To map transcriptome-wide N6-methyladenosine (m6A) profile at different stages of type 1 diabetes (T1D). RNA extracted from islet tissues of non-obese diabetic mice at different ages (4-week-old control group, 8-week-old pre-diabetes group, and 14-week-old diabetes group) was analyzed by MeRIP-seq and mRNA-seq. Bioinformatics analyses, including m6A motif enrichment, differential methylation, gene ontology and pathway analysis. Bioinformatic analysis revealed a progressive increase in m6A methylation sites and unique peaks throughout diabetes progression. The predominant m6A motif was "GGACU" in the control and pre-diabetes stages, shifting to "GGACU/A" in the diabetes stage. m6A modifications were primarily enriched at the start codon, coding region, and stop codon. Integrated analysis found pre-diabetes, diabetes groups showed distinct m6A and mRNA changes versus control. Pathway analysis indicated that differentially expressed mRNAs with m6A methylation were predominantly enriched in insulin/IGF-MAPKK/MAPK cascades, apoptosis, T-cell activation, interleukins, CCKR, and inflammation-related pathways in the pre-diabetes stage. As diabetes progressed, additional pathways, including Wnt, EGF receptor, PDGF, GnRH receptor, and angiogenesis, became involved in disease development. In vitro, cytokine stimulation of INS-1 cells increased m6A methylation, upregulated METTL3, downregulated ALKBH5. m6A methyl group dynamics in T1D disease progression, potentially influencing mRNA expression and signal transduction pathways.

The ubiquitin proteasome system (UPS), comprising of ubiquitinases, deubiquitinases and 26S proteasome plays a significant role in directly or indirectly regulating epigenetic players. DNA-templated processes like replication, repair and transcription require chromatin decondensation to allow access to specific DNA sequence. A thorough survey of literary articles in PubMed database revealed that the UPS functions as a key regulator, determining the precise state of open and closed chromatin by influencing histones and histone modifiers through proteolytic or non-proteolytic means. However, a comprehensive understanding of how specific UPS components affect particular epigenetic pathways in response to environmental cues remains underexplored. This axis holds substantial potential for deciphering mechanisms of tumorigenesis. Although our current knowledge is limited, it can still guide the development of novel therapeutic strategies that can potentially bridge the gap between cancer chemotherapeutics in bench and bedside.

Epigenomics is a rapidly emerging field that has gathered significant attention as a "non-genetic determinant" implicated in the manifestation of non-communicable diseases. Exploring epigenetic modifications provides novel insights into the management of cardiometabolic disease (CMD). Epigenetics signatures are influenced by environmental stressors such as air pollution, toxins, and urban noises as well as by established cardiovascular risk factors including smoking, sedentary lifestyle, obesity, and diabetes. Understanding how epigenetic alterations lead to CMD as well as inter-individual differences in epigenetic makeup could unveil new molecular targets and new epi-drugs to be employed for precision medicine approaches in the growing population of patients with cardiometabolic disease to reduce cardiovascular risk. Herein, we provide an overview of the latest advancements in epigenetic mechanisms implicated in CMD and possible therapeutic opportunities.

Endometrial function, crucial for successful embryo implantation, is significantly influenced by epigenetic regulation. This review investigates the crucial roles of DNA methylation, histone modifications, chromatin remodeling, and RNA methylation in endometrial receptivity and implantation, based on a survey of recent literature on knockout mouse models with implantation defects. These models illuminate how epigenetic disruptions contribute to implantation failure, a significant human reproductive health concern. DNA methylation and histone modifications modulate endometrial receptivity by affecting gene silencing and chromatin structure, respectively. Chromatin remodeling factors also play a critical role in endometrial dynamics, influencing gene expression. Furthermore, RNA methylation emerges as critical in implantation through transcriptional and translational control. While human studies provide limited epigenetic snapshots, mouse models with suppressed epigenetic regulators reveal direct causal links between epigenetic alterations and implantation failure. Understanding these epigenetic interactions offers potential for novel therapies addressing reproductive disorders.

Solid tumors are significant causes of global mortality and morbidity. Recent research has primarily concentrated on finding pathology-specific molecules that can be acquired non-invasively and that can change as the disease progresses or in response to treatment. The focus of research has moved to RNA molecules that are either freely circulating in body fluids or bundled in microvesicles and exosomes because of their great stability in challenging environments, ease of accessibility, and changes in level in response to therapy. In this context, there are many non-coding RNAs that can be used for this purpose in liquid biopsies. Out of these, microRNAs have been extensively studied. However, there has been an increase of interest in studying long non-coding RNAs, piwi interacting RNAs, circular RNAs, and other small non-coding RNAs. In this article, an overview of the most researched circulating non-coding RNAs in solid tumors will be reviewed, along with a discussion of the significance of these molecules for early diagnosis, prognosis, and therapeutic targets. The publications analyzed were extracted from the PubMed database between 2008 and June 2024.

Cardiovascular diseases (CVDs) represent a prominent contributor to global morbidity and mortality rates, with projections indicating a rise in this burden due to population aging. While extensive research has underscored the efficacy of exercise in mitigating the risk of CVDs, the precise mechanisms, particularly within the realm of epigenetics, remain nascent. This article delves into cutting-edge research concerning exercise-induced epigenetic alterations and their impact on CVDs. Initially, we examine the cardiac implications stemming from exercise-induced epigenetic influences across varying intensities. Subsequently, our focus shifts toward delineating the mechanisms governing exercise-induced DNA methylation, lactylation modifications, and N6-methyladenosine (m6A) RNA modifications, alongside addressing associated challenges and outlining prospective research directions. These findings suggest that exercise-mediated epigenetic modifications offer promising therapeutic potential for the prevention and comorbidity management of CVDs. However, the heterogeneity and tissue specificity of these effects necessitate more targeted research to unlock their full therapeutic potential.

A complex interaction among sensory, social and epigenetic determinants in psychiatric conditions was described across all age strata. The high prevalence of mental disorders in individuals with sensory deficits might be attributed to the interaction among social isolation, cognitive functioning and sensory processing. The epigenetic implications of such interactions were examined: environmental and social factors can affect gene expression and impact the pathogenesis of psychiatric disorders also through sensory processing. This article discussed the role of social determinants, in other words, social isolation, loneliness and chronic stress, in promoting psychiatric disorders and, in a vicious circle, sensory deficits (vision, hearing, olfaction and somatosensation). We emphasized the importance of integrating social, sensory and epigenetic factors to target different treatments for psychiatric conditions.