Tuberculosis (TB) continues to pose a significant public health burden in endemic regions, remaining a leading cause of morbidity and mortality. Although TB is associated with a range of complications, the occurrence of intracardiac thrombus is an exceptionally rare manifestation. We report the case of a 62-year-old male with active pulmonary TB, who had been on anti-tubercular therapy for one month and presented with recurrent syncope and exertional dyspnea. Transthoracic 2D echocardiography revealed a large, mobile thrombus in the left ventricular apex. Evaluation for underlying hypercoagulable states was unremarkable. The patient was managed with anticoagulation therapy in conjunction with ongoing anti-tubercular treatment. This case underscores the importance of clinical vigilance for rare thrombotic complications in TB to facilitate timely diagnosis and appropriate management.

The interaction between cancer and coronavirus disease 2019 (COVID-19) poses significant challenges, particularly for immunocompromised individuals who are at heightened risk for acute infections and long-term complications. The pandemic has exacerbated existing vulnerabilities in cancer care by disrupting treatment protocols and delaying diagnoses, leading to worsened health outcomes. This article emphasizes the importance of investigating the potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on cancer progression and highlights the need for effective strategies to protect this high-risk population. Long-term health consequences, including the emergence of long COVID, further emphasize the need for ongoing surveillance and comprehensive healthcare planning for cancer patients during and after pandemics. A multifaceted approach is essential, incorporating vaccination, timely therapeutic interventions, and sustained support for patients with lingering symptoms. This article also discusses and urges continued research into the oncogenic risks associated with SARS-CoV-2, which is crucial for enhancing our understanding of the broader health implications of COVID-19 and for informing public health strategies aimed at safeguarding cancer patients in future pandemics. Moreover, effective data collection and the development of refined clinical guidelines are vital for improving patient outcomes and preparing healthcare systems to support cancer patients during crises. Additionally, this article discusses the importance of investigating the mechanisms by which SARS-CoV-2 may increase cancer susceptibility, including chronic inflammation, cellular senescence, and immune dysregulation. Understanding these mechanisms is crucial for elucidating the virus’s long-term oncogenic potential, particularly among cancer survivors and individuals with chronic infections. Ensuring continuity and resilience in cancer care during global crises requires strategies to mitigate healthcare disruptions, enhance access to screenings and treatments, and address the specific challenges faced by cancer patients experiencing long COVID.

In the context of severe asthma, one of the causes of poor disease control has been identified in mucus plugs, which are real obstacles to the physiological flow of air in the bronchi. This clinical case will present the efficacy of dupilumab, as measured by respiratory function and chest computed tomography (CT) imaging, in reducing mucus plugs with consequent improvement in symptoms and function.

Neoantigen-based immunotherapy has emerged as a transformative approach in cancer treatment, offering precision medicine strategies that target tumor-specific antigens derived from genetic, transcriptomic, and proteomic alterations unique to cancer cells. These neoantigens serve as highly specific targets for personalized therapies, promising more effective and tailored treatments. The aim of this article is to explore the advances in neoantigen-based therapies, highlighting successful treatments such as vaccines, tumor-infiltrating lymphocyte (TIL) therapy, T-cell receptor-engineered T cells therapy (TCR-T), and chimeric antigen receptor T cells therapy (CAR-T), particularly in cancer types like glioblastoma (GBM). Advances in technologies such as next-generation sequencing, RNA-based platforms, and CRISPR gene editing have accelerated the identification and validation of neoantigens, moving them closer to clinical application. Despite promising results, challenges such as tumor heterogeneity, immune evasion, and resistance mechanisms persist. The integration of AI-driven tools and multi-omic data has refined neoantigen discovery, while combination therapies are being developed to address issues like immune suppression and scalability. Additionally, the article discusses the ongoing development of personalized immunotherapies targeting tumor mutations, emphasizing the need for continued collaboration between computational and experimental approaches. Ultimately, the integration of cutting-edge technologies in neoantigen research holds the potential to revolutionize cancer care, offering hope for more effective and targeted treatments.

Chronic upper limb pain is rather common among people in general and is characterized by a complex diagnosis due to the wide variety of factors that are involved in its development. In terms of treatment, pharmacology and manual therapy have classically been the most used options. However, based on current evidence, recommendations are more inclined to apply multimodal treatments, mainly with exercise therapy and pain education, based on the patient-centered care model. This case report details the evaluation and treatment of a 23-year-old woman with chronic upper limb pain using a multimodal physical therapy with a biobehavioral approach. The intervention lasted 12 weeks with a total of 9 sessions, in which manual therapy, therapeutic exercise, pain neuroscience education, motion representation methods, and sensory retraining were applied. The treatment resulted in a substantial improvement in the patient’s health condition. This case report indicates that a multimodal physical therapy treatment based on a biobehavioral approach may offer benefits in reducing pain symptoms and enhancing somatosensory, motor-functional, and affective-cognitive abilities in patients with chronic upper limb pain, as observed in the described case. Accordingly, this treatment can be a therapeutic option for patients with chronic upper limb pain.

Emerging cancer immunotherapy methods, notably cytokine-based ones that modify immune systems’ inflammatory reactions to tumor cells, may help slow gastric cancer progression. Cytokines, tiny signaling proteins that communicate between immune cells, may help or hinder cancer growth. Pro-inflammatory cytokines encourage tumor development, whereas antitumor ones help the host reject cancer cells. This study considers cytokine-targeted methods for gastric cancer pro-inflammatory and antitumor immune responses. Researchers want to renew immune cells like cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells by delivering cytokines like interleukin-2 (IL-2), interferons (IFNs), and tumor necrosis factor-alpha (TNF-α) to activate inflammatory pathways and combat tumors. Since cytokines have significant pleiotropic effects, their therapeutic use is difficult and may cause excessive systemic inflammation or immunological suppression. This review covers current advancements in synthetic cytokines, cytokine-conjugates, and local administration of these aimed to enhance the therapeutic index: increase the potential to kill cancer cells while minimizing off-target damage. The study examines the relationship between cytokines and tumor microenvironment (TME), revealing the role of immunosuppressive cytokines like IL-10 and transforming growth factor-beta (TGF-β) in promoting an immune-evasive phenotype. These results suggest that inhibitory pathway targeting, and cytokine-based therapy may overcome resistance mechanisms. Cytokine-based immunotherapies combined with immune checkpoint inhibitors are predicted to change gastric cancer therapy and rebuild tumor-immune microenvironment dynamics, restoring antitumor immunity. Comprehensive data from current clinical studies will assist in establishing the position of these treatments in gastric cancer.

We report a rare case of a female patient with multiple rheumatological conditions. The patient initially presented with periodic, diffuse abdominal pain. This complaint was not fully investigated because polyarthritic symptoms became the predominant ones. This led to the diagnosis of rheumatoid arthritis. Afterward, the patient complained of xerostomia, xerophthalmia, and diffuse rash. After investigations, she was diagnosed with Sjögren’s syndrome. Suspecting a case of methotrexate-induced vasculitis, her initial prescription was changed to azathioprine and then to etanercept. Eventually, her persistent abdominal pain, combined with her Armenian origin, prompted her physician to order a genetic analysis of the MEFV gene, which revealed the V726A/P369S mutation, giving rise to the diagnosis of Familial Mediterranean Fever. In her routine follow-up, the patient was in a stable condition, adherent to the medications, and showed improvement in her symptoms. Therefore, this case shows the importance of early genetic testing in similar cases, which in turn will allow timely diagnosis and treatment.

Preterm birth, defined as delivery before 37 weeks of gestation, represents a global health concern linked to substantial cardiovascular risk later in life. Individuals born preterm, especially at earlier gestational ages, exhibit increased rates of hypertension, heart failure, and ischemic heart disease. The underlying mechanisms include disrupted fetal programming, impaired vascular remodeling, chronic neonatal inflammation, neuroendocrine immaturity, and epigenetic alterations. This review synthesizes current epidemiological evidence from large cohort studies and meta-analyses, integrating mechanistic insights from developmental biology. We discuss distinct prematurity categories—extremely preterm (< 28 weeks), very preterm (28–32 weeks), and moderate to late preterm (33–37 weeks)—highlighting their association with graded cardiovascular risk. Recent findings emphasize the role of non-transmitted parental genes and prenatal environmental toxic metal exposure as additional critical factors influencing fetal cardiovascular programming. A total of 57 articles, identified through a systematic search of PubMed, Embase, and Cochrane databases, were included to address these topics comprehensively. Early identification of preterm-born individuals as a high-risk cardiovascular group is essential for targeted screening, prevention, and interventions from childhood into adulthood. Future studies leveraging multi-omics and epigenetic approaches will further clarify these mechanisms, informing evidence-based guidelines to reduce cardiovascular morbidity associated with preterm birth.

The ultrastructural morphology of eosinophil cytolysis and extracellular trap cell death (ETosis) has predominantly been examined in non-neoplastic eosinophil-associated diseases, with a limited investigation in neoplasms. This current electron microscopy study examined the ultrastructural characteristics of eosinophil cytolysis and ETosis across four distinct gastric cancer cases: three cases (cases 1–3) exhibited non-ETotic cytolysis, while one case (case 4) presented eosinophils at various stages of ETosis. In cases 1–3, eosinophil non-ETotic cytolysis was characterized by localized plasma membrane disruption, the presence of free extracellular granules (FEGs), and the maintenance of a round or oval nuclear lobe profile. In case 4, eosinophils were observed in progressive stages of ETosis, arbitrarily subdivided into early, intermediate, and advanced. Although early ETosis and non-ETotic cytolysis exhibited overlapping ultrastructural features, chromatin decondensation and nuclear envelope enlargement were more pronounced in early ETosis. Nuclear envelope disruption, loss of the round or oval nuclear lobe profile (intermediate stage), extracellular DNA trap deposition, and the appearance of Charcot-Leyden crystals (advanced stage) were all distinctive features of ETosis. The findings of this case report confirm previous observations of eosinophil cytolysis with or without ETosis in non-neoplastic diseases and extend them to advanced gastric carcinoma. Since Charcot-Leyden crystals were only seen in case 4, their correlation with ETosis was further supported. In gastric cancer, the release of FEGs during non-ETotic cytolysis and the release of both FEGs and DNA traps during ETotic cytolysis may contribute to the formation of an antitumor microenvironment.

