Rameen Asif, Ruihan Liu, Russell J de Souza, Sandi Azab, Michael Chong, Sonia S Anand, Wei Q Deng
{"title":"A Scoping Review of Epigenetic Signatures of Diet and Diet-related Metabolites: Insights from Epigenome-Wide Association Studies and Their Implications for Cardiometabolic Health and Diseases.","authors":"Rameen Asif, Ruihan Liu, Russell J de Souza, Sandi Azab, Michael Chong, Sonia S Anand, Wei Q Deng","doi":"10.59249/BDGN2070","DOIUrl":"10.59249/BDGN2070","url":null,"abstract":"<p><p>Epigenome-wide association studies (EWASs) have emerged as a powerful approach to investigate how dietary exposures shape the epigenome and subsequently influence metabolic and cardiovascular health. A growing number of EWAS have examined the effects of various dietary factors, including overall dietary patterns, specific food groups, micronutrients, and food-related metabolites, on DNA methylation (DNAm) across diverse populations. In this review, we map the landscape of nutritional EWAS, identifying the types of dietary exposures studied, the genomic regions where epigenetic signals emerge, and overarching trends across studies. Across studies, consistent associations were reported at nine CpG sites in genes such as <i>AHRR</i>, <i>CPT1A</i>, and <i>FADS2</i>, particularly in relation to fatty acid consumption, and certain diet patterns. Biological pathways enriched included fatty acid metabolism and the PPAR signaling pathway. In conclusion, our review identified a pattern of epigenetic convergence that may underlie diet-related disease risk. While promising, key knowledge gaps were also noted, including limited longitudinal follow-up, unclear causal pathways, and underrepresentation of ethnic diversity. Moving forward, we highlighted several complementary approaches for translating nutritional EWAS findings into actionable public health and precision nutrition strategies, including integrating multi-omics, mediation analyses, and population-wide epigenetic risk profiling.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"203-225"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Khyobeni Mozhui, Beck A Henriksen, Lauren A Bell, Ingrid Bretherton, Ada S Cheung, Boris Novakovic
{"title":"Tracking Epigenetic Biomarkers of Health and Aging During the Initial Year of Gender-Affirming Hormone Therapy.","authors":"Khyobeni Mozhui, Beck A Henriksen, Lauren A Bell, Ingrid Bretherton, Ada S Cheung, Boris Novakovic","doi":"10.59249/XMGO7523","DOIUrl":"10.59249/XMGO7523","url":null,"abstract":"<p><p>Gender-affirming hormone therapy (GAHT) is a necessary treatment for many transgender people, and there is a critical need to further improve treatment experience and mitigate possible risks. Here we investigated whether DNA methylation (DNAm) biomarkers of health and aging are modified during the first year of GAHT and whether these vary by treatment type. Cohort consisted of 13 trans women (TW) and 13 trans men (TM). Sampling occurred at baseline (pre-GAHT), and at 6- and 12-month follow-up. We tracked the longitudinal dynamics of three epigenetic clocks (Horvath, Hannum, PhenoAge), DNA methylation-based telomere length (DNAmTL), and DunedinPACE. At baseline, the Horvath and Hannum showed accelerated epigenetic aging, particularly pronounced among TM, while the PhenoAge and DunedinPACE showed lower pace of aging in both groups. This discrepancy may reflect possible effects of minority stress in an otherwise healthy cohort. While GAHT did not affect the three clocks, DNAmTL and DunedinPACE showed treatment-specific patterns but with notable inter-individual variability in trajectories. TW had increased DunedinPACE (estimate = 0.057, p=0.002) and slight DNAmTL gains (estimate = 0.024, ns); TM exhibited stable to slight decline in DunedinPACE (estimate = -0.013, ns), and reduction in DNAmTL (estimate = -0.057, p=0.037). The marked heterogeneity is indicative of an individualized response to treatment and highlights the potential value of incorporating such biomarkers in comprehensive health monitoring. Our findings emphasize the need for larger, long-term studies to optimize personalized strategies for gender-affirming healthcare.