Search Results (4,650)

Traumatic brain injury (TBI) can lead to persistent adverse outcomes, including cognitive and emotional dysfunction, with recent estimates indicating that up to 50% of individuals with mild TBI experience long-term symptoms. Growing evidence suggests that biological sex influences TBI outcomes and recovery trajectories; however, the molecular underpinnings driving these sex-specific differences remain poorly understood. In this study, a preclinical TBI model was used to directly compare chronic glutamatergic alterations in adult male and female Sprague Dawley rats. To define frontocortical molecular signatures associated with sex-specific glutamatergic dysfunction, proteomic analyses were conducted. Proteomic data revealed dysregulation of key pathways, cellular processes, and molecular regulators involved in excitatory signaling and synaptic function in both sexes. Biomarker profiling identified a single common biomarker between males and females, along with multiple biomarkers unique to each sex. Furthermore, two key brain regions highly susceptible to TBI, the prefrontal cortex and hippocampal subregions, were examined for chronic alterations in key glutamatergic signaling proteins, including N-methyl-D-aspartate (NMDA) receptors and the excitatory synaptic marker postsynaptic density protein 95 (PSD95). Immunofluorescence analyses revealed both sex- and region-specific alterations in the expression of NMDA receptor subunits, as well as in PSD95. Notably, many of these changes were concentrated within the hippocampal subregions, suggesting long-term dysregulation of hippocampal glutamatergic circuitry following injury. Together, these findings indicate the emergence of chronic sex-specific pathophysiology in glutamate signaling after TBI and highlight the importance of incorporating sex as a biological variable in the development of precision medicine-based therapeutic strategies for TBI. Full article

Spermatogenesis is a metabolically intensive process that is highly sensitive to perturbations in proteostasis. The integrated stress response (ISR) and its central effector, ATF4, orchestrate adaptive responses to maintain cellular homeostasis under stress; however, the functional significance of ATF4 in mammalian spermatogenesis has not been established. To investigate this, we engineered a conditional knockout mouse model with germ cell-specific deletion of the Atf4 gene. Results showed that Atf4 deletion did not impair spermatogenesis or male fertility, with knockout mice exhibiting normal testicular histology and standard sperm parameters. Proteomic analysis, however, revealed that ATF4 contributes to testicular protein expression homeostasis, as its deficiency caused marked dysregulation of the testicular proteome, especially impacting SQSTM1/p62 downregulate through endoplasmic reticulum (ER) stress pathway. We conclude that ATF4’s role in regulating proteostatic balance is functionally decoupled from its necessity for the core progression of spermatogenesis. These findings define ATF4 as a potential resilience agent safeguarding testicular function under ER stress, rather than a direct regulator of male germ cell development. Full article

Osteoarthritis (OA) is increasingly conceptualized as a whole-joint disorder, in which pathological processes across articular cartilage, subchondral bone, synovium, and periarticular tissues are tightly interconnected. Within this context, miRNAs have emerged as central post-transcriptional regulators capable of integrating mechanical, inflammatory, and metabolic cues at the network level. In human OA, extensive evidence links miRNA dysregulation to cartilage catabolism, impaired stress adaptation, inter-tissue communication, and the emergence of extracellular and circulating miRNA (cmiRNA) signatures with diagnostic and translational relevance. In contrast, miRNA research in canine OA remains limited, despite dogs developing a naturally occurring form of the disease that closely mirrors human OA in clinical presentation, joint pathology, and biomechanical drivers. To date, only a single pilot study has systematically investigated miRNA expression in spontaneous canine OA, underscoring both the feasibility of miRNA profiling and the substantial gaps that persist in tissue validation and functional characterization. This review critically synthesizes miRNA-mediated regulatory mechanisms in human OA and leverages this evidence to define research priorities in canine OA, where experimental validation remains limited. By focusing on shared molecular contexts rather than assumed equivalence, the review defines a comparative framework highlighting cmiRNAs as promising non-invasive translational targets. Full article

