Search Results (5,110)

Colorectal cancer (CRC) remains one of the most prevalent malignancies worldwide and is the second largest contributor to both incidence and mortality, underscoring the urgent need for effective prevention strategies. This comprehensive review provides the most up-to-date evidence on the protective role of plant-based dietary patterns against CRC carcinogenesis, with particular emphasis on underlying cellular and molecular level mechanisms. Accumulating research demonstrates that plant-based foods, rich in dietary fibre, polyphenols, and multiple other bioactive compounds, promote gut microbial eubiosis, support immune regulation, and modulate adipose tissue homeostasis. These effects are accompanied by intestinal barrier integrity, enhanced production of short-chain fatty acids, and the induction of apoptosis in malignant cells. Moreover, plant-derived nutrients reduce the abundance of pro-inflammatory microbial taxa, decrease oxidative, nitrosative and carbonyl stress, and downregulate pro-inflammatory cytokines and signalling pathways, implicated in tumourigenesis. As a result, plant-based dietary patterns have high potential to reduce CRC risk through modulating the intricate interplay between epigenetics, inflammation, immune dysregulation, metabolic and hormonal disruptions, and gut microbiota, suggesting a highly promising, cost-effective and equitable strategy for CRC prevention. Full article

Background: DNA methylation alterations represent a key epigenetic mechanism linking environmental exposures to disease pathogenesis. The present study aimed to identify differentially methylated genes and shared biological processes associated with lung cancer (LuCa), chronic obstructive pulmonary disease (COPD) and tobacco exposure. Methods: A comprehensive literature search was performed in PubMed to identify studies evaluating DNA methylation in LuCa, COPD and smoking-related models. A total of 117 articles were selected, including 83 studies on lung cancer, 18 on COPD and 16 on smoking exposure. Genes exhibiting statistically significant methylation changes relative to controls were extracted from each study. To provide additional support for these findings, differential methylation signatures were further evaluated using The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets. Functional and transcription factor motif enrichment analyses were subsequently conducted to identify shared biological pathways and regulatory mechanisms. Results: In total, 324 genes displaying altered methylation patterns across these conditions were identified. Seven tumor suppressor genes (CDKN2A, CDH13, MGMT, MIR137, DAPK1, RARB, and RASSF1A) consistently exhibited hypermethylation in both lung cancer and in association with smoking exposure. In addition, AHRR hypomethylation emerged as a shared epigenetic hallmark across all three conditions. TCGA-based analyses confirmed several of these methylation patterns and revealed subtype-specific methylation profiles associated with smoking history. Functional enrichment highlighted common biological processes and signaling pathways, particularly those related to transcriptional regulation, apoptosis and cancer-associated pathways. Conclusions: These results provide an integrative overview of shared DNA methylation alterations associated with smoking exposure, COPD, and lung cancer, and suggest potential DNA methylation candidates that may be relevant for future biomarker development and mechanistic studies. Full article

Background/Objectives: Nuclear receptor corepressors NCOR1 and NCOR2 are key regulators of transcriptional repression, chromatin remodelling, and immunometabolic signalling. While NCOR1 has already been linked to vascular biology, its relevance in abdominal aortic aneurysm (AAA) remains unclear, particularly for NCOR2. This study aimed to investigate the expression, cellular localisation, and molecular interactions of NCOR1/2 in human AAA tissue. Methods: Human AAA samples (elective and ruptured) (n = 45) and non-aneurysmal control aortas (n = 18) were obtained from our Swiss Vascular Biobank. Transcriptomic profiling was performed using ribosomal RNA-depleted RNA sequencing. Differential expression and correlation analyses were performed using DESeq2/EdgeR and Spearman rank correlation with Benjamini–Hochberg correction. Cellular localisation was assessed through immunohistochemistry (IHC). Results: Bulk transcriptomic analyses showed no significant differences in NCOR1 or NCOR2 expression between AAA and controls. IHC revealed that NCOR1 was found in endothelial cells (ECs), smooth muscle cells (SMCs), and inflammatory infiltrates, while NCOR2 was primarily associated with macrophages. Correlation analyses suggest that NCOR1 interacts with various cellular markers, proteolytic enzymes, inflammatory mediators, and epigenetic regulators, including the lncRNA MALAT1. NCOR2 showed distinct associations with remodelling enzymes, TGFB1 signalling, selective epigenetic modifiers, and lncRNA H19. Conclusions: The lack of transcriptional differences in NCOR1 and NCOR2 between AAA and controls does not exclude cell-type-specific regulation or functional relevance. The specific cellular distributions and molecular associations in human AAA imply that NCOR1 and NCOR2 play non-redundant roles in vascular remodelling, inflammation, and epigenetic regulation. Our findings highlight NCOR pathways as potential modulators of AAA pathophysiology and promising targets for future therapies. Full article

