel coronavirus 2 (nCoV2) was reported to be highly conserved compared to its spike (S) protein which was shown to undergo several alterations in their amino acid sequences in the span of one year (2020–2021). Therefore, it is aimed to consider highly conserved structural protein of nCov2 namely envelope (E) protein to design the polytope for the formulation of the vaccine against coronavirus disease 2019 (Covid-19). Methods: Online in silico tools were employed to decipher the conservancy and antigenicity of E-protein of nCoV2. They are: to evaluate the molecular affinities among the chosen representatives of alpha and beta coronaviruses, the Molecular Evolutionary Genetics Analysis (MEGA) X 10.1.1 was used. Immune Epitope Database (IEDB)-NetMHCpan (ver. 4.1) tool was used to predict the epitopes of E protein binding to the frequently distributed major histocompatibility complex (MHC) I alleles. ProtParam, VaxJen, ToxinPred and AllerTop online tools were used to assess the physicochemical features, antigenicity, non-toxin and non-allergen aspects of constructed polytope. Secondary structure analysis and homology modelling validation of polytope were done using Phyre2 online tool. Discontinuous and linear epitopes of the designed polytope were predicted through IEDB Ellipro tool. Population coverage of epitopes of the polytope was performed using IEDB online tool with the frequent distribution of human leukocyte antigen (HLA) I alleles in the South Indian Asian population. Results: The phylogeny of envelope proteins of chosen representatives of Coronaviridae confirmed its conservancy and possible origin of nCoV2 from alpha coronaviruses through vampire CoV2. The designed polytope of E-protein was with 53 amino acid residues. The same was developed by linking with cysteine and serine (CS) residues in between epitopes. Conclusion: The antigenicity, non-allergen, non-toxin, homology modelling, discontinuous and linear epitopes of the designed polytope authenticate to explore the envelope protein for prophylactic measures. The epitopes of polytope were found to restrict to MHC I alleles occurring frequently among South Indian Asians. Original Article Wed, 01 Sep 2021 00:00:00 GMT KrupanidhiSreerama, Wed, 01 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100312 https://www.explorationpub.com/Journals/ei/Article/100315 There are various types of skin immune responses including inflammatory skin diseases and skin malignancy. Macrophages and fibroblasts are skin resident cells that had been overlooked in terms of immunological research targets. In this review, cross talk among macrophages, fibroblasts, and migratory immune cells in skin diseases such as atopic dermatitis (AD), contact hypersensitivity, psoriasis, systemic sclerosis, melanoma, and cutaneous T-cell lymphoma is described. Macrophages are important in AD by antigen-presenting phagocytosis, production of inflammatory cytokines, removal of apoptotic cells, and mediating clusters between dendritic cells (DCs) and T cells. They are also increased in lesional skin of psoriasis, especially in stable plaques, and an increased ratio of M1/M2 macrophages and tumor necrosis factor-α production by macrophages are essential for development of psoriasis. The progression of skin malignancy is mediated by macrophages through promotion of tumor survival pathways via expression of cytokines and growth factors, interaction with regulatory T cells (Tregs) and myeloid-derived suppressor cells, and suppression of function of tumor-infiltrating T cells by immunosuppressive cytokines and programmed death-ligand (PD-L)1. Fibroblasts play important roles in development and maintenance of AD lesions through expression of CC chemokine ligand (CCL)17, CCL11, CCL26, C-X-C motif chemokine ligand (CXCL)12, CCL19, and periostin, interacting with T helper (Th)2 cells, natural killer T (NKT) cells, DCs, and keratinocytes. They also play important roles in psoriasis, expressing interleukin (IL)-8 and vascular endothelial growth factor, production of fibronectin, and changes in the proteomic profiles. Fibroblasts have a critical role in the progression skin malignancy via expression of cytokines, suppression natural killer (NK) functions, and establishment of Th2-dominant microenvironment. Thus, cross talk among macrophages, fibroblasts, and migratory immune cells including T cells, DCs, and NK cells in skin diseases is important and those skin-resident cells are attracting therapeutic targets in the near future. Review Wed, 01 Sep 2021 00:00:00 GMT MakotoSugaya, Wed, 01 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100315 https://www.explorationpub.com/Journals/ei/Article/100317 Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase, catabolic enzyme from KYN or 3HK to downstream. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy. Original Article Thu, 30 Sep 2021 00:00:00 GMT MarikoSeishima, YasukoYamamoto, MasashiSakurai, RikaSakai, KentoFujii, YokoMizutani, KuniakiSaito, Thu, 30 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100317 https://www.explorationpub.com/Journals/ei/Article/100316 There have been significant developments in the design of nanostructured scaffolds for eliciting robust immune responses named vaccine. The technique is to produce strong immune responses is to manipulate the appearance of a pathogen. Subsequently pathogens such as viruses and bacteria often demonstrate of multiple copies of ligands on their surfaces, the immune system is predominantly sensitive towards multivalent presentations of antigens. Consequently, when designing a vaccine, it is beneficial to garnish a nanostructured surface with multiple copies of an antigen so it can effectively act as an immune booster. Different methods are there for the development of the vaccine, from them most of the techniques are well developed and reported and some of in the developing state. This review focuses primarily on cellular and non-cellular vaccines, the whole cells or cellular proteins either as the source of antigens or the platform in which to deliver the antigens. Purpose of this review, understand and discussion on the various vaccine platforms which will contribute noteworthy information to vaccine research and development (R and D). Review Thu, 30 Sep 2021 00:00:00 GMT Eknath D.Ahire, Sanjay J.Kshirsagar, Thu, 30 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100316 https://www.explorationpub.com/Journals/ei/Article/100318 Aim: Previously, we reported increased number of T helper 17 (Th17) cells in vitiligo. However, in our recent study, tryptase and interleukin (IL)17 double positive cells which identified by polyclonal anti-IL17 antibody with specificity for IL17A, B, D, F was observed, but these mast cells cannot be stained by monoclonal anti-IL17 antibody with specificity for IL17A. Therefore, this study was aimed to clarify the role of mast cells in induction and progression of vitiligo. Methods: Mast cells were stained with two antibodies against IL17 and one antibody against tryptase by immunofluorescent staining. Furthermore, immunoelectron microscopy (IEM) analyses were conducted using anti-tryptase. In vitro, cultured epidermal keratinocytes were treated with agents which released by mast cells. Expression levels of mRNA were analyzed by real-time polymerase chain reaction (PCR), expression of protein levels was analyzed by western blotting. Results: An increased number of tryptase positive mast cells was observed at the lesional skin of upper dermis in vitiligo and rhododendrol-induced leukoderma (RDIL). These mast cells showed prominent degranulation in vitiligo. Interestingly, the melanosome forming glycoprotein non-metastatic melanoma protein B (GPNMB) is downregulated in the lesional basal keratinocytes in vitiligo and mast cell tryptase contributes to this phenomenon. In addition, small interfering GPNMB RNA (siGPNMB RNA)-introduced keratinocytes increased melanocyte survival through stem cell factor (SCF) production in the melanocyte/keratinocyte co-culture system. Conclusions: Mast cells might be two-faced in vitiligo induction, progression, and recovery through the differential function of histamine and tryptase. Original Article Sat, 09 Oct 2021 00:00:00 GMT IchiroKatayama, LingliYang, AyaTakahashi, FeiYang, MariWataya-Kaneda, Sat, 09 Oct 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100318 https://www.explorationpub.com/Journals/ei/Article/100319 Both innate and adaptive immune cells exist in the skin, predominantly in the dermis layer. Recent studies have focused on how and which circadian rhythms contribute to maintain good health. Over recent years, we have gained a better understanding of the molecular mechanisms that control biological clocks and circadian rhythms. Circadian rhythms maintain homeostasis by providing day and night information to various physiological functions of our body. However, excessively high immune system activity can lead to a risk of developing autoimmune or allergic diseases. Recently, increasing numbers of studies with human and mouse models have been conducted to investigate the mechanisms underlying circadian regulation of the skin homeostasis. In this review, circadian regulation in the skin will be discussed from different points of view. Skin is referred as the largest organ of the body and is directly exposed to the external environment, including large changes in diurnal temperature, light, and pathogens. Immune cells as well as skin cells are the ones protecting us from these stimulants. Associations of the circadian system and these cells have been revealed in many ways, however, the specific roles of the peripheral clocks in these cells remain unknown. Circadian regulation in the skin diseases is discussed specifically in atopic dermatitis and other skin allergic symptoms as well as psoriasis. Review Thu, 21 Oct 2021 00:00:00 GMT KanamiOrihara, Thu, 21 Oct 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100319 https://www.explorationpub.com/Journals/ei/Article/100320 Viral vectors have been frequently applied for vaccine development. It has also been the case for vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to tackle the coronavirus disease 2019 (COVID-19) pandemic. A multitude of different viral vectors have been mainly targeting the SARS-CoV-2 spike (S) protein as antigen. Intramuscular injection has been most commonly used, but also intranasal administration has been tested. Adenovirus vector-based vaccines are the most advanced with several vaccines receiving Emergency Use Authorization (EUA). The simian ChAdOx1 nCoV-19 vaccine applied as a prime-boost regimen has provided 62.1–90% vaccine efficacy in clinical trials. The Ad26.COV2.S vaccine requires only one immunization to provide protection against SARS-CoV-2. The rAd26-S/rAd5-S vaccine utilizes the Ad26 serotype for the prime immunization followed by a boost with the Ad5 serotype resulting in 91.2% vaccine efficacy. All adenovirus-based vaccines are used for mass vaccinations. Moreover, vaccine candidates based on vaccinia virus and lentivirus vectors have been subjected to clinical evaluation. Among self-replicating RNA viruses, vaccine vectors based on measles virus, rhabdoviruses, and alphaviruses have been engineered and tested in clinical trials. In addition to the intramuscular route of administration vaccine candidates based on influenza viruses and adenoviruses have been subjected to intranasal delivery showing antibody responses and protection against SARS-CoV-2 challenges in animal models. The detection of novel more transmissible and pathogenic SARS-CoV-2 variants added concerns about the vaccine efficacy and needs to be monitored. Moreover, the cause of recently documented rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) must be investigated. Review Mon, 01 Nov 2021 00:00:00 GMT KennethLundstrom, Mon, 01 Nov 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100320 https://www.explorationpub.com/Journals/ei/Article/100323 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; βCoV), the causative agent of coronavirus disease 2019 (COVID-19), causes severe lower respiratory tract infections and acute respiratory failure syndrome (ARDS). Deaths due to the ongoing COVID-19 pandemic for more than a year are still seen worldwide. Therefore, vaccine trials have gained importance. The discovery of the genome and protein structure of SARS-CoV-2 in a short time allowed the development of nucleic acid-based vaccines (mRNA and DNA vaccines), vector vaccines, inactivated virus vaccines, protein-based vaccines, virus-like particle vaccines, and live attenuated virus vaccines. Many companies, universities, and institutes around the world continue to develop effective vaccines against SARS-CoV-2. In this review, the structural features, classification, genome, and intracellular entry of SARS-CoV-2 coronaviruses, stimulation of the immune system and immunity, COVID-19 vaccine types, and the latest status of clinical trials of these vaccines have been reviewed. Review Mon, 13 Dec 2021 00:00:00 GMT SevilayHintistan, HaticeDemirağ, Mon, 13 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100323 https://www.explorationpub.com/Journals/ei/Article/1003217 Aim: This retrospective study was performed to evaluate the efficacy and tolerability of cyproheptadine versus montelukast as adjuncts to ongoing second-generation antihistamines in adults with refractory chronic urticaria. Methods: This study included adult patients diagnosed with chronic urticaria who did not respond to standard treatment, divided into two groups. Group A received antihistamines plus oral cyproheptadine for one month, and group B received antihistamines in addition to standard-dose montelukast daily (10 mg) for four months. The weekly urticaria activity score (UAS7), chronic urticaria quality of life questionnaire (CU-Q2oL), and dermatology life quality index (DLQI) scores were measured at the end of grading after four months. Results: After four months, both groups showed significant improvements in UAS7 and CU-Q2oL scores, and group A also saw a notable increase in DLQI score compared to baseline. Group A showed more pronounced improvements overall. Both groups saw a reduction in background antihistamine usage, with group A experiencing a more significant decrease. Additionally, more patients in group A reported daytime sedation and weight gain compared to group B. Conclusions: Cyproheptadine, along with second-generation antihistamines, was found to be efficacious and safe as compared to montelukast along with second-generation antihistamines in patients with chronic urticaria. Original Article Mon, 22 Sep 2025 00:00:00 GMT Shambo S.Samajdar, AnupamDas, SaibalMoitra, ShatavisaMukherjee, NandiniChatterjee, Shashank R.Joshi, Mon, 22 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003217 https://www.explorationpub.com/Journals/ei/Article/100322 The maternal syndrome preeclampsia is triggered by syncytiotrophoblast (STB) stress; the heterogeneity of the syndrome is caused by the different pathways leading to this STB stress. Inflammation plays a pivotal role in the pathogenesis of preeclampsia. While, the immune system at large is therefore intimately involved in the causation of this heterogeneous syndrome, the role of the adaptive immune system is more controversial. The classic paradigm placed preeclampsia as the disease of the nulliparous pregnant women. Up to the later part of the 20th century, human reproduction, particularly in Western societies, was characterised by a low rate of pre-marital sex, and the great majority of children being born within one stable sexual relationship. More prolonged periods of regular sexual intercourse within a stable relationship have been demonstrated to reduce the risk of preeclampsia and fetal growth restriction. Primarily animal studies have indeed shown that repetitive sperm exposure leads to partner specific mucosal tolerance. Societal changes made partner change over the reproductive period of individual women extremely common. For the adaptive immune system of multiparous women, being pregnant in a new sexual relationship (primipaternity) would represent being faced with a new “hemi-allograft”. In these pregnancies, potential couple-specific immune “maladaptation” could lead to the superficial cytotrophoblast invasion of the spiral arteries, known to be associated with early-onset preeclampsia. Having a new pregnancy in a different relationship does indeed increase the risk for this type of preeclampsia. Large epidemiologic population studies identified prolonged birth interval but not “primipaternity” as a risk factor for preeclampsia in multiparous women. This apparent contradiction is explained by the fact that the great majority of preeclampsia cases in these population studies involve term preeclampsia. In late-onset preeclampsia, the far more common phenotype of the syndrome, STB stress is not caused by lack of proper spiral artery modification, but involves maternal genetic predisposition to cardiovascular and metabolic disease, with in particular obesity/metabolic syndrome representing major players. Partner or couple specific issues are not detectable in this disease phenotype. Review Mon, 13 Dec 2021 00:00:00 GMT Gustaaf AlbertDekker, Pierre YvesRobillard, Mon, 13 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100322 https://www.explorationpub.com/Journals/ei/Article/100321 The testis is designated as one of the immune previleged sites in the body and harbours a unique immunoregulatory environment, which is important for preventing an immune response against sperm antigens which otherwise are recognized as “foreign” by the immune system. The blood-testis barrier along with the unique immune cells repertoire and various immunoregulatory & immunosuppressive factors secreted by the Leydig cells, Sertoli cells and peritubular cells act in concert to maintain the tolerogenic environment in the testis. Abberations in immunotolerant mechanisms in the testis can lead to generation of anti-sperm antibodies that have an association with male infertility. It can also lead to inflammatory conditions of the male reproductive tract manifested as epididymitis and orchitis, generally due to bacterial or viral infections. In addition, non-infectious epididymitis and orchitis, having autoimmune origin have also been reported in males. While the immune privilege status of human testis protects the germ cells from an immune attack, it can also make the testis a succeptible reservoir for viruses such as human immunodeficiency virus-1, Zika virus and severe acute respiratory syndrome coronavirus-2, all of which have adverse consequences on male reproduction. Review Mon, 13 Dec 2021 00:00:00 GMT KushaanKhambata, Deepak N.Modi, Satish K.Gupta, Mon, 13 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100321 https://www.explorationpub.com/Journals/ei/Article/100324 Vaccination against coronavirus disease 2019 (COVID-19) is one of the most effective tools to curb the pandemic. Multiple vaccine candidates based on different platforms are available for emergency use presently. However, in common all the vaccines target spike protein, which is a dominant immunogen of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Adequate immunogenicity and efficacy are demonstrated by many of the vaccines in clinical phase III trials. The emergence of the new variant of concern is believed to be associated with less susceptibility to the post-infection or post-vaccination mounted immunity. It is a global concern currently threatening the progression of the vaccination drive. Nevertheless, the results of the presently available phase III clinical trials promote COVID-19 vaccination to prevent disease severity and COVID-19 related deaths. Cross-immunity towards the new variants of concern especially against the South African variant is yet to be explored and managed adequately. Review Mon, 13 Dec 2021 00:00:00 GMT MandeepGarg, MunirajuMaralakunte, YashwantKumar, HarishBhujade, Inder PaulSehgal, VikasSuri, SuruchiGarg, Mon, 13 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100324 https://www.explorationpub.com/Journals/ei/Article/100325 Coronavirus disease 2019 (COVID-19) emerges as an expeditiously growing pandemic, in the human population caused by the highly transmissible RNA virus severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). Prognosis of SARS-CoV-2 infection predominantly occurs at the angiotensin-converting enzyme 2 receptor and transmembrane protease serine type 2 positive (ACE2 + TMPRSS2)+ epithelial cells of the mucosal surface like nasal, oral mucosae, and/or the conjunctival surface of the eye where it has interacted along with the immune system. The primary host response towards the pathogen starts from an immune microenvironment of nasopharynx-associated lymphoid tissue (NALT) and mucosa-associated lymphoid tissue (MALT). The presence of exhausted lymphocytes, lymphopenia, pneumonia and cytokine storm is the hallmark of COVID-19. The multifaceted nature of co-morbidity factors like obesity and type 2 diabetes and its effects on immunity can alter the pathogenesis of SARS-CoV-2 infection. Adipose tissue is a crucial endocrine organ that secretes a plethora of factors like adipokines, cytokines, and chemokines that have a profound impact on metabolism and augments the expression of mucosal pro-inflammatory cytokines, like tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and the interleukin-12 (IL-12)/IL-23. Mucosal immunization could be a superior approach to activate mucosal and systemic immune responses against pathogenic invasion at mucosal surface entry ports. Mucosal vaccines are also able to generate strong systemic humoral immunity—required to neutralize any virus particle that dodges the primary immune response. To develop an efficient vaccine against mucosal pathogens, considering the designing of the delivery route, immunomodulatory features, and adjuvants are very important. In this article, we further provide evidence to understand the significant role of mucosal immunity, along with secretory and circulating immunoglobulin A (IgA) antibodies in generating a novel mucosal vaccine against COVID-19. Moreover, along with mucosal vaccines, we should look for combination treatment strategies with plant bioactive molecules. Glycan-binding lectins against viral proteins for targeted activation of mucosal immune response are one of such examples. This might play a promising role to halt this emerging virus. Review Thu, 16 Dec 2021 00:00:00 GMT Swapan K.Chatterjee, SnigdhaSaha, Maria Nilda M.Munoz, Thu, 16 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100325 https://www.explorationpub.com/Journals/ei/Article/100326 This article is a tribute and homage to Gerard Chaouat who invited me to contribute this article. My years in France have remained very memorable to me. Reviewed briefly is the vaccine that was made against human chorionic gonadotropin (hCG) to prevent unwanted pregnancy in sexually active women. It has now been developed as a genetically engineered recombinant vaccine and passed onto industry for its production under good manufacturing practices (GMP) conditions for confirmatory trials. The trials have received the approval of the Drugs Controller General of India. The trials have started but have been interrupted by the coronavirus disease 2019 (COVID-19) pandemic. This vaccine is likely to have another highly beneficial application in the treatment of cancers expressing ectopically hCG. Review Thu, 16 Dec 2021 00:00:00 GMT Gursaran P.Talwar, Jagdish C.Gupta, ShilpiPurswani, Hemant K.Vyas, Kripa N.Nand, PriyankaPal, Krishna M.Ella, Thu, 16 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100326 https://www.explorationpub.com/Journals/ei/Article/100327 The foetus expressing paternal antigens ought to be “rejected” by the maternal immune system. However, the immunological relationship of the mother and the foetus does not follow the rules of transplantation immunology. Maternal immune functions are re-adjusted during pregnancy, to create a tolerant environment for the developing foetus. Progesterone and its downstream mediator; the progesterone induced blocking factor (PIBF) are important in this process. The mRNA transcribed from the PIBF1 gene contains 18 exons, and codes for a 90 kDa protein. The 90 kDa form is associated with the centrosome and plays a role in cell cycle regulation, while smaller isoforms produced by alternative spicing are secreted, and bind to the glycosylphosphatidylinositol (GPI) anchored PIBF receptor. Upon ligation, the former forms a heterodimer with the alpha chain of the interleukin-4 (IL-4) receptor and activates the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway, via which, PIBF induces increased production of T helper2 (Th2) cytokines. PIBF regulates natural killer (NK) cytotoxicity, by inhibiting perforin release from the cytoplasmic granules of NK cells. During normal human pregnancy, the serum concentrations of PIBF increase with gestational age, and lower than normal serum levels predict spontaneous pregnancy termination. Depletion of PIBF during the peri-implantation period in mice, results in lower implantation and increased resorption rates, together with increased decidual and peripheral NK activity, downregulation of the genes implicated in T cell activation in CD4+ cells, and Th1 differentiation of the T cells. PIBF is expressed in rapidly proliferating immature cells as well as several tumours, and regulates invasion. The PIBF gene has been identified in the chromosomal region 13q21-q22—which is a common site for somatic deletions in a variety of malignant tumours. These data suggest that PIBF might be involved in tumorigenesis. Review Mon, 20 Dec 2021 00:00:00 GMT JuliaSzekeres-Bartho, Mon, 20 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100327 https://www.explorationpub.com/Journals/ei/Article/100328 Cutaneous homeostasis is maintained by dynamic cellular communications between different cell types in the skin through interactions with various mediators, including cytokines, chemokines and antimicrobial peptides/proteins (AMPs). Keratinocytes, as the major cell type of the epidermis, not only form a passive physical barrier, but also actively participate in the pathogenesis of many, if not all, inflammatory skin diseases. Keratinocytes highly interact with immune cells to shape, amplify or regulate inflammatory responses, thus triggering and/or sustaining these inflammatory skin diseases. In this review, crosstalk between keratinocytes and immune cells is summarized, and its contributions to two major inflammatory skin disorders including psoriasis and atopic dermatitis are highlighted. Review Fri, 31 Dec 2021 00:00:00 GMT XinhuiNi, YupingLai, Fri, 31 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100328 https://www.explorationpub.com/Journals/ei/Article/100329 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic β-coronavirus, is the etiologic agent of coronavirus disease 2019 (COVID-19), which gave rise to a difficult to control pandemic, especially in Brazil. Approximately 4,000 mutations have been identified in SARS-CoV-2, with the majority being redundant without having any biological effect on the virus. The aim of the present study was to objectively understand how new SARS-CoV-2 variants can affect vaccine response, in addition to highlighting the current situation in Brazil in the face of the pandemic and considering epidemiological and immunological aspects of COVID-19. The main protective correlate investigated in most vaccines is the neutralizing antibody titer induced by immunizing agents, observed in the pre-clinical phase in animals, whose action is to block the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, preventing infection. Up to the second half of 2021, the variants that are of greatest concern worldwide and require molecular surveillance are Alpha variant (or B.1.1.7 lineage), Beta (or B.1.351 lineage), Gamma (or P1 lineage) and Delta (or B.1.617.2 lineage). Brazil finds itself in a highly unfavorable scenario, with the circulation of variants of concern, mainly Gamma and Delta, with high fatality rates for COVID-19 and low vaccination rate. Given the still latent situation of the COVID-19 pandemic in Brazil, the lack of global planning for action strategies for non-pharmacological prevention measures, there is an imminent risk of the emergence of new variants due to the finding of susceptible hosts and the high proliferative rate of SARS-CoV-2. It is urgent to increase the genotyping of positive samples isolated from infected individuals, the speed of vaccination of the entire population and the unification of non-pharmacological preventive measures throughout the country. Review Fri, 31 Dec 2021 00:00:00 GMT Marileia ChavesAndrade, Luiza GambaGomes, Vitória KallásMendes, Hellen OliveiraRosa, Fri, 31 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100329 https://www.explorationpub.com/Journals/ei/Article/100330 The coronavirus disease 2019 (COVID-19) results from the infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and primarily affects the respiratory tissue. Since first reported from Wuhan, China in December 2019, the virus has resulted in an unprecedented pandemic. Vaccination against SARS-CoV-2 can control the further spread of the ongoing pandemic by making people immunised to SARS-CoV-2. Several vaccines have been approved for use in clinics, a lot many are in different stages of development. Diligent interpretations from the preclinical evaluation are crucial to identify the most effective and safest vaccine candidates. Multiple vaccine candidates/variants have been tested in small animal models with relative ease and further in non-human primate models before being taken into clinical development. Here, we review the state-of-the-art strategies employed for a thorough preclinical evaluation of COVID-19 vaccine candidates. We summarise the methods in place to identify indicators which make the vaccine candidate effective in controlling SARS-CoV-2 infection and/or COVID-19 and are safe for administration as inferred by their (1) biophysical/functional attributes (antigen expression, organization, functionality, and stability); (2) immunogenicity in animal models and protective correlates [SARS-CoV-2 specific binding/neutralising immunoglobulin titer, B/T-cell profiling, balanced T-helper type-1 (Th1) or type-2 (Th2) response (Th1:Th2), and anamnestic response]; (3) protective correlates as interpreted by controlled pathology of the respiratory tissue (pulmonary clinical and immunopathology); and finally, (4) strategies to monitor adverse effects of the vaccine candidates. Review Fri, 31 Dec 2021 00:00:00 GMT DevlinaGhosh, BingxinBai, QunJi, SoumyaPalliyil, GuangYang, AlokKumar, AbhishekSaxena, Fri, 31 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100330 https://www.explorationpub.com/Journals/ei/Article/100331 It is well recognized that immune tolerance is important to prevent semiallografted fetuses from rejection by maternal immunocompetent cells; however, immune activation also plays an important role in placental development and fetal growth. Basic and clinical studies have shown that an imbalance between immune activation and regulation can lead to implantation failure, miscarriage, and preeclampsia. Here, the balance between immunostimulation and immunoregulation in reproduction will be reviewed. Review Fri, 31 Dec 2021 00:00:00 GMT ShigeruSaito, AkitoshiNakashima, TomokoShima, SayakaTsuda, Fri, 31 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100331 https://www.explorationpub.com/Journals/ei/Article/100332 One of the most troubling developments of 2021 has been the number of fertile-age women who have been led to believe that mRNA vaccines against severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2, coronavirus disease 2019 (COVID-19)] can cause infertility via cross-reactivity of immune response. Specifically, cross-reactivity of developed antibodies to syncytin-1, a protein found in human cell fusion, placentation and recently identified in the envelope gene of a human endogenous defective retrovirus, HERV-W (see “Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis”. Nature. 2000;403:785–9. doi: 10.1038/35001608). The mechanism, evidence, and evaluation of the claim is presented concluding in a rejection due to lack of evidence. Perspective Fri, 11 Feb 2022 00:00:00 GMT Iosif M.Gershteyn, Fri, 11 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100332 https://www.explorationpub.com/Journals/ei/Article/100333 A few pieces of research exist about the protective titer against severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2; SARS-CoV-2) in monkeys and humans in which the protection could be shown as dose-dependent. Early studies supposed that higher levels of pre-existing neutralizing antibodies (Nabs) against SARS-CoV-2 can potentially correlate with the protection to consequent infection. The data so far showed that cellular immunity is as essential as the humoral one. If needed, its presence can be beneficial if the titer of immunoglobulins is not optimal. It is also known that the immune response to the vaccine is similar to the one after natural infection with a production of very high naturalization titers antibodies. However, medical community is still unaware of the immunoglobulin titer needed for protection against the virus. The answers to the questions regarding correlates of protection are yet to be discovered. Still, no studies indicate a specific virus-Nab titer, so one can assume a patient is protected from being infected in the future. The evoked immunological response is indeed encouraging, but a future investigation is needed. Nonetheless, it remains a mystery how long the immunity lasts and whether it will be enough to shield the patients in the long run. Therefore, identifying immune protection correlations, including neutralization titer of antibodies and T cell immune response against SARS-CoV-2, could give a clue. Unfortunately, recent studies in the field have been more controversial than concise, and the data available is far from consensus. Review Fri, 11 Feb 2022 00:00:00 GMT YoannaSlabakova, DilyanaGerenska, NedelchoIvanov, TsvetelinaVelikova, Fri, 11 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100333 https://www.explorationpub.com/Journals/ei/Article/100334 Endometriosis is an inflammatory oestrogen-dependent chronic disease and is mainly expressed by pain and increased infertility. Several studies showed an increased prevalence of autoimmune systemic diseases and various autoantibodies in endometriosis. The association of these autoimmune markers and diseases could raise the fact that endometriosis is an authentic autoimmune or inflammatory disease and thus could argue for the use of immunomodulatory therapies. Usually, it is considered that the autoantibodies did not directly act in endometrium implants growth, and could be rather implicated in endometriosis-related infertility. The use of immunomodulatory strategies could be an important alternative or additional strategy to the use of hormones and surgery but need prospective well-designed trials. Perspective Thu, 17 Feb 2022 00:00:00 GMT NoémieAbisror, KamilaKolanska, MeryemCheloufi, LiseSelleret, Emmanuelled’Argent, GillesKayem, ArseneMekinian, Thu, 17 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100334 https://www.explorationpub.com/Journals/ei/Article/100335 In recent decades, abundant methods for targeted tumor cell immunotherapy have been developed. It was recently discovered that excellent curative effects observed in hematological tumors cannot be achieved in solid tumors, as serious side effects will occur. These are all derived from engineered adaptive immune cells, the use of which will bring limitations. γδT cells have a unique ability to respond to a variety of tumor cells while linking innate immunity and adaptive immunity, and thus, they are an ideal source of therapeutic allogeneic cells. This review introduces strategies that can optimize the clinical application of γδT cells to provide novel ideas for adoptive immunotherapy in the future. Review Thu, 17 Feb 2022 00:00:00 GMT XiangjinZhang, YiXu, HuiChen, JianminZhang, WeiHe, Thu, 17 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100335 https://www.explorationpub.com/Journals/ei/Article/100336 γδ T cells are one of the immune cell types that express antigen receptors. γδ T cells are able to recognize pathogens or cancer cells independently of human leukocyte antigen restriction, which is an important feature of αβ T cells. Therefore, γδ T cells are considered the bridge between innate and adaptive immunity. These cells exhibit important roles in immune surveillance, exert immune defense against tumors and have become promising effector cells for cancer immunotherapy. However, in particular circumstances, the tumor microenvironment seems to render γδ T cells immunosuppressive and even tumor-promoting, emphasizing the importance of regulating γδ T functions in realizing their translation into practical cancer immunotherapy. In recent years, increasing evidence has demonstrated that the intratumoral and peritumoral microbiota can have complex effects on tumor immunology. Thus, understanding the role of microbiota in the crosstalk between γδ T cells and tumors will provide insights for developing adjuvant immunotherapy with precise regulation of tumor-related microbiota. In the present review, the effects of microbiota on γδ T cell receptor repertoire and the roles of microbiota in some common tumors will be discussed, with implications for future cancer therapy. Review Fri, 18 Feb 2022 00:00:00 GMT HuidiWang, JieLi, YanHe, JiaYin, Fri, 18 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100336 https://www.explorationpub.com/Journals/ei/Article/100337 In recent years, immunologists have been working to utilize the functional mechanism of the immune system to research new tumor treatment methods and achieved a major breakthrough in 2013, which was listed as one of the top 10 scientific breakthroughs of 2013 by Science magazine (see “Cancer immunotherapy”. Science. 2013;342:1417. doi: 10.1126/science.1249481). Currently, two main methods are used in clinical tumor immunotherapy: immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. Clinical responses to checkpoint inhibitors rely on blockade of the target neoantigens expressed on the surfaces of tumor cells, which can inhibit T cell activity and prevent the T cell immune response; therefore, the therapeutic effect is limited by the tumor antigen expression level. While CAR-T cell therapy can partly enhance neoantigen recognition of T cells, problems remain in the current treatment for solid tumors, such as restricted transport of adoptively transferred cells to the tumor site and off-targets. Immunologists have therefore turned their attention to γδ T cells, which are not restricted by the major histocompatibility complex (MHC) for neoantigen recognition and are able to initiate a rapid immune response at an early stage. However, due to the lack of an understanding of the antigens that γδ T cells recognize, the role of γδ T cells in tumorigenesis and tumor development is not clearly understood. In the past few years, extensive data identifying antigen ligands recognized by γδ T cells have been obtained, mainly focusing on bisphosphonates and small-molecule polypeptides, but few studies have focused on protein ligands recognized by γδ T cells. In this paper, we reviewed and analyzed the tumor-associated protein ligands of γδ T cells that have been discovered thus far, hoping to provide new ideas for the comprehensive application of γδ T cells in tumor immunotherapy. Review Wed, 23 Feb 2022 00:00:00 GMT ChangLiu, YiXu, HuiChen, JianminZhang, WeiHe, Wed, 23 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100337 https://www.explorationpub.com/Journals/ei/Article/100338 Antitumor immunity relies on the ability of T cells to recognize and kill tumor targets. γδ T cells are a specialized subset of T cells that predominantly localizes to non-lymphoid tissue such as the skin, gut, and lung where they are actively involved in tumor immunosurveillance. γδ T cells respond to self-stress ligands that are increased on many tumor cells, and these interactions provide costimulatory signals that promote their activation and cytotoxicity. This review will cover costimulatory molecules that are known to be critical for the function of γδ T cells with a specific focus on mouse dendritic epidermal T cells (DETC). DETC are a prototypic tissue-resident γδ T cell population with known roles in antitumor immunity and are therefore useful for identifying mechanisms that may control activation of other γδ T cell subsets within non-lymphoid tissues. This review concludes with a brief discussion on how γδ T cell costimulatory molecules can be targeted for improved cancer immunotherapy. Review Thu, 24 Feb 2022 00:00:00 GMT Joseph M.McGraw, Deborah A.Witherden, Thu, 24 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100338 https://www.explorationpub.com/Journals/ei/Article/100339 γδ T cells express unique T cell receptor (TCR) γ and TCR δ chains, with structural and functional heterogeneity. Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)—independent manner, thereby activating downstream pleiotropic effects. γδ T cells recruited into the tumor microenvironment can act as effector cells to mediate cancer immune surveillance. Their advantage lies in the ability to perceive tumors with a low mutation load, thus establishing the first line of defense against pathogens. Activated γδ T cells exhibit strong cytotoxic activity and cytokine secretion functions and are effective antitumor lymphocytes with simple and direct recognition modes and rapid responses. However, the clinical application of tumor—infiltrating γδ T cells has certain limitations. First, γδ T cells exposed to complicated cytokine networks are potentially affected by multiple inhibitory mechanisms. Additionally, these cells show highly flexible and dynamic plasticity and are extremely easily polarized into regulatory phenotypes. This review further emphasizes the diversified cross-talk between γδ T cells and other immune cells. Effective immunity of the body is often manifested by counterbalance under mutual restriction. Therefore, an in-depth understanding of γδ T cells that play conflicting roles in the tumor microenvironment is necessary. These cells may be a key factor ultimately mediating the deviation of the antagonistic response between tumor inhibition and tumor promotion. Finally, it retrospectively analyze the activation strategies and clinical relevance of existing γδ T cell adoptive immunotherapies. According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. It is hoped that the host immune status can be accurately predicted and gradually advance γδ T cell precise individualized medicine. Review Fri, 25 Feb 2022 00:00:00 GMT YueWang, YiXu, HuiChen, JianminZhang, WeiHe, Fri, 25 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100339 https://www.explorationpub.com/Journals/ei/Article/100340 Avidity of immunoglobulin G (IgG) is defined as its binding strength to its target antigen. As a consequence of affinity maturation of the IgG response, avidity is maturing as well. Therefore, acute infections are characterized by low-avidity IgG, whereas past infections are usually associated with high-avidity IgG. Avidity maturation is also observed as a consequence of optimal vaccination. Avidity has been shown to play a significant role in protective humoral immunity in many microbial systems. After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation is different compared to other viral infections, as the moderate degree of avidity reached in most cases of infection is similar to that reached after only one vaccination step. In contrast, two vaccination steps lead to a much higher avidity of IgG directed towards viral spike protein S1 (S1) in the majority of vaccinated individuals. Therefore, it seems that two vaccination steps allow for a more extended affinity/avidity maturation than natural infection. The degree of avidity maturation after two vaccination steps is heterogeneous. It can be further enhanced by a third vaccination step. Complete avidity maturation seems to depend on sustained availability of antigen during the maturation process. Variants of concern seem to increase the affinity of their receptor-binding domain (RBD) to angiotensin-converting enzyme-2 (ACE2) and/or to decrease the susceptibility for neutralizing antibodies. Classical neutralization tests do not necessarily reflect the avidity of neutralizing IgG, as they operationally dissect the binding reaction between S1 and IgG from the binding of the S1 to ACE2. This approach fades out critical competition reactions between IgG and ACE for RBD of the S1. Quantitative avidity determination might be an essential tool to define individuals that only possess suboptimal protective immunity after vaccination and therefore might benefit from an additional booster immunization. Review Wed, 16 Mar 2022 00:00:00 GMT GeorgBauer, Wed, 16 Mar 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100340 https://www.explorationpub.com/Journals/ei/Article/100341 Allogeneic stem cell transplantation is currently the only curative approach for a variety of malignant and non-malignant diseases. In the early transplant era, the intent of this treatment was to apply an intensive myeloablative regimen to eliminate residual malignant cells followed by the hematopoietic rescue of the patients with donor hematopoietic stem cells. However, the focus has shifted over time and allogeneic transplantation is nowadays seen as a cellular therapy in which the donor-derived immune system mounts an anti-infectious and especially an anti-tumor effect in the posttransplant phase. In order to further augment the anti-tumor effect, various approaches have been developed, including the manipulation of the donor-derived immune system in vivo or the adoptive transfer of ex vivo-expanded donor-derived effector cells. Based on their lack of alloreactivity, γδ+ T cells are shifting into the spotlight of research in the context of allogeneic transplantation. Their exploitation with regard to their anti-infectious and anti-tumor properties and their in vivo and ex vivo manipulation will lead to new therapeutic approaches to improve the outcome of patients after allogeneic stem cell transplantation. In this review, the important role of γδ+ T cells in allogeneic matched and mismatched transplantation is summarized and an outlook is discussed on how to best make use of this unique cell population. Review Wed, 16 Mar 2022 00:00:00 GMT RupertHandgretinger, PeterLang, ManonQueudeville, Wed, 16 Mar 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100341 https://www.explorationpub.com/Journals/ei/Article/100342 Gamma delta lymphocytes (γδ T) sit at the interface between innate and adaptive immunity. They have the capacity to recognize cancer cells by interaction of their surface receptors with an array of cancer cell surface target antigens. Interactions include the binding of γδ T cell receptors, the ligands for which are diverse and do not involve classical major histocompatibility complex (MHC) molecules. Moreover, a variety of natural killer-like and fragment crystallizable gamma (Fcγ) receptors confer additional cancer reactivity. Given this innate capacity to recognize and kill cancer cells, there appears less rationale for redirecting specific to cancer cell surface antigens through chimeric antigen receptor (CAR) expression. Several groups have however reported research findings that expression of CARs in γδ T cells can confer additional specificity or functionality. Though limited in number, these studies collectively identify the potential of CAR-T engineering to augment and fine tune anti-cancer responses. Together with the lack of graft versus host disease induced by allogeneic γδ T cells, these insights should encourage researchers to explore additional γδ T-CAR refinements for the development of off-the-shelf anti-cancer cell therapies. Review Thu, 17 Mar 2022 00:00:00 GMT Gabrielle M.Ferry, JohnAnderson, Thu, 17 Mar 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100342 https://www.explorationpub.com/Journals/ei/Article/100343 Although a large number of preventative human immunodeficiency virus (HIV) vaccine trials have been carried out during the last 30 years, it is remarkable that an effective HIV vaccine has not yet been developed. Research paradigms correspond to theoretical assumptions and particular strategies that scientists use when they try to solve a particular problem. Many paradigms used successfully in vaccinology were ineffective with HIV. For instance: 1) The structure-based reverse vaccinology approach failed because investigators tried to generate a vaccine starting with the antigenic structure of HIV-envelope (Env) epitopes bound to neutralizing monoclonal antibodies (mAbs) derived from HIV-infected individuals. They assumed that this antigenic structure would also possess the immunogenic capacity of inducing in vaccinees a polyclonal antibody (Ab) response with the same neutralizing capacity as the mAb. 2) The structures observed in epitope-paratope crystallographic complexes result from mutually induced fit between the two partners and do not correspond to the structures present in the free molecules before they had interacted. 3) The affinity-matured neutralizing mAbs obtained from chronically infected individuals did not recognize the germline predecessors of these Abs present in vaccinees. 4) The HIV p17 matrix protein that lines the inner surface of the viral membrane is one of the most disordered proteins identified on our planet and this prevents the induced Abs from binding to the glycosylated HIV gp120 protein. 5) Vaccinologists need to solve so-called inverse problems, for instance, guessing what are the multiple causes that produced an earlier wanted beneficial effect such as the absence of deleterious HIV infection in elite controllers. Since the immune system consists of numerous subsystems that have not yet been elucidated, it is impossible to solve the inverse problems posed by each subsystem. 