Breath analysis is a relatively new topic of study that has a lot of potential for both therapeutic and scientific applications. The volatile organic compounds (VOCs) found in breath are created internally by the body due to environmental interactions, gut and air passage bacteria, and metabolites of ingested precursors. Breath analysis may help diagnose disorders linked to changes in breath composition, according to several recent research. An analytical technique that shows promise for the metabolic examination of breath is infrared spectroscopy. Chemical substances found in exhaled human breath can be used to diagnose illnesses, determine physiological states, or evaluate environmental exposure. Exhaled breath (EB) is the perfect biological fluid because it is nearly limitless and causes little to no discomfort for the patient, which promotes collaboration. Furthermore, EB can be sampled without requiring medical professionals or privacy, and it usually doesn’t produce infectious waste (despite airborne infections), which makes breath analysis a desirable method for a variety of applications. Breath analysis is a non-invasive method that solely uses the volatile composition of the EB to characterize the bloodstream and airways’ volatile content, which indicates the state and condition of the entire body’s metabolism. The absorption strength of the metabolites is still very modest, though, because EB contains minimal amounts of them. Several of the most recent uses of infrared spectroscopy for breath analysis, published between 2020 and 2024, are presented in this study.

Pediatric adrenocortical tumors (pACTs) are rare endocrine neoplasms with variable prognosis, commonly associated with germline pathogenic variants (PVs) in the tumor suppressor gene TP53. Here, we report the case of a 3.1-year-old female presenting with virilization and Cushing syndrome due to a left-sided adrenal mass. The tumor was completely resected and confirmed as stage II adrenocortical carcinoma (ACC) based on the Wieneke index. Comprehensive molecular profiling revealed heterozygous germline PVs in BRCA2 [c.9382C>T p.(Arg3128*)] and CHEK2 [c.1232G>A p.(Trp411*)]. These findings suggest a potential role of impaired DNA damage repair in ACC pathogenesis, as both PVs are associated with hereditary breast and ovarian cancer (HBOC) syndromes and genomic instability. This case expands the genetic spectrum of pACT and underscores the importance of advanced molecular analyses in identifying rare germline alterations that may inform personalized treatment strategies and cancer prevention programs. Although no additional treatment was required in this case, BRCA2 status highlights the potential for tailored therapeutic approaches, including poly(ADP-ribose) polymerase (PARP) inhibitors, in selected patients. Further research is warranted to explore the specific contributions of BRCA2 and CHEK2 PVs to ACC tumorigenesis and their implic ations for targeted therapies.

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.

Thanks to improvements in asthma care and availability of new biologic treatments, a relatively novel population of adolescents and young adults (AYA) with severe asthma (SA) is growing. Transition from pediatric to adult care represents a critical phase in the management of SA. We herein describe clinical outcomes, therapeutic adjustments and disease management in a group of SA patients transitioning from the pediatric to the adult care center. This is a retrospective study in which demographic and clinical (comorbidities, baseline treatment, number of asthma attacks, spirometry, airway inflammation [fractional exhaled nitric oxide (FeNO) measurements], patient’s compliance) data of four SA patients during visits in the Pediatric center as well as after transition into the Adult Center, were retrospectively recollected. All patients transitioned at 18 years of age. Clinical parameters, spirometry and FeNO showed significant improvement following the addition of biologics to baseline asthma regimen during pediatric follow-up and the early transition phase. Several months after transition to the Adult Center, two males experienced SA exacerbations following voluntary discontinuation of the biologic treatment. Symptom control was gained after a phenotype driven re-introduction of a biologic drug in the regimen. Male patients were less compliant and independent than females in the adult setting. Transition from pediatric to adult care for patients with SA can be effectively managed with coordinated and structured transition processes. While some patients maintain stable clinical and respiratory outcomes, others risk to lose asthma control. A personalized approach supporting both patient’s independence and adherence to treatment is requested for a successful long-term management.

Diabetes mellitus is a major risk factor for both cardiovascular and chronic kidney disease (CKD) while CKD is also associated with cardiovascular morbidity. In fact, cardiovascular disease is the leading cause of death in patients with diabetes mainly from heart failure or myocardial infarction. The newer therapeutic agents in diabetes have positive impact on both cardiovascular and renal outcomes. Thus, the American Diabetes Association (ADA)’s annual update on the Standards of Medical Care in Diabetes is an important resource for all caregivers involved in diabetes management as it incorporates the latest scientific research, clinical evidence, and emerging technologies in diabetes management. The 2025 guidelines present significant updates that reflect a deeper understanding of diabetes management, emphasizing expanded usage of technologies such as continuous glucose monitoring, personalized pharmacological approaches, and lifestyle interventions. This commentary provides an analysis of the key updates in the 2025 ADA guidelines exploring implications for clinical practice, laboratory assessments, and public health policy. Where relevant, comparisons to the 2024 version will be made.

Agriculture is pivotal in securing global food security and sustainability, especially in pressing challenges such as climate change, population growth, and resource depletion. This review examines the interconnections between agriculture, food security, and sustainability, focusing on current challenges, innovations, and strategies to address these critical issues. The global demand for food is projected to increase substantially, necessitating agricultural systems that boost productivity and ensure environmental sustainability. However, conventional farming practices have exacerbated soil degradation, water scarcity, and greenhouse gas emissions, posing significant threats to long-term food security. This review aims to evaluate the role of sustainable agricultural practices in enhancing food security while mitigating environmental impacts. It also identifies existing gaps in farming systems and explores innovative solutions to promote resilient and sustainable food systems. A comprehensive review of peer-reviewed literature, policy documents, and global agricultural reports was conducted. The analysis focuses on key themes such as sustainable farming practices, the impacts of climate change on agriculture, advancements in agrotechnology, and the socio-economic dimensions of food security. Synthesized findings provide actionable insights into best practices and emerging trends. Sustainable agriculture offers a viable pathway to address the dual challenges of food security and environmental conservation. Precision farming, agroecology, and regenerative agriculture enhance productivity while preserving resources and reducing ecological footprints. Integrating advanced technologies, including artificial intelligence and genetic innovations, can optimize agricultural efficiency. However, global food security requires coordinated efforts among governments, the private sector, and local communities to implement equitable resource distribution and climate-resilient policies. Future research should prioritize scalable, region-specific solutions that align with sustainability principles to ensure a secure and resilient global food system.

The study investigated the role of probiotics and prebiotics in treating COVID-19. It focuses on their mechanisms of action in modulating the immune system and mitigating the disease’s impact. The research focused on the significance of the gut-lung axis and the potential benefits of probiotics and prebiotics against COVID-19. The research identified several findings: probiotics have shown potential in reducing the severity of COVID-19 symptoms and improving patient outcomes. The gut microbiota plays a critical role in the body’s immune response to COVID-19, with probiotics aiding in restoring its balance. Both can modulate the immune system, reducing the inflammatory response associated with COVID-19. While there is evidence supporting the benefits of probiotics and prebiotics, limitations exist due to the lack of studies on their use to improve COVID-19 outcomes. The originality of the study is focused on the gut-lung axis and the review of probiotics and prebiotics as potential therapies for COVID-19. By analyzing recent literature, the research contributes to understanding the interactions between diet, gut health, and respiratory infections. It also shows the need for further studies to determine the efficacy of COVID-19, toward new directions for research in the emerging field.

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.

Vanishing bile duct syndrome (VBDS) is a rare condition, representing approximately 0.5% of small bile duct diseases, characterized by progressive destruction of intrahepatic bile ducts, leading to ductopenia. This condition encompasses various etiologies, with drug-induced VBDS (D-VBDS) accounting for 7% of VBDS cases. D-VBDS arises from liver injury due to chemical drugs, traditional medicines, and dietary supplements, often resulting in inflammatory responses and necrosis of bile duct epithelium. Recent years have seen a rise in reported cases, making drug-related injuries a leading cause of acute liver failure in Western countries. This review provides a comprehensive analysis of VBDS, focusing on the histopathological features of acute and chronic D-VBDS, alongside exploring its clinical presentation, prognostic implications, and future research directions. Understanding the diverse etiologies, clinical manifestations, and biochemical parameters associated with D-VBDS is essential for improving diagnosis, treatment strategies, and patient outcomes.

Artificial intelligence (AI) increasingly influences biomedical scientific writing and clinical practice. The recent article by Fornalik et al. (Explor Digit Health Technol. 2024;2:235–48. doi: 10.37349/edht.2024.00024) explores AI’s capabilities, challenges, and ethical considerations in scientific communication, particularly highlighting tools like ChatGPT and Penelope.ai. This commentary aims to reflect on and expand the key themes presented by Fornalik et al. (Explor Digit Health Technol. 2024;2:235–48. doi: 10.37349/edht.2024.00024), emphasizing AI’s role in auditory healthcare, particularly in otolaryngology and auditory rehabilitation. The discussion is based on a critical review and synthesis of recent literature on AI applications in scientific writing and auditory healthcare. Key technologies such as generative AI platforms, machine learning algorithms, and mobile-based auditory training systems are highlighted. AI has shown promising results in enhancing manuscript preparation, literature synthesis, and peer review workflows. In clinical practice, adaptive AI models have improved cochlear implant programming, leading to up to 30% gains in speech perception accuracy. Mobile apps and telehealth platforms using AI have also improved listening effort, communication confidence, and access to care in remote settings. However, limitations include data privacy concerns, lack of population diversity in datasets, and the need for clinician oversight. AI presents transformative opportunities across biomedical science and healthcare. To ensure its responsible use, interdisciplinary collaboration among clinicians, researchers, ethicists, and technologists is essential. Such collaboration can help develop ethical frameworks that enhance innovation while safeguarding patient well-being and scientific integrity.

Acetaminophen (APAP)-induced liver injury and acute liver failure is a significant clinical problem worldwide; in addition, APAP overdoses in animals or in cell culture are used as popular models to study drug-induced liver injury mechanisms and test therapeutic interventions. Early assumptions that APAP toxicity is caused by a single mechanism resulting in a defined mode of cell death in hepatocytes had to be questioned when over the years many different mechanisms and modes of cell death were reported. Although many of the contradictory results and conclusions reported over the years can be attributed to lack of understanding of established mechanisms, methodological problems, and misinterpretation of data, it is increasingly recognized that some of the reported differences in signaling mechanisms and even a switch in the mode of cell death can be caused by variations in the experimental conditions. In this review, examples will be discussed how experimental conditions (dose, solvent, etc.), the experimental system (species, strain, and substrain in vivo, cell type, and in vitro conditions), and also adaptive responses and off-target effects of genetic manipulations and chemical interventions, can impact the mechanisms of cell death. Given that the conditions will determine the results, it is therefore of critical importance to keep in mind the translational aspect of the experiments, i.e., the conditions relevant to the human pathophysiology. Only the full appreciation of these issues will lead to reproducible and clinically relevant results that advance our understanding of all facets of the human pathophysiology and identify clinically relevant therapeutic targets.

