IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-03-04 DOI: 10.1080/15592294.2025.2471127

Mark Hieromnimon, Daniel P Regan, R Peter Lokken, Lawrence B Schook, Ron C Gaba, Kyle M Schachtschneider

{"title":"Single and multi-omic characterization of a porcine model of ethanol-induced hepatic fibrosis.","authors":"Mark Hieromnimon, Daniel P Regan, R Peter Lokken, Lawrence B Schook, Ron C Gaba, Kyle M Schachtschneider","doi":"10.1080/15592294.2025.2471127","DOIUrl":"10.1080/15592294.2025.2471127","url":null,"abstract":"Cirrhosis is a form of end-stage liver disease characterized by extensive hepatic fibrosis and loss of liver parenchyma. It is most commonly the result of long-term alcohol abuse in the United States. Large animal models of cirrhosis, as well as of one of its common long-term sequelae, HCC, are needed to study novel and emerging therapeutic interventions. In the present study, liver fibrosis was induced in the Oncopig cancer model, a large animal HCC model, via intrahepatic, intra-arterial ethanol infusion. Liver sections from five fibrosis induced and five age-matched controls were harvested for RNA-seq (mRNA and lncRNA), small RNA-seq (miRNA), and reduced representation bisulfite sequencing (RRBS; DNA methylation). Single- and multi-omic analysis was performed to investigate the transcriptomic and epigenomic mechanisms associated with fibrosis deposition in this model. A total of 3,439 genes, 70 miRNAs, 452 lncRNAs, and 7,715 methylation regions were found to be differentially regulated through individual single-omic analysis. Pathway analysis indicated differentially expressed genes were associated with collagen synthesis and turnover, hepatic metabolic functions such as ethanol and lipid metabolism, and proliferative and anti-proliferative pathways including PI3K and BAX/BCL signaling pathways. Multi-omic latent variable analysis demonstrated significant concordance with the single-omic analysis. lncRNA's associated with UHRF1BP1L and S1PR1 genes were found to reliably discriminate the two arms of the study. These genes were previously implicated in human cancer development and vasculogenesis, respectively. These findings support the validity and translatability of this model as a useful preclinical tool in the study of alcoholic liver disease and its treatment.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2471127"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MSC-mediated mitochondrial transfer promotes metabolic reprograming in endothelial cells and vascular regeneration in ARDS. 间质干细胞介导的线粒体转移促进ARDS内皮细胞的代谢重编程和血管再生。

IF 5.2 2区生物学

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-03-13 DOI: 10.1080/13510002.2025.2474897

Jinlong Wang, Shanshan Meng, Yixuan Chen, Haofei Wang, Wenhan Hu, Shuai Liu, Lili Huang, Jingyuan Xu, Qing Li, Xiaojing Wu, Wei Huang, Yingzi Huang

{"title":"MSC-mediated mitochondrial transfer promotes metabolic reprograming in endothelial cells and vascular regeneration in ARDS.","authors":"Jinlong Wang, Shanshan Meng, Yixuan Chen, Haofei Wang, Wenhan Hu, Shuai Liu, Lili Huang, Jingyuan Xu, Qing Li, Xiaojing Wu, Wei Huang, Yingzi Huang","doi":"10.1080/13510002.2025.2474897","DOIUrl":"10.1080/13510002.2025.2474897","url":null,"abstract":"Background: Mesenchymal stem cells (MSCs) are a potential therapy for acute respiratory distress syndrome (ARDS), but their mechanisms in repairing mitochondrial damage in ARDS endothelial cells remain unclear.Methods: We first examined MSCs' mitochondrial transfer ability and mechanisms to mouse pulmonary microvascular endothelial cells (MPMECs) in ARDS. Then, we investigated how MSC-mediated mitochondrial transfer affects the repair of endothelial damage. Finally, we elucidated the mechanisms by which MSC-mediated mitochondrial transfer promotes vascular regeneration.Results: Compared to mitochondrial-damaged MSCs, normal MSCs showed a significantly higher mitochondrial transfer rate to MPMECs, with increases of 41.68% in vitro (P < 0.0001) and 10.50% in vivo (P = 0.0005). Furthermore, MSC-mediated mitochondrial transfer significantly reduced reactive oxygen species (P < 0.05) and promoted proliferation (P < 0.0001) in MPMECs. Finally, MSC-mediated mitochondrial transfer significantly increased the activity of the tricarboxylic acid (TCA) cycle (MD of CS mRNA: 23.76, P = 0.032), and further enhanced fatty acid synthesis (MD of FAS mRNA: 6.67, P = 0.0001), leading to a 6.7-fold increase in vascular endothelial growth factor release from MPMECs and promoted vascular regeneration in ARDS.Conclusion: MSC-mediated mitochondrial transfer to MPMECs activates the TCA cycle and fatty acid synthesis, promoting endothelial proliferation and pro-angiogenic factor release, thereby enhancing vascular regeneration in ARDS.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2474897"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioinformatics analysis identifies key secretory protein-encoding differentially expressed genes in adipose tissue of metabolic syndrome. 生物信息学分析鉴定代谢综合征脂肪组织中关键分泌蛋白编码差异表达基因。