6) Vaccinology is an empirical science that only sometimes succeeds because we do not understand the complex mechanisms that lead to protective immune responses. Review Fri, 18 Mar 2022 00:00:00 GMT Marc H.V.Van Regenmortel, Fri, 18 Mar 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100343 https://www.explorationpub.com/Journals/ei/Article/100344 Aim: The aim of this article is to characterize in detail the γδ T lymphocytes from an adult patient with primary cutaneous T-cell lymphoma of γδ subtype (γδ CTCL). Methods: Here this article reports trajectory mapping on high-resolution differentiation trajectories of γδ T lymphocytes digitally extracted from a scRNAseq dataset. Results: In the patch-to-plaque progression of CTCL, the TCRVγnon9 subset of γδ T cells differentiated from naive T cells (Tn) and central memory T cells (Tcm) to abundant effector memory T cells (Tem) while other cutaneous γδ T and CD8 T cells remained unchanged. Conclusions: This transcriptomic switch underlies the emergence of a CTCL-like progression of the TCRVγnon9 γδ T subtype and suggests new routes for treating these diseases. Original Article Fri, 15 Apr 2022 00:00:00 GMT Juan-PabloCerapio, MarionPerrier, FrédericPont, CamilleLaurent, StéphaneBertani, Jean-JacquesFournie, Fri, 15 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100344 https://www.explorationpub.com/Journals/ei/Article/100345 Aim: Thymosin alpha 1 (Tα1) is a promising treatment for the improvement of sepsis patients. Until now, its function in reducing acute organ damage of sepsis patients is still unclear. The aim of this study was to determine whether Tα1 can alleviate organ dysfunction in sepsis patients. Methods: This study retrospectively enrolled sepsis patients from a multicenter randomized controlled trial [efficacy of Tα1 for severe sepsis (ETASS)]. The sequential organ failure assessment (SOFA) score on day 0 (initial), day 3, and day 7 was collected. Absolute SOFAday07 was defined as initial SOFA score minus SOFA score on day 7 (initial SOFA–SOFA day7). Delta SOFA score (ΔSOFAday07) was provided by the formula: (initial SOFA–SOFA day7) × 100/initial SOFA, and it was expressed as a percentage. After propensity score matching (1:1 ratio), baseline characteristics were well-balanced between the Tα1 group and placebo group. The primary outcome was evaluated with a comparison of ΔSOFAday07 decline between patients treated with or without Tα1 therapy. Results: Among 288 enrolled patients, 149 patients received both Tα1 and standard therapy (Tα1 group), and 139 patients received both placebo and standard therapy (placebo group). Compared with the placebo group, the Tα1 group had significantly lower Absolute SOFAday07 [95% confidence interval (CI) 0.8 (0–1.7), P = 0.049]. Among 111 pairs of patients matched by propensity score, the Tα1 group still had lower Absolute SOFAday07 [95% CI 1.0 (0.1–1.9), P = 0.029]. Meanwhile, Tα1 treatment could significantly improve ΔSOFAday07. When the amplitude of ΔSOFAday07 was graded, one third of patients in the Tα1 group had an increase of more than 60%, compared with 22% in the placebo group. Subgroup analysis found that the ΔSOFAday07 improved significantly after Tα1 therapy in sepsis patients with no immunoparalysis at baseline, no complications, and early intervention. Conclusions: For sepsis patients, Tα1 treatment can alleviate organ dysfunction, and ΔSOFAday07 can be used as an indicator of its therapeutic effect (ClinicalTrials.gov identifier: NCT00711620). Original Article Fri, 22 Apr 2022 00:00:00 GMT FeiPei, YishanLiu, LingyunZuo, BinGu, LiqunLiang, LuhaoWang, YaoNie, MinyingChen, XiangdongGuan, JianfengWu, , Fri, 22 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100345 https://www.explorationpub.com/Journals/ei/Article/100346 Until now, despite 30 years of intensive work, the RV144 human immunodeficiency virus (HIV) vaccine trial initiated in 2003 remains so far the most protective vaccine prototype of all those tested (32% reduction in the infection rate three years after the vaccination) and the HIV epidemic is still spreading worldwide. In addition, antiretroviral therapy (ART) for people living with HIV is given for life as no other pharmacological intervention has allowed to maintain an undetectable viral load after ART withdrawal. Pr Andrieu and colleagues discovered tolerogenic CD8+T-cells that suppress simian immunodeficiency virus (SIV) specific activation, ensuing SIV reverse transcription suppression and viral replication-defective in Chinese macaques vaccinated by intragastric route with inactivated SIV particles + Lactobacillus rhamnosus. Moreover, in HIV-infected elite controllers with specific genetic features (HLA-1-Bw4-80i and KIR3DL1 genes), Pr Andrieu found out that similar tolerogenic CD8+T-cells suppress in the same manner HIV-specific activation, HIV reverse transcription, and HIV replication. These data justify the development of a tolerogenic vaccine composed of inactivated HIV particles + Lactobacillus rhamnosus that could be used as a preventive or therapeutic vaccine. Review Sun, 24 Apr 2022 00:00:00 GMT ChristineJacomet, Sun, 24 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100346 https://www.explorationpub.com/Journals/ei/Article/100347 Recent anti-cancer strategies are based on the stimulation of anti-tumor immune reaction, exploiting distinct lymphocyte subsets. Among them, γδ T cells represent optimal anti-cancer candidates, especially in those tissues where they are highly localized, such as the respiratory or gastrointestinal tract. One important challenge has been the identification of stimulating drugs able to induce and maintain γδ T cell-mediated anti-cancer immune response. Amino-bisphosphonates (N-BPs) have been largely employed in anti-cancer clinical trials due to their ability to upregulate the accumulation of pyrophosphates that promote the activation of Vγ9Vδ2 T cells. This activation depends on the butyrophilin A family, which is crucial in contributing to Vγ9Vδ2 T cells stimulation but is not equally expressed in all cancer tissues. Thus, the clinical outcome of such treatments is still a challenge. In this viewpoint, a critical picture of γδ T cells as effective anti-cancer effectors is designed, with a specific focus on the best immune-stimulating therapeutic schemes involving this lymphocyte subset and the tools available to measure their efficacy and presence in tumor tissues. Some pre-clinical models, useful to measure γδ T cell anti-cancer potential and their response to stimulating drugs, therapeutic monoclonal antibodies, or bispecific antibodies are described. Computerized imaging and digital pathology are also proposed as a help in the identification of co-stimulatory molecules and localization of γδ T cell effectors. Finally, two types of novel drug preparation are proposed: nanoparticles loaded with N-BPs and pro-drug formulations that enhance the effectiveness of γδ T lymphocyte stimulation. Perspective Thu, 28 Apr 2022 00:00:00 GMT AlessandroPoggi, Maria RaffaellaZocchi, Thu, 28 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100347 https://www.explorationpub.com/Journals/ei/Article/100348 Alzheimer’s disease (AD) is a common neurological disease in the elderly, and the major manifestations are cognitive dysfunction, neuronal loss, and neuropathic lesions in the brain. In the process of AD pathogenesis, the inflammatory response plays an indispensable role. The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome containing NOD, leucine-rich repeat (LRR), and pyran domains is a multi-molecular complex that can detect dangerous signals related to neurological diseases. The assembly of NLRP3 inflammasome promotes the maturation of interleukin-1beta (IL-1β) and IL-18 mediated by caspase-1 in microglia, which leads to neuroinflammation and finally contributes to the occurrence and development of AD. This review aimed to clarify the structure and activating mechanism of NLRP3 inflammasome and its key role in the pathogenesis of AD, summarize the latest findings on the suppression of NLRP3 inflammasome activation for the treatment of AD, as well as indicate that targeting regulation of NLRP3 inflammasome assembly may be a potential strategy for the treatment of AD, providing a theoretical basis for the research of AD. Review Sat, 07 May 2022 00:00:00 GMT XiaohanGao, XiaoxiaZhang, YaxuanSun, XuelingDai, Sat, 07 May 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100348 https://www.explorationpub.com/Journals/ei/Article/100349 The crown-like shaped viruses known as coronaviruses which were first reported in the 1960’s have caused three epidemics in the past two decades namely, coronavirus disease-19 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). SARS coronavirus 2 (SARS-CoV-2) was first reported in the latter half of December in Wuhan, a city of China, with people affected by deadly pneumonia with unknown etiology. Since then, the world has experienced two phases of virus spread with different symptoms and disease severity. This review embarks on the journey to investigate candidate molecules of this virus which can and are being investigated for various vaccine formulations and to discuss immunity developed against this virus. Review Tue, 17 May 2022 00:00:00 GMT Balram JiOmar, ArpanaSingh, VanyaSingh, AshishKothari, Manju O.Pai, Tue, 17 May 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100349 https://www.explorationpub.com/Journals/ei/Article/100350 Self-replicating RNA viruses have been commonly used for preventive and therapeutic interventions in the fields of infectious diseases and cancers. Both RNA viruses with single-stranded RNA genomes of positive and negative polarity have been utilized. Expression of viral surface proteins from self-replicating RNA virus vectors has elicited strong immune responses and provided protection against challenges with lethal doses of pathogens in various animal models using recombinant viral particles, RNA replicons, or plasmid-based replicon vectors. Similarly, immunization with self-replicating RNA virus vectors expressing tumor antigens has induced tumor-specific antibody (Ab) responses, inhibited tumor growth, eradicated tumors, and protected immunized animals against tumor challenges. Clinical trials have demonstrated good safety and tolerance of self-replicating RNA viruses. Although the number of clinical trials is low, robust immune responses and protection against challenges with pathogens and tumor cells have been achieved. The Ervebo vaccine against Ebola virus disease has been approved by both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Review Thu, 19 May 2022 00:00:00 GMT KennethLundstrom, Thu, 19 May 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100350 https://www.explorationpub.com/Journals/ei/Article/100351 Treatment of sepsis currently relies on eliminating the causal pathogen and supportive care, whereas almost no approaches to interfere with the defining event of a “dysregulated host response” are available. This review points to the striking correlation of two phenotypes of sepsis etiopathology with the concept of bipartite response patterns of higher organisms to microbial attacks. According to this concept, the phenotypes of sepsis can be interpreted as either resistance or tolerance responses to infection that got out of hand. This concept might allow focusing sepsis research and related patient studies on key conundrums of current sepsis research: how do resistance responses result in immunopathology and how can tolerance lead to systemic immunosuppression or even immunoparalysis? The heuristic vigor of these questions might inspire experimental efforts and clinical studies and ultimately advance the therapeutic armamentarium for sepsis care. Review Wed, 25 May 2022 00:00:00 GMT MichaelBauer, ReinhardWetzker, Wed, 25 May 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100351 https://www.explorationpub.com/Journals/ei/Article/100352 Lower respiratory tract infections caused over 4 million deaths per year worldwide, especially in low-income countries. Viral respiratory infections often occur as rapidly spreading seasonal endemic or epidemic, and sometimes due to new respiratory viruses including corona viruses. The first level of host defense against viral infection is based on the innate immune system and intracellular killing mechanisms. The latter is activated by the release of viral DNA or RNA into the cytosol of the infected cells during the initial phase of virus replication. Viral DNA and RNA are recognized by the cyclic guanosine monophosphate (cGMP)-adenosine monophosphate (AMP) synthase (cGAS)–stimulator of interferon (IFN) genes (STING) sensing pathway, leading to the activation of type-I and -III IFN synthesis, with the aim to limit viral replication. However, the efficacy of the cGAS-STING sensing mechanism seems to vary with different viruses, and therefore, so is the efficacy of the host defense mechanism. Viral DNA can be sensed by different proteins including DNA-dependent activator of IFN regulating factor (DAI), cGAS, and toll-like receptor-9 (TLR-9). Viral RNA is recognized by retinoid acid-inducible gene 1 (RIG-1), TLR-7 and TLR-8. The question if cGAS also recognizes viral RNA remains unclear. The activation of IFN synthesis by cGAS is initiated by the recognition of purines and pyrimidines and their enzymatic conversion into cGMP and cyclic AMP (cAMP), followed by the activation of STING. In addition, it is indicated that several viruses can evade the cGAS-STING signaling and escape the host defense. This review aims to summarize the role of cGAS-STING as a host defense mechanism against viral respiratory tract infections. Review Tue, 31 May 2022 00:00:00 GMT LeiFang, MichaelRoth, Tue, 31 May 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100352 https://www.explorationpub.com/Journals/ei/Article/100353 Obesity has become a worldwide scourge, affecting more than 10% of adults worldwide. While widely recognized to be associated with increased incidence of medical conditions such as diabetes mellitus and atherosclerosis, obesity also accounts for 9% of the cancer burden in some populations. This is due in part to perturbation of protective immune mechanisms involving natural killer cells, macrophages, and neutrophils. Recent studies indicate that γδ T cells play a prominent protective role against cancer, but in some circumstances are detrimental and pro tumorogenic. In this review, the current scientific literature was explored to determine whether and how obesity affects the anti- and pro-tumoral functions of γδ T cells. Considerable perturbations of γδ T cells by obesity were revealed, suggesting that the “obesity-γδ T cell axis” may profoundly impact the increased incidence of cancer in obese individuals and is worthy of further study. Review Tue, 31 May 2022 00:00:00 GMT IlanBank, Tue, 31 May 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100353 https://www.explorationpub.com/Journals/ei/Article/100354 Cancer immunotherapy, especially T-cell driven targeting, has significantly evolved and improved over the past decade, paving the way to treat previously refractory cancers. Hematologic malignancies, given their direct tumor accessibility and less immunosuppressive microenvironment compared to solid tumors, are better suited to be targeted by cellular immunotherapies. Gamma delta (γδ) T cells, with their unique attributes spanning the entirety of the immune system, make a tantalizing therapeutic platform for cancer immunotherapy. Their inherent anti-tumor properties, ability to act like antigen-presenting cells, and the advantage of having no major histocompatibility complex (MHC) restrictions, allow for greater flexibility in their utility to target tumors, compared to their αβ T cell counterpart. Their MHC-independent anti-tumor activity, coupled with their ability to be easily expanded from peripheral blood, enhance their potential to be used as an allogeneic product. In this review, the potential of utilizing γδ T cells to target hematologic malignancies is described, with a specific focus on their applicability as an allogeneic adoptive cellular therapy product. Review Wed, 08 Jun 2022 00:00:00 GMT NavdeepJhita, Sunil S.Raikar, Wed, 08 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100354 https://www.explorationpub.com/Journals/ei/Article/100355 Humans are afflicted by a wide spectrum of autoimmune disorders, ranging from those affecting just one or a few organs to those associated with more systemic effects. In most instances, the etiology of such disorders remains unknown; a consequence of this lack of knowledge is a lack of specific treatment options. Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disorder; pathology is believed to be antibody-mediated, and multiple organs are targeted. Periods of disease “flares” are often followed by long periods of remission. The fact that SLE is more commonly observed in females, and also that it more particularly manifests in females in the reproductive age group, has quite naturally drawn attention to the potential roles that hormones play in disease onset and progression. This review attempts to shed light on the influences that key hormones might have on disease indicators and pathology. Databases (Google Scholar, PubMed) were searched for the following keywords (sometimes in certain combinations), in conjunction with the term “lupus” or “SLE”: autoantibodies, recurrent abortion, polycystic ovarian syndrome (PCOS), preeclampsia, pre-term delivery, estrogens, progesterone, androgens, prolactin, leptin, human chorionic gonadotropin (hCG). Cited publications included both research articles and reviews. Review Wed, 08 Jun 2022 00:00:00 GMT RuchiSachdeva, RahulPal, Wed, 08 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100355 https://www.explorationpub.com/Journals/ei/Article/100356 Among decidual immune cells, regulatory T cells (Tregs) have been unanimously recognized as central contributors to tolerance and maintenance of healthy pregnancy. Numerical and functional downregulation of Tregs or disturbed interaction of Tregs with trophoblasts and other immune cells have been linked to early pregnancy loss such as idiopathic infertility and miscarriage and later-onset adverse pregnancy outcomes including preeclampsia. This review focuses on the mechanisms for regulating the generation, expansion, and function of Tregs, the roles of Tregs in maintaining maternal immune tolerance through crosstalk with trophoblasts and other decidual regulatory immune cells, and how Tregs may play foes to pregnancy and contribute to the programming of pregnancy-related complications. Therapeutic options for implantation failure and adverse pregnancy outcomes are now part of the emerging significance of Tregs in pregnancy tolerance and maintenance. Review Tue, 14 Jun 2022 00:00:00 GMT ShibinCheng, ZhengkeWang, SurendraSharma, Tue, 14 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100356 https://www.explorationpub.com/Journals/ei/Article/100357 Conventional immunohistochemistry methods though once fundamental for the individual staining of cell markers, have now been superseded by multispectral immunohistochemistry (mIHC). mIHC enables simultaneous detection of multiple cell markers in situ using single formalin-fixed paraffin-embedded (FFPE) tissue sections. In addition to conserving patient tissue specimens, the ability to visualise more than one marker on individual cells allows for further refining of cell phenotypes, and provides insight into cell-to-cell interactions and spatial arrangements across single tissue sections. Here, a comprehensive protocol is described for the in situ interrogation of γδ T cells and phosphoantigen-presenting butyrophilin (BTN) molecules (BTN2A1 and BTN3A1) in human FFPE tissue using Opal™ tyramide signal amplification (TSA)-based mIHC. It is demonstrated that an effectively optimised Opal™-TSA 7-marker [CD3, Pan-γδ T cell receptor (TCR), granzyme B, BTN2A1, BTN3A1, tumour marker, 4’,6-diamidino-2-phenylindole (DAPI)] mIHC panel can be used to define the presence, localisation, and activation status of γδ T cells and the BTN2A1 and BTN3A1 ligands. Protocol Fri, 17 Jun 2022 00:00:00 GMT Jessica Da GamaDuarte, Luke T.Quigley, ElnazTavancheh, SimoneOstrouska, AndreasBehren, Fri, 17 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100357 https://www.explorationpub.com/Journals/ei/Article/100358 Polycystic ovary syndrome (PCOS) is one of the most frequently observed endocrinopathies among women of reproductive age that redound to subfertility. The specific etiology of this heterogenic syndrome remains ambiguous. Metabolic complications, hormonal imbalance, deregulation in the immune system and their interrelationship make PCOS more complex. Hyperandrogenism and chronic low-grade inflammation modulate each other and enhance the self-perpetuation of PCOS. Even though there are many literature studies on PCOS and immune deregulation, this review focuses on the endocrine-immune nexus and how the altered endocrine system is embroiled in the immunopathology of PCOS. Review Mon, 27 Jun 2022 00:00:00 GMT Betcy SusanJohnson, MaliniLaloraya, Mon, 27 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100358 https://www.explorationpub.com/Journals/ei/Article/100359 “There is many a slip twist the cup and the lip” is a proverb that dates back to the 3rd century. This proverb comes to mind while writing a review on pregnancy loss; so many complications can occur between fertilization and development of the embryo through the long period of gestation until successful delivery of the baby. These include failure of implantation of the embryo, spontaneous miscarriage in the first trimester, pre-eclampsia in the second trimester, premature rupture of fetal membranes, pre-term labour, and pre-term delivery. The maternal immune system which does a phenomenal job of protecting the host from a daunting variety of infections, sometimes also mounts adverse reactions that complicate pregnancy and endanger the fetus. Maternal immune reactions that can adversely affect pregnancy have been shown to be mediated by lymphocytes, macrophages and natural killer cells, and by cytokines secreted by these cellular effectors. This review summarizes the deleterious effects of cytokines leading to recurrent spontaneous miscarriage, pre-eclampsia and pre-term delivery, which are the major complications of pregnancy. It then goes on to discuss the potential use of progesterone and dydrogesterone, an orally-administered progestogen, as immunomodulatory molecules that can be considered for the prevention and/or treatment of these complications. Review Tue, 28 Jun 2022 00:00:00 GMT RajRaghupathy, Tue, 28 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100359 https://www.explorationpub.com/Journals/ei/Article/100360 Immunity is usually classified into two categories: innate immunity and adaptive immunity, distinguished by the process and characteristics of the immunological impact. It was widely assumed that only adaptive immunity possessed memory features; however, current research has revealed that innate immunity, like adaptive immunity, possesses memory properties as well. “Trained immunity”, also known as “innate immune memory”, is a phenomenon that occurs when the immune system’s innate cells are stimulated and then undergo epigenetic reprogramming and metabolic alterations. When it comes to innate immunity, macrophages are essential since they have immunological memory capabilities and play a significant role in the body’s immunity. The concept of innate immune memory expands the definition of immunological memory and offers a broader view of immune response research. This article reviews the properties, mechanism, and significance of macrophage innate immune memory in disease. Review Wed, 29 Jun 2022 00:00:00 GMT Safir UllahKhan, Munir UllahKhan, Wed, 29 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100360 https://www.explorationpub.com/Journals/ei/Article/100361 This review pretends to shed light on the immune processes occurring in the coronavirus disease 2019 (COVID-19) from a perspective based on the antigens size, lower or larger than 70 kDa. This cutoff size point explains the host type of immune response against the antigenic proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to the development of the memory B cells or, conversely, the immune suppression, apoptosis, viral escape, and sepsis. Here, based on previous experimental work and the review of related literature, the following is proposed: antigens < 70 kDa can access the germinal center through the follicular conduits, where the activated B cells can present the processed antigen to specific naive CD4+ T cells that, in interaction with the major histocompatibility complex class II (MHC-II), trigger the immune response T helper type 2 (Th2). Conversely, antigens > 70 kDa cannot circulate through the narrow follicular conduits network and might be captured within the subcapsular sinus by the macrophages and dendritic follicular cells. Then, these cognate antigens are presented, via complement receptors, to the B cells that acquire and present them through the MHC-II to the specific naive CD4+ T cells, triggering the immune response Th1. The sustained infected cells lysis can overfeed high levels of unassembled viral proteins < 70 kDa, which can lead to a strong and persistent B cell receptor (BCR) activation, enhancing the Th2 immune response, releasing interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β) that may lead to the immune paralysis, apoptosis, sepsis, and death. Finally, it is suggested that the polymerization of the viral antigens < 70 kDa into an antigenic polymer > 70 kDa could shift the immune response type from Th2 to Th1, developing the memory B cells and immunoglobulin G2 (IgG2) production, and avoiding the sepsis. Review Mon, 18 Jul 2022 00:00:00 GMT Francisco Javier MartínOncina, Mon, 18 Jul 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100361 https://www.explorationpub.com/Journals/ei/Article/100362 Endometriosis (EMS) is an inflammatory, gynaecologic disease characterized by the growth of endometrial tissues outside the uterus. With no satisfactory therapies or non-invasive diagnostics available, a shift in perspectives on EMS pathophysiology is overdue. The implication of immune dysregulation in EMS pathogenesis and disease progression has been an evolving area of research, with numerous immune and inflammatory pathways identified. Traditional theories regarding the establishment of endometriotic lesions have lacked mechanistic explanations for their proliferation and survival until recent research unearthed the involvement of mesenchymal stem cell (MSC) and myeloid-derived suppressor cells (MDSCs) in a complex network of immune-endocrine signaling. The unique immunology of EMS is likely owing to estrogen dominance, as endocrine imbalance reliably cultivates immune dysregulation. Many of the phenomena observed in EMS parallel immune biology seen in various cancers, including accelerated somatic mutations in endometrial epithelial cells. Here, the high mutational load leads to EMS neoantigen development which potentially contributes to the lesion immune microenvironment. As well, EMS manifests comorbidity with several chronic inflammatory diseases that share common dysregulation of the interleukin-23 (IL-23)/IL-17 pathway (as seen in inflammatory bowel disease, psoriasis, and rheumatoid arthritis). EMS is especially relevant to the study of chronic pelvic pain (CPP) as 60% of EMS patients experience this symptom and chronic inflammation is believed to be central to the process of pain sensitization. Since the onset of the disease usually occurs in adolescence, and diagnosis only occurs years later once moderate to severe symptoms have developed, it is vital to innovate non-invasive diagnostic tools for earlier detection. Several potential biomarkers are being studied, including some cytokines, gene signatures, and extracellular vesicle (EV) signatures. By incorporating the immune perspectives of EMS into our research, approaches to diagnosis, and treatment solutions, the field has more promising avenues to clearly define EMS and offer patients relief. Review Wed, 27 Jul 2022 00:00:00 GMT AlisonMcCallion, Danielle J.Sisnett, Katherine B.Zutautas, DonyaHayati, Katherine G.Spiess, StanimiraAleksieva, HarshavardhanLingegowda, MadhuriKoti, ChandrakantTayade, Wed, 27 Jul 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100362 https://www.explorationpub.com/Journals/ei/Article/100363 Sepsis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and its severe form coronavirus disease 2019 (COVID-19), represent the major medical challenges of the modern era. Therapeutic options are limited, mostly symptomatic, partially relying on antibodies and corticosteroids and, in the case of SARS-CoV-2 infection, supplemented by the antiviral drug remdesivir, and more recently by molnupiravir, nirmatrelvir/ritonavir, and the Janus kinase (JAK) inhibitors tofacitinib and baricitinib. Sepsis and severe SARS-CoV-2 infection/COVID-19 share many features at the level of pathophysiology and pro-inflammatory mediators, thus enabling a common disease management strategy. New ideas in successfully targeting the prognostic severity and mortality marker pentraxin 3 (PTX3) in sepsis and severe SARS-CoV-2 infection/COVID-19; the complement (C3/C3a/C3aR and C5/C5a/C5aR axis); tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 expression; IL-6-triggered expression of C5aR receptor in vascular endothelial cells; and release of anti-inflammatory IL-10 are still missing. Small molecules with lysosomotropic characteristics such as the approved drugs amitriptyline, desloratadine, fluvoxamine, azelastine, and ambroxol have demonstrated their clinical benefits in rodent models of sepsis or clinical trials in COVID-19; however, their exact mode of action remains to be fully elucidated. Addressing disease-relevant targets such as viral infection of host cells, shedding of toll-like receptors (TLRs), expression of pro-inflammatory mediators such as TNF-α, IL-1β, IL-6, PTX3, and the complement receptor C5aR, highlight the advantages of this multi-target approach in comparison to current standards. Rational drug repurposing of approved drugs or screening for active compounds with virtually exclusively lysosomotropic pharmacologic effects is a major opportunity to improve prophylaxis and treatment of sepsis and/or SARS-CoV-2 infection, and its severe form COVID-19. Review Thu, 11 Aug 2022 00:00:00 GMT MarkusBlaess, OliverSommerfeld, RenéCsuk, Hans-PeterDeigner, Thu, 11 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100363 https://www.explorationpub.com/Journals/ei/Article/100364 Antiphospholipid syndrome (APS) is defined by recurrent pregnancy morbidity and/or vascular thrombosis associated with the persistent presence of antibodies against anionic phospholipid-binding proteins. Beta 2 glycoprotein I (β2GPI) and prothrombin (PT) are the major antigens for antiphospholipid antibodies (aPL) detectable by functional coagulation [lupus anticoagulant (LA)] or solid-phase assays [anti-β2GPI-dependent cardiolipin (aCL) and anti-β2GPI]. β2GPI-dependent aPL are responsible for the positivity of the three classification laboratory criteria. While medium/high titers of antibodies against β2GPI are risk factors for both the vascular and the obstetric manifestations of APS, persistent low titers are also associated with pregnancy complications. There is evidence from animal models of aPL-dependent fetal loss and from in vitro systems that β2GPI-dependent aPL can be pathogenic. β2GPI is physiologically found in large quantities at the placental level being available for the specific antibodies circulating in the maternal blood. Once bound to the protein, the antibodies trigger a local inflammation via the activation of the complement cascade and affect trophoblast and decidual function. The final result is represented by defective placentation, while thrombotic events are apparently less important. β2GPI is a pleiotropic molecule with scavenging properties towards several molecules including apoptotic material and displays anti-oxidant activity. These functions may explain the β2GPI placental localization in an area of intensive tissue remodeling and low oxygen tension. Since β2GPI interacts also with the complement and the coagulation cascade, its binding with specific antibodies may affect the physiology of placentation in several ways. Review Fri, 19 Aug 2022 00:00:00 GMT Pier LuigiMeroni, ClaudiaGrossi, FrancescoTedesco, Fri, 19 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100364 https://www.explorationpub.com/Journals/ei/Article/100365 Uterine natural killer (uNK) cells, a specific type of natural killer (NK) cells, are important cells at the foeto-maternal interface in humans as well as in mice. uNK cells are part of the innate lymphoid cells group 1. Especially in the mouse, but also in the rat, many in vivo studies have been performed to evaluate the role of uNK cells in placental development. These studies have shown that uNK cells are not indispensable to pregnancy, but that they play an important role in optimal decidual angiogenesis in early pregnancy, trophoblast invasion and spiral artery remodelling in the mouse placenta. Based on the mouse studies, various in vitro studies, as well as immunohistological studies of the human placenta from elective abortions, have shown that uNK cells have similar functions in the human placenta. In the present narrative review, the role of the uNK cells in the development of the mouse and rat placenta will be discussed first. Thereafter, studies on the role of human uNK cells in the human placenta will be reviewed and these studies will be discussed in the light of the knowledge on mouse uNK cells. Review Fri, 26 Aug 2022 00:00:00 GMT Marijke M.Faas, Fri, 26 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100365 https://www.explorationpub.com/Journals/ei/Article/100366 Human γδ T cells are unconventional lymphocytes that function in innate and adaptive immune responses and immunosurveillance. These cells show potent cytotoxicity against tumor cells in a major histocompatibility complex unrestricted manner and have recently gained considerable attention as a sparkling star for clinical immunotherapy. Clinical immunotherapy trials with activated γδ T cells are tolerated well. However, clinical benefits are still unsatisfactory. Therefore, anti-tumor effects need to further increase the cytotoxicity of γδ T cells via several mechanisms, including the novel nitrogen-containing bisphosphonate products, adjuvant use with a bispecific antibody and chimeric antigen receptor, co-immunotherapy with γδ T cells plus immune checkpoint inhibitors, and adoptive immunotherapy with Vδ1 T cells and T cells engineered to express a defined γδ T cell receptor. Here, this article describes the crucial role of γδ T cells in anti-tumor immunity, concludes transduction strategies and summarizes the different development of novel approaches for clinical applications and cancer immunotherapy, which may be effective in overcoming current therapeutic limitations. Review Fri, 26 Aug 2022 00:00:00 GMT JiamianZheng, XuanJiang, HaotianZhao, WandiWang, XiuliWu, ZhenyiJin, Fri, 26 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100366 https://www.explorationpub.com/Journals/ei/Article/100367 Infertility affects millions of people of reproductive age. The failure of a blastocyst to implant is a leading cause of psychological distress. It became increasingly evident that an effective immune dialogue occurs at each step in the fluids surrounding the oocyte, the spermatozoa, the embryo, or the endometrium. Exploring and deciphering this dialogue could potentially help understand why 50% of healthy euploid blastocysts fail to implant. Introducing immunology into reproductive medicine requires a change of mindset to bring immune hypothesis to clinical applications. Implantation of an embryo requires a prepared uterus in order to dialogue with the embryo, which is able to express and repair itself. Exploring the uterine immune profile of patients with previous implantation failures (IF) or recurrent miscarriages (RM) has already been developed and is under evaluation as a precision tool to equilibrate the uterine environment before implantation to increase the subsequent live birth rate after the embryo transfer. Immunology may also be fundamental in the future to identify through non-invasive procedure the competence of oocytes or embryos through reliable immune biomarkers quantified in follicular fluids or embryo supernatants during the in vitro fertilization (IVF) process. Non-invasive biomarkers would allow physicians to identify competent oocytes or embryos based on their ability to communicate with the mother and their energetic potential for all the self-repair processes that should occur during the preimplantation and the implantation period. This area of research is only beginning. Review Fri, 26 Aug 2022 00:00:00 GMT AlaaKazhalawi, MariePetitbarat, MonaRahmati, NathalieLédée, Fri, 26 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100367 https://www.explorationpub.com/Journals/ei/Article/100368 The immune system, whose nature lies in being a complex network of interactions, lends itself well to being represented and studied using graph theory. However, it should be noted that although the formalization of models of the immune system is relatively recent, the medical use of its signaling network structure has been carried out empirically for centuries in vaccinology, immunopathology, and clinical immunology, as evidenced by the development of effective vaccines, the management of transplant rejection, the management of allergies, and the treatment of certain types of cancer and autoimmune diseases. A network optimization analogy is proposed through the employment of the system dynamic formalism of causal loop diagrams (CLDs), where current network operations (also known as NetOps) in information technology (IT), are interpreted as immune NetOps in coronavirus disease 2019 (COVID-19) treatment. Traffic shaping corresponds to signaling pathway modulation by immunosuppressors. Data caching corresponds to the activation of innate immunity by application of Bacillus Calmette-Guerin (BCG) and other vaccines. Data compression corresponds with the activation of adaptative immune response by vaccination with the actual approved COVID-19 vaccines. Buffer tuning corresponds with concurrent activation of innate and adaptative or specialized immune cells and antibodies that attack and destroy foreign invaders by trained immunity-based vaccines to develop. The present study delineates some experimental extensions and future developments. Given the complex communication architecture of signal transduction in the immune system, it is apparent that multiple parallel pathways influencing and regulating each other are not the exception but the norm. Thus, the transition from empirical immune NetOps to analytical immune NetOps is a goal for the near future in biomedicine. Perspective Fri, 26 Aug 2022 00:00:00 GMT JavierBurgos-Salcedo, Fri, 26 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100368 https://www.explorationpub.com/Journals/ei/Article/100369 The human microbiome has emerged as an intriguing field of scientific research. Its role in human physiology impacts both health and disease, contributing to the enhancement or impairment of metabolic and immune functions. Sometimes referred to as our body’s “second genome”, the alteration of the microbiome’s bacterial ecology (dysbiosis), is linked to increasing numbers of illnesses, including cancer. The tumor microenvironment (TME) is the environment in which tumors grow and modulate the tumorigenic process depending on a myriad of distinct factors, including cell types, vascular system, and cytokines. Given the emerging relationship between the microbiome and the TME, this perspective aims to distill some of the key factors regulating the crosstalk between the microbiome and the TME. It also outlines why manipulating the microbiome may be a feasible strategy for anti-cancer therapy. Perspective Mon, 29 Aug 2022 00:00:00 GMT Joseph F.Murphy, Mon, 29 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100369 https://www.explorationpub.com/Journals/ei/Article/100370 Sepsis is a life-threatening condition caused by dysregulated host immune response to infection, leading to persistent inflammation followed by immunosuppression. Sepsis represents a substantial global health problem owing to protracted inflammation, immune suppression, and susceptibility to nosocomial infections. Despite continuing progress in the development of antibiotics, fluid resuscitation, and other supportive care therapies, no specific immunomodulatory drugs or immunotherapeutic adjuncts for the treatment of sepsis are available to date. The advances in tertiary care facilities and patient care have improved the survival of sepsis patients in the initial hyper-inflammatory phase of sepsis. However, the majority of sepsis patients succumb later due to prolong immunosuppression. The sepsis-induced immune dysregulation and its long-term effects on mortality are under meticulous investigations that are still poorly defined. Sepsis leads to the impaired functions of the innate and adaptive immune systems. The exhaustion of T cells, reduced expression of human leukocytes antigen (HLA)-DR on monocytes, and induced uncontrolled apoptosis of immune cells have been reported as hallmark features of sepsis. Sepsis-induced immune cell apoptosis of immune cells is a primary contributing factor to the immunosuppression in sepsis. Preclinical studies have identified several new therapeutic targets for therapy in sepsis, including monoclonal antibodies (Abs) and anti-apoptotic agents to reduce T cells exhaustion, immune cells apoptosis, and restoring immune cells functions. Recent studies have centered on immune-modulatory therapy. The review article will focus solely on sepsis’ effects on innate and adaptive cells functions that contribute to immunosuppression. Finally, it is discussed how immune cells responsible for immunosuppression might be directly targeted to provide potential therapeutic benefits in treating sepsis and improving long-term survival. Review Mon, 29 Aug 2022 00:00:00 GMT Dablu LalGupta, TejprakashSinha, RichaPathak, SanjeevBhoi, D. N.Rao, Mon, 29 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100370 https://www.explorationpub.com/Journals/ei/Article/100371 In ultrarare cases, patients vaccinated with DNA adenovirus vector vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), develop a vaccine-induced immune thrombotic thrombocytopenia (VITT), with a high incidence of fatal cases. The causative agent is the development of platelet factor 4 (PF4)-dependent antibodies that resemble heparin-induced thrombocytopenia (HIT) complication, although many differences can be noticed in clinical presentation, antibody reactivity, involved epitopes on the PF4 protein, and pathological mechanisms. From the literature review, and the experience of HIT and testing a few plasmas from patients with VITT, this review analyzes the possible mechanisms, which show the strong immunoglobulin G (IgG) antibody reactivity to PF4 alone, in the absence of heparin, and to a lesser extend to stoichiometric complexes of PF4 and heparin (H-PF4). In addition, much lower heparin concentrations are required for inhibiting antibody binding to PF4. These concentrations are much lower than those required for disrupting the stoichiometric H-PF4 complexes. This confirms that IgG antibodies responsible for HIT bind preferentially to PF4, to epitopes that are readily masked by low concentrations of heparin. These antibodies are at a much higher concentration than the current ones observed for HIT, keeping a strong reactivity even for plasma dilutions as high as 1/500 to 1/5,000, whilst the current dilution for testing heparin-dependent antibodies in HIT is 1/100. Although VITT anti-PF4 antibodies can be detected with the current anti-H-PF4 enzyme-linked immunosorbent assays (ELISAs) designed for HIT, some assays have low sensitivity or are unreactive, like lateral immunofiltration methods or chemiluminescent automated assays. The preferred method should concern the use of capture assays using PF4 coated solid surfaces. This report proposes that the immune response is only targeted to the binding domain of PF4 with the hexons present on the adenovirus vector, through an epitope spreading mechanism, without any exposure of neo-epitopes on PF4 protein. Review Wed, 31 Aug 2022 00:00:00 GMT JeanAmiral, ElodieLegros, MarionVivant, DelphineRossi, GwenaëlleRenaud, Wed, 31 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100371 https://www.explorationpub.com/Journals/ei/Article/100372 Complement component 1q (C1q) is the recognition molecule of the classical pathway of the complement system that can bind to an array of closely spaced antigen-bound immunoglobulin G (IgG) and IgM antibodies. In addition to its involvement in defence against a range of pathogens and clearance of apoptotic and necrotic cells, C1q has also been implicated in immune and non-immune homeostasis. C1q is locally produced by immune cells such as monocytes, macrophages, and dendritic cells. C1q is also synthesized by decidual endothelial cells, thus acting as a link between decidual cells and trophoblasts, as well as contributing to the remodelling of spiral arteries. Furthermore, C1q is produced by the extravillous trophoblasts (EVTs) invading the decidua. As a pro-angiogenic molecule, C1q is also important for normal placentation processes as it favors the active angiogenesis in the developing decidua. These observations have been validated by C1q gene knock-out mice which showed pre-eclampsia (PE)-like symptoms, characterized by hypertension, proteinuria, glomerular endotheliosis, and increased soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio, and increased oxidative stress. The role of C1q in normal and adverse human pregnancy is being studied extensively due to its absence or low level as a likely precipitating factor for the development of PE. Review Wed, 31 Aug 2022 00:00:00 GMT ChiaraAgostinis, AlessandroMangogna, AndreaBalduit, UdayKishore, RobertaBulla, Wed, 31 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100372 https://www.explorationpub.com/Journals/ei/Article/100373 Chemokines are homeostatic or inflammatory small proteins regulating immune cell migration and are structurally characterized by cysteine disulfide bridges. Around 50 human chemokines binding almost 20 seven-transmembrane G-protein coupled receptors have been discovered. The finding that two of them were the main human immunodeficiency virus (HIV) co-receptors intensified the research on the binding mechanism to block the viral entrance. Blockade of chemokine/chemokine receptor signaling ultimately modulates cell migration, then immune responses. Particular nanotechnologies can be designed to interfere with chemokine signaling or to exploit the ligand-receptor interaction. Surface chemical modification of nanomaterials with chemokines or specific peptides can find several applications in bio-medicine, from tissue-specific drug delivery to reduced cell migration in pathological conditions. Recent highlights on peculiar chemokine-nanoparticle design and their potential to modulate immune responses will be discussed. Review Thu, 01 Sep 2022 00:00:00 GMT GiuseppeBardi, Thu, 01 Sep 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100373 https://www.explorationpub.com/Journals/ei/Article/100374 Coronavirus disease 2019 (COVID-19) is currently a major public health concern causing devastating sociological, economic, and psychological damage to livelihood all over the world. The most intense severity of COVID-19 is not only acute respiratory distress syndrome (ARDS), it also causes multi-organ failure, the post-infection secondary effect as well as death. The fast-mutating ability and high transmissibility rate of the virus cause emergence of the new variants and also the occurrence of breakthrough infections. Evidence suggests that vaccination against COVID-19 has been effective at preventing the severity of illness, hospitalization, and death. The efficacy of vaccines depends on multiple factors including the host’s ability to mount a robust and sustainable immune response, the virus’s ability to mutate its genome, and programmatic factors such as vaccine dose, storage, dosing schedules, etc. In this article, an overview of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, its pathogenesis, host immune responses to infection, and different type of COVID-19 vaccines, including vaccine efficacy and adverse effects are described. Review Wed, 21 Sep 2022 00:00:00 GMT Basista RabinaSharma, P. VeerannaRavindra, Wed, 21 Sep 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100374 https://www.explorationpub.com/Journals/ei/Article/100375 Sepsis was defined in 1991 by the systemic inflammatory response syndrome (SIRS) criteria which consisted mostly of physiologic responses to infection or inflammation (fever, tachycardia, tachypnea, and leukocytosis). These criteria were initially proposed to identify patients with gram-negative bloodstream infection (BSI). However, most patients with BSI are not critically ill at initial presentation using objective clinical scores for acute severity of illness, such as the Pitt bacteremia score (PBS). Lack of specificity and low positive predictive value (PPV) are other pitfalls of the SIRS criteria. Moreover, the implementation of sepsis interventions based on this outdated definition failed to improve patients’ outcomes and in some settings was associated with increased use of broad-spectrum antibiotics and Clostridioides difficile (C. difficile) infection. In 2016, sepsis was redefined as a dysregulatory host response to life-threatening infections using quick sequential organ failure assessment (qSOFA) score. The presence of two of three bedside clinical variables (hypotension, respiratory distress, and altered mental status) that have consistently predicted mortality in patients with infections now constitutes sepsis. The scientific debate continues in the medical literature regarding the performance of the new criteria. Some medical professionals and quality organizations consider these changes to the sepsis definition too revolutionary and are resistant to altering existing medical practice. This narrative review presents infection as a continuum from localized to systemic infection (pre-sepsis) with the potential progression into sepsis and septic shock if appropriate antibiotic therapy and source control are delayed. The review assesses host and microbial factors that may influence the rate of progression through the sepsis cascade and proposes diagnostic considerations and management decisions at each step of the way. It emphasizes the need to utilize precision medicine concepts in selecting empirical antibiotic therapy based on patient-specific risk factors for infections due to resistant bacteria and potential benefits from appropriate therapy across the sepsis spectrum. Review Tue, 25 Oct 2022 00:00:00 GMT NicholasDaering, Majdi N.Al-Hasan, Tue, 25 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100375 https://www.explorationpub.com/Journals/ei/Article/100376 Menopause signals the end of the reproductive period in women. However, fertility and fecundity decrease with increasing age prior to menopause demonstrating that changes in the premenopausal female reproductive tract (FRT) are already occurring that negatively impact reproductive success. The effects of age on the endometrium are poorly understood, in contrast to the ovary