Genes & Diseases最新文献

{"title":"Single-cell landscape of immunological responses in patients with juvenile idiopathic arthritis","authors":"Yun Liu ,&nbsp;Xiwen Luo ,&nbsp;Liuqing Yang ,&nbsp;Qiang Luo ,&nbsp;Xiya Luo ,&nbsp