The glucocorticoid receptor alpha (GRα), a vital component of the ancient glucocorticoid (GC) signaling system, is essential for vertebrate survival. It regulates fertility, fetal development, organ function, vascular and neural integrity, metabolism, immune responses, and stress adaptation. While GRα’s anti-inflammatory properties have been acknowledged since the mid-20th century, its crucial role as the master regulator of homeostatic corrections in both health and critical illness has only recently come to light. In critical illness, GRα facilitates a seamless transition through three essential phases of homeostatic correction. Initially, in the Priming Phase, it activates immune responses and mobilizes energy reserves to defend against stressors like infection and injury, enhancing glucose metabolism, supporting mitochondrial function, and strategically deploying immune cells to areas of damage. Next, during the Modulatory Phase, GRα fine-tunes inflammatory responses, manages oxidative stress, regulates vascular tone, and maintains cellular integrity. Finally, in the Restorative Phase, GRα plays a crucial role in resolving inflammation, initiating tissue repair, supporting cellular regeneration, facilitating debris clearance, and reestablishing anatomical and physiological balance for long-term recovery. GRα coordinates complex molecular interactions, including co-regulation with pro-inflammatory transcription factors, ensures mitochondrial stability, and metabolic balance under stress. However, depleted bioenergetic and micronutrient reserves in critically ill patients can impair GRα’s capacity, increasing morbidity and mortality risks. This review highlights the need to reassess current GC treatment strategies and integrate micronutrient support to optimize GRα function. Such an approach could strengthen immediate immune defenses, enhance long-term recovery, reduce GC dose and duration, and minimize adverse effects.

Glioblastoma (GBM), the most aggressive and lethal primary brain tumor, poses a significant therapeutic challenge due to its highly invasive nature and resistance to conventional therapies, including surgery, chemotherapy, and radiotherapy. Despite advances in standard treatments, patient survival remains limited, requiring the exploration of innovative strategies. Photodynamic therapy (PDT) has emerged as a promising approach, leveraging light-sensitive photosensitizers (PSs), molecular oxygen, and specific light wavelengths to generate reactive oxygen species (ROS) that selectively induce tumor cell death. Originally developed for skin cancer, PDT has evolved to target more complex malignancies, including GBM. The refinement of second- and third-generation PS, coupled with advancements in nanotechnology, has significantly improved PDT’s selectivity, bioavailability, and therapeutic efficacy. Moreover, the combination of PDT with chemotherapy, targeted therapy, and immunotherapy, among other therapeutic modalities, has shown potential in enhancing therapeutic outcomes. This review provides a comprehensive analysis of the preclinical and clinical applications of PDT in GBM, detailing its mechanisms of action, the evolution of PS, and novel combinatory strategies that optimize treatment efficacy. However, several challenges remain, including overcoming GBM-associated hypoxia, enhancing PS delivery across the blood-brain barrier, and mitigating tumor resistance mechanisms. The integration of PDT with molecular and genetic insight, alongside cutting-edge nanotechnology-based delivery systems, may revolutionize GBM treatment, offering new prospects for improved patient survival and quality of life.

Folic acid (FA) residue is a well-known and widely spread targeting ligand, or biovector, used as a component in engineering artificial nanosized and submicron particles (NSPs) to target various cells and treat a variety of diseases that are associated with FA (or folate) receptors (FR) overexpression. A particular place in the list of these diseases is held by various cancer types, for which overexpression of FR on the cell surface is often accompanied by a more severe disease course, increased resistance to the conventional chemotherapy, and poorer prognosis. The incorporation of albumin into NSPs has been shown to enhance their biocompatibility, give high compatibility with drug molecules, prolong their circulation, reduce thrombogenic activity, and improve their colloidal stability. Nowadays albumin-based NSPs with FA residue as a targeting agent are used for chemotherapy, photothermal and photodynamic therapy, combined therapy, visualization, and theranostics (also known as theragnostics) for various types of cancer: breast, cervical, ovarian, prostate, nasopharyngeal, gastric, colorectal, liver cancer, and brain tumors. A limited number of studies have also focused on the use of NSPs in rheumatoid arthritis treatment. In this review, we discuss the ways of FA-albumin conjugation and conjugation of FA to albumin-modified NSPs systems. An application of nanosized and submicron delivery systems on the base of serum albumin and FA for therapy and diagnostics is discussed.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes a global epidemic named COVID-19. It still continues to plague humans with severe complications and unique sequelae, causing huge economic losses in the world. Pathophysiological studies showed that important life organs, such as the lungs, brain, kidneys, heart, liver, and immune system, and even reproductive ones are affected directly or indirectly in patients with COVID-19. Classically and newly discovered drugs, concerning antiviral replication, anti-inflammation, blockage of pathogenic processes, alleviation of symptoms, and especially distinctive multi-actions of Traditional Chinese Medicine, were screened out and tested, presenting promising therapeutic effects on the virus before or even though abundant effective vaccines come out. Moreover, other strategies are underway, including the use of plasma therapy, monoclonal neutralizing antibodies, vaccine trials, and emerging drugs with distinct interference mechanisms. This review features the novel progress on the latest-discovered antiviral drugs and the effective Traditional Chinese Medicine, and highlights the advantages and shortages of different therapeutic strategies and the predicted potential targets of the used Traditional Chinese Medicine components, which provides a valuable reference for clinical treatment continuously to combat COVID-19.

Bladder cancer (BCa) is among the most frequently diagnosed urinary tract cancers, characterized by a high recurrence rate and significant clinical heterogeneity. Effective diagnosis and treatment of BCa demand continuous advancements in medical technologies, particularly given the limitations of classical methods such as cystoscopy and urine cytology. A comprehensive search of PubMed and Web of Science was conducted using relevant keywords to structure this narrative review. Additionally, specialist journals were reviewed. Only articles in English were included, with selection based on titles, abstracts, and availability of full texts. In recent years, biomarkers have emerged as crucial tools complementing traditional techniques, providing more precise, sensitive, and non-invasive methods for early detection, prognosis, and monitoring treatment response in BCa. Molecular, genetic, and protein biomarkers enable a deeper understanding of BCa biology, creating opportunities for personalized therapy tailored to individual patient needs. However, despite their potential, certain challenges remain, including standardization, validation, and integration into routine clinical practice. This review highlights recent advancements in BCa biomarkers and their transformative potential in oncological care. It underscores the importance of incorporating these innovations to refine diagnostic and therapeutic approaches, ultimately improving patient outcomes. Modern diagnostic and prognostic tools for BCa can enhance treatment outcomes by enabling early disease detection and reducing recurrence risks. This progress promises to improve patients’ quality of life by minimizing disease burden and fostering effective, tailored care strategies.

Proteins from the neurotrophin family perform trophic and regulatory functions in the nervous and other body systems. Understanding the mechanisms of neurotrophin action is crucial not only for the evolution of fundamental scientific knowledge but also for developing new treatment strategies targeting neurotrophin signaling regulation. At our center, dimeric dipeptide mimetics of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have been obtained based on the structure of neurotrophins’ individual loops β-turns. These mimetics activated tyrosine kinase (Trk) receptors TrkA, TrkB, or TrkC specific to their respective neurotrophins, but exhibited varied activation patterns in the main post-receptor signaling cascades. Thus, some dipeptides activated all three main phosphoinositide 3-kinase (PI3K)/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phospholipase C-gamma (PLC-γ) pathways, while others triggered only PI3K/Akt and PLC-γ or MAPK/ERK and PLC-γ. Herewith, dipeptides exhibited a specific set of effects (neuroprotective, differentiating, antidepressant-like, anxiolytic, memory-enhancing, analgesic, antidiabetic) within the spectrum of biological activities of their corresponding native neurotrophin. It was revealed that these effects are influenced by both the patterns of post-receptor signaling activation and the nature of progenitor neurotrophin, uncovering significant correlations. This article is dedicated to reviewing the data that has been collected.

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.

4-Aminobenzoic acid (PABA, para-aminobenzoic acid) exhibits multifaceted therapeutic potential in neuropsychiatric disorders through its roles in neurotransmitter modulation, anti-inflammatory action, and antioxidant defense. Experimental and clinical evidence demonstrates that PABA enhances serotonin and dopamine synthesis by activating key enzymes (e.g., tryptophan hydroxylase and tyrosine hydroxylase), thereby stabilizing mood and improving cognitive function. Mechanistically, PABA suppresses neuroinflammation by inhibiting NF-κB signaling and cytokine production (e.g., IL-1β, TNF-α) while scavenging reactive oxygen species (ROS) to mitigate oxidative stress and protect neuronal integrity. Clinical studies indicate that PABA may synergize with traditional antidepressants by targeting serotonin reuptake transporters (SERT) and monoamine oxidase (MAO), offering improved outcomes in major depressive disorder. Despite promising results, further research is needed to optimize dosing regimens, validate long-term safety, and explore pharmacogenomic interactions. Crucially, experimental validation through cellular and animal models is required to substantiate PABA’s proposed mechanisms, particularly its regulation of NF-κB signaling and enzyme activity in neurotransmitter synthesis. This review underscores PABA’s potential as a neuroprotective agent and calls for integrated strategies to translate mechanistic insights into clinical applications for complex neurological conditions.

Pancreatic cancer is a challenging disease with limited treatment options and a high mortality rate. Just few therapy advances have been made in recent years. Tumor microenvironment, immunosuppressive features and mutational status represent important obstacles in the improvement of survival outcomes. Up to now, first-line therapy did achieve a median overall survival of less than 12 months and this discouraging data lead clinicians all over the world to focus their efforts on various fields of investigation: 1) sequential cycling of different systemic therapy in order to overcome mechanisms of resistance; 2) discovery of new predictive bio-markers, in order to target specific patient population; 3) combination treatment, in order to modulate the tumor microenvironment of pancreatic cancer; 4) new modalities of the delivery of drugs in order to pass the physical barrier of desmoplasia and tumor stroma. This review shows future directions of treatment strategies in advanced pancreatic cancer through a deep analysis of these recent macro areas of research.

