Clinical Epigenetics最新文献

{"title":"Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases.","authors":"Wanhui You, Siyu Wang, Yue Zhang, Xin Su, Fangyuan Liu, Danni Ding, Fengjuan Han, Ying Guo","doi":"10.1186/s13148-026-02185-y","DOIUrl":"10.1186/s13148-026-02185-y","url":null,"abstract":"<p><p>Lactic acid modification of histones represents an emerging post-translational modification that establishes a critical link between cellular metabolic reprogramming and epigenetic regulation through the covalent binding of lactic acid to histone lysine residues. In recent years, the mechanisms underlying this modification in the pathogenesis of various diseases have been progressively elucidated, revealing its extensive biological impact and potential clinical translational value. As research progresses, the functional role of histone lactylation in gynecological diseases has become increasingly evident, offering a novel epigenetic perspective for deciphering the pathogenesis of gynecological-related disorders. This review outlines the mechanisms underlying histone lactylation and focuses on its regulatory role in common benign and malignant gynecological diseases. The malignant diseases discussed include ovarian, endometrial, and cervical cancers, while the benign conditions include endometriosis and polycystic ovary syndrome. Furthermore, it undertakes an analysis of the therapeutic potential of histone lactylation modifications and reviews emerging targeted therapeutic strategies. These include targeting lactate production, lactate transport, lactylation-associated enzymes, or downstream effectors, highlighting their potential to intervene in disease progression. The present study aims to systematically elucidate the core value of histone lactylation as a novel epigenetic link between metabolism and gynecological disease pathogenesis. In addition, it provides clear research directions and robust theoretical support for developing targeted therapeutic strategies based on lactylation modifications.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATAD2 suppresses senescence and SASP via SIRT7-p53/p21 to drive progression and immune evasion in endometrial cancer.","authors":"Can Wang, Anastasiia Osipova, Yuanyuan Wang, Fei Li, Hengyu Wang, Jingshu Hu, Xiuwei Chen","doi":"10.1186/s13148-026-02182-1","DOIUrl":"10.1186/s13148-026-02182-1","url":null,"abstract":"<p><strong>Background: </strong>Endometrial cancer is one of the gynecological malignancies, currently ranking first in mortality among the three major gynecological cancers. Effective treatment options remain scarce. ATAD2, a chromatin remodeler, is implicated in solid tumor progression, but its role in endometrial cancer (EC) and tumor microenvironment (TME) remodeling remains unclear. This study investigated the functional impact and mechanisms of ATAD2 in EC pathogenesis.</p><p><strong>Methods: </strong>Based on the publicly available TCGA Uterine Corpus Endometrioid Carcinoma (UCEC) dataset, we preliminarily clarified the pro-cancer role of ATAD2. To explore its mechanism, this study constructed EC cell lines with stable ATAD2 overexpression and knockdown, and assessed cell proliferation, migration, and invasion capabilities; combined with bioinformatics analysis, we screened potential regulatory pathways. We verified the interaction between ATAD2 and SIRT7 protein using immunoprecipitation, molecular docking, GST-pull-down, and proximity ligation (PLA) techniques. Flow cytometry was used to detect macrophage polarization status, SA-β-galactosidase activity and p53/p21 expression levels were used to assess cellular senescence, and enzyme-linked immunosorbent assay (ELISA) was used to quantitatively analyze senescence-related secreted phenotypic factors. Furthermore, through immune cell infiltration atlas analysis and combined with a xenograft tumor model, we evaluated the in vivo antitumor effect of the ATAD2 inhibitor BAY-850.</p><p><strong>Results: </strong>High ATAD2 expression correlated with poor EC prognosis and enhanced cancer cell proliferation, migration, and invasion. Mechanistic studies have shown that ATAD2 interacts directly with SIRT7 through its bromine domain and enhances its protein stability. SIRT7 regulates p21 transcription by deacetylation of the lysine K382 site of p53 protein, thereby inhibiting cell senescence and SASP secretion.High ATAD2 expression was linked to increased TP53 mutation burden and suppressed anti-tumor immunity. ATAD2 inhibition promotes SASP secretion and induces M1 macrophage polarization, an effect that can be reversed by SIRT7 upregulation. BAY-850 inhibits tumor growth and metastasis in vivo.