China has rich bamboo resources, with Moso bamboo (Phyllostachys edulis) being the most economically important species. Bamboo shoot bud development directly determines the eating quality of the shoots and the properties of bamboo materials; however, the intrinsic biological characteristics of this process have hindered foundational research. Traditional methods using whole shoot buds or mixed tissues obscure cellular and tissue heterogeneity, limiting our mechanistic understanding. This review synthesizes cytological features, molecular networks, and technical limitations pertaining to Moso bamboo shoot bud development, identifying four key bottlenecks: tissue homogenization masking cellular heterogeneity, loss of spatial positional information impeding analysis of position effects, challenges in single-cell technology application due to sample preparation and data interpretation issues, and unresolved coupling between chromatin accessibility and transcriptional regulation. To address these, we propose a core strategy centered on constructing a single-cell resolution, spatially resolved, multi-omics integrated, and functionally validated framework. Key approaches include developing bamboo-specific single-cell sequencing and spatial transcriptomics, integrating positional information with multi-omics data to identify spatially distinct regulatory targets, standardizing technical pipelines and functional validation platforms, and elucidating epigenetic–transcriptional coupling. Overcoming these bottlenecks will reveal the molecular basis of bamboo’s unique developmental patterns and provide key targets for the genetic improvement of the shoot quality and mechanical properties of bamboo. Full article

Environmental pollutants, lifestyle factors, and intrinsic metabolism can amplify reactive oxygen and nitrogen species (ROS/RNS) generation beyond antioxidant capacity. The resulting oxidative stress damages macromolecules, perturbs redox signaling, and may accelerate biological aging. This review synthesizes evidence published mainly in 2020–2025 on how major pollutant classes (air pollutants, metals, pesticides, nanoparticles, and micro-/nanoplastics) induce ROS through shared nodes mitochondrial electron transport disruption, NADPH oxidase activation, and redox cycling/Fenton chemistry and how these signals propagate to epigenetic remodeling (DNA methylation, histone modifications, and non-coding RNAs). To move beyond descriptive cataloging, we grade the strength of evidence by study context (cell culture, animal models, human observational studies, and clinically oriented biomarker research), highlight convergent findings and unresolved controversies, and specify key methodological limits. We then compare oxidative-stress biomarker platforms by analytical specificity, pre-analytical susceptibility, and translational readiness, distinguishing validated markers from exploratory redox-epigenetic and multi-omics signatures. Finally, we discuss how exposomics and AI-assisted multi-omics integration may support biomarker discovery while emphasizing current constraints (confounding, batch effects, and limited prospective validation) that must be addressed for clinical translation. Full article

