Cardiovascular disease (CVD) is the leading cause of death among women globally. Pregnancy complications, such as hypertensive disorders of pregnancy (HDP), are known to increase the risk of developing CVD. Over 10% of pregnancies globally are affected by HDP, a condition characterized by increased blood pressure and a multiorgan disorder (preeclampsia) associated with a 2- to 8-fold higher risk of hypertension, ischemic heart disease, stroke, and heart failure. Altered epigenetic regulation of angiogenesis, endothelial function, and gene expression may help explain the link between HDP and later-life CVD risk. However, studies investigating how epigenetic modifications mediate the progression from HDP to CVD remain limited. This review provides an overview on how epigenetic mechanisms may influence the long-term cardiovascular consequences of HDP. It also highlights key research gaps, including the need for long-term longitudinal studies to show causality. Further research on this topic may result in better screening, prevention strategies, and personalized therapies for women's cardiovascular health. However, epigenetic markers should be viewed as complementary to established clinical predictors, with near-term value in mechanistic risk refinement rather than as replacements for current approaches.

Alterations of the DNA methylation (DNAm) status of the genome underlie an increasing number of rare diseases. Recently, DNAm has also emerged as a highly informative biomarker for diagnosing rare disorders, which can be associated with distinctive genome-wide DNAm patterns (., episignatures). Indeed, episignature testing has proven to represent an effective orthogonal omics technology, providing independent functional evidence to support or prioritize specific diagnostic hypotheses for hundreds of rare diseases, and reclassify variants of uncertain significance (VUS) emerging from genomic sequencing. Furthermore, the stability and plasticity inherent in DNAm make it a promising tool for personalized medicine, including patient stratification and therapeutic monitoring. This review outlines current technologies and analytical methodologies for genome-wide DNAm profiling and explores potential avenues of research, emphasizing artificial intelligence and multiomics integration to effectively manage patients with rare and complex phenotypes. We critically assess the current limitations and future directions of genome-wide DNAm profiling to expand the implementation of DNAm signatures as functional biomarkers, highlighting their importance as supplementary tools to genomic sequencing in clinical and research settings.

This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

The effects of conventional cigarette (c-cig) use on DNA methylation are well established, but the impact of electronic cigarettes (e-cigs) remains unclear. Objective: This scoping review aimed to map and synthesize available evidence regarding the effects of e-cig use on DNA methylation profiles in human studies. Methods: PubMed, Lilacs, Scopus, Web of Science and Cochrane were searched using terms related to e-cigs and DNA methylation up to April 2025.

Ketamine antidepressant effects go beyond immediate receptor action, involving lasting transcriptional and epigenomic changes that support its rapid, long-lasting benefits. The present systematic review synthesized existing preclinical and clinical evidence on the epigenetic mechanisms of ketamine in the treatment of depression.

Matrix metalloproteinases (MMPs) promote prostate cancer (PCa) progression by degrading the extracellular matrix and enhancing metastasis. PCa is considered an "epigenetic catastrophe" due to disrupted histone modifications caused by chromatin-modifying enzyme dysregulation. We previously showed that lysine demethylase 6A (KDM6A) and 6B (KDM6B) are higher in metastatic PCa (LNCaP) versus benign prostatic hyperplasia (BPH-1). We investigated whether their elevation contributes to MMP upregulation.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide. N6-methyladenosine (m6A) modification plays a critical role in post-transcriptional gene regulation. This study aimed to elucidate the molecular mechanism by which the RNA demethylase ALKBH5 regulates GC progression through m6A modification of thioredoxin domain-containing protein 5 (TXNDC5).

The integration of genetic and epigenetic information is essential for a comprehensive understanding of genome function and regulation. Traditional sequencing methods often fall short in capturing both genetic variants and epigenetic modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) simultaneously. Recent advances in 6-base sequencing have enabled the simultaneous, base-resolution detection of canonical bases and key cytosine modifications in a single workflow. This review explores the biological significance of 5mC and 5hmC, discusses current methods to achieve 6-base sequencing, and highlights recent applications in academic and clinical settings.

