Search Results (1,653)

Curcuminoids demonstrate diverse pharmacological activity as antioxidant, neuroprotective, antitumor, and anti-inflammatory drugs. Dimethoxycurcumin (DMC) is a metabolically stable analog of curcumin, and both drugs modify the activity of several epigenetic enzymes that affect DNA methylation and histone modifications. 5-hydroxymethylcytosine (5hmC) is an epigenetic mark involved in active demethylation and in gene expression regulation. The effect of curcuminoids on the activity and expression of TET enzymes involved in 5hmC oxidation and active demethylation in leukemia cells is unclear. In this study, we investigated the impact of curcumin and DMC on the activity and expression of the three isoforms of TET enzymes. We also studied their effect on global 5hmC and performed a genome-wide analysis of 5hmC distribution at the single CpG level using oxidative bisulfite sequencing, which can differentiate between 5hmC and 5-methylcytosine. Both curcumin and DMC increased the activity and the mRNA expression of the three isoforms of TET. Concordantly, they also increased the global 5hmC level in leukemia cells. Single CpG analysis showed that both drugs induced a 5hmC increase and active demethylation at gene promoters, CpG islands and shores, exons, introns, and intergenic regions. Curcumin induced a promoter 5hmC increase in 194 genes and promoter-active demethylation in 154 genes. On the other hand, DMC induced a promoter 5hmC increase in 173 genes and promoter-active demethylation in 171 genes. Our study identifies curcuminoids as active demethylators through the activation of TET enzymes and provides a rationale for testing their combination with DNA hypomethylating agents in leukemia animal models. Full article

Background: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and are strongly influenced by dietary habits. Beyond caloric intake, nutrients act as molecular signals that regulate cardiac metabolism, mitochondrial function, inflammation, and epigenetic remodeling. Objectives: This review aims to synthesize current evidence on how dietary patterns and specific nutritional interventions regulate cardiac metabolism and function through interconnected molecular and epigenetic mechanisms, highlighting their relevance for cardiovascular disease prevention. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2006 and 2025. Experimental, translational, and clinical studies addressing diet-induced modulation of cardiac metabolic pathways, oxidative and inflammatory signaling, epigenetic regulation, and gut microbiota-derived metabolites were included. Results: The analyzed literature consistently shows that unbalanced diets rich in saturated fats and refined carbohydrates impair cardiac metabolic flexibility by disrupting key nutrient-sensing pathways, including AMP-activated protein kinase (AMPK), proliferator-activated receptor alpha (PPARα), mammalian target of rapamycin (mTOR), and sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1/PGC-1α), leading to mitochondrial dysfunction, oxidative stress, chronic inflammation, and maladaptive remodeling. In contrast, cardioprotective dietary patterns, such as caloric restriction (CR), intermittent fasting (IF), and Mediterranean and plant-based diets, enhance mitochondrial efficiency, redox balance, and metabolic adaptability. These effects are mediated by coordinated activation of AMPK-SIRT1 signaling, suppression of mTOR over-activation, modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, and favorable epigenetic remodeling involving DNA methylation, histone modifications, and non-coding RNAs. Emerging evidence also highlights the central role of gut microbiota-derived metabolites, particularly short-chain fatty acids, in linking diet to epigenetic and metabolic regulation of cardiac function. Conclusions: Diet quality emerges as a key determinant of cardiac metabolic health, acting through integrated molecular, epigenetic, and microbiota-mediated mechanisms. Targeted nutritional strategies can induce long-lasting cardioprotective metabolic and epigenetic adaptations, supporting the concept of diet as a modifiable molecular intervention. These findings provide a mechanistic rationale for integrating personalized nutrition into cardiovascular prevention and precision cardiology, complementing standard pharmacological therapies. Full article

