Forecast of cytotoxic T lymphocyte epitope using sequence weighting and artificial neural network based on EasyPred modeler

Features of peripheral blood Treg and Th17 subsets during physiological pregnancy

Understanding mpox pathogenesis: therapeutic potential of marine-derived drugs

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.

Harnessing mRNA vaccines for viral diseases: bottleneck and breakthrough

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.

Macrophages and fibroblasts in cardiac fibrosis: interactions and transformation

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.

Association of circulating IL-6 and IL-10 levels during mid-gestation with recurrent pregnancy loss history and severity: a South Indian study

Cytokine dynamics in vitiligo: the roles of interleukin-10 and interleukin-17

Rheumatoid arthritis unmasked: the immune complex as a key driver of disease progression

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.

Selective IgG4 deficiency and autoimmune cytopenias

Fibromyalgia syndrome and the immune system: a review with comparative perspectives on chronic immune-related syndromes including CFS/ME and IBS

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.

Unraveling the connection: M2 macrophage polarization and cancer metabolism

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.

The dual promise of oncolytic viruses: selective targeting and therapeutic enhancement in cancer treatment

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.

Advancements in viral vaccine development: from traditional to modern approaches

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.

Exploring immunotherapeutic strategies for bacterial and viral diseases

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.

Harnessing monocyte-derived dendritic cells for evaluating T cell response by mixed leukocyte reaction

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.

The neutrophil-to-lymphocyte ratio in aging and immunosenescence In recent years the number of publications reporting the use of the neutrophil/lymphocyte ratio (NLR) in disparate fields of human and veterinary medicine has swelled in the medical literature from less than 50/year in 2010 to 892 in 2019, and this figure has more than doubled up to 1,857 in 2024 [1].

Reflections on immune system lessons for societal resilience

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.

Elevation of cytokines and antibodies in guinea pigs experimentally infected with Tunga penetrans

Prognostic values of sera IL-6/IL-10 and high titration of anti-SSA/Ro and anti-SSB/La autoantibodies in female patients with connective tissue diseases

Immune-checkpoint inhibitor resistance in patients with cancer

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.