Genes & Diseases最新文献

MyoAAV-delivered sup-tRNA increases full-length dystrophin expression myoaav递送的sup-tRNA增加全长肌营养不良蛋白的表达

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-05-03 DOI: 10.1016/j.gendis.2025.101666

Xiuyi Ai , Yue Chang , Ruo Wu , Jie Liu , Pei Zhang , Yayu Wang , Zhuoyin Zheng , Shu Zhang , Yongchang Chen , Shiwen Wu

引用次数: 0

Otof gene transfer in DFNB9 mice carrying human founder non-truncating alleles 携带人类创始人非截断等位基因的DFNB9小鼠的Otof基因转移

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-06 DOI: 10.1016/j.gendis.2025.101590

Yehree Kim , Yoojin Chung , Ju Ang Kim , Kyu Hee Han , Kwon Woo Kang , Ngoc-Trinh Tran , Min Young Kim , Eunyoung Yi , Sangyong Jung , Bong Jik Kim , Quynh-Anh Artinian , Seth D. Koehler , Ning Pan , Tyler M. Gibson , Lars Becker , Joseph W. Goodliffe , Molly Kalker , Madeline Barnes , Luke A. Shaheen , Meghan C. Drummond , Byung Yoon Choi

引用次数: 0

Elucidating the pathogenesis of bladder cancer through single-cell chromatin accessibility and DNA methylation analysis 通过单细胞染色质可及性和DNA甲基化分析阐明膀胱癌的发病机制

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-03 DOI: 10.1016/j.gendis.2025.101578

Yu Xiao , Lingao Ju , Gang Wang , Wan Jin , Hongwei Peng , Zongning Zhou , Mengxue Yu , Yi Zhang , Kaiyu Qian , Xinghuan Wang

引用次数: 0

New genetic insights into HIV-associated neurocognitive disorder and Alzheimer's disease hiv相关神经认知障碍和阿尔茨海默病的新遗传见解

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-26 DOI: 10.1016/j.gendis.2025.101576

Hai Duc Nguyen , Woong-Ki Kim

引用次数: 0

SIRT5 promotes the osteo-inductive potential of BMP9 by stabilizing the HIF-1α protein in mouse embryonic fibroblasts SIRT5通过稳定小鼠胚胎成纤维细胞中HIF-1α蛋白来促进BMP9的成骨诱导潜能

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-18 DOI: 10.1016/j.gendis.2025.101563

Lu Liu , Fanglin Ye , Yue Jiang , Wenting Liu , Dongmei He , Wenge He , Xiang Gao , Hang Liu , Junyi Liao , Baicheng He , Fang He

{"title":"SIRT5 promotes the osteo-inductive potential of BMP9 by stabilizing the HIF-1α protein in mouse embryonic fibroblasts","authors":"Lu Liu , Fanglin Ye , Yue Jiang , Wenting Liu , Dongmei He , Wenge He , Xiang Gao , Hang Liu , Junyi Liao , Baicheng He , Fang He","doi":"10.1016/j.gendis.2025.101563","DOIUrl":"10.1016/j.gendis.2025.101563","url":null,"abstract":"<div><div>Bone morphogenetic protein 9 (BMP9) exhibits remarkable osteogenic potential. However, the intricate mechanisms driving this function of BMP9 remain elusive. This study endeavors to investigate the potential role of sirtuin 5 (SIRT5) in enhancing BMP9's osteogenic capacity and decipher the underlying molecular pathways. To achieve this aim, we employed real-time PCR, western blotting, histochemical staining, and a cranial defect repair model to assess the impact of SIRT5 on BMP9-mediated osteogenesis. We utilized real-time PCR, western blotting, immunofluorescent staining, and immunoprecipitation assay to explore the associated mechanisms. Our results revealed that SIRT5 significantly up-regulated BMP9-induced osteogenic markers, while SIRT5 knockdown reduced their expression. Concurrently, hypoxia-inducible factor 1 subunit alpha (HIF-1α) level was increased by SIRT5, but reduced by SIRT5 knockdown. Notably, HIF-1α potentiated the SIRT5's ability to strengthen BMP9's osteogenic potential, whereas HIF-1α silencing reduced this effect, which was confirmed by bone defect repair assay. The acetylation and malonylation levels of HIF-1α were reduced by SIRT5, which may enhance its stability to promote BMP9's osteogenic effect. Conversely, SIRT5 knockdown reversed these effects and promoted the degradation of HIF-1α. Collectively, our results demonstrated that the BMP9's osteogenic potential could be promoted by SIRT5, potentially through stabilizing HIF-1α by reducing its acetylation and malonylation modification. This discovery may offer a novel strategy to accelerate bone tissue engineering by enhancing osteogenic differentiation, and it also sheds light on the possible mechanisms underlying BMP9-mediated osteogenic differentiation.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 4","pages":"Article 101563"},"PeriodicalIF":6.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactate transporter MCT4 regulates the hub genes for lipid metabolism and inflammation to attenuate intracellular lipid accumulation in non-alcoholic fatty liver disease 乳酸转运体MCT4调节脂质代谢和炎症中枢基因，以减轻非酒精性脂肪性肝病的细胞内脂质积累

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-15 DOI: 10.1016/j.gendis.2025.101554

Yannian Gou , Aohua Li , Xiangyu Dong , Ailing Hao , Jiajia Li , Han Xiang , Saidur Rahaman , Tong-Chuan He , Jiaming Fan