Background: Hepatocellular carcinoma (HCC) stands as a prevalent global health issue with increasing incidence and mortality rates. Hepatocellular carcinoma (HCC) exhibits profound molecular and clinical heterogeneity, which limits the effectiveness of current therapeutic strategies. Circadian rhythm disruption has been implicated in metabolic reprogramming, proliferation, and immune modulation in cancer, but its role in shaping HCC heterogeneity remains poorly defined. Methods: Four public HCC transcriptomic cohorts (TCGA-LIHC, CHCC, LIRI, LICA) were integrated using RMA normalization and ComBat for batch correction. Consensus clustering based on 31 core circadian clock genes (CCGs) identified robust molecular subtypes. Multi-omics characterization—including genomic alterations, pathway activity (GSEA/GSVA), immune microenvironment profiling (CIBERSORT, EPIC, MCP-counter, xCell), and drug-sensitivity prediction (pRRophetic/oncoPredict)—was performed to delineate subtype-specific biological properties. A nine-gene CCG-based RiskScore model was constructed using LASSO Cox regression to internally validate subtype robustness and intra-subtype risk stratification. Results: Using consensus clustering of 31 core CCGs in TCGA-LIHC and three independent validation cohorts (CHCC, LIRI, LICA), we identified three reproducible subtypes—Cluster-1 (metabolic–quiescent), Cluster-2 (transition–intermediate), and Cluster-3 (proliferation–inflammatory)—which were recapitulated across cohorts and showed distinct overall survival (Cluster-3 worst; log-rank p values significant across datasets). Multi-omic characterization revealed that Cluster-3 exhibits the highest tumor mutational burden and CNV burden with enrichment of TP53/AXIN1/TERT alterations, strong activation of cell-cycle, E2F, and G2M programs, and an immune-hot yet immunosuppressed microenvironment enriched for TAMs, Tregs and MDSCs. By contrast, Cluster-1 shows relative genomic stability, dominant hepatic metabolic signatures (fatty-acid oxidation, bile-acid and xenobiotic metabolism) and an immune-cold phenotype. Single-cell mapping linked ALAS1 expression to malignant hepatocytes predominating in Cluster-1, whereas NONO and CSNK1D localized to stromal (CAFs/TECs) and both malignant/immune compartments respectively in Cluster-3, providing a cellular mechanism for subtype-specific metabolism, angiogenesis and immune modulation. Finally, a nine-gene CCG-based RiskScore validated prognostic stratification and drug-sensitivity predictions indicated subtype-specific therapeutic vulnerabilities (notably increased predicted TKI sensitivity in Cluster-3). Conclusion: In conclusion, this study proposes a robust circadian rhythm-based molecular classification of hepatocellular carcinoma, revealing three biologically and clinically distinct subtypes characterized by divergent genomic alterations, metabolic programs, immune microenvironment states, and prognostic patterns. By integrating bulk and single-cell transcriptomic data, we identify subtype-specific roles of key circadian regulators—including ALAS1, NONO, and CSNK1D—in shaping tumor metabolism, proliferation, stromal remodeling, and immune suppression. These findings highlight circadian dysregulation as a potential upstream factor associated with HCC heterogeneity and provide a conceptual framework for developing subtype-tailored mechanistic studies and circadian-informed therapeutic strategies. Full article