Mineral nanoparticles and osteoinductive biomaterials are essential in advancing bone regeneration by addressing skeletal conditions and injuries that compromise structural integrity and functionality. These biomaterials stimulate the differentiation of precursor cells into osteoblasts, creating biocompatible environments conducive to bone tissue regeneration. Among the most promising innovations, mineral-based nanoparticles and nanocomposite hydrogels have emerged as effective strategies for enhancing osteoinductive potential. This review explores the diverse types of osteoinductive biomaterials, including natural sources, synthetic compounds, and hybrid designs that incorporate mineralized nanoparticles. Emphasis is placed on polymeric hydrogels as delivery platforms for these materials, highlighting their dual role as structural supports and bioactive agents that promote osteogenesis. Challenges such as immune rejection, biodegradability, mechanical stability, and short in vivo residence time are critically discussed, alongside their impact on clinical translation. By presenting a comprehensive analysis of mechanisms, applications, and limitations, this review identifies opportunities for integrating osteoinductive biomaterials with emerging fields like immunology and biomechanics. Ultimately, this work aims to provide actionable insights and advance the development of novel, clinically relevant solutions that improve patient outcomes and address the growing global need for effective bone repair and regeneration.

Esketamine, the S-enantiomer of ketamine, has gained prominence as an adjunct in pain management during general anesthesia due to its higher potency and ability to achieve therapeutic effects at lower doses than ketamine. While its benefits for pain relief and mental health are well-established, the specific effects of esketamine on cardiac function during anesthesia remain under investigation. Anesthesia itself induces physiological changes in the cardiovascular system, and esketamine can exacerbate these effects by increasing sympathetic activity, heart rate, blood pressure, and cardiac output. Additionally, it can induce peripheral vasoconstriction, raising systemic vascular resistance. These cardiovascular effects are particularly concerning in patients with pre-existing heart conditions, underscoring the importance of preoperative assessment, continuous monitoring, and potential dose adjustments. This review examined the hemodynamic effects of esketamine, the associated cardiovascular risks, and the clinical implications for patients with cardiac conditions, offering recommendations for its safe use in anesthesia.

This review explored the physiological mechanisms underlying arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus) and AVP resistance (AVP-R, formerly nephrogenic diabetes insipidus), with a focus on water balance regulation. Vital components include the hypothalamic-pituitary-AVP axis, renal AVP responsiveness, and neural mechanisms of thirst regulation. Recent insights on thirst generation within circumventricular brain nuclei (subfornical organ, median preoptic nucleus, and organum vasculosum of the lamina terminalis) are discussed, along with the diagnostic utility of copeptin in polyuric states. This review highlighted the critical role of hypothalamic-pituitary integrity and renal AVP responsiveness in maintaining water-electrolyte homeostasis. Understanding these mechanisms provided the foundation for optimizing therapeutic strategies and advancing research on AVP-related disorders.

Bunium persicum Boiss. Fedtsch., a highly valued spice crop from the Apiaceae family, is renowned for its rich phytochemical profile, including compounds such as cuminaldehyde, α-terpinene-7-al, γ-terpinene-7-al, γ-terpinene, p-cymene, and β-pinene. These bioactive constituents contribute to its diverse therapeutic properties, including antioxidant, antimicrobial, anti-inflammatory, lipid and glucose-lowering, and anti-carcinogenic activities. Due to its limited growth in specific wild regions and over-exploitation, B. persicum faces significant conservation challenges, both in vitro and in situ. In India, its primary hotspots are in Jammu and Kashmir, Himachal Pradesh, and Uttarakhand. This review provides a comprehensive examination of B. persicum’s functional properties, with a focus on its traditional uses, phytochemistry, and pharmacological activities, highlighting the need for its conservation and sustainable use.

Glioblastoma, an aggressive and lethal brain tumor, presents enormous clinical challenges, including molecular heterogeneity, high recurrence rates, resistance to conventional therapies, and limited therapeutic penetration across the blood-brain barrier. The glioblastoma microenvironment, characterized by a dynamic interplay of cellular and non-cellular components, is a key driver of tumor growth and therapeutic resistance. Neuroinflammatory cytokines, particularly interleukins and tumor necrosis factor-alpha, play pivotal roles in this microenvironment, contributing to tumor progression and immune evasion. This review highlights oncolytic virotherapy as a promising therapeutic avenue, focusing on its potential to modulate neuroinflammatory responses, induce localized immune reactions, and deliver immunomodulatory factors directly to the tumor site. While encouraging outcomes have been observed, challenges such as overcoming the blood-brain barrier, managing host antiviral immunity, and mitigating potential risks to normal neuronal cells remain critical barriers to clinical translation. By analyzing the intricate interactions of oncolytic viruses with the glioblastoma microenvironment and synthesizing findings from preclinical and clinical trials, this review provides actionable insights into developing personalized and effective therapeutic strategies for this aggressive tumor based on oncolytic virotherapy alone or when using it combined with conventional therapies, immunotherapy, natural killer-cell therapy, chimeric antigen receptor-T cell therapy, and dendritic cell therapy.

Ischemic stroke (IS) is a leading cause of death globally. IS occurs due to a blockage of cerebral arteries, leading to neuronal injury, tissue death, and brain infarcts. This induces lack of oxygenation to the brain which induces neuroinflammation, characterised by interactions involving molecules which can exacerbate brain damage but also aid recovery through processes like microglial phagocytosis. Post-stroke depression (PSD) affects 30–33% of stroke survivors, complicating recovery with various symptoms. The pathophysiology of PSD involves disruptions in the glutamatergic and monoaminergic systems, the gut-brain axis, and neuroinflammation. Agomelatine, an atypical antidepressant, can potentially treat both IS and PSD. It acts as a melatonin receptor agonist and a serotonin receptor antagonist, enhancing dopamine and norepinephrine availability in the prefrontal cortex. Agomelatine’s neuroprotective, anti-inflammatory, antioxidative, and antiapoptotic properties have been demonstrated in research, where it reduces reactive oxygen species (ROS) levels and activates the Nrf2 pathway, promoting antioxidative enzyme expression. Additionally, it prevents microglial activation by inhibiting the toll-like receptor 4 (TLR4)/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) pathway, thus reducing inflammation. This review examines the pathophysiology of IS and PSD, highlighting agomelatine’s multifaceted therapeutic potential. Agomelatine’s distinct pharmacological profile and minimal side effects make it a compelling candidate for IS and PSD treatment, necessitating further exploration to optimise stroke management and improve patient outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging and rapidly growing health problem that currently affects more than one-third of the world general population and more than two-thirds of patients with obesity or type 2 diabetes. MASLD is associated with one or more cardio-metabolic risk factors (CMRFs) that determine the complexity of its natural history and management. Although the term MASLD encompasses a single disease, each CMRF has a different impact on MASLD, and the number of overlapping CMRFs results in a different rate of progression and outcomes of both liver and systemic disease. Its pathogenesis is characterized by insulin resistance, lipotoxicity and a complex cross-talk between liver, adipose tissue, muscle, intestine through the release of hepatokines, cytokines, myokines and inflammatory products. The stage of liver fibrosis is the best predictor of liver outcomes, such as liver failure and mortality, and also predicts the high risk of all-cause mortality associated with the disease. In many cases, the development of hepatocellular carcinoma (HCC) is associated with advanced fibrosis or cirrhosis, although it can occur at all stages of the disease, making prevention difficult. MASLD is characterized by increasing very low-density lipoprotein (VLDL) secretion and chronic low-grade systemic inflammation, which increase the risk of cardio-vascular, renal, and endocrine diseases and extrahepatic cancer. Thus, the management of MASLD requires a holistic approach and treatment of CMRFs through multispecialty collaboration. Currently, diet and physical activity are the effective first-line approaches. There are no approved drugs for the treatment of MASLD, apart from resmetirom, which in a percentage of cases improves metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. We summarize the wide and varied recent literature on the complex etiopathogenetic, clinical and therapeutic aspects of MASLD, connecting and interpreting it to facilitate clinical and management approaches.

Cholera continues to pose a significant public health challenge in Nigeria, driven by poor sanitation, inadequate water quality, and climatic factors that create favorable conditions for outbreaks. Since the first epidemic in 1972, Nigeria has experienced recurrent outbreaks, with the most severe in 1991, resulting in over 7,000 deaths. Current surveillance systems and diagnostic methods are limited by infrastructural gaps, insufficient skilled personnel, and inadequate reporting, leading to delays in outbreak detection and response. These limitations exacerbate the public health burden, increasing mortality and the economic impact of cholera epidemics. This paper explores the potential of artificial intelligence (AI) and machine learning (ML) to address these challenges. AI technologies, including predictive modeling and ML algorithms such as random forests and convolutional neural networks (CNNs), can analyze diverse data sources—such as meteorological, environmental, and health records—to detect patterns and predict outbreaks. Case studies from other cholera-endemic regions, where AI achieved high predictive accuracy, demonstrate its transformative potential. By integrating AI into Nigeria’s public health infrastructure, early detection and response can be improved, resource allocation optimized, and disease transmission minimized. However, challenges such as data quality, standardization, and infrastructural deficits must be addressed. Multi-sectoral collaboration involving public health authorities, AI specialists, and policymakers is essential for the successful deployment of these technologies. This article concludes that AI-powered cholera surveillance systems have the potential to revolutionize public health outcomes, reducing cholera-related morbidity and mortality in resource-limited settings like Nigeria.

Metabolic disorders are due to a deficiency of enzymes, which can severely impact health or cause serious complications without treatment. This study aimed to identify the molecular causes of an infant death who had been hospitalized with complicated health problems and metabolism syndrome. Whole-exome sequencing (WES) was used to screen pathogenic variants in the patient’s genome, followed by examination of variants segregation in her parents. The WES analysis identified two homozygous variants, c.[614C>G; 649A>G] in the HMGCL gene of the patient. These two variants co-locate within the exon 7 of the HMGCL gene, resulting in 2 amino acid substitutions, p.[T205S; M217V], in the conservative region of enzyme protein. Sanger sequencing showed that the patient’s unaffected mother and father carried one mutant allele of the HMGCL gene containing two c.[614C>G; 649A>G] variants. The HMGCL gene encodes the 3-hydroxy-3-methylglutaryl-CoA lyase enzyme, which is critical in the ketogenic pathway. The deficiency of this enzyme was reported to be a life-threatening illness in the neonatal period, and two variants detected in this study were also found in a Japanese patient with sudden, unexpected death in infancy. The frequency of these two variants in the Vietnamese in-hour database and their further functional analysis were also reported in this study. The results of this study have explored the molecular etiology that causes the severe, deadly condition of the patient and provide an understanding of the risk of disease in her family.