Preterm birth and very low birth weight (VLBW; <1500 g) increase risks for poor health outcomes, potentially mediated by epigenetic modifications such as DNA methylation (DNAm). We hypothesized that DNAm differs between VLBW adults and their siblings in blood and adipose tissue.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affects an estimated 6.8 million individuals worldwide. Although biological or small molecule drug therapies can improve patient outcomes, loss of response to treatment over time remains high, highlighting the need for new precision medicine strategies. Dysbiosis of the gut microbiome is characterized by the loss of beneficial microbes and an overgrowth of pro-inflammatory pathobionts. In IBD, gut dysbiosis contributes to chronic intestinal inflammation via altered metabolite profiles and epithelial barrier disruption. Recent advancements in multi-omics integration offer approaches to better understand the pathogenesis of IBD. Epigenomic studies have revealed disease-specific DNA methylation and enhancer activation patterns that reshape immune pathways and compromise epithelial barrier integrity, key mechanisms in IBD pathophysiology. These molecular signatures allow for the stratification of IBD patients into distinct subgroups, allowing for more targeted therapeutic strategies. Here we explore the potential benefits of integrating gut microbiome and both host transcriptomics and epigenomics to improve disease management in IBD patients. While challenges remain - such as data standardization, computational complexity, and cost - the progression of multi-omics methodologies is expected to improve patient outcomes by reducing high treatment failure rates in IBD patients.

Transcriptional regulation is a crucial biological process that enables accurate gene expression, allowing cells to maintain their identity and respond to environmental stimuli. CCCTC-binding factor is a fundamental protein that actively involves itself in transcriptional regulation, serving as a highly conserved architectural regulator. CTCF is traditionally acknowledged for its function in chromatin organization and insulation. It coordinates active or repressed transcription by establishing topologically associated domains and also helps in preserving enhancer-promoter identity. In addition to its DNA-binding roles, CTCF significantly participates in RNA biology. It engages with nascent RNA, pre-mRNA, and long non-coding RNAs via its RNA-binding domain, thereby affecting different transcriptional dynamics. Simultaneously, the swiftly advancing domain of epitranscriptomics has revealed other RNA modifications, such as N6-methyladenosine (mA), 5-methylcytosine (mC), and pseudouridine (Ψ), which jointly regulate RNA stability, transport, translation, and destruction. Hence, the dysregulation of these changes or CTCFactivity is closely linked to oncogenesis, developmental problems, and resistance to therapy. The intersection of CTCF-mediated genomic architecture with epitranscriptomic regulation highlights its function as a complex integrator of chromatin and RNA networks. This review consolidates contemporary understanding of CTCF's twin activities in DNA and RNA binding, examining how their interaction influences transcriptional regulation, RNA processing, and disease relevance.

Titanium dioxide nanoparticles (TiONPs) are relevant nanomaterials (NMs) for biomedicine and industry, which raise concerns about its effects on human health, particularly through ingestion. Several studies found that exposure to NMs can lead to DNA methylation changes. DNA methylation regulates gene expression, playing a vital role in development and disease, with aberrant methylation linked to cancer and other health conditions.

Rapid methodological breakthroughs over the past ten years have transformed epigenomics from bulk, population-averaged assays into single-cell, multi-omic, and intracellular spatial investigations. This review surveys the interconnected technology pillars that now map the epigenome with unprecedented breadth and resolution. First, advances in next-generation and long-read sequencing empower investigators to chart chromatin accessibility, histone and DNA modifications, and three-dimensional higher-order chromatin structure in thousands of individual cells while retaining allele-specific information across kilobase-long molecules. Second, live-cell fluorescence probes and multiplexed chromatin tracing enable visualizing the dynamic organization of epigenetic marks and genome architecture of intact nuclei and tissues. Third, integrative platforms merge base-level reads with their native 3D coordinates, providing a holistic view of gene regulation in physiologic context. We distill key biological insights yielded by each methodology, discuss unresolved and persistent limitations, and outline future directions toward routine, cost-effective investigations. Together, these innovations are redefining how we interrogate chromatin biology in health and disease.