Background: Fibromyalgia (FM) and eating disorders (ED) represent distinct clinical entities traditionally managed within separate medical specialties, yet emerging evidence suggests significant comorbidity and potential shared pathophysiological mechanisms. Both conditions disproportionately affect women, involve complex multifactorial etiologies and substantially impair quality of life. Despite documented clinical overlaps, the mechanistic connections linking these conditions remain poorly characterized, and integrated treatment approaches are lacking. Objective: This narrative review examines the role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway dysfunction as a unifying molecular mechanism connecting fibromyalgia and eating disorders, with emphasis on implications for integrated rehabilitation strategies. Methods: We synthesized current evidence on oxidative stress pathophysiology in fibromyalgia and eating disorders, focusing on Nrf2-Keap1 pathway function, clinical comorbidity patterns and rehabilitation interventions targeting antioxidant defense mechanisms. In PubMed, representative search strings included “(fibromyalgia [MeSH] OR fibromyalgia [Title/Abstract]) AND (“eating disorders” [MeSH] OR “anorexia nervosa” [MeSH] OR “bulimia nervosa” [MeSH])” and “fibromyalgia AND (“oxidative stress” OR Nrf2 OR “redox”)”. Articles in English published through December 2025 were considered, with additional records identified by manually screening reference lists. Results: Fibromyalgia patients exhibit elevated oxidative stress markers, impaired antioxidant enzyme function and compromised Nrf2 activity correlating with disease severity, with studies reporting approximately 30–50% reductions in coenzyme Q10 levels compared with healthy controls. Similarly, eating disorders demonstrate mitochondrial dysfunction and oxidative stress dysregulation, though patterns differ across eating disorder phenotypes. Nrf2 serves as the master regulator of cellular antioxidant defense, coordinating expression of over 500 genes involved in detoxification, cytoprotection, inflammation modulation and metabolic regulation. Evidence suggests Nrf2 activity is regulated by energy balance, potentially linking nutritional status with cellular stress responses. Rehabilitation interventions, including graduated exercise and nutritional optimization with Nrf2-activating foods (cruciferous vegetables, polyphenols, omega-3 fatty acids), offer mechanism-based therapeutic approaches through hormetic Nrf2 activation and direct Keap1 modification. Conclusions: Multidisciplinary rehabilitation programs integrating physical therapy, exercise prescription and nutritional strategies targeting Nrf2 activation offer evidence-based, mechanism-driven approaches to address shared oxidative stress pathophysiology. Nrf2 pathway dysfunction represents a promising and biologically plausible molecular target that may help to unify our understanding of fibromyalgia and eating disorders pending confirmation from prospective clinical studies in comorbid populations. Future research should prioritize prospective clinical trials testing Nrf2-targeted interventions in comorbid populations and collaborative patient-centered care models. Full article

Background/Objectives: Alcohol-related liver cirrhosis is a systemic disorder characterized by profound immune, metabolic and gut–liver axis dysregulation. Emerging evidence highlights a bidirectional interaction between the intestinal microbiota and host microRNAs (miRNAs), positioning this axis as a potential regulator of systemic homeostasis. However, human data exploring the impact of microbiota modulation on miRNA expression in advanced liver disease remain limited. Methods: Six patients with alcohol-induced liver cirrhosis underwent fecal microbiota transplantation (FMT). Safety was assessed through clinical and paraclinical monitoring at predefined intervals. Quality of life was evaluated pre- and post-intervention using a validated liver-specific questionnaire. Fecal expression of miR-21-5p, miR-122-5p, miR-125-5p, miR-146-5p and miR-155-5p was analyzed and correlations with clinical domains, demographic variables and hepatic encephalopathy severity were explored. Results: FMT was well tolerated, with no severe adverse events reported. Preliminary improvements were observed in total clinical score (3.22 [3.06–3.57] vs. 4.25 [4.20–4.26], p = 0.001) and in several quality-of-life domains, including abdominal symptoms, fatigue, systemic manifestations, activity and emotional function (p < 0.05), while worry/concern scores remained unchanged. miR-125 and miR-146 demonstrated consistent associations with clinical status both before and after FMT, whereas miR-21 correlated mainly with age and body mass index. Notably, miR-125 and miR-146 were also associated with post-FMT hepatic encephalopathy severity, supporting their potential value as molecular correlates of clinical response in this exploratory study. Conclusions: In this pilot study, FMT appeared safe and was temporally associated with improvements in clinical parameters in alcohol-related cirrhosis, alongside dynamic changes in fecal miRNA expression. These preliminary findings support a potential microbiota–miRNA interaction and warrant validation in larger, controlled longitudinal studies. Full article