Cadmium (Cd) induces oxidative stress and disrupts nuclear organization and chromatin-associated metabolic processes in plant cells. Therefore, identifying natural, biodegradable, non-bioaccumulative compounds that enhance plant tolerance to heavy metals is crucial. We hypothesized that Cd exposure (175 µM CdCl₂, 24 h) activates mitogen-activated protein kinases (MAPKs), triggering defined epigenetic modifications that lead to transcriptional repression, and that thyme oil (TO; 0.03% (v/v), emulsified) mitigates these effects by stabilizing chromatin organization. We analyzed nuclear MAPK (p44/42) activation, global DNA methylation (5-methylcytosine; 5-mC), and selected histone modifications as key components of early stress signaling and epigenetic regulation. We found that Cd exposure doubled global 5-mC levels and caused pronounced alterations in histone marks, including decreases in H3K4Me2 (~34%), H3T45Ph (~48%), and H4K5Ac, accompanied by strong increases in H3K9Ac (~57%) and H3K56Ac (~148%). These changes were associated with chromatin condensation and reduced transcriptional activity. In contrast, co-treatment with TO maintained MAPK activity and epigenetic parameters close to control levels, preventing chromatin compaction and transcriptional repression. Together, these findings indicate that TO stabilizes the nuclear signaling–epigenetic interface under Cd stress and represents a promising bioprotective strategy. This work provides the first demonstration that TO modulates both MAPK activation and Cd-induced histone modifications in plants. Full article

Cellular memory, or epigenetic memory, represents the capacity for cells to retain information beyond the underlying DNA sequence. This heritable characteristic is primarily governed by epigenetic mechanisms which enable cells to maintain specialized characteristics across divisions. This persistent cellular state is essential for fundamental biological processes, such as maintaining tissue identity and facilitating cell differentiation, especially embryonic cells. Early-stage perturbations such as assisted reproductive technologies (ART) and nutritional stress links embryonic exposures to adult health and disease within the Developmental Origins of Health and Disease (DOHaD) framework. Crucially, memory established during early embryogenesis links these epigenetic modifications to adult long-term phenotypes related to metabolic disorders. These modifications—including DNA methylation, histone modifications, and non-coding RNAs—support cellular memory transmission across cell divisions, and in certain organisms, can be transmitted across generations without alterations to the DNA sequence. This review synthesizes recent advances in epigenetic pathways that mediate cellular memory, highlights critical preimplantation windows of vulnerability and outlines gaps necessary for mammalian developing interventions that safeguard future generations. Full article

Mass spectrometry has become an indispensable tool for the identification and quantification of epigenetic modifications, offering both high sensitivity and structural specificity. The two major classes of epigenetic modifications identified—DNA methylation and histone post-translational modifications—play fundamental roles in cancer development, underscoring the relevance of their precise quantification for understanding tumorigenesis and potential therapeutic targeting. In this scoping review, we included 89 studies that met the inclusion criteria for detailed methodological assessment. Among these, we compared pre-treatment workflows, analytical platforms, and acquisition modes employed to characterize epigenetic modifications in human samples and model systems. Our synthesis highlights the predominance of bottom-up strategies combined with Orbitrap-based platforms and data-dependent acquisition for histone post-translational modifications, whereas triple quadrupole mass spectrometers were predominant for DNA methylation quantification. We critically evaluate current limitations, including heterogeneity in validation reporting, insufficient coverage of combinatorial post-translational modifications, and variability in derivatization efficiency. Full article

Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1’s role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell fate. Retinoic acid-induced differentiation downregulated INSM1 and N-Myc, linking INSM1 to tumor cell immaturity. INSM1 overexpression in SH-SY-5Y cells upregulated neuroendocrine and thyroid hormone-related genes (CHGA, CHGB, DDC, NCAM1, DIO3, TH), while suppressing genes involved in cell cycle (RRM, CDC25A), methionine metabolism (AHCY, MAT2A), transcriptional regulation (MYBL2, EZH2), and oncogenic signaling (ALK, LINC011667). These findings suggest that INSM1 promotes NB aggressiveness by sustaining a neuroendocrine progenitor-like phenotype through metabolic-epigenetic coupling. Full article