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"105-115"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transgenerational Transmission of Epigenetic Marks During Reproduction in <i>Arabidopsis</i>.","authors":"Jong-Joo Cheong","doi":"10.59249/EWLZ5537","DOIUrl":"10.59249/EWLZ5537","url":null,"abstract":"<p><p>Epigenetics has described non-DNA sequence-based transgenerational inheritance, in which phenotypic traits acquired over a lifetime by parents are passed to their progeny across several generations. Transgenerational epigenetic inheritance may be achieved by transmitting repressive epigenetic marks such as DNA methylation and histone 3 lysine 27 trimethylation (H3K27me3) in parental chromatin through sexual reproduction. In general, with infrequent exceptions, epigenetically modified architectures in parental chromatin are extensively erased by reprogramming during reproduction, leaving little possibility of being inherited by offspring. In comparison, plants exhibit transgenerational epigenetic inheritance with relatively greater frequency, although the underlying molecular mechanisms have remained unclear. Recent studies with the flowering plant <i>Arabidopsis</i> (<i>Arabidopsis thaliana</i>) have identified plant-specific mechanisms enabling the transgenerational transmission of epigenetic marks during reproduction. <i>Arabidopsis</i> achieves <i>de novo</i> chromatin methylation through the small interfering RNA (siRNA)-directed DNA methylation (RdDM) pathways. In addition, Polycomb repressive complex 2 (PRC2) catalyzes H3K27me3 deposition on exchangeable histone variants during reproduction in a plant-specific manner. This review describes recent progress in <i>Arabidopsis</i> research of transgenerational epigenetic inheritance, focusing on transmitting epigenetic marks through reproduction steps: meiosis, gametogenesis, and embryogenesis.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"245-251"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Usama Ahmad, Anas Islam, Mohd Muazzam Khan, Juber Akhtar
{"title":"Nanotechnology-driven Epigenetic Cancer Therapy: Precision Delivery and Sustained Release of DNA Methylation Modulators.","authors":"Usama Ahmad, Anas Islam, Mohd Muazzam Khan, Juber Akhtar","doi":"10.59249/GVNM8843","DOIUrl":"10.59249/GVNM8843","url":null,"abstract":"<p><p>Aberrant DNA methylation contributes to cancer by silencing tumor suppressor genes and facilitating tumor growth. DNA methyltransferase inhibitors (DNMTis), including 5-azacytidine (5-AZA) and decitabine (DAC), can potentially mitigate these consequences and revive gene expression. Their therapeutic effectiveness is hindered by factors like poor bioavailability, swift degradation, and unintended toxicity. Advances in nanotechnology enable targeted DNMTi delivery, enhancing efficacy while minimizing toxicity. This mini-review explores several key types of nanoformulations for DNMTi delivery, including PLGA nanoparticles, liposomes, solid lipid nanoparticles (SLNs), bentonite-based nanoparticles, gold nanoparticles (AuNPs), amphiphilic prodrugs, PEGylated nanoparticles, bionic nanoparticles, gelatinase-sensitive nanoparticles, and chitosan-based pH-responsive systems. This paper emphasizes the integration of epigenetic therapies and nanotechnology in oncology, focusing on the creation of nanocarriers for precise delivery of methylation modulators and new formulations for prolonged drug release. By addressing these advancements, the review underscores the potential of nanotechnology to revolutionize epigenetic cancer therapy, offering new hope for improved patient outcomes in precision oncology.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"227-235"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jatniel E Servian, Brianna Brady, Pritam Biswas, T K Sukumar, Stephanie E King