Background/Objectives: Iron deficiency anemia (IDA) is a widespread nutritional disorder characterized by impaired iron absorption, inflammation-associated iron restriction, and disrupted iron homeostasis. Increasing evidence suggests that gut microbiota play an important role in iron metabolism; however, the mechanisms underlying probiotic-assisted iron supplementation remain unclear. Our research group previously conducted in vitro fermentation screening experiments and obtained a bacterial strain, B. lactis Ca360, which possesses iron absorption-enhancing activity. Methods: In this study, an IDA mouse model induced by a low-iron diet was used to investigate whether B. lactis Ca360 could synergistically improve iron metabolism when combined with iron supplementation. Mice were treated with FeSO₄ alone or FeSO₄ combined with B. lactis Ca360, and hematological parameters, organ indices, serum iron-related markers, histopathological changes, duodenal iron metabolism-related gene expression, hepatic inflammatory responses, gut microbiota composition, short-chain fatty acid (SCFA) levels, and correlation networks were analyzed. Results: Iron deficiency induced typical anemia phenotypes, multi-organ dysfunction, intestinal iron absorption dysregulation, hepatic inflammation, and gut microbiota dysbiosis. Compared with FeSO₄ alone, the combined intervention more effectively improved hematological parameters, reduced organ indices, restored liver and spleen histological integrity, normalized intestinal iron metabolism-related gene expression, and alleviated hepatic inflammation. In addition, B. lactis Ca360 markedly reshaped gut microbiota composition, enriching SCFA-producing anaerobic genera, including Ruminococcus, Roseburia, Acetatifactor, Intestinimonas, Eubacterium_coprostanoligenes_group_unclassified, and Oscillibacter, accompanied by increased acetate, propionate, and butyrate levels. Spearman correlation analysis further revealed close associations between gut microbiota remodeling, improved iron metabolism, reduced inflammatory status, and recovery of anemia-related phenotypes. Conclusions: Overall, these findings demonstrate that B. lactis Ca360 enhances the efficacy of iron supplementation by modulating SCFA-producing and anti-inflammatory gut microbiota, thereby coordinately regulating intestinal iron absorption, inflammation, and systemic iron homeostasis, supporting probiotic-assisted iron supplementation as a promising nutritional strategy for IDA management. Full article

Background and Aims: The rising global incidence of cholangiocarcinoma (CCA) coincides with epidemics of type 2 diabetes (T2D) and chronic hepatitis B virus (HBV) infection. Although both are established independent risk factors, the shared molecular mechanisms by which they contribute to cholangiocarcinogenesis remain poorly understood. We hypothesized that T2D and HBV converge on a state of chronic metabolic inflammation (“metaflammation”) that drives CCA progression through a conserved transcriptomic network. Methods: We performed an integrative bioinformatics analysis of transcriptomic data from public repositories, including samples of CCA (TCGA-CHOL, n = 45; GSE107943, n = 163), T2D-affected liver (GSE23343, n = 20), and HBV-infected liver (GSE58208, n = 102). Acknowledging that the T2D and HBV datasets were derived from whole-liver tissue, whereas CCA originates in the biliary epithelium, we identified differentially expressed genes (DEGs) across conditions and defined a core gene set shared among them. Subsequent analyses included functional enrichment, construction of protein–protein interaction (PPI) networks, survival analysis, and protein validation. Results: We identified a core metaflammation signature comprising 156 genes that were consistently dysregulated across T2D, HBV, and CCA. Pathway analysis revealed significant enrichment in PPAR signaling, cytokine–cytokine receptor interaction, PI3K-Akt, and TNF signaling pathways. Protein–protein interaction (PPI) network analysis identified IL6, TNF, AKT1, STAT3, and PPARG as the top hub genes. These hubs were functionally modularized into clusters associated with inflammatory signaling, metabolic regulation, and cell growth and survival. In the TCGA CCA cohort, high expression of IL6, TNF, AKT1, and STAT3 and low expression of PPARG correlated with advanced tumor stage and poorer overall survival (e.g., IL6: ρ = 0.42, p = 0.01). A metaflammation score derived from these hubs (weighted combination of the five genes) emerged as an independent prognostic factor (HR = 2.8, p < 0.001). Protein-level dysregulation of these hubs was confirmed via immunohistochemistry. Conclusions: This study defines a conserved metaflammation network that links T2D and HBV to CCA, identifying key hub genes and pathways. This signature provides a mechanistic explanation for epidemiological risks, serves as a novel prognostic tool, and offers a rationale for targeting metaflammation in prevention and therapy for high-risk populations. Full article