Plant viral diseases cause significant agricultural losses worldwide and are shaped by complex virus-host and virus-virus interactions. Unlike fungal or bacterial pathogens, viruses cannot be directly controlled with chemicals, and their management relies on insect vector control and the development of virus-resistant plant varieties. Plants deploy endogenous epigenetic (DNA/chromatin-based) and epitranscriptomic (RNA-based) mechanisms to limit viral infections. RNA silencing pathways, particularly post-transcriptional gene silencing (PTGS) mediated by small RNAs, restrict viral replication and shape viral populations. Additional layers, including RNA-directed DNA methylation (RdDM), N6-methyladenosine (m⁶A) RNA modifications, histone modifications and chromatin remodeling, further modulate host–virus interactions. DNA methylation can be inherited and may confer resistance to future generations, although its stability is partial and context-dependent. Virus-derived 24-nt small interfering RNAs (siRNAs) act as mobile signals, inducing systemic gene silencing and potentially influencing viral population dynamics. Understanding these epigenetic and epitranscriptomic mechanisms can improve virus diagnosis, pathogenesis studies and disease management, while also providing insights into viral diversity and co-infection dynamics. This review synthesizes current knowledge of these mechanisms and discusses their implications for developing sustainable antiviral strategies. Full article

Although cancer biology has advanced considerably, the impact of environmental toxins on carcinogenesis remains underrecognized and scattered across disciplines. Evidence increasingly shows that chronic exposure to a broad range of toxins—including persistent organic pollutants, heavy metals, pesticides, phthalates, microplastics, and fine particulate matter (PM2.5), which significantly contributes to cancer initiation, progression, and treatment resistance. This review synthesizes mechanistic, molecular, and epidemiological findings from 2015 to 2025, identified through systematic searches of PubMed, Scopus, Web of Science, and MeSH. Key pathways include oxidative stress-mediated DNA damage, epigenetic reprogramming (DNA methylation, histone modifications, miRNA dysregulation), hormone receptor modulation, chronic inflammation, immune evasion, and tumor microenvironment remodeling. Case studies of benzene, arsenic, aflatoxins, pesticides, and microplastics detail exposure routes, molecular targets, and associated cancers, highlighting significant public health risks. Ongoing debates persist regarding safe exposure thresholds, latency periods, and the effects of mixed toxin exposures. The review also highlights recent innovations in environmental oncology, including AI-based predictive models, CRISPR screens for susceptibility genes, organoid/3D models, green chemistry interventions, and real-time exposure monitoring, which provide mechanistic insight and inform early detection and personalized prevention strategies. Additionally, regional data gaps, particularly in low- and middle-income countries, indicate the need for stronger interdisciplinary collaboration. By integrating molecular mechanisms, epidemiology, and technological advances, this review offers a comprehensive framework for understanding toxin-induced carcinogenesis and guiding future research, public health policy, and preventive strategies. Full article

Diabetic retinopathy (DR), a leading cause of vision loss in diabetic patients, involves complex pathological mechanisms including neurodegeneration, microvascular damage, inflammation, and oxidative stress. Recent studies have identified ferroptosis—a ferrodependent cell death mechanism—as playing a pivotal role in DR development. Existing evidence indicates that oxidative stress and mitochondrial dysfunction induced by hyperglycemia may contribute to retinal damage through the ferroptosis pathway in DR. Ferroptosis inhibitors such as Ferostatin-1 have demonstrated protective effects against DR in animal models. The core mechanisms of ferroptosis involve iron homeostasis imbalance and lipid peroxidation, with key regulatory pathways including GPX4-dependent and non-dependent mechanisms (such as FSP1-CoQ10). Within the signaling network, Nrf2 inhibits ferroptosis, p53 promotes it, while Hippo/YAP functions are environment-dependent. Non-coding RNAs and epigenetic modifications (e.g., DNA methylation and histone modifications) also participate in regulation. In DR, iron overload, GPX4 dysfunction, and p53 upregulation collectively induce ferroptosis in various types of retinal cells, making these pathways potential therapeutic targets. This review not only elaborates the role of iron metabolism imbalance and ferroptosis pathway in the occurrence and development of DR but also summarizes the new therapeutic approaches of DR targeting ferroptosis pathway. Investigating the relationship between ferroptosis and DR not only helps unravel its core pathophysiological mechanisms but also provides theoretical foundations for developing novel therapeutic approaches. Full article