where changes occur with increasing age that negatively affect successful reproduction. The endometrial immune system is essential for generating a receptive endometrium, but the link between the immune and reproductive systems in the endometrium in the years prior to menopause has not been well-defined. Since the endometrial immune system is tightly regulated to maximize reproductive success and pathogen protection, changes in immune function with increasing premenopausal age have the potential to impact reproduction. Review Sun, 30 Oct 2022 00:00:00 GMT Mickey V.Patel, ZhengShen, Charles R.Wira, Sun, 30 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100376 https://www.explorationpub.com/Journals/ei/Article/100377 Natural killer (NK) cells have a dual role in human reproduction for maternal-fetal tolerance and protection from infection. During the ovarian cycle and pregnancy, peripheral NK (pNK) and uterine NK (uNK) cells dynamically change their proportions and cytotoxicities to prepare and accommodate invading trophoblast and maintain pregnancy. However, dysregulated pNK and uNK cell proportions and cytotoxic activities have been associated with aberrant spiral artery remodeling and trophoblast invasion, leading to implantation failures and recurrent pregnancy losses (RPLs). This review will focus on the role of NK cells in RPLs reviewing the ontogeny of NK cells, changes in pNK and uNK cell levels, and activities during the ovarian cycle, normal pregnancy, and RPL. In addition, the immunopathological role of NK cells in endometrial/decidual vascular development and killer immunoglobin-like receptor (KIR) and human leukocyte antigen (HLA)-C interactions are discussed. Review Mon, 31 Oct 2022 00:00:00 GMT ThanhLuu, LujainAlSubki, KatherineWolf, AmyThees, UmidaGanieva, SvetlanaDambaeva, KennethBeaman, JoanneKwak-Kim, Mon, 31 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100377 https://www.explorationpub.com/Journals/ei/Article/100378 Microbiome research has enormous potential in cancer research and the use of formalin-fixed paraffin-embedded (FFPE) tissues could offer many advantages. The tumor microenvironment represents a suitable niche for specific microbes and evidence proves the presence of an endogenous tumor microbiota, here referred to as oncobiota. Awareness of the oncobiota role in tumorigenesis could have a large influence on cancer care, in terms of diagnosis, prevention, and treatment. Moreover, understanding the microbial-related tumor microenvironment, and its influence on tumor immune response and cancer cells will help define important pathogenetic mechanisms in cancer starting or progression. Routine collection of histopathological FFPE samples provides a large availability of specimens essential for affordable and impactful retrospective analyses and for getting robust statistical results. The FFPE tissues are common in the analysis of tumor biopsies including the tumor microbiota characterization which has an important role in the modulation of our immune system and consequently of tumor cells. However, the microbiota analysis starting from FFPE tissues presents methodological pitfalls and limits that may negatively affect the oncobiota research. After examining the methodological and analytical difficulties of this approach, this work seeks to offer workable solutions to promote that research area. Perspective Mon, 31 Oct 2022 00:00:00 GMT LeandroDi Gloria, ElenaNiccolai, Mon, 31 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100378 https://www.explorationpub.com/Journals/ei/Article/100379 The absence of advancement in finding efficient vaccines for several human viruses, such as hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and herpes simplex viruses (HSVs) despite 30, 40, and even 60 years of research, respectively, is unnerving. Among objective reasons for such failure are the highly glycosylated nature of proteins used as primary vaccine targets against these viruses and the presence of neotopes and cryptotopes, as well as high mutation rates of the RNA viruses HCV and HIV-1 and the capability to establish latency by HSVs. However, the lack of success in utilization of the structure-based reverse vaccinology for these viruses is likely to be related to the presence of highly flexible and intrinsically disordered regions in human antibodies (Abs) and the major immunogens of HIV-1, HCV, and HSVs, their surface glycoproteins. This clearly calls for moving from the rational structure-based vaccinology to the unstructural vaccinology based on the utilization of tools designed for the analysis of disordered and flexible proteins, while looking at intrinsically disordered viral antigens and their interactions with intrinsically disordered/flexible Abs. Review Mon, 31 Oct 2022 00:00:00 GMT Vladimir N.Uversky, Mon, 31 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100379 https://www.explorationpub.com/Journals/ei/Article/100380 Aim: Human leukocyte antigen (HLA) population genetics has been a historical field centralizing data resource. HLA genetics databases typically facilitate access to frequencies of allele, haplotype, and genotype format information. Among many resources, the Allele Frequency Net Database (AFND) is a typical centralized repository that allows users to research and analyze immune gene frequencies in different populations around the world. With the massive increase in medical data and the strengthening of data governance laws, the proposal for a new distributed and secure model for the historical centralization method in population genetics has become important. In this paper, a new model of HLA population genetic resources, an alternative distributed version of HLA databases has been developed. It allows users to perform the same research and analysis with other remote sites without sharing their original data and monitoring data access. Methods: This new version uses the Master/Worker distributed model and offers distributed algorithms for the calculation of allelic frequencies, haplotypic frequencies and for individual genotypic calculations. The new model was evaluated on a distributed testbed for experiment-driven research Grid’5000 and has obtained good results of accuracy and execution time compared to the original centralized scheme used by researchers. Results: The results show that distributed algorithm applied to HLA population genetics resources enables usage control and enables enforcing the security framework of the data-owning institution. It gives the same results for all counting methods in population immunogenetics. With the same frequencies’ estimations, it yields a much quicker computation time in many cases, in particular for large samples. Conclusions: Distributing previously centralized resources is an interesting perspective enhancing better control of data sharing. Original Article Wed, 02 Nov 2022 00:00:00 GMT SirineSayadi, VenceslasDouillard, NicolasVince, MarioSüdholt, Pierre-AntoineGourraud, Wed, 02 Nov 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100380 https://www.explorationpub.com/Journals/ei/Article/100381 Psoriasis is a skin disease characterized by scaly erythema, parakeratosis, and epidermal hyperplasia. Application of imiquimod (IMQ), a ligand for Toll-like receptor 7, produces a mouse model for psoriasis. IMQ application induces scaling, erythema, and thickness in skin lesions, and the symptoms are milder in interleukin-23 p19 (Il23p19)-deficient and Il17a-deficient mice than in wild-type mice; this suggests that the interleukin-23 (IL-23)/T helper 17 (Th17) axis and Th17 cell-secreting cytokines play essential roles in the IMQ-induced psoriasis model. It is notable that a genome-wide association study identified the human tyrosine kinase 2 (TYK2) gene within the psoriasis susceptibility locus. After IMQ application, mice lacking Tyk2, a mouse homologue of the human TYK2 gene, exhibited significantly lower symptom scores of psoriasis and diminished inflammatory cell infiltration in the skin lesions. Tyk2-deficient mice also failed to increase CD4+IL-17+ or CD4+ interferon-γ+ (IFN-γ+) T cells in the draining lymph nodes or to produce Th17 cell-related cytokines after IMQ application. Furthermore, Tyk2 deficiency led to diminished skin inflammation induced by IL-23 and IL-22 injections. These results indicate that Tyk2-mediated signals in mice contribute to multiple steps of immune and inflammatory responses during the development of psoriasis; therefore, TYK2 targeting may be a promising strategy to treat patients with psoriasis. Recent clinical trials have shown that TYK2 inhibitors have a high overall response rate with good tolerability in the management of psoriasis. This review describes the fundamental mechanisms of Tyk2 inhibition in immune/inflammatory diseases. Review Tue, 27 Dec 2022 00:00:00 GMT RyutaMuromoto, KenjiOritani, TadashiMatsuda, Tue, 27 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100381 https://www.explorationpub.com/Journals/ei/Article/100382 Immune responses are orchestrated by controlling the initiation, magnitude, and duration of various signaling pathways. Adaptor proteins act as positive or negative regulators by targeting critical molecules of signaling cascades. Signal-transducing adaptor protein-2 (STAP-2) contains typical features of adaptor proteins, like a pleckstrin homology (PH) domain in the N-terminal region and a Src homology 2 (SH2) domain in the central region. STAP-2 binds to a variety of signaling or transcriptional molecules to control multiple steps of inflammatory/immune responses. STAP-2 enhances T-cell receptor (TCR)-mediated signaling via the association with TCR-proximal CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (Lck). STAP-2 decreases adherence of T-cells to fibronectin (FN) through an association with focal adhesion kinase (Fak) and Casitas B-lineage Lymphoma (c-Cbl), and increases chemotaxis of T-cells toward stromal cell-derived factor-1α (SDF-1α) through interactions with Vav1 and Ras-related C3 botulinum toxin substrate 1 (Rac1). STAP-2 positively regulates activation-induced cell deathrough the association with Fas and caspase-8. This review describes the current knowledge of the roles of STAP-2 in T-cell-dependent immune responses and the possible clinical utility of STAP-2-targeting therapies. Review Wed, 28 Dec 2022 00:00:00 GMT TadashiMatsuda, YutoSasaki, KotaKagohashi, KodaiSaitoh, YuichiSekine, Jun-IchiKashiwakura, KenjiOritani, Wed, 28 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100382 https://www.explorationpub.com/Journals/ei/Article/100383 Aim: As the primary response antibody with increasing use as a therapeutic immunoglobulin (Ig) format, IgM is also the largest antibody structure among the five major human isotypes. Spontaneously formed pentamers and hexamers of IgM have avidity effects that could compensate for weaker interactions in monomeric Igs. However, this advantage is counterbalanced by potential steric clashes when binding to multiple large antigens. Recent findings have challenged the expected canonical independence of Fc receptor (FcR) binding at the heavy chain constant (C)-region where the heavy chain C-region isotypes affected antigen binding at the variable (V)-regions, and the variable heavy (VH) families of the V-region affected FcR engagement at the antibody C-regions. With such effects found on other Ig isotypes, IgM candidates need to be investigated with regards to such effects, especially when considering its natural oligomerisation at the C-region that can amplify or modulate such allosteric effects. Methods: Through a panel of 14 recombinant complementarity determining regions (CDRs)-grafted trastuzumab and pertuzumab VH1-7 IgMs subjected to bio-layer interferometry measurements, the interactions with the antigen human epidermal growth factor receptor 2 (Her2), Fc-mu receptor (FcμR), and superantigen Protein L (PpL) were investigated. Results: Significant effects from the V-regions to mitigate FcμR binding and the IgM C-region bidirectional effect modulating Her2 antigen engagements at the V-regions were found. Additional modulatory effects from superantigen PpL binding on the V-region of the kappa chain (Vκ) mitigating antigen binding were also found, revealing possible novel mechanisms of antibody superantigens that can be moderated by the antibody VH frameworks. Conclusions: These findings show that the oligomerisation of IgMs plays a significant role in FcμR, antigen, and superantigen binding that made IgM distinct from the other antibody isotypes and how these features should be considered during further development and protein engineering of IgM therapeutics. Original Article Thu, 29 Dec 2022 00:00:00 GMT Wei-LiLing, Samuel Ken-EnGan, Thu, 29 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100383 https://www.explorationpub.com/Journals/ei/Article/100384 The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the human host can lead to various clinical manifestations, from symptomless carriers to mild to moderate to severe/critical illness. Therefore, the clinical classification of SARS-CoV-2 disease, based on severity, is a reliable way to predict disease states in SARS-CoV-2 infection. Recent studies on genomics, transcriptomics, epigenomics, and immunogenomics, along with spatial analysis of immune cells have delineated and defined the categorization of these disease groups using these high throughout technologies. These technologies hold the promise of providing not only a detailed but a holistic view of SARS-CoV-2-led pathogenesis. The main genomic, cellular, and immunologic features of each disease category, and what separates them spatially and molecularly are discussed in this brief review to provide a foundational spatial understanding of SARS-CoV-2 immunopathogenesis. Review Fri, 30 Dec 2022 00:00:00 GMT NitinSaksena, Srinivasa R.Bonam, MonicaMiranda-Saksena, Thyago H.Cardoso, Fri, 30 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100384 https://www.explorationpub.com/Journals/ei/Article/100385 Immunoinformatics is an emerging area focused on development and applications of methods used to facilitate vaccine development. There is a growing interest in the field of vaccinology centered on the new omic science named ‘vaccinomics’. However, this approach has not succeeded to provide a solution against major infections affecting both animals and humans, since tick vaccines are still being developed based on conventional biochemical or immunological methods to dissect the molecular structure of the pathogen, looking for a candidate antigen. The availability of complete genomes and the novel advanced technologies, such as data mining, bioinformatics, microarrays, and proteomics, have revolutionized the approach to vaccine development and provided a new impulse to tick research. The aim of this review is to explore how modern vaccinology will contribute to the discovery of new candidate antigens and to understand the research process to improve existing vaccines. Under this concept, the omic age of ticks will make it possible to design vaccines starting from a prediction based on the in silico analysis of gene sequences obtained by data mining using computer algorithms, without the need to keep the pathogen growing in vitro. This new genome-based approach has been named “reverse vaccinology 3.0” or “vaccinomics 1.0” and can be applied to ticks. Review Fri, 24 Feb 2023 00:00:00 GMT RodrigoRosario-Cruz, Delia InésDomínguez-García, SaúlLópez-Silva, FernandoRosario-Domínguez, Fri, 24 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100385 https://www.explorationpub.com/Journals/ei/Article/1003161 Complement is both evolutionary and scientifically old. It predates the adaptive immunity by some 600 million years and was first described in 1905 by Jules Bordet and Paul Ehrlich. For the most of its, the existence complement system has been ignored by most scientists and clinicians due to the perception of it being complicated and its relevance for the pathogenesis of human disease being unclear. With the recent US Food and Drug Administration (FDA) approvals of pegcetacoplan for both paroxysmal nocturnal haemoglobinuria (PNH) and geographic atrophy (GA), avacincaptad pegol for GA and iptacopan and danicopan for PNH, we are at a crucial juncture for complement-targeting therapies. A number of companies and academic institutions are developing next-generation complement therapies, which is resulting in an increasingly competitive landscape. If one looks at the serum complement cascade, all 3 pathways now have biotechnology or pharmaceutical industry players with 1 or multiple clinical-stage inhibitors that are expected to be FDA approved within the next few years. Furthermore, with the limited number of clinically validated targets in complement-mediated disease, the competition in this space is set to further intensify in the coming years. In this review, we will discuss the timeline of the academic discoveries that led to the development of the current crop of FDA-approved complement therapeutics. We follow with a discussion of an increasingly crowded complement therapy space and of the scientific advances that have emerged in recent two decades underpinning future innovation, including advances in our understanding of complement biology, such as local and intracellular complement, emerging complement targets, combinational approaches of complement and non-complement therapeutics to unlock new disease indications and new technologies such as gene therapy. We will also give a comprehensive overview of the gene therapy landscape and how it can be utilized to target complement dysregulation. Review Fri, 18 Oct 2024 00:00:00 GMT MartinKolev, Kollu NageswaraRao, MichaelYeh, AtmanParikh, PascalDeschatelets, Fri, 18 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003161 https://www.explorationpub.com/Journals/ei/Article/100386 Human cytomegalovirus (HCMV), whose genome is around 235 kb, is a ubiquitous human herpesvirus that infects between 40% and 95% of the population. Though HCMV infection is commonly asymptomatic and leads to subtle clinical symptoms, it can promote robust immune responses and establish lifelong latency. In addition, in immunocompromised hosts, including individuals with acquired immunodeficiency syndrome (AIDS), transplant recipients, and developing fetuses it can lead to severe diseases. Immunosenescence, well-defined as the alterations in the immune system, is linked mainly to aging and has been recently gathering considerable attention. Senescence was characterized by an elevated inflammation and hence considered a powerful contributor to “inflammaging” that is measured mainly by tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) levels as well as latent viral infections, for instance, cytomegalovirus (CMV). Inflammaging resulted in a senescence-associated secretory phenotype (SASP). HCMV is markedly associated with accelerated aging of the immune system as well as several age-associated diseases that accumulate and subsequently deteriorate the immune responses, thus have been linked to mortality, declined vaccine efficacy, serious diseases, and tumors in the elderly. HCMV triggers or exacerbates immunosenescence; on the other hand, the weakened immune responses and inflammaging favor viral reactivation and highlight the role of HCMV in aging as well as viral-associated tumors. HCMV reactivation resulting in sequential lytic and latent viral cycles could contribute to HCMV genomic variability. Besides the oncomodulatory role and transforming capacities of HCMV, the immune-privileged tumor microenvironment has been considered the main element in tumor progression and aggressiveness. Therefore, the interplay between HCMV, immunosenescence, and cancer will aid in discovering new therapeutic approaches that target HCMV and act as immune response boosters mainly to fight cancers of poor prognosis, particularly in the elderly population. Review Fri, 24 Feb 2023 00:00:00 GMT FidaaBouezzedine, Ranim ElBaba, StéphanieMorot-Bizot, MonaDiab-Assaf, GeorgesHerbein, Fri, 24 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100386 https://www.explorationpub.com/Journals/ei/Article/100387 Coronavirus disease caused by the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a major public health that has submerged the world into a crisis unprecedented in the modern era. A better understanding of the innate immune response could help to fight this pandemic and be better prepared for potential future outbreaks. Interestingly, innate immune cells can develop a non-specific memory termed trained immunity. This review details recent evidence concerning the interaction of SARS-CoV-2 with innate immune cells, in particular those in which the trained immunity activity has been demonstrated. Review Mon, 27 Feb 2023 00:00:00 GMT Naima G.Cortes-Perez, Mon, 27 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100387 https://www.explorationpub.com/Journals/ei/Article/100388 Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a family of intracellular signaling adaptors that associate with the cytoplasmic tails of a diverse range of lymphocyte receptors, including members of the TNFR superfamily, the Toll-like receptor (TLR)/interleukin-1 (IL-1) receptor superfamily, and the IL-6 receptor family that are major targets for therapeutic intervention for inflammatory diseases. TRAF5 is one of the seven family members of the TRAF family and is highly expressed by B- and T-lymphocytes. As compared to other family members, the biological and pathophysiological functions of TRAF5 have remained ambiguous since its discovery. TRAF5 promotes lymphocyte signaling for the TNFR family molecules such as glucocorticoid-induced TNFR family-related protein (GITR), CD27, and CD40. In contrast, TRAF5 limits the activity of the common signaling receptor subunit glycoprotein 130 kDa (gp130) in CD4+ T cells that requires signaling by IL-6 and IL-27. TRAF5 also restrains TLR signaling in B cells. Thus, TRAF5 regulates lymphocyte signaling in both positive and negative ways. This review will summarize the findings of recent studies of TRAF5 in terms of how TRAF5 regulates signaling in lymphocytes and other cell types and how TRAF5 expression contributes to inflammatory and autoimmune diseases in mice and humans. Review Tue, 28 Feb 2023 00:00:00 GMT Mari HikosakaKuniishi, NaotoIshii, TakanoriSo, Tue, 28 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100388 https://www.explorationpub.com/Journals/ei/Article/100390 Lung cancer is the leading cause of cancer-related deaths worldwide. The main risk factor for lung cancer is exposure to chemicals present in cigarettes and atmospheric pollutants, which, among other mechanisms, can increase the risk of cancer by inducing pulmonary inflammation. Among the complex features of inflammatory processes, the role of inflammasomes has attracted increasing attention due to their role in different stages of carcinogenesis. Inflammasomes are intracellular multiprotein complexes that when activated promote the maturation of interleukin-1beta (IL-1β) and IL-18, pro-inflammatory cytokines involved in the promotion, progression, epithelial-mesenchymal transition, metastasis, and resistance to therapy of lung cancer. In this way, this review summarizes the recent findings of inflammasome research in different stages of lung cancer, with a focus on non-small cell lung carcinoma (NSCLC), and highlights these multiprotein complexes as promising targets for cancer therapy. Review Wed, 15 Mar 2023 00:00:00 GMT Vitor Rodriguesda Costa, Olívia FonsecaSouza, Michelli RamiresTeixeira, Anderson LucasAlievi, HugoVigerelli, Rodrigo PinheiroAraldi, Wed, 15 Mar 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100390 https://www.explorationpub.com/Journals/ei/Article/100389 The infection of COVID-19 is directly linked to the destruction of lung epithelial cells, and the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) system has been implicated in the pathology of respiratory infections. This study aimed to systematize the relationship between the pathophysiology of COVID-19 and the cGAS-STING system’s activation in the lungs. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is an RNA virus that belongs to the Coronaviridae family whose genetic material is produced by a single positive RNA molecule (RNA+). The cGAS-STING signaling pathway has emerged as a key mediator of injury caused by infection and cellular or tissue stress. The cGAS-STING cyclic pathway is part of innate immunity and is activated from cytosolic DNA responses present in newly formed syncytia, by cell-to-cell fusion, in target of angiotensin-converting enzyme 2 (ACE2) expression and SARS-CoV-2 Spike protein. Although this pathway is canonically understood to be responsive to both pathogen-derived and host-derived DNA, it has been demonstrated to cross-communicate with the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). cGAS-STING activation is significant to interferon production, mainly type-I interferons (IFN-I), in a SARS-CoV-2 infection scenario, indicating a major antiviral role of the cGAS-STING pathway. It was identified that in SARS-CoV-2 the cGAS-STING axis is activated, but the inflammatory response could be specific for nuclear factor-κB (NF-κB) in infected cells, and that this axis is potentiated by a cytokine storm produced by the immune system’s cells. Review Wed, 01 Mar 2023 00:00:00 GMT Gislei F.Aragão, Sthefane G.Feitosa, Herlice Do NascimentoVeras, Cícero Gilmário A. P.de Lima Filho, Karinne da S.Assunção, Luana M.Arrais, Sara Lívia M.Teixeira, Wed, 01 Mar 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100389 https://www.explorationpub.com/Journals/ei/Article/100391 In the last years, multiple efforts have been made to accurately predict neoantigens derived from somatic mutations in cancer patients, either to develop personalized therapeutic vaccines or to study immune responses after cancer immunotherapy. In this context, the increasing accessibility of paired whole-exome sequencing (WES) of tumor biopsies and matched normal tissue as well as RNA sequencing (RNA-Seq) has provided a basis for the development of bioinformatics tools that predict and prioritize neoantigen candidates. Most pipelines rely on the binding prediction of candidate peptides to the patient’s major histocompatibility complex (MHC), but these methods return a high number of false positives since they lack information related to other features that influence T cell responses to neoantigens. This review explores available computational methods that incorporate information on T cell preferences to predict their activation after encountering a peptide-MHC complex. Specifically, methods that predict i) biological features that may increase the availability of a neopeptide to be exposed to the immune system, ii) metrics of self-similarity representing the chances of a neoantigen to break immune tolerance, iii) pathogen immunogenicity, and iv) tumor immunogenicity. Also, this review describes the characteristics of these tools and addresses their performance in the context of a novel benchmark dataset of experimentally validated neoantigens from patients treated with a melanoma vaccine (VACCIMEL) in a phase II clinical study. The overall results of the evaluation indicate that current tools have a limited ability to predict the activation of a cytotoxic response against neoantigens. Based on this result, the limitations that make this problem an unsolved challenge in immunoinformatics are discussed. Review Tue, 25 Apr 2023 00:00:00 GMT IbelCarri, ErikaSchwab, EnriquePodaza, Heli M.Garcia Alvarez, JoséMordoh, MortenNielsen, María MarcelaBarrio, Tue, 25 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100391 https://www.explorationpub.com/Journals/ei/Article/100394 Linker for activation of T cells (LAT) is a central adaptor protein in proximal T cell activation. A key element of its adaptor function is the efficiency with which LAT interacts with its binding partners. Such efficiency is controlled by the local concentration of LAT as well as the vicinity to up- and downstream interaction partners, i.e. LAT localization. Several factors control LAT localization. LAT is a palmitoylated transmembrane protein and traffics between vesicular compartments and the plasma membrane. Membrane heterogeneity and protein-protein interactions can drive LAT clustering, at scales from a few to hundreds if not more molecules. LAT vesicular trafficking through the small, crowded cytoplasm of a T cell and the commonly nm scale clusters are difficult to access experimentally, in particular in the physiological interaction of T cells binding to antigen presenting cells (APCs) with a highly undulating interface. Only in recent years have technological advances begun to provide better access. Based on such advances, three elements of LAT localization are discussed in conjunction: vesicular trafficking as it regulates LAT transport towards, insertion into, and removal from the plasma membrane; LAT clustering as it increases local LAT concentrations; LAT-anchored supramolecular signaling complexes as they embed LAT in a dense network of interaction partners. Consistent with the important role of LAT localization for its function, each of these processes regulates LAT activity and the efficiency of T cell activation. Perspective Fri, 28 Apr 2023 00:00:00 GMT Laura E.McMillan, ChristophWülfing, Fri, 28 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100394 https://www.explorationpub.com/Journals/ei/Article/100392 Mesenchymal stem/stromal cells (MSCs) are known as multipotent cells due to their ability to differentiate into various cell lineages of mesoderm origin. Recent developments in stem cell biology have provided a new ray of hope for the treatment of diseases and disorders that are yet to be treated. These cells have been widely used in animals and clinical trials in humans. To date, there are more than 920 clinical trials on humans related to MSCs as cell-based therapy in various conditions. The purpose of this review is to provide a summary of the characteristics of MSCs, evaluate their immunological properties, activation of MSCs that dictate their soluble factors, possible pathway, and mechanisms involved by MSCs and immune cell interaction, and various application of MSCs in different diseases. Review Fri, 28 Apr 2023 00:00:00 GMT MehakVohra, Sunil K.Arora, Fri, 28 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100392 https://www.explorationpub.com/Journals/ei/Article/100393 Surgery, chemotherapy, radiation therapy, and immunotherapy are potential therapeutic choices for many malignant and metastatic cancers. Despite adverse side effects and pain, surgery and chemotherapy continue to be the most common cancer treatments. However, patients treated with immunotherapy had better cancer control than those who got other treatments. There are two methods to activate immunological pathways: systemically and locally. To modify the tumor microenvironment (TME), the former uses systemic cytokine/chemokine (CK) delivery, whilst the latter uses immunological checkpoints or small molecule inhibitors. Organic and inorganic nanomaterials (NMs) enhanced the efficacy of cancer immunotherapy. NMs can transmit drugs, peptides, antigens, antibodies, whole cell membranes, etc. Surface-modified NMs precisely target and enter the tissues. The inner core of surface-modified NMs is composed of chemicals with limited bioavailability and biocompatibility, resulting in prolonged blood retention and decreased renal clearance. These platforms hinder or prevent many immune cell activities and modify the TME, enhancing the efficiency of cancer immunotherapy. By inhibiting CK/CK receptor signaling, cell migration and other immune responses could be controlled. Developing CK-targeted nanoparticles (NPs) that inhibit CK signaling or take advantage of the ligand-receptor connection is possible. Surface chemical modification of NMs with CKs or specific peptides has several medicinal applications, including tissue-specific drug delivery and limited cell migration in cancer-afflicted conditions. This review covers current developments in the role of different groups of CK-loaded NP in tumor therapy targeting immune cells and cancer. It also covers the role of NP targeting CK signaling which aids in immunogenic cell death (ICD) and induction of antitumor immunity. In addition, CK gene silencing and its capacity to prevent cancer metastasis as well as inhibition of immune cell migration to modulate the TME are discussed. Review Fri, 28 Apr 2023 00:00:00 GMT RanjeetSingh, PrateekSrivastava, Partha PratimManna, Fri, 28 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100393 https://www.explorationpub.com/Journals/ei/Article/100395 The growth and differentiation of normal cells are controlled by protein-tyrosine kinases, which serve as receptors for a wide variety of external signals. Small protein modules called Src homology 2 (SH2) and SH3 domains mediate protein-protein interactions in signaling pathways that are triggered by protein tyrosine kinases. The SH2 domain, a protein module of around 100 amino acids, is present in tyrosine kinase targets within the cell. SH2 domains are recruited to activated and autophosphorylated growth factor receptors by directly recognizing tyrosine phosphorylation sites. Growth factor receptors and other phosphoproteins have short phosphotyrosine (pTyr)-containing sequences that are bound by SH2 domains. The SH3 domain, a distinct element of approximately 50 residues that recognizes proline-rich and hydrophobic-amino-acid-containing regions, is frequently found in SH2-containing proteins. Tyrosine kinases can be coupled to downstream targets with SH3-binding sites by proteins with SH2 and SH3 domains acting as adaptors. These intricate and precise biochemical signaling pathways result in the regulation of gene expression, cytoskeletal architecture, and cell metabolism. The role of SH2/SH3 proteins in T cell signaling will be discussed. A special focus will be on the role of the hematopoietic signal transducer with SH2/SH3 domains, Vav1, in health and cancer. Review Fri, 28 Apr 2023 00:00:00 GMT ShulamitKatzav, Fri, 28 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100395 https://www.explorationpub.com/Journals/ei/Article/100396 Aim: Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease. Thymic stromal lymphopoietin (TSLP) is highly expressed in the epidermis of patients with AD and induces T helper 2 (Th2) immune responses and itching. Although the mechanism underlying the stimulus-induced TSLP production in normal keratinocytes has been intensively studied, whether the production capability of TSLP is naturally enhanced in epidermal cells in AD conditions remains unclear. Previous studies demonstrated that a deficiency of polyunsaturated fatty acid (PUFA) causes AD-like pruritic skin inflammation in special diet-fed hairless mice. The aim of the study was to examine the TSLP production capability of epidermal cells isolated from diet-induced AD mouse model and its mechanism. Methods: Epidermal cells were isolated from normal and AD mice and incubated under unstimulated culture conditions to assess spontaneous TSLP production. Messenger ribonucleic acid (mRNA) and protein levels of TSLP were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: TSLP level was markedly increased in the skin of AD mice. When epidermal cells were isolated from AD mice and cultured without stimulation, Tslp gene expression was upregulated, and a large amount of TSLP protein was extracellularly released. Such TSLP overproduction was not observed in the epidermal cells of normal mice. TSLP overproduction in AD epidermal cells was almost completely inhibited by extracellular calcium chelation, interference with plasma membrane interaction of stromal interaction molecule 1 (STIM1), blockade of the calcium release-activated calcium (CRAC) channels Orai1 and Orai2, or treatment with a PUFA γ-linolenic acid (GLA). Conclusions: Epidermal cells isolated from AD mice can spontaneously produce TSLP through STIM/Orai-mediated calcium entry, and GLA may negatively regulate this TSLP production. Original Article Mon, 12 Jun 2023 00:00:00 GMT MasanoriFujii, ShuheiKobayashi, AyaneUeda, MisakiSakagami, RiekoMatsui, YumekaYamada, TakeshiNabe, SusumuOhya, Mon, 12 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100396 https://www.explorationpub.com/Journals/ei/Article/100397 Human germinal center (GC)-associated lymphoma (HGAL) is a multi-domain adaptor protein expressed in GC B lymphocytes, T follicular helper (Tfh) cells and lymphomas derived from these cells. HGAL expression is an independent predictor of longer survival of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin’s lymphoma (HL) patients. HGAL regulates B cell receptor (BCR) signaling and immunological synapse formation by binding to either the downstream effectors [e.g., spleen tyrosine kinase (Syk)] or other signaling regulators [e.g., growth factor receptor-bound protein 2 (Grb2)]. HGAL regulates the cytoskeleton that reshapes B cell morphology during BCR signaling and cell motility by at least two molecular mechanisms: enhanced Ras homolog gene family member A (RhoA) signaling and inhibition of myosin-actin translocation. These effects on the cytoskeleton decrease lymphoma dissemination in animal models and contribute to decreased lymphoma dissemination in patients. The latter may contribute to the association of HGAL protein expression with longer survival of patients with DLBCL and HL tumors. The ability to regulate multiple and distinct functions simultaneously in B cells implies that the HGAL protein level is tightly regulated. It was demonstrated that HGAL can be regulated by PR/SET domain 1 (PRDM1)/B lymphocyte-induced maturation protein-1 (BLIMP1) and interleukin-4 (IL-4) at the transcription level, by microRNA-155 (miR-155) at the post-transcriptional level, and by F-box protein 10 (FBXO10) at the post-translational level. Constitutive enforced expression of HGAL at physiological levels leads to lymphoid hyperplasia and DLBCL in mice. Future studies need to focus on identifying HGAL interactome, dissecting its interaction network, and understanding HGAL spatiotemporal signaling in live cells in physiological conditions. Further, the recent demonstration of HGAL expression in Tfh cells requires the determination of its function in these cells. These studies will contribute to new insights into the biology of these cellular subsets and how immune dysregulation contributes to lymphomagenesis. Review Wed, 28 Jun 2023 00:00:00 GMT XiaoyuJiang, Izidore S.Lossos, Wed, 28 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100397 https://www.explorationpub.com/Journals/ei/Article/100398 Periodontal tissue destruction can cause complaints for sufferers. Inflammatory conditions of the gingiva, bleeding gums, and even tooth loss are clinical features of the destruction of the periodontal tissues. Periodontitis is an inflammatory disease involving the periodontal tissues. The prevalence of periodontium destruction increases with aging. Changes in innate and adaptive immunity that occur in the elderly also play a role in the severity of periodontitis. “Inflammaging” is a chronic inflammatory state associated with old age in humans. Periodontitis contributes to inflammaging since periodontitis in the elderly is associated with increased markers of systemic inflammation. Age-related changes also affect neutrophil function, especially antimicrobial activity, so neutrophils may become more pathological. After infiltration into the tissue, neutrophils are equipped with several antimicrobial strategies to reduce the number of antigens. Phagocytosis is the ability of neutrophils to engulf and kill microbes, but neutrophil phagocytosis is weakened in the elderly. Age-related changes affecting neutrophils, macrophages, and T cells appear to promote pathogenic immune responses and contribute to the increased prevalence of periodontal disease in aging individuals. Proper regulation of the host immune response is critical in maintaining periodontal health. This paper aims to describe the aging process and its relation to periodontal conditions. Review Fri, 30 Jun 2023 00:00:00 GMT PituWulandari, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100398 https://www.explorationpub.com/Journals/ei/Article/100399 The Src homology 2 (SH2) and SH3 domain-containing chicken tumor virus number 10 (CT10) regulator of kinase (Crk) adaptor proteins include three cellular members that serve as integral constituents of multiple receptor-linked signal transduction pathways. CrkI and CrkII are products of alternative RNA-splicing which is transcribed from a single gene, while Crk-like (CrkL), which is highly homologous to CrkII, is encoded by a different gene. Thanks to their modular structure, the Crk adaptor proteins can simultaneously interact with activated receptors and a wide range of effector molecules, and orchestrate the assembly of complexes containing enzymes and substrates at the receptor site. They are involved in the regulation of a large number of cellular processes which control cell growth, differentiation, transformation, and apoptosis. Cell activation-dependent tyrosine phosphorylation of CrkII and CrkL serves as a major posttranslational modification mechanism that introduces conformational changes in the proteins by promoting an intramolecular interaction between the phosphotyrosine and the self SH2 domain. The resulting conformational change induces downregulation of CrkII- and CrkL-dependent biological processes. A second type of posttranslational modification mechanism regulates the structure and function of the CrkII adaptor protein by immunophilin-mediated protein isomerization. Two of the most abundant immunophilins in T lymphocytes which function as peptidyl-prolyl cis-trans isomerases (PPIases), namely cyclophilin A (CypA) and FK506-binding proteins (FKBPs), can associate with CrkII and catalyze its reciprocal cis-trans isomerization. This mechanism is of special importance for the regulation of T lymphocyte functions and for T cell-mediated immune responses, since immunophilin inhibitors, such as cyclosporin A (CsA) and FK506, function as immunosuppressive drugs that can prevent allotransplanted graft rejection. The present manuscript focuses on selected functions of Crk adaptor proteins, predominantly in T lymphocytes, and reviews in more detail the current knowledge on the immunophilin-dependent regulation of the structure and function of the CrkII adaptor protein. Review Fri, 30 Jun 2023 00:00:00 GMT NoahIsakov, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/100399 https://www.explorationpub.com/Journals/ei/Article/1003100 Besides trauma, several pathological conditions which directly affect the normal functioning of organs, require new therapeutic strategies to repair damaged or diseased tissues. Tissue regeneration is a complex and spatiotemporal process involving a plethora of cell types, including various immune cells and stem cells in a synchronized relationship. However, individual parameters, namely ageing, obesity, diabetes, and chronic conditions, have been intrinsically correlated with poor regenerative properties of adult tissues. While vast progress has been made regarding stem cell-based therapy to direct self-healing, the immune response is still the Achilles’ heel of such strategies. Whereas the role of effector immune cells has been well defined along the regenerative process, an understanding of the behavior of the main adult stem cells, namely mesenchymal stem cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs), along the different phases of the regenerative process could clarify how these stem cells can be used to positively influence the immune response. In this scope, this review highlights the main interactions between these stem cells and immune cells during tissue repair, exploring the most important regenerative properties of stem cells and correlating them with the modulation of the immune response during tissue regeneration. Furthermore, the utmost strategies used to explore how the behavior and stem cell fate are affected by specific microenvironments and/or stimuli usually found during a regenerative process, are emphasized. This clarification may provide critical insight into the molecular mechanisms by which stem cells modulate the immune response in a positive feedback loop toward tissue repair. Review Fri, 30 Jun 2023 00:00:00 GMT Cláudia S.Oliveira, Freni K.Tavaria, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003100 https://www.explorationpub.com/Journals/ei/Article/1003101 The coronavirus disease-2019 (COVID-19) pandemic is a significant threat in the modern era. Clinical studies show that the most common symptom of severe COVID-19 is viral pneumonia-induced acute respiratory distress syndrome (ARDS). The underlying mechanisms by which severe respiratory disease syndrome-coronavirus-2 (SARS-CoV-2) results in ARDS and how certain host factors confer an increased risk of developing severe disease remain unknown. Therefore, identifying the distinctive features of this severe and fatal disease and the therapeutic approaches to COVID-19-induced ARDS remains an immediate need to serve as a basis for best practice models of standardized ARDS treatment. This review article aims to comprehensively discuss the immunopathology of ARDS and provides an overview of the precise role of both the innate and adaptive immune system, with emphasis on the current treatment strategies being tested in the COVID-19-induced ARDS patients. This knowledge will supposedly help in revealing further mechanistic insights into understanding COVID-19-induced ARDS. Review Fri, 04 Aug 2023 00:00:00 GMT SnehaDas, TamannaSharma, AshaBhardwaj, Rupesh K.Srivastava, Fri, 04 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003101 https://www.explorationpub.com/Journals/ei/Article/1003139 Ebola virus (EBOV) is a zoonotic virus comprising of six known different species, designated within the family Filoviridae and genus Ebolavirus. The first recorded outbreak of an EBOV disease (EVD) was in Yambuku, Zaire EBOV (ZEBOV) in 1976, followed by the Sudan EBOV (SUDV) later that year. Outbreaks have been increasing throughout the 21st century, and mortality rates can reach up to 90%. Such extraordinary virulence is evidenced by a few pathogens, similar to the Marburg virus (MARV) that originated in Uganda and was first detected in Germany in 1967. The virulent nature of filovirus disease has established these related viruses as a formidable global concern. There are currently four types of Ebolaviridae species known to infect humans, with two more recently identified in other animals that are genomically different concerning cellular pathogenesis or aetiology of disease. Recent advances in understanding the pathogenesis of filovirus disease infections have been remarkable, yet the immunological response to filovirus infection remains unknown. Scientific analysis of cellular mechanisms can provide insight into virulence factors utilised by other pathogenic viruses that also cause febrile illness with occasional haemorrhagic fever in humans. In this review, a brief summary of EBOV protein structure and functional cellular effects is covered. The role of innate and adaptive immune cells known since 1976 is considered with the relevance and implications of immunological proteins measured by cluster of differentiation (CD) molecule, alongside cytokine, chemokine, and other biologically relevant pathways, and through genetic research. A thorough understanding of immunological correlates affecting host responses to EBOV will facilitate clinical and applied research knowledge, contributing to protection against potential public health threats. Review Fri, 26 Apr 2024 00:00:00 GMT BrentBrown, ChinuaImarogbe, EnriqueChacon-Cruz, IngoFricke, Fri, 26 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003139 https://www.explorationpub.com/Journals/ei/Article/1003102 The emergence and re-emergence of pathogens is a public-health concern, which has become more evident after the coronavirus disease 2019 (COVID-19) pandemic and the monkeypox outbreaks in early 2022. Given that vaccines are the more effective and affordable tools to control infectious diseases, the authors reviewed two heterologous effects of vaccines: the trained immunity and the cross-reactivity. Trained immunity, provided by attenuated vaccines, was exemplified in this article by the decreased the burden of COVID-19 in populations with high Bacille Calmette-Guerin (BCG) coverage. Cross-reactive responses were exemplified here by the studies which suggested that vaccinia could help controlling the monkeypox outbreak, because of common epitopes shared by orthopoxviruses. Although modern vaccination is likely to use subunit vaccines, the authors discussed how adjuvants might be the key to induce trained immunity and improve cross-reactive responses, ensuring that heterologous effects would improve the vaccine’s response. Review Thu, 24 Aug 2023 00:00:00 GMT Amanda IzeliPortilho, ElizabethDe Gaspari, Thu, 24 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003102 https://www.explorationpub.com/Journals/ei/Article/1003103 In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in LA cases; therefore, immunological confirmation of antibodies against coagulation factors is recommended. Additionally, acquired hemophilia A (AHA), caused by autoantibodies against FVIII, is a typical acquired hemorrhagic diathesis, although affected patients may present with thrombosis associated with LA. Thus, it is important to remember that hemorrhagic diathesis due to autoantibodies against clotting factors can also result in thrombosis, as demonstrated by the co-detection of LA. When clotting factor inhibitors are detected in LA-positive individuals, it is important to confirm the presence of autoantibodies against coagulation factors using immunological methods, such as ELISA, to avoid false-positive results. Review Wed, 30 Aug 2023 00:00:00 GMT MasahiroIeko, KazumasaOhmura, SumiyoshiNaito, MikaYoshida, HisaomiSasaki, TsuyoshiSato, NorifumiSugawara, NobuhikoTakahashi, AkitadaIchinose, Wed, 30 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003103 https://www.explorationpub.com/Journals/ei/Article/1003106 Changes occurring in the immune system along the ageing process increase the risk of infection, susceptibility to tumor development, and autoimmunity. Interventions such as physical exercise, supplements, and probiotics have been proposed in order to circumvent these conditions. Vitamin D supplementation could contribute to the immune system homeostasis in older adults since a large proportion of this population has low levels of circulating vitamin D. Additionally, observational studies have shown the association between vitamin D status and infections, chronic diseases such as cancer, diabetes, and cardiovascular disease. Recently it was observed that old patients with COVID-19 and vitamin D deficiency