Background: Autophagy is a conserved intracellular degradation pathway essential for maintaining cellular homeostasis by recycling damaged organelles and proteins. Dysregulation of autophagy has been implicated in pregnancy-related complications such as preeclampsia and fetal growth restriction, underscoring its importance in maternal and fetal health. However, the autophagy status in the placental tissue of COVID-19-infected pregnant women remains unknown. Objective: To investigate autophagy activity in term placentas from pregnant women infected with COVID-19 compared to those from uninfected control pregnant women. Methods: In this prospective cross-sectional single-center study, 15 COVID-19-positive and 15 COVID-19-negative term pregnant women who delivered at Sultan Qaboos University Hospital between January 2020 and December 2022 were included. Immediately after delivery, the placental tissue samples were collected and assessed for autophagy activity using immunohistochemistry for LC3B and p62 markers, histopathological examination, and transmission electron microscopy. The proportion and intensity of LC3B and p62 staining were quantified. Statistical analysis was performed using the Mann–Whitney U test. Results: There was a significant reduction in p62 and LC3B expression in both the proportion and intensity in COVID-19 placentas compared to the control group. The proportion of p62 (p = 0.001) and LC3B (U = 46.000, p = 0.003) was significantly reduced in infected placentas. Similarly, intensity levels of both markers showed significant differences (p < 0.05), supporting the evidence of reduced LC3B/p62, suggesting autophagy modulation in COVID-19 patients’ placentas. Additionally, abnormal ultrastructural changes were observed in COVID-19–positive placentas, including mitochondrial injury, endoplasmic reticulum stress, microvillus loss, and basement membrane thickening. Conclusion: The study results from a limited sample size demonstrate a significantly altered autophagy flux in the placental tissues of term pregnant women with COVID-19 infection. These findings highlight the potential impact of COVID-19 infection on placental function and fetal development and underscore the need for further investigation into autophagy-modulating strategies to improve maternal–fetal health. Full article

The physiological impact of neoadjuvant therapy on vascular and thermal responses in breast cancer patients remains poorly understood, despite its clinical relevance for predicting treatment outcomes and managing therapy-related side effects. Sensor-based monitoring technologies, such as thermography and Doppler ultrasound, provide non-invasive approaches to assess circulatory and thermal changes, potentially serving as predictive biomarkers of therapeutic efficacy. This study aimed to evaluate vascular impairment and correlate circulatory alterations with skin surface temperature in women undergoing neoadjuvant therapy for breast cancer. A total of 38 women were enrolled and distributed into two groups: patients receiving eight cycles of neoadjuvant chemotherapy and healthy controls. Thermographic imaging was employed to measure upper-limb surface temperature, while Doppler ultrasound assessed arterial and venous blood flow in the cubital fossa. Paired Student’s t-tests compared experimental moments (C1, C5, C8), with normality assessed from difference scores (Δ) and results expressed as mean differences with 95% CIs (p < 0.05, two-tailed). Associations between surface temperature and arterial blood flow were examined using simple linear regression (R², F-statistic, β, p-values). Analyses were performed in SPSS 20.0 (SPSS Inc., Chicago, IL, USA). Significant increases in surface temperature (p < 0.001) and blood flow velocity (p < 0.004) were observed in patients compared with controls prior to therapy, suggesting pre-existing vascular and thermal dysregulation. Neoadjuvant therapy significantly altered thermal and vascular dynamics, reinforcing the utility of sensor-based monitoring to capture subtle physiological responses during treatment. Full article