{"title":"Pharmacoepigenetic Biomarkers in Inflammatory Bowel Diseases: A Narrative Review.","authors":"Jatniel E Servian, Brianna Brady, Pritam Biswas, T K Sukumar, Stephanie E King","doi":"10.59249/FTXB7704","DOIUrl":"10.59249/FTXB7704","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic, autoimmune disorder characterized by inflammation along the gastrointestinal tract. Global prevalence of the disease is increasing and patients often experience delays in diagnosis accessing effective therapy, highlighting an urgent need to develop a predictive biomarker for therapeutic response to reduce healthcare costs and disease burdens. Despite the advances to identifying genetic biomarkers for prediction of disease remission in IBD, patient responses vary widely, suggesting that inherited genetic variations alone cannot account for these differences. As autoimmune diseases like IBD are largely environmental in etiology, epigenetic modifications like DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) also have the potential to be candidates for predictive biomarkers of patient disease development and treatment response. This review will explore the novel field of pharmacoepigenetics and the development of predictive epigenetic biomarkers for treatment response in IBD, highlighting new research in the field. While research is still in the early stages, the studies reviewed have demonstrated that epigenetic profiling can be utilized to predict treatment response in IBD patients. Additional pharmacoepigenetic cohorts with more diverse participants could help enhance current models, improving predictability of treatment response and clinical outcomes. As research in this field progresses, epigenetic biomarkers should be integrated into the clinical environment to expedite diagnosis, reduce trial-and-error approach to treatment, and lay the foundations for individualized therapeutic strategies for IBD patients.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"171-186"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epigenetics Through Generations and Across Phylogenies: An Interview with Dr. Bluma Lesch.","authors":"Reem Abu-Shamma, Andriana Marijic Buljubasic","doi":"10.59249/IIUD8470","DOIUrl":"10.59249/IIUD8470","url":null,"abstract":"","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"253-256"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"miRNAs and T cell-mediated Immune Response in Disease.","authors":"Paul Holvoet","doi":"10.59249/PAYJ6872","DOIUrl":"10.59249/PAYJ6872","url":null,"abstract":"<p><p>We reviewed the role of miRNAs in the regulation of T cell differentiation and function in cardiometabolic inflammatory diseases, such as obesity, type 2 diabetes, atherosclerosis, and autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, asthma, and cancer. Cardiometabolic diseases, type 1 diabetes, and rheumatoid arthritis are characterized by miRNA expression profiles that favor the differentiation of T helper 1 and 17 cells and cytotoxic cells and a decrease in T helper 2 cells, regulatory T cells, and myeloid-derived suppressor cells. Asthma is characterized by changes in miRNAs that favor the differentiation of T helper 2 cells. Finally, cancer is characterized by miRNA profiles that cause a decrease in T helper 1 and 17 cells and cytotoxic cells and an increase in T helper 2 cells, regulatory T cells, and myeloid-derived suppressor cells. In particular, differences in the expression of miR-155 and a cluster containing Let-7, miR-10a, miR-17-92, miR-34a, miR-142, and miR-150 may determine whether the balance flips towards cytotoxicity or immunosuppression. High levels of miR-21 and miR-29 and low levels of miR-150 are associated with T cell profiles that protect against inflammatory and autoimmune diseases associated with tissue damage but also induce tumor growth. All these miRNAs were found to be associated with disease progression and/or response to therapy in one or more of the diseases under study. Therefore, studies on the value of the identified miRNA clusters in predicting disease progression and selecting therapies that may yield gains in treatment costs are warranted.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"187-202"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kinase Signaling: An Interview with Dr. Adriana Kahn.","authors":"Rahul Gupta","doi":"10.59249/BTHB2229","DOIUrl":"10.59249/BTHB2229","url":null,"abstract":"","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 1","pages":"69-75"},"PeriodicalIF":2.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rodrigo Guedes Hakime, Luís Fernando Peinado Nagano, María Sol Brassesco