had enhanced severity of lung damage, longer stay at the hospital, and increased risk of death, suggesting that vitamin D plays an important role in the patient outcome from COVID-19. A high dose of vitamin D supplementation improved clinical recovery in a case-series report but in another study, no evident link between levels of vitamin D and risk of COVID-19 infection was found. Results also remain debatable for vitamin D supplements and improvement of immune response after vaccination, tuberculosis, pneumonia, and sepsis. It has been hypothesized that vitamin D could modulate the immune system and thus provide both efficacies in the immune response to pathogens/vaccinations and reduction of the inflammatory phenotype. This review will discuss vitamin D and homeostasis of the immune system; the literature-based clinical data on vitamin D and infections; and the possible link between vitamin D and immune response after vaccination. Review Thu, 31 Aug 2023 00:00:00 GMT ValquiriaBueno, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003106 https://www.explorationpub.com/Journals/ei/Article/1003104 Accurate lupus anticoagulant (LA) detection is crucial to antiphospholipid syndrome (APS) diagnosis. Detection is based on LA functional behavior in coagulation assays irrespective of epitope specificity. LA screening tests employ dilute phospholipids to accentuate in vitro inhibition by LAs, although they are not LA-specific and can be elevated by other coagulation abnormalities. Elevated screening tests are reflexed to mixing tests to distinguish between factor deficiency and inhibition. Confirmatory tests with high phospholipid concentration swamp LA to generate shorter clotting times than screening tests, whilst prolongation persists with non-phospholipid-dependent inhibitors. LA heterogeneity means that no single screening test detects every LA and the screen/mix/confirm medley must be applied to at least two assay types, usually dilute Russell’s viper venom time (dRVVT) and an LA-sensitive activated partial thromboplastin time (aPTT). Most laboratories restrict LA testing to these two assays, yet others, such as dilute prothrombin time (dPT), can perform with equal diagnostic efficacy, and additionally detect LA unreactive with dRVVT and aPTT. Converting clotting times to normalized ratios improves assay performance, and practitioners must choose between normal pooled plasma (NPP) clotting time denominators to reflect on-the-day assay performance, or reference interval (RI) mean clotting times to negate the effects of NPP variation. Cut-offs can be generated parametrically from normally distributed data, or different percentiles applied depending on the preferred balance between sensitivity and specificity. Sourcing sufficient donors for accurate cut-off estimations is problematic and transference exercises can be undertaken on low donor numbers. Analytical limitations of mixing tests have led to the adoption of alternative algorithms to the screen/mix/confirm test order, whilst some continue to rigidly apply the latter despite those limitations. Strategies to reduce or eliminate the effects of therapeutic anticoagulation have limitations, whilst the Taipan snake venom time (TSVT) screening test with an ecarin time (ET) confirmatory test is insensitive to vitamin K antagonist (VKA) and direct activated factor X anticoagulation. Review Thu, 31 Aug 2023 00:00:00 GMT Gary W.Moore, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003104 https://www.explorationpub.com/Journals/ei/Article/1003109 Aim: A number of questions remain unanswered concerning how infected individuals regulate their immune response to Plasmodium falciparum (P. falciparum) parasites at varying levels of exposure. Due to the interactions of inflammatory mediators and cytokines with the P. falciparum parasite complex density, several mediators influence parasitaemia and may give some indications of disease severity and represent effective signs in clinical manifestations of malaria disease. Methods: In this study, various levels of immune response mediators of interleukin 8 (IL-8), tumor necrosis factor-beta (TNF-β, also known as lymphotoxin-α), interferon-gamma (IFN-γ), IL-6, and IL-10 were investigated to the different phases of infection with P. falciparum in hyperendemic states in Sudan (White Nile, Blue Nile). This study vetted the association between certain inflammatory mediators during malaria infection and parasite density. This study was based on a total of 108 cases, in which 86 patients (62.0%) were uncomplicated and (17.6%) were severe, all met the diagnostic criteria and were clinically admitted for malaria infections. Commercial enzyme-linked immunosorbent assay (ELISA) kits were employed to determine the inflammatory mediator’s serum concentration. Results: The analysis of data indicated that older infected children had substantially raised levels of IFN-γ (P < 0.05), among study groups, levels of IFN-γ, TNF-β, and IL-8 were strongly linked with the severity of malaria, in severe and uncomplicated cases (P < 0.001), IL-6 and IL-10 were significantly associated with severe malaria cases uniquely (P < 0.001). Furthermore, we reported a positive correlation between IL-8 and TNF-β during all infection cases (r = 0.760, P < 0.001). Additionally, in severe malaria cases IL-6 was positively correlated with IL-10 (r = 0.575, P = 0.010). Conclusions: Eliminating P. falciparum blood-stage infection needs effective, specific, and tuned immune response strategies, which may present in the mediator’s correlations and depend on the density of the infection. Besides the effective levels contribution of certain cytokines that play protective roles during different stages of an infection. Original Article Thu, 31 Aug 2023 00:00:00 GMT Dia AldeenAlfaki, MohajirHussein, MustafaHassan, Amanda G.Eloraish, Mohamed MubarakElbasheir, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003109 https://www.explorationpub.com/Journals/ei/Article/1003105 Interest in the mechanisms of aging of the immune system has not faded over the past 100 years, and it is caused by the immune-mediated development of age-related pathology, including autoimmune organ damage, reduced vaccination efficiency, atherosclerosis, the development of cardiovascular pathology, etc. In contrast to many other organs and systems, the immune system aging begins at an early age and has more pronounced changes that lead to the development of secondary pathology, which significantly affects life expectancy. But an effective strategy to restore immune function has not been developed yet. During this time, the mechanisms of age-related dysfunction of organs and cells of both the adaptive and innate immune systems were studied in detail—thymus involution, a decrease in the potential of hematopoietic stem cells, impaired differentiation and functions of immunocompetent cells, as well as the ways of their interaction. Numerous potential therapeutic targets have been identified and various approaches have been used to implement such therapeutic interventions. The review is devoted to replacement therapy using transplantation of hematopoietic stem cells (HSCs) and young lymphoid cells and tissues, cellular and systemic factor exchange in heterochronic parabiosis, and some other widely used life extension approaches. It has been proven that cell therapy using young cells to rejuvenate the old immune system, unfortunately, often turns out to be ineffective because it does not eliminate the root cause of age-related changes. The phenomenon of inflamm-aging that develops with age can significantly affect both the aging of the organism in general and the functioning of immunocompetent cells in particular. Therefore, the most promising direction in the restoration of immune functions during aging is systemic approaches that have a complex effect on the organism as a whole and can slow down the aging process. Review Thu, 31 Aug 2023 00:00:00 GMT IrynaPishel, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003105 https://www.explorationpub.com/Journals/ei/Article/1003107 Vaccination has made an enormous contribution to global health. Treatment resistance for infectious diseases is growing quickly, and chemotherapeutic toxicity in cancer means that vaccines must be made right away to save humanity. But subunit vaccinations alone don’t give enough strong and long-lasting protection against infections that can kill. Nanoparticle (NP)-based delivery vehicles, such as dendrimers, liposomes, micelles, virosomes, nanogels, and microemulsions, offer interesting ways to get around the problems with traditional vaccine adjuvants. The nanovaccines (50–250 nm in size) are most efficient in terms of tissue targeting, staying in the bloodstream for a long time. Nanovaccines can improve antigen presentation, targeted delivery, stimulation of the body’s innate immune system, and a strong T-cell response without putting people at risk. This can help fight infectious diseases and cancers. Also, nanovaccines can be very helpful for making cancer treatments that use immunotherapy. So, this review highlights the various types of NPs used in the techniques that have worked in the new paradigm in viral vaccinology for infectious diseases. It gives a full rundown of the current NP-based vaccines, their potential as adjuvants, and the ways they can be delivered to cells. In the future, the best nanovaccines will try to be more logically designed, have more antigens in them, be fully functionalized, and be given to the right people. Review Thu, 31 Aug 2023 00:00:00 GMT ChittaranjanBaruah, PankajDas, PapariDevi, Palash MoniSaikia, BhabeshDeka, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003107 https://www.explorationpub.com/Journals/ei/Article/1003108 Cancer stem cells (CSCs) are a small subpopulation of cells that drive the formation and progression of tumors. However, during tumor initiation, how CSCs communicate with neighbouring immune cells to overcome the powerful immune surveillance barrier in order to form, spread, and maintain the tumor, remains poorly understood. It is, therefore, absolutely necessary to understand how a small number of tumor-initiating cells (TICs) survive immune attack during (a) the “elimination phase” of “tumor immune-editing”, (b) the establishment of regional or distant tumor after metastasis, and (c) recurrence after therapy. Mounting evidence suggests that CSCs suppress the immune system through a variety of distinct mechanisms that ensure the survival of not only CSCs but also non-stem cancer cells (NSCCs), which eventually form the tumor mass. In this review article, the mechanisms via which CSCs change the immune landscape of the tissue of origin, which contains macrophages, dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, and tumor-infiltrating lymphocytes, in favour of tumorigenesis were discussed. The failure of cancer immunotherapy might also be explained by such interaction between CSCs and immune cells. This review will shed light on the critical role of CSCs in tumor immune evasion and emphasize the importance of CSC-targeted immunotherapy as a cutting-edge technique for battling cancer by restricting communication between immune cells and CSCs. Review Thu, 31 Aug 2023 00:00:00 GMT SourioChakraborty, SumonMukherjee, UditBasak, SubhadipPati, ApratimDutta, SaikatDutta, SubhankiDhar, TaniaSarkar, AharnaGuin, GaurisankarSa, TanyaDas, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003108 https://www.explorationpub.com/Journals/ei/Article/1003110 Antiphospholipid syndrome (APS) is defined as an autoimmune and prothrombotic disorder in patients with the persistent presence of antiphospholipid antibodies (aPLs). In the classification criteria, aPL expresses lupus anticoagulant (LA) activity, which is detected by prolongation of coagulation assays. The LA detection algorithm is a sequential flow including screening tests, mixing tests, and confirmatory tests to differentiate between LA-positive and other anticoagulant abnormalities. Two types of assays are used, like dilute Russell’s viper venom time (dRVVT) and activated partial thromboplastin time (APTT) because no single test is sensitive to all LAs. The anticoagulant drugs prescribed for the prevention and treatment of thrombosis disorders can interfere with the assays, and it is important to know the effects of these drugs in the assays. Especially, new generation anticoagulant drugs, called direct oral anticoagulants (DOACs), affect the results. In this review, the following points are discussed: i) LA detection flow and data interpretation, ii) the principles of coagulation assays proposed and their characteristics, and iii) the effects of anticoagulant drugs in LA detection. Review Sun, 08 Oct 2023 00:00:00 GMT OsamuKumano, MariePeyrafitte, JeanAmiral, Sun, 08 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003110 https://www.explorationpub.com/Journals/ei/Article/1003115 One of the greatest challenges in the study of coronavirus disease 2019 (COVID-19) has been to establish the determining factors in the severity of the disease. Through extensive research efforts, a crucial factor responsible for disease control or exacerbation in COVID-19 has been identified—the regulation of the immune response. The abnormal release of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α) has been extensively studied in the context of the altered immune response observed in severe cases of COVID-19. However, recent attention has turned towards the excessive release of IL-17 and the increased presence of T helper 17 (Th17) cells, the main secretory cells of this cytokine. These factors have garnered interest due to their potential involvement in the cytokine storm observed in severe cases of COVID-19. In this review, it will be delved into the intricate mechanisms by which IL-6 contributes to the differentiation of Th17 cells, resulting in an increase in the population of Th17 cells. Moreover, it will be explored the proportional relationship between the increase of these lymphocytes and the release of IL-17 and other chemokines, which all together play a key role in promoting the chemotaxis and activation of neutrophils. Ultimately, this cascade of events culminates in the generation of tissue damage by neutrophils. Additionally, therapeutic options targeting these lymphocytes and cytokines are explored, providing insights into potential avenues for intervention. Review Mon, 16 Oct 2023 00:00:00 GMT Miguel AngelPardiño-Vega, Norma EstelaHerrera-González, Mon, 16 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003115 https://www.explorationpub.com/Journals/ei/Article/1003111 Vaccines are prophylactic medical products effectively used against infectious diseases. Although a high amount of vaccine studies are conducted at the preclinical stage, the number of approved vaccines is less than 10%. Development of vaccines from the research stage to the approval of administrative institutions takes about 5 years to 10 years conventionally. However, this period of time for vaccine development is not convenient during public health emergencies because an effective vaccine is required in a short time to restrict the speed of high mortality and morbidity. The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had its catastrophic effects worldwide quickly. Therefore, an atypical process was followed for the development of COVID-19 vaccines. Great effort was spent in terms of cooperation among the governmental institutions, academia, and medical companies as well as a high amount of budget was allocated to develop effective vaccines against COVID-19. As of March 2023, the numbers of COVID-19 vaccines in clinical and preclinical development were 183 and 199, respectively. An emergency use authorization (EUA) process was applied to accelerate the approval of the vaccines. Consequently, vaccinations could be started in less than a year, which decelerated the speed of the pandemic. Although EUA caused hesitancy among some people questioning the safety and efficacy of the vaccines, the vast majority of the population was vaccinated. Currently, more than 5.5 billion people (about 70% of the world population) have received 13.38 billion doses of 11 different COVID-19 vaccines, and 73% of the doses were Comirnaty manufactured by Pfizer/BioNTech. Review Wed, 11 Oct 2023 00:00:00 GMT SezerOkay, Wed, 11 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003111 https://www.explorationpub.com/Journals/ei/Article/1003112 Immunosenescence encompasses multiple age-related adaptations that result in increased susceptibility to infections, chronic inflammatory disorders, and higher mortality risk. Macrophages are key innate cells implicated in inflammatory responses and tissue homeostasis, functions progressively compromised by aging. This process coincides with declining mitochondrial physiology, whose integrity is required to sustain and orchestrate immune responses. Indeed, multiple insults observed in aged macrophages have been implied as drivers of mitochondrial dysfunction, but how this translates into impaired immune function remains sparsely explored. This review provides a perspective on recent studies elucidating the underlying mechanisms linking dysregulated mitochondria homeostasis to immune function in aged macrophages. Genomic stress alongside defective mitochondrial turnover accounted for the progressive accumulation of damaged mitochondria in aged macrophages, thus resulting in a higher susceptibility to excessive mitochondrial DNA (mtDNA) leakage and reactive oxygen species (ROS) production. Increased levels of these mitochondrial products following infection were demonstrated to contribute to exacerbated inflammatory responses mediated by overstimulation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and cyclic GMP-ATP synthase (cGAS)-stimulator of interferon genes (STING) pathways. While these mechanisms are not fully elucidated, the present evidence provides a promising area to be explored and a renewed perspective of potential therapeutic targets for immunological dysfunction. Review Wed, 11 Oct 2023 00:00:00 GMT Rafael MouraMaurmann, Brenda LandvoigtSchmitt, NeginMosalmanzadeh, Brandt D.Pence, Wed, 11 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003112 https://www.explorationpub.com/Journals/ei/Article/1003113 The etiology of recurrent spontaneous abortion (RSA) is extremely complex, as there are 40–50% of patients with unexplained miscarriages, known as unexplained RSA (URSA). URSA affects approximately 1–2% of females of childbearing age and has a massive impact on the physical and mental conditions of both patients and their families. The pathogenesis of the disease remains unclear, making its treatment complicated. In recent years, considerable progress has been made in the exploration of the URSA immune balance mechanism and it has been universally acknowledged that a balanced immune response (as abnormal immunity) may be the root cause of poor pregnancy outcomes. This review discussed and summarized the effects of immune cells and blocking antibodies (BAs) on URSA based on the current state of knowledge in this area. Additionally, molecular genetics also plays an essential role in the incidence rate of URSA since the role of genetic polymorphism in the pathogenesis of URSA has been thoroughly studied. Nonetheless, the outcomes of these studies are inconsistent, particularly across populations. This paper reviewed previous studies on URSA and maternal genetic polymorphism, focusing on and synthesizing the most important findings to date, and providing diagnostic recommendation for URSA patients with clinical symptoms. Review Thu, 12 Oct 2023 00:00:00 GMT YafeiKang, QinyingXie, ShutingChen, QinlanLi, XinyiDong, TianyuZhang, SenFu, QinghuaLei, DonghuiHuang, Thu, 12 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003113 https://www.explorationpub.com/Journals/ei/Article/1003114 Aim: The study aims to evaluate the incidence of recurrent thromboses in patients with primary antiphospholipid syndrome (PAPS) and its association with the presence of different antiphospholipid antibodies (aPLs) and known thrombogenic risk factors. Methods: This retrospective study included 52 patients. The median age of the patients was 38.5 years [31.5; 43.5], and the duration of the disease was 9.0 years [3.1; 13.0]. aPLs, including IgG/IgM/IgA antibodies to cardiolipin (aCLs), IgG/IgM/IgA anti-beta2-glycoprotein I (anti-β2-GPI), IgG anti-domain I-β2-GPI (anti-β2-GPIDI) antibodies, IgG/IgM antibodies to the phosphatidylserine/prothrombin complex (aPS/PT), and other thrombosis risk factors were included for analysis. Results: Recurrent thrombosis was reported in 34 (65%) out of 52 patients and 18 (35%) did not have it. The main reason for the recurrence of thrombosis was the lack of anticoagulant therapy: in 18 (52.9%) out of 34 patients with recurrent thrombosis. Three patients were taking warfarin at the time of thrombosis recurrence, but target international normalized ratio (INR) levels were not achieved. Other patients with recurrent thrombosis were taking direct oral anticoagulants (DOACs). The risk of recurrent thrombotic events with positive IgG aCL was 10.33 (P = 0.002) and 21 (P = 0.007) times higher were examined in enzyme-linked immunoassay (ELISA) and chemiluminescent assay (CLA), respectively. The risk of thrombosis was 4.58 times higher in patients who were IgA aCL-positive (P = 0.01). Compared with other antibodies, with positive IgG values of anti-β2-GPI and IgG aPS/PT by ELISA, a lower probability of thrombosis recurrence was observed: 7.56 and 7.25, respectively. A high risk of recurrent thrombosis [odds ratio (OR) = 32.0] was observed in IgG anti-β2-GPI (CLA). The combination of IgG aCL with IgG anti-β2-GPI and with IgG anti-β2-GPIDI is more informative with respect to the risks of thrombosis recurrence compared to double positivity for aCL with anti-β2-GPI (OR = 20.71 vs. OR = 10.18). Triple positivity for IgG aCL with IgG anti-β2-GPI and with IgG aPS/PT also shows better results compared to positivity for aCL with anti-β2-GPI (OR = 6.06 vs. OR = 5.79). Among other risk factors, arterial hypertension (AH) and obesity were significant in relation to the recurrence of thrombosis. AH occurred in 22 (42%) of 52 patients with PAPS. AH was associated with recurrent thrombosis in PAPS patients: 18 (53%) out of 34 with recurrent thrombosis had AH versus 4 out of 18 without recurrent thrombosis (P = 0.003). Conclusions: Recurrent thrombosis in antiphospholipid syndrome (APS) is largely associated with IgG aCL, IgG anti-β2-GPI, IgG anti-β2-GPIDI, IgG aPS/PT, and IgA aCL positivity. AH was a significant risk factor for recurrent thrombosis. Original Article Fri, 13 Oct 2023 00:00:00 GMT Fariza A.Cheldieva, Anastasiia A.Shumilova, Mariya V.Cherkasova, Svetlana I.Glukhova, Aleksander M.Lila, Evgeny L.Nasonov, Tatiana M.Reshetnyak, Fri, 13 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003114 https://www.explorationpub.com/Journals/ei/Article/1003116 Not applicable. Editorial Fri, 27 Oct 2023 00:00:00 GMT Joris C.Verster, EminaIšerić, JohanGarssen, Fri, 27 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003116 https://www.explorationpub.com/Journals/ei/Article/1003117 Immunotherapeutic treatment of autoimmune diseases should aim to inactivate autoaggressive memory T-cells and restore immune tolerance. It is envisaged that three approaches could be used to achieve this goal: stimulation of anti-idiotypic immune responses by vaccination with pathogenic T-cells; administration of suboptimal doses of antibodies (Abs) against two or more surface T-cell markers to provide selective Ab-mediated destruction of activated pathogenic memory T-cells; and induction of oral immune tolerance. The proposal entails the use of T-cell vaccination (TCV) or Ab-based therapy as an initial approach to reduce autoantigenic T-cell sensitization. Subsequently, the implementation of oral immunotherapy (OIT) is recommended to reinstate a consistent immune tolerance. Perspective Mon, 30 Oct 2023 00:00:00 GMT Victor IvanovichSeledtsov, Galina V.Seledtsova, Alexei A.von Delwig, Mon, 30 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003117 https://www.explorationpub.com/Journals/ei/Article/1003118 Aim: To describe the clinical characteristics and frequency of anti-factor H (FH) autoantibody-associated atypical hemolytic uremic syndrome (aHUS) in the first cohort of Argentine patients. Methods: The presence of anti-FH autoantibodies in 70 pediatric patients with suspected aHUS was investigated between 2013 and 2022. Clinical and laboratory parameters were collected and compared between patients who were positive and negative for anti-FH antibodies. Results: The 70 patients screened for anti-FH autoantibodies presented clinical features of non-immune microangiopathic hemolytic anemia, thrombocytopenia and renal injury. Positive titers were found in 14 children [mean: 1,938 arbitrary units per mL (AU/mL), range 179–8,500]. Due to missing clinical data, two patients who tested positive for anti-FH and 20 patients who tested negative for anti-FH were excluded from the data analysis. The laboratory features and clinical manifestations of anti-FH-positive aHUS cases (n = 12) were very similar to those of subjects with no autoantibodies detected (n = 36). Treatment administration was heterogeneous among the 12 patients analyzed. Dialysis was performed in six patients in total. Five children received plasmapheresis, while three patients were treated with plasma exchange followed by administration of eculizumab. Two patients received eculizumab only and one showed significant improvement solely through supportive care. Eight patients in total received immunosuppressive therapy. Follow-up of three patients showed a significant decrease of anti-FH autoantibody titers in 2/3 after treatment and during clinical remission. Conclusions: The cohort of 70 pediatric patients in this study demonstrated that the frequency of anti-FH autoantibody-associated aHUS in Argentina is 20%. The implementation of anti-FH testing in the country can potentially contribute to improved treatment and follow-up for patients with autoimmune aHUS. Original Article Fri, 10 Nov 2023 00:00:00 GMT CéliaDos Santos, JesicaTrinidad, SantiagoCastera, LauraAlconcher, Paula AlejandraCoccia, Federico JavierManni, María FabianaAlberto, AnalíaSánchez-Luceros, Fri, 10 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003118 https://www.explorationpub.com/Journals/ei/Article/1003119 Since 2019, notable global viral outbreaks have occurred necessitating further research and healthcare system investigations. Following the coronavirus disease 2019 (COVID-19) pandemic, in 2022, whilst severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains evolved, monkeypox virus (MPXV) infections became more evident. MPXV is of the Orthopoxviridae genus, belonging to the family Poxviridae. Zoonotic transmission (animal-to-human transmission) may occur. The Orthopoxviridae genus includes other orthopoxviruses (OPXVs) present in animal host reservoirs that include cowpox viruses (CPXVs), vaccinia virus (VACV), and variola virus (VARV), with the latter being a causal agent of smallpox and excessive mortality. This review aims to present facts about MPXV-specific pathogenesis, epidemiology, and immunology alongside historical perspectives. MPXV was rarely reported outside Africa before April 2000. Early research since 1796 contributed towards the eradication of VARV leading to immunisation strategies. The World Health Organisation (WHO) announcement that VARV had been eradicated was confirmed in 1980. On the 23rd of July 2022, the WHO announced MPXV as a health emergency. Therefore, concern due to the propagation of MPXV causing monkeypox (mpox) disease requires clarity. Infected hosts display symptoms like extensive cellular-initiated rashes and lesions. Infection with MPXV makes it difficult to differentiate from other diseases or skin conditions. Antiviral therapeutic drugs were typically prescribed for smallpox and mpox disease; however, the molecular and immunological mechanisms with cellular changes remain of interest. Furthermore, no official authorized treatment exists for mpox disease. Some humans across the globe may be considered at risk. Historically, presenting symptoms of mpox resemble other viral diseases. Symptoms include rashes or lesions like Streptococcus, but also human herpes viruses (HHVs), including Varicella zoster virus (VZV). Review Wed, 22 Nov 2023 00:00:00 GMT BrentBrown, IngoFricke, ChinuaImarogbe, Alexander ArielPadrón González, Osvaldo AguileraBatista, PascalMensah, EnriqueChacon-Cruz, Wed, 22 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003119 https://www.explorationpub.com/Journals/ei/Article/1003120 Protein Z (PZ) is a vitamin K-dependent protein that acts as a cofactor for the inhibition of activated factor X by the PZ-dependent protease inhibitor, an anticoagulant protein of the serpin superfamily. The presence of antibodies against PZ (aPZ-Abs) was first described in women with unexplained recurrent embryo loss, pre-eclampsia, or foetal death, independently from habitual antiphospholipid/anti-cofactor antibodies. Other studies suggested that aPZ-Ab could be associated with a small birthweight for the gestational age. The mechanism of action of these antibodies is not yet understood. At this time, even aPZ-Abs are frequently observed in patients with lupus anticoagulant or anticardiolipin antibodies, there is no evidence that aPZ-Abs increase systemic venous or arterial thrombotic risk. The comparison of the various published studies shows that the threshold suggesting an obstetric risk is not clearly defined. At present, it is not known whether one isotype of immunoglobulin (G or M, or both) is particularly involved in certain obstetric manifestations, or these antibodies persist during time, or can be induced by infectious diseases. Consequently, detection of these antibodies is not routinely warranted and should only be performed in randomized clinical trials. Review Wed, 06 Dec 2023 00:00:00 GMT TiffanyPascreau, SaraZia-Chahabi, Tojoniaina-HerinjakaAndriamandimbisoa, MarcVasse, Wed, 06 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003120 https://www.explorationpub.com/Journals/ei/Article/1003121 Aim: Non-healing wounds are one of the most substantial and difficult problems to treat. Wound healing involves a sequence of complex biological processes, but often the oral cavity microbiota adversely affects healing and forms a chronic non-healing wound. Methods: In this study, a biologically active membrane (BAM) is present, consisting of decellularized human amniotic membrane and bone marrow stem cells (BMSCs). The efficacy of BAM was evaluated in a model of non-healing oral wounds in rats with streptozotocin (STZ)-induced diabetes mellitus. Results: Studies have shown that BAM enhanced the healing of chronic oral wounds in animals with induced diabetes mellitus, reduced scarring, and reduced risk of infection. Paracrine freeze-dried BMSCs stimulated angiogenesis and improved wound conditions. Conclusions: BMSCs may lower glucose levels in rats with STZ-induced diabetes mellitus and improve the healing process of chronic diseases. However, more studies are needed to study the paracrine factors of BMSCs and their role in the treatment of non-healing wounds. Original Article Fri, 08 Dec 2023 00:00:00 GMT LiaKaralashvili, DavidChakhunashvili, MariamKakabadze, TeonaParesishvili, ZurabKakabadze, Fri, 08 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003121 https://www.explorationpub.com/Journals/ei/Article/1003122 The complement component C1q plays a role as a pro-angiogenic factor in different contexts, acting in a complement-independent way. For example, this molecule is able to foster the remodeling of the spiral arteries for a physiological pregnancy and to promote the wound healing process. It is also involved in angiogenesis after post-stroke ischemia. Furthermore, it has a role in supporting the tumor vessel growth. Given its role in promoting angiogenesis both under physiological and pathological situations, other studies are needed to understand its potential therapeutic implications. Review Fri, 15 Dec 2023 00:00:00 GMT MariagiuliaSpazzapan, SilviaPegoraro, ChiaraAgostinis, RobertaBulla, Fri, 15 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003122 https://www.explorationpub.com/Journals/ei/Article/1003123 Aim: To observe the effects of Ningmitai capsule on semen parameters of infertile patients with chronic prostatitis (CP) and explore the mechanisms. Methods: A total of 43 patients diagnosed with CP were included in the study and administered Ningmitai capsules (4 capsules per dose) for a duration of 6 weeks. Subsequently, assessments were conducted on parameters including sperm concentration, forward progressive motility, total motility, oxidative and anti-oxidative indicators, as well as the concentration of interleukin-8 (IL-8) in seminal plasma before and after the treatment period. Results: Compared to pre-treatment, forward progressive motility and total motility of the semen increased significantly (37.15% ± 18.77% vs. 45.44% ± 19.08%, P < 0.05 and 42.56% ± 21.22% vs. 51.64% ± 19.48%, P < 0.05). And the expression of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) increased significantly after treatment as well (11.36 μmol/L ± 3.28 μmol/L vs. 12.79 μmol/L ± 2.87 μmol/L, P < 0.05 and 9.34 U/mL ± 3.22 U/mL vs. 11.21 U/mL ± 4.87 U/mL, P < 0.05). In addition, the expression of malondialdehyde (MDA) and IL-8 decreased significantly after treatment (41.06 μmol/L ± 24.39 μmol/L vs. 32.17 μmol/L ± 15.04 μmol/L, P < 0.05 and 79.69 ng/L ± 26.24 ng/L vs. 61.35 ng/L ± 23.41 ng/L, P < 0.05). No significant difference in sperm concentration and sperm DNA fragmentation index was observed after the treatment (P > 0.05). Conclusions: Ningmitai capsule can enhance the antioxidant capacity and down-regulate the expression of cytokines in the semen, thereby improving the semen parameters of infertile patients with CP. Original Article Fri, 15 Dec 2023 00:00:00 GMT XiaoyuWu, ZhenYe, LihuaLi, HuipingZhang, XunbingHuang, JingsongChai, XinzongZhang, Fri, 15 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003123 https://www.explorationpub.com/Journals/ei/Article/1003124 Exome and RNAseq files prepared from blood samples can be mined for adaptive immune receptor recombinations and thus for the complementarity determining region-3 (CDR3) amino acid (AA) sequences, important for antigen binding. In this report, the T-cell receptor gamma (TRG) recombinations were mined from amyotrophic lateral sclerosis (ALS) blood sample exome and RNAseq files, mainly inspired by: (i) a high level of gamma-delta T-cells in Parkinson’s disease and (ii) TRG CDR3 AA features associated with a higher Braak stage in Alzheimer’s disease. Results indicated a high percentage of V9-JP recombinations from ALS blood sample genomics files, in comparison to TRG recombinations obtained from a large number of blood and other tissue samples not representing ALS. This result is discussed in the context of potential phospholipid sponging by adaptive immune receptors and potential impacts on membrane rigidity and amyloid development. Commentary Fri, 22 Dec 2023 00:00:00 GMT GeorgeBlanck, Taha I.Huda, Konrad J.Cios, GeorgeAngelakakis, Joanna J.Song, Fri, 22 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003124 https://www.explorationpub.com/Journals/ei/Article/1003125 Adaptor proteins are involved in various immune responses via the modulation of many signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that contains typical domains such as the pleckstrin homology (PH) domain, Src homology domain, and a proline-rich region from the N-terminal region. In T cells, STAP-2 positively regulates T cell receptor (TCR)-mediated signaling by associating with CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (LCK). Therefore, a peptide that inhibits the interaction between STAP-2 and CD3ζ ITAMs is likely to suppress TCR-mediated T cell activation, as well as T cell-mediated diseases. As expected, the peptide successfully inhibited the STAP-2/CD3ζ ITAM interaction and suppressed TCR-mediated signaling, cell proliferation, and interleukin (IL)-2 production in human/murine T cells. Furthermore, this inhibitor suppressed the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which is widely recognized as a mouse model of multiple sclerosis, via the downregulation of T cell activation and infiltration of T helper (Th) 1/Th17 cells. These results suggest a new strategy for the treatment of multiple sclerosis and other immune diseases. Perspective Thu, 28 Dec 2023 00:00:00 GMT YutoSasaki, ShoyaKawahara, YuichiSekine, Jun-IchiKashiwakura, KenjiOritani, TadashiMatsuda, Thu, 28 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003125 https://www.explorationpub.com/Journals/ei/Article/1003126 The coronavirus disease 2019 (COVID-19) pandemic cost 7–8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in acute respiratory distress syndrome (ARDS) and lung injury. Anti-inflammatory intervention with anti-interleukin-6 (anti-IL-6) receptor monoclonal antibodies (mAbs; e.g., sarilumab and tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and/or steroid-based approach leads to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this review, the authors have summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus-host immune cross talks and presenting the possibilities of therapeutic intervention. Review Wed, 31 Jan 2024 00:00:00 GMT Om SaswatSahoo, KarthikeyanPethusamy, ArnabNayek, RashmiMinocha, RubyDhar, SubhradipKarmakar, Wed, 31 Jan 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003126 https://www.explorationpub.com/Journals/ei/Article/1003127 Many acquired bleeding and thrombotic complications are provoked by autoantibodies to blood coagulation factors, or to hemostasis inhibitors and regulatory proteins. If occurrence of those antibodies remains rare or ultra-rare, affected patients are not always well-identified and associated pathologies are not always understood. Today, autoantigens tend to be better characterized. New available methods allow investigating structural changes of body components, responsible for auto-immunization. This renders it possible to develop laboratory assays for detecting autoantibodies and estimating their blood concentration. This review analyzes the major autoantibodies reported to be associated with hemorrhagic or thrombotic pathologies and their possible inducing causes when known. Pathogenicity is strongly patient- and context-dependent and is related to autoantibodies’ concentration, avidity, and capacity to bind to autoantigen structures in-vivo, misdirecting the immune system to the own body’s cells or organs. Identification of autoantigens allows for developing laboratory methods for testing autoantibodies and following their evolution kinetics. In-vitro investigations concern functional assays, to evaluate autoantibody’s capacity to inhibit physiological activities, or autoantigen-capture-based assays to detect autoantibodies, like with enzyme-linked immuno-sorbent assay (ELISA) methods. Exploring patients with autoimmune complications remains difficult as few specific assays are available. They mainly concern diseases with the highest incidence, like anti-phospholipid antibodies, lupus anticoagulants, or heparin-dependent antibodies. The present understanding suggests that antibodies to ubiquitous components, like phospholipids or polysaccharides, are actually targeted to proteins with a strong affinity binding to those components: Autoantibodies are not directed to phospholipids, but to phospholipid-binding proteins, and heparin-dependent antibodies are not directed to anticoagulant polysaccharides, but to platelet factor 4. Most pathogenic autoantibodies are of immunoglobulin G (IgG) isotype, but in some cases, IgM or IgA isotypes can be involved. Identification and characterization of autoantibodies associated to hemorrhagic or thrombotic pathologies remains complex at the laboratory level, although they are of high relevance for the right management of concerned patients. Review Mon, 05 Feb 2024 00:00:00 GMT JeanAmiral, Mon, 05 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003127 https://www.explorationpub.com/Journals/ei/Article/1003128 Mammals depend on the secretion of milk to rear their offspring, which exposes the organ in charge of the function, the mammary gland (MG), to bacterial threat. The essential driving force that conditions the interactions of bacteria with the MG is the abundant secretion of milk, a nutritious fluid which endows the common mastitis-causing pathogens with a doubling time of less than 30 min. From this angle, mammals rely on a potential bacterial bioreactor for the survival of their offspring. The MG is lined with a two-layered epithelium devoid of protective mucus. This means that the mammary epithelium is exposed directly to bacteria once they have passed through the opening lactiferous canal. To cope with the threat, the MG resorts to neutrophilic inflammation to check bacterial proliferation in its lumen and at its epithelial lining. Promptness of neutrophil recruitment is a necessity, which requires a low threshold of activation on the part of the mammary epithelium. Constrained by natural selection, the MG has evolved an innate and adaptive immunity intolerant to bacteria regardless of their level of virulence. The evolutionary issue has been to find a compromise between the deleterious tissue-damaging side effects of inflammation and the maintenance of the secretory function indispensable for the offspring’s survival. It appears that the MG relies mainly on neutrophilic inflammation for its protection and is regulated by type 3 immunity. Advances in knowledge of type 3 immunity in the MG will be necessary to induce immune protection adapted to the physiology of this peculiar organ. Review Tue, 06 Feb 2024 00:00:00 GMT PascalRainard, Tue, 06 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003128 https://www.explorationpub.com/Journals/ei/Article/1003129 Autoimmune and autoinflammatory diseases affecting the inner ear can cause symptoms such as hearing loss, imbalance, vertigo, and tinnitus, presenting demanding and often underdiagnosed conditions. Diagnostic challenges arise due to their diverse manifestations, potential long-term consequences, and the absence of specific serological markers, necessitating a multidisciplinary approach combining clinical evaluation, audiological assessments, and imaging techniques. Various autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome, have been implicated in immune-mediated damage to auditory structures, resulting in inner ear dysfunction. Inflammatory processes in autoinflammatory diseases like Cogan’s syndrome and relapsing polychondritis can also affect the inner ear. While the exact mechanisms of inner ear involvement in these conditions are still being studied, immune-mediated inflammation, damage to auditory structures, and vascular involvement play significant roles in auditory impairments. Treatment strategies primarily focus on immunomodulation and inflammation control using corticosteroids, immunosuppressants, and targeted biologic agents to ameliorate symptoms and preserve hearing function. Hearing aids and cochlear implants may be also considered for severe hearing loss. Individualized approaches are necessary due to patient response heterogeneity. This review provides a concise overview of key autoimmune and autoinflammatory diseases impacting the inner ear, highlighting clinical manifestations, diagnostics, pathophysiology, and treatment options. Early recognition and appropriate management are crucial for optimizing patient outcomes. Further research is needed to understand underlying mechanisms and identify novel therapeutic targets. Collaboration between otolaryngologists, rheumatologists, and immunologists is crucial for improving the quality of life in these complex conditions. Review Fri, 23 Feb 2024 00:00:00 GMT MichailAthanasopoulos, PinelopiSamara, IoannisAthanasopoulos, Fri, 23 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003129 https://www.explorationpub.com/Journals/ei/Article/1003130 The intestinal mucosal barrier plays a critical role in maintaining the integrity of the gastrointestinal (GI) tract and protecting the body from harmful toxins and pathogens. Nutrition additionally serves as a vital component in maintaining bodily homeostasis. Macronutrients, micronutrients, and specific dietary habits exert profound effects on the immune system. The complex interactions of the immune system reflect a multifaceted, integrated epithelial and immune cell-mediated regulatory system. While several factors can influence the intestinal mucosal barrier and its pro- and anti-inflammatory processes, such as myeloid cell, regulatory T cell (Treg), or intraepithelial lymphocyte populations, there is growing evidence that macronutrients play an essential role in regulating its function. Herein this is a review of the peer-reviewed literature pertaining to dietary effects on mucosal integrity, including intraepithelial lymphocyte populations and immune function. This review is intended to explore the underlying mechanisms by which macronutrients impact and modulate the mucosal immune system. Review Wed, 28 Feb 2024 00:00:00 GMT Lindsey B.Cundra, ManasaVallabhaneni, KevinHouston, MichaelSaadeh, AlejandraVargas, Steven M.D’Souza, David A.Johnson, Wed, 28 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003130 https://www.explorationpub.com/Journals/ei/Article/1003132 Aim: The current study aimed to describe various types of myelitis associated with a novel coronavirus infection [coronavirus disease 2019 (COVID-19)] as well as to analyze cytokine profiles and cerebrospinal fluid (CSF) parameters in affected patients and to compare them to patients with other immune-mediated disorders—multiple sclerosis (MS), in order to identify possible common pathogenetic pathways and consequently treatment targets. Methods: Clinical, radiological, and laboratory characteristics were studied based on patients’ history. CSF from patients with myelitis associated with COVID-19 (11 patients) was compared with CSF of healthy controls (HC) (7 patients) and patients with MS (37 patients) from the non-COVID era. CSF cytological examination, protein levels and oligoclonal bands (OCBs) evaluation, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus detection and cytokine profiling using Bio-Plex Pro Human Inflammation Panel 1, 37-Plex were performed. Results: In total 11 patients with different types of myelitis developed up to 3 months after COVID-19 were enrolled in the study. Radiological findings were diverse: short transverse myelitis (lesion of fewer than 3 segments) (n = 6), longitudinal extensive transverse myelitis (LETM) (n = 2), multifocal spinal cord lesions (n = 1), and myelitis involving dorsal and lateral columns (n = 2). The most pronounced response to treatment was observed in patients with partial transverse myelitis and patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG Abs). Multiple comparisons have demonstrated decreased levels of interleukin-10 (IL-10), interferon-α2 (IFN-α2), IFN-β, and thymic stromal lymphopoietin (TSLP), and increased IL-19 and B cell activating factor (BAFF) in patients with COVID-19 myelitis (CM) compared to the MS group. The highest BAFF and a proliferation-inducing ligand (APRIL) concentrations were found in patients with the most profound neurological disability. Conclusions: Myelitis associated with COVID-19 is clinically and radiologically heterogeneous. Evaluation of cytokine profiles in patients with myelitis associated with COVID-19 revealed their relative similarity with ones of MS patients, except for a few cytokines. BAFF/APRIL system as well as IL-10 is well-known for the role in the development and progression of autoimmune diseases, however, their links with COVID-19 and effects on the development of immune-mediated central nervous system (CNS) disorders after SARS-CoV-2 remain to be further studied. Original Article Thu, 29 Feb 2024 00:00:00 GMT AleksandraKozlova, AlinaDzharullaeva, AmirTukhvatulin, InessaZakroyshchikova, TarasSimaniv, LolaAskarova, DariaEliseeva, NataliaStoida, IvanKochergin, EkaterinaBaydina, MariaZakharova, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003132 https://www.explorationpub.com/Journals/ei/Article/1003131 Epididymitis or epididymo-orchitis is a common urological condition in males characterized by scrotal pain, swelling, and potential urinary symptoms. Although antibiotics can eliminate the causative pathogens, persistent inflammation may compromise spermatogenesis and steroidogenesis. The testis, an immune-privileged organ, possesses a specialized immune microenvironment that shields germ cells (GCs) from autoimmune attacks and orchestrates immune defenses against pathogens. This review focuses on the complex interplay between immune cells, including macrophages, dendritic cells (DCs), mast cells (MCs), and T cell subsets, in the testis. The roles of these immune cells in infection-induced orchitis were deliberated upon, emphasizing their involvement in inflammation and immune tolerance. Furthermore, the implications of testicular fibrosis and its effect on male infertility are discussed, emphasizing the role of MCs in tissue remodeling. The objective of this review is to expand comprehension of male reproductive health and foster the identification of potential therapeutic targets for epididymo-orchitis. Mini Review Wed, 28 Feb 2024 00:00:00 GMT YimingZhang, JianhuaZhu, MingWang, Wed, 28 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003131 https://www.explorationpub.com/Journals/ei/Article/1003133 Periodontitis is a ubiquitous chronic inflammatory worldwide disease. The multiplicity of gram-negative microbiomes and their endotoxins, such as lipopolysaccharides (LPS), play a crucial role in its pathogenesis. The detection and consequent effects of LPS occur either via membrane-based cluster of differentiation 14 (CD14)/myeloid differentiation factor 2 (MD2)/Toll-like receptor (TLR)-4 complex activation or through intracellular cytosolic LPS detection that further cascades its effects, resulting in a variety of cell death processes, including apoptosis, pyroptosis, necroptosis, NETosis, and their crosstalk. Irrespective of the detection of LPS, the cellular response is for protecting and resolving the inflammation. However, chronic and exaggerated responses in periodontitis result in the destruction of periodontal structures. This review summarizes the extracellular and cytosolic detection of LPS and its further consequences. Then, it sheds light on methods reported to mitigate the adverse effects of LPS. Review Thu, 29 Feb 2024 00:00:00 GMT Spoorthi RaviBanavar, Eng LaiTan, FabianDavamani, Suan PhaikKhoo, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003133 https://www.explorationpub.com/Journals/ei/Article/1003134 