Postprandial hyperglycemia represents a critical therapeutic target in type 2 diabetes mellitus (T2DM), requiring interventions that simultaneously address glycemic dysregulation and oxidative stress. This study evaluated the anti-hyperglycemic and antioxidant properties of Sclerocarya birrea leaf crude extract (CE) and biosynthesized silver nanoparticles (AgNPs). Phytochemical screening, nanoparticle characterization (UV–Vis, XRD, TEM, SEM, DLS, FTIR), enzyme inhibition assays (α-amylase, α-glucosidase, DPP-IV), glucose dynamics in Caco-2 cells, and antioxidant assays (DPPH, total antioxidant capacity, H₂O₂ cytoprotection) were performed. Phytochemical analysis identified flavonoids, tannins, alkaloids, and terpenoids as major constituents of Sclerocarya birrea leaf extract. AgNPs exhibited spherical morphology (36.8 ± 8.6 nm, n = 100 particles analyzed), face-centered cubic crystallinity (crystallite size: 32.1 nm), and characteristic surface plasmon resonance at 451 nm. Both formulations inhibited α-amylase (CE IC₅₀: 14 µg/mL; AgNPs IC₅₀: 14.07 µg/mL, n = 3) and α-glucosidase (CE IC₅₀: 15.96 µg/mL; AgNPs IC₅₀: 15.82 µg/mL, n = 3), showing substantial inhibition, though less potent than acarbose. Uniquely, AgNPs demonstrated selective DPP-IV inhibition (IC₅₀: 220.5 µg/mL, n = 3, p < 0.001 vs. CE), completely absent in CE. In antioxidant assays, DPPH scavenging potency was comparable between formulations (CE IC₅₀: 23.45 µg/mL; AgNPs IC₅₀: 22.26 µg/mL, n = 3), while CE achieved higher maximal scavenging at the tested concentrations. Conversely, AgNPs provided superior intracellular cytoprotection against H₂O₂-induced oxidative stress in kidney cells (80.2 ± 2.1% viability at 76 µg/mL vs. CE 69.8 ± 3.4% at 190 µg/mL, n = 3, p < 0.001), representing a 2.5-fold dose advantage. Neither formulation significantly altered glucose uptake or SGLT1 expression in intestinal epithelial cells (p > 0.05, two-way ANOVA, n = 3). These findings establish S. birrea-based formulations, particularly AgNPs, as promising multifunctional candidates for managing postprandial hyperglycemia and oxidative complications in T2DM. They also highlight nanotechnology-enhanced phytomedicine as an innovative therapeutic strategy. Full article

Background/Objectives: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and remains associated with poor prognosis despite multimodal therapy. Metabolic reprogramming, particularly increased dependence on glutamine, supports GBM bioenergetic, biosynthetic, and redox demands. This study aimed to systematically identify glutamine-associated metabolic regulators with prognostic relevance and biological plausibility in GBM. Methods: Transcriptomic data from TCGA and GTEx were analyzed using GEPIA2, with survival validation performed using the CGGA. Functional pathway enrichment, protein expression assessment, protein–protein interaction network analysis, tumor microenvironment evaluation, epigenetic profiling, and single-cell RNA sequencing validation were integrated to contextualize candidate genes. Pharmacogenomic correlation analysis and structure-based molecular docking were applied as supportive validation layers. Results: Ceruloplasmin (CP), Solute Carrier Family 25 Member 13 (SLC25A13), and Solute Carrier Family 38 Member 2 (SLC38A2) were selectively dysregulated and associated with poor clinical outcomes in GBM. CP was linked to redox regulation and stress-adaptive survival programs, SLC25A13 to mitochondrial metabolite exchange and glutamine-coupled nucleotide biosynthesis, and SLC38A2 to glutamine uptake, nutrient sensing, and mTORC1-MYC-associated growth signaling. Conclusions: CP, SLC25A13, and SLC38A2 emerge as clinically relevant glutamine-associated metabolic regulators in GBM, linking redox regulation, mitochondrial metabolite exchange, and glutamine-driven growth signaling. These findings highlight transport- and exchange-centered metabolic nodes as potential biomarkers and candidates for future metabolic targeting in GBM. Full article

Endometrial cancer (EC) is the leading gynecological malignancy worldwide. Obesity is reported to be associated with 50% of EC cases. Significant gaps remain in investigating specific molecular mechanisms behind the obesity-driven EC. Women diagnosed with EC undergoing total hysterectomy were recruited. Patients were divided into two groups: EC-obese with BMI > 29.9 kg/m² (n = 10) and EC-Non-obese with BMI ≤ 29.9 kg/m² (n = 10). Tumor tissues were subjected to label-free quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins were identified and subjected to pathway enrichment and network analyses to characterize obesity-associated alterations. Proteomic profiling showed a significant dysregulation of 456 proteins: 171 upregulated and 285 downregulated. Proteins involved in endoplasmic reticulum quality control particularly endoplasmic reticulum lectin 1 (ERLEC1), were reduced. Conversely, EC-obese demonstrated upregulation of hepatocyte growth factor (HGF), integrin-linked kinase (ILK), CTTNBP2 N-terminal-like protein (CTTNBP2NL), and lysyl oxidase homolog 1 (LOXL1), implicating activation of inflammatory pathways. Bioinformatic analysis showed downregulation of immune-related pathways, including neutrophil degranulation, complement activation in the EC-obese group. ROC analysis identified apolipoprotein(a), phospholipase B-like 1, CTTNBP2NL, and ILK as significant proteins that can differentiate between the obese and non-obese states. Our findings provide insights into obesity-associated proteomic changes in EC and highlight candidate proteins that can be used for molecular stratification after further validation. Full article

