Sepsis, a life-threatening condition marked by systemic inflammation and multi-organ dysfunction, poses a persistent clinical challenge. Post-translational modifications (PTMs) dynamically regulated inflammatory signaling, immune responses, and cell death, positioning them as a pivotal focus in sepsis research. This review systematically explores the regulatory networks of five key PTMs - phosphorylation, ubiquitination, SUMOylation, acetylation, and lactylation - in sepsis. In this review, we highlight recent discoveries of genes and molecules that modulate these PTMs, influencing inflammation and organ dysfunction, and evaluate their potential as therapeutic targets or prognostic biomarkers. Furthermore, we discuss how PTMs offer novel therapeutic opportunities, providing novel insights to address the shortcomings of traditional anti-infective approaches.

Varicella-zoster virus (VZV) is a highly prevalent pathogen primarily recognized for causing chickenpox during primary infection, and herpes zoster (HZ), also known as shingles, upon reactivation. While post-infectious complications of VZV, such as encephalitis, pneumonia, and post-herpetic neuralgia, are well-established, recent large population-based studies suggest that HZ may increase the risk of occult cancers. This has sparked discussions on the need for cancer screening in patients with HZ to improve early diagnosis and prognosis. However, the specific types of cancers most strongly associated with VZV reactivation have not been systematically identified, and the subsequent cancer risk remains inconclusive. Emerging evidence suggests that VZV may also modulate key oncogenic pathways, such as the inhibition of apoptosis, alteration of cell cycle regulatory enzymes, and interference with immunosurveillance, which could potentially promote cancer development. These findings indicate that VZV’s role in cancer biology extends beyond merely increasing cancer risk and may involve direct cellular manipulation that facilitates oncogenesis. Understanding the interplay between VZV and cancer is critical for public health. Further exploration of the mechanisms of viral oncogenesis could provide valuable insights into how VZV contributes to cancer development and open avenues for targeted preventive and therapeutic strategies.

The historical journey of probiotics is fascinating, from their ancient roots in fermented foods to their potential as personalized medicine. This paper honors the pioneers who paved the path to current advancements. Significant progress has been made in understanding probiotics, including their mechanisms of action, such as competitive exclusion and immune modulation. For example, Lactobacillus plantarum has been shown to improve eczema and the common cold, whereas Bifidobacterium longum aids in nutrient absorption and fights off harmful organisms. In addition, Saccharomyces boulardii has been demonstrated to be effective in preventing antibiotic-associated diarrhea. Probiotics are applied in various fields, including digestive health, immunity enhancement, and chronic condition management. This review discusses the applications of probiotics and addresses challenges such as strain specificity, safety considerations, and regulatory oversights. The future of probiotics lies in precision medicine, with personalized interventions combined with prebiotics (food for probiotics) to unlock their full potential for enhancing human health and well-being. The paper serves as a valuable resource and a gateway for further research.

The lungs emerge from the foregut during the embryonic stage, and as they mature, they go through additional morphological and functional changes that extend into the postnatal stage of development. Each developmental stage of the lung is tightly regulated by specific signaling pathways. Nkx2.1 signaling, which is essential for lung specification, is improved by Wnt/β-catenin signaling but necessitates active bone morphogenic protein signaling. Branching morphogenesis of the lungs requires fibroblast growth factor, while vascular endothelial growth factor signaling promotes endothelial cell survival and capillary development. Disruption at any of these developmental stages can result in congenital lung disorders. Although the lungs are quiescent in adulthood, they retain the capacity for regeneration in response to injury caused by infectious and non-infectious agents. Essentially, the lung’s microbiota plays a role in maintaining lung health and disease. Treatment with probiotics has been established in many infectious lung diseases; however, further research is necessary to fully establish their therapeutic potential in treating these conditions.

The resurgence of phage therapy as a potent countermeasure against antimicrobial resistance has been accompanied by significant challenges in patent protection. This perspective paper examines the patentability of natural phages as therapeutics, focusing on the United States and extending to the European Union and Australia-jurisdictions at the forefront of this biotechnological innovation. We dissect the legal frameworks and identify the patent claims that have successfully navigated the complex intellectual property landscape. Our analysis reveals a dichotomy between the natural origin of therapeutic phages and the inventive steps required for patent eligibility. Despite hurdles, we highlight strategic innovations and specific patent claims that have been granted, suggesting a path forward for the commercialization and protection of phage therapy. We conclude with a call for a more adaptive legal framework to foster innovation and recognize the transformative potential of phage therapy in modern medicine.