Background: EHMT2 (G9a) is a key epigenetic regulator frequently overexpressed in various cancers. While several inhibitors exist, their in vivo efficacy and pharmacokinetic (PK) properties remain poorly characterized. Methods: We compared the biochemical, cellular, and PK profiles of two widely used EHMT2 inhibitors, BIX-01294 and UNC0642, and evaluated their antitumor efficacy in xenograft and syngeneic mouse models. Results: Despite a higher enzymatic potency of UNC0642 (IC₅₀ = 0.277 μM) compared to BIX-01294 (IC₅₀ = 1.983 μM), BIX-01294 demonstrated superior cellular growth inhibition and higher intracellular accumulation. PK analysis further revealed that BIX-01294 achieved higher systemic exposure (AUC) and a wider therapeutic window via intraperitoneal administration, whereas UNC0642 exhibited dose-limiting lethality above 8 mg/kg. In HT-29 and MIA PaCa-2 xenografts, BIX-01294 (40 mg/kg) achieved up to 70.6% tumor growth inhibition (TGI), substantially surpassing UNC0642. Furthermore, in MC38 syngeneic models, a BIX-01294/anti-PD-L1 antibody combination produced an additive effect. This combination markedly increased the number of tumor-infiltrating CD8α⁺ T cells and NK1.1⁺ cells. Conclusions: These results suggest that BIX-01294 is more effective in vivo than UNC0642 due to its favorable PK profile and superior cellular uptake. Our findings support the further development of EHMT2 inhibitors as potent partners for immune checkpoint blockades. Full article

The liver is a central regulator of systemic metabolism and exhibits exceptional regenerative capacity, yet aging progressively impairs hepatic resilience through metabolic dysregulation, mitochondrial dysfunction, epigenetic instability, and chronic inflammation. Marine ecosystems constitute a vast and underexplored source of structurally diverse bioactive compounds that have evolved to modulate conserved stress response and homeostatic pathways. This review synthesizes current preclinical evidence demonstrating how marine-derived metabolites target key molecular axes implicated in liver aging, including energy sensing, redox balance, mitochondrial quality control, inflammatory signaling, and chromatin-associated regulation. Rather than focusing solely on isolated hepatoprotective effects, we frame marine bioactives within an aging biology perspective, highlighting their ability to modulate pathways associated with cellular plasticity and resilience. We further propose that this mechanistic convergence provides a theoretical framework for exploring marine compounds as potential adjunctive modulators within emerging, experimental liver rejuvenation strategies, including partial cellular reprogramming approaches that require coordinated metabolic and epigenetic control. While acknowledging that direct reversal of liver aging remains to be clinically established, integrating marine chemodiversity with contemporary aging and regenerative biology outlines a conceptual roadmap for developing liver-directed interventions targeting aging-related vulnerability as a fundamental driver of disease. Full article

Adolescence is a metabolically vulnerable period, during which rapid physiological maturation coincides with the dynamic remodelling of the gut microbiome. This narrative review summarises evidence from 2015 to 2025 to clarify how disturbances to the gut–liver axis driven by dysbiosis contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD) in young people. Based on a systematic search of the databases PubMed, Scopus and Web of Science, we outline the basis of bidirectional communication between the gut and liver and emphasise how microbial imbalance alters the handling of lipids in the liver by enhancing de novo lipogenesis, impairing fatty acid oxidation and disrupting AMPK signalling and mitochondrial function. Consistent findings from clinical and experimental studies show that adolescents with NAFLD exhibit reduced microbial diversity, the enrichment of ethanol- and LPS-producing taxa, and altered short-chain fatty acid profiles. Each of these is associated with hepatic inflammation and metabolic reprogramming. Microbial molecules, including LPS, secondary bile acids and branched-chain amino acid metabolites, activate TLR4–NF-κB pathways, promote Kupffer cell activation and intensify oxidative stress. These mechanisms intersect with factors specific to adolescence, such as increased adiposity, hormonal shifts and diet-induced metabolic strain. Dietary patterns emerge as key modulators of these processes. Westernised diets promote dysbiosis and endotoxemia, whereas Mediterranean, fibre-rich and plant-based diets enhance SCFA production, strengthen epithelial integrity and modulate adiponectin-dependent hepatic metabolism. Micronutrient-sensitive epigenetic regulation, particularly that involving folate, choline and polyphenols, also plays a role in shaping lipid homeostasis and inflammatory tone. We also highlight emerging evidence that the activation of cytoprotective pathways, especially Nrf2, is dependent on lifestyle factors and links antioxidant-rich functional foods and physical activity to improved mitochondrial resilience and microbiome stability. We evaluate therapies targeting the microbiome, including probiotics, prebiotics, synbiotics and postbiotics, which reduce endotoxemia, restore microbial balance and complement dietary strategies. Thus, these findings emphasise the importance of age-specific, mechanistically informed interventions that integrate diet quality, microbial ecology, and the molecular pathways that govern metabolic health in adolescents with NAFLD. Full article