</p><p><strong>Conclusion: </strong>ATAD2 suppresses cellular senescence and SASP phenotypes via the SIRT7-p53/p21 axis, promoting immune-suppressive TME and driving EC progression and immune evasion. ATAD2 represents a promising therapeutic target for EC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation marks associated with body composition in children from India and the Gambia: findings from the EMPHASIS study.","authors":"Prachand Issarapu, Manisha Arumalla, Elie Antoun, Chiara di Gravio, Kate A Ward, Caroline H D Fall, Andrew M Prentice, Giriraj Ratan Chandak, Matt J Silver","doi":"10.1186/s13148-026-02172-3","DOIUrl":"10.1186/s13148-026-02172-3","url":null,"abstract":"<p><strong>Background: </strong>Differences in body composition during childhood can influence long-term health, with notable links to cardiometabolic disorders in later life. While genetic associations with body composition traits are well-studied, less is known about the role of epigenetic mechanisms, particularly in low- and middle-income countries where the burden of cardiometabolic disease is high. We investigated links between DNA methylation and three compartments of body composition: fat mass, lean mass, and bone measures using data from children enrolled in the Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa (EMPHASIS) study.</p><p><strong>Results: </strong>We conducted an epigenome-wide association study of 11 body composition traits assessed through dual-energy X-ray absorptiometry in children from India (mean [range] age = 5.8 [5-7] years; n = 686) and The Gambia (age = 9.0 [7-9] years; n = 284), with blood DNA methylation measured at ~ 800,000 CpGs sites on the Illumina EPIC array. Cohort-specific analysis identified 8 unique differentially methylated CpGs associated with traits across all three body composition compartments (p < 3.6 × 10^-8), with none overlapping both cohorts. Cross-cohort meta-analysis revealed four CpGs associated with lean mass and bone area mapping to SOCS3 and ZBTB16. Region-level analyses identified 29 differentially methylated regions (DMRs) in India and 18 in The Gambia. 29 DMRs were identified in the meta-analysis, 25 of which were not detected in either cohort individually. Many DMRs were associated with more than one body composition trait.</p><p><strong>Conclusion: </strong>We report novel DNA methylation signatures associated with body composition traits in children from two low- and middle-income countries. Identified loci map to genes linked to inflammatory signalling, energy metabolism and cellular stress response pathways, highlighting a potential role for epigenetic mechanisms in shaping early-life body composition.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic entropy, socioeconomic differences, and health and lifespan in the Women's Health Initiative.","authors":"Khyobeni Mozhui, Athena Starlard-Davenport, Yangbo Sun, Aladdin H Shadyab, Ramon Casanova, Fridtjof Thomas, Robert B Wallace, Jay H Fowke, Karen C Johnson","doi":"10.1186/s13148-026-02180-3","DOIUrl":"10.1186/s13148-026-02180-3","url":null,"abstract":"<p><strong>Background: </strong>Aging is marked by changes in DNA methylation (DNAm) including an increase in randomness or entropy in the epigenome. Here, we computed epigenetic entropy using DNAm data from the Women's Health Initiative (WHI) ancillary study AS315 (n = 2192), and tested for replication in WHI ancillary studies, BA23 (n = 1989) and AS311 (n = 868). We investigated how different metrics of epigenetic stochasticity relate to demographic variables, health, and mortality risk, and how these compare to machine-learning based models of aging such as the DunedinPACE.</p><p><strong>Results: </strong>Epigenetic entropy had robust and consistent negative associations with income and education in the WHI. Notably, low income was related to increased stochasticity and higher methylation in DNA regions that are targeted by the polycomb proteins-key regulators of cellular memory and embryonic development. While higher income was associated with reduced entropy scores and lower DunedinPACE in White women, this effect of income was diminished in Black and Hispanic women, and on average, Black and Hispanic women had relatively higher stochastic variability. Painting a complex picture, our analysis of the polycomb regions in a small cohort of children showed significant positive associations with parental income. Additionally, in the WHI, higher DunedinPACE predicted higher mortality risk, while the maintenance of methylation at enhancer regions was associated with improved survival.