Chemical modifications of RNA add a dynamic regulatory layer to gene expression beyond the genome and epigenome. Among these modifications, 5-methylcytidine (m⁵C) has emerged as a key epitranscriptomic modification that influences RNA stability, translation, localization, and stress responses across diverse biological systems. Recent advances in high-resolution mapping and functional interrogation of m⁵C have revealed its involvement in development, metabolism, immune regulation, and disease pathogenesis. Notably, many of these processes are highly relevant to women’s health, which is shaped by hormone-responsive tissues, reproductive transitions, and pregnancy-associated physiological adaptations. In this review, we provide a comprehensive and integrative overview of m⁵C RNA modification with a focus on its roles in female biology and disease. We summarize the molecular machinery responsible for m⁵C deposition, recognition, and regulation, as well as current detection technologies. We further highlight emerging evidence linking m⁵C dysregulation to early embryonic development, women-specific cancers, gynecologic and reproductive disorders, pregnancy complications, and metabolic and cardiovascular diseases. In addition, we discuss the interplay between m⁵C and sex hormone signaling, as well as the potential of m⁵C as a biomarker and therapeutic target. Finally, we identify key knowledge gaps, including the need for tissue-specific, longitudinal, single-cell, and spatial epitranscriptomic studies in women. By integrating epitranscriptomics into women’s health research, this review underscores m⁵C as a previously underappreciated regulatory layer with significant implications for precision medicine and clinical translation.

In the Middle East and North Africa (MENA) region, the prevalence of Type 2 Diabetes (T2D) is 17–18%, substantially higher than the ~9–10% reported in Western populations, with some Gulf states approaching 25% in adults. Historically, Arab diets, characterized by high fiber intake from whole grains, legumes, and fermented dairy products, have contrasted markedly with the Western dietary pattern increasingly prevalent among urbanized Arab populations. These nutritional shifts have been associated with changes in gut microbial composition, including lower representation of short-chain fatty acid–producing bacteria and higher abundance of dysbiosis-associated taxa. Concurrently, diet-derived compounds and microbial metabolites have been associated with changes in DNA methylation, histone modifications, and non-coding RNA expression. Epigenome-wide association studies revealed both shared and population-specific methylation signatures in patients with T2D. However, integrated multi-omics studies remain limited in Arab populations, where the disease burden is highest. This review integrates emerging evidence on diet-linked epigenetic alterations, microbiome-associated metabolic pathways, and their intersection in potentially contributing to T2D risk and progression. Given the heterogeneity of T2D across populations, there is a pressing need for culturally contextualized precision medicine frameworks that integrate population-specific diet–microbiome–epigenome dynamics rather than extrapolating findings across populations. Additionally, this review synthesizes evidence that dietary patterns are associated with T2D-relevant pathways through the diet–microbiome–epigenome axis, with emphasis on Arab/MENA populations and Western comparator cohorts.

Background/Objectives: Gliomas arise from distinct subgroups driven by different genetic alterations. Gain-of-function mutations in isocitrate dehydrogenase 1/2 (IDH1/2) are frequent in a subset of gliomas and are associated with improved survival compared with wild-type tumors. IDH-mutant gliomas can be classified as having the CpG island methylator phenotype (G-CIMP), which is characterized by widespread epigenetic changes associated with IDH1 mutations. G-CIMP-based stratification provides an added improvement in glioma classification when considered alongside grade and histology. Despite the success of G-CIMP-based stratification in predicting outcome in some patients, it does not fully account for non-responders, largely due to heterogeneity within G-CIMP gliomas. Methods: Using a The Cancer Genome Atlas (TCGA) glioblastoma, IDH-wildtype discovery cohort, we identified gene-level DNA methylation and expression patterns associated with clinical outcomes, including epigenetically regulated genes such as TUBB2A and TM4SF1. Results: In an independent TCGA diffuse glioma validation cohort enriched for IDH-mutant tumors, canonical IDH-defined G-CIMP classification was applied, and promoter methylation of TUBB2A and TM4SF1 showed significant associations with overall survival. Conclusions: These findings highlight molecular heterogeneity within IDH-defined G-CIMP gliomas and demonstrate that gene-specific methylation events can refine prognostic stratification beyond IDH status alone.