Background: This study investigates the role of N6-methyladenosine (m6A) regulators in osteoporosis (OP) and their interplay with the immune microenvironment, aiming to identify potential m6A-related biomarkers for OP risk assessment and treatment. Methods: Transcriptomic data from GEO datasets were analyzed for differential expression of 22 m6A regulators and immune infiltration patterns. Consensus clustering and m6Ascore grouping defined molecular subtypes, while machine learning algorithms identified potential biomarkers, leading to the construction and validation of a nomogram. Experimental validation involved peripheral blood monocytes (PBMCs) transcriptome sequencing and Western blot of bone tissue. Results: FTO, HNRNPC, and METTL4 were upregulated, while CBLL1 and YTHDF2 were downregulated in OP, with two distinct m6A modification patterns and immune phenotypes identified. METTL4, HIRA, MATN4, and YTHDF2 were selected as potential biomarkers, and the nomogram demonstrated favorable predictive performance in training and external datasets. Single-cell RNA sequencing confirmed the cellular distribution of these biomarkers. HIRA heterogeneity in Marrow Mesenchymal Stem Cells (BMSCs) was associated with distinct cell–cell communication patterns. Transcriptome sequencing confirmed HIRA RNA downregulation in OP PBMCs, and Western blot verified decreased HIRA protein in OP bone tissue. Conclusions: This study establishes a potential m6A-related biomarker signature for OP and provides multi-level experimental evidence that HIRA is a consistently downregulated biomarker, linking epigenetic modification to immune dysregulation in osteoporosis. Full article

Non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression and cellular homeostasis, and their dysregulation is now recognized as a hallmark of cancer. Over the past decades, extensive research has demonstrated that diverse ncRNA classes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other small ncRNA species, participate in complex regulatory networks that influence tumor initiation, progression, metastasis, and therapy response. Through mechanisms such as transcriptional regulation, post-transcriptional gene silencing, epigenetic modulation, and competitive endogenous RNA interactions, ncRNAs shape the molecular circuitry underlying cancer development. In addition to their functional roles in tumor biology, many ncRNAs are released into biological fluids and can be detected as circulating molecules in blood, urine, saliva, and other biofluids. Their remarkable stability in extracellular environments has generated considerable interest in their use as minimally invasive biomarkers in liquid biopsy applications. Emerging evidence has shown that circulating ncRNAs (c-ncRNAs) can support cancer detection, disease stratification, and treatment monitoring. This narrative review provides an integrated view that links ncRNA-mediated regulatory networks with their application as liquid biopsy biomarkers, positioning ncRNAs as comprehensive indicators of tumor conditions. Particular emphasis is placed on c-ncRNA biomarkers, the integration of multiple ncRNA classes, and multi-analyte biomarker strategies that combine ncRNAs with complementary circulating molecules such as cell-free DNA and protein markers. Finally, we discuss the technical and clinical challenges that currently limit the translation of ncRNA-based diagnostics into clinical practice and highlight future directions for advancing ncRNA-guided liquid biopsy approaches in precision oncology. Full article