IF 3.5 4区生物学

Adipocyte Pub Date : 2025-12-01 Epub Date: 2025-01-16 DOI: 10.1080/21623945.2024.2446243

Jiandong Zhou, Yunshan Guo, Xuan Liu, Weijie Yuan

{"title":"Bioinformatics analysis identifies key secretory protein-encoding differentially expressed genes in adipose tissue of metabolic syndrome.","authors":"Jiandong Zhou, Yunshan Guo, Xuan Liu, Weijie Yuan","doi":"10.1080/21623945.2024.2446243","DOIUrl":"10.1080/21623945.2024.2446243","url":null,"abstract":"The objective of this study was to identify key secretory protein-encoding differentially expressed genes (SP-DEGs) in adipose tissue in female metabolic syndrome, thus detecting potential targets in treatment. We examined gene expression profiles in 8 women with metabolic syndrome and 7 healthy, normal body weight women. A total of 143 SP-DEGs were screened, including 83 upregulated genes and 60 downregulated genes. GO analyses of these SP-DEGs included proteolysis, angiogenesis, positive regulation of endothelial cell proliferation, immune response, protein processing, positive regulation of neuroblast proliferation, cell adhesion and ER to Golgi vesicle-mediated transport. KEGG pathway analysis of the SP-DEGs were involved in the TGF-beta signalling pathway, cytokine‒cytokine receptor interactions, the hippo signalling pathway, Malaria. Two modules were identified from the PPI network, namely, Module 1 (DNMT1, KDM1A, NCoR1, and E2F1) and Module 2 (IL-7 R, IL-12A, and CSF3). The gene DNMT1 was shared between the network modules and the WGCNA brown module. According to the single-gene GSEA results, DNMT1 was significantly positively correlated with histidine metabolism and phenylalanine metabolism. This study identified 7 key SP-DEGs in adipose tissue. DNMT1 was selected as the central gene in the development of metabolic syndrome and might be a potential therapeutic target.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2446243"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca²⁺/AMPK pathway. 鱼藤酮通过ROS/Ca2+/AMPK通路调节ZO-2的表达和定位，从而抑制骨肉瘤转移。

IF 5.2 2区生物学

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-04-17 DOI: 10.1080/13510002.2025.2493556

Xiang Ma, Zhen Li, Hengwei Ma, Kun Jiang, Bao Chen, Weiquan Wang, Ziqiang Zhu, Jianqiang Wang, Zuozhang Yang, Wang Yunqing, Suwei Dong

{"title":"Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathway.","authors":"Xiang Ma, Zhen Li, Hengwei Ma, Kun Jiang, Bao Chen, Weiquan Wang, Ziqiang Zhu, Jianqiang Wang, Zuozhang Yang, Wang Yunqing, Suwei Dong","doi":"10.1080/13510002.2025.2493556","DOIUrl":"https://doi.org/10.1080/13510002.2025.2493556","url":null,"abstract":"Background: Pulmonary metastases in osteosarcoma (OS) are associated with a poor prognosis. Rotenone has shown anti-cancer activity. However, its effects on metastasis and the underlying mechanisms remain unknown. This study investigated the potential use of Rotenone for OS treatment.Methods: The effect of Rotenone and ROS/Ca2+/AMPK/ZO-2 pathway on metastasis and EMT was evaluated by Western blot, Transwell and Wound healing. Flow cytometer was employed to measure the intracellular Ros and Ca2+ levels. The subcellular location of ZO-2 was detected by IF, interaction between AMPK and ZO-2 were examined by Co-IP. Then, subcutaneous tumor and metastasis models were used to evaluate the function of Rotenone in OS metastasis.Results: Rotenone-induced ROS led to increased intracellular Ca2+, which promoted the EMT of OS cells through activation of AMPK and ZO-2 nuclear translocation. Inhibition of ROS production decreased intracellular Ca2+, restraining AMPK activity. Knock-down of ZO-2 significantly suppressed the anti-metastasis effects of Rotenone in OS cells. Moreover, Rotenone elevated p-AMPK and ZO-2 expression but inhibited EMT and lung metastasis in vivo.Conclusion These results provide evidence supporting an anti-metastatic effect of Rotenone. These findings support the use of Rotenone in the prevention of OS metastasis.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2493556"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miR-6402 targets Bmpr2 and negatively regulates mouse adipogenesis. miR-6402靶向Bmpr2，负调控小鼠脂肪生成。

IF 3.5 4区生物学

Adipocyte Pub Date : 2025-12-01 Epub Date: 2025-03-03 DOI: 10.1080/21623945.2025.2474114

Malaz Elsheikh, Tomomi Sano, Akiko Mizokami, Yusuke Nakatsu, Tomoichiro Asano, Takashi Kanematsu

{"title":"miR-6402 targets Bmpr2 and negatively regulates mouse adipogenesis.","authors":"Malaz Elsheikh, Tomomi Sano, Akiko Mizokami, Yusuke Nakatsu, Tomoichiro Asano, Takashi Kanematsu","doi":"10.1080/21623945.2025.2474114","DOIUrl":"10.1080/21623945.2025.2474114","url":null,"abstract":"Obesity is characterized by macrophage infiltration into adipose tissue. White adipose tissue remodelling under inflammatory conditions involves both hypertrophy and adipogenesis and is regulated by transcription factors, which are influenced by bone morphogenetic protein (BMP) signalling. MicroRNAs (miRNAs) regulate gene expression and are involved in obesity-related processes such as adipogenesis. Therefore, we identified differentially expressed miRNAs in the epididymal white adipose tissue (eWAT) of mice fed a normal diet (ND) and those fed a high-fat diet (HFD). The expression of miR-6402 was significantly suppressed in the inflamed eWAT of HFD-fed mice than in ND-fed mice. Furthermore, Bmpr2, the receptor for BMP4, was identified as a target gene of miR-6402. Consistently, miR-6402 was downregulated in the inflamed eWAT of HFD-fed mice and in 3T3-L1 cells (preadipocytes) and differentiated 3T3-L1 cells (mature adipocytes) , and BMPR2 expression in these cells was upregulated. Adipogenesis was induced in WAT by BMP4 injection (in vivo) and in 3T3-L1 cells by BMP4 stimulation (in vitro), both of which were inhibited by miR-6402 transfection. Inflamed eWAT showed higher expression of BMPR2 and the adipogenesis markers C/EBPβ and PPARγ, which was suppressed by miR-6402 transfection. Our findings suggest that miR-6402 is a novel anti-adipogenic miRNA that combats obesity by inhibiting the BMP4/BMPR2 signalling pathway and subsequently reducing adipose tissue expansion.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2474114"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines. α -亚麻酸介导的宫颈癌细胞系表观遗传重编程。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-02 DOI: 10.1080/15592294.2025.2451551

Amrita Ulhe, Prerna Raina, Amol Chaudhary, Ruchika Kaul-Ghanekar

{"title":"Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines.","authors":"Amrita Ulhe, Prerna Raina, Amol Chaudhary, Ruchika Kaul-Ghanekar","doi":"10.1080/15592294.2025.2451551","DOIUrl":"10.1080/15592294.2025.2451551","url":null,"abstract":"Cervical cancer, the fourth most common cancer globally and the second most prevalent cancer among women in India, is primarily caused by Human Papilloma Virus (HPV). The association of diet with cancer etiology and prevention has been well established and nutrition has been shown to regulate cancer through modulation of epigenetic markers. Dietary fatty acids, especially omega-3, reduce the risk of cancer by preventing or reversing the progression through a variety of cellular targets, including epigenetic regulation. In this work, we have evaluated the potential of ALA (α linolenic acid), an ω-3 fatty acid, to regulate cervical cancer through epigenetic mechanisms. The effect of ALA was evaluated on the regulation of histone deacetylases1, DNA methyltransferases 1, and 3b, and global DNA methylation by ELISA. RT-PCR was utilized to assess the expression of tumor regulatory genes (hTERT, DAPK, RARβ, and CDH1) and their promoter methylation in HeLa (HPV18-positive), SiHa (HPV16-positive) and C33a (HPV-negative) cervical cancer cell lines. ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines. ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines. ALA reduced methylation in the 5' CpG island of CDH1, RARβ, and DAPK1 promoters and reduced global DNA methylation in cervical cancer cell lines. These results suggest that ALA regulates the growth of cervical cancer cells by targeting epigenetic markers, shedding light on its potential therapeutic role in cervical cancer management.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2451551"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circular RNA Circ_0002762 promotes cell migration and invasion in cervical squamous cell carcinoma via activating RelA/nuclear factor kappa B (Nf-kB) signalling pathway. 环状RNA Circ_0002762通过激活RelA/核因子κ B （nf-kB）信号通路促进宫颈鳞状细胞癌的细胞迁移和侵袭。

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-03-24 DOI: 10.1080/15476286.2025.2478539

Lei Ji, Youguo Chen, Xiaoping Chen

{"title":"Circular RNA Circ_0002762 promotes cell migration and invasion in cervical squamous cell carcinoma via activating RelA/nuclear factor kappa B (Nf-kB) signalling pathway.","authors":"Lei Ji, Youguo Chen, Xiaoping Chen","doi":"10.1080/15476286.2025.2478539","DOIUrl":"10.1080/15476286.2025.2478539","url":null,"abstract":"Cervical cancer is a leading cause of cancer-related deaths, with cervical squamous cell carcinoma (CSCC) accounting for a majority of cases. Circular RNAs (circRNAs) have been repeatedly suggested as crucial effectors in modulating the development of multiple malignancies. The expression of circ_0002762 was predicted to be high in CSCC tissues in GEO dataset, but the functional role and underlying regulatory mechanism of circ_0002762 in CSCC was unclear. By series of functional assays and mechanism assays, supported by bioinformatics analysis, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis and western blot assays, we identified that circ_0002762 aberrantly up-regulated in CSCC, promoting CSCC cell migration and invasion. Mechanically, circ_0002762 was transcriptionally activated by Fork head box A1 (FOXA1). Moreover, the involvement of nuclear factor kappa B (NF-kB) signalling in circ_0002762 regulation mechanism in CSCC cells was ascertained. Additionally, circ_0002762, predominantly accumulated in cell cytoplasm, was proved to recruit Mov10 RISC complex RNA helicase (MOV10) to enhance RelA mRNA stability, thus affecting CSCC cell migration and invasion. In summary, FOXA1-mediated circ_0002762 up-regulation could enhance the migratory and invasive abilities of CSCC cells via the MOV10/RelA/NF-kB pathway.","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-13"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies. rna结合蛋白在胃肠道恶性肿瘤肿瘤免疫微环境中的调控作用。

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2024-12-24 DOI: 10.1080/15476286.2024.2440683

Dongqi Li, Xiangyu Chu, Weikang Liu, Yongsu Ma, Xiaodong Tian, Yinmo Yang

{"title":"The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies.","authors":"Dongqi Li, Xiangyu Chu, Weikang Liu, Yongsu Ma, Xiaodong Tian, Yinmo Yang","doi":"10.1080/15476286.2024.2440683","DOIUrl":"10.1080/15476286.2024.2440683","url":null,"abstract":"The crosstalk between the tumour immune microenvironment (TIME) and tumour cells promote immune evasion and resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal to GI tumours progression, and RNA-binding proteins (RBPs) serve as key regulators via their RNA-binding domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing the TIME through the modulation of mRNAs and non-coding RNAs expression, as well as post-transcriptional modifications, primarily N6-methyladenosine (m6A). Aberrant regulation of RBPs, such as HuR and YBX1, typically enhances tumour immune escape and impacts prognosis of GI tumour patients. Further, while targeting RBPs offers a promising strategy for improving immunotherapy in GI cancers, the mechanisms by which RBPs regulate the TIME in these tumours remain poorly understood, and the therapeutic application is still in its early stages. This review summarizes current advances in exploring the roles of RBPs in regulating genes expression and their effect on the TIME of GI tumours, then providing theoretical insights for RBP-targeted cancer therapies.","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blood transcriptomic associations of epigenetic age in adolescents. 青少年表观遗传年龄的血液转录组学关联。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-16 DOI: 10.1080/15592294.2025.2503824

Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas

{"title":"Blood transcriptomic associations of epigenetic age in adolescents.","authors":"Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas","doi":"10.1080/15592294.2025.2503824","DOIUrl":"10.1080/15592294.2025.2503824","url":null,"abstract":"Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14-15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the limma-voom pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of MYO6 and ZBTB38 across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40-54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2503824"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Varespladib attenuates Naja atra-induced acute liver injury via reversing Nrf2 signaling-mediated ferroptosis and mitochondrial dysfunction. Varespladib通过逆转Nrf2信号介导的铁下垂和线粒体功能障碍，减轻Naja atra诱导的急性肝损伤。

IF 5.2 2区生物学

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-05-21 DOI: 10.1080/13510002.2025.2507557

Jiahao Liu, Linfeng Wang, Mengxia Xie, Wenjie Zhao, Jiaqi Sun, Yuji Jin, Meiling Liu, Jianqi Zhao, Lixia Cheng, Cheng Wen, Xiaowen Bi, Chunhong Huang

{"title":"Varespladib attenuates Naja atra-induced acute liver injury via reversing Nrf2 signaling-mediated ferroptosis and mitochondrial dysfunction.","authors":"Jiahao Liu, Linfeng Wang, Mengxia Xie, Wenjie Zhao, Jiaqi Sun, Yuji Jin, Meiling Liu, Jianqi Zhao, Lixia Cheng, Cheng Wen, Xiaowen Bi, Chunhong Huang","doi":"10.1080/13510002.2025.2507557","DOIUrl":"10.1080/13510002.2025.2507557","url":null,"abstract":"Objective: To investigate the protective effects of varespladib against Naja atra-induced acute liver injury (ALI) and to elucidate the toxic mechanism of snake venom phospholipase A2 (SVPLA2)-induced hepatic oxidative stress, with a particular focus on the role of Nrf2 signaling and its downstream pathways.Methods: A combination of in vivo and in vitro models of N. atra envenomation was employed to assess liver injury, oxidative stress, and mitochondrial dysfunction. The interaction between SVPLA2 and Nrf2 was analyzed, and the effects of varespladib treatment on these processes were evaluated using histological analysis, biochemical assays, and molecular techniques targeting oxidative stress, ferroptosis, mitophagy, and apoptosis.Results: Varespladib significantly alleviated N. atra-induced ALI. SVPLA2 was found to directly bind to Nrf2, leading to severe oxidative stress. This oxidative stress initiated a cascade involving Nrf2-mediated ferroptosis, mitochondrial dysfunction, excessive mitophagy, and mitochondria-dependent apoptosis. Treatment with varespladib effectively reversed these pathological events by inhibiting SVPLA2 activity.Conclusion: Varespladib shows strong therapeutic potential for N. atra envenomation by targeting SVPLA2. Nrf2 was identified as a direct toxic target of SVPLA2, and Nrf2-mediated ferroptosis and mitochondrial dysfunction were key mechanisms underlying SVPLA2-induced hepatic injury.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2507557"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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