This review provides a detailed examination of CD4+ T lymphocyte subsets, crucial components of the immune system originating from the thymus. This study explores the distinct roles and mechanisms of various T helper (Th) cell subsets, including Th1, Th2, Th17, Th22, regulatory T cells (Tregs), Th9, and T follicular helper (Tfh) cells, focusing on their induction by specific cytokines, regulation by transcription factors, and the production of post-induction cytokines. The study traces the historical origins of Th lymphocyte research, emphasizing the unique cytokine profiles and functional implications of each subset in immune regulation and pathology, including autoimmune diseases, allergies, and cancer. Key findings include the delineation of cytokine-mediated induction processes, highlighting factors like interferon-gamma (IFN-γ), interleukin-4 (IL-4), transforming growth factor-beta (TGF-β), and IL-6. The review delves into transcription factors such as T-box transcription factor 21 (T-bet), GATA binding protein 3 (GATA3), and forkhead box P3 (Foxp3), underlying the lineage-specific development of these cells, and discusses the significant roles of post-induction cytokines. The research underscores the clinical relevance of CD4+ T cell subset dysregulation in various diseases, advocating for a nuanced understanding of these subsets for potential therapeutic advancements in immune-related disorders. Review Wed, 06 Mar 2024 00:00:00 GMT Murilo Porfírio deAguiar, Julia HailerVieira, Wed, 06 Mar 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003134 https://www.explorationpub.com/Journals/ei/Article/1003135 Cancer stem cells (CSCs) are a unique population of tumor cells with stem cell-like properties. They are believed to be involved in drug resistance, potential therapy failure, tumor relapse after treatment, and ultimately reduced overall survival of cancer patients. One of the causal factors that may lead to CSC formation is chromosomal instability (CIN), a dynamic event leading to numerical and structural changes in the chromosomes. The CIN is also proposed to aid the maintenance of CSCs, contribute towards their heterogeneity, and facilitate their immune escape. However, the role of CIN in the modulation of the immune system in tumors remains contradictory. Studies have revealed that it can lead to both activation and suppression of the immune system. Previous literature suggests that the CIN, CSCs, and cancer immunity (3Cs), interact with and complement each other to create a pro-tumor environment. However, the mechanisms underlying such an interaction are poorly understood. So, in this review article, an attempt has been made to understand the nature of the interaction between the triad of CIN, CSC, and the immune response in tumors and some of the pathways governing the same. Understanding the above may be a positive step towards the complete cure for malignant diseases. Review Tue, 02 Apr 2024 00:00:00 GMT LaxmiKumari, SaloniMunjal, ReenaYadav, YashwantKumar, AlkaBhatia, Tue, 02 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003135 https://www.explorationpub.com/Journals/ei/Article/1003136 Dendritic cells (DCs) play an important role in the formation of the immune response, and they are involved in the pathogenesis of autoimmune diseases. Targeting DCs has thus emerged as a new therapeutic modality in the management of inflammatory and autoimmune diseases. DCs can be manipulated ex vivo and then injected back into humans to suppress the immune response. They can also be manipulated in vivo by delivering specific molecules into the DCs. Co-stimulatory molecules that shape DCs interaction with T cells can also be targeted to suppress immunity. This review tackles the latest advances in each of the 3 presented approaches. Review Tue, 02 Apr 2024 00:00:00 GMT Mazen ElJamal, FarahShibli, Tue, 02 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003136 https://www.explorationpub.com/Journals/ei/Article/1003137 Not applicable. Commentary Thu, 18 Apr 2024 00:00:00 GMT FranciscoPitanga, Thu, 18 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003137 https://www.explorationpub.com/Journals/ei/Article/1003196 The introduction of immune checkpoint inhibitors (ICIs) has transformed the landscape of oncology, offering significant improvements in patient survival and achieving remarkable long-term outcomes. Despite these advances, the therapeutic benefits of ICIs are not universal, and existing biomarkers often fall short in accurately predicting patient responses. A comprehensive understanding of the mechanisms underlying resistance to ICIs is essential for the development of strategies to mitigate these challenges and enhance therapeutic efficacy. This review provides a detailed exploration of the resistance mechanisms associated with ICIs, focusing on the role of the tumor microenvironment and intrinsic tumor cell alterations in mediating both primary and secondary resistance. Furthermore, it evaluates emerging strategies to overcome resistance, including combination therapies and innovative therapeutic approaches. By dissecting the molecular and immunological pathways implicated in ICI resistance, this review aims to highlight novel predictive and prognostic biomarkers and outline optimized therapeutic strategies to maximize the clinical impact of ICIs in cancer management. Review Wed, 21 May 2025 00:00:00 GMT LuisCabezón-Gutiérrez, SaraCustodio-Cabello, MagdaPalka-Kotlowska, BeatrizChacón-Ovejero, VilmaPacheco-Barcia, Wed, 21 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003196 https://www.explorationpub.com/Journals/ei/Article/1003138 Primary immune regulatory disorders (PIRDs) constitute a subset of inborn errors of immunity and are characterized by lymphoproliferation, autoimmunity, malignancy, and infection. Unlike classical primary immune deficiencies, initial symptoms of PIRDs can manifest as autoimmunity such as cytopenias or enteropathy, which can often prove resistant to conventional treatments and occur years prior to the onset of infectious complications. Raising awareness about PIRDs among specialists and adopting a multidisciplinary approach is crucial for early diagnosis, intervention, and potential prevention of severe organ damage. Significant progress has been made in identifying several PIRDs, which has contributed to a more comprehensive comprehension of their underlying immunological mechanisms. This knowledge has paved the way for targeted therapies focusing on specific molecules, which tend to offer superior disease control compared to traditional immunosuppressants. This review, informed by the latest literature, explores prevalent PIRDs, detailing their clinical manifestations and recent advancements in treatment modalities. Review Tue, 23 Apr 2024 00:00:00 GMT NadiaMakkoukdji, ValishtiPundit, MatthewWyke, JheisonGiraldo, TravisSatnarine, Gary I.Kleiner, MelissaGans, Tue, 23 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003138 https://www.explorationpub.com/Journals/ei/Article/1003140 Repeated inoculation with messenger RNA (mRNA) vaccines elicits immunoglobulin G4 (IgG4) antibody production. Such an increase in the concentration of specific and non-specific IgG4 antibodies allows the growth of some types of cancer by blocking the activation of effector immune cells. This work proposes the hypothesis that cancer growth may be indirectly promoted by increased concentrations of non-specific IgG4 antibodies by the following mechanisms: 1) IgG4 antibodies can bind to anti-tumor IgG1 antibodies and block their interaction with receptors located on effector cells, thus preventing the destruction of cancer cells, 2) IgG4 can interact with fragment crystallizable gamma receptor IIb (FcγRIIB) inhibitory receptors, thus reducing effector functions of innate immune cells, and 3) targeting of specific epitopes by IgG4 could be oncogenic by inducing the production of a microenvironment that can promote cancer development. This article reviews the supporting literature and suggests several experimental protocols to evaluate this hypothesis in the context of repeated inoculation with mRNA vaccines. Additionally, this work proposes some management options aimed at reducing the unfavorable molecular consequences that could mediate cancer development when encountering high concentrations of IgG4 antibodies. Review Fri, 26 Apr 2024 00:00:00 GMT MikolajRaszek, DavidCowley, Elrashdy M.Redwan, Vladimir N.Uversky, AlbertoRubio-Casillas, Fri, 26 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003140 https://www.explorationpub.com/Journals/ei/Article/1003141 Dendritic cells (DCs) are part of the specific and innate immune system and present antigens for lymphocytes but also regulate the actions of cells of the innate immune system such as eosinophilic and neutrophilic granulocytes. There are several types of DCs, which might have opposite functions: some enhance an immune reaction, and others activate regulatory T (Treg) lymphocytes and thus can induce tolerance towards an antigen. Normally DCs migrate to regional lymph nodes and there they present modified antigens to cells of the immune system, however, in disease this might not function, resulting in the accumulation of DCs. The role of DCs in lung disease has not gotten much attention in the past, as investigations were predominantly focused on lymphocytes, macrophages, and granulocytes. Only in the last decades, DCs been more recognized. Several investigations are focusing on their role in immunotherapy in lung cancer, another focus is on inflammatory disorders including infections and allergies. In this review, non-tumor and non-infectious lung diseases with a focus on smoking-induced, autoimmune, and allergic diseases are discussed. Review Tue, 30 Apr 2024 00:00:00 GMT HelmutPopper, Tue, 30 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003141 https://www.explorationpub.com/Journals/ei/Article/1003142 Testicular sperm maturation is critical for establishing male fertility. Spermatozoa undergo remodeling of sperm proteins and changes in lipid and ribonucleic acid composition during transport in the epididymal ducts, which play an important role in sperm maturation. The anatomy, epithelial cell types, physiological functions, and epigenetic inheritance of the epididymis are explored, and recent findings in epididymal research are analyzed. Suggesting possible directions for future research on the epididymis. Using the keywords “epididymis”, “sperm”, and “sperm maturation”, a search of the epididymis was performed through databases and official websites of journals related to reproduction. The epididymis was searched in databases and on the official websites of journals related to reproduction. This review introduces the characteristics of the epididymis, as well as the biological functions of cell types such as principal cells, clear cells, and basal cells, providing a detailed description of the overall physiological functions of the epididymis. It highlights current research hotspots in the field of epididymis, including single-cell analysis, epigenetics, and extracellular vesicles, aiming to offer a comprehensive understanding for beginners. The review emphasizes the importance of the epididymis, its impact on sperm maturation and subsequent embryo development, and how it advances research on epididymal diseases while providing new directions for the study and treatment strategies of infertility. Review Fri, 17 May 2024 00:00:00 GMT ChuxiongWang, YeXie, JiangLiu, QinyingXie, YafeiKang, XinyiDong, DonghuiHuang, Fri, 17 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003142 https://www.explorationpub.com/Journals/ei/Article/1003143 As the most severe novel infectious disease in this century, coronavirus disease 2019 (COVID-19) faces tremendous challenges due to the hysteresis of drugs and vaccine development. Elucidating the panoramic mechanism of coronavirus-host immune interaction is a strategy for disease surveillance, diagnosis, treatment, prevention, and immunity assessment of COVID-19. A robust carbon nanotube (CNT)-based photic vaccine technology contributes to address the core scientific issues of these challenges. This perspective states the latest prevention and control strategy of CNT-based photic vaccine and its broad-spectrum resistance to high transmissible and pathogenic variants. Furthermore, this perspective covers the potential immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under the CNT-based photic vaccine intervention and finally evaluates its efficacy and the underlying interactive mechanisms. In the future, findings of the highly efficient and conservative T cell epitopes depending on an intelligent chem-physical modulation would provide a promising basis for the development of next generation vaccines. Ideally, these next generation vaccines are prone to be with the function of dynamic allostery responding to the chem-physical changing and present the allosteric epitopes which are affinity to the viral variation. Perspective Fri, 17 May 2024 00:00:00 GMT JunmingChen, QiangWang, FenfenZhang, JiansheYang, Fri, 17 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003143 https://www.explorationpub.com/Journals/ei/Article/1003144 Aim: Antigen (Ag) presentation by Ag-presenting cells (APCs) is the first step in the generation of adaptive humoral and cellular immune responses. However, there have been few studies on the effects of flavonoids on APC function. In this study, we examined the effects of five polymethoxyflavones, two isoflavones, and one flavanol on CD11c+ dendritic cell function. Methods: CD11c+ dendritic cells were differentiated from bone marrow cells by culturing with granulocyte macrophage-colony stimulating factor. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The Ag-presenting ability was determined by a mixed lymphocyte reaction assay. Expressions of MHC class II, CD40, CD80, and CD86 molecules on CD11c+ cells were determined by flow cytometric analysis. Lipopolysaccharide-induced inflammatory cytokines productions were determined by enzyme-linked immunosorbent assay. Results: The flavonoids used in the study did not show strong toxicity to CD11c+ cells. Nobiletin, heptamethoxyflavone, and genistein enhance Ag-presenting function. Nobiletin and heptamethoxyflavone increased the expression of MHC class II and CD80 molecules. A direct correlation between APC function and lipopolysaccharide-induced cytokine production was not found. Conclusions: The results of the in vitro study indicate that flavonoids, nobiletin, heptamethoxyflavone, and genistein regulate innate dendritic cell function. Original Article Thu, 30 May 2024 00:00:00 GMT YukoTanaka, AkikoNakamoto, HarukaOhashi, MarikoNakamoto, TohruSakai, Thu, 30 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003144 https://www.explorationpub.com/Journals/ei/Article/1003145 Aim: The clinical symptoms of autoantibody (AAb)-mediated autoimmune diseases (AID) usually correlate with the AAb-titer. Immunoglobulins (Igs) of the IgG type are actively recycled by the neonatal crystallizable fragment receptor (FcRn). The most common Ig type of AAb is IgG. This explorative study evaluates the safety and tolerability of a fully human anti-FcRn monoclonal antibody (mAb) in patients with thyroid autoimmunity (TA). Methods: Adverse events (AEs) and serious AEs (SAEs) were documented and coded according to the standardized Medical Dictionary for Regulatory Activities (MedDRA). AEs were followed up, and seriousness, as defined by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)-guideline E6, was documented. All AEs were analyzed for a possible underlying cause, and if not identified, were graded as side effects (SEs). Additionally, safety-relevant serological parameters (liver function and blood cell counts) were evaluated. Furthermore, laboratory parameters influenced by other anti-FcRn agents in clinical studies were considered. Results: Of 31 patients with TA, 19 were administered the anti-FcRn mAb subcutaneously once weekly for 12 weeks, while 12 were on placebo. Compared to placebo, there was no increased occurrence of AE and/or SE in the mAb group. mAb treatment increased total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol. A mAb treatment-induced transient decrease in serum albumin strongly correlated with an increase in total cholesterol (r = –0.893, P = 0.012). Overall compared to placebo, there were no significant changes in blood cell counts, complement factors, or liver enzymes. Serological changes were transient and spontaneously normalized after treatment completion. Two SAEs were deemed no-drug induced (dysthyroid optic neuropathy and a post-COVID infection associated autoimmune encephalomyelitis). Conclusions: The anti-FcRn mAb is a safe and well-tolerated therapy for AAb-mediated AID. Original Article Thu, 20 Jun 2024 00:00:00 GMT JanWolf, IreneKrämer, George J.Kahaly, Thu, 20 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003145 https://www.explorationpub.com/Journals/ei/Article/1003146 Rheumatoid arthritis (RA) is a complex autoimmune disorder characterized by a spectrum of hypersensitivity reactions, encompassing Type II, Type III, and Type IV responses. Firstly, RA is marked by Type II hypersensitivity reactions driven by autoantibodies, such as rheumatoid factor (RF) and anti-(cyclic) citrullinated protein antibodies (ACPAs). These autoantibodies serve not only as serological markers for RA but also actively participate in inflammation, bone erosion, and clinical outcomes, with concurrent activation of the complement system involving C1q, C3, and C5 components specifically linked to RA progression and bone damage. Secondly, RA exhibits traits of Type III hypersensitivity, marked by the formation of immune complexes inciting inflammatory reactions. Immunoglobulin G (IgG) autoantibodies like RF and ACPA play pivotal roles in immune complex formation and the ensuing inflammatory responses. RA also demonstrates Type IV hypersensitivity propelled by CD4+ T cells, encompassing T helper 1 (Th1) and Th17 subsets. Th1 cells release interferon (IFN)-γ, promoting proinflammatory cytokines, while Th17 cells secrete IL-17, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF), contributing to synovial inflammation, bone and cartilage damage, and angiogenesis. RA concurrently exhibits features of Type II, Type III, and Type IV hypersensitivity. It is crucial to comprehend the presence and complex interplay of hypersensitivity responses and specific immune cell subsets in RA to create precise and efficient therapeutic approaches for the management of this incapacitating autoimmune condition. Thus, in this review, we aim to provide a comprehensive overview of the hypersensitivity features of RA. Review Fri, 21 Jun 2024 00:00:00 GMT JihyeHeo, SoohyunHeo, Joo RiKang, JooyoungKweon, YeonwooLee, Jea-HyunBaek, Fri, 21 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003146 https://www.explorationpub.com/Journals/ei/Article/1003147 Aim: Severe dengue is correlated with a decrease in the circulating complement regulator, factor H (FH) and prior work has shown that dengue virus (DENV) infection induces FH mRNA but not FH protein release. Here, the mechanisms of this phenomenon were defined. Methods: HEK293 cells were infected with DENV-2 and changes in FH mRNA and protein were analyzed by real time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and fluorescent microscopy. Additionally, cells were stimulated with size fractionated supernatants from DENV-infected cells, supernatant containing DENV non-structural protein-1 (NS1) without virus particles, and infections performed with or without the toll-like receptor-4 (TLR4) antagonist, TAK-242. Mass spectrometry was used to define the protein content of the fractionated supernatant, and treatment of cells with sialidase or heparinase was used to define cell-associated FH protein. Results: DENV-infection induced full-length FH mRNA and cell-associated FH protein. Microscopy demonstrated membrane and intracellular-associated FH with a cytoskeletal and perinuclear localisation, in both DENV positive and uninfected neighboring bystander cells. Fractionation of cultured supernatant from DENV-infected cells demonstrated that secreted factors > 50 (kilodaltons) kDa induced FH mRNA and this could be blocked with TAK-242 but was not simulated by the TLR4 agonist, DENV NS1. Mass spectrometry detected DENV envelope, membrane and NS1, complement component 5 (C5), and complement FB, and indicated a > 20-fold increase in C4, inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), and alpha-2-macroglobulin in the > 50 kDa fraction from DENV-infected compared with conditioned media from uninfected cells. Sialic acid levels were unchanged and cleavage did not affect release of FH from DENV-infected compared to uninfected cells. In contrast, sulphated glycosaminoglycans (GAGs) were reduced in the cultured supernatant and cell lysates following DENV-infection, and heparinase cleavage released significantly more FH from DENV-compared with uninfected cells. Conclusions: Following DENV-infection, secreted molecules induce FH that remains intracellular and with increased binding to cell surface heparan sulphate. The mediators of induction of FH mRNA act in trans and via TLR4 but this is not likely to be via DENV NS1. The retention of FH in the local environment of the infected cell could benefit the virus by negating local complement killing of cells, and/or benefit the host by inhibition of heparan sulphate-mediated DENV infection to restrict viral spread. Original Article Mon, 24 Jun 2024 00:00:00 GMT Joshua G.Dubowsky, BinoyAppukuttan, EvangelineCowell, ValeriaSanders, David L.Gordon, Jillian M.Carr, Mon, 24 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003147 https://www.explorationpub.com/Journals/ei/Article/1003148 The skin, as the first physical barrier for invading pathogens, also serves as an immunologically active organ. Breaching the skin barrier is thus essential for pathogens to enter the body. The skin contains various immune responsive cells that initiate both the innate and adaptive immune response upon invasion. Activated immune cells help to regulate cytokine response and their differentiation to promote or suppress the crucial immune response against invading pathogens. Human herpes simplex viruses (HHSVs) are the oldest pathogen that can escape immune surveillance of the human host by a well-developed escape mechanism within ganglia, as their evolutionary strategy. In primary infection, a non-specific defense of the host initiates the response against the invading virion. The initial direct antiviral action of the host is regulated by activated macrophages, via the release of cytokines like tumor necrosis factor (TNF), and type-1 interferon (IFN-1). The host-derived cytokines including IFN-12, TNF, and IFN-1 in turn induce natural killer (NK) cells to release IFN-γ. Their positive feedback with synergistic interactions collectively releases nitric oxide (NO) and reactive oxygen species (ROS) against the invading virus. Simultaneously, the combination of cytokines, macrophages, and other cells activates the immune system to eliminate the pathogen. However, the virus has also evolved various mechanisms to counter the host defense strategies. This review will highlight virus-mediated skin infections, especially by HSV, and portray a detailed role of virus-induced cytokines in host-immunity to challenge the invading virion during mucocutaneous HSV infection. Further, this review will discuss the viral-interference on host defense to provide a simplistic overview of the complications of cutaneous HSV infection. Review Mon, 01 Jul 2024 00:00:00 GMT AparnaMukhopadhyay, SubhashisIndra, JoyetaGhosh, SaptarshiBiswas, ParthaPalit, DebprasadChattopadhyay, Mon, 01 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003148 https://www.explorationpub.com/Journals/ei/Article/1003149 Aim: This article presents an investigation into various mathematical models for cell population growth, including tumor cells, and their dynamics. Methods: We classify the models into five categories: exponential, logistic, time-tested, heterogeneous, and immunology. Mathematical modeling provides insights into the development of tumors over time and how their proliferation rate becomes more dangerous. To explore the impact of immune response on tumor heterogeneity, we develop a reaction-diffusion model of tumor growth that incorporates tumor-immune interactions and a mechanism for tumor mutation and clonal expansion. We use numerical simulations to investigate how variation in immune response affects tumor heterogeneity. Results: Our findings show that a stronger immune response leads to greater homogeneity in the tumor population, which suggests that enhancing immune response could reduce tumor heterogeneity and improve treatment outcomes. Conclusions: These results have important implications for the development of therapeutic strategies targeting the immune system to combat tumor heterogeneity. Original Article Thu, 18 Jul 2024 00:00:00 GMT DikshaGautam, SanjeevKumar, RashmiSharma, DeepshikhaDixit, Thu, 18 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003149 https://www.explorationpub.com/Journals/ei/Article/1003151 The control of the immune system, neuroendocrine system, and energy metabolism is essential for the physiological process of male reproduction. The hypothalamic-pituitary-testicular (HPT) axis regulates the generation of gonadal steroid hormones in the testes, which in turn controls spermatogenesis. For the growth and maturation of germ cells, the immune cells and cytokines in the testes offer a safe microenvironment. The cellular reactions and metabolic activities in the testes produce energy and biosynthetic precursors that control the growth of germ cells, as well as testicular immunology and inflammation. Both inflammatory and anti-inflammatory responses depend on immune cell metabolism, which is thought to influence testicular spermatogenesis. The significance of immunometabolism in male reproduction will be underlined in this review. Review Mon, 05 Aug 2024 00:00:00 GMT PrityYadav, Pratap ChandMali, Mon, 05 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003151 https://www.explorationpub.com/Journals/ei/Article/1003150 Aim: Currently, malignant diseases represent a health issue worldwide. Among these, lung cancer is of growing importance, due to its high incidence and mortality. Chemotherapy, one of the most frequently used treatments, has shown its ability to induce accelerated immunosenescence in classic and as well non-classic lymphocyte compartments, being less described in the latter. The immune restoration strategies have demonstrated their ability to reverse immunosenescence and exhaustion markers in conventional lymphocyte subpopulations after chemotherapy. However, the possible immunorestorative effect on non-classical lymphocytes has not been widely reported. The aim of this study was to evaluate the effect of chemotherapy and the administration of a thymic polypeptide factor on non-classical lymphocyte populations in patients with advanced lung cancer. Methods: Eighteen patients with advanced lung cancer, were evaluated at baseline before and after platinum-based chemotherapy (4–6 cycles). All patients could complete treatment with a thymic polypeptide factor [Biomodulina T (BT)] at the end of chemotherapy. Blood from patients was collected by venipuncture in heparinized tubes before and after chemotherapy and at the end of BT treatment to analyze the frequencies of non-classical immune subpopulations by flow cytometry. Results: Natural killer (NK), natural killer T cells (NKT), and double-positive T lymphocyte (DPT) proportions reached normal values in patients diagnosed with advanced lung cancer before receiving cytotoxic treatment. Chemotherapy did not induce modifications in the total percent of NK, NKT, and DPT populations in these patients. However, the administration of BT decreased DPTs and NK cells expressing the cluster of differentiation (CD)57 molecule, which is considered a marker of immunosenescence. Conclusions: These results suggest a lower influence of platinum-based chemotherapy on non-classical lymphocytes and the potential to generate a reconstitution of lymphocyte subpopulations in patients with advanced lung cancer by using the thymic factor BT, which reveals a new possibility for improving the response to cancer immunotherapies [Cuban Public Registry of Clinical Trial (RPCEC, https://rpcec.sld.cu/en/trials/RPCEC00000358-En) identifier: RPCEC00000358]. Original Article Mon, 05 Aug 2024 00:00:00 GMT Gisela MaríaSuárez, MauricioCatalá, YadiraPeña, SusanaPortela, Ana LauraAñé-Kourí, AmnelyGonzález, PatriciaLorenzo-Luaces, ManuelDíaz, María de los A.Molina, KarlaPereira, Jenysbel de la C.Hernández, Mary CarmenReyes, NurisLedón, ZaimaMazorra, TaniaCrombet, AgustinLage, AntonioBencomo-Hernandez, DanaySaavedra, Mon, 05 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003150 https://www.explorationpub.com/Journals/ei/Article/1003152 The reproductive axis of male mammals implies a coordinated interaction of its three components: a population of gonadotropin-releasing hormone (GnRH)—producing neurons of the hypothalamus, gonadotropic cells of the adenohypophysis, and most distally located testes that produce male sex hormone (testosterone) and germ cells (spermatozoa). It is generally believed that for the accurate and constant realization of reproductive function, the testes must be isolated from the internal environment of the whole organism with the help of a hematotesticular barrier. The internal immune system of the testes is primarily represented by testicular macrophages. They are located primarily in the peritubular space and provide the physical organization of peritubular myoid cells into niche-like clusters that can form an environment conducive to the differentiation of spermatogonia A1 in sperm cells. The development of this complex system occurs in mammals over a long period and is determined by the timely synchronization of all its parts. Maternal immune activation (MIA) is associated with the powerful production of proinflammatory cytokines in the mother’s body and further in the placenta and fetal region. Many of these cytokines have a pleiotropic effect and act as morphogenetic factors. Thus, cytokines can influence the development of testes even in the prenatal period. The review is focused on the effect of MIA on testicular development during prenatal state and on the holistic nature of the development of the reproductive axis of mammals on the example of laboratory rodents. Laboratory rodents (especially mice) are often used to develop models of the development of certain human systems and are the generally accepted standard for the introduction of these models into medical practice. Review Wed, 07 Aug 2024 00:00:00 GMT MarinaIzvolskaya, Wed, 07 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003152 https://www.explorationpub.com/Journals/ei/Article/1003153 Interleukin-6 (IL-6) plays a critical role in the pathogenesis of various chronic inflammatory diseases, tracked across numerous fields of research. Despite this, a crucial aspect often overlooked in studies is the differentiation between IL-6 classic-signaling and trans-signaling, leading to potential confounding of their findings; less than half of selected IL-6 studies included differentiation. This review delves into the distinction between IL-6 classic- and trans-signaling and their role in chronic inflammatory diseases and endometriosis. The unique pro-inflammatory nature of IL-6 trans-signaling, contrasted with the anti-inflammatory character of IL-6 classic-signaling, presents significant implications for research methodology, particularly in studies investigating anti-inflammatory interventions or interleukin inhibitors. Diagnostic failure to account for these distinct pathways may inadvertently misrepresent beneficial immune responses or the efficacy of interventions, posing significant challenges in predicting health outcomes. Interventions that do not differentiate these pathways could face reduced efficacy or safety. This review proposes adjustments to research methodologies and stresses the importance of careful interpretation of inflammatory markers in IL-6-related research. Examples of differentiation issues are discussed across the topics of endometriosis and multiple inflammatory diseases. By addressing this methodological issue, researchers could potentially improve patient outcomes, enhance the efficacy of interventions, and contribute to public health advancements. Review Tue, 20 Aug 2024 00:00:00 GMT Ryan D.Castle, Tue, 20 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003153 https://www.explorationpub.com/Journals/ei/Article/1003154 The male reproductive immune system plays a pivotal role in safeguarding sperm from immune attacks and preventing the incursion of foreign pathogens. Nucleotide-binding and oligomerization domain-like receptors (NOD-like receptors, NLRs) family protein domain containing 3 (NLRP3) is a cytoplasmic sensor binding to the inflammasome and critically involved in inducing innate immunity in the testes. It also has a substantial impact on male reproductive immunity, which is closely associated with male infertility stemming from disorders related to the male reproductive immune system. This review introduces the distinct characteristics of the NLR family, elucidates the activation pathways and factors of NLRP3 inflammasomes, and discusses how they participate in male reproductive immune diseases such as bacterial orchitis, autoimmune orchitis, varicocele, and epididymitis. In bacterial orchitis, elevated levels of NLRP3 inflammasomes exacerbate the testicular inflammatory injury and lead to decreased testosterone, thus contributing to male infertility. In autoimmune orchitis, the NLRP3 inflammasomes inhibit testosterone synthesis by decreasing the expression of cytochrome P450, thereby impacting male reproductive function. Therefore, targeting NLRP3 could offer novel immunological strategies for the clinical treatment of male infertility. Review Thu, 22 Aug 2024 00:00:00 GMT XueZhang, XinyiDong, YafeiKang, XiaohangLiu, ChengchangZhang, JiaxinZhang, ShutingChen, DonghuiHuang, Thu, 22 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003154 https://www.explorationpub.com/Journals/ei/Article/1003156 Our immune system acts to protect us in times of stress and traumatic injury. As part of the immune response, the body produces various cytokines, which mediate or modulate immune functions. Such cytokines include tumor necrosis factor (TNF) and interleukin 6 (IL-6) and IL-17. These cytokines can also act on the nervous system to influence pain perception. TNF-α triggers an inflammatory response and two forms of programmed cell death, apoptosis and necroptosis, depending on the pathological state. For individuals with chronic conditions relating to immune deficiency, the actions of these cytokines can present as chronic pain states, significantly altering quality of life. One attractive potential solution for treating this immune linked pain is by altering signaling pathways of pain-enhancing cytokines. Infliximab and etanercept are TNF inhibitors that are currently on the market for use in the treatment of chronic pain. Secukinumab and tocilizumab serve as IL inhibitors, utilized for a similar purpose. These novel immunotherapies have shown efficacy in numerous clinical studies with acceptable side effect profiles. In this review, we summarize the pharmacological profiles of these drugs and discuss their usage in treating chronic pain. Mini Review Wed, 28 Aug 2024 00:00:00 GMT Rucha A.Kelkar, Alan D.Kaye, Dominique M.Perilloux, Alison M.Hawkins, Grace C.Wester, Amanda R.Ragland, Sage V.Hebert, SaharShekoohi, GiustinoVarrassi, Wed, 28 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003156 https://www.explorationpub.com/Journals/ei/Article/1003157 Diabetic wound healing presents a unique and complex challenge due to the impaired cellular and molecular functions associated with diabetes. Chronic wounds in diabetic patients are characterized by prolonged inflammation, reduced angiogenesis, and impaired collagen deposition, which significantly hinder the healing process. This comprehensive review focuses on the innovative applications of designer cytokines in precision therapy for diabetic wound healing, emphasizing the remarkable advancements made in overcoming the limitations of natural cytokines, such as their short half-life, potential cytotoxicity, and lack of specificity. We begin by detailing the intricate biological characteristics of diabetic wounds and the essential role that cytokines play in orchestrating the healing process. The review critically examines the constraints of natural cytokines and traces the evolution of synthetic alternatives, with a particular emphasis on peptide-based and nucleic acid-based artificial cytokines. Advanced strategies for designing these artificial cytokines are discussed, including molecular modifications, functional enhancements, and specificity improvements to better target pathological conditions in diabetic wounds. Furthermore, we explore the utilization of synthetic biology techniques to engineer effective cytokine-based therapies. The promising therapeutic potential of rationally designed cytokines is highlighted, showcasing their ability to modulate the wound microenvironment, enhance tissue regeneration, and reduce chronic inflammation. This review not only provides valuable perspectives on the future research directions but also offers insights into the potential clinical applications of these innovative therapies, aiming to significantly improve the outcomes for patients suffering from diabetic wounds. Review Thu, 29 Aug 2024 00:00:00 GMT XinxinZhang, TingtingWang, XiangqingFan, TianzeZhang, RuiQiu, YuqiWu, MeixiaWang, YizhiZhang, MengLi, NaCai, YingGuan, Hong-HuiWang, Thu, 29 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003157 https://www.explorationpub.com/Journals/ei/Article/1003155 Keratinocytes play an integral role in the human epidermis, serving as a barrier between the internal and external environment. They are immune-competent cells involved in both innate and adaptive cutaneous immune responses, crucial for maintaining skin integrity. Keratinocytes are essential for epidermal repair, facilitating proliferation and re-epithelialization following injury. They secrete pro-inflammatory markers such as cytokines and chemokines, which promote the recruitment of inflammatory cells like polymorphs and macrophages to the site of skin injury. The immune response mediated by keratinocytes involves signaling molecules like tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6. Langerhans cells respond to factors secreted by keratinocytes, migrating towards draining lymph nodes to activate T cells and initiate an adaptive immune response. Additionally, keratinocytes express Toll-like receptors (TLRs), enabling them to detect molecular patterns of pathogens. Recent studies have focused on understanding these interactions of keratinocytes to develop therapeutic strategies for managing various skin diseases. Genetic defects in keratinocytes underlie conditions like psoriasis. We also discuss the role of keratinocytes and the effect of neuro-endocrinal signaling and interventions, associated corticosteroidogenic pathways, and response to UV radiations to maintain a state of homeostasis. This article underlines and improves our understanding of the immune function of keratinocytes, which is crucial for developing more effective therapies against skin diseases. Review Wed, 28 Aug 2024 00:00:00 GMT Rakesh KumarGupta, PoonamWasnik, DeepankarMondal, DhananjayShukla, Wed, 28 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003155 https://www.explorationpub.com/Journals/ei/Article/1003158 Not applicable. Editorial Mon, 02 Sep 2024 00:00:00 GMT CalogeroCaruso, Mon, 02 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003158 https://www.explorationpub.com/Journals/ei/Article/1003159 Aim: Testing the feasibility of the determination to what extent the inability to repair DNA lesions in xeroderma pigmentosum (XP) patients, contributes to the alteration of immune responses, in the course of skin carcinogenesis. Methods: Serum samples from 11 (five XP, six non-XP) bearing skin carcinomas and from three healthy donors, were available for the quantification of IL-2, IL-4, IL-10, IFN‐γ and TNF-α cytokines concentrations. We used kits for ELISA test, by a non-competitive sandwich method. Statistical analysis of the results was performed, using non-parametric Mann-Whitney U test, with an accuracy of 5%. Results: Our results showed that the majority of XP and non-XP cancer patients showed a significant increase in the secretion of TNF-α cytokine above healthy individuals (controls). TNF-α was also found to be significantly high in the serum of XP patients above that reported for the studied non-XP cancer patients. At the same time, TNF-α was not detected in the serum of non-XP and of healthy controls. This increase in the expression level of TNF-α was statistically significant between XP and non-XP patients, and between XP patients and controls. In contrast, there were no significant differences between XP patients and healthy controls, as well as between XP and non-XP patients, for the level of serum IL-2, IL-4 and IL-10 cytokines. On the other hand, we found no detectable levels of IFN‐γ cytokine in the serum of all the studied subgroups. Conclusions: In this study, we demonstrate a general tendency to secrete inflammatory cytokines, in the cancerous groups of patients (XP and non-XP), in comparison to healthy controls, while a significantly higher propensity to develop inflammation, in XP than in non-XP cancer patients. Original Article Wed, 04 Sep 2024 00:00:00 GMT KalthoumAbid, JiheneBettaieb, FaouziEl Mezni, HamoudaBoussen, Wed, 04 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003159 https://www.explorationpub.com/Journals/ei/Article/1003160 Type I diabetes susceptibility is caused by both environmental and genetic factors, the latter comprising approximately half of the total risk as evidenced by the fact that identical twins have approximately 50% concordance, suggesting 50% of the disease risk is environmental. The human leukocyte antigen (HLA) genes account for approximately half of the genetic risk, as demonstrated by the concordance between HLA identical siblings. Because environmental and genetic differences vary between racial groups, the incidence of type 1 diabetes (TID) differs across the world, being highest in Caucasians. Recent GWAS (genome-wide association studies) studies have suggested there may be up to 50 genomic regions contributing to the non-major histocompatibility complex (MHC) genetic risk contribution. This review presents and discusses the latest research on the MHC and non-MHC genes. Only the non-MHC regions, which have been confirmed in multiple studies and which are considered definite regions of genetic susceptibility, are included in the review. Review Wed, 25 Sep 2024 00:00:00 GMT Brian D.Tait, Wed, 25 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003160 https://www.explorationpub.com/Journals/ei/Article/1003162 Autoimmune diseases result from the immune system’s response to autoantigen components, leading to damage to one’s own tissues and organs. The correlation between long noncoding RNAs (lncRNAs) and autoimmune diseases remains inconclusive. However, recent studies have revealed that the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a vital role in the development of various autoimmune diseases. Here, this review briefly summarizes the progress in understanding NEAT1 expression variations and related mechanisms in different autoimmune diseases, and discusses its potential use for future therapeutic applications. Mini Review Fri, 18 Oct 2024 00:00:00 GMT ChengBao, Li-LiTian, Xiao-LiuLi, MinXu, Hong-WeiChen, Fri, 18 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003162 https://www.explorationpub.com/Journals/ei/Article/1003163 Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease associated with cholangiopathies. The detection of antimitochondrial autoantibodies (AMAs) plays an important role in the diagnosis of classical PBC. AMAs are formed against the antigenic component associated with the dihydrolipoyl transacetylase of pyruvate dehydrogenase complex (E2 PDC) localized on the inner membrane of mitochondria. The loss of immune tolerance of E2 PDC in PBC is thought to be the cause of the mechanism of AMA formation and immune-mediated destruction of biliary epithelial cells (BECs) of the small- and medium-sized intrahepatic bile ducts. E2 PDC is not only present in BECs, but is also abundant in the mitochondria of all nucleated cells. The question remains as to why E2 PDC of only small BECs is the target of autoimmune attack. There is no evidence that AMAs have a deleterious effect on BECs. New scientific data has emerged that explains the damage to BECs in PBC by the defect of the biliary bicarbonate (HCO3–) “umbrella” that protects BECs from the detergent action of bile acids under physiological conditions. Disruption of HCO3– production by BECs in PBC leads to changes in the pH of hepatic bile, accompanied by accumulation of bile acids in the small BECs. The detergent action of bile acids leads to damage of membrane structures of BECs and their apoptosis, development of ductulopenia, and intrahepatic cholestasis. For the first time, it has been suggested that under the influence of bile acids, the E2 PDC antigen may undergo conformational changes that alter its immunological properties. E2 PDC becomes a neoantigen that is recognized by the normal (“healthy”) immune system as a foreign antigen, leading to the production of AMAs. For the first time, the authors of this review provide an explanation for why only small BECs are damaged in PBC. Review Fri, 18 Oct 2024 00:00:00 GMT Vasiliy IvanovichReshetnyak, Igor VeniaminovichMaev, Fri, 18 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003163 https://www.explorationpub.com/Journals/ei/Article/1003164 The impaired function of regulatory T (Treg) cells and the imbalance of Treg/Th17 cells play a central role in developing autoimmune diseases such as systemic lupus erythematosus (SLE). Treg cells are crucial for maintaining immune homeostasis and tolerance to self-antigens. One of the most important transcription factors that regulate the differentiation and function of Treg cells is the FOXP3 protein. Aberrant epigenetic modifications affecting FOXP3 gene expression and consequently dysregulated function of Treg cells have been implicated in the pathogenesis of SLE. Therefore, understanding the intricate interplay between FOXP3 expression pattern in Treg cells and epigenetic regulatory mechanisms (e.g., DNA methylation, histone modifications and non-coding RNAs such as microRNAs and long non-coding RNAs) is crucial for unravelling the underlying mechanisms of SLE. Moreover, targeting these epigenetic pathways may offer novel therapeutic strategies for restoring immune balance and ameliorating autoimmune pathology. This review report aimed to provide an update on the epigenetic controlling of FOXP3 gene expression in SLE disease. Review Mon, 21 Oct 2024 00:00:00 GMT ParnianFakour, AtaShirizadeh, AhmadTahamoli-Roudsari, GhasemSolgi, Mon, 21 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003164 https://www.explorationpub.com/Journals/ei/Article/1003165 Primary biliary cholangitis (PBC) is a rare immune-mediated disease, commonly affecting women in their 40s, and ultimately progressing to liver failure. The incidence and prevalence of the disease are increasing worldwide, possibly due to better diagnostic tools. This review will focus on its epidemiology, pathophysiology, diagnosis, prognosis, and new developments in therapy. Review Wed, 30 Oct 2024 00:00:00 GMT Mohamed Bassyouny AboueleininElnaggar, IsmailElkhattib, Ahmed Abdelsatar AliAbomhya, James LorenzenBoyer, Wed, 30 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003165 https://www.explorationpub.com/Journals/ei/Article/1003166 Aim: Assessing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies among healthcare workers (HCWs) is crucial in understanding the durability of humoral immune response due to vaccination and the post-pandemic era. Therefore, this study aimed to evaluate IgG antibody seroprevalence, IgG levels, and long-term durability responses after the coronavirus disease 2019 (COVID-19) pandemic in HCWs. Methods: The cross-sectional study recruited HCWs aged ≥ 18 years, vaccinated at least once, and without autoimmune diseases at Dr. Wahidin Sudirohusodo Hospital Makassar. Antibody titers against spike protein, nucleocapsid protein, and spike-nucleocapsid conjugate were quantified using dried blood spot (DBS) samples and multi-antigen profiling (xMAP) technology to measure seroprevalence. Results: The results showed that there was a total of 103 participants with the majority being female (59.22%), ≤ 40-year-old (87.38%), nurses (56.31%), had no comorbidities (88.35%), and were infected with COVID-19 (70.87%). A significant proportion received three times vaccination (76.7%), while 102 of 103 (99.03%) showed seropositivity. IgG showed the highest mean antibody titers for spike protein [10,819.38 ± 2,554.23 mean fluorescence intensity (MFI)] in the first 6–12 months after the last vaccinations. Meanwhile, the IgG titer (MFI) showed a long duration over 30 months. Vaccine significantly influenced spike protein antibody levels, with the highest observed in the group receiving a combination of two inactivated vaccines followed by two messenger ribonucleic acid (mRNA) vaccines (p < 0.05). Conclusions: HCWs showed a sustained humoral immune response to SARS-CoV-2 for over 24 months post-vaccination. The type and combination of vaccines administered were significantly correlated with the IgG antibody levels, suggesting the long-term efficacy of the vaccination regimens. The application of DBS and xMAP technology in the study facilitated the assessment of SARS-CoV-2 IgG responses, offering valuable insights into the dynamics of immune persistence following vaccination. Original Article Wed, 30 Oct 2024 00:00:00 GMT ImamNurjaya, ErwinArief, Nur AhmadTabri, IrawatyDjaharuddin, BulkisNatsir, SittiNurisyah, JokoHendarto, AnsariadiAnsariadi, RasihaRasiha, Moh. Anfasa GiffariMakkaraka, Wed, 30 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003166 https://www.explorationpub.com/Journals/ei/Article/1003171 Immunotherapy, a primary anti-neoplastic treatment, exploits the patient’s immune system to kill neoplastic cells by modulating immune checkpoints such as cytotoxic T-lymphocyte antigen 4 and programmed cell death 1. Despite an apparent anti-neoplastic efficacy, immunotherapeutic agents are often accompanied by multiorgan toxicity, including gastrointestinal ones. This particular class of immunotherapy-related adverse events, mainly represented by diarrhea and colitis, necessitates a nuanced treatment strategy. Current treatments are primarily based on standardized severity grading systems to guide and proportion therapeutic interventions, ranging from simple behavioral modifications or conventional molecules (such as anti-diarrheal) to advanced biological treatments. Tofacitinib, a pan-Janus kinase inhibitor, emerged as a potential option for managing immune-related (IR) colitis by targeting hyperactivated T cells within the colic microenvironment. However, evidence supporting the use of tofacitinib in IR colitis is primarily derived from case reports and small case series, lacking robust randomized clinical trial data. While preliminary findings demonstrate encouraging clinical control of IR colitis with tofacitinib, further research is warranted to elucidate its efficacy, safety, optimal dosage, and treatment duration. Although there are some worries about its effects on cancer response and safety, current evidence indicates that tofacitinib could be seen as a possible treatment choice if other therapies with more robust evidence profiles have not been successful. Review Fri, 22 Nov 2024 00:00:00 GMT RaffaelePellegrino, GiovannaPalladino, GiuseppeImperio, Antonietta GerardaGravina, Fri, 22 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003171 https://www.explorationpub.com/Journals/ei/Article/1003172 The tripartite network, including the nervous, immune, and endocrine systems, plays a significant role in regulatory and effector processes in the male body. On the one hand, males perform their reproduction function by generating spermatozoa in conditions of self-tolerance maintenance because most spermatozoa antigens (“sequestrated antigens”) are unknown to the immune system. On the other hand, in everyday life, a male body encounters hostile external infections, some of which colonize the skin and barrier surfaces and present a cancer threat to male genital tracts. This is human papillomavirus (HPV), the “silent killer”. Therefore, the male immune system has to function in a contradictory situation using either active immune responses, self-tolerance mechanisms, or both simultaneously. This review focused on the functional organization of the male immune system, including its coordination with the nervous and endocrine systems, and immune processes at the level of the whole organism, as well as on obvious changes, which have currently happened. The male immune system should function in conditions of the strong influence of testosterone and biosocial impulses coming from the nervous system. In the last century, researchers obtained data showing a decrease in the male reproduction function because of a stable negative dynamic of spermatozoa count and quality. Nowadays, depressing statistical indicators of male fertility have been published. 