High-grade gliomas (HGGs), including glioblastoma and diffuse midline glioma, highlight one of the most aggressive brain tumors in adults and children with dismal prognosis despite intensive treatment regimens. Recently, epigenetic dysregulation has emerged as a fundamental hallmark of HGG biology, and the epigenetic alterations contribute not only to the molecular classification of HGGs but also to their malignant functional biology. Another notable feature of epigenetic dysregulation in HGGs is its influence on intratumoral heterogeneity, via possible modification of the neuron-glioma network in the brain. In this review, we aim to compile recent advances in our understanding of epigenetic dysregulation in HGGs, focusing on key mechanisms such as DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs. Furthermore, we will update our knowledge on the unexpected biology of glioma interaction with neuronal components from a standpoint of epigenetic heterogeneity. By discussing the epigenetic landscape of HGGs, we aim to provide a framework for future research and therapeutic innovation in the management of these devastating tumors.

The intrinsic and acquired resistance of ovarian cancer to conventional platinum/taxane chemotherapy is approximately 80-85%, with a high recurrence rate, making it one of the most lethal gynecological cancers. Epigenetic dysregulation, a key factor in tumor growth and chemoresistance, includes abnormal DNA methylation and 5-hydroxymethylcytosine (5hmC) loss. The ten-eleven translocation (TET) family of dioxygenases (TET1/TET2/TET3) mediates DNA demethylation, causing oxidation of 5-methylcytosine to 5hmC, potentially altering gene expression due to cancer cell plasticity and impacting treatment responses. This review discusses the multiple effects of TETs in ovarian cancer, highlighting the regulation of epithelial mesenchymal transition (EMT), cancer stem cells (CSCs), and the Wnt/β-catenin and TGF-β signaling pathways by TET enzymes. TET1 plays a dual role, promoting chemoresistance via CSC enrichment and suppressing tumors by replenishing Wnt antagonists. TET2, primarily a tumor suppressor, reduces 5hmC; TET2 loss is associated with poor therapeutic results. Elevated expression of TET3, which controls EMT and miRNA expression, is linked to a worse prognosis. In addition, we reviewed the potential resensitization of resistant tumors to multiple modalities of treatment by reactivating/modulating TET activity and function via cofactors and epigenetic treatment. Regulation of the TET-5hmc axis appears promising to overcome chemoresistance and improve therapeutic outcomes.

Brain disorders are among the most debilitating, costly and therapeutically challenging conditions worldwide. Therefore, there is a growing need for identification of biomarkers to support diagnostic, prognostic and therapeutic procedures. Technological advances are enabling increasingly precise, high-throughput profiling of epigenetic modifications, and the potential reversibility of epigenetic marks makes them a promising target for therapeutic intervention. Recent research on models, brain samples and peripheral tissues from living individuals has suggested that epigenetic mechanisms are involved in the pathogenesis of chronic mental illnesses, functioning as distal or proximal risk factors and mediating the long-term effects of environmental stressors on brain function. In brain cancers, including the highly lethal glioblastoma, epigenetic dysregulation (especially DNA methylation patterns) is already implicated in tumor classification as it contributes to cellular heterogeneity and may drive tumor progression. This review examines the multifaceted role of epigenomic regulation of brain gene expression, focusing on psychiatric disorders and primary brain malignancies such as glioblastoma. We summarize the technological advances that have enabled high-throughput and high-resolution exploration of the epigenome. Furthermore, we present the current knowledge of epigenomic signatures that may contribute to brain pathology and discuss their potential for biomarker discovery and the advancement of personalized medicine.

