Search Results (1,484)

Fetal growth restriction (FGR) is a major contributor to perinatal morbidity and mortality, most commonly arising from placental dysfunction, with increasing evidence implicating aberrant DNA methylation in its pathogenesis. To identify robust epigenetic alterations associated with FGR, we analyzed placental chorionic villi from an in-house early-onset FGR cohort and compared them with a publicly available dataset (GSE100197). DNA methylation profiling was performed using Illumina EPIC (in-house) and 450K (public) arrays, processed with identical normalization and quality-control pipelines, including adjustment for gestational age and estimation of placental cell-type composition. Differentially methylated positions (DMPs) were identified using linear regression models, revealing 10,427 DMPs in the in-house cohort and 7467 in the public dataset, with 108 shared DMPs showing consistent direction of change across both cohorts. Promoter-associated DMPs were mapped to genes involved in angiogenesis, morphogenesis, immune regulation, and transcriptional control, including EPHA1, ANGPTL6, ITGAX, BCL11B, and CYP19A1, while additional novel candidates such as SLC39A12, YEATS4, and MIR515 family members were also identified. Functional annotation suggests that these methylation changes may influence pathways essential for placental vascular development and structural organization. Overall, this cross-cohort comparison highlights reproducible epigenetic signatures of FGR and underscores the need for standardized approaches to clarify the molecular mechanisms underlying placental insufficiency. Full article

Cancer remains a leading cause of morbidity and mortality worldwide, and effective strategies for cancer prevention are urgently needed to complement therapeutic advances. While dietary factors are known to influence cancer risk, the molecular mechanisms that mediate inter-individual responses to nutritional exposures remain poorly defined. Emerging evidence identifies long non-coding RNAs (lncRNAs) as pivotal regulators of gene expression, chromatin organization, metabolic homeostasis, immune signaling, and cellular stress responses, the core processes that drive cancer initiation and progression and are highly sensitive to nutritional status. In parallel, advances in precision nutrition have highlighted how variability in genetics, metabolism, microbiome composition, and epigenetic landscapes shape dietary influences on cancer susceptibility. This review integrates these rapidly evolving fields by positioning lncRNAs as molecular conduits that translate dietary exposures into transcriptional and epigenetic programs governing cancer development, progression, and therapeutic vulnerability. We provide mechanistic evidence demonstrating how dietary bioactive compounds and micronutrients, including polyphenols [such as curcumin, resveratrol, epigallocatechin gallate (EGCG)], flavonoids, alkaloids such as berberine, omega-3 (ω-3) fatty acids, folate, vitamin D, probiotic metabolites (such as butyrate and propionate), and trace elements (such as selenium and zinc), modulate oncogenic and tumor-suppressive lncRNAs. These nutrient–lncRNA interactions influence cancer-relevant pathways controlling proliferation, epithelial–mesenchymal transition (EMT), inflammation, oxidative stress, and metabolic rewiring. We further discuss emerging lncRNA signatures that reflect nutritional and metabolic states, their potential utility as biomarkers for individualized dietary interventions, and their integration into liquid biopsy platforms. Leveraging multi-omics datasets and systems biology, we outline AI-driven frameworks to map nutrient–lncRNA regulatory networks and identify targetable nodes for cancer chemoprevention. Finally, we address translational challenges, including compound bioavailability, inter-individual variability, and limited clinical validation, and propose future directions for incorporating lncRNA profiling into precision nutrition-guided cancer prevention trials. Together, these insights position lncRNAs at the nexus of diet and cancer biology and establish a foundation for mechanistically informed precision nutrition strategies in cancer chemoprevention. Full article