15% of couples are unable to conceive a child, where 50% of the causes of infertility relate to males, and up to 15% of male infertility cases are due to immunological disorders. It can be assumed that the male immune system starts to function when self-tolerance is partially lost, and the previous balance has been destroyed. Furthermore, sperm allergy has become a new topic in male immunology. Review Thu, 28 Nov 2024 00:00:00 GMT VladimirKlimov, AndrewKlimov, Thu, 28 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003172 https://www.explorationpub.com/Journals/ei/Article/1003173 Aim: Hashimoto’s thyroiditis is a polygenic auto-immune disease with a complex etiopathogenesis. It is more common in females. An imbalance between pro-inflammatory and anti-inflammatory cytokines may play an important role in the disease pathogenesis. Numerous studies have been conducted to find an association between genetic polymorphisms and the development of Hashimoto’s thyroiditis. In this context, we proposed to study the impact of the interleukin-6 (IL-6) gene polymorphism (rs1800795) on the genetic susceptibility to Hashimoto’s thyroiditis. Methods: Polymorphism in IL-6 gene (rs1800795) was assessed in a case-control study involving a population of Western Algeria with 81 Hashimoto’s thyroiditis patients and 211 unrelated healthy subjects, matched in age and sex. The DNA was extracted by a magnetic bead-based technique. The genetic study was performed by molecular biology: real-time PCR using TaqMan single nucleotide polymorphism (SNP) genotyping assay with Applied Biosystems 7500 device. Results: Results showed that the GG and GC genotypic distribution is similar between patient and control groups with a higher frequency of the GG genotype (80.25% in patients and 78.67% in controls vs. 19.75% of patients and 20.38% of controls with the GC genotype). The CC genotype is absent in patients and present in only 02/211 healthy subjects. The frequency of the polymorphic G allele was similar in the two groups, with 90.1% and 88.8% in patients and controls respectively (P > 0.05). Conclusions: This study reports no significant difference in IL-6 (-174 G/C) gene polymorphism at the allelic or the genotypic level between Hashimoto’s patients and the control group (P > 0.05). No association between the SNP IL-6 rs1800795 and susceptibility to Hashimoto’s thyroiditis in Western Algerian population. Original Article Tue, 03 Dec 2024 00:00:00 GMT NawalLabiad, MoussaMessatfa, YoucefBouali-Youcef, HouriaKadiri, NardjessOuikhlef, Tue, 03 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003173 https://www.explorationpub.com/Journals/ei/Article/1003174 Cancer-related pain represents one of the most common complaints of cancer patients especially for those with advanced-stage of disease and/or bone metastases. More effective therapeutic strategies are needed not only to improve the survival of cancer patients but also to relieve cancer-related pain. In the last decade, immune checkpoint inhibitor (ICI)-based immunotherapy targeting programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) has revolutionized cancer care. Beyond its anticancer role, PD-1/PD-L1 axis pathway is involved in many other physiological processes. PD-L1 expression is found in both malignant tissues and normal tissues including the dorsal root ganglion, and spinal cord. Through its interaction with PD-1, PD-L1 can modulate neuron excitability, leading to the suppression of inflammatory, neuropathic, and bone cancer pain. Therefore, since the intricate relationship between immunotherapy and pain should be largely dissected, this comprehensive review explores the complex relationship between PD-1/PD-L1-based immunotherapy and cancer-related pain. It delves into the potential mechanisms through which PD-1/PD-L1 immunotherapy might modulate pain pathways, including neuroinflammation, neuromodulation, opioid mechanisms, and bone processes. Understanding these mechanisms is crucial for developing future research directions in order to optimize pain management strategies in cancer patients. Finally, this article discusses the role of artificial intelligence (AI) in advancing research and clinical practice in this context. AI-based strategies, such as analyzing large datasets and creating predictive models, can identify patterns and correlations between PD-1/PD-L1 immunotherapy and pain. These tools can assist healthcare providers in tailoring treatment plans and pain management strategies to individual patients, ultimately improving outcomes and quality of life for those undergoing PD-1/PD-L1-based immunotherapy. Review Wed, 04 Dec 2024 00:00:00 GMT MarcoCascella, BrigidaMiranda, CarmenGagliardi, LuciaSantaniello, MilenaMottola, AlidaMancusi, LauraFerrara, FedericaMonaco, FrancescaGargano, FrancescoPerri, AlessandroOttaiano, MaurizioCapuozzo, OrnellaPiazza, StefanoPepe, AnnaCrispo, AgostinoGuida, GiovanniSalzano, GiustinoVarrassi, LuigiLiguori, FrancescoSabbatino, , Wed, 04 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003174 https://www.explorationpub.com/Journals/ei/Article/1003175 Aim: The immune system can experience temporary suppression following acute or prolonged strenuous exercise, potentially increasing susceptibility to infections. Young athletes, who must balance school, training, studies, and social life, may further disrupt their immune-inflammatory responses. This study aimed to investigate the effects of an 8-week pre-season training on circulating leukocyte responses in well-trained adolescent soccer-players at different stages of puberty. Methods: Thirty-six soccer players, divided into two groups based on their biological age-under sixteen (U16) and above sixteen (A16)-underwent two rounds of assessments. These included evaluations of anthropometrics, physical fitness, and immune parameters before and after an 8-week pre-season soccer training program. Results: No significant treatment or interaction effects were found for erythrocyte sedimentation rate (ESR), platelets, total leucocyte count, immune inflammation markers (IIM), weekly rating of perceived exertion, body composition, sit-and-reach flexibility, or VO2max (P > 0.05). However, post-intervention neutrophil counts were increased, while lymphocyte counts decreased, and IIM levels rose in both groups (P < 0.05). Neuromuscular explosiveness and strength endurance were significantly higher in the A16 group compared to the U16 group (P < 0.05). Body fat was reduced, and all physical fitness parameters improved in both groups over time (P < 0.05). Conclusions: The 8-week soccer-specific training program did not lead to different effects on immune-inflammatory parameters between youth soccer players at different stages of puberty. However, training adaptations, including improvements in physical fitness, were observed in both groups. This suggests that when the same training load (frequency, duration, intensity) is applied to adolescents at different stages of puberty, immune-inflammatory responses are not significantly influenced by age, but physical fitness improves regardless of puberty stage. A key limitation of this study is the lack analysis of lymphocyte subpopulations, which could provide a deeper understanding of the cellular effects of training on immune function. Original Article Wed, 11 Dec 2024 00:00:00 GMT MariosHadjicharalambous, EleannaChalari, NikolaosZaras, Wed, 11 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003175 https://www.explorationpub.com/Journals/ei/Article/1003176 The efficacy of chimeric antigen receptor (CAR)-T therapy may not match initial expectations due to the influence of multiple circumstances, some of which cannot be predicted. CAR-T treatment groups include high-risk patients, particularly those with TP53 mutations. A significant body of research has demonstrated that mutations in the TP53 gene play a pivotal role in cancer development and progression. Any aberration in the TP53 gene in cancer is invariably associated with complications and a poor prognosis. Moreover, mutations in the TP53 gene have been observed to correlate with resistance to conventional chemotherapy, prompting the use of alternative therapeutic approaches, including CAR-T therapy. However, there is a possibility that abnormalities in the TP53 gene may affect patients after CAR-T cell administration reducing the efficacy of therapy. This review examines the link between TP53 mutations in cancer and the efficacy of CAR-T therapy, as well as the potential implications of this aspect in therapeutic planning. Review Mon, 16 Dec 2024 00:00:00 GMT ReginaMirgayazova, RaniyaKhadiullina, MariaFilimonova, VitalyChasov, EmilBulatov, Mon, 16 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003176 https://www.explorationpub.com/Journals/ei/Article/1003177 Ovarian cancer is the deadliest malignant tumor in the female reproductive system. Despite advancements in standard treatments such as tumor debulking surgery and platinum-based chemotherapy, the overall survival rate remains low. The emergence of targeted therapies, including Poly(ADP-ribose) polymerase (PARP) inhibitors and anti-angiogenic agents, has provided new avenues for treatment. However, drug resistance and disease heterogeneity continue to pose significant challenges. Immune checkpoint inhibitors (ICIs), as an emerging therapeutic approach, primarily target the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways to restore anti-tumor immune responses. Although ICIs have shown significant efficacy in other malignancies, their effectiveness in ovarian cancer is limited, with a response rate of only 10–15% for monotherapy. Recent studies have focused on combining ICIs with chemotherapy, anti-angiogenic agents, or PARP inhibitors to enhance therapeutic outcomes. This article reviews the progress of ICIs in ovarian cancer, including monotherapy and combination treatment strategies, and explores emerging therapeutic targets and strategies aimed at improving patient prognosis and achieving personalized treatment. By gaining a deeper understanding of the tumor microenvironment and its immune evasion mechanisms, there is hope for developing more effective treatment options in the future, ultimately improving the survival rates and quality of life for ovarian cancer patients. Review Wed, 18 Dec 2024 00:00:00 GMT LingliZhao, YanhongZhai, GaoliNiu, Wed, 18 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003177 https://www.explorationpub.com/Journals/ei/Article/1003178 Nociplastic pain is the fourth category of pain defined in recent years. It is a pain arising from altered nociception, despite the lack of clear evidence of actual or threatened tissue damage that causes activation of peripheral nociceptors nor evidence for disease or lesion of the somatosensory system causing the pain. This type of pain is usually multifocal, more diffuse or intense than expected and it is usually associated with other central nervous system-derived symptoms, such as fatigue, sleep, memory, and mood problems. It can occur in isolation or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain. It is associated with increased social and sanitary costs due to the difficulty of adequately treating it. Its pathogenesis is still poorly understood, even if a mounting body of evidence suggests a pivotal role in inflammation and immunity, which may be triggered by an infection and/or a trauma. This narrative review aims to summarise the current knowledge about the interplay of the immune system and nociplastic pathways activation and amplification. The challenge for the future will be to identify the exact role of inflammation and immunity, the cause of this activation, and its link to other pathogenetic factors of nociplastic pain, such as diet or microbiota alteration, social and phycological factors, together with a genetic and epigenetic predisposition. Review Tue, 14 Jan 2025 00:00:00 GMT MariateresaGiglio, AlbertoCorriero, AngelaPreziosa, GiustinoVarrassi, FilomenaPuntillo, Tue, 14 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003178 https://www.explorationpub.com/Journals/ei/Article/1003180 Aim: This study aims to identify the factors affecting the formation of neutralizing antibodies (NAbs) in healthy adults four weeks post-COVID-19 vaccination. Methods: A cross-sectional study was conducted among mass vaccination attendees using inactivated CoronaVac. Collected the peripheral blood serum four weeks following the second vaccine dose. Forty-four adults aged 26–85 were split into two groups based on age (≤ 60 years and > 60 years) and BMI (non-obese ≤ 25 kg/m2 and obese > 25 kg/m2). Variables like age, gender, BMI, and the presence of comorbidities were recorded. CD4/CD8 ratio and vitamin D levels were examined for their influence on NAbs formation. NAbs were measured using ELISA, T-cells via flow cytometry, and vitamin D through radioimmunoassay. Descriptive data analysis was performed as mean ± standard deviation to show the characteristics of the sample. Students’ t-tests and multivariate and univariate regression analyses were used to evaluate the data. Results: Significant variations in NAbs levels were observed with age (P = 0.013), BMI (P = 0.004), and comorbidities (P = 0.034). The elderly demonstrated higher NAb levels, potentially due to the high vitamin D levels compared to the adult group. The vitamin D levels strongly correlated with NAb titer (P < 0.001; R = 0.843). A collective correlation was found between NAb levels and the factors of age, BMI, and CD4/CD8 ratio (P = 0.033). A negative correlation existed between BMI and NAb levels (P = 0.018; R = –0.356) and between age and the CD4/CD8 ratio (P = 0.440; R = –0.119), but age alone did not correlate with NAb titer. Conclusions: Age, BMI, CD4/CD8 ratio, and comorbidities influence the production of post-vaccination NAbs. Sufficient vitamin D levels in the elderly significantly boost post-vaccination NAb levels. Maintaining a healthy body weight is also vital, as studies have revealed a significant and negative correlation between BMI and the level of NAbs, suggesting a possible need for adjusted vaccine doses in obese individuals. Original Article Thu, 23 Jan 2025 00:00:00 GMT HanaRatnawati, FenTih, GracePuspasari, Allen A.Pelapelapon, StevenFelim, Thu, 23 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003180 https://www.explorationpub.com/Journals/ei/Article/1003181 Aim: Immunization with meningococcal vaccine (MV) is the most effective measure to control and prevent the transmission of meningococcal infections. In this study, in order to support the appropriate use of various MVs in the prevention of meningococcal meningitis (MM), the effects of MVs, especially single-dose and inter-booster administered, on inflammatory parameters in < 5-year-old children were investigated. Methods: A total of 464 healthy children were included in this study. The data of those who received the first 2 doses at 2-month intervals and the next dose between 8–12 months were included. Nimenrix® (Pfizer) administered as a single dose to children from 12 months of age. Bexsero® (GSK) was administered as 2 + 1 doses under 2 years of age and 2 doses 2 months apart over 2 years of age. Neutrophil, lymphocyte, monocyte, platelet counts, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIR-I), and systemic immune inflammation index (SII) were evaluated. Results: Of the 464 participants, 58.2% were male, with a mean age of 3.81 years, and both sex ratios and ages were similar across the Nimenrix and Bexsero groups. The laboratory and inflammatory parameters of the two vaccine groups were similar. In both vaccine groups, changes in laboratory parameters before and 3-months after vaccination were similar. The changes in laboratory parameters over time between vaccine groups and their interactions were not significant. Conclusions: The NLR, dNLR, PLR, SIR-I, and SII are useful biomarkers indicating the inflammatory response of Nimenrix and Bexsero vaccines. Inflammatory markers can be used as both a safety endpoint and a protection endpoint for MVs (Nimenrix and Bexsero). However, further studies involving larger patient cohorts as well as detailed laboratory data on specific markers of inflammation are needed to draw comprehensive conclusions regarding the inflammatory response following vaccination. Original Article Thu, 23 Jan 2025 00:00:00 GMT OmerOkuyan, NevalElgormus, SeymaDumur, UgurcanSayili, HafizeUzun, Thu, 23 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003181 https://www.explorationpub.com/Journals/ei/Article/1003182 Coronavirus disease 2019 (COVID-19) infected individuals showed either mild symptoms or were paucisymptomatic, with severe impact on human health, revealing heightened risk and direct effects on health. Among various factors contributing to complications, bacterial and fungal co-infection remains very common and is highly lethal. This narrative review aims to focus on the collective role of gut microbiota and mycobiota in COVID-19. Fungal infection has been identified as a key risk factor for the spread of COVID-19 and mortality. Gut mycobiomes diversity and abundance also vary due to the different types of SARS-CoV-2 variant infection. Their cross-talk plays a vital role in immune regulation and disease severity, with an emphasis on understanding the altered condition as a predictive marker. On the other hand, the gut microbiome is well known for shaping metabolic functions, generating immune responses, and deciphering the signal to decide the healthy state and disease condition of an individual. Immune response during COVID-19 infection was also linked with metabolites produced by the gut microflora, specifically amino acids, sugar metabolites, and neurotransmitters. The cross-talk between gut microbiota and gut mycobiota for clinical implications in terms of early detection, identification of the disease severity, and even therapeutic alternatives will open newer avenues. A deep dive understanding of the cross-talk between the microbiome and mycobiome, and their role in immune response will take scientific discovery knowledge to develop gut-targeted safe therapeutic approaches in the form of FMT (fecal microbiota transplantation) probiotics, peptides, antibacterial, and antifungal metabolites. Overall cross-talk and immune interplay are critical determinants of host immunity, providing insights into their role and key take home lessons for better management of crisis in the future. Review Tue, 11 Feb 2025 00:00:00 GMT SunnyKumar, ZeelBhatia, SriramSeshadri, Tue, 11 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003182 https://www.explorationpub.com/Journals/ei/Article/1003183 Wound healing is an area of growing importance in the healthcare field, especially chronic wounds associated with comorbidities like diabetes mellitus (DM), hypoxic stress, obesity, and malnutrition. Chronic wounds significantly increase healthcare costs and reduce patients’ quality of life. Cytokines are a promising therapeutic target, as they regulate all stages of wound healing, and dysfunction in cytokine production can cause inflammatory non-healing wounds. Interleukin-1 (IL-1), IL-2, IL-6, IL-8, and tumour necrosis factor-α (TNF-α) facilitate leukocyte recruitment and clear dead cells during the initial inflammation stage while transforming growth factor-β (TGF-β), IL-4, and IL-13 inhibit inflammation and stimulate proliferation of fibroblasts to begin extracellular matrix (ECM) deposition. Given the complexity of cytokine interactions and their diverse cellular targets, a comprehensive understanding of these signaling pathways is crucial. This review examines the multifaceted roles of cytokines in wound healing and discusses recent advancements in the therapeutic application of cytokine modulation for improved wound care outcomes. Despite significant advancements in improving the specificity of cytokine therapies, further research is needed to focus on targeting downstream signaling pathways or specific receptors to minimize the adverse effects associated with these treatments. Review Tue, 11 Feb 2025 00:00:00 GMT Rachel Si-YinWong, TimothyTan, Alexander Shao-RongPang, Dinesh KumarSrinivasan, Tue, 11 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003183 https://www.explorationpub.com/Journals/ei/Article/1003167 Measles virus (Morbillivirus abbreviated as MV, but more recently MeV) is the causal agent of measles disease, thought to have existed at least 4,000 years ago, affecting predominantly infants, but also immunocompromised individuals remaining a public health issue today globally. In this review, we discuss the historical background about MeV infection to modern-day research on measles disease, current epidemiology, but also what is known about immunisation against it. We report what is known about the viral structure and the function of the viral proteins. This additionally covers the cellular structure of MeV, mechanisms, and clinical aspects of infection. Including a review of topics like cellular receptor-associated entry factors, to the immunology of MeV infection. In this review, the current knowledge of innate immune responses during infection is explained, which involves changes to chemokine and cytokine expression, finalised by the present understanding of adaptive immune responses to MeV. The genomic stability of the MeV proteins is explained and suggestive that it could be the third pathogen with eradication potential (after the variola and rinderpest viruses). Further biological and immunological clarification as to how this could occur is explained below. Review Fri, 01 Nov 2024 00:00:00 GMT BrentBrown, ChinuaImarogbe, IngoFricke, Fri, 01 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003167 https://www.explorationpub.com/Journals/ei/Article/1003168 The narrative review aims to shed light on the influence of inflammation in the comorbid chronic pain and major depressive disorder (MDD). This connection is known to be multifactorial, with a dynamic interaction between genetic and epigenetic factors. However, a growing body of evidence has shown that the co-presence of MDD and pain is underlain by immune mechanisms involved in the persistence of the inflammatory process. In particular, the cytokines released following activation of the innate immune system during inflammation cause changes at the endocrine level that result in glucocorticoid resistance, as well as altering the synthesis and metabolism of some central nervous system (CNS) mediators. Cytokines appear to generate neuroinflammation by activating normally protective microglia. Various other mechanisms, including changes in the function of the glutamatergic, GABAergic, and serotonergic systems are also implicated, but inflammation-induced reduction of BDNF (brain-derived neurotrophic factor) appears to be the deciding factor. In turn, neuroinflammation leads to sickness behavior, which is characterized by anhedonia and social withdrawal. This review explored these mechanisms, which may be at the root of comorbid pain and MDD. Although intriguing, however, most available evidence comes from animal studies, and rigorous clinical exploration is warranted. Review Mon, 04 Nov 2024 00:00:00 GMT AntonellaCiaramella, GiancarloCarli, Mon, 04 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003168 https://www.explorationpub.com/Journals/ei/Article/1003169 Not applicable. Correction Thu, 07 Nov 2024 00:00:00 GMT , Thu, 07 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003169 https://www.explorationpub.com/Journals/ei/Article/1003179 Aim: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality and is characterized by T-cell exhaustion, particularly in effector CD8+ T-cells. This exhaustion, driven by persistent immunosuppressive signals in the tumor microenvironment, impairs immune function and hinders effective immunotherapy. This study aimed to identify key exhaustion-related marker genes in CD8+ T-cells linked to PDAC and assess the potential of repurposing anti-inflammatory drugs to counteract T-cell exhaustion and enhance immune responses against PDAC. Methods: We employed a multi-omics approach, integrating single-cell RNA sequencing data with whole genome sequencing to identify dysregulated exhaustion-related immune markers in CD8+ T-cells in PDAC. We examined gene expression profiles and conducted functional enrichment analysis to evaluate their roles in immune exhaustion. We analyzed mutations in the shortlisted biomarkers from The Cancer Genome Atlas (TCGA) and performed in silico mutational analysis using Maestro to evaluate the impact of an IL7R mutation (K110N) on protein function. Virtual screening using a deep learning framework, GNINA, explored the inhibitory features of the anti-inflammatory drugs oxaprozin and celecoxib on IL7R. Results: Key dysregulated exhaustion-related immune markers were identified including PRF1, GZMA, CD8A, CD3D, NKG7, IL7R, and IL2RG. Pathway enrichment analysis indicated significant involvement in T-cell receptor signaling, Th1 and Th2 differentiation, and Th17 differentiation pathways, correlating with reported poor survival outcomes in PDAC patients. Mutational analysis of IL7R revealed a likely pathogenic mutation (K110N) located in the IL-7Ralpha fibronectin type III domain. Drug repurposing of oxaprozin and celecoxib showed favorable binding interactions with both wild and mutant IL7R proteins. Conclusions: The K110N mutation, despite not causing significant structural changes, may impact T-cell and B-cell homeostasis and development. Our findings suggest that oxaprozin and celecoxib could effectively inhibit T-cell exhaustion through favorable interactions with IL7R. Further clinical studies are necessary to validate the therapeutic potential of these anti-inflammatory drugs in enhancing immune responses in pancreatic cancer. Original Article Tue, 21 Jan 2025 00:00:00 GMT RawaaAlChalabi, RaghdaMakia, Semaa A.Shaban, Ahmed AbdulJabbarSuleiman, Tue, 21 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003179 https://www.explorationpub.com/Journals/ei/Article/1003170 The complement system is a key component of the innate immune system that mediates the clearance of pathogens, apoptotic cells, and cellular debris. However, the complement system also has diverse roles in the central nervous system (CNS), where it regulates synaptic pruning, neural plasticity, and neuroinflammation. Dysregulation of the complement system has been implicated in various neurodegenerative disorders such as Alzheimer’s disease, multiple sclerosis, epilepsy, stroke, and traumatic brain injury. In these conditions, excessive or chronic activation of the complement system may lead to synaptic loss, neuronal damage, immune dysregulation, and inflammation, which leads to exacerbating the disease’s progression and severity. Moreover, the complement system may interact with infectious agents that invade the CNS, such as bacteria, viruses, fungi, and parasites, and modulate their pathogenicity and host response. Therefore, understanding the complex interplay between the complement system and the CNS is crucial for developing novel therapeutic strategies to prevent or treat neurodegenerative and neuroimmune disorders. Natural compounds, such as plant extracts, phytochemicals, and nutraceuticals, have emerged as promising candidates for modulating the complement system and its effects on the CNS. These compounds may exert anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory effects by regulating the expression of various complement components and pathways. In this review, we summarized the current knowledge on the roles of the complement system in human neurodegenerative disorders and the benefits of natural compounds for complement-targeted therapy. Review Fri, 15 Nov 2024 00:00:00 GMT JeyaparthasarathyNarayanaperumal, GaneshGopal, Fri, 15 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003170 https://www.explorationpub.com/Journals/ei/Article/1003184 Aim: The objectives of our study were to evaluate a range of circulating biomarkers in COVID-19-related long-term neurological dysfunction. Methods: The study involved 30 patients with post-COVID syndrome (PCS) and 28 patients after COVID-19 without PCS. The third cohort consisted of 29 patients with acute COVID-19 of varying severity. The severity of COVID-19 was classified as mild and moderate to severe. The Montreal Cognitive Assessment (MOCA) and the SAGE test were used to study cognitive functions. The Hospital Anxiety and Depression Scale (HADS), the Sheehan Anxiety Scale, and the Beck Depression Inventory were used to study affective functions. The levels of serum cytokines and IgM, IgG, IgA to the SARS-CoV-2 coronavirus were determined using the Vector-Best test systems (Novosibirsk, Russia). We also studied the IgG subclasses to the spike protein of the SARS-CoV-2. Results: А mild to moderate COVID-19 infection primarily increases the risk of affective disorders and asthenia and, to a lesser extent, the development of cognitive impairment. The levels of IFN-α, IL-6, as well as serum antibodies to the SARS-CoV-2 among patients with PCS were significantly higher compared to convalescents without PCS. IgM to the SARS-CoV-2 was detected in the blood of patients with PCS during 2–7 months after the disease. After moderate and severe COVID-19, IgG2 and IgG4 were predominant in the blood of patients with PCS and neurological symptoms. The levels of IL-1, IL-4, IL-6, IL-8 in the blood serum of patients with PCS were higher after moderate and severe COVID-19 compared to patients who had mild COVID-19. Conclusions: The obtained data on an elevated level of cytokines and IFN-α in the blood of PCS patients can suggest the hypothesis about the participation of chronic inflammation in neurological disorders. The main limitation of the study is the relatively small sample size, which limits the statistical analyses. Original Article Tue, 25 Feb 2025 00:00:00 GMT YuliaDesheva, ZamiraMuruzheva, OlgaTumashova, TamaraShvedova, PolinaKudar, GeorgyMatveev, IrinaKoroleva, GalinaLeontieva, AnnaLerner, StanislavPonkratov, ElviraFirova, AlexanderSuvorov, Tue, 25 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003184 https://www.explorationpub.com/Journals/ei/Article/1003185 In hematological malignancies, autologous immunotherapy with T lymphocytes expressing a chimeric antigen receptor (CAR-T) has been successfully applied. CAR enhances the immuno-cellular effector system directly against cells expressing target antigens. The objective here was to discuss the prospects of applying CAR-T and its variants in autoimmune diseases (AIDs) to deplete pathogenic autoantibodies by eliminating B lymphocytes and plasma cells. B cells play a crucial role in the pathogenesis of AID through the production of autoantibodies, cytokine dysregulation, antigen presentation, and regulatory dysfunction. In AID with numerous autoreactive clones against various autoantigens, such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, myositis, and systemic sclerosis, CAR-T targeting CD19/CD20 and B-cell maturation antigen (BCMA) have shown success in preclinical and clinical studies, representing an innovative option for refractory patients when standard treatments fail. The suppression of B lymphocytes reactive against specific antigens using cytolytic T cells carrying a chimeric autoantibody receptor (CAAR-T) offers a promising approach for managing various AIDs, especially those with characterized pathogenic autoantibodies, such as pemphigus vulgaris, myasthenia gravis, and anti-NMDAR autoimmune encephalitis. CAAR-T allows the elimination of autoreactive B lymphocytes without compromising the general functionality of the immune system, minimizing common side effects in general immunosuppressive therapies, including immunobiologicals and CAR-T. In vitro, preclinical, and clinical (phase 1) studies have demonstrated the efficacy and specificity of CAR-T and CAAR-T in several AIDs; however, extensive clinical trials (phase 3) are required to assess their safety and clinical applicability. These advances promise to enhance precision medicine in the management of AIDs, offering personalized treatments for individual patients. Review Tue, 04 Mar 2025 00:00:00 GMT María FernandaSegovia, DianaLandoni, YohanaDefranchi, RodrigoCalderón Jofré, Carlos A.Flores Olivares, Gerson D.Keppeke, Tue, 04 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003185 https://www.explorationpub.com/Journals/ei/Article/1003186 Aim: Plasma cell disorders (PCD), a group of B-cell neoplasms, have undefined etiology. Mast cells (MC) have been found to promote the proliferation and differentiation of B cells in several B cell lymphoproliferative disorders; however, their role in PCD is unclear. The study therefore aims to evaluate bone marrow MC (BM-MC) in the context of PCD. Methods: Thirty patients with PCD and 20 control subjects were selected. The BM sample was collected and mononuclear cells were isolated to identify the MC percentage among mononuclear cells using flow cytometry. A 24-hour BM culture was also performed and tryptase levels in the culture supernatant were measured by an enzyme immunoassay. Results: In the patient group, the median of MC was 0.04% compared to 0.002% in the control group (p = 0.00001). Median BM-MC tryptase levels were also high in patients (10.1 ng/mL) against the control levels of 7.0 ng/mL (p = 0.011). While 50% of patients were found to have raised tryptase levels, only 10% of controls had tryptase levels beyond the cutoff levels of (p = 0.003). Conclusions: BM-MC number and tryptase levels are increased in PCD, suggesting their role in disease pathogenesis. Original Article Thu, 13 Mar 2025 00:00:00 GMT RaveenaYadav, RajeshTandan, Ranjana W.Minz, PankajMalhotra, YashwantKumar, Thu, 13 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003186 https://www.explorationpub.com/Journals/ei/Article/1003187 Immune response, inflammation, and lipid metabolism have important effects on cancer development and progression. Several proteins in tumoral cells and/or tumor microenvironment are involved in any of these processes, whereas some of them participate in all three, such as the zinc finger E-box-binding homeobox 1 (ZEB1) protein. This protein has been proposed to have an important role in invasion and metastasis of cancer cells, as well as to be involved in malignant transformation and resistance to cancer treatments. So, in this study, we present the participation of ZEB1 in immune, inflammatory, and membrane remodeling (lipid metabolism) processes, as well as its interaction with proteins that participate in them. Due to the importance of ZEB1 in cancer progression, it may be a potential biomarker of cancer prognosis and a target for the development of new cancer therapies. Review Thu, 20 Mar 2025 00:00:00 GMT Alicia MariaReveles-Espinoza, RoxanaRamírez Roque, Alba AdrianaVallejo-Cardona, Thu, 20 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003187 https://www.explorationpub.com/Journals/ei/Article/1003188 Cutaneous reactions present a diagnostic challenge, mainly when multiple factors, such as infections, medications, and environmental triggers, contribute to the clinical picture. Erythema multiforme (EM) is an acute, self-limiting mucocutaneous disorder that is most commonly triggered by herpes simplex virus (HSV) but can also be associated with drug-induced hypersensitivity reactions. Diagnosing EM becomes even more complex in patients taking photosensitizing medications, such as doxycycline, which can cause phototoxic or photoallergic reactions. Differentiating between drug-induced and infection-associated EM, as well as distinguishing it from more severe conditions like Stevens-Johnson syndrome (SJS), is crucial for appropriate management. This case report presents a case of a 57-year-old Caucasian female with a history of penicillin allergy who developed a phototoxic reaction to doxycycline following sun exposure. She was treated with silver sulfadiazine for her skin lesions but subsequently developed EM, with target-like lesions predominantly on the legs and a concurrent herpes simplex labialis infection. Laboratory findings were unremarkable, and there was no mucosal involvement. Given the suspected drug-induced nature of the reaction and the presence of HSV, a cautious approach was taken. Treatment with oral prednisone led to the resolution of symptoms without recurrence. Patch testing for doxycycline and silver sulfadiazine was omitted due to the risk of severe cutaneous adverse drug reactions (SCARs) and their non-essential status. Instead, penicillin testing was prioritized due to its clinical importance, and the patient successfully passed the oral amoxicillin challenge. This case highlights the diagnostic challenges of differentiating between drug-induced, infection-triggered, and photosensitivity-related cutaneous reactions. A careful evaluation of medication history, infection status, and clinical presentation is essential to guide the management of this condition. Case Report Thu, 20 Mar 2025 00:00:00 GMT VesnaVukičević Lazarević, Thu, 20 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003188 https://www.explorationpub.com/Journals/ei/Article/1003189 Aim: To assess circulating levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in mid-gestation pregnant women from South India, with (RPL) and without history of recurrent pregnancy loss (non-RPL) and its correlation with neutrophil to lymphocyte ratio (NLR). Methods: Blood samples were collected from 400 pregnant women attending government maternity hospital, Hyderabad, and subjected to enzyme linked immunosorbent assay (ELISA) for cytokines. NLR was calculated from absolute cell counts obtained from hospital records. Mann-Whitney U and Spearman r correlation was conducted as data followed non-normal distribution. Results: We found significantly decreased level of TGF-β and elevated TNF-α, TNF-α/TGF-β (P < 0.0001), and NLR (P = 0.0007) in patients over controls. Receiver operating curve characteristics of TNF-α/TGF-β (area under curve: 0.96) were superior to individual cytokines and NLR for patients when compared to the control group. A negative correlation was noted between NLR and TGF-β in the RPL group (P = 0.0041). Conclusions: Our results are indicative of predominant pro-inflammatory environment during mid-gestation in patients contrary to the anti-inflammatory milieu in controls. This is first study that attempted to connect cytokines with cellular ratio in RPL. The affordability of NLR to track inflammation is promised by its inverse correlation with TGF-β. However, further longitudinal studies are warranted spanning all stages of gestation in normal pregnant and RPL women to establish our observations. The limitations of the study include other factors that drive pro-inflammatory status like emotional dysregulation in women associated with chronic pro-inflammatory status is unexplored. Original Article Wed, 09 Apr 2025 00:00:00 GMT RashmiBhuwalka, SufayaJameel, FazulRahaman, RajeshwariBonu, ParveenJahan, Wed, 09 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003189 https://www.explorationpub.com/Journals/ei/Article/1003190 Neoantigen vaccines are a promising strategy in cancer immunotherapy that leverage tumor-specific mutations to elicit targeted immune responses. Although they have considerable potential, development challenges related to antigen prediction accuracy, manufacturing complexity, and scalability remain key obstacles to their widespread clinical use. This literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases to identify relevant studies. Keywords included “neoantigen vaccines,” “personalized cancer immunotherapy,” “tumor heterogeneity,” “bioinformatics pipelines,” and “prediction algorithms”. Clinical trial data were sourced from ClinicalTrials.gov, Trialtrove, and other publicly available registries. Eligible studies included peer-reviewed research articles, systematic reviews, and clinical trials focusing on neoantigen vaccine development, bioinformatic strategies, and immunotherapy. Tumor heterogeneity and clonal evolution significantly impact vaccine efficacy, necessitating multi-epitope targeting and adaptive vaccine design. Current neoantigen prediction algorithms suffer from high false-positive and false-negative rates, requiring further integration with multi-omics data and machine learning to enhance accuracy. Manufacturing remains complex, time-intensive, and costly, necessitating advancements in standardization and automation. Combination therapies, such as immune checkpoint inhibitors and adoptive cell therapies, counteract the immunosuppressive tumor microenvironment, improving treatment outcomes. Neoantigen vaccines hold great potential for personalized cancer therapy but require advancements in bioinformatics, manufacturing scalability, and immunomodulatory strategies to enhance clinical efficacy. Continued research and interdisciplinary collaboration are essential for refining clinical applications. Review Wed, 09 Apr 2025 00:00:00 GMT Alaa A. A.Aljabali, YassmenHamzat, AlaaAlqudah, LorcaAlzoubi, Wed, 09 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003190 https://www.explorationpub.com/Journals/ei/Article/1003191 Diet plays a complex role in the management of inflammatory bowel disease (IBD), significantly influencing the microbiome and metabolome. Three key metabolites implicated in IBD are short chain fatty acids, bile acids and tryptophan, all of which can be modulated through diet. This study analyses the impact of various diets on these metabolites. Despite the anti-inflammatory effects of short chain fatty acids, their levels do not increase during successful remission with exclusive enteral nutrition. Additionally, changes in tryptophan and bile acids are non-specific across different diets, suggesting these metabolic shifts are secondary to dietary efficacy in IBD. Dietary therapies vary in efficacy across individuals, as the established microbiome may not produce the desired metabolites. This variability is further compounded by differences in immune responses influenced by genetic factors and disease duration. Furthermore, inflammation and symptom resolution do not always coincide, revealing a discrepancy in dietary impacts on IBD. These limitations highlight the need for a deeper understanding of the interconnectedness of disease heterogeneity, dietary effects, the microbiome, and their influence on the mucosal immune system to develop more personalised dietary therapies. While no single diet is universally effective for all IBD patients, future research should focus on establishing a more rigid definition of dietary interventions for IBD and their long-term effects on clinical outcomes. Review Wed, 09 Apr 2025 00:00:00 GMT HebeMendez, GerRijkers, Wed, 09 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003191 https://www.explorationpub.com/Journals/ei/Article/1003192 Monogenic muscular dystrophies (MDs), such as Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy (LGMD), are characterized by chronic inflammation, progressive fibrosis, and impaired muscle regeneration. Central to these pathological processes are macrophages, which exhibit dynamic polarization states that influence the dystrophic microenvironment. In early disease stages, macrophages support tissue repair and regeneration, but chronic inflammation skews their activity toward pro-fibrotic phenotypes, driving excessive extracellular matrix (ECM) deposition and muscle dysfunction. Macrophages also interact with other immune cells, such as T cells and neutrophils, and non-immune cells, including fibroblasts and satellite cells, to regulate inflammatory and fibrotic responses. These interactions establish a dysregulated immune environment that exacerbates muscle damage and impairs effective regeneration. Preclinical studies using the mdx mouse model of DMD highlight the critical role of macrophages in sustaining inflammation and fibrosis, particularly through transforming growth factor-beta (TGF-β) signaling and fibro-adipogenic progenitor (FAP) activation. Therapeutically, targeting macrophages offers significant potential to mitigate disease progression. Strategies include modulating macrophage polarization toward a pro-regenerative M2 phenotype, inhibiting macrophage recruitment via chemokine signaling, and reprogramming macrophage metabolism to support oxidative phosphorylation and mitochondrial function. Additionally, anti-fibrotic interventions targeting TGF-β signaling or macrophage-FAP crosstalk have shown promise in reducing ECM deposition and preserving muscle architecture. In this review, we curate relevant studies and provide insights into the molecular mechanisms governing macrophage behavior in dystrophic muscle. Herein, we discuss how emerging therapeutic strategies targeting macrophage-mediated pathways can be leveraged to mitigate inflammation and fibrosis, enhance muscle regeneration, and improve clinical outcomes. Review Thu, 17 Apr 2025 00:00:00 GMT Jae HyungKim, Jea-HyunBaek, Thu, 17 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003192 https://www.explorationpub.com/Journals/ei/Article/1003193 Primary immunodeficiency disease (PID) now known as inborn errors of immunity (IEI) is genetic disorder(s) that impair the immune system. IEI is a heterogeneous group of diseases of more than 485 lifelong genetic disorders mainly due to intrinsic defect(s) in human immune system. Adults, children, and neonates can be affected by IEI diseases. The first IEI defects were reported in the 1950s, but Bruton’s use of immunoglobulin in 1952 to treat an 8-year-old boy suffering from pneumonia and other bacterial sino-pulmonary infections brought the PID or IEI and associated diseases into limelight. This review will focus on a general description of IEI (history, epidemiology, pathophysiology, and diagnosis), inborn errors of metabolism, and the management (cure or therapy) of IEI diseases. Review Tue, 13 May 2025 00:00:00 GMT IftekharMahmood, Tue, 13 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003193 https://www.explorationpub.com/Journals/ei/Article/1003194 Aim: Mutations in key regulators of apoptosis have necessitated exploring the alternative cell death pathways like necroptosis in breast cancer (BC). Necroptosis is immunogenic due to the release of damage-associated molecular patterns (DAMPs) into extracellular environment, which can trigger pro- or anti-tumor immune responses. Inducing necroptosis in estrogen receptor-positive (ER+) BC cells leads to the release of DAMPs, which can influence macrophages polarisation within the tumor microenvironment. The study aims to identify and characterize the DAMPs released from ER+ BC cells after necroptosis induction and to investigate their effects on macrophage properties. Methods: Necroptosis was induced by treating T-47D cells with Z-VAD-FMK and TNF-α (24 hours). The culture medium was collected as induction medium (IM). Necrostatin-1 alongside Z-VAD-FMK and TNF-α was added to inhibit necroptosis, the culture medium was collected as inhibition medium (InM) and used as a negative control for necroptosis. IM also referred as conditioned medium (CM), was analyzed using LC-MS/MS for the identification of DAMPs. THP-1 macrophages were incubated with the CM (24 hours), and their differentiation into M1 or M2 subtypes was assessed using qPCR, by evaluating the expression of specific M1 and M2 markers. Results: A total of 35 unique proteins with potential DAMP activity were identified in the IM. Functional and pathway analyses using PANTHER and DAVID revealed their involvement in immune regulation, metabolism, stress responses, and key pathways such as glycolysis, signaling, and inflammation. These proteins were primarily intracellular or secretory and included cytoskeletal components, chaperones, and binding modulators. Furthermore, IM treatment promoted THP-1 monocyte differentiation into both M1 and M2 macrophage subtypes. Conclusions: These findings highlight the role of necroptosis in generating DAMPs, which can modulate macrophage differentiation within the BC microenvironment. The identified DAMPs hold potential for further investigation as prognostic or predictive biomarkers and therapeutic targets in future studies. Original Article Thu, 15 May 2025 