{"title":"ROCK2 Downregulation in Pediatric Medulloblastoma Increases Migration and Predicts the Involvement of SHH Non-canonical Signaling.","authors":"Rodrigo Guedes Hakime, Luís Fernando Peinado Nagano, María Sol Brassesco","doi":"10.59249/QTVT7676","DOIUrl":"10.59249/QTVT7676","url":null,"abstract":"<p><p>The participation of the Rho-associated protein kinases (ROCK1 and 2) in the regulation of actin cytoskeleton organization, cell adhesion, motility, and gene expression has been extensively investigated in many tumors of different histology. However, their pathogenic roles in medulloblastoma (MB) remain understudied, demanding a deeper appreciation of their participation in cancer cell dissemination and tumor progression. Herein, we show that <i>ROCK2</i> is downregulated in MB tumor samples and functionally increases migration of cell lines belonging to the SHH subgroup. A comprehensive comparative bioinformatic scrutiny of differentially expressed genes within a list of ROCK2 candidate substrates, uncovered a network of 21 dysregulated genes from which <i>DYPSL3</i> (dihydropyrimidinase-related protein 3) denoted a strong positive correlation. Enrichment analysis revealed SHH/RHOA/ROCK2/DYPSL3 as top hub genes and the intersection between two biological processes of most importance in MB: actin cytoskeleton remodeling and neuron development. Of note, evidence shows that both ROCK2 and DYPSL3, interact with RHOA and in many tumor types they act as tumor suppressors, mitigating cell spreading. Alternatively, their impaired activity leads to undifferentiated phenotypes and inappropriate cytoskeletal dynamics affecting cell shape, attachment to the extracellular matrix, and cell movement. In parallel, cell motility is considered a prototypical non-canonical response to SHH mediated by RHOA. Therefore, we propose a model in which the interplay between these pathways may lead to a perturbation of proper cytoskeletal dynamics that underpins cell migration.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 1","pages":"3-19"},"PeriodicalIF":2.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of p16 and NF-κB Oncogenic Activity in Human Papillomavirus-Infected Cervical Cancer Cells: A New Role for Activating Transcription Factor-3.","authors":"Zahra Bagheri, Haniyeh Abuei, Alireza Jaafari, Shayan Taki, Amirhossein Akbarpour Arsanjani, Ali Farhadi","doi":"10.59249/XCAB1680","DOIUrl":"10.59249/XCAB1680","url":null,"abstract":"<p><p><b>Objective</b>: Activating transcription factor 3 (ATF3) has attracted recent scientific attention as a novel mediator of tumor suppression, particularly within the context of cervical cancer (CC). Our prior research demonstrated that ATF3 overexpression induces cell cycle arrest and apoptosis in human papillomavirus (HPV)16- and HPV18-positive CC cells. The present study aims to examine the impact of ATF3 overexpression on the expression levels of p16 and NF-κB, two proteins with pro-tumorigenic roles in HPV-induced CC. <b>Methods</b>: Ca Ski and HeLa cells underwent transfection with pCMV6-AC-IRES-GFP plasmids containing the <i>ATF3</i> gene. To establish the optimal plasmid DNA quantities for transfection, MTT assay was conducted. Furthermore, fluorescence microscopy and flow cytometric analysis were employed to assess the efficiency of transfection. The expression levels of p16 and NF-κB were evaluated by RT-qPCR and western blotting prior and subsequent to ATF3 overexpression. <b>Results</b>: The overexpression of ATF3 induced a decrease in <i>p16</i> mRNA levels in both Ca Ski and HeLa cells (p<0.04), along with the concomitant reduction of p16 protein expression within both cellular populations (p<0.005). Additionally, it led to a reduction in NF-κB p65 protein levels in both cell lines (p<0.005), with no discernible impact on its mRNA expression. <b>Conclusion</b>: Given ATF3's demonstrated capability to downregulate p16 and NF-κB, both of which play important pro-tumorigenic roles in HPV-related CC, ATF3 emerges as a promising therapeutic candidate with the potential for application in the treatment of CC.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 1","pages":"21-32"},"PeriodicalIF":2.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}