Carotenoids, known for their immunomodulatory and gut microbiota-modulating effects, have drawn attention as potential dietary adjuvants to enhance vaccine efficacy and maintain gut health. This study aimed to evaluate the effect of carotene supplementation on immune response with insight into gut microbiome using an in vivo animal model. The BALB/c mice were fed daily with CaroGaia (50 mg/kg of body weight), a carotene supplement that contained 33.3% α-carotene and 66.6% β-carotene, by oral gavage for 70 days. Mice fed with the vehicle served as controls. The mice in the vaccinated groups received two doses of the CoronaVac inactivated virus vaccine on days 14 and 42. Flow cytometry revealed no significant modulation of lymphocyte subsets (total T lymphocytes, T-helper cells, cytotoxic T lymphocytes, and B cells) with carotene supplementation. In addition, there were no significant differences in the levels of SARS-CoV-2 immunoglobulin G and interferon-gamma in plasma between treatment and control groups. In contrast, the vaccinated carotene group showed an increased SARS-CoV-2 antigen-specific splenocyte proliferation. In the gut microbiome, carotene supplementation appeared to alter the gut microbiota composition. However, no significant changes were observed in the short-chain fatty acids (SCFA) levels, such as acetic acid, butyric acid, and propionic acid. Furthermore, the differential abundance analysis showed that carotene supplementation reduced the levels of SCFA producers (Odoribacter and Monoglobus genera) in unvaccinated mice compared to the control group, while it enriched the level of SCFA producers (Ruminococcaceae family) and reduced pathobiont levels, commensal bacteria that have pathogenic potential (Mucispirillum genus), in the vaccinated group.

The present classification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants plays a central role in shaping public health policies, vaccine strategies, and global risk communication. However, existing designations of variants of concern (VOCs) rely on evolving epidemiological and phenotypic criteria rather than quantitative genetic divergence thresholds. In this study, we evaluated the genetic divergence of SARS-CoV-2 variants relative to human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), and influenza A virus, and proposed a framework integrating genetic, functional, and epidemiological criteria for variant classification. Comparative phylogenetic analysis assessed the divergence of SARS-CoV-2 (S) relative to HIV-1 (env), HCV (E1), and influenza A virus (HA). Maximum likelihood phylogenies with bootstrap support were constructed using MEGA6, and pairwise genetic distances were calculated through the maximum composite likelihood model. Monte Carlo simulations (n = 1,000) using adjusted SARS-CoV-2 evolutionary rates (0.0006 - 0.003 substitutions/site/year) estimated time to reach divergence thresholds defined by other viruses. SARS-CoV-2 variants showed a maximum divergence of 0.006 substitutions/site - far below thresholds for HIV-1 (0.157), HCV (0.371), and influenza A (1.956). Projections estimate HIV-1-like divergence in 53.7 years, HCV-like in 126.8 years, and influenza A-like in 668.6 years. No present VOC met all proposed functional criteria: transmissibility, immune escape, disease severity, and global dominance. Omicron exhibited partial immune escape but insufficient divergence for lineage reclassification. While present classification supports short-term response, integrating evolutionary benchmarks would enhance their biological relevance as the virus continues to diversify. A new evidence-based framework is needed to reduce public alarm, guide rational policymaking, and prioritize durable countermeasures over variant-specific responses.

The COVID-19 pandemic has driven the need for accurate data analysis and forecasting to support public health decision-making. This study applied autoregressive integrated moving average (ARIMA) models and ARIMA models with exogenous variables to predict short-term trends in confirmed COVID-19 cases across several regions, including the United States of America, Asia, Europe, and Africa. Model performance was compared between ARIMA and the automated model selection function, auto.arima, and anomaly detection was performed to investigate discrepancies between predicted and observed case numbers. Additionally, the study explored the relationship between vaccination rates and new case trends while also examining the influence of socioeconomic factors—such as gross domestic product per capita, human development index, and healthcare resources availability—on COVID-19 incidence across countries. The findings provide valuable insights into the effectiveness of predictive models and highlight the significant role of socioeconomic factors in the spread of the virus, thereby contributing to the development of more effective strategies for future epidemic prevention and control.

The World Health Organization’s 2016 and 2021 classifications of central nervous system (CNS) tumors emphasize the integration of histopathological and molecular profiling for improved prognostic and therapeutic precision. Understanding the molecular hallmarks of low-grade CNS tumors is essential for enabling precision therapies and minimizing off-target effects while preventing malignant transformation. This study investigated key oncogenic features in surgically resected low-grade CNS tumors of varying cellular lineages and anatomical locations, alongside associated clinical metadata. Tumors were histologically classified and analyzed for molecular markers using immunohistochemistry, immunofluorescence microscopy, and flow cytometry. Assessed hallmarks included proliferation (Ki-67, propidium iodide index), invasiveness (matrix metalloproteinase [MMP]-2), neovascularization (vascular endothelial growth factor receptor 2 [VEGFR2], epigenetic modulation (DNA methyltransferase 1 [DNMT1], and immune microenvironment (Cluster of Differentiation 11b [CD11b], Iba1, silver-gold macrophage staining). Statistical analyses included t-tests, one-way ANOVA, and Kruskal-Wallis tests (p<0.05). In diffuse astrocytoma and myxopapillary ependymoma, a proliferation-invasion dichotomy was observed, with lower-proliferative ependymomas exhibiting higher MMP-2 expression. Astrocytomas exhibited elevated DNMT1 expression, indicative of increased epigenetic alterations. Immune profiling revealed tumor-specific differences: CD11b+ macrophages were more prominent in meningiomas, while Iba1+ microglia were enriched in astrocytomas, reflecting distinct immune microenvironments. Despite their low-grade classification, these tumors demonstrated hallmark cancer characteristics, variably expressed across astrocytoma, ependymoma, and meningioma. The combined assessment of Ki-67, MMP-2, VEGFR2, DNMT1, CD11b, and Iba1 provides a prognostically informative and therapeutically exploitable profile. These findings support the integration of molecular profiling into risk stratification and adjunctive treatment strategies to improve prognosis and reduce malignant progression in low-grade CNS tumors.