The design of effective treatments for critical size bone defects, which result from various conditions such as trauma, infection, injury, or tumor resection, presents a significant challenge in clinical practice. While autologous grafts are commonly regarded as gold standard treatments in these complex healing scenarios, they are often associated with notable limitations, including donor site morbidity and limited graft volume. As a result, recent research trends have shifted towards developing biomaterials that better emulate the inherent complexity of the native bone structure and function through implementation of a “Diamond Concept” polytherapy strategy. Central to this approach is the utilization of biomaterials, increasingly composed of composite materials that integrate bioactive osteoinductive factors and cell sources to enhance healing outcomes. The usage of Wnt signaling specific agonists as osteoinductive mediators has been recently shown to be a promising strategy for promoting healing, as this pathway is well established to have an important role in both osteogenic differentiation and bone formation processes. Implementation of a localized delivery system through scaffold incorporation is necessary in this scenario, however, to minimize any potential off-target effects caused by the Wnt signaling cascade’s non-specificity to bone. Findings in the literature clearly show that this approach holds promise to improve clinical healing outcomes, paving the way for more effective treatment options. In this review, we will generally discuss the design of biomaterials, specifically bulk materials and composites, for the treatment of critical size bone defects. Additionally, we will highlight recent work on the design of chitosan-based scaffolds modified with purine crosslinking, to overcome cytotoxicity issues associated with other chemical crosslinkers. In this context, we focus on optimizing material design for this bone healing application and discuss the benefits of localized Wnt agonist as mediators to improve the scaffold’s osteoinductive behavior.

L-Carnitine (LC) is integral to energy production and fatty acid metabolism, facilitating the transport of long-chain fatty acids into mitochondria for β-oxidation. It modulates metabolic pathways, including pyruvate dehydrogenase activity, proteolysis, and protein synthesis, while also having anti-inflammatory and antioxidant characteristics. LC can be commonly applied to win the battle against HIV and cancer cachexia. Also, it can be recruited with the aim of improving physical and cognitive functions in athletes and the elderly. Despite these benefits, long-term LC administration has been associated to cardiovascular risks due its conversion to trimethylamine-N-oxide (TMAO) by the gut microbiota. Elevated TMAO levels are linked to atherosclerosis, oxidative stress, and an increased risk of cardiovascular disease, diabetes, and chronic kidney disease. Managing TMAO levels using dietary treatments and gut microbiota-targeting techniques, such as probiotics, may reduce these risks. This comprehensive review presents the state-of-the-art information on LC’s dual role, emphasizing the balance between its therapeutic potential and the risks of prolonged supplementation. It aims to guide clinicians and researchers in optimizing LC’s benefits while addressing its long term cardiovascular safety concerns.

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.

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.

The International Agency for Research on Cancer (IARC) Monographs Programme plays an important role in cancer prevention by identifying potential carcinogenic hazards. However, the terminology used in IARC’s classifications and Monographs can confuse the public, health professionals, and policymakers. Terms like “carcinogenic to humans” imply causation, although classifications only indicate increased risk under certain conditions. For example, the lifetime incidence of mesothelioma among firefighters is approximately 14 in 10,000, compared to 7 in 10,000 in the general population. Despite doubling the risk, occupational exposure as a firefighter does not cause this type of cancer in 9,986 out of 10,000 firefighters. However, the IARC concludes that “occupational exposure as a firefighter causes mesothelioma” (IARC Working Group on the Identification of Carcinogenic Hazards to Humans. Occupational Exposure as a Firefighter. Lyon: IARC; 2023. pp. 1–730. PMID: 37963216). In addition, the lack of essential information about dosage and context in the IARC carcinogen lists can lead to agents with health benefits under certain conditions (e.g., solar radiation, red meat consumption, approved drugs) being perceived as universally harmful, discouraging beneficial exposures, behaviors, or treatments. Here, I propose renaming the groups of agents classified by the IARC and adding basic labels to specific agents to improve the accuracy and interpretability of the IARC classification lists. These adjustments do not interfere with the IARC’s objective of identifying potential hazards, are easy to implement, and enhance accuracy and clarity, providing stronger support to guide cancer prevention strategies.

Pyogenic arthritis (PA) related mortality trends have not been studied well across various demographics in the United States (US). This cross-sectional study aimed to evaluate these trends among the US population aged ≥ 25 years from 1999–2020 using data from the CDC WONDER database. We identified all the deaths where PA was listed as the underlying or contributing cause of death, using the ICD-10 code M00. Age-adjusted mortality rates (AAMRs) were calculated per 1 million US population and the Joinpoint regression model was used to assess the annual mortality trends by calculating the annual percent change (APC) in AAMRs. Between 1999 and 2020, 13,965 total deaths occurred among US adults aged ≥ 25 years with an AAMR of 2.94. The overall AAMR of PA increased significantly from 1999 to 2020 with an APC of 2.01 (p < 0.01). Males and older adults had consistently higher AAMRs than their respective counterparts. Non-Hispanic (NH) American Indians/Alaska Natives and NH Blacks/African Americans had higher mortality rates compared with other racial groups. The Midwest had the highest overall AAMR, followed by the West, Northeast, and South regions. In conclusion, PA mortality has been on the rise and targeted interventions are warranted to reduce disproportionate mortality rates among vulnerable populations.

Antibiotic resistance is a significant threat to public health and drug development, driven largely by the overuse and misuse of antibiotics in medical and agricultural settings. As bacteria adapt to evade current drugs, managing bacterial infections has become increasingly challenging, leading to prolonged illnesses, higher healthcare costs, and increased mortality. This review explores the critical role of antibiotics in fighting infections and the mechanisms that enable bacteria to resist them. Key antibiotics discussed include carvacrol, dalbavancin, quinolones, fluoroquinolones, and zoliflodacin, each with unique actions against bacterial pathogens. Bacteria have evolved complex resistance strategies, such as enzyme production to neutralize drugs, modifying drug targets, and using efflux pumps to remove antibiotics, significantly reducing drug efficacy. Additionally, the review examines the challenges in antibiotic development, including a declining discovery rate of novel drugs due to high costs and regulatory complexities. Innovative approaches, such as structure-based drug design, combination therapies, and new delivery systems, are highlighted for their potential to create compounds with enhanced action against resistant strains. This review provides valuable insights for researchers and developers aiming to combat antibiotic resistance and advance the development of robust antibacterial therapies for future health security.

Bladder cancer is currently the most common malignant tumor of the urinary system. The traditional treatment methods for bladder cancer are mainly surgery, chemotherapy, radiotherapy, and targeted therapy; however, these treatment methods do not improve the clinical prognosis of patients with advanced or metastatic bladder cancer. Consequently, there is an urgent need to develop new treatment methods to improve the survival rate and quality-of-life of patients with bladder cancer. Over recent years, the rapid development of tumor immunotherapy has become a significant alternative to traditional treatment, and provides new hope to patients. This review aims to introduce neoantigens and their possible role in the treatment of bladder cancer, and to explore the current limitations of neoantigens for the treatment of bladder cancer.

Gelatin is extracted from beef, pork, and fish tissues. An increasing number of cases of gelatin-induced anaphylaxis are associated with α-Gal syndrome (AGS). Only a few cases of anaphylaxis to bovine gelatin (BG) without AGS (BG-woAG) have been described. We report two new cases of anaphylaxis to BG-woAG, highlight the characteristics of this entity, and propose a procedure in cases of suspected anaphylaxis to BG. We selected articles on gelatin allergy between 1987 and 2024. Results: we report two new cases of severe anaphylaxis BG-woAG. Diagnosis was established using skin tests (ST), IgE, and basophil activation tests (BAT). We confirm the existence of allergies to BG-woAG. The main characteristic of these allergies seems to be the presence of BG IgE which differentiates them from AGS-related allergies. These initial data need to be confirmed by larger case series. We propose a diagnostic algorithm for better patient management. To confirm the diagnosis, ST and IgE to BG and α-Gal should be performed. The role of BAT to Gelofusine^® in the diagnostic strategy remains to be defined.

By offering their expertise, reviewers help authors improve their work and also support editors in selecting high-quality studies, thereby reinforcing the integrity of scientific literature. Much like in a Sergio Leone film, your manuscript encounters three possible types of reviewers on its editorial journey: the Good, the Bad, and the Ugly. The Good Reviewer is, for reasons unknown, favorably disposed toward both you and your manuscript. They find it “well-written, with literary and enjoyable style”, “original and timely”, and addressing a topic that is “scientifically and socially relevant”. Their comments are respectful, constructive, and focused on minor but meaningful improvements. Unfortunately, the Good Reviewer is as rare as a white unicorn; some researchers reach the end of their careers without ever encountering one, leading them to question their very existence. The Bad Reviewer is both bad at reviewing and a bad influence on your work. They reject your manuscript, but their reasons are vague and unconvincing. Their objections are often asinine, and when you respond thoroughly and decisively, they counter with even more nonsensical arguments. They may pressure you to cite irrelevant literature—often their work or that of their colleagues. In the end, your once-solid and cohesive manuscript emerges in a far worse state than the original. None of this would have been possible without the Bad Reviewer, who, unleashed by a negligent editor, exerts their detrimental influence on your article. The Ugly Reviewer appears with unsettling regularity—at least once a month. They believe your article is truly terrible, and often, they are right. The Ugly Reviewer, though harsh, is no fool. Their critiques are brutal and unforgiving, yet accurate. Years later, you may find yourself grateful to them for preventing you from publishing work that, in hindsight, would have irreparably tarnished your already modest scientific reputation.