DNMT1 variants are linked to complex neurodegenerative syndromes, yet their variant-specific functional and epigenomic consequences remain poorly defined. DNMT1 variants were identified in eight patients using gene-panel or whole-exome sequencing. Functional effects were assessed by site-directed mutagenesis and transient expression in HEK293T cells. Genome-wide methylation profiling of peripheral blood leukocyte DNA was performed using Nanopore sequencing, enabling direct quantification of 5-methylcytosine (5mC). CpG island-level differential methylation and gene set enrichment analysis (GSEA) were conducted. Variants in the replication foci targeting sequence (RFTS) domain (p.Y511H, p.Y540C, p.H569R) exhibited reduced DNMT1 protein expression, decreased enzymatic activity, and cytosolic aggregation. Variants in the C-terminal catalytic domain (p.A1334V and p.P1546S) showed reduced protein expression with relatively mild enzymatic impairment. Patients carrying the p.Y511H variant demonstrated a significant reduction in global 5mC levels compared with controls. Principal component analysis revealed distinct methylomic profiles separating most patients from controls, with marked intra- and inter-familial heterogeneity. CpG island-level analysis identified a single significantly hypomethylated region in p.Y511H carriers, and GSEA revealed differential enrichment of multiple Gene Ontology biological pathways. This study defines domain-dependent functional effects of DNMT1 variants and provides the first nanopore-based methylome analysis, revealing variant-specific and heterogeneous epigenomic alterations. Full article

Advances in omics disciplines—particularly those directly involved in gene function and regulation, including genomics, epigenomics, exomics, transcriptomics, and proteomics, as well as fields addressing genomic responses to pharmacological interventions such as pharmacogenomics and metabolomics—have enabled an increasingly comprehensive characterization of gene activity in health and disease [...] Full article

Background/Objectives: Coupled with the already-problematic background rates of traditional cigarette consumption during pregnancy, the surging epidemic of electronic cigarette usage among pregnant women redoubles the importance of understanding the impacts of nicotine exposure during critical periods of development. To date, a burgeoning body of human epidemiological and animal model research indicates that not only the children but also the grandchildren of maternal smokers are at higher risk for neurodevelopmental disorders such as ADHD, autism, and schizophrenia and are predisposed to neurodevelopmental abnormalities which transcend these diagnoses. However, the roles of discrete cellular sub-populations in these and other intergenerational consequences of smoking during pregnancy remain indeterminate. Methods: Toward the resolution of this void in the literature, the present study characterized alterations in the gene expression profiles of dopamine receptor D1-expressing striatal cells from the first- and second-generation male progeny of female mice that were continuously exposed to nicotine beginning prior to conception, continuing throughout pregnancy, and concluding upon weaning of offspring. Results: Dopamine receptor D1-expressing striatal cells from our mouse models of the children and grandchildren of maternal smokers exhibit differential expression patterns for a multitude of genes that are (1) individually associated with neurodevelopmental disorders, (2) collectively overrepresented in gene set annotations related to brain, behavioral, neurobiological, and epigenomic phenotypes shared among neurodevelopmental disorders, and (3) orthologous to human genes that exhibit differential DNA methylation signatures in the newborns of maternal smokers. Conclusions: Together with our and others’ previous findings, the results of this study support the emerging theory that, by inducing extensive alterations in gene expression that in turn elicit cascading neurobiological changes which ultimately confer widespread neurobehavioral abnormalities, nicotine-induced epigenomic dysregulation may be a primary driver of neurodevelopmental deficits and disorders in the children and grandchildren of maternal smokers. Full article

Bisphenol AF (BPAF), a prevalent bisphenol A (BPA) substitute, raises concerns due to its environmental persistence and endocrine-disrupting potency. While metabolic effects of direct exposure are documented, its intergenerational consequences remain unclear. Here, we demonstrated that perinatal BPAF exposure induced persistent metabolic syndrome in offspring, including glucose intolerance, hepatic steatosis, and adipose hypotrophy. Integrating multi-omics data, we observed that BPAF exposure shaped offspring’s hepatic epigenome, as demonstrated by genome-wide alterations in H3K27ac-marked regulatory elements. This epigenetic rewiring indicated a dual regulatory effect on transcriptomes that suppressed interferon-γ responses while activating sterol biosynthesis, ultimately perturbating hepatic metabolome, including depleted pantothenate levels and accumulation of pro-inflammatory eicosanoids. Our findings suggest that BPAF may act as a developmental toxicant capable of persistently disrupting the immune–metabolic axis through epigenomic mechanisms, highlighting the need for careful re-evaluation of its use as a BPA substitute in consumer products. Full article