00:00:00 GMT BanitaThakur, RohitVerma, AdityaDod, Anil KRam, YashwantKumar, AlkaBhatia, Thu, 15 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003194 https://www.explorationpub.com/Journals/ei/Article/1003195 Aim: This study aims to analyze the impact of sucrose consumption on inflammatory and immunological parameters of newborn offspring of females with gestational diabetes mellitus (GDM). Methods: 4 groups of pregnant female CD1 mice were created (n = 6): A, without GDM, without sucrose supplementation; B, without GDM, with sucrose supplementation; C, with GDM, without sucrose supplementation; and D, with GDM, with sucrose supplementation. GDM was induced by subcutaneous injection of streptozotocin, with a dose of 230 mg/kg. Sucrose supplementation was administered at a concentration of 41.66 mg/mL per oral stool (500 μL volume) to each female daily at 8:00 am from confirmation of gestational diabetes until the end of pregnancy. Immediately after birth, the pups were sacrificed in the first 2 h of life. The following were quantified in each group of 8 newborns: body weight, glycaemia, leptin, adiponectin, insulin, HOMA-IR index, percentage of lymphocytes: CD3, CD4, and CD8, immunoglobulins (IgA and IgG), cytokines (IL-1β, IL-6, TNF-α, and IFN-γ), and redox activity: (carbonylated proteins, malondialdehyde, superoxide dismutase, catalase, reduced glutathione, total antioxidant capacity). Results: Sucrose consumption increased the levels of adiponectin, IL-1β, IL-6 and decreased the concentration of IgA in the offspring. Group C and D caused lower body weight and higher concentration of carbonylated proteins. The combination of sucrose and GDM favored an increase in blood glucose, the HOMA-IR index, the percentage of T lymphocytes, the concentration of proinflammatory cytokines, and reduced glutathione, with reduction of catalase. Conclusions: Sucrose consumption by mothers during pregnancy and the presence of GDM generate alterations at the cellular, immunological, metabolic, hormonal, and redox levels in newborns. This results in an inflammatory state, with an imbalance in the redox state, which predisposes the newborn to short and medium-term metabolic problems from birth. Original Article Wed, 21 May 2025 00:00:00 GMT Beatriz ElinaMartínez-Carrillo, EfrénAguilar-Rodríguez, RoxanaValdés-Ramos, Aldo ArturoReséndiz-Albor, Cristian ÁngelRosales-Gómez, Rosa AdrianaJarillo-Luna, Ana LauraGuadarrama-López, Wed, 21 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003195 https://www.explorationpub.com/Journals/ei/Article/1003197 Aim: The high levels of anti-SSA/Ro and anti-SSB/La autoantibodies are closely associated with a group of diseases related to connective tissues, also known as connective tissue diseases (CTD). The current study attested to profile the multifactorial association between interleukin IL-6 and IL-10 in sera from the study cohort to underline its putative prognostic and therapeutic characteristics for future application in CTD. Methods: The study cohort was recruited from government hospitals and screened for autoantibody using Enzyme Immunoassay (EIA) and Immunofluorescence Assay (IFA) while cytokine levels were measured using ELISA. Results: Our data showed the mean age of female patients is 38.1 years. Higher mean levels of both cytokines were observed in the first year of disease onset and menopause autoimmune-CTD patients. The mean levels of IL-6 and IL-10 were significantly higher in positive anti-Ro/La compared to the control group (p < 0.05). Also, the significant correlation of IL-6 and IL-10 in CTD patients as opposed to healthy control has underlined the putative role of these biologics. Conclusions: These data suggest the putative manipulation of IL-6 and IL-10 as prognostic and therapeutics molecules in managing CTD, as an alternative to steroid-based medications to control the disease manifestations. Original Article Wed, 21 May 2025 00:00:00 GMT Nor Effa S.Zulkafli, Anisah AbdulZubir, BalqissiahBaharudin, Chuo LuanTan, Nurul AuliaZakaria, ErnestMangantig, Wed, 21 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003197 https://www.explorationpub.com/Journals/ei/Article/1003198 Aim: Tungiasis caused by Tunga penetrans is a neglected tropical disease that majorly affects children, the elderly and persons living with disabilities in rural homes in sub-Saharan Africa. The disease is characterized by swelling and inflammation symptoms, especially on the hands and feet. However, it is unclear whether inflammatory responses induced by T. penetrans may be associated with alterations of cytokine and antibody profiles. The study evaluated the immunological changes: cytokine and antibody profiles of experimentally raised guinea pigs exposed to T. penetrans. Methods: A total of 24 guinea pigs were experimented on; 16 were exposed to T. penetrans while 8 were controls. Blood samples were collected before and after exposure. Enzyme-linked immunosorbent assay (ELISA) technique was used to quantify cytokines and antibodies. Data analysis was performed using GraphPad Prism 10.4. Results: At day 10 of post-infection, guinea pigs showed significant elevation (p < 0.05) of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α) (235 pg/mL), and interferon gamma (IFN-γ) (425 pg/mL) in the serum. Anti-inflammatory cytokine had a delayed elevation, with interleukin-4 (IL-4) peaking to 357 pg/mL by day 15, while IL-10 rose to 367 pg/mL by day 15 of post-infection. Total systemic circulating levels of antibodies in serum were significantly elevated (p < 0.05), with immunoglobulin E (IgE) elevating to 232 ng/mL while IgG peaking at 272 ng/mL on day 15 post-infection. Conclusions: Pro-inflammatory cytokines elevated during the early stages of infection may serve as early markers for the infection, and their potential role in the pathogenesis of tungiasis needs to be explored further. The study has established that IgE and IgG are important antibodies that are produced in response to tungiasis, and their efficacy in controlling the infection needs to be further explored for potential alleviation of severe forms of the infection. Original Article Tue, 27 May 2025 00:00:00 GMT JanetTarus, JohnMuoma, Dennis M.W.Ochieno, MauriceOmolo, KelvinKiprotich, NicholasKitungulu, JacksonCheruiyot, Tue, 27 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003198 https://www.explorationpub.com/Journals/ei/Article/1003199 The immune system is a masterclass in balance and adaptation. Its ability to distinguish self from non-self, to tolerate internal diversity, to learn from past encounters, and to respond to environmental cues offers more than just biological insight—it offers a framework for thinking about resilient societies. In this perspective, I reflect on the parallels between immune function and the ways communities withstand adversity, adapt, and rebuild. When the immune system falters—through intolerance, loss of memory, or failure to regulate—it mirrors the kinds of dysfunction we see in divided or unjust societies. By learning from the immune system’s strengths and failures, we may find guidance for healing fractured communities and fostering more cohesive, adaptable, and resilient social systems. Perspective Wed, 11 Jun 2025 00:00:00 GMT AlaaAli, Wed, 11 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003199 https://www.explorationpub.com/Journals/ei/Article/1003200 Not applicable. Editorial Mon, 16 Jun 2025 00:00:00 GMT RobertoPaganelli, AngeloDi Iorio, Mon, 16 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003200 https://www.explorationpub.com/Journals/ei/Article/1003201 The mixed leukocyte reaction (MLR) is a pivotal in vitro assay for evaluating T-cell responses stimulated by allogeneic antigen-presenting cells (APCs). Dendritic cells (DCs) are the most efficient stimulatory cells. However, the scarcity of circulating DCs in peripheral blood limits their isolation for research or clinical use. In contrast, monocytes, which are abundant and easily accessible, can be differentiated into monocyte-derived DCs (moDCs) in vitro and have emerged as the most practical and efficient stimulatory cells for MLR due to their accessibility and robust allostimulatory capabilities. This review aims to describe the scientific rationale and evidence for using moDCs in MLR assays to assess T-cell alloreactivity. Its methodology outlines the protocols for experimental, preclinical, and biosafety assays that have demonstrated the practicality of moDCs in evaluating and quantifying the alloresponse of naïve and memory CD4+ and CD8+ T cells, as well as the effects of immunomodulatory factors, immune monitoring, and tolerogenic strategies in the context of transplantation. Additionally, it illustrates how moDC-mediated MLRs have provided critical insights into understanding alloimmunity processes and antigen-specific T-cell responses in cancer immunotherapy, autoimmune diseases, and vaccine development, with potential implications for personalized medicine and immunotherapy optimization. In conclusion, despite ongoing challenges such as standardization and scalability in massive cell production, the current understanding and reproducible results of moDC applications in MLRs highlight their potential to develop innovative strategies focused on immune monitoring. Review Mon, 30 Jun 2025 00:00:00 GMT HonorioTorres-Aguilar, Sorely AdelinaSosa-Luis, AlexiaAlmaraz-Arreortua, William de JesúsRíos-Ríos, Mon, 30 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003201 https://www.explorationpub.com/Journals/ei/Article/1003202 The global socioeconomic and health impacts of microbial diseases cannot be overemphasized. The emergence of the coronavirus in 2019 and the ongoing threat of infectious diseases, such as HIV/AIDS, tuberculosis, and hepatitis, remind us of the impact these infections have on economic stability and global health. Gaps in the treatment of microbial infections and their contribution to increased mortality necessitate holistic and long-term solutions, as opposed to antibiotics, which were previously relied upon. Immunotherapy is becoming increasingly promising for the treatment of microbial infections. This study reviews recent advances in immunotherapeutic strategies, particularly cytokine-based therapies, adoptive cell therapy, monoclonal antibodies, and immune checkpoint inhibitors, for the control of antimicrobial resistance. New inventive approaches, such as chimeric antigen receptor T cell therapy and mucosal-associated invariant T cells, have been discussed in the context of bacterial and viral infections, highlighting promising results from clinical trials and addressing the challenges of toxicity, immune evasion, and therapy resistance that are inherent in these diseases. Future priorities include optimizing combination therapies and exploring new immunomodulatory targets to improve the effectiveness of these interventions in treating antimicrobial resistance and other infectious diseases. Review Fri, 11 Jul 2025 00:00:00 GMT Ayodele IsaacAdedokun, Olaniyi AbideenAdigun, Adamu MuhammadIbrahim, IbrahimIdris, Paul YiranNtasin, Babatunde IbrahimOlowu, Chinyere M.Ikele-Awaogu, Precious KehindeFadele, Ernesto OluwafemiDibia, Olalekan JohnOkesanya, Mohamed MustafAhmed, Fri, 11 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003202 https://www.explorationpub.com/Journals/ei/Article/1003203 Advancements in viral vaccine development have revolutionized public health by reducing the burden of infectious diseases worldwide. The development of vaccinology started with Jenner’s smallpox vaccine and Salk’s polio vaccine among other live attenuated and inactivated vaccines before shifting to modern platforms that include subunit, protein-based, and viral vector vaccines as well as messenger RNA (m-RNA) vaccines. Subunit and protein-based vaccines are the ones that protect specific subpopulations and contain low risks; reverse vaccinology, built on genome sequencing and using computational methods for identification of the antigens, helps to cut the time for vaccination development. The COVID-19 experience by itself has shown the feasibility of faster and easily scalable m-RNA development that provides a very strong immunogenicity and safety profile. These advancements are crucial in the fight against new and resurging pathogens, for example, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV), and influenza. They allow the creation of vaccines for highly mutable pathogens or those that evolve strategies to avoid the immune system. Truly innovational approaches in delivering vaccines are lipid nanoparticles, microneedle patches, and thermostability that improve the stability, accessibility, and administration of vaccines in low- and middle-income countries (LMICs). Furthermore, computational immunology, artificial intelligence, and bioinformatics are involved in creating precision vaccines that are likely to suit different populations in society. This review presents solutions to critical barriers including vaccine refusal among the population and unequal distribution systems and transportation requirements along with clinical trial gender bias. Recent strategies employing nanotechnology-based delivery methods and universal vaccines receive assessment regarding their solutions to present challenges. The need for joint public-private collaborations combined with strong health programs and systematic research investments stands essential for developing extensive scalable vaccination strategies. These findings present a detailed guide for improving both the effectiveness and accessibility of vaccines as well as readiness against current and future viral infections. Review Wed, 16 Jul 2025 00:00:00 GMT AnkitKumar, FaizAhmad, Bikash KumarSah, Alaa A. A.Aljabali, YachanaMishra, VijayMishra, Wed, 16 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003203 https://www.explorationpub.com/Journals/ei/Article/1003204 Oncolytic virotherapy (OVT) employs genetically engineered or naturally occurring viruses to selectively replicate within tumor cells, leading to direct lysis and induction of systemic anti-tumor immune responses. This dual mechanism distinguishes OVT from conventional therapies and positions it as a promising candidate in precision oncology. This review synthesizes recent advancements in understanding the molecular mechanisms underlying OVT efficacy, including viral entry, replication kinetics, immunogenic cell death, and modulation of the tumor microenvironment. We highlight innovations in viral engineering, such as promoter targeting, microRNA control, and immune-modulatory gene insertions that enhance tumor specificity and therapeutic safety. Clinically, OVT has shown measurable benefits in various solid tumors, with several viruses, such as talimogene laherparepvec, entering regulatory approval and others progressing through late-phase clinical trials. When combined with immune checkpoint inhibitors, OVT has demonstrated synergistic effects by improving antigen presentation and reversing immunosuppressive signaling. Integration with targeted therapies and nanotechnology-based delivery systems has further refined viral biodistribution and pharmacodynamics. However, therapeutic resistance, immune clearance, stromal barriers, and heterogeneous tumor responses remain key limitations. Overcoming these challenges requires optimized delivery routes, predictive biomarkers, and combination strategies tailored to immune and genetic tumor profiles. As OVT evolves from proof-of-concept to a platform-based therapeutic strategy, its integration into multimodal cancer treatment protocols will depend on refined bridge oncolytic activity with durable immunotherapy effects. Review Tue, 29 Jul 2025 00:00:00 GMT Alaa A. A.Aljabali, RashaBashatwah, OmarGammoh, Tue, 29 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003204 https://www.explorationpub.com/Journals/ei/Article/1003205 Cancer remains one of the leading causes of morbidity and mortality globally, driven by genetic alterations, uncontrolled cell proliferation, and metabolic reprogramming. The tumor microenvironment (TME) is a highly dynamic and heterogeneous system composed of tumor cells, immune cells, stromal cells, and extracellular matrix (ECM) components, which influence cancer progression. Tumor-associated macrophages (TAMs), especially those polarized into the M2 phenotype, play a critical role in modulating this environment. M2 macrophages promote tumor progression through mechanisms such as immune suppression, angiogenesis, and metastasis. This polarization is heavily influenced by the altered metabolic landscape of tumors, where the Warburg effect leads to excessive lactate production, which in turn drives M2 polarization through G protein-coupled receptor 132 (GPR132). M2 macrophages secrete cytokines like IL-10, transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF), which contribute to immune escape, tumor growth, and metastasis. The metabolic shifts within TAMs, especially the transition from oxidative phosphorylation to glycolysis, further support the pro-tumoral functions of these cells. This review explores the intricate relationship between M2 macrophage polarization bias, tumor metabolism, and the resulting impact on cancer progression, highlighting the potential of targeting these pathways for therapeutic strategies. The findings suggest that M2 macrophage polarization could serve as a key prognostic factor for cancer outcomes and provide a basis for future research into therapeutic interventions that target macrophage polarization and the tumor metabolic milieu. Review Wed, 06 Aug 2025 00:00:00 GMT José DanielMoreno-Ocampo, Miguel ÁngelPardiño-Vega, Norma EstelaHerrera-González, Wed, 06 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003205 https://www.explorationpub.com/Journals/ei/Article/1003206 Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, cognitive impairments, and sleep disturbances. Although traditionally considered psychogenic, recent research supports a multifactorial etiology involving central nervous system (CNS) dysregulation and significant immune involvement. This narrative review synthesizes current evidence regarding the role of immune mechanisms in FMS, with comparative insights into chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and irritable bowel syndrome (IBS)—previously grouped under functional somatic syndromes (FSS). In FMS, immune dysregulation is evidenced by elevated levels of pro-inflammatory cytokines (e.g., IL-6, IL-8, TNF-α) and decreased anti-inflammatory mediators such as IL-10, contributing to symptomatology including pain amplification and fatigue. Neuroinflammation, as indicated by microglial activation in pain-processing CNS regions, further supports the role of immune signaling in central sensitization. Other contributing factors include oxidative stress, mitochondrial dysfunction, and immune cell alterations, particularly involving regulatory T cells and natural killer (NK) cells. Compared to FMS, CFS/ME exhibits greater systemic immune activation and more severe mitochondrial impairment, correlating with profound fatigue and cognitive decline. IBS, on the other hand, shows immune activation localized to the gastrointestinal tract, emphasizing the gut-brain axis. These findings highlight both shared and syndrome-specific immune features. To better reflect their systemic and immunological complexity, this review refers to these conditions collectively as chronic multisystem immune-related disorders (CMIRDs). The evidence supports the development of biomarker-based diagnostics and personalized immunomodulatory therapies. A multidisciplinary approach that integrates immunology and neurology is essential to improve outcomes for patients with FMS and related disorders. Review Thu, 07 Aug 2025 00:00:00 GMT MartaNizzero, VittorioSchweiger, AlviseMartini, LeonardoGottin, GiustinoVarrassi, GiovannaDel Balzo, EricaSecchettin, LucaPolati, StefanoCoaccioli, EnricoPolati, Thu, 07 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003206 https://www.explorationpub.com/Journals/ei/Article/1003207 Aim: Autoimmune cytopenias are disorders driven by immune-mediated destruction of hematopoietic cells. Recent studies have linked these conditions to inborn errors of immunity (IEI), particularly in patients with recurrent and/or chronic forms. Common variable immunodeficiency (CVID) is the most common IEI in humans, and autoimmune cytopenias represent the most prevalent autoimmune manifestations of the disease. TNFRSF13B/TACI alterations are the most common genetic defects in CVID patients. The aim of this study was to investigate both the incidence of hypogammaglobulinemia—including immunoglobulin subclass deficiencies—in patients with autoimmune cytopenias, as well as possible correlations with common TNFRSF13B/TACI defects in selective patients. Methods: A cohort of 123 patients (110 adults and 13 children, male/female: 58/65, median age at diagnosis: 50.0 years, range: 1.5–87.0) with autoimmune cytopenias [113 with autoimmune thrombocytopenia (AIT), 8 with autoimmune hemolytic anemia (AHA), and 2 with Evans syndrome] were enrolled in the study. The main immunoglobulin types (IgG, IgM, and IgA) were measured in all patients, while serum for the estimation of IgG subclass levels was available in 84 patients. Genetic analysis of TNFRSF13B/TACI was performed by PCR and Sanger sequencing. Results: Although no deficiency of main immunoglobulin types was detected in any patient, 8 of 84 patients (9.5%) displayed selective IgG4 deficiency (sIgG4D). Among them, three suffered from acute/newly diagnosed AIT, three from chronic AIT, and two from AHA. Interestingly, two patients with sIgG4D exhibited a family history of IEI. Furthermore, one patient (12.5%) carried a pathogenic missense mutation (c.542C>A, p.A181E, rs72553883) in a heterozygous state, while the remaining patients carried only common polymorphisms. Conclusions: IgG4 could be considered a useful biomarker in patients with autoimmune cytopenias, while further studies may elucidate its precise role in disease pathogenesis and prognosis. Original Article Fri, 08 Aug 2025 00:00:00 GMT MariaLoutsou, NikolaosGiannakoulas, EmmanouelΗatzipantelis, HelenPergantou, AthinaDettoraki, VasilikiAntari, AikateriniMichalopoulou, GeorgeVassilopoulos, StylianiSarrou, VasilikiKalaitzidou, ChristosHadjichristodoulou, FaniKalala, MatthaiosSpeletas, Fri, 08 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003207 https://www.explorationpub.com/Journals/ei/Article/1003208 Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterised by synovial joint destruction and systemic complications. Central to its pathogenesis is the formation and deposition of immune complexes (ICs), which result from antigen-antibody interactions involving autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). These ICs infiltrate joint tissues, activate the complement system, and initiate a cascade of inflammatory responses. The ensuing recruitment of polymorphonuclear leukocytes and release of pro-inflammatory cytokines and chemokines contribute to sustained inflammation, tissue degradation, and joint deformity. RA is thus classified as a type III hypersensitivity disorder, wherein IC-mediated mechanisms perpetuate a self-amplifying inflammatory loop. This review explores the evolving understanding of IC-driven pathophysiology in RA, emphasising the three-stage progression of IC formation, deposition, and inflammatory activation. By elucidating the interplay between hypersensitivity reactions and immune-mediated mechanisms in RA, the review underscores potential therapeutic targets that may help disrupt this pathogenic cycle. Enhanced comprehension of IC dynamics not only deepens insight into RA progression but also opens avenues for more precise and effective interventions in autoimmune diseases. Review Tue, 12 Aug 2025 00:00:00 GMT VeshaliniKasiraja, Noor Azlina AbuBakar, Noor AzuinSuliman, Tue, 12 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003208 https://www.explorationpub.com/Journals/ei/Article/1003209 Aim: Recurrent pregnancy loss (RPL) is defined as the loss of two or more clinical pregnancies before the 20th week of gestation. Globally, RPL affects 1–5% of couples, with approximately 50% of cases remaining idiopathic. This study aimed to assess the circulating levels of interleukin-6 (IL-6) and IL-10 cytokines in pregnant women with and without a history of RPL. Methods: A total of 170 pregnant women in their second trimester with and without a history of RPL were enrolled from Niloufer Hospital, South India. Serum samples isolated from blood were analyzed using a sandwich-enzyme linked immunosorbent assay (ELISA) to estimate IL-6 and IL-10 levels. Results: The median age was significantly higher in the RPL group (25 years) compared to the non-RPL (NRPL) group (22 years) (p = 0.0001). Similarly, body mass index (BMI) was significantly elevated in the RPL group (25.64 kg/m2) vs. the NRPL group (22.51 kg/m2) (p = 0.0001). The analysis revealed significantly elevated IL-6 and reduced IL-10 levels in the RPL group compared to the NRPL group (p = 0.0001). Additionally, the IL-6/IL-10 ratio differed significantly between the two groups. Receiver operating characteristic (ROC) curve analysis indicated that IL-6 was a better marker for RPL than IL-6/IL-10 ratio and IL-10. IL-10 levels were found to be a reliable marker in relation to the extent of pregnancy loss history. Conclusions: The study highlights the presence of a pro-inflammatory systemic milieu in mid-gestation among women with a history of RPL, potentially reflecting the immunological environment at the feto-placental interface. Further research to establish a distinct cytokine signature between RPL and NRPL groups may facilitate the development of targeted preventive and therapeutic strategies. However, the current findings are limited by a modest sample size and a homogenous ethnic population, which may affect generalizability. Larger, multi-ethnic studies are warranted to validate these observations and enhance clinical applicability. Original Article Mon, 18 Aug 2025 00:00:00 GMT SufayaJameel, RashmiBhuwalka, ParveenJahan, Mon, 18 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003209 https://www.explorationpub.com/Journals/ei/Article/1003210 Aim: Vitiligo is an autoimmune skin disorder characterized by melanocyte destruction and progressive depigmentation. Cytokine imbalance plays a key role in its pathogenesis. This study aims to evaluate and compare serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine IL-17 in vitiligo patients and healthy individuals, to explore their potential as biomarkers of disease activity. Methods: A total of 60 vitiligo patients and 40 age- and sex-matched healthy controls were recruited. Serum concentrations of IL-10 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). Disease severity and duration were also assessed in relation to cytokine levels. Results: Vitiligo patients showed significantly lower IL-10 levels (9.37 ± 0.17 pg/mL) compared to controls (11.38 ± 0.22 pg/mL, P < 0.01), and significantly higher IL-17 levels (326.48 ± 5.49 pg/mL) compared to controls (270.47 ± 8.48 pg/mL, P < 0.01). Conclusions: These findings suggest an inflammatory cytokine imbalance in vitiligo, characterized by decreased IL-10 and elevated IL-17 levels. The significant correlation of IL-17 with disease progression supports its role as a potential biomarker of disease activity. Targeting cytokine pathways may offer new directions for immunomodulatory treatment strategies in vitiligo. Original Article Mon, 18 Aug 2025 00:00:00 GMT Hanan MohammedSaied, Mon, 18 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003210 https://www.explorationpub.com/Journals/ei/Article/1003211 Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition, plays a central role in the progression of heart diseases such as myocardial infarction, heart failure, and hypertensive cardiomyopathy. The dynamic interplay between fibroblasts and macrophages is pivotal in regulating ECM remodeling and the fibrotic response. Fibroblasts, as primary ECM producers, undergo phenotypic changes during pathological conditions, transitioning into myofibroblasts that exacerbate fibrosis. Macrophages, both resident and non-resident, contribute to cardiac fibrosis by influencing fibroblast activation through cytokine secretion and direct cell interactions. Emerging evidence from preclinical studies highlights the transformation of macrophages into myofibroblast-like cells, known as macrophage-to-myofibroblast transformation (MMT), a key mechanism linking chronic inflammation to fibrosis. During MMT, macrophages acquire characteristics like myofibroblasts. This process is driven by signaling pathways such as TGF-β/Smad3, ALKBH5, and mineralocorticoid receptor (MR)/connective tissue growth factor (CTGF) pathways. Recent single-cell transcriptomics and lineage-tracing studies have provided deeper insights into the molecular regulation of MMT and its contribution to myocardial remodeling. Additionally, the balance between resident cardiac macrophages and monocyte-derived macrophages plays a crucial role in determining the fibrotic outcome following cardiac injury. This review discusses the cellular composition of the heart, the interactions between macrophages and fibroblasts, and the mechanisms driving MMT. By synthesizing these insights, we aim to evaluate MMT as a therapeutic target for mitigating cardiac fibrosis and improving clinical outcomes in cardiovascular diseases. Review Mon, 18 Aug 2025 00:00:00 GMT DaehunKim, Jea-HyunBaek, Mon, 18 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003211 https://www.explorationpub.com/Journals/ei/Article/1003212 Messenger RNA (mRNA) vaccines represent a novel category of vaccinations with significant potential for the future. Recent studies have demonstrated the effectiveness of mRNA vaccines in combating various viral infections and cancer, particularly in cases where traditional vaccine platforms may not produce protective immune responses. In particular, mRNA vaccines have gained attention due to their quick development, scalable manufacturing, and ability to elicit strong immune responses. This review elucidates the synthesis of mRNA and mRNA vaccines, their mechanisms of action, and the strategies to enhance their delivery and address their advantages and limitations for viral disease. Many delivery strategies have been investigated in recent years, concentrating on nanoparticle-mediated mRNA vaccine delivery. The delivery mechanism is crucial for improving mRNA vaccine stability, biocompatibility, and targeting specific cells and tissues. By preventing mRNA degradation and increasing cellular uptake, nanocarriers significantly contribute to the stability and immunogenicity of mRNA vaccines. Nanoformulation functions not only as a carrier but also as a compartment that safeguards the mRNA from biological, chemical, and physical processes that may compromise its safety and efficacy. Despite these advances, challenges such as long-term safety and innate immune activation remain. Eventually, this review concentrated on future considerations necessary for the more efficient and safer deployment of mRNA, emphasizing the merits and drawbacks of the existing viral disease mRNA vaccines, with an eye toward future innovations and clinical applications. Review Fri, 22 Aug 2025 00:00:00 GMT VijayMishra, AbhigyanRanjan, YachanaMishra, Fri, 22 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003212 https://www.explorationpub.com/Journals/ei/Article/1003214 Aim: Regulatory T (Treg) cells and interleukin-17-producing T helper (Th17) cells play a critical role in successful pregnancy. Treg and Th17 cells differentiate predominantly in the thymus. Despite steroid-induced pregnancy thymic involution, the peripheral blood Treg number increases, indicating peripheral expansion. Thymic atrophy is accompanied by a decrease in T-cell receptor diversity, but is compensated for by activation of RAG2 (recombination activating genes) in the periphery, which initiates extrathymic T-cell differentiation. In addition, naive Treg enhance their suppressive activity during pregnancy, which may play an important role in the development of maternal tolerance to fetal antigens. The changes in naive Th17 thymic output during pregnancy have not been studied. The aim of the study is to determine the percentages of peripheral blood Treg and Th17 and the expression of CD45RA, CD31, RAG2, and Tim-3 on these subsets during physiological pregnancy and in non-pregnant (NP) women. Methods: Peripheral blood samples (n = 80) from healthy NP and pregnant women (1st, 2nd, and 3rd trimesters) were analyzed by flow cytometry to determine Treg (CD4+CD25+FOXP3+) and Th17 (CD4+RORγt+IL-17A+), and the expression of RAG2 and Tim-3 in these subsets. Treg and Th17 then subdivided into mature naive (MN, CD45RA+CD31–), recent thymic migrants (RTE, CD45RA+CD31+), CD31– memory, and CD31+ memory cells. Results: An increase in the Treg percentage, a decrease in Th17, and a shift in the Treg/Th17 ratio shift towards Treg were revealed in pregnant women compared to NP. A Tim-3+ Treg increase in the 1st and 3rd trimesters and Tim-3+ Th17 in the 3rd trimester were found. There was a decrease in RTE-Treg and RTE-Th17, an increase in the MN-Treg percentage, but MN-Th17 did not change during pregnancy. The RAG2 expression was increased only in Treg. Conclusions: The obtained data indicate that a healthy pregnancy is characterized by significant changes in the composition of naive Th17 and Tregs in peripheral blood. Original Article Wed, 27 Aug 2025 00:00:00 GMT OlgaGorbunova, EkaterinaOrlova, OlgaLoginova, SergeyShirshev, Wed, 27 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003214 https://www.explorationpub.com/Journals/ei/Article/1003213 Mpox, caused by the monkeypox virus (MPXV), has re-emerged as a global health concern due to recent outbreaks and the emergence of new variants. Current antiviral options are limited, prompting the search for alternative therapeutic strategies. This review explores the therapeutic potential of marine-derived bioactive compounds as antiviral agents against MPXV, focusing on their mechanisms of action and clinical relevance. Marine phytoconstituents, including mycosporine-like amino acids, carrageenan, fucoidans, and griffithsin, exhibit diverse antiviral, immunomodulatory, and anti-inflammatory properties. Understanding their role may offer innovative solutions for mpox management and address gaps in current treatment approaches. A comprehensive literature search was performed across PubMed, Scopus, and Web of Science to identify peer-reviewed articles published between 2010 and June 2024 using keywords such as “mpox”, “monkeypox virus”, “marine-derived antivirals”, and “orthopoxvirus”. Emphasis was placed on studies from 2021–2024 to capture recent developments in mpox pathogenesis and marine-based therapeutics. Eligible sources included original research, systematic reviews, meta-analyses, and official health reports published in English. Marine-derived compounds demonstrate promising antiviral and immunomodulatory effects against MPXV in preclinical models. While further research is needed to confirm their clinical efficacy and address issues of scalability and safety, these agents represent a valuable adjunct or alternative for future mpox therapeutics. Review Wed, 27 Aug 2025 00:00:00 GMT SouravPal, ShayanSamanta, BiprojitBhowmick, KhokanBera, Wed, 27 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003213 https://www.explorationpub.com/Journals/ei/Article/1003215 Aim: Cytotoxic T lymphocytes (CTL) examine the major histocompatibility complex (MHC) class I ligands on nucleated cells to detect antigens derived from pathogens and cancer cells. Accurate prediction of T-cell epitopes is therefore crucial for the development of a wide range of biopharmaceuticals, including vaccines. Methods: The present study involved the development of position-specific scoring matrices (PSSM) and artificial neural networks (ANN) based models for 22 MHC class I molecules, including the integrated forecast of CTL epitopes using the EasyPred modeler. Similarity-reduced peptides dataset was used to train and evaluate models with performance assessed using the area under the receiver operating characteristic curve (Aroc) as the primary metric. Results: Comparative analysis revealed that the ANN-based predictor achieved superior performance for the HLA-A*0202 molecule by achieving the maximum Aroc value of 0.97 as compared to the PSSM predictor, having a value of 0.93. Furthermore, most natural MHC binders were identified within the top 5% with an average relative rank (%) of 2.23 and 3.13 for predictors PSSM and ANN, respectively, on the NetCTLpan dataset. Likewise, evaluation on the SARS-CoV-2 dataset of HLA-A*0201 revealed that the PSSM predictor (2.46%) performed better than the other contemporary CTL epitope forecast methods like naturally eluted ligands (EL) of NetMHCpan 4.0 (2.66%), NetCTLpan 1.1 (2.69%), and binding affinity (BA) of NetMHCpan 4.0 (3.33%), respectively. Conclusions: The application of these predictive models offers a significant reduction of approximately 97% in the resources typically required for epitope identification, including costs related to materials, labor, and time. As such, these models represent a valuable advancement in the rational design of more efficient, cost-effective, and innovative biotherapeutics. Original Article Wed, 10 Sep 2025 00:00:00 GMT Satarudra PrakashSingh, GarimaSingh, Bhartendu NathMishra, Wed, 10 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003215 https://www.explorationpub.com/Journals/ei/Article/1003216 Aim: Despite advances in lymphoma treatment, resistance to conventional therapies and insufficient immune-mediated tumor clearance remain major challenges. This study investigates the dual antitumor mechanisms of the mushroom-derived triterpenoid, ganoderic acid DM (GA-DM), exploring its ability to induce programmed cell death while enhancing immune recognition in diffuse large B-cell lymphoma (DLBCL). Methods: DLBCL cells (DB and Toledo) were treated with GA-DM (0–40 μM), and cell viability was assessed via MTS assay. Apoptosis was evaluated through caspase-3 activation and inhibition by ZVAD-FMK, while autophagy was measured via LC3 protein expression. Flow cytometry analyzed HLA class II surface expression and antigen presentation to CD4+ T cells (via IL-2 production), with autophagy’s role further confirmed using the inhibitor 3-MA. Results: GA-DM exhibited potent and dose-dependent cytotoxicity against DLBCL cells, with concentrations of 30–40 μM inducing over 60% cell death within 24 h. Mechanistic studies revealed that GA-DM activated the intrinsic apoptotic pathway, as evidenced by caspase-3 cleavage and the significant reduction in cell death upon ZVAD-FMK treatment. Concurrently, GA-DM treatment upregulated the autophagy marker LC3-II, indicating the induction of autophagy. Strikingly, GA-DM also enhanced the immunogenicity of lymphoma cells by increasing surface expression of HLA class II molecules. This led to improved antigen presentation and subsequent activation of CD4+ T cells, as demonstrated by a 2.5-fold increase in IL-2 production (amount of IL-2 in pg/mL) compared to untreated controls. The critical role of autophagy in this process was confirmed by the near-complete abrogation of HLA class II-mediated T-cell activation upon 3-MA treatment. Conclusions: GA-DM synergistically induces apoptosis and autophagy while promoting immune-mediated tumor clearance through enhanced HLA class II antigen presentation. These findings highlight GA-DM as a promising multi-modal therapeutic candidate for lymphoma immunotherapy. Original Article Fri, 12 Sep 2025 00:00:00 GMT KayceBlumenstock, Faisal F. Y.Radwan, VandanaZaman, Narendra L.Banik, AzizulHaque, Fri, 12 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003216 https://www.explorationpub.com/Journals/ei/Article/1003220 Cancer is a multifaceted and heterogeneous disease characterized by uncontrolled growth, evasion of immune surveillance, and resistance to conventional therapies. The immune system plays a crucial role in tumor surveillance. However, tumors exploit immune checkpoint pathways to inhibit T cell activation and evade immune destruction. Immune checkpoint inhibitors (ICIs) have markedly improved outcomes in certain cancers by restoring T cell function and enhancing anti-tumor immunity. Despite these advances, the presence of immune resistance mechanisms contributes to variability in responses and ongoing challenges in overcoming resistance. Triple-negative breast cancer (TNBC), compared to other breast cancer (BC) subtypes, exhibits higher immunogenicity, but its anti-tumor immunity is profoundly suppressed by immune checkpoint molecules, creating a paradoxical scenario of “high immunogenic potential yet restrained by inhibitory signals”. Consequently, TNBC has become a significant target for ICI therapy. However, response rates vary among BC subtypes, with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) BC demonstrating lower immunogenicity. Hematological malignancies, including leukemia, lymphoma, and multiple myeloma, also exhibit distinct immune checkpoint dynamics, influencing their responsiveness to ICIs. This review comprehensively examines the mechanisms of immune checkpoint regulation, their role in cancer immune evasion, and the clinical applications of ICIs in both solid and hematological malignancies. It further discusses emerging strategies to counteract ICI resistance, such as dual checkpoint blockade, tumor microenvironment modulation, metabolic targeting, and epigenetic reprogramming. An enhanced understanding of immune checkpoint biology is essential for optimizing immunotherapy strategies and improving patient outcomes. The literature selection for this study was guided by relevance to the research topic, focusing on peer-reviewed articles, monographs, and conference proceedings published between 2010 and 2025, sourced from databases like PubMed and Google Scholar. Review Tue, 30 Sep 2025 00:00:00 GMT QingBao, HaomingChen, SongWu, ZhiTian, HailinTang, Tue, 30 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003220 https://www.explorationpub.com/Journals/ei/Article/1003218 The skin covers the entire surface of the body and therefore is the largest organ in humans. The skin has various functions, primarily defence from infections and trauma. With aging, profound changes occur that compromise its key functions, leading to impaired barrier protection and immune responses. This is in part due to the increased low-grade systemic inflammation known as inflammaging, driven by senescent cells, and release of pro-inflammatory cytokines, to which the skin also significantly contributes. As a consequence of inflammaging, the skin’s function is compromized. The cellular and molecular components involved are summarized in this review. Mini Review Tue, 30 Sep 2025 00:00:00 GMT NatasaStrbo, SujadYounis, DanielaFrasca, AlessiaPaganelli, Tue, 30 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003218 https://www.explorationpub.com/Journals/ei/Article/1003219 Eosinophilic granulomatosis with polyangiitis (EGPA) is an uncommon form of necrotizing vasculitis that affects the respiratory system and other organs, characterized by asthma, eosinophilia, and multiple organ involvement that complicates the diagnosis and treatment. There are no definitive open-label clinical data on the diagnosis or treatment of EGPA to guide clinicians. The diverse presentation of the disease, distinct from other eosinophilic disorders; the presence of competing conditions such as allergy and asthma, which also have potential biomarkers; lack of a definitive test to confirm diagnosis; difficulties in obtaining endoscopic biopsies for histologic confirmation, etc., are significant barriers to early detection. Even with recent advances in imaging, immunological approaches, and molecular testing to determine the disease’s identity and characteristics, clinicians still misdiagnose or delay treatment, sometimes leading to life-threatening and irreversible complications. Though EGPA is pharmacotherapeutically controlled with glucocorticoids, it has typically included the use of cytotoxic agents such as cyclophosphamide for induction in cases of severity. Recently, several clinical trials have examined targeted biologic treatments (such as mepolizumab, benralizumab, and omalizumab) and demonstrated that these medications can reduce exacerbations, decrease the need for glucocorticoids, and improve asthma control. New drugs such as dupilumab and new anti-IL-5/IL-5R monoclonal antibodies are being studied in phase II and phase III trials, and these drugs may provide additional avenues for refractory disease. Treatment will be organized based on individualization of treatment strategy, depending on disease severity, organ involvement, and biomarker profile. Vertical investment in multicenter longitudinal studies is necessary to formulate therapeutic algorithms and evaluate new targets. Review Tue, 30 Sep 2025 00:00:00 GMT PriyaKomre, AkashGupta, Sanjay KumarGupta, Tomy MuringayilJoseph, Debarshi KarMahapatra, Tue, 30 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003219 https://www.explorationpub.com/Journals/ei/Article/1003221 T cell-based immunotherapies increasingly include personalized neoantigen vaccines that target tumor-specific mutations. However, despite their promise, current neoantigen vaccines show limited and unpredictable clinical benefit, with T cell responses observed in only a subset of patients. To overcome these limitations, we developed the VERDI (Vaccine Epitopes Ranked by Digital Intelligence) System—a cloud-based computational platform that integrates a patient’s human leukocyte antigen (HLA) class I and II genotype with selected tumor-associated antigens (TAAs), including cancer-testis antigens (CTAs), to identify peptides with high predicted immunogenicity and low risk of immune-related adverse events (irAEs). Using the VERDI System, we designed ten personalized peptide vaccines for a patient with metastatic signet ring cell carcinoma (SRCC), a rare and aggressive gastric cancer with limited treatment options. All ten VERDI vaccines were well tolerated and consistently induced tumor-specific T cell responses following a single administration, without the need for checkpoint inhibitors. The patient survived for 15 months—substantially longer than the reported median survival of 5.6 months in metastatic SRCC—highlighting the potential of this individualized, predictive vaccine platform to improve outcomes in advanced cancer. Case Report Tue, 14 Oct 2025 00:00:00 GMT JuliannaLisziewicz, AndrasSzasz, TamasKos, AbrisHeisz, AlfredoMinguela, Miguel MarinVera, SantiagoMolina, Carlos Manuel MartinezCaceres, Miguel BlanquerBlanquer, FrancoLori, Jose MariaMoraleda, Bartolome GarciaPerez, Tue, 14 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003221 https://www.explorationpub.com/Journals/ei/Article/1003222 Cutaneous lupus erythematosus (CLE) is the most common organ manifestation in individuals diagnosed with systemic lupus erythematosus (SLE). CLE can occur either alone or in association with SLE; in the latter case, it substantially increases the occurrence of disease flares and can cause disfigurement. The clinical pathogenesis of CLE is well established, as exposure to ultraviolet (UV) light and/or other environmental triggers, such as smoking or drug use, can lead to keratinocyte death in genetically susceptible individuals. This in turn activates cytotoxic T cells, plasmacytoid dendritic cells (pDCs), and B cells, creating a continuous interaction between the innate and adaptive immune systems. This interaction plays a pivotal role in CLE development, driving the formation of skin lesions. However, the molecular mechanisms underlying these cutaneous manifestations are not yet fully understood. While significant advances have been made in SLE treatment over the past few decades, U.S. Food and Drug Administration (FDA)-approved therapies remain limited to hydroxychloroquine, glucocorticoids, belimumab, and anifrolumab. Although new therapies for CLE have emerged, given the highly heterogeneous nature of the condition, personalized medicine is essential to prevent disfigurement and systemic disease flares. Understanding the molecular pathogenesis of CLE is crucial for developing targeted therapies and improving patient outcomes. This review presents current insights into CLE pathogenesis, highlighting key mechanisms driving the disease and exploring recent advances in treatments that have shown promise in clinical practice. Review Fri, 24 Oct 2025 00:00:00 GMT Fatima K.Alduraibi, JoshGoldsmith, Peter C.Chien, Fri, 24 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003222 https://www.explorationpub.com/Journals/ei/Article/1003223 The human vaginal microbiome plays a pivotal role in maintaining female reproductive health through its Lactobacillus-dominated microbial ecology. These bacteria contribute to the acidic pH of the vagina by producing lactic acid, ultimately preventing the colonization of pathogens. Additionally, they produce bacteriocins and hydrogen peroxide, which are detrimental to other microorganisms. Human vaginal microbiota is subjected to alterations with advancement in age, hormonal status, puberty, menstruation cycle, pregnancy and gestation, vaginal tract diseases, exposure to antibiotics, etc. Diet, lifestyle factors, obesity, and gestational diabetes are also reported to cause a shift in vaginal microbiota. This review thoroughly illustrates the perpetually changing dynamics of vaginal microbiota throughout women’s lives, as well as focuses on the impact of dysbiosis in bacterial vaginosis. More emphasis is given on immunological changes observed during bacterial vaginosis, mainly IL-1β, and its involvement in the development of preeclampsia. Thereby, this review highlights a mechanistic link between lower genital tract disease, bacterial vaginosis, and a hypertensive disorder of pregnancy, preeclampsia, via IL-1β–ROR-γt–Th17 axis, which is regulated by vitamin D, with a suggestion on how shifts in vaginal microbial community may pose a risk for preeclampsia. Review Fri, 24 Oct 2025 00:00:00 GMT DevanshiGajjar, SriramSeshadri, Fri, 24 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003223 https://www.explorationpub.com/Journals/ei/Article/1003224 Cancer treatment regimens are significantly more intricate than commonly perceived. Nonetheless, both immunotherapy and chemotherapy may produce adverse consequences. Immunotherapy represents a significant advancement in the battle against cancer; nonetheless, it is not devoid of challenges. This research elucidates the mechanisms underlying immunotherapy-induced cardiovascular damage, highlighting the significant role of immune regulators, such as soluble urokinase plasminogen activator receptor (suPAR), in inducing vascular leakage. We also examine the role of matrix metalloproteinase (MMP14/15) in this process, and antigens associated with cardiovascular illness and malignancies, including native proteins, mutated tumor antigens, and viral components. Besides, we studied predictive biomarkers, such as circulating T-cell populations associated with the probability of myocarditis. We discuss treatment approaches and strategies to mitigate these issues, particularly through the use of antihypertensive medications to reduce their impact. Losartan alters the tumor microenvironment (TME) to improve immunotherapy. It restores immune effector cells in triple-negative breast cancer (TNBC), overcomes resistance in unresponsive tumors, and modifies TMEs’ immune system suppression in ovarian cancer and melanoma. It is important to note that its effects differ by cancer kind. It may promote fibrosarcoma tumor growth and improve cholangiocarcinoma treatment. This shows that losartan’s dangers in cancer treatment should be carefully considered and that more research is needed. This suggests that there must be careful consideration of the potential risks associated with losartan use in cancer treatment and underscores the requirement for additional research on this topic. This study may enhance our comprehension and management of cardiovascular adverse effects in cancer immunotherapy by integrating novel insights on immunological predictors and vascular dysfunction. Experts assert that oncology programs must provide and promote continuous monitoring of cardiac health for breast cancer patients. To mitigate the risk of cardiovascular disease in this demographic, comprehensive patient care must be administered. Review Tue, 28 Oct 2025 00:00:00 GMT FakherRahim, ShamimGozin, Salar HuseinKarim, Ainur BakdauletkyzyQumar, KobraDoostali, IssenovaBalday, Tue, 28 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003224 https://www.explorationpub.com/Journals/ei/Article/1003227 Tumor-infiltrating lymphocytes (TILs) play a critical role in the ability of the immune system to combat cancer, offering a foundation for personalized immunotherapies. However, the effectiveness of TILs is often reduced by problems like becoming less active, the tumor making the immune system weaker, and not lasting long in the tumor environment. Recent advancements in single-cell technologies, including single-cell RNA sequencing (scRNA-seq), single-cell T-cell receptor sequencing (scTCR-seq), and mass cytometry (CyTOF), have revolutionized our understanding of TIL heterogeneity and dynamics. These tools offer new perspectives on the diverse phenotypes, functional states, and spatial organization of TILs, enabling the identification of key exhaustion markers, regulatory pathways, and neoantigen-specific clones. Concurrently, genetic reprogramming strategies have emerged to address TIL limitations by reversing exhaustion, enhancing metabolic resilience, and improving persistence in vivo. This review explores the synergistic integration of single-cell technologies and genetic engineering in refining TIL-based therapies. We talk about how spatial transcriptomics can help us understand how TILs work in different areas of the body and how changing their epigenetics can help them become more effective at fighting cancer. Additionally, we highlight emerging approaches to overcome immunosuppressive barriers in the tumor microenvironment (TME), including targeting regulatory immune cells, neutralizing suppressive cytokines, and enhancing antigen presentation. Together, these strategies promise to unlock the full therapeutic potential of TILs, paving the way for more effective and durable cancer immunotherapy. Review Tue, 18 Nov 2025 00:00:00 GMT ChaitanyaKumar, RaviVerma, AshokSharma, Veeraraghavan VishnuPriya, Tue, 18 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003227 https://www.explorationpub.com/Journals/ei/Article/1003226 Innate lymphoid cells are lymphocytes that are neither T cells nor B cells. They are relatively rare in lymphoid tissues and peripheral blood and are distinguished by their absence of an adaptive antigen receptor. In the present study, we describe the mechanisms underlying the generation of the various cell populations and highlight the functional importance of their plasticity. These cells are indeed capable of transdifferentiating from one type to another. This adds complexity to their functional program, and this feature appears to be crucial for adapting and modulating immune responses under different conditions. These lymphoid cells are of great hematological interest due to their pathophysiological and therapeutic role in many onco-hematological pathologies such as acute myeloid leukemia, multiple myeloma, and several types of lymphomas. In hematological disorders, innate lymphoid cells may exert differential effects on the pathogenesis of hematologic malignancies. Furthermore, within the same disease, certain cell populations have been shown to play a protective role in antitumor immune responses, whereas others appear to suppress these responses. This review aims to provide an integrated description of innate lymphoid cells, their alterations in hematological malignancies, and potential preventive strategies, by proposing new specific targets for correcting anomalies. We also discuss the use of innate lymphoid cells as new therapies by applying chimeric antigen receptor-modified natural killer cells. We examine the current knowledge and outline future perspectives. Review Tue, 18 Nov 2025 00:00:00 GMT MarioDi Gioacchino, AntonioPagana, GiuseppeMirabile, Loredanadella Valle, FabioStagno, SebastianoGangemi, AlessandroAllegra, Tue, 18 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003226 https://www.explorationpub.com/Journals/ei/Article/1003225 Not applicable. Editorial Thu, 06 Nov 2025 00:00:00 GMT AnnaCalabrò, CalogeroCaruso, Thu, 06 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003225 https://www.explorationpub.com/Journals/ei/Article/1003228 Background: Oral squamous cell carcinoma (OSCC), a significant health burden in developing nations, is linked to risk factors such as tobacco use, alcohol consumption, betel nut chewing, HPV infection, and genetic susceptibility. A hallmark of OSCC is impaired T cell function, driven in part by the PD-L1/PD-1 immune checkpoint pathway, which enables tumor immune evasion and progression. Despite growing interest in immunotherapy, a focused synthesis of PD-L1 expression and its clinical implications in OSCC remains limited. This review aims to consolidate existing evidence on PD-L1 in OSCC, evaluating its expression patterns, correlation with disease progression, and therapeutic relevance. Methods: A systematic search was conducted across multiple databases to identify studies examining PD-L1 expression in OSCC and its relationship with clinicopathological parameters and immune response. Results: The findings revealed a higher PD-L1 positivity in female patients, non-smokers, and non-drinkers. Positive PD-L1 expression rate correlated with poor differentiation, lymph node metastasis, and advanced TNM stage. Although it didn’t significantly impact overall survival, higher PD-L1 expression was observed in HPV-positive patients and correlated with increased CD8+ TIL levels. Discussion: Understanding the role of PD-L1 in OSCC elucidates immune evasion mechanisms and offers insights into potential treatments, such as checkpoint inhibitors, for personalized therapies and innovative cancer treatments. This comprehensive synthesis provides valuable insights into the complex interplay between PD-L1 expression and OSCC progression, laying the groundwork for additional studies in this area. Systematic Review Tue, 18 Nov 2025 00:00:00 GMT NehaKannan, KarthikeyanRamalingam, PratibhaRamani, Maria MaddalenaMarrapodi, RoccoFranco, DianaRusso, MarcoCicciù, GiuseppeMinervini, Tue, 18 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003228 https://www.explorationpub.com/Journals/ei/Article/1003229 Killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) molecules play an essential role in regulating immune responses against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. HLA-KIRs interactions are crucial for activating and inhibiting the natural killer (NK) cell system through a modulation that shapes these cells to kill infected cells and release cytokines. Regulation underlies the anti-viral function of the NK cell and profoundly affects viral clearance, immune evasion, and the course of disease. Activating KIRs such as KIR2DS1 and KIR3DS1 cooperate with specific HLA ligands in boosting NK cell responses against the virus, thereby facilitating viral elimination. In contrast, inhibitory KIRs like KIR2DL1 and KIR3DL1 bind to HLA-C2 and HLA-Bw4, respectively, imposing a dampening influence on NK cell activation, which allows the virus to persist and progress to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). These variations in KIRs and HLA genes will also affect an individual’s susceptibility to infections, disease severity, and their response to antiviral therapies. Observation of the role of KIRs and their interaction with HLA at the immunogenetic level provides valuable insight into host-virus dynamics and opens up many therapeutic avenues. Targeting immunotherapies toward NK cell pathways and developing personalized medicine may boost antiviral immune responses and improve treatment outcomes in chronic viral hepatitis patients. This review recognizes HLA-KIRs interactions as potent biomarkers for disease progression and determining treatment strategies. Review Mon, 24 Nov 2025 00:00:00 GMT AtaShirizadeh, Amir MohammadZargar, TohidKazemi, GhasemSolgi, Mon, 24 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003229 https://www.explorationpub.com/Journals/ei/Article/1003230 Aim: Develop A/H1N1pdm09-based live attenuated influenza vaccines (LAIVs) presenting chimeric hemagglutinin (HA) fused to fragments of Streptococcus pneumoniae (PspA, Spr1875) or S. agalactiae (ScaAB) to elicit combined anti-influenza and anti-bacterial immunity. Methods: Recombinant LAIVs were generated by reverse genetics. Replicative fitness was measured in embryonated chicken eggs (CE; log10 EID50/0.1 mL, n = 5 per delution) and MDCK cells (log10 TCID50/mL, n = 5). BALB/c mice (n = 20 per group; serology n = 6 per group; lung titers n = 5 per group) received intranasal 106 EID50. Systemic IgG and mucosal IgA to influenza and to the recombinant pneumococcal peptide were quantified by ELISA (GMT ± SD). Early cytokine responses were profiled in THP-1 cells. Results: All recombinant strains replicated in CE at 33°C but were temperature-sensitive at 39°C. H1-ScaAB retained relatively high replication and exhibited a cold-adapted phenotype despite a large N-terminal insert. In MDCK cells, H1-PspA showed significantly reduced replication compared with the parental LAIV. In mouse lungs, replication on day 3 post-immunization was significantly lower for H1-ScaAB and H1-PspA compared with the parental LAIV strain (p < 0.05). The parental LAIV induced robust systemic anti-influenza IgG and, uniquely for H1-ScaAB, significant mucosal anti-influenza IgA (p < 0.05). H1-Spr generated stronger antibody responses to the inserted pneumococcal peptide (p < 0.05). THP-1 assays revealed construct-specific cytokine patterns (unmodified H1N1: highest IFN-α; H1-Spr: elevated IL-6; H1-ScaAB: greatest MCP-1). Conclusions: Multiple A/H1N1pdm09-based recombinant LAIVs with chimeric HA can replicate in eggs and murine respiratory tract and induce dual influenza/pneumococcal antigen responses. Expanded biophysical validation, functional antibody assays and challenge studies are needed to optimize insert design without compromising viral fitness. Original Article Fri, 28 Nov 2025 00:00:00 GMT YuliaDesheva, IrinaMayorova, AndreyRekstin, PolinaKudar, AndreyTrulioff, DariaPetrachkova, TatianaKotomina, NinaKopylova, AnastasiiaMatushkina, DaniilSokolovsky, DanilaGuzenkov, IrinaIsakova-Sivak, Fri, 28 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003230 https://www.explorationpub.com/Journals/ei/Article/1003231 Aim: To determine whether PepTivator® melanoma-associated antigen-A3 (MAGE-A3) primes early T-cell activation and memory skewing in human peripheral blood mononuclear cells (PBMCs). Methods: PBMCs from 10 donors were stimulated with MAGE-A3 (manufacturer-recommended dose), negative control (NC), or CD3/CD28 and CytoStim™ (PC: positive control). Activation [CD69, CD25, HLA-DR (human leukocyte antigen-DR isotype)], proliferation, cytokines [24 h; GM-CSF (granulocyte-macrophage colony-stimulating factor), IFN-γ (interferon-gamma), IL-2 (interleukin-2), TNF-α (tumor necrosis factor-alpha)], and memory phenotypes (CD45RO/CD27 at days 0/7/14) were quantified by flow cytometry and MACSPlex. Paired statistics used repeated-measures models with Šidák correction; cytokines were analyzed on log10 scale. Results: MAGE-A3 significantly increased early activation (CD69 ↑, CD25 ↑) and modestly increased proliferation, with selective IL-2/TNF-α rise and minimal IFN-γ and modest HLA-DR. Across two weeks, 6/10 donors showed increased central memory T cell (TCM)/effector memory T cell (TEM) with a corresponding decline in naïve cells relative to NC. Variability across donors was evident. Conclusions: MAGE-A3 primes partial activation and memory skewing of human T cells in vitro, suggesting utility as a component antigen that likely benefits from professional antigen-presenting cell (APC) presentation and/or costimulation. We discuss limitations (single dose, in vitro context, donor variability) and implications for future dose-response, HLA-stratified, and APC-supported studies. Original Article Thu, 18 Dec 2025 00:00:00 GMT GaurangTelang, SmritiMishra, AnuragSureshbabu, SamruddhiKulkarni, SagarBarage, A.W. SanthoshKumar, RajshriSingh, Thu, 18 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003231 https://www.explorationpub.com/Journals/ei/Article/1003232 Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract with significant clinical impact, leading to debilitating symptoms, impaired quality of life, and an increased risk of complications such as colorectal cancer. This review provides a comprehensive overview of current and emerging therapeutic strategies for IBD. We conducted a narrative review to explore therapeutic advances in IBD treatment, focusing on mechanisms of action, clinical development, and current therapeutic challenges. We analyzed existing knowledge on clinical drug development for IBD, up to July 2025. Our search encompassed databases including PubMed, ClinicalTrials.gov, and Google Scholar, using keywords such as “Inflammatory bowel disease”, “Crohn’s disease”, “Ulcerative colitis”, “therapeutics”, and relevant drug names. We delve into key progress in approved drugs in recent years, including biologic and targeted small molecule therapies, which have advanced the treatment paradigms by offering more precise targeting of inflammatory pathways. This review also covers investigational drugs in clinical development, including biologics and small molecules against novel molecular targets, cell and gene therapies, precision medicine approaches, and microbiome-based interventions. Those novel therapies could potentially address unmet medical needs by achieving deeper and more durable responses, inducing remission, preventing disease progression, and ultimately improving long-term patient outcomes. This review summarizes the latest progress in IBD treatment, outlines the advantages, pitfalls, and research prospects of various drugs and therapies, aiming to provide a foundational understanding for both clinical decision-making and future IBD research. Review Wed, 24 Dec 2025 00:00:00 GMT YuZhou, FangShen, Wed, 24 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003232 https://www.explorationpub.com/Journals/ei/Article/1003233 Aim: The benefit of topical application of probiotics on pain and itching associated with skin disorders has become an increasingly intriguing topic in recent years. These effects are mainly associated with the anti-inflammatory activity of probiotics. Given the crucial role of the endocannabinoid system (ECS) in skin pathophysiology, here, the ability of Streptococcus thermophilus was evaluated, in comparison with Lactobacillus acidophilus, to inhibit two enzymes involved in endocannabinoid (eCB) degradation: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Methods: Bacterial lysates were obtained from both probiotics. FAAH and MAGL activities were assayed using fluorometric and colorimetric methods. The effect of probiotic lysates on FAAH and MAGL activities was also evaluated on human keratinocytes stimulated with lipopolysaccharide (LPS). Results: S. thermophilus inhibited both FAAH and MAGL, although to varying extents. In comparison, L. acidophilus had a minimal effect on FAAH and did not influence MAGL activity. Conclusions: Although preliminary, our findings suggest that S. thermophilus may exert both potential analgesic and anti-inflammatory effects by modulating the ECS and reducing the degradation of EC, known to play a key role in immune regulation and inflammation. Results presented confirm the selective actions of probiotics and propose a novel mechanism that may contribute to the beneficial effects of S. thermophilus in alleviating signs and symptoms associated with inflammatory skin conditions. Our evidence shows significant inhibitory activity of S. thermophilus on FAAH and MAGL activity, suggesting its ability to influence skin conditions by modulating ECS and preventing the eCB degradation. Original Article Wed, 31 Dec 2025 00:00:00 GMT SerenaAltamura, ElonaDybeli, FrancescaLombardi, PaolaPalumbo, Francesca RosariaAugello, SkenderTopi, Maria GraziaCifone, BenedettaCinque, Wed, 31 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003233 https://www.explorationpub.com/Journals/ei/Article/1003234 Vaccines can be highly safe and effective tools for disease prevention. However, improvements in the areas of cost, ease of manufacture, distribution, and administration are sought in the next generation of vaccine platforms. A promising candidate is the recombinant flagellin fusion protein platform, which comprises a protein antigen of interest genetically fused to the bacterial protein flagellin. As flagellin stimulates two distinct pattern recognition receptors of the human innate immune system (Toll-like receptor 5 and nucleotide-binding and oligomerization domain-like receptor family apoptosis inhibitory protein) and contains helper T-cell epitopes, it is capable of serving as both a carrier and an adjuvant for the target antigen. Studies in animal models and human clinical trials have shown that flagellin fusion proteins can induce diverse humoral (including various subtypes of IgG), mucosal (including secreted IgA), and cell-mediated (TH1 and TH2 CD4+ helper T-cell and CD8+ cytotoxic T-cell) responses to the covalently linked antigen. Such fusions are also capable of eliciting protective immunity in diverse experimental models of infection and cancer. They are effective via numerous routes of administration, including intranasal delivery, without the requirement for adjuvant or complex delivery vehicles. This review aims to cover recent progress in the investigation of flagellin fusion proteins for their potential to stimulate humoral and cellular immune responses to partner antigens, and their prospects for the prevention or treatment of viral infections and cancer. Review Mon, 05 Jan 2026 00:00:00 GMT ClettErridge, Mon, 05 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003234 https://www.explorationpub.com/Journals/ei/Article/1003235 Pulsed radiofrequency (PRF) has emerged as a promising and versatile technology in pain management and immunological modulation. PRFʼs effects extend beyond pain modulation, demonstrating the ability to regulate inflammatory processes through cytokine modulation, reduction of microglial hyperactivity, and promotion of autophagy. These mechanisms position PRF as a potential therapeutic tool not only for neuropathic and musculoskeletal pain but also for conditions associated with neuroinflammation and immune dysfunction, including chronic inflammatory and degenerative diseases. Clinically, PRF has demonstrated potential in alleviating neuropathic pain in several clinical studies—including a limited number of small RCTs. However, most of the available evidence remains of low methodological quality, with many studies being observational, retrospective, or underpowered. Moreover, the lack of standardized protocols remains a barrier to its broader adoption. Establishing evidence-based guidelines and enhancing practitioner expertise are critical to ensuring consistent and optimal patient outcomes. Future research should focus on optimizing PRF technical parameters, elucidating molecular mechanisms, and expanding its clinical applications. Integrating PRF with emerging therapies, such as orthobiologics, biological drugs, and electrical stimulation, may further enhance its efficacy. Moreover, advancements in predictive biomarkers and device technologies hold promise for personalized treatments, improving the precision and effectiveness of PRF interventions. This narrative review explores the primary clinical applications, underlying biological mechanisms, and potential future directions of PRF, emphasizing its ability to address complex therapeutic challenges. Review Mon, 12 Jan 2026 00:00:00 GMT FeliceOcchigrossi, JacopoMosca, Matteo Luigi GiuseppeLeoni, AlbertoPasqualucci, RobertoGazzeri, MarcoCascella, GiustinoVarrassi, Mon, 12 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003235 https://www.explorationpub.com/Journals/ei/Article/1003236 Pneumococcal disease remains a major global health challenge despite the availability of polysaccharide and conjugate vaccines. Although these platforms have reduced invasive disease, their limitations, such as poor immunogenicity in infants, lack of durable protection, and restricted coverage, highlight the need to explore innovative preventive strategies. Next-generation vaccines that provide comprehensive protection, sustained immunity, and cost-effectiveness are urgently required. Live attenuated vaccines (LAVs) represent a promising frontier in this effort, with recent advances focused on overcoming developmental and safety challenges. This review highlights the evolving pneumococcal vaccine landscape, with emphasis on LAV strategies. We summarize the strengths and shortcomings of current vaccines, examine recent advances in LAV development, including key aspects of attenuation, immune-protective mechanisms, and delivery approaches. LAVs demonstrate potential to induce balanced mucosal, humoral, and cellular immunity, addressing critical gaps left by existing platforms. Key challenges related to genetic stability, safety, and translational applicability are also discussed. By synthesizing established knowledge and highlighting advancements, this review underscores the promise of LAVs as next-generation candidates that can provide broader, longer-lasting protection against pneumococcal disease. Review Tue, 27 Jan 2026 00:00:00 GMT MarinaYusoff, Chew ChiengYeo, MalikAmonov, Tue, 27 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003236 https://www.explorationpub.com/Journals/ei/Article/1003237 For decades, vaccines have been a key tool against microbial infections. However, the high cost of production and purification renders vaccines largely inaccessible to many developing countries. The limitations of conventional vaccines can be overcome by edible vaccines. To produce an oral vaccine, favourable vectors, such as plants and probiotics, are used. Recent studies have revealed the immunomodulatory effects of probiotics. To improve the efficacy of these vaccines, several adjuvant approaches have been employed. Postbiotics can be used as promising therapy for preventing infections and enhancing the host immune system due to their unique biochemical and microbial-derived properties. In this review, we discuss the feasibility of postbiotics as adjuvants for oral vaccines, highlighting their mechanisms of action, safety profile, and potential to enhance both mucosal and systemic immune responses. Review Fri, 13 Feb 2026 00:00:00 GMT RoyaAbedi Soleimani, JalilHoushyar, SimaVadaei, SoheilaAbachi, PayamGonbari Milani, AzarAbedi Soleimani, NaderKhani, MohammadrezaZiavand, Aziz HomayouniRad, Fri, 13 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003237 https://www.explorationpub.com/Journals/ei/Article/1003239 Atopic dermatitis is a chronic inflammatory skin condition characterized by immune dysregulation and dysfunction of the epidermal barrier. Although occludin, a vital tight junction protein, is essential for preserving barrier integrity, very little is known about its potential as a serum biomarker in atopic dermatitis. This pilot case-control study measured serum occludin levels in 30 adult atopic dermatitis patients and 30 age- and sex-matched healthy controls between May and August 2025, using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Findings showed serum occludin levels were significantly higher in atopic dermatitis patients (mean: 2.50 ± 1.10 ng/mL) compared to healthy controls (mean: 0.68 ± 0.69 ng/mL; p < 0.001), with levels showing a decreasing trend with age. Serum occludin exhibited high diagnostic performance [area under the curve (AUC) = 0.92] and represents a sensitive and specific, non-invasive biomarker for atopic dermatitis. These preliminary findings lay the groundwork for future studies exploring serum occludin as a potential biomarker for atopic dermatitis assessment. Short Communication Thu, 12 Mar 2026 00:00:00 GMT Sheron TuneJawahar, ManonmoneyJayaraman, PriyatharsiniThamaraiselvan, Kakithakara VajraveluLeela, Thu, 12 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003239 https://www.explorationpub.com/Journals/ei/Article/1003238 Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are microbial metabolites generated through the fermentation of dietary fibers by the gut microbiota and are increasingly recognized as critical regulators of host immune homeostasis. Beyond their metabolic roles, SCFAs exert potent immunomodulatory effects across mucosal tissues, including the periodontium, by shaping both innate and adaptive immune responses. This review synthesizes current evidence on the dual roles of SCFAs in periodontal health and disease, with particular emphasis on the contrasting effects of systemically derived versus locally accumulated SCFAs within periodontal tissues. Gut-derived SCFAs absorbed into the circulation modulate immune function through activation of G protein-coupled receptors (GPR41, GPR43, and GPR109A) and inhibition of histone deacetylases. These pathways promote regulatory T cell differentiation, skew macrophage polarization toward anti-inflammatory M2 phenotypes, and regulate neutrophil and dendritic cell activity. These effects support immune tolerance, epithelial barrier integrity, and resolution of inflammation, thereby contributing to periodontal homeostasis. In contrast, SCFAs produced locally within periodontal pockets can reach millimolar concentrations that disrupt epithelial and fibroblast function, induce oxidative stress, and amplify inflammatory signalling, ultimately driving tissue destruction and disease progression. Emerging evidence links gut microbial composition and systemic SCFA availability to periodontal inflammation through immune and neuroimmune crosstalk, supporting a biologically plausible gut-oral axis. Translational strategies aimed at harnessing the immunoregulatory properties of SCFAs are critically evaluated in this review. While these approaches are promising, challenges related to dosing, delivery, inter-individual variability, and limited human interventional data remain, underscoring the need for rigorously designed translational studies. Review Thu, 12 Mar 2026 00:00:00 GMT DevlinaGhosh, AnshikaYadav, DaminiPandey, Thu, 12 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003238 https://www.explorationpub.com/Journals/ei/Article/1003240 Pain is among the most prevalent and debilitating symptoms experienced by patients with cancer, significantly impairing functional status and overall quality of life. Its origin is multifactorial, involving direct tumor infiltration, treatment-induced tissue and neural injury, and immune-mediated inflammatory processes. This section examines the epidemiology of cancer-related pain, delineates its complex pathophysiology with particular focus on neuroimmune interactions, and reviews current pharmacological and interventional approaches for managing both acute and chronic pain in oncological settings. Advancing knowledge of immune-driven pain mechanisms holds promise for the development of more targeted, effective, and personalized analgesic strategies in cancer care. Review Mon, 16 Mar 2026 00:00:00 GMT GiustinoVarrassi, DariuszMyrcik, Matteo Luigi GiuseppeLeoni, Mon, 16 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003240 https://www.explorationpub.com/Journals/ei/Article/1003242 Immuno-materials, which represent a confluence of immunology and materials science, are dramatically transforming the fields of healthcare. Through the targeted modulation of immune responses, these innovative materials offer promising avenues for advancements in vaccine development, immunotherapy, tissue engineering, and diagnostics. This review examines the fundamental principles of immuno-materials, elucidating key concepts and methodologies pertinent to their development. We investigate strategies for engineering materials that can elicit customized immune responses, capable of both stimulation and suppression, and we discuss their potential roles as adjuvants, carriers, or scaffolds. Furthermore, we address the challenges and opportunities associated with the clinical translation of these materials, emphasizing the critical importance of biocompatibility, safety, and efficacy. This review aims to critically evaluate and contextualize the transformative potential of immuno-materials, mapping their journey from laboratory design to proven clinical applications in enhancing human health. Review Mon, 30 Mar 2026 00:00:00 GMT MarcoTatullo, AndreaPacifici, RobertaRuggiero, FabianaInnocenzi, GianfrancoPalumbo, AnastasiaFacente, FrancescoPaduano, Mon, 30 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003242 https://www.explorationpub.com/Journals/ei/Article/1003241 Autoimmune diseases (ADs) comprise a heterogeneous group of disorders characterised by a breakdown of immune tolerance and chronic immune-mediated tissue damage. Their onset and progression result from a complex interplay between genetic susceptibility, hormonal influences, immune regulatory mechanisms, and environmental exposures collectively referred to as the exposome. A striking feature of ADs is their pronounced sexual dimorphism, with a markedly higher prevalence in women for most conditions, alongside sex-specific differences in clinical presentation, severity, and prognosis. This review provides a comprehensive overview of the genetic and environmental determinants contributing to autoimmunity, with particular emphasis on how sex- and gender-related factors shape immune tolerance and disease susceptibility. We discuss central and peripheral tolerance mechanisms, the role of key regulators such as AIRE and FOXP3, sex chromosome-linked effects including X-chromosome inactivation, and the immunomodulatory impact of sex hormones across different life stages. Furthermore, we examine how environmental exposures, infections, and geographic variability interact with genetic background and sex-specific immune regulation to influence autoimmune disease risk. By integrating biological sex and gender-related factors within the framework of immune tolerance and the exposome, this review highlights the need for a sex-aware and personalised approach to understanding, diagnosing, and treating ADs. Review Tue, 24 Mar 2026 00:00:00 GMT AnnaCalabrò, GiuliaAccardi, AnnaAiello, RosaZarcone, GiuseppinaCandore, Tue, 24 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003241 https://www.explorationpub.com/Journals/ei/Article/1003244 This review highlights the significant sex-based differences in immune responses to influenza infection and vaccination. Men are generally more susceptible to severe influenza outcomes, while women often mount stronger immune responses but experience more adverse effects. These disparities are influenced by biological factors, including sex hormones and genes, as well as gender-related social and environmental conditions. Evidence from both human and animal studies reveals sex-specific variations in antibody production, vaccine effectiveness, and clinical outcomes. Age, hormonal status, and stress further modulate these differences. Understanding these complex interactions is essential for developing tailored and equitable vaccination and treatment strategies. Review Tue, 14 Apr 2026 00:00:00 GMT AnnaCalabrò, AnnaAiello, EmanueleMontomoli, GrahamPawelec, Claudia MariaTrombetta, CalogeroCaruso, Tue, 14 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003244 https://www.explorationpub.com/Journals/ei/Article/1003246 Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction marked by fluctuating muscle weakness, driven by pathogenic antibodies targeting acetylcholine receptors, muscle-specific kinase, or lipoprotein receptor-related protein 4. Traditional treatments such as corticosteroids and immunosuppressants provide symptomatic relief but are limited by systemic toxicity and variable efficacy. Advances in immunology have led to targeted biologics that address specific disease mechanisms, such as B-cell depleting antibodies like rituximab and inebilizumab, complement inhibitors such as eculizumab, ravulizumab, and zilucoplan, and neonatal Fc receptor antagonists like efgartigimod and rozanolixizumab that lower pathogenic IgG levels. Emerging molecular and cellular therapies, including T-regulatory cell therapy, RNA-based modulation, and chimeric antigen receptor T-cell therapy approaches, seek to achieve durable immune tolerance rather than transient suppression. However, therapeutic response varies due to immunologic heterogeneity, long-term safety concerns, and limited global access. Future directions focus on precision medicine, biomarker-guided treatment, and AI-assisted disease monitoring, alongside next-generation therapeutics such as long-acting FcRn inhibitors (IMVT-1402), bispecific antibodies (gefurulimab), and oral small molecules (remibrutinib, iptacopan). Collectively, these developments mark a shift from generalized immunosuppression toward mechanism-based, patient-centered care aimed at restoring lasting immune balance and improving quality of life in MG. This narrative review discusses these aspects to comprehend the existing understanding and challenges. Review Tue, 14 Apr 2026 00:00:00 GMT ShaanPatel, SankalpNigam, HusseinMaatouk, TanmaySinghal, VikrantRai, Tue, 14 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003246 https://www.explorationpub.com/Journals/ei/Article/1003245 Breast cancer exhibits substantial clinical and molecular heterogeneity, partly shaped by interactions between tumor biology and the host immune system. Germline variants in immune-related genes may influence inflammatory tone, immune regulation, and tumor-immune interactions. However, evidence linking inherited immune genetic variation to breast cancer risk and clinical behavior remains fragmented and heterogeneous across studies. We conducted a structured integrative review of 33 human genetic associations evaluating germline variants in immune-related genes and their associations with breast cancer risk, prognosis, and clinicopathological features. Data were synthesized using a comparative, pathway-oriented analytic framework. Variants in cytokine genes, particularly TGFB1, IL6, IL1B, and IL10, were the most frequently associated with susceptibility, although effect directions varied across populations and genetic models. In contrast, variants in chemokine pathways (CXCL12) and immune checkpoint regulator genes (B7-H4/VTCN1, PD-1/PDCD1) showed consistent associations with tumor progression, immune evasion, and subtype-specific clinical features, including human epidermal growth factor receptor 2 (HER2)-positive disease and metastatic presentation. Across studies, substantial heterogeneity was observed, driven by differences in ethnic composition, sample size, methodological design, and deviations from the Hardy-Weinberg equilibrium. The findings support a pathway-oriented interpretation in which germline immune variation differentially influences immune regulation and tumor progression rather than uniformly determining disease risk. While inflammatory and immunoregulatory pathways appear to shape basal immune tone, immune effector function is less consistently associated with germline variation. Further progress will require extensive, multiethnic studies integrating genetic, transcriptomic, and functional data to clarify how inherited immune variation contributes to breast cancer biology. Review Tue, 14 Apr 2026 00:00:00 GMT MuriloPorfírio de Aguiar, Julia HailerVieira, Jéssica FerreiraVieira, Tue, 14 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003245 https://www.explorationpub.com/Journals/ei/Article/1003243 Genistein, a soy-derived isoflavone, has attracted considerable interest for its anti-inflammatory and anticancer properties. Chronic inflammation is a major driver of tumour initiation, progression, metastasis, and therapeutic resistance, creating a need for multi-target agents capable of modulating both inflammatory and oncogenic pathways. This review critically evaluates the molecular mechanisms, pharmacological basis, and translational prospects of genistein in inflammation-related cancers, incorporating recent advances in omics technologies and nanotechnology-based delivery systems. A comprehensive survey of the literature from major scientific databases was conducted, and evidence was assessed based on mechanistic depth, strength of data, and relevance to clinical translation. Genistein modulates multiple interconnected signalling pathways, including NF-κB, MAPK, PI3K/Akt, JAK/STAT, and apoptotic cascades, leading to reduced pro-inflammatory cytokine production, oxidative stress, and tumour cell proliferation. Epigenetic regulation, growth-factor pathway inhibition, and non-coding RNA modulation further contribute to its pleiotropic effects. Nanotechnology-based delivery platforms are being explored to improve their poor oral bioavailability and therapeutic performance in preclinical models. However, clinical translation remains limited by low bioavailability, context-dependent estrogenic activity, inter-individual metabolic variability, and the lack of large-scale, well-controlled clinical trials, standardized dosing, and validated biomarkers. Genistein represents a promising multi-target lead compound at the intersection of inflammation, immunology, and oncology, with future progress dependent on integrating multi-omics data and advanced delivery technologies for personalised clinical applications. Review Thu, 09 Apr 2026 00:00:00 GMT SatyajitTripathy, Motlalepula GilbertMatsabisa, Thu, 09 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003243 https://www.explorationpub.com/Journals/ei/Article/1003248 Recurrent infections in children often prompt evaluation for primary immunodeficiency diseases, particularly those affecting humoral immunity. Assessment of memory B cell subsets and vaccine-specific antibody responses provides critical insight into long-term protective immunity. While peripheral blood mononuclear cell (PBMC) isolation is common, direct whole blood staining offers faster processing, reduced cell loss, and better preservation of fragile B cell populations. This comprehensive protocol describes a standardised whole blood flow cytometry method for memory B cell phenotyping, alongside ELISA-based measurement of vaccine-specific antibody titres as part of assessing children with recurrent infections. Protocol Tue, 21 Apr 2026 00:00:00 GMT JalilahJamaluddin, Siti MardhianaMohamad, Intan HakimahIsmail, Tue, 21 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003248 https://www.explorationpub.com/Journals/ei/Article/1003249 Aim: To evaluate the relationship between serum calprotectin and serum amyloid A with musculoskeletal ultrasonographic findings in rheumatoid arthritis (RA) patients, as RA is the most common chronic inflammatory joint disease in which the infiltration and activation of inflammatory cells are important. Calprotectin and serum amyloid A protein are over-secreted in response to acute and chronic inflammation. Musculoskeletal ultrasound is more sensitive than physical examination for the evaluation of synovitis. Methods: A control group of 30 healthy individuals, 30 patients with active RA, and 30 patients with inactive RA participated in this cross-sectional study. Utilizing the RA disease activity (Disease Activity Score 28, DAS28) score was evaluated. Serum amyloid A and serum calprotectin were measured in all participants, and musculoskeletal ultrasound on the hands and wrists were done for all subjects. Results: A significant difference was observed among the studied groups with respect to serum calprotectin and serum amyloid A levels (P < 0.001). A significant positive correlation was observed between serum amyloid A and several inflammatory and clinical parameters, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), DAS28 score, serum calprotectin, and synovitis. Similarly, serum calprotectin levels demonstrated a significant positive correlation with ESR, DAS28 score, serum amyloid A, and synovitis. These findings highlight the potential value of both serum amyloid A and serum calprotectin as biomarkers reflecting disease activity and inflammatory burden in RA. Conclusions: Serum amyloid A and serum calprotectin can be used as markers of RA activity. Original Article Tue, 21 Apr 2026 00:00:00 GMT Noura Mohamed Abd El MaksoudShehata, Mostafa Taha YousefGabr, Abeer Abdel MoniemShahba, Amal SaidEl Bendary, Thanaa FaragMansour, Tue, 21 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003249 https://www.explorationpub.com/Journals/ei/Article/1003247 Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition of the urogenital system, with an elusive and multifactorial pathogenesis. Recent data show that there is a potential interplay between dysregulated autophagy and altered exosomal communication that may contribute to the persistent inflammation and pain characteristic of CP/CPPS. This review synthesizes recent advances to propose a hypothetical model: cellular stress in the prostate may trigger dysfunctional autophagy, which could reprogram secreted exosomes biogenesis and cargo in a series of lipid-raft microdomain-involved mechanisms and secretory autophagy. The outcomes of this process include the release of pro-inflammatory cytokines (e.g., IL-1β, TNF-α) enriched exosomes, damage-associated molecular patterns (DAMPs), microRNAs (e.g., miR-155), and fibrotic mediators (e.g., TGF-β1). These signalosomes are hypothesized to transmit the inflammatory and nociceptive signals and may contribute to coordinating the dysregulation of immune cells (such as the M1 polarization of macrophages), sensitization of neurons, and tissue fibrosis, thereby potentially perpetuating the presence of a chronic disease. We critically assess the available evidence based on human studies, animal models, and in vitro systems, but recognize that there is a present requirement for additional CP/CPPS-specific mechanistic evidence. Furthermore, we explore the translational implications of this axis, discussing its promise for yielding novel exosome-based diagnostic biomarkers and its potential as a therapeutic target, while also highlighting the significant preclinical challenges and risks that must be overcome. Ultimately, the autophagy-exosome axis presents a new, integrative concept of CP/CPPS, which shifts the paradigm to the mechanisms of intercellular communication and provides new possibilities to carry out mechanism-selective research and future treatment options. Review Thu, 16 Apr 2026 00:00:00 GMT Daniel KofiNyame, FrancisGoku, Emmanuel Delali KofiFiagbey, AshnaAsim, Brian RoyOgony, FredAmoah, XiaohuiZhou, Thu, 16 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003247 https://www.explorationpub.com/Journals/ei/Article/1003250 Aim: Pneumonia is the leading cause of morbidity and mortality among elderly individuals. This has led to the search for reliable tools such as inflammatory biomarkers, including C-reactive protein (CRP), procalcitonin (PCT), and neutrophil-to-lymphocyte ratio (NLR), to predict disease severity and prognosis. However, the prognostic value of inflammatory biomarkers in elderly women is not fully understood, as the population is often underrepresented in clinical studies. Methods: This retrospective study was conducted at Wahidin Sudirohusodo Hospital, Indonesia. The samples used were elderly women aged ≥ 60 years who were hospitalized with community-acquired pneumonia (CAP) between January and December 2023. CRP, PCT, and NLR levels collected within 24 hours of admission were evaluated and correlated with pneumonia severity index (PSI) scores and in-hospital mortality (IHM). Subsequently, receiver operating characteristic (ROC) curve analysis, logistic regression, and Kaplan-Meier survival analysis were performed. Results: A total of 262 patients (median age 66 years) were included, of whom 83.2% had mild CAP, and 87.0% survived. Among inflammatory biomarkers, CRP showed the highest, with limited discriminatory ability for mortality [area under the curve (AUC) 0.543], followed by NLR (AUC 0.495), and PCT (AUC 0.466). All markers had high sensitivity (91.2%) but low specificity, and CRP ≥ 14.5 mg/L was significantly associated with reduced survival (p = 0.018). Conclusions: CRP shows a modest prognostic value in predicting mortality among elderly women with CAP, while NLR and PCT have limited utility. These results show the need for gender- and age-specific studies to improve risk stratification and outcomes in the vulnerable population. Original Article Thu, 23 Apr 2026 00:00:00 GMT IrawatyDjaharuddin, Dewi RizkiNurmala, ImamNurjaya, RasihaRasiha, Demak LumbanTobing, Thu, 23 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003250 https://www.explorationpub.com/Journals/ei/Article/1003251 Opioids remain central to managing moderate to severe pain, yet they also produce significant and often under-recognized effects on the immune system. In this narrative review, we synthesize evidence from 1994 to 2025 across preclinical, translational, observational, and limited interventional studies in adults to examine how different opioid classes modulate immunity and the clinical relevance of these effects. Opioids act directly on immune cells via mu-opioid receptors (MORs), nociceptin/orphanin FQ receptors (NOR), and Toll-like receptor 4 (TLR4), and indirectly through neuroendocrine, autonomic, neuroinflammatory, and gut microbiota-mediated pathways. Immunologic consequences are drug specific: Morphine, fentanyl, and to a lesser extent methadone exhibit pronounced immunosuppressive profiles; oxycodone appears comparatively less suppressive; and buprenorphine and tramadol generally preserve, and may in some contexts enhance, immune function. Clinically, chronic or intensive opioid exposure is associated with increased risk of infection and sepsis-related mortality, potential facilitation of tumor progression or recurrence, impaired perioperative and transplant outcomes, and contributions to tolerance and opioid-induced hyperalgesia, with convergent data indicating these immune effects are intrinsic to opioid pharmacology. Framing opioid-induced immunomodulation as a clinically meaningful, agent-specific phenomenon argues for incorporating immunologic risk into analgesic selection—prioritizing less immunosuppressive opioids where appropriate, considering rotation and tapering strategies, using peripherally acting antagonists, and implementing multimodal analgesia—while underscoring the need for standardized immunologic endpoints, rigorously controlled clinical studies, and development of next-generation analgesics that maintain effective pain relief while minimizing detrimental immune effects. Review Wed, 29 Apr 2026 00:00:00 GMT Lucia DaianaVoiculescu, ThomasLi, Franzes AnneLiongson, SanjayMenghani, Wed, 29 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003251 https://www.explorationpub.com/Journals/ei/Article/1003253 Aim: Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. While antibody-drug conjugates (ADCs) offer targeted therapeutic options, they are often limited by toxicity, immunogenicity, complex pharmacokinetics, and high production costs. Polyclonal antibodies—capable of recognizing multiple epitopes—present a promising, yet underexplored, alternative for targeted drug delivery. The stage-specific presence of secreted, stable immunoglobulins (IGs) in CRC and their potential utility in drug conjugation strategies remain largely uncharacterized. Methods: This study utilized electrospray ionization nano-liquid chromatography tandem mass spectrometry (ESI-nanoLC-MS/MS) proteomic analysis on pre-treatment plasma samples across CRC stages to identify stage-specific IGs. Venn diagram comparisons refined IG candidates, while protein stability was assessed using ProtParam. Molecular docking simulations (via CB-Dock2), epitope mapping (via CABS-dock), and cell-penetrating peptide (CPP) prediction were integrated to explore epitope pairing between IGs and Kirsten rat sarcoma viral oncogene homolog (K-Ras) neoantigen, evaluating their potential for polyclonal drug conjugates (pPDCs). Results: A total of 325 secreted IGs were initially identified, with 46 found to be stage-specific. Protein stability analysis shortlisted 5 IGs—3 for early-stage and 2 for advanced-stage CRC. Molecular docking revealed that IG heavy variable 3-64 (IGHV3-64) exhibited high-affinity binding with Irinotecan [binding free energies (ΔG) = −10.0 kcal/mol] and showed epitope-level pairing with K-Ras at residues 2–17 and 106–114. Additional CPP motif analysis supported the potential of IGHV3-64-derived peptides for intracellular delivery, reinforcing their promise in pPDC development. Conclusions: IGHV3-64 emerges as a strong candidate biomarker for advanced-stage CRC, demonstrating consistent binding affinity to Irinotecan and epitope pairing with K-Ras. Its inherent CPP features further support its potential for targeted, intracellular delivery in pPDCs design. These findings highlight a novel direction in personalized cancer immunotherapy, warranting further in vitro and in vivo validation to confirm clinical utility. Original Article Wed, 29 Apr 2026 00:00:00 GMT RaajeshAnand, SivaKaliyamoorthy, VinothBoopathy, JawaharRamasamy, RavikumarSambandam, Wed, 29 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/ei/Article/1003253