Transposable elements (TEs) are major contributors to genome plasticity and can reshape gene regulation through stress-responsive activation and the formation of TE-gene chimeric transcripts. Although therapeutic stress is known to perturb transcriptional networks in cancer cells, its impact on canonical TE transcription and TE-gene chimera formation in esophageal squamous cell carcinoma (ESCC) remains poorly defined. To address this, we performed a comprehensive transcriptome-wide analysis of TE expression and TE-gene chimeric transcripts in KYSE150 ESCC cells following combined 125I radiation and carfilzomib treatment. The TE analysis showed 148 dysregulated TEs, characterized by ERV1 LTR element enrichment and distinct treatment-control sample separation, indicating structured remodeling of the TE transcriptome. We identified 301 significant TE-gene chimeric events, indicating category-specific remodeling with an increase in TE-initiated and TE-exonic chimeras and a decrease in TE-terminal events. The TE families that underwent the most transcriptional changes were not those that drove chimeric events, indicating that global TE activation does not passively cause chimera remodeling. The gene repression was strongly associated with chimeric transcripts, and gene expression changes were negatively correlated with chimerism frequency. SPANXN1, IL1RL1, and RSAD2, strongly downregulated genes, produced novel TE-derived isoforms and were high-potential functional candidates. Epigenetic context analysis showed considerable overlap between exonized chimeras and candidate cis-regulatory elements, suggesting a potential association with regulatory genomic contexts. Pathway enrichment analysis showed synchronized transcriptomic reprogramming and cell cycle and DNA repair pathway activation and autophagy inhibition. In esophageal cancer cells, concurrent genotoxic and proteotoxic stress causes complex TE remodeling, linking traditional TE transcriptional alterations to structured TE-gene chimera development and stress-related transcriptome reprogramming. Full article

Background: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality among individuals with type 2 diabetes mellitus (T2DM). Although women generally exhibit a more favorable cardiovascular risk profile than men in the general population, this protection is substantially reduced in the presence of diabetes, resulting in a disproportionately greater relative increase in CVD risk among women. Objective: This review aims to integrate the roles of metabolic phenotypes, dietary exposures, and genetic susceptibility in shaping cardiovascular risk in women with T2DM, with a focus on diet–gene and diet–epigenetic interactions across critical stages of the female life course. Methods: A narrative review of epidemiological, clinical, and mechanistic evidence from recent literature was conducted to synthesize current knowledge on sex-specific cardiometabolic pathways and nutritional determinants of vascular risk in T2DM. Results: Current evidence indicates that several interconnected mechanisms contribute to enhanced cardiovascular vulnerability in diabetic women, including (i) adipose tissue dysfunction and ectopic fat accumulation; (ii) insulin resistance with metabolic inflexibility and lipotoxicity; and (iii) endothelial and microvascular dysfunction driven by impaired nitric oxide signaling. Dietary patterns modulate these pathways through effects on inflammation, oxidative stress, postprandial lipid metabolism, and vascular function. Emerging evidence highlights that genetic variants (e.g., APOE; CETP; TCF7L2) significantly modify metabolic responses to dietary exposures in patients with T2DM; supporting a role for nutrigenetic interactions in shaping cardiovascular risk. In parallel, diet-related epigenetic mechanisms—including metabolic memory and early-life programming—may contribute to long-term and potentially intergenerational cardiometabolic risk. Conclusions: Integrating dietary patterns with genetic susceptibility and epigenetic regulation provides a mechanistic framework for understanding the disproportionate cardiovascular risk in diabetic women and supports the development of sex-specific, life-course-oriented precision nutrition strategies for cardiovascular risk reduction Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer defined by the absence of estrogen and progesterone receptors, as well as the lack of human epidermal growth factor 2 receptor overexpression. TNBC is associated with early onset, high metastatic potential, therapeutic resistance, and poor clinical outcomes exacerbated by the limited availability of effective targeted therapies. Advances in multi-omics profiling have further stratified TNBC into distinct molecular subtypes, each exhibiting unique genomic, epigenomic, and immune-related features that influence therapeutic responsiveness. This review explores the interplay between TNBC molecular heterogeneity, immune evasion mechanisms, and epigenetic regulation. TNBC demonstrates variable immunogenicity, with tumor-infiltrating lymphocytes serving as important prognostic and predictive biomarkers. However, immune escape commonly occurs through tumor microenvironment remodeling, T-cell exhaustion, cancer stem cell enrichment, and immune checkpoint pathways activation. Although immune checkpoint inhibitors have improved outcomes in selected patients, particularly in combination with chemotherapy, primary and acquired therapeutic resistance remain a significant challenge. Emerging evidence highlights the central role of epigenetic mechanisms in regulating immune-related gene expression and shaping the tumor immune microenvironment. Epigenetic silencing of antigen presentation machinery, interferon signaling pathways, and chemokine expression contributes to immune evasion and immunotherapy resistance. Importantly, pharmacological modulation of epigenetic regulators can restore immune recognition and induce “viral mimicry” through reactivation of endogenous retroelements, thereby enhancing antitumor immunity. Collectively, this review underscores the therapeutic potential of integrating epigenetic therapies with immunotherapy and chemotherapy to overcome immune resistance in TNBC. A deeper understanding of epigenetic-immune interactions may facilitate the development of more precise and effective treatment strategies tailored to TNBC molecular subtypes. Full article