Chronic pain is a common problem in rheumatology. A distinction is made between nociceptive pain and nociplastic pain. Nociceptive pain is, for example, mechanistically explained by persistent inflammation. Neuropathic pain is caused by nerve damage of various possible causes. In contrast, nociplastic pain is not due to tissue damage or a lesion in the somatosensory nervous system—at least not with the currently available techniques. Nociplastic pain is based on an altered perception of pain through modulation of stimulus processing. The concept of central sensitization, together with other neurobiological and psychosocial mechanisms, is considered to be the best explanation for such pain conditions. The syndrome of fibromyalgia (FM), considered to be due to central sensitization, plays a major role in rheumatology—both in terms of differential diagnosis and because the management of inflammatory rheumatic diseases can be made more difficult by the simultaneous presence of FM. During the coronavirus pandemic, persistent pain syndromes with similarities to FM were described following a COVID-19 infection. There is a growing scientific controversy as to whether the so-called long COVID syndrome (LCS) is a separate entity or just a variant of FM.

In a previous study, we conducted an in vitro comparison of two sublingual allergy immunotherapy products, namely, house dust mite (HDM) Staloral 300 IR/mL produced by Stallergenes Greer, and HDM Osiris 300 IR/mL produced by ALK-Abelló. Although both products are labeled with the same unit, that is, the index of reactivity (IR), the definition of this unit is different depending on the product. This resulted in HDM Staloral 300 IR/mL displaying a higher total allergenic activity (TAA) and higher contents in major allergens and proteins. The aim of this study was to extend the comparison to cat sublingual extracts, that is, to cat Staloral 300 IR/mL from Stallergenes Greer and cat Osiris 300 IR/mL from ALK-Abelló. While both cat allergen extracts were qualitatively similar, in that they exhibited similar protein and allergen profiles, cat Staloral 300 IR/mL displayed a 2 times higher TAA than cat Osiris 300 IR/mL (according to an in-house method) and contained 1.6 time more proteins, 1.3 and 1.9 time more major allergens Fel d 1 and Fel d 4, respectively. No conclusions on clinical efficacy or safety can be drawn from these data.

Glucagon-like peptide-1 (GLP-1) is a hormone that regulates blood glucose levels and is produced by the enteroendocrine glands in the large and small intestines in response to the consumption of foods that contain carbohydrates, fats, and proteins. When GLP-1 is secreted, it acts on the pancreas to increase insulin production and secretion, while decreasing pancreatic glucagon secretion in order to lower serum glucose. However, GLP-1 also regulates metabolism through the gut-brain axis. While GLP-1 is primarily produced in the gut and released into the bloodstream, small quantities of it can also be synthesized in distinct areas of neurons located in the hindbrain. Recent studies have proposed that GLP-1 receptor (GLP-1R) agonists (GLP-1RAs) may protect against neuroinflammatory diseases. GLP-1RAs may also be a therapeutic target for asthma as animal models show that these drugs reduce allergen-induced airway inflammation, as the GLP-1R is expressed on lung epithelial and endothelial cells. There is a notable association between insulin resistance and the onset of asthma, particularly among obese people, with this association suggesting that metabolic dysfunction may play a role in asthma development. There is also evidence that there may be a link between asthma pathobiology and neuroinflammation, suggesting that GLP-1 and its analogs may regulate neuroinflammatory pathways that contribute to asthma pathogenesis. Interest is growing, though research remains limited, in how inflammation in the nervous system and lung might be linked. This review will explore how GLP-1R signaling could inhibit interdependent inflammation in both the lung and nervous system. This review will first focus on the inflammation that is known to exist in asthma, then pivot to the current state of neural regulation of asthma, and finally speculate on how GLP-1RA signaling could inhibit both neural and lung inflammation in asthma treatment.

Liver inflammation, injury, and hepatic cell death are caused by external agents (viruses, bacteria, drugs, alcohol, etc.) along with the genetic susceptibility of an individual. Persistent activation of the fibrogenic response in cells leads to liver fibrosis which in turn progresses to cirrhosis and cancer. The dysregulation of the immune system generates reactive oxygen species which in turn induce necrosis of hepatocytes. This process activates hepatic stellate cells and myofibroblasts to produce a huge quantity of collagens, alpha-smooth muscle actin, and extracellular matrix deposition in liver parenchyma. Due to the multifactorial nature of this disease, conventional therapies increasingly attempted combinatorial therapy or polytherapy to target multiple mechanistic sites in order to prevent entry into further complicated irreversible stages. Despite advancements in conventional therapy, several cases aggravate fibrosis (grade 3 to 4) and cirrhosis. The inconsistency in treatment outcomes and limited organ donors for liver transplantation have led to an ever-increasing and challenging demand for alternative therapies. In this review, we analyze the mechanism and causative factors of liver diseases, conventional mode, and alternative therapeutic options. The central to liver diseases are immune dysregulation, hence bioactive agents with immunomodulatory properties should be searched and exploited to meet therapeutic needs. Mesenchymal stem cells (MSCs) with their specialized anti-inflammatory and immunomodulatory properties could be utilized as an effective alternative therapeutic candidate in treating inflammatory liver diseases. MSC-derived exosome further provides an additional immunomodulatory option that could work in tandem with MSC in a synergistic form. In this series, we have reviewed preconditioned and genetically edited MSCs to augment homing, proliferation, and differentiation. Importantly, all the clinical challenges should be noted and addressed before stem cell cytotherapy should be considered safe and effective for patients with liver diseases. Published literature indicated that MSC therapy has the potential to substitute conventional options in the treatment of high-grade fibrosis and cirrhosis.

The integration between the tumor-suppressive and oncogenic signaling pathways controls various cellular activities of cancer cells, including cell growth and apoptosis. While the activation of oncogenes fuels cancer progression and escape mechanisms, tumor suppressors regulate and counterbalance the negative effects of oncogenic signaling. Notably, phosphatase and tensin homolog (PTEN) constitute one of the important family members of tumor suppressor genes, which play critical roles in regulating the activities of tumor cells. Thus, an impaired, mutated, or loss of PTEN is associated with low survival or high tumor recurrence rates in cancer patients. Importantly, high tumor expression of a G-protein coupled platelet-activating factor-receptor (PAFR) is associated with increased tumor progression as well as decreased overall survival and poor prognosis in malignancies such as non-small cell lung cancer (NSCLC). Along similar lines, overactivation or mutations in epidermal growth factor receptor (EGFR) signaling are detected in various human malignancies and associated with poor prognosis. The goal of the current minireview was to highlight the significance of the mechanistic insights between the PTEN and PAFR as well as the PAFR and EGFR pathways in impacting cancer growth and/or efficacy of therapeutic agents in experimental model systems.

Alcohol is a well-known toxic etiologic factor for liver injury. Metabolic substrates of alcohol (especially acetaldehyde) have a major responsibility and genetic susceptibility, alterations in microbiota and immune system are important co-factors for this injury. Major injury in liver is hepatocellular lipid accumulation. Therefore the relationship between non-alcoholic and alcoholic fatty liver diseases should have been defined clearly. Recently two major liver committees adopted new terminologies such as metabolic-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcoholic liver disease (ALD) instead of non-alcoholic fatty liver disease (NAFLD). These terminologies were based on the effects of metabolic syndrome on liver. Alcohol consumption was defined differently according to these nomenclatures. MAFLD defined alcohol intake (regardless of amount) as “dual etiology fatty liver disease” and the Delphi consensus defined MASLD, MetALD, or ALD according to daily consumption of alcohol amount.

According to research, hepatocellular carcinoma (HCC), ranks third globally in terms of cause of death and is the fifth most common type of cancer overall. Finding novel means of diagnosis and treatment is therefore crucial. The use of nanotechnology as a cancer treatment has drawn a lot of interest recently. Despite significant advancements in detection and treatment, there is still a long way to go before this disease is completely eradicated. Therefore, it’s critical to find innovative ways to diagnose and cure conditions. In particular, the substantial inertness of metallic nanoparticles (NPs) and their nanoscale structures, which have sizes comparable to many biological molecules, attract a great deal of interest in the biomedical field. Due to their exceptional optical qualities, chemically modified surface through the attachment of various ligands, biocompatibility (bio-inertness and low cytotoxicity), and superior optical properties, gold NPs (AuNPs) have garnered significant interest. The current review discusses the efficiency of AuNPs in various fields, including imaging, immunotherapy, and photothermal therapy for treating liver cancer. Finally, this review summarized the limitations of the prospects of the AuNPs.

Ventilator-associated pneumonia (VAP) is a common and serious complication in critically ill patients, particularly those requiring prolonged mechanical ventilation. Extensively drug-resistant (XDR) Acinetobacter baumannii has emerged as a significant threat in VAP cases, complicating treatment due to its exceptionally high level of antibiotic resistance. We present a case of a 62-year-old male patient with severe acute ischemic stroke, who developed VAP during his stay in the intensive care unit (ICU). Cultures confirmed XDR Acinetobacter baumannii as the causative organism. The infection was further complicated by the development of a lung abscess, a rare but severe consequence of VAP. The patient was treated with a targeted antimicrobial regimen consisting of colistin, vancomycin, and tigecycline. Despite the pathogen’s resistance profile, the patient’s infection showed gradual improvement with sustained treatment. However, the recovery process was significantly prolonged due to the complexity of the infection, necessitating extended supportive care during hospitalization. This case highlights the challenges posed by XDR infections in critically ill patients and the importance of a tailored antimicrobial approach to effectively manage severe complications such as lung abscess.

Severe pediatric asthma is a very challenging type of asthma for both physicians and patients. Precision medicine in severe pediatric asthma has undergone important developments in recent years. This therapeutic approach requires an adequate diagnosis and clinical phenotyping of patients and is useful for predicting the prognosis and response to treatment in this type of patient. This article summarizes the scientific information of the last five years in the diagnosis of severe pediatric asthma, focusing on topics such as genetic markers, biomarkers, lung function, radiological techniques, and bronchoscopy.

Papillary muscle rupture is a rare but fatal complication of acute myocardial infarction. The incidence of this complication has been reduced to less than 0.1% of patients due to the advent of primary percutaneous coronary intervention. Cardiogenic shock and acute pulmonary edema are the most common clinical presentations. In this review, we describe the role of transthoracic and transesophageal echocardiography in identifying the type, location, and hemodynamic consequences of the three different echocardiographic patterns of papillary muscle rupture. This information is crucial for managing medical therapy and determining the appropriate surgical or percutaneous treatment.