</p><p><strong>Conclusions: </strong>These findings indicate close ties between social and economic factors and aspects of epigenetic aging, and highlight the polycomb targeted CpGs as potential sensors of the social environment and related exposures across demographic groups.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood DNA methylation of EIF5A and TGIF1 is associated with adipose tissue health and metabolic outcomes in obesity: a multi-cohort study.","authors":"Sophie Ruf, Anne Hoffmann, Luise Müller, Kathrin Landgraf, Mandy Vogel, Emil Jørsboe, Phil Kubitz, Arne Dietrich, Adhideb Ghosh, Falko Noé, Christian Wolfrum, Melina Claussnitzer, Hans Hauner, Michael Stumvoll, Ronny Baber, Matthias Blüher, Antje Körner, Peter Kovacs, Maria Keller","doi":"10.1186/s13148-026-02177-y","DOIUrl":"10.1186/s13148-026-02177-y","url":null,"abstract":"<p><strong>Background: </strong>Blood-based DNA methylation has been linked to obesity and metabolic health, yet its relationship to adipose tissue function remains incompletely understood. This study aimed to investigate the epigenetic regulation of EIF5A (Eukaryotic translation initiation factor 5A-1) and TGIF1 (TGFB Induced Factor Homeobox 1) across blood and adipose tissue in obesity.</p><p><strong>Methods: </strong>Candidate genes were identified using a multi-step gene selection approach integrating transcriptomic and epigenomic data from blood and adipose tissue samples obtained from children and adults across four diverse population- and disease-focused cohorts. Genes were prioritized based on differential DNA methylation and gene expression in obesity. Targeted bisulfite sequencing of EIF5A and TGIF1 was conducted in blood samples from adults across BMI-defined groups and from children prior to the development of obesity, to validate candidate loci and to examine associations with metabolic and adipocyte-related phenotypes.</p><p><strong>Results: </strong>In adults from the Leipzig Obesity BioBank, blood DNA methylation (N = 150) of both EIF5A and TGIF1 was significantly increased in individuals with obesity. EIF5A mRNA expression (N = 1554) was significantly higher in omental-visceral adipose tissue compared with subcutaneous adipose tissue. Blood DNA methylation of EIF5A was associated with body mass index (BMI), glycated hemoglobin (HbA1c), and leukocyte counts, particularly among individuals with type 2 diabetes mellitus. In children, blood DNA methylation (N = 75) of EIF5A was associated with longitudinal HbA1c trajectories. For TGIF1, DNA methylation levels were increased in subcutaneous adipose tissue (N = 219) of children with obesity and correlated with fasting serum insulin concentrations. Across cohorts, TGIF1 regulation in both blood and adipose tissue showed consistent associations with adipocyte size. Notably, blood DNA methylation of TGIF1 in childhood was associated with body fat mass and HbA1c at later follow-up despite normal weight at baseline.</p><p><strong>Conclusion: </strong>EIF5A and TGIF1 DNA methylation represent cross-tissue epigenetic signatures linking blood-based DNA methylation to adipose tissue dysfunction, adipocyte hypertrophy, and early metabolic risk. These findings support the potential of blood DNA methylation markers to reflect adipose tissue health and metabolic outcomes across the lifespan.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular-kidney-metabolic syndrome and risk of all-cause and cause-specific mortality among cancer survivors: a population-based cohort study.","authors":"Yumeng Liu, Zhongguang Yang, Yulin Yin","doi":"10.1186/s13148-026-02178-x","DOIUrl":"10.1186/s13148-026-02178-x","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interplay of metabolic dysfunction, chronic kidney disease (CKD), and cardiovascular disease (CVD). However, the prognostic implications of CKM syndrome stages in this population remain unclear.</p><p><strong>Methods: </strong>Data were drawn from the fasting subsample of NHANES III (1988-1994) and NHANES 1999-2018. A total of 2598 cancer survivors aged ≥ 20 years were included. Cox proportional hazards models accounting for the complex survey design were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>During a median follow-up of 7.92 years (IQR: 4.00-12.58), 1165 all-cause deaths, 352 CCD deaths, and 350 cancer deaths occurred. In fully adjusted models, compared with Stage 0, Stage 4 was associated with 3.48-fold higher all-cause mortality (HR = 3.48; 95% CI 2.62-4.63), 7.77-fold higher CCD mortality (HR = 7.77; 95% CI 4.21-14.32), and 2.55-fold higher cancer mortality (HR = 2.55; 95% CI 1.52-4.28). Advanced CKM syndrome was associated with elevated risks of all-cause, and cancer mortality. Sensitivity analyses confirmed the robustness of these findings.