Background: People living with HIV (PLWH) have a substantially increased risk of both AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs), which remain a major cause of morbidity despite effective antiretroviral therapy (ART); this review aims to integrate current epidemiological, molecular, and clinical evidence on HIV-associated oncogenesis. Methods: A structured literature search was conducted in PubMed (2000–2026) using predefined keywords, including “HIV”, “cancer”, “oncogenesis”, and “immune dysregulation”, with inclusion of original studies, systematic reviews, and meta-analyses meeting predefined quality criteria. Results: Available evidence indicates that HIV contributes to cancer development through both direct and indirect mechanisms: viral proteins such as Tat, Nef, and Vpr disrupt apoptosis, DNA repair, and cell cycle regulation, while chronic immune activation, persistent inflammation, and immunosuppression impair tumor immune surveillance and facilitate oncogenic viral co-infections, including Epstein–Barr virus, human papillomavirus, and human herpesvirus 8. Emerging pathways, such as epigenetic alterations, microRNA dysregulation, metabolic reprogramming, and the contribution of HIV reservoirs to pro-tumorigenic microenvironments, further modulate cancer risk. Conclusions: HIV may function as a cofactor that enhances the effects of oncogenic viruses by promoting viral persistence and immune dysregulation; while biologically plausible, direct evidence linking HIV to amplification of tumorigenesis in humans remains limited. Full article

The Chinese mitten crab (Eriocheir sinensis) is widely distributed along eastern China, where northern and southern populations may have evolved different environmental adaptation mechanisms. DNA methylation, as an important epigenetic modification, plays a key regulatory role in environmental adaptation. In this study, muscle and hepatopancreas tissues from E. sinensis populations of the Liaohe River (LH) and Beilunhe River (BLH) were subjected to integrated RNA-seq and whole-genome bisulfite sequencing (WGBS) analyses, generating 12 mRNA libraries and 12 DNA methylation libraries. RNA-seq analysis identified 622 and 783 differentially expressed genes (DEGs) in muscle and the hepatopancreas, respectively, in the LH group compared with the BLH group, with downregulated genes accounting for a larger proportion. WGBS analysis showed that genome-wide DNA methylation in E. sinensis was predominantly in the CG context, with the highest methylation levels observed in gene body regions. A total of 972 and 991 differentially methylated regions (DMRs) were identified in muscle and the hepatopancreas, respectively. Integrated analysis further identified 10 differentially methylated and expressed genes (DMEGs) in muscle and 26 DMEGs in the hepatopancreas. Notably, no single fixed pattern was observed between methylation changes and gene expression changes in either tissue. These findings suggest that DNA methylation may participate in environmental adaptation in northern and southern populations of E. sinensis by modulating gene expression. Our results highlight the important role of epigenetic regulation in the evolutionary adaptation of crustaceans to different environments and provide a theoretical basis for the development of environment-associated molecular markers and the evaluation of adaptive germplasm resources. Full article