{"title":"Lactate transporter MCT4 regulates the hub genes for lipid metabolism and inflammation to attenuate intracellular lipid accumulation in non-alcoholic fatty liver disease","authors":"Yannian Gou , Aohua Li , Xiangyu Dong , Ailing Hao , Jiajia Li , Han Xiang , Saidur Rahaman , Tong-Chuan He , Jiaming Fan","doi":"10.1016/j.gendis.2025.101554","DOIUrl":"10.1016/j.gendis.2025.101554","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) patients have multiple metabolic disturbances, with markedly elevated levels of lactate. Lactate accumulations play pleiotropic roles in disease progression through metabolic rearrangements and epigenetic modifications. Monocarboxylate transporter 4 (MCT4) is highly expressed in hepatocytes and responsible for transporting intracellular lactate out of the cell. To explore whether elevated MCT4 levels played any role in NAFLD development, we overexpressed and silenced MCT4 in hepatocytes and performed a comprehensive <em>in vitro</em> and <em>in vivo</em> analysis. Our results revealed that MCT4 overexpression down-regulated the genes for lipid synthesis while up-regulating the genes involved in lipid catabolism. Conversely, silencing MCT4 expression or inhibiting MCT4 expression led to the accumulation of intracellular lipid and glucose metabolites, resulting in hepatic steatosis. In a mouse model of NAFLD, we found that exogenous MCT4 overexpression significantly reduced lipid metabolism and alleviated hepatocellular steatosis. Mechanistically, MCT4 alleviated hepatic steatosis by regulating a group of hub genes such as <em>Arg2</em>, <em>Olr1</em>, <em>Cd74</em>, <em>Mmp8, Irf7</em>, <em>Spp1</em>, and <em>Apoe</em>, which in turn impacted multiple pathways involved in lipid metabolism and inflammatory response, such as PPAR, HIF-1, TNF, IL-17, PI3K-AKT, Wnt, and JAK-STAT. Collectively, our results strongly suggest that MCT4 may play an important role in regulating lipid metabolism and inflammation and thus serve as a potential therapeutic target for NAFLD.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 4","pages":"Article 101554"},"PeriodicalIF":6.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancer profiling uncovers Jmjd1c as an essential suppressor in neuropathic pain by targeting Socs3 增强子分析揭示了Jmjd1c通过靶向Socs3在神经性疼痛中发挥重要的抑制作用

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-23 DOI: 10.1016/j.gendis.2025.101545

Le Zhang , Yan Xie , Shun Wang , Moxuan Gong , Zheping Chen , Chuanxin Wang , Peilong Li

{"title":"Enhancer profiling uncovers Jmjd1c as an essential suppressor in neuropathic pain by targeting Socs3","authors":"Le Zhang , Yan Xie , Shun Wang , Moxuan Gong , Zheping Chen , Chuanxin Wang , Peilong Li","doi":"10.1016/j.gendis.2025.101545","DOIUrl":"10.1016/j.gendis.2025.101545","url":null,"abstract":"<div><div>Neuropathic pain (NP) is a chronic debilitating disease caused by nerve damage or various diseases, significantly impairs patients’ quality of life. Super-enhancers (SEs) are important cis-regulatory elements, but how they affect NP remains elusive. Therefore, we aim to explore the molecular mechanism by which SEs are involved in NP progression and identify potential drug candidate targets. We first established a NP model in rats, and subsequently performed H3K27ac ChIP-Seq and RNA-Seq on their spinal cord tissues to analyze the active enhancers. By integrated analysis of ChIP-seq data and RNA-seq data, we clarified a series of SE-associated genes involved in NP progression. qPCR and double immunofluorescence staining results suggested that <em>Jmjd1c</em> mRNA and protein levels were significantly down-regulated in the NP model. In addition, a dual-luciferase reporter assay showed that <em>KLF15</em> could activate <em>Jmjd1c</em> transcription by binding to the SE of <em>Jmjd1c</em>. Functionally, enhanced <em>Jmjd1c</em> can inhibit the levels of inflammatory cytokines such as IL-6, TNF-α, IL-1β, and inhibited the progression of NP, whereas silencing <em>Jmjd1c</em> had the opposite effect. Mechanistic exploration identified <em>Jmjd1c</em> exerted its anti-NP effect via positively regulating <em>Socs3</em> expression by increasing the activity of H3K9 demethylation, and the <em>Jmjd1c/Socs3/JAK/STAT3</em> regulatory pathway was finally validated as downstream effectors. In conclusion, our study suggests that SE-associated <em>Jmjd1c</em> was suppressed during NP progression due to the decreased recruitment of <em>KLF15</em>. The reduction of <em>Jmjd1c</em> downregulated <em>Socs3</em> through the demethylation of H3K9 at <em>Socs3</em> promoter region, leading to NP progression.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101545"},"PeriodicalIF":6.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

VEXAS syndrome caused by a UBA1 mutation is complicated by recurrent infections leading to hemophagocytic lymphohistiocytosis 由UBA1突变引起的VEXAS综合征并发复发性感染，导致噬血细胞性淋巴组织细胞增多症

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-22 DOI: 10.1016/j.gendis.2025.101540

Yu Tang, Hongfei Cui, Hongjun Zhao, Hui Luo, Xiaoxia Zuo, Junjiao Wu

引用次数: 0

A causal association between immune cells and hypertrophic cardiomyopathy: A bidirectional Mendelian randomization study 免疫细胞与肥厚性心肌病之间的因果关系：一项双向孟德尔随机研究

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-21 DOI: 10.1016/j.gendis.2025.101539

Fang He , Qiangzhong Pi , Jun Yang , Mengning Wan , Jiang Yu , Ding Yang , Yongzheng Guo , Xiaorong Li

引用次数: 0

In vivo consequences of varying degrees of OTOA alteration elucidated using knock-in mouse models and pseudogene contamination-free long-read sequencing 使用敲入小鼠模型和假基因无污染长读测序阐明了不同程度的OTOA改变的体内后果