Throughout history, biopharmaceuticals have been essential in addressing health crises and enhancing human well-being. With advancements in genetic engineering, biotechnology, and bioinformatics, the development and approval rates of new biopharmaceuticals have surged, placing them at the forefront of the pharmaceutical field. Modern manufacturing processes and streamlined regulatory pathways have further expedited approval timelines, providing hope for previously untreatable conditions and significantly improving patients’ quality of life worldwide. However, despite these advancements, ambiguity persists regarding the definition of biopharmaceuticals due to the use of varied terms and a lack of standardized definitions. This article addresses this confusion by proposing a clear and comprehensive definition of biopharmaceuticals. Additionally, we present a reclassification of biopharmaceuticals into seven distinct verticals based on their functions. We assert that biopharmaceuticals not only offer superior therapeutic benefits for human health but also contribute to environmental sustainability, promoting a healthier planet. Thus, this article aims to clarify the scope of biopharmaceuticals and advocate for their broader adoption in the pursuit of global health and environmental integrity.

Repeat expansion diseases (REDs) are genetic disorders caused by unusual expansions of DNA sequences within certain genes. They cause several neurodegenerative diseases including Huntington’s disease (HD), myotonic dystrophy (DM), spinal and bulbar muscular atrophy (SBMA), fragile X syndrome (FXS), and others. The pathogenic repeat expansions disrupt normal cellular processes by producing aberrant RNA repeat sequences, leading to toxic protein aggregation, RNA foci, and altered gene expression. Although they belong to the rare disease group, such diseases must be investigated to understand integral mechanisms and prevention. Current methods for alleviating these diseases involve—gene silencing therapies by antisense oligonucleotides (ASOs) and RNA interference (RNAi), CRISPR/Cas9 gene editing, small molecule therapies, etc. ASOs and RNAi reduce toxic protein production genes while CRISPR/Cas9 excise or alter expanded repeats. Small molecule therapies targeting RNA repeat-binding or proteostasis regulation are being developed to alleviate toxic protein accumulation, prevent RNA toxic foci formation, and promote the degradation of misfolded proteins. Additionally, gene replacement and regulatory element modification restore normal gene function. Some researchers tried to modulate toxic protein aggregation using heat shock proteins and chemical chaperones. This is a comprehensive review on the available research on RED treatment and their ongoing challenges, such as efficient delivery of therapies to the central nervous system, minimizing off-target effects in gene editing, sustaining therapeutic efficacy, and addressing toxicity and scalability in large-scale applications.

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.

Nanoparticles (NPs) are at the forefront as they are providing unprecedented solutions to obstacles and issues in treating neurodegenerative diseases. Due to their size, surface characteristics, and ability to be functionalized, these carriers can directly deliver therapeutics across what is considered one of the main barriers to central nervous system (CNS) treatment, the blood-brain barrier (BBB). Through nano-technology, anti-disease agents such as Alzheimer’s, Parkinson’s, and Huntington’s therapies become more bioavailable, specific in action, and with fewer side effects. The NPs serve as molecular carriers that facilitate transport across the BBB by receptor-mediated transcytosis or by disruption of the barrier with a view to properly delivering drugs to the neural tissues. Some of the therapeutic applications of nanotechnology also present the concept of molecular medicine since the NPs are designed to deliver drugs in accordance with specific biomolecule signals. Besides the therapeutic applications, NPs replace the traditional contrast media for magnetic resonance imaging (MRI) and positron emission tomography (PET) scans for better diagnosis as well as disease tracking in the early stages. In addition, their effects on solubility increase the therapeutic potential of earlier useless compounds, and the preservation of bioactive molecules from degradation increases the therapeutic capacity of medications. Neurodegenerative disorders are marked by oxidative stress and inflammation that contribute to the disease severity; thus, liposomes, dendrimers, and polymeric NPs encapsulate antioxidants and anti-inflammatory compounds, so they target the areas most affected by the disease. Such sophisticated systems minimize the extension of neuronal deterioration and enhance the lot of such patients. The “theranostic” NPs allow for continuous diagnosis and treatment by containing both diagnostic and therapeutic features. These have created unprecedented opportunities to meet the unmet needs in CNS disorders and may revolutionize the evolution of managing neurodegenerative diseases and innovative neuroimaging procedures in the future.

Despite the fact that life expectancies are increasing and the burden of infectious diseases is decreasing, global cancer incidence rates are on the rise. Cancer outcome metrics are dismal for low- and middle-income countries (LMICs), including sub-Saharan Africa, where adequate resources and infrastructure for cancer care and control are lacking. Nigeria, the most populous country in Africa, exemplifies the miserable situation. However, the investigation of medicinal plants for better and safer anti-cancer drugs has now increased tremendously. While scientific evidence is emerging of the potential of some constituents of medicinal plants used in traditional medicine in Nigeria to have anti-cancer effects, there is now a critical need for platforms that integrate ethnomedicinal information on such plants with emerging scientific data on them, to support and accelerate the discovery and development of more efficacious and safer anti-cancer drugs and recipes. Thus, this review highlights the scientific evidence to date for the anti-cancer potential of plants commonly used in traditional medicine to treat cancers in Nigeria. Scientific databases such as PubMed, Science Direct, Scopus, Google Scholar, and Web of Science, as well as related sources, were searched to retrieve relevant information on anti-cancer medicinal plants. Ethnobotanical/ethnomedicinal details of the identified plants were then linked with the available scientific data on their anti-cancer potential, including the cytotoxicity to cancer and normal cells of the extracts and constituent compounds responsible for the activity. This annotated chronicle of Nigerian medicinal plants with potential anticancer activity is a great resource for all stakeholders in the prevention and management of cancers.

The FDA’s approval of resmetirom (Rezdiffra) marks a significant breakthrough in treating metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, conditions linked to non-alcoholic fatty liver disease (NAFLD). MASH is a growing global health concern, and resmetirom offers a novel therapeutic option by targeting liver pathophysiology through thyroid hormone receptor-beta activation. This mechanism effectively reduces fibrosis markers, improves liver enzyme levels, and minimizes liver fat buildup. Clinical trials have shown that resmetirom has a favorable safety profile, with manageable side effects like diarrhea and nausea. Additionally, it may lower cardiovascular risks associated with MASH, enhancing patient outcomes and quality of life. As the first FDA-approved drug for MASH, resmetirom’s introduction fills a crucial treatment gap, providing new hope for millions of patients and representing a pivotal moment in hepatology.

Molluscum contagiosum (MC) is a common skin infection caused by a poxvirus, primarily affecting children and immunocompromised adults. It manifests as single or multiple raised, pearl-like papules and is highly contagious, spreading through skin contact or contaminated objects. Traditional treatments include cryosurgery, curettage, and pulsed dye laser ablation. However, in early 2024, berdazimer topical gel, 10.3% (ZELSUVMI^TM), was approved as the first topical treatment for MC. This review explores the potential of Zelsuvmi gel as a significant advancement in treatment due to its nitric oxide (NO)-producing properties. NO is a naturally occurring molecule in the body with multiple roles, including immune defense, antimicrobial activity, and modulation of apoptosis, inflammation, and cytokine production. The novel mechanism of action of Zelsuvmi, utilizing NO’s antiviral properties, has demonstrated compelling efficacy in clinical settings. The article also considers the broader implications of this treatment, not only for current dermatological practice but also for future research into innovative therapies for viral skin infections. Through an evaluation of clinical data, this review highlights Zelsuvmi’s potential to transform treatment approaches for MC, offering a non-invasive, effective option that may influence both clinical management and future prevention strategies.

In this perspective article, several internationally recognized experts, members of the editorial team of this journal, discuss a selection of current hot topics identified in Food Science and Foodomics. The topics are comprised of the main areas of Food Science and Foodomics, namely, food safety, food authenticity, food processing, and food bioactivity. Logically, several of the discussed topics involve more than one of the mentioned main areas. Regarding food safety, the topics discussed are the use of analytical nanotechnology, nanometrology, nano-chromatography; the determination of organic contaminants based on MS and NMR; the impact of microplastics and nanoplastics on food or the contamination of foods with plant toxins. Regarding food authenticity, the paper discusses the role of MS, NMR, biosensors and the new trends in foodomics for food authentication. In terms of food processing, the work shows interesting perspectives on novel processing technologies, the effect of food processing on the gut microbiota or in the interaction among secondary metabolites and macromolecules; the development of active packaging, and the potential effects of introducing recycled plastics in food packaging; the new green extraction and encapsulation strategies of bioactive compounds from food by-products; and the anti-biofilm capacity of natural compounds/extracts/vegetal oils and essential oils. Food bioactivity and the relation between food and health includes the bioavailability and bioaccessibility of bioactive compounds; new trends and challenges in the interaction of nutraceuticals with biological systems; how food matrix impacts the bioaccessibility of nutrients and bioactive compounds; or the study of biodiversity, food and human health through one-health concept. We anticipate elaborations on these hot topics will promote further studies in Food Science and Foodomics.

The fusion of biomaterial science with clinical practice in oculoplastic and orbital surgery, particularly in the reconstruction of the posterior lamella of the eyelid, the lacrimal system, orbital floor fractures, and the development of implants for anophthalmic sockets, represents a frontier where materials meet surgical techniques. This review, which spans research from 2015 to 2023, delves into the application and integration of biopolymers and functional biomaterials in these complex areas. The discussion begins by reviewing the key anatomy of the external ocular surface, lacrimal system, and orbit. It then summarizes the various current surgical approaches for treating diseases affecting the external ocular surface and orbital involvement, with an emphasis on the associated challenges. The discussion continues with a comprehensive overview of the advantages and disadvantages of current and emerging biomaterials, including synthetic and natural polymers, used in reconstructive surgeries. These include applications for eyelid structure reconstruction, lacrimal system repair, orbital bone fracture repair, and orbital socket reconstruction. Throughout the review, the pathophysiology and challenges associated with these reconstructive procedures are explored, with an emphasis on surgical nuances and the ongoing pursuit of optimal reconstruction techniques. Finally, this review serves as a valuable resource for familiarizing clinicians with current knowledge and generating future hypotheses. It concludes that no evidence-based guidelines currently exist in oculoplastic surgery regarding the use of biopolymers in reconstructive procedures. Further research is needed to evaluate the efficacy and reproducibility of these biopolymers.

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.