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection induces heterogeneous immune responses that influence both acute disease severity and long-term immune remodeling. A key question in the context of infection and vaccination is whether SARS-CoV-2 exerts direct oncogenic effects or instead acts as a transient immunological stressor capable of reinforcing tumor-permissive pathways. Current evidence does not support classical viral oncogenesis. Rather, severe infection is characterized by early interferon (IFN) imbalance followed by NF-κB-dominant inflammatory amplification, promoting sustained IL-6/JAK–STAT3 and MAPK signaling, chronic cytokine production, metabolic reprogramming, and impaired antitumor immune surveillance. At the molecular level, viral structural proteins modulate host signaling networks. The spike (S1) protein engages TLR2/TLR4–MyD88 pathways, activating NF-κB and MAPK cascades, while the membrane (M) protein reinforces NF-κB–STAT3 circuits linked to epithelial–mesenchymal transition and inflammatory gene expression. These mechanisms intensify pre-existing oncogenic signaling without initiating malignant transformation. Tissue-specific responses are further shaped by IFN competence, renin–angiotensin system balance, and metabolic context. In parallel, immune evasion programs shared by chronic viral infection and cancer, including checkpoint upregulation, impaired antigen presentation, and suppressive myeloid expansion, may be transiently reinforced following severe infection. In contrast, SARS-CoV-2 vaccination induces spatially restricted, self-limited innate activation without sustained inflammatory signaling or persistent antigen exposure. By preventing severe disease and chronic immune dysregulation, vaccination interrupts pathways hypothesized to intersect with cancer biology, with no evidence of increased cancer incidence. Ongoing longitudinal studies are required to clarify the long-term oncologic implications of post-infectious immune remodeling. Full article

Background: Oral Submucous Fibrosis (OSMF) is a significant global oral health problem, particularly prevalent in India, with a high risk of progression to Oral Squamous Cell Carcinoma (OSCC). This study investigates the molecular mechanisms involved in the transformation of OSMF to OSCC using transcriptomic profiling. Methods: High-throughput RNA sequencing was performed on fresh de novo OSCC samples (n = 8) and OSMF derived OSCC using Illumina-compatible NEXTflex Rapid Directional RNA Sequencing. Normalization and differential gene expression analysis were conducted, and genes exhibiting an absolute log2 fold change of ≥2 with a co-variate-adjusted p-value ≤ 0.05 were identified as significant. Results: Upregulated genes were associated with cytokine and immune responses (ABRA, TTTY14, EIF1AY), cellular proliferation and apoptosis (LINC00314, RPS4Y1, SERPINA5, TRIM63, FABP7), and energy metabolism, indicating metabolic adaptations during malignant progression. Pathway analysis showed increased expression of TNNT1, TNNI1, MYL4, and ACTN3, implicating muscle development and embryonic pathways in OSMF transformation. Conversely, genes related to epithelial differentiation and keratinization (FLG, FLG2, HRNR, TCHH, KRT73), immune regulation and tumor suppression (HLA-G, UNC5D), and metabolic signaling were downregulated, reflecting loss of tissue integrity and immune control. Conclusions: OSMF-derived OSCC exhibits a distinct transcriptomic landscape compared with de novo OSCC, characterized by altered epithelial differentiation, immune modulation, and activation of developmental pathways. The observed gene dysregulation findings establish that OSCC developing in the background of OSMF is molecularly distinct from de novo OSCC, underscoring the biological impact of the pre-existing fibrotic milieu on tumor transcriptional architecture. Full article