Egg quality is a critical economic trait in poultry production, influencing consumer preference and production efficiency. The genetic and epigenetic regulation of egg quality involves complex biological pathways across various traits such as shell quality, albumen composition, and yolk biochemistry. This review synthesizes recent advances in the genetic, molecular, and epigenetic mechanisms that determine poultry egg quality. Specifically, it focuses on external traits such as eggshell strength, color, and thickness, and internal traits including albumen height, yolk composition, and the Haugh unit. Through genome-wide association studies (GWAS), quantitative trait loci (QTL) mapping, whole-genome sequencing (WGS), and multi-omics approaches, key candidate genes such as OC-116, CALB1, CA2 (shell formation), OVAL, SPINK5, SERPINB14 (albumen quality), and FGF9, PIAS1, NOX5 (lipid metabolism) have been identified. These genes play a pivotal role in shell biomineralization, albumen protein regulation, and yolk lipid transport. This review also explores the heritability of these traits, emphasizing the challenges posed by polygenic architecture and the influence of environmental factors. Furthermore, it addresses the dynamic spatiotemporal regulation of egg quality traits, including epigenetic layers such as DNA methylation, histone modifications, RNA methylation, and post-translational protein modifications. This paper highlights the application of these findings to breeding programs via genomic selection, marker-assisted breeding, and epigenetic engineering approaches. Future directions for precision breeding and the development of functional eggs with enhanced quality are also discussed. Full article

In animals and humans, nutrients influence signaling cascades, transcriptional programs, chromatin dynamics, and mitochondrial function, collectively shaping traits related to growth, immunity, reproduction, and stress resilience. This review synthesizes evidence supporting nutrient-mediated regulation of DNA methylation, histone modifications, non-coding RNAs, and mitochondrial biogenesis, and emphasizes their integration within metabolic and developmental pathways. Recent advances in epigenome-wide association studies (EWAS), single-cell multi-omics, and systems biology approaches have revealed how diet composition and timing can reprogram gene networks, sometimes across generations. Particular attention is given to central metabolic regulators (e.g., PPARs, mTOR) and to interactions among methyl donors, fatty acids, vitamins, and trace elements that maintain genomic stability and metabolic homeostasis. Nutrigenetic evidence further shows how genetic polymorphisms (SNPs) in loci such as IGF-1, MSTN, PPARs, and FASN alter nutrient responsiveness and influence traits like feed efficiency, body composition, and egg quality, information that can be exploited via marker-assisted or genomic selection. Mitochondrial DNA integrity and oxidative capacity are key determinants of feed conversion and energy efficiency, while dietary antioxidants and mitochondria-targeted nutrients help preserve bioenergetic function. The gut microbiome acts as a co-regulator of host gene expression through metabolite-mediated epigenetic effects, linking diet, microbial metabolites (e.g., SCFAs), and host genomic responses via the gut–liver axis. Emerging tools such as whole-genome and transcriptome sequencing, EWAS, integrated multi-omics, and CRISPR-based functional studies are transforming the field and enabling DNA-informed precision nutrition. Integrating genetic, epigenetic, and molecular data will enable genotype-specific feeding strategies, maternal and early-life programming, and predictive models that enhance productivity, health, and sustainability in poultry production. Translating these molecular insights into practice offers pathways to enhance animal welfare, reduce environmental impact, and shift nutrition from empirical feeding toward mechanistically informed precision approaches. Full article

Background/Objectives: Endocrine autoimmune diseases, including autoimmune thyroid, pituitary, parathyroid, adrenal, and gonadal diseases, result from complex interactions between genetic susceptibility and environmental triggers. Advances in genomics and epigenomics have provided novel insights into the molecular pathways leading to immune dysregulation and endocrine tissue destruction. This review summarizes recent progress in understanding the genetic and epigenetic bases, emphasizing shared and disease-specific mechanisms that contribute to autoimmunity and endocrine dysfunction. Methods: A comprehensive literature search was performed in PubMed, Scopus, and Web of Science up to August 2025, focusing on genome-wide association studies (GWAS), next-generation sequencing, and epigenetic profiling (DNA methylation, histone modification, and non-coding RNA regulation). Results: More than 60 susceptibility loci have been identified across endocrine autoimmune diseases (EADs), including key genes in immune tolerance (HLA, CTLA4, PTPN22) and endocrine-specific pathways. Epigenetic studies reveal that altered DNA methylation and histone acetylation patterns in immune and endocrine cells modulate gene expression without changing the DNA sequence, linking environmental exposures to disease onset. Dysregulated microRNAs further influence immune signaling and cytokine networks. Conclusions: Genetic and epigenetic discoveries highlight the multifactorial nature of EADs and reveal potential biomarkers for early detection and targets for precision immunotherapy. Future research integrating multi-omics and longitudinal analyses will be crucial to unravel causal mechanisms and develop personalized preventive strategies. Full article