</p><p><strong>Conclusion: </strong>Advanced CKM syndrome is independently associated with increased risk of all-cause, cardiovascular, and cancer mortality among U.S. cancer survivors.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNAm landscape up to 4 months post SARS-CoV-2 infection: insights from four population-based cohorts.","authors":"Pamela R Matías-García, Liye Lai, Thomas Delerue, Jochen Ohnmacht, Klaus J Stark, Robert Warmerdam, Alexey Kolodkin, Julia Six-Merker, Nina Mangold, Kathrin Günther, Marc P O'Sullivan, Armin Rauschenberger, Barbara Bohn, Klaus Berger, Julia Fricke, Peter Ahnert, Lude Franke, Rejko Krüger, Olaf Gefeller, Klaus Überla, Iris M Heid, Ralf Wagner, Melanie Waldenberger, Annette Peters","doi":"10.1186/s13148-026-02166-1","DOIUrl":"10.1186/s13148-026-02166-1","url":null,"abstract":"<p><strong>Background: </strong>Evidence for persistent epigenetic changes in individuals who had a mild SARS-CoV-2 infection is limited, as most DNA methylation (DNAm) studies to date have focused on either the acute phase of infection or on the months following infection in severe cases requiring hospitalization.</p><p><strong>Methods and results: </strong>Using the Infinium Human MethylationEPIC BeadChip, we investigated blood DNA methylation (DNAm) up to four months after SARS-CoV-2 infection in cases and controls from four population-based cohorts (NAKO, Lifelines, CON-VINCE, and TiKoCo; n = 675) within the framework of the ORCHESTRA Consortium. We observed DNAm changes at 16 differentially methylated positions (DMPs) and 21 differentially methylated regions (DMRs), with 89% of these DMPs/DMRs hypomethylated in cases compared to age- and sex-matched controls. Genes mapped to these CpGs were annotated with Gene Ontology terms and pathways related to immune responses to viral infection. eQTM analyses in whole blood from an independent cohort (KORA FF4 study) produced 49 significant CpG-transcript pairs, including IFI44L and GNA12. Despite inter-individual variability and cohort heterogeneity, our findings regarding four DMPs (IFI44L, MX1, DDX60, and RABGAP1L) and two DMRs (PARP9 and GNA12) replicate changes described both in the acute phase of infection and at long-term follow-up. Differential methylation at other novel loci may reflect the systemic nature of post-infection epigenetic changes.</p><p><strong>Conclusion: </strong>Our findings suggest moderate but persistent epigenetic changes up to four months after SARS-CoV-2 infection in mild cases from population-based cohorts. These changes partially mirror those reported during the acute phase of both mild and severe COVID-19 and overlap with pathways dysregulated in autoimmune, metabolic and neurological disease. Future research should examine epigenetic changes associated with persisting symptoms in long COVID, investigate downstream effects of DNAm changes on other -omics, and consider longer follow-up periods to further elucidate the molecular mechanisms underlying SARS-CoV-2 induced epigenetic changes.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Chromatinopathies: clinically overlapping disorders, revealing novel variants and their DNA methylation signatures.","authors":"Asuman Koparir, Jennifer Kerkhof, Jessica Rzasa, Eva Metzger, Paulina Bahena Carbajal, Konstantinos Kolokotronis, Erkan Koparir, Yvonne Jelting, Michaela A H Hofrichter, Jörg Klepper, Thomas König, Eva Runkel, Wahyu Eka Prastyo, Jonas Deinlein, Neda Dragicevic Babic, Juliane Spiegler, Nicole Stachelscheid, Erdmute Kunstmann, Thomas Haaf, Bekim Sadikovic, Eva Klopocki","doi":"10.1186/s13148-026-02173-2","DOIUrl":"10.1186/s13148-026-02173-2","url":null,"abstract":"","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRONDEX: a web-based platform for exploring links between chromatin-related genes and neurodevelopmental disorders.","authors":"Javier Guerrero-Flores, Bárbara S Viegas, Marian A Martínez-Balbás, Xavier de la Cruz","doi":"10.1186/s13148-026-02176-z","DOIUrl":"10.1186/s13148-026-02176-z","url":null,"abstract":"<p><strong>Background: </strong>Chromatin regulatory genes are essential for orchestrating neurodevelopment by controlling DNA accessibility and the expression of genes required for neuronal differentiation and maturation. Mutations affecting these regulators-including histone modifiers, chromatin remodelers, and chromatin-binding factors-are a major cause of neurodevelopmental disorders (NDDs), many of which display overlapping yet mechanistically heterogeneous clinical features. As the catalogue of chromatin-related NDD genes has expanded, so too has the availability of phenotypic, functional, and pathway annotations. However, these data remain dispersed across multiple resources, making it difficult to integrate them in order to systematically compare genes or explore shared mechanisms. Existing platforms such as the Human Phenotype Ontology and the Monarch Initiative offer powerful phenotype-gene mapping tools, but they operate across the full genomic space and do not provide the focused framework needed to examine chromatin-related NDD genes as a coherent group.