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors primarily involving the adrenal medulla and its associated paraganglia, with heterogeneous clinical behavior and complex molecular drivers. This study aimed to characterize DNA methylation and gene expression patterns in PPGLs to understand the molecular differences between tumor subtypes and malignancy. We performed an integrative analysis of DNA methylation (Illumina EPIC 850K) and gene expression profiles (Affymetrix microarrays) in 24 PPGLs, comparing these with The Cancer Genome Atlas (TCGA) data, to delineate cluster- and malignancy-specific epigenetic patterns. Comparison between pseudohypoxic Cluster I and kinase-signaling Cluster II tumors revealed 13 differentially methylated CpG sites, with a specific CpG within DSCAML1 showing hypermethylation in Cluster II accompanied by increased expression, suggesting context-dependent gene body methylation effects. Benign versus malignant comparisons identified 101 differentially methylated CpGs, including hypermethylated CpG in BAIAP2L1 and hypomethylated CpG in SHANK1 in malignant tumors. Pathway enrichment of differentially methylated genes revealed alterations in Notch signaling, adherens junctions, cytoskeletal regulation, and intracellular transport. Gene expression analysis demonstrated partial overlap between clusters, with malignant tumors exhibiting distinct transcriptional profiles involving RNA processing, metabolism, and adhesion pathways. Correlation between methylation and expression was generally limited, emphasizing that methylation-dependent gene regulation is a locus-specific and context-dependent regulation. These findings illustrate a complex interplay between epigenetic modifications and transcriptional programs in PPGLs, enhancing our understanding of molecular heterogeneity and tumor classification, and identifying candidate biomarkers and therapeutic targets for malignant progression. Full article

Background: Tic spectrum disorder (TSD), encompassing Tourette syndrome and chronic tic disorder, is a childhood-onset neurodevelopmental condition with complex genetic and environmental contributions. Heritable components have been implicated in TSD, but no clear genetic mechanisms have been identified. Significant aspects of TSD etiology remain unclear, with key uncertainties concerning the role of environmental influences in its development. In this study, we aimed to identify environmentally induced epigenomic and transcriptomic changes contributing to TSD pathology by investigating genetically similar monozygotic twins discordant for TSD. Methods: To investigate environmentally driven mechanisms, we analyzed peripheral blood from eleven monozygotic twin pairs, either discordant or concordant for TSD, using RNA sequencing and DNA methylation analysis. Results: Differential expression analysis identified a dozen differentially expressed genes between TSD and non-TSD individuals, most of which were long non-coding RNAs or pseudogenes. Expression of the small RNA gene RNY1 was significantly associated with tic severity, suggesting involvement of immune-related processes. DNA methylation (DNAm) analysis revealed ~30,000 probes with a nominal p < 0.05, however none of these were significant after multiple testing correction. Expression quantitative trait methylation (eQTM) analysis identified 236 methylation-associated genes. Gene set enrichment analysis demonstrated broad downregulation in TSD individuals for pathways related to translation, RNA processing, and neurobiological functions, with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including ribosome, nucleocytoplasmic transport, pluripotency signaling, and nicotine addiction. Conclusions: These results suggest that environmentally influenced gene expression may contribute to TSD pathogenesis through dysregulation of immune and neuronal pathways. Despite a small sample size, the monozygotic twin design provides strong control for genetic background and identifies significant differences that contribute to the understanding of the underlying molecular mechanisms of TSD. Full article