Candida is traditionally considered an opportunistic pathogen. However, recent research, accelerated by COVID-19, has raised thought-provoking questions about the limitations of this view. Dietary carbohydrates and ethanol have been shown to enable its pathogenic transition. Its hyphae express epitopes that may initiate celiac and Crohn’s diseases. Hyphal mannan is potentially linked to Gq-coupled G-protein coupled receptors. Antibodies to these receptors include chemotactic cytokine receptors, which may mediate the escape of latent Epstein-Barr virus. Candida hyphae induce mast cells to release histamine and tryptase, which are associated with paroxysmal orthostatic tachycardia syndrome, mast cell activation syndrome, and hypermobility spectrum disorder—conditions frequently observed in long COVID (LC). Hyphae are also implicated in periodontitis, a condition linked to and potentially serving as a sentinel risk indicator for cancer, dementia, autoimmune disease, atherosclerotic cardiovascular disease, and chronic diseases in general. Candida yeast and hyphae can produce their own indoleamine dioxygenase (IDO), which antagonizes host IDO, impacting tryptophan metabolism. Altered tryptophan metabolism is observed in cancer, dementia, autoimmune diseases, and LC. Candida overgrowth (CO) also releases candidalysin, a toxin that suppresses competing intestinal bacteria, triggers inflammasomes, and causes hypercitrullination, a process associated with several autoimmune diseases and cancers. In addition, CO produces aspartyl protease, leading to the release of zonulin from intestinal epithelial cells, which increase intestinal and endothelial permeability - hallmarks of autoimmune diseases. Candida-induced acetaldehyde amplifies the harmful effects of a genetic variant, highly prevalent in Americans, linked to cancer, dementia, and autoimmune diseases. The gut microbiome is increasingly recognized as critical to overall health, and hyphae may play a major role in determining its composition. In this review, the roles of cholecalciferol, tryptophan, and magnesium in counteracting the yeast-to-hyphae transition and invasion are explored. The approach presented here is conceptual rather than empirical.

Synovitis, acne, pustulosis, hyperostosis, and osteomyelitis (SAPHO) syndrome is a rare polygenic autoinflammatory disorder that is associated with headaches of different etiological origins. Herein we report the case of a patient with SAPHO syndrome and provide a literature review. The patient was a 64-year-old female who complained of a recurrent headache, which had persisted for several years, and diffuse arthralgias. A computed tomography-angiogram demonstrated the narrowing of the left carotid canal. The patient had an erythrocyte sedimentation rate of 19 mm/s, and her cerebrospinal fluid contained 20 leukocytes/μL (13 mononuclear) and 0.43 g/L of proteins. Bone scintigraphy showed radiotracer uptake in the frontal bones and spine. The patient’s son had previously been diagnosed with SAPHO syndrome; therefore, the possibility of a disorder in the same spectrum was considered. Corticotherapy followed by sulphasalazine resolved the symptoms. This case illustrates an atypical cranial and meningeal involvement of the SAPHO autoinflammatory process. Our findings underscore the importance of considering immune-mediated disorders in the differential diagnosis of headaches.

Ephrin type-B receptor 2 (EphB2) is a member of the Eph family tyrosine kinase receptors. EphB2 binds to ephrin-B1, ephrin-B2, and ephrin-B3, which are critical regulators of vascular and neural development, influencing cell migration and axon guidance. EphB2 is overexpressed in several tumors, including glioma, breast cancer, hepatocellular carcinoma, and malignant mesothelioma, where it functions as a tumor promoter. Therefore, the development of monoclonal antibodies (mAbs) targeting EphB2 is essential for the diagnosis and treatment of EphB2-positive tumors. In this study, we developed novel mAbs for human EphB2 using the Cell-Based Immunization and Screening method. Among the established anti-EphB2 mAbs, Eb₂Mab-12 (mouse IgG1, kappa) showed reactivity toward EphB2-overexpressed Chinese hamster ovary-K1 cells (CHO/EphB2) and an endogenously EphB2-expressing cancer cell line (LS174T), as confirmed by flow cytometry. The dissociation constant (KD) values of Eb₂Mab-12 for CHO/EphB2 and LS174T were determined to be 1.7 × 10⁻⁹ M and 4.4 × 10⁻¹⁰ M, respectively, using flow cytometry. Furthermore, Eb₂Mab-12 exhibited no cross-reactivity with other members of the EphA and EphB receptors. These results indicate that Eb₂Mab-12 possesses high affinity and specificity in detecting EphB2, suggesting its potential application in tumor therapy.