Malaria remains one of the devastating illnesses, and drug-resistant malaria has incurred enormous societal costs. A few host kinases are vital for the liver stage malaria and might be promising drug targets against drug-resistant malaria. STK35L1 is one of the host kinases that is highly upregulated during the liver stage of malaria, and the knockdown of STK35L1 significantly suppresses Plasmodium sporozoite infection. In this study, we retrieved the promoter region of STK35L1 based on 5′ complete transcripts, transcription start sites, and cap analysis of gene expression tags. Furthermore, we identify transcriptionally active regions by analyzing CpG islands, histone acetylation (H3K27ac), and histone methylation (H3K4me3). It suggests that the identified promoter region is active and has cis-regulatory elements and enhancer regions. We identified various putative transcription factors (TFs) from the various high-throughput ChIP data that might bind to the promoter region of STK35L1. These TFs were differentially regulated during the infection of Plasmodium sporozoites in HepG2 cells. Our molecular modeling study suggests that, except for SMAD3, the identified TFs may be directly bound to the promoter. Together, the data suggest that these TFs may play a role in sporozoite infection and in regulating STK35L1 expression during the liver stage of malaria. Full article

Personalizing therapy using medical marijuana (MM) is based on understanding the pharmacogenomics (PGx) and drug–drug interactions (DDIs) involved, as well as identifying potential epigenetic risk markers. In this work, the evidence regarding the role of variants in phase I (CYP2C9, CYP2C19, CYP3A4/5) and II (UGT1A9/UGT2B7) genes, transporters (ABCB1), and selected neurobiological factors (AKT1/COMT) in differentiating responses to Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been reviewed. Data indicating enzyme inhibition by CBD and the possibility of phenoconversion were also considered, which highlights the importance of a dynamic interpretation of PGx in the context of current pharmacotherapy. Simultaneously, the results of epigenetic studies (DNA methylation, histone modifications, and ncRNA) in various tissues and developmental windows were summarized, including the reversibility of some signatures in sperm after a period of abstinence and the persistence of imprints in blood. Based on this, practical frameworks for personalization are proposed: the integration of PGx testing, DDI monitoring, and phenotype correction into clinical decision support systems (CDS), supplemented by cautious dose titration and safety monitoring. The culmination is a proposal of tables and diagrams that organize the most important PGx–DDI–epigenetics relationships and facilitate the elimination of content repetition in the text. The paper identifies areas of implementation maturity (e.g., CYP2C9/THC, CBD-CYP2C19/clobazam, AKT1, and acute psychotomimetic effects) and those requiring replication (e.g., multigenic analgesic signals), indicating directions for future research. Full article

The cannabinoid receptor type 2 (CB₂) is increasingly recognized as a crucial regulator of neuroimmune balance in the brain. In addition to its well-established role in immunity, the CB₂ receptor has been identified in specific populations of neurons and glial cells throughout various brain regions, and its expression is dynamically increased during inflammatory and neuropathological conditions, positioning it as a potential non-psychoactive target for modifying neurological diseases. The expression of the CB₂ gene (CNR2) is finely tuned by epigenetic processes, including promoter CpG methylation, histone modifications, and non-coding RNAs, which regulate receptor availability and signaling preferences in response to stress, inflammation, and environmental factors. CB₂ signaling interacts with TRP channels (such as TRPV1), nuclear receptors (PPARγ), and orphan G Protein-Coupled Receptors (GPCRs, including GPR55 and GPR18) within the endocannabinoidome (eCBome), influencing microglial characteristics, cytokine production, and synaptic activity. We review how these interconnected mechanisms affect neurodegenerative and neuropsychiatric disorders, underscore the species- and cell-type-specificities that pose challenges for translation, and explore emerging strategies, including selective agonists, positive allosteric modulators, and biased ligands, that leverage the signaling adaptability of the CB₂ receptor while reducing central effects mediated by the CB₁ receptor. This focus on the neuro-centric perspective repositions the CB₂ receptor as an epigenetically informed, context-dependent hub within the eCBome, making it a promising candidate for precision therapies in conditions featuring neuroinflammation. Full article