Colorectal cancer (CRC) develops through evolutionary processes involving genomic alterations, epigenetic regulation, and microenvironmental interactions. While traditionally explained by the stepwise accumulation of driver mutations, contemporary evidence supports a ‘Big Bang’ model in which many early-arising clones expand simultaneously to establish extensive heterogeneity. We reviewed recent studies employing spatially resolved multi-omic sequencing of tumour glands combined with computational modelling. These approaches enable high-resolution reconstruction of clonal architecture, transcriptional states, and chromatin accessibility. Findings show that although early clonal mutations shape tumour expansion, gene expression variability can be independent of genetic ancestry and instead reflects phenotypic plasticity driven by microenvironmental cues. Epigenomic analyses identified recurrent somatic chromatin accessibility alterations in promotors and enhancers of oncogenic pathways, frequently in the absence of DNA mutations, suggesting alternative mechanisms of gene regulation. Immune-focused studies demonstrated that early silencing of antigen-presenting genes and loss of neoantigens facilitate immune escape despite active surveillance. CRC is shaped by an interplay of genome, epigenome, and immune evolution, with non-genetic mechanisms and tumour plasticity emerging as important drivers of progression and therapeutic resistance. Full article

Maize (Zea mays L.), a vital crop for global food and economic security, faces intensifying biotic and abiotic stresses driven by climate change, including drought, heat, and erratic rainfall. This review synthesizes emerging biotechnology-driven strategies designed to enhance maize resilience under these shifting environmental conditions. We present an integrated framework that encompasses CRISPR/Cas9 and next-generation genome editing, Genomic Selection (GS), Environmental Genomic Selection (EGS), and multi-omics platforms—spanning transcriptomics, proteomics, metabolomics, and epigenomics. These approaches have significantly deepened our understanding of complex stress-adaptive traits and genotype-by-environment interactions, revealing precise targets for breeding climate-resilient cultivars. Furthermore, we highlight enabling technologies such as high-throughput phenotyping, artificial intelligence (AI), and nanoparticle-based gene delivery—including novel in planta and transformation-free protocols—that are accelerating translational breeding. Despite these technical breakthroughs, barriers such as genotype-dependent transformation efficiency, regulatory landscapes, and implementation costs in resource-limited settings remain. Bridging the gap between laboratory innovation and field deployment will require coordinated policy support and global collaboration. By integrating molecular breakthroughs with practical deployment strategies, this review offers a comprehensive roadmap for developing sustainable, climate-resilient maize varieties to meet future agricultural demands. Full article

Late-onset sporadic Alzheimer’s disease (LOAD) is the most common form of dementia. The disease is characterized by progressive loss of memory and behavioral changes followed by neurodegeneration of all cortical areas. While the contribution of genetic and environmental factors is important, advanced aging remains the most important disease risk factor. Because LOAD does not naturally occur in most animal species, except humans, studies have traditionally relied on the use of transgenic mouse models recapitulating early-onset familial Alzheimer’s disease (EOAD). Hence, the development of more representative LOAD models through reprograming of patient-derived cells into neuronal, glial, and immune cells became a necessity to better understand the disease’s origin and pathophysiology. Herein, and focusing on neurons, we review current work in the field and compare results obtained with two different reprograming methods to generate LOAD patient’s neuronal cells: the induced pluripotent stem cell and induced neuron technologies. We also evaluate if these models can faithfully mimic cellular and molecular pathologies observed in LOAD patients’ brains. Full article

