Oq Al-Lela

Celiac disease (CeD) is a chronic autoimmune disease triggered by gluten consumption in genetically susceptible individuals, primarily those with HLA‐DQ2 or HLA‐DQ8 haplotypes. Although these genetic factors are responsible for a substantial portion of disease risk, they do not fully explain disease heritability or the rising incidence observed worldwide. Recent clinical studies highlight epigenetic modifications—including DNA methylation, histone modifications, non‐coding RNA regulation, and RNA methylation—as critical mediators bridging genetic susceptibility and environmental influences, such as gut microbiota dysbiosis, dietary patterns, early‐life exposures, infections, and pharmaceutical interventions. These epigenetic mechanisms modulate immune responses, intestinal barrier function, and inflammatory pathways, contributing to the loss of gluten tolerance and perpetuation of mucosal damage. Key players, including tissue transglutaminase 2 (TG2) and interferon‐gamma (IFN‐γ), form amplifying feedback loops that exacerbate pathogenesis. Bacterial metabolites and lifestyle factors further influence epigenetic landscapes, offering reversible targets for intervention. This review synthesizes current evidence on epigenetic alterations in CeD, emphasizing their interplay with microbiota and metabolites, tissue‐specific patterns, and potential as biomarkers. It also explores implications for novel therapeutic strategies beyond the gluten‐free diet, including epigenetic modulators and microbiota‐targeted approaches, to advance personalized prevention and management of CeD.

Background: The gut microbiome has emerged as a potential contributor to cardiovascular diseases (CVDs), including atherosclerosis, acute coronary syndrome (ACS), and peripheral arterial disease (PAD). While observational studies link dysbiosis to CVD, causal relationships remain uncertain. Methods: This narrative review synthesizes evidence from human observational studies, clinical interventions, and experimental models to distinguish association from mechanistic plausibility and clinical causality. Literature was searched through July 2026 in PubMed/MEDLINE, Web of Science, and Scopus. Results: Microbial metabolites—including trimethylamine N‐oxide (TMAO), short‐chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)—modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor‐mediated signaling and epigenetic regulation. SCFAs demonstrate potentially protective effects via GPCR and HDAC pathways, while TMAO is associated with atherothrombotic risk. However, much mechanistic evidence derives from preclinical studies. Heterogeneity from diet, geography, host characteristics, renal function, and medications substantially influences microbiota‐CVD associations. Conclusion: The gut‐vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome‐directed therapies (dietary modulation, pre/pro/synbiotics, targeted metabolite inhibition) are investigational. Prospective, standardized, adequately powered human studies with clinically meaningful outcomes are essential before routine cardiovascular application.

From the perspective of both the host cell and the virus, cholesterol (CHO) plays a critical role during viral infection. Proprotein convertase subtilisin/

Oral malignancies, particularly oral squamous cell carcinoma (OSCC), are among the most prevalent head and neck cancers and remain associated with high morbidity, therapeutic resistance, and frequent recurrence. Despite multimodal treatment approaches, long-term survival remains suboptimal, highlighting the need for novel adjunctive strategies. Quercetin, a naturally occurring dietary flavonoid abundant in fruits and vegetables, has attracted attention due to its antioxidant, anti-inflammatory, and anticancer properties, with growing evidence supporting its relevance in oral cancer. In vitro studies demonstrate that quercetin significantly reduces oral cancer cell viability, proliferation, and clonogenic potential in a dose- and time-dependent manner. These effects are mediated by modulation of key cell-cycle regulators, resulting in arrest at the G1 and G2/M phases. Quercetin also promotes apoptosis through increased intracellular reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, cytochrome c release, and activation of caspase-9 and caspase-3, indicating involvement of the intrinsic pathway. Concurrent activation of Fas/Fas-L signaling and caspase-8 suggests engagement of the extrinsic apoptotic pathway as well. Beyond cytotoxicity, quercetin suppresses migration and invasion by inhibiting epithelial-mesenchymal transition (EMT), characterized by increased E-cadherin and reduced N-cadherin and vimentin expression. It also downregulates MMP-2, MMP-9, and VEGF, thereby limiting extracellular matrix degradation and angiogenesis. In vivo studies further confirm reductions in tumor volume and growth kinetics without significant systemic toxicity. Nonetheless, although these findings underscore quercetin's multi-targeted anticancer potential, clinical translation is limited by poor bioavailability and rapid metabolism. Optimized delivery systems and well-designed clinical trials are necessary to clarify its therapeutic applicability in oral malignancies. This review will summarize current evidence on quercetin's anticancer effects in oral malignancies and highlight the molecular mechanisms underlying its therapeutic potential.

Therapy resistance remains a formidable challenge in hematologic malignancies despite significant advances in targeted therapies. This comprehensive review examines integrin-linked kinase (ILK) as a critical molecular hub at the nexus of cell adhesion, signal transduction, and therapy resistance across leukemias, lymphomas, and multiple myeloma. Unlike in solid tumors, where ILK primarily drives invasion and metastasis, in hematologic malignancies it uniquely mediates microenvironmental protection and therapy resistance through distinct signaling networks. ILK functions as a central mediator connecting microenvironmental signals to intracellular survival pathways, with expression levels 5-20-fold higher in malignant cells compared to normal counterparts. Through systematic analysis of structural properties, expression patterns, downstream signaling, and microenvironmental interactions, we present compelling evidence for ILK as a promising therapeutic target capable of overcoming resistance mechanisms. Current data demonstrate that ILK inhibition simultaneously disrupts multiple survival pathways, sensitizes resistant cells to established therapies, and selectively targets therapy-resistant leukemic stem cells while sparing normal progenitors. This review provides a comprehensive framework for translating ILK-targeted approaches into innovative therapeutic strategies with significant potential to improve outcomes in treatment-refractory hematologic malignancies.

Probiotics are well recognized for their ability to modulate host immune responses; however, growing evidence indicates that many of their beneficial effects are mediated by structural components rather than by viable microorganisms. Among these components, probiotic-derived peptidoglycan has emerged as a key immunologically active molecule with a critical role in regulating both innate and adaptive immunity. Although substantial experimental data exist regarding its underlying mechanisms, the context-dependent immunomodulatory and anti-inflammatory functions of peptidoglycan have not been comprehensively integrated. In this review, we provide an up-to-date and comprehensive overview of the molecular and cellular mechanisms that govern the immunoregulatory properties of probiotic-derived peptidoglycan. We first discuss the structural diversity and processing of peptidoglycan and their implications for host recognition via pattern-recognition receptors, particularly Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain proteins 1 and 2 (NOD1/2). We then critically evaluate current evidence supporting the therapeutic potential of probiotic-derived peptidoglycan in infectious diseases, inflammatory bowel disease (IBD), autoimmune disorders, allergic inflammation, and cancer. Collectively, these findings suggest that peptidoglycan holds considerable promise for the development of next-generation microbiota-based immunotherapeutic strategies.