</p><p><strong>Results: </strong>We present CRONDEX (ChROmatin and NeuroDevelopmental disorder-related genes EXploratory platform), a user-friendly web resource developed to meet this need by supporting integrative exploration of relationships among chromatin-related genes implicated in NDDs. The database was constructed by intersecting curated chromatin (EpiFactors) and neurodevelopmental (SysNDD+Orphanet+SFARI+NDD-GeneHub) gene sets while excluding transcription factors, and enriched with annotations from Gene Ontology, KEGG, and the Human Phenotype Ontology. CRONDEX provides two complementary query modes: (i) a Gene-Based Query, which identifies genes with phenotypic profiles similar to a user-defined target using Jaccard similarity metrics; and (ii) a Criteria-Based Query, which retrieves genes matching specific phenotypic, functional, or pathway filters. Through representative examples, we show how the Gene-Based Query recovers biologically coherent relationships-from paralogous pairs such as CREBBP-EP300 to functionally convergent modules like the BAFopathies-while the Criteria-Based Query enables hypothesis-driven exploration, exemplified by the intersection of thermogenesis and chromatin-related NDDs, and by chromatin-binding genes linked to status epilepticus. By enabling rapid, integrative, and hypothesis-oriented analyses, CRONDEX facilitates the discovery of shared mechanisms across chromatin-related NDDs and supports both basic and translational research. The platform is freely accessible at https://jgf-bioinfo.shinyapps.io/CRONDEX/ .</p><p><strong>Conclusion: </strong>CRONDEX provides a domain-focused platform that enables phenotype-guided exploration of chromatin-related genes, supporting mechanistic hypothesis generation in NDDs.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic vulnerability in endocrine disruption: bridging mechanisms, models, and environmental inequities.","authors":"Fernando Lizcano, María Camila Ramírez-Bohorquez, María Camila Ballesteros-Garcia, Valentina Vargas, Sebastián Cardenas","doi":"10.1186/s13148-026-02158-1","DOIUrl":"10.1186/s13148-026-02158-1","url":null,"abstract":"<p><p>This narrative mini-review examines how endocrine-disrupting chemicals (EDCs) induce persistent epigenetic alterations that shape endocrine, metabolic, and developmental trajectories across the lifespan. It addresses the emerging gap in integrating mechanistic epigenetic evidence with population-level vulnerability, particularly in underrepresented regions such as Latin America. These effects are especially critical during sensitive windows-including fetal development, childhood, and puberty-when DNA methylation, histone modifications, and non-coding RNA networks establish long-term molecular programming. While animal models have provided key mechanistic insights, their translational limitations highlight the need for human-relevant systems capable of capturing endocrine-specific and epigenetic endpoints under environmentally realistic conditions. We propose that epigenetic programming represents a central biological interface linking EDC exposure to context-dependent vulnerability. New Approach Methodologies (NAMs)-including organoids, micro-physiological systems, and computational models-offer a translational bridge aligned with Adverse Outcome Pathway frameworks. Importantly, susceptibility to endocrine disruption is shaped not only by biological factors but also by environmental, nutritional, and socioeconomic determinants. Evidence from Latin American populations-including altitude gradients, nutritional transitions, and structural inequalities-illustrates how these contextual factors interact with epigenetic mechanisms to influence metabolic and endocrine outcomes. This integrative perspective supports the development of more equitable and context-sensitive approaches to endocrine toxicology.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13465674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}