The clinical case presented describes a 44-year-old woman with a history of mucinous carcinoma in the right breast, who is diagnosed with a pituitary adenoma. Physical examination revealed signs of acromegaly, such as macroglossia and palmar hyperhidrosis. Hormonal tests were performed and showed elevated levels of insulin-like growth factor type 1 (IGF-1). The patient received GnRH analogues for breast cancer; and started medical treatment with somatostatin analogues for acromegaly, which provided improvement in symptoms. Pituitary bleeding was detected during hormone treatment, which caused the growth of the adenoma, causing it to contact the optic chiasm, although no symptoms of pituitary apoplexy were present. Transsphenoidal endoscopic surgery was performed to remove the adenoma, and the diagnosis of pituitary adenoma was confirmed by pathology. The importance of the evaluation of comorbidities in patients with acromegaly is discussed. Pituitary apoplexy as an uncommon complication of pituitary adenomas, which may be associated with the use of GnRH analogues, is addressed. Pre-surgical medical treatment in acromegaly is also discussed, highlighting the importance of a comprehensive assessment of prognostic factors and appropriate treatment selection to improve clinical outcomes. In conclusion, the importance of a multidisciplinary and personalized approach in the management of patients with GH-producing pituitary adenomas to improve quality of life and clinical outcomes is highlighted.

Somalia’s healthcare system faces significant challenges, including limited infrastructure, a shortage of healthcare professionals (2.5 physicians per 10,000 people), and geographic disparities in access to care, leading to only 35% of the population having access to basic health services. Despite these, Somalia is embracing digital health technologies to address these challenges and to improve healthcare delivery. Telehealth platforms such as Baano and SomDoctor provide remote consultations and specialized care to overcome geographical barriers. mHealth solutions, including Hello! Caafi, leverages Somalia’s expanding telecommunications network to deliver healthcare information and services. The development of an electronic immunization registry demonstrated the role of digital health records in streamlining health services and improving data accuracy. Despite the potential benefits, challenges persist, including limited and unreliable Internet access (27.6% penetration rate), and the need to ensure data privacy and security. Capacity building and digital literacy enhancement among healthcare providers and populations are crucial. Learning from successful digital health initiatives in African countries that have effectively used digital health technologies for medical supply delivery and for improved healthcare access is essential. The roadmap for Somalia emphasizes government leadership, public-private partnerships, context-specific solutions, and investment in digital infrastructure, capacity building, and data privacy measures. This perspective explores current digital health innovations in Somalia and their potential impact on healthcare access and quality, outlining a roadmap for establishing a sustainable digital health ecosystem.

The health sector in Yemen has experienced significant challenges due to prolonged conflict and suboptimal governance, making the development of digital health (DH) crucial. This study highlights the urgent need for the strategic implementation of health interventions in a country where fully functional healthcare facilities, low-income levels, damaged infrastructure, and suboptimal governance limit the effectiveness of traditional interventions. It discusses the prioritized step for advancing DH as a root issue that needs to be addressed first and highlights the importance of effective and efficient management of available resources. The development of telecommunication infrastructure is a fundamental pillar for advancing DH in the country. This comes along with consideration of effective management of the available resources and collaborative efforts among all parties, which are critically important to remove restrictions and constraints relevant to the administrative division and fragmentation of the healthcare system and objectively ensure universal coverage of telecommunications and healthcare services nationwide. By leveraging DH technologies (DHTs), Yemen can overcome these obstacles and revolutionize healthcare delivery. Implementing DHTs and related projects can ensure equitable access to high-quality healthcare services, particularly for impoverished individuals. However, the success of these initiatives relies on a well-established supportive policy and regulatory framework, improved public communication systems, targeted strategies, community engagement, and collaboration between medical service providers and community healthcare workers. Awareness campaigns, workshops, research collaborations, and engagement with international organizations are highly recommended to address challenges and foster the growth and development of DH in Yemen.

Pheochromocytomas (PCCs) and paragangliomas (PGLs; together PPGLs) are uncommon neuroendocrine tumors arising from adrenal medullary chromaffin cells and sympathetic/parasympathetic paraganglia. Though PPGLs predominate in adult populations, pediatric cases of PPGLs represent more aggressive disease outcomes with 12% being diagnosed as metastatic. Metastatic disease (spread to bone, lung, lymph nodes, or liver) occurs in a subset of PPGLs, ranging from 15% to 17% depending on the underlying pathogenic variants. Historically, pulmonary metastases present clinically as multiple small lesions; however, cases of PPGLs with innumerable small metastases (a miliary pattern) overwhelming lung parenchyma define a novel yet exceptionally challenging disease presentation. This pattern of pulmonary lesions upon treatment and/or cellular lysis may lead to both respiratory decompensation as well as prolific catecholamine release, incurring significant morbidity and mortality if not appropriately managed. Of the 2,649 PPGL patients enrolled in our protocol from January 1, 2000, to April 30, 2023, 500 had metastatic disease, 122 were children/adolescents, and 3 of the 122 children/adolescents had extensive pulmonary metastatic disease. All three adolescent patients with extensive pulmonary metastases had cluster 1 PPGLs and suffered hypoxemia (due to pulmonary metastases) leading to overactive hypoxia signaling and catecholamine-induced signs and symptoms [among them hypertension and/or tachyarrhythmia(s)]. Interventions including surgery, chemotherapy, and radiotherapy were pursued. Two patients achieved disease stability, while one patient succumbed to disease. Ultimately these divergent outcomes emphasize the importance of recognizing poor prognostic factors and aggressive disease early, to select appropriate treatments. Optimal management of these patients must consider complications of catecholamine excess and the profound influence of hypoxia. Herein, we describe three adolescent cases of extensive pulmonary metastatic PPGL and the unique clinical challenges faced in treating these tumors alongside relevant literature to provide guidance on appropriate interventions (ClinicalTrials.gov identifier: NCT00004847).

This review examined the potential of hemp components as functional feed and food ingredients, focusing on their impact on the quality and nutritional value of animal products. Following hemp legalization, there was growing interest in its potential to enhance animal diets and processed animal products due to its rich nutritional profile, including high levels of polyunsaturated fatty acids (PUFA), essential amino acids, and fibre. Incorporating hemp components into feed for monogastric animals, particularly poultry, improved lipid stability, sensory attributes, and the fatty acid composition of meat and eggs. Hemp supplementation for ruminants, especially in goats, increased PUFA and conjugated linoleic acid (CLA) content in milk, improved meat tenderness, and enhanced oxidative stability. However, research on hemp supplementation for pigs and beef remained limited, indicating the need for further exploration of these species. Hemp cake, rich in protein, fibre, and essential fatty acids, was the most widely used hemp component due to its economic viability, nutritional benefits, and sustainability, contributing to improved meat and milk quality. Regulatory concerns about the transfer of tetrahydrocannabinol (THC) residues in the produced animal products restricted the use of hemp biomass. In processed animal products, hemp components were studied for their potential to enhance nutritional value, replace animal fats, and serve as natural preservatives. Although they improved the fatty acid profile and antioxidant properties of meat products, challenges such as textural changes and increased lipid oxidation needed to be addressed for optimal use. Limited studies on dairy products indicated promising nutritional enhancements, but textural issues could impact consumer acceptance. In conclusion, hemp components show significant potential for improving the quality and nutritional value of animal products. Further research is necessary to address regulatory, sensory, and formulation challenges and to expand their application across different animal species and processed animal products.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are integral to diabetes treatment, facilitating renal glucose excretion and offering benefits in cardiovascular risk reduction, kidney function preservation, and weight management. However, their integration into diabetes care presents challenges due to associated adverse effects. This review assesses the efficacy of SGLT2 inhibitors in diabetes management. A comprehensive literature search using PubMed and Google Scholar yielded pertinent studies. Clinical evidence demonstrates the effectiveness of SGLT2 inhibitors in glycemic control and in reducing cardiovascular risks in diabetes patients. Moreover, these agents exhibit positive effects on cardiovascular and renal functions. Despite their therapeutic promise, careful consideration is warranted when integrating SGLT2 inhibitors into diabetes care. Common adverse effects such as genitourinary infections, hypoglycemia, and sporadic diabetic ketoacidosis necessitate rigorous patient monitoring and education. Nonetheless, SGLT2 inhibitors offer a comprehensive approach to diabetes management, showing efficacy across multiple domains. In summary, SGLT2 inhibitors play a crucial role in diabetes care, offering benefits beyond glycemic control. However, their use requires careful patient selection, education, and monitoring to manage associated risks effectively. Awareness of potential adverse effects is essential for optimizing the therapeutic benefits of SGLT2 inhibitors in T2DM (type 2 diabetes mellitus) management.

Immune checkpoint inhibitors (ICI) such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1), and lymphocyte activation gene-3 (LAG-3) are increasingly used to treat cancer patients since they were shown to reduce tumor progression and increase survival of patients with different types of cancer. However, ICI may also affect self-tolerance and lead to immune-related adverse events (irAEs) which are not very frequent but can present in almost all organ systems including joints, tendons, and muscles. Indeed, arthritis and myositis are among the most frequent irAEs. Glucocorticoids, immunosuppressants, and biologics are used to treat affected patients. This commentary deals with the question of whether Janus kinase inhibitors could be an option in this clinical situation.

Exposure to ionizing radiation has recognized detrimental cancer and non-cancer health effects. These effects are now well-proven not only for high doses > 1,000 millisieverts (mSv) associated with head radiotherapy but also for moderate (100–1,000 mSv) and even low (< 100 mSv) doses, of interest for professionally exposed cardiologists. The head of interventional cardiologists is highly exposed to ionizing radiation, with possible damage to the eye and brain. Unprotected interventional cardiologists experience head radiation doses up to ten times greater than chest doses below lead aprons, with marked exposure to the left hemisphere of the brain reaching up to 2 Sv—equivalent to 10,000 chest X-rays over a professional lifetime. This narrative review aims to provide an overview of the background of radioprotection, the biological mechanisms involved, and the epidemiological evidence regarding the health effects of head exposure to ionizing radiation in invasive cardiologists. These health effects include cataracts, brain cancer, cerebrovascular diseases, neurodegeneration, and mood disorders. The evidence gathered from other exposed populations, which experienced similar eye and brain doses, has also been reviewed. This is important because the doses, risks, and effects are consistent in cases of repeated exposures, which occur more frequently for patients, and in situations involving chronic low doses, as seen with interventional cardiologists. Despite these risks, effective protective measures—such as suspended lead ceilings, curtains, and specialized eyewear—can reduce radiation exposure to near-zero levels. In some fields, like interventional cardiac electrophysiology, a groundbreaking near-zero radiation approach using non-fluoroscopic methods has been created, eliminating radiation exposure and alleviating orthopedic stress and operational discomfort. The race to zero radiation in interventional cardiology is ongoing.