MicroRNA-17-5p (miR-17-5p) is a regulatory molecule underpinning a range of diseases and for which various innovative therapeutic strategies across diverse pathologies are possible. Encoded by the miR-17-92 cluster, miR-17-5p exerts pleiotropic functions across cancers, inflammatory conditions, and genetic disorders such as cystic fibrosis (CF). Its capacity to fine-tune processes including autophagy, epithelial-mesenchymal transition, inflammation, and immune modulation places miR-17-5p at the nexus of disease progression and therapeutic intervention. In cancer, miR-17-5p exhibits context-dependent duality, acting as a tumor promoter or suppressor by regulating proliferation, metastasis, and therapeutic resistance pathways. In inflammatory and genetic diseases, including CF and neurodegenerative disorders, miR-17-5p orchestrates immune homeostasis, autophagy, and tissue remodeling, contributing to either disease exacerbation or resolution. Recent advances in RNA delivery technologies including nanocarriers, exosome-based systems, and receptor-targeted delivery platforms have unlocked new possibilities for miR-17-5p modulation with enhanced precision and minimized off-target effects. These innovations hold promise for restoring cellular homeostasis in CF, Alzheimer's disease, and cancers by precisely tuning miR-17-5p expression to match disease-specific requirements. This review highlights the versatile role of miR-17-5p in diverse pathological processes and emphasizes its promise as a biomarker and therapeutic target, offering a path toward more personalized and effective treatments across multiple disease areas.

Leishmaniasis is a complex immuno-metabolic infectious disease regulated by epigenetic mechanisms in both the parasite and host. Epigenetic modifications such as chromatin remodeling, histone post-translational modifications (PTMs), and non-coding RNAs (ncRNAs) modulate gene expression to promote parasite survival and alter host immune responses. This review highlights species-specific epigenetic changes across species contributing to pathogenesis and explains how the parasite manipulates host immune signaling through epigenetic pathways, including co-infection and co-morbidity models. Host factors like nuclear factor of activated T cells 5 (NFAT5) and Src homology 2 domain-containing phosphatase-1 (SHP-1), along with parasite-derived proteins such as Su(var)3-9, enhancer of zeste [E(z)], trithorax (SET) proteins, and histones, are emerging as promising epigenetic therapeutic targets. Furthermore, histone PTMs and transcription factors are critical epigenetic modifications supporting parasite survival. Synthetic gene circuits can modulate host and parasite epigenomes. Synthetic biology enables the assembly of genetic parts and pools to engineer cells with novel biological functions. A structured literature review using Web of Science, PubMed, and Scopus was performed, using keywords like epigenetics of , epigenetics alterations in host with leishmaniasis, and comorbidity and disease-specific terms. This review underscores the future potential of epigenetics and synthetic biology-based strategies in controlling leishmaniasis.

G-quadruplex (G4) structures are enriched in key genomic regions and regulate gene expression and chromosomal stability. However, their role in de novo DNA methylation remains unclear. DNA methyltransferase 3A (DNMT3A) and DNA methyltransferase 3B (DNMT3B) are vital for cancer initiation and progression. This study investigated the role of G4 structures in regulating DNMT3A and DNMT3B expression and their epigenetic function in breast cancer.

Liver diseases represent a major global health challenge, responsible for over two million deaths annually. Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are the primary contributors to liver fibrosis and hepatocarcinoma (HCC). Epigenetic mechanisms, including DNA methylation, histone modifications, and miRNAs, play a crucial role in the pathogenesis of liver disorders, presenting promising therapeutic targets due to their reversibility. Pirfenidone, an antifibrotic agent approved for idiopathic pulmonary fibrosis (IPF) and hepatic fibrosis in Mexico, has shown significant potential to modulate epigenetic pathways. This review discusses the molecular and epigenetic mechanisms by which PFD exerts hepatoprotective effects, including modulation of miRNA expression, restoration of DNA methylation patterns, and regulation of histone acetylation and methylation. Notable findings include PFD-mediated downregulation of pro-fibrotic miRNAs, hypermethylation of TGFB1, and inhibition of JMJD2B histone demethylase. Together, these findings suggest that PFD not only targets fibrotic and inflammatory pathways but also acts as a novel epigenetic regulator, positioning it as a promising therapeutic candidate for MASLD, MASH, and HCC.

A large scale detection of MLH1 methylation is lacking in esophageal cancer. MLH1 is a well-known mismatch repair gene. The mechanism of MLH1 in DNA double strand break (DSB) repair remains unclear.