Purpose: The reversible deviant in epigenomic modulations is the highlight of developing new anti-cancer drugs, necessitating the use of fisetin as an epigenetic modifier in the study. Methods: In silico and molecular studies were performed to analyze the modulatory effect of fisetin on various writers and erasers. Further, whole genome DNA methylation sequencing and expression studies were performed. Global DNA methylation-LINE 1 kit was used to check global DNA methylation. Additionally, the effect of fisetin on migration was evaluated by colony, scratch, and invasion assays and qPCR and protein expression studies of migration-related genes were carried out on HeLa cells. Results: In silico studies have supported that fisetin interacts with writers and erasers in their catalytic site and the simulation studies showed minimum fluctuations in energy and temperature over a 10 ns timescale indicating that these complexes are likely to remain stable. Fisetin (20–50 µM) dose-dependently inhibited DNA methyltransferases (DNMT), histone deacetyl transferases (HDAC), histone acetyl transferases (HAT), and histone methyltransferases (HMT) activities at 48 h, with inhibition ranging from 24 to 72% compared to the control. The expression and enzymatic activity of these proteins, along with various H4 and H3 modification marks, were observed to be altered following fisetin treatment at 48 h. Fisetin treatment reduced promoter methylation in various tumor suppressor genes ranging from 15.29% to 76.23% and leading to the corresponding reactivation of important tumor suppressor genes; however, it did not lead to any alteration in the global DNA methylation compared to untreated controls linked with the anti-migratory properties of fisetin as the percentage of migrated cells dropped from ~40% to ~8%. Conclusions: This study gives a mechanistic insight of fisetin as a potential epigenetic modifier in HeLa cells. Full article

Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose–lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR’s capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub–axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling. Full article

Alzheimer’s disease (AD) and related dementias (ADRD) are neurodegenerative conditions that cause gradual deterioration of cognition, memory and language in the elderly. AD has been declared as a health priority by the World Health Organization (WHO) considering its severity and unavailability of a permanent cure. Although the global AD/ADRD population is made up of many ethno-racial groups, the majority of AD studies have focused on the Caucasian population. The few AD studies conducted on minority populations in the US have found that significant AD health disparities exist, demonstrating that African Americans and Hispanics have a significantly higher prevalence of AD and related dementias, with their risk often approaching twice that of White individuals. For the past few years, epigenomic research has played an important role in understanding health disparities among diverse racial and ethnic groups. Unlike genetic studies, which focus on the DNA sequence that one is born with, epigenomics investigates how changes in gene expression due to extrinsic environmental exposures may impact disease pathophysiology. Recent epigenomic studies appear to be promising in not only understanding disease pathology but also in developing diagnostic and therapeutic tools for AD with population specificity. However, there is only a handful of studies and review articles available addressing the epigenomic applications in irradicating racial disparities in AD/ADRD. Therefore, the aim of this review is to discuss the recent findings of epigenomic studies in AD and related dementias, their contribution in irradicating racioethnic disparities and insights into the future direction of their application in precision medicine. Full article

Background: Pituitary neuroendocrine tumours (PitNETs) are clinically and biologically heterogeneous neoplasms that remain challenging to diagnose, prognosticate, and treat. Although recent WHO classifications using transcription-factor-based markers have refined pathological categorisation, histopathology alone still fails to predict tumour behaviour or support individualised therapy. Objective: This systematic review aimed to evaluate how machine learning (ML) and knowledge extraction approaches can complement pathology by integrating multi-dimensional omics datasets to generate predictive and clinically meaningful insights in PitNETs. Methods: The review followed the PRISMA 2020 statement for systematic reviews. Searches were conducted in PubMed, Google Scholar, arXiv, and SciSpace up to June 2025 to identify omics studies applying ML or computational data integration in PitNETs. Eligible studies included original research using genomic, transcriptomic, epigenomic, proteomic, or liquid biopsy data. Data extraction covered study design, ML methodology, data accessibility, and clinical annotation. Study quality and validation strategies were also assessed. Results: A total of 726 records were identified. After the reviewing process, 98 studies met inclusion criteria. PitNET research employed unsupervised clustering or regularised regression methods reflecting their suitability for high-dimensional omics datasets and the limited sample sizes. In contrast, deep learning approaches were rarely implemented, primarily due to the scarcity of large, clinically annotated cohorts required to train such models effectively. To support future research and model development, we compiled a comprehensive catalogue of all publicly available PitNET omics resources, facilitating reuse, methodological benchmarking, and integrative analyses. Conclusions: Although omics research in PitNETs is increasing, the lack of standardised, clinically annotated datasets remains a major obstacle to the development and deployment of robust predictive models. Coordinated efforts in data sharing and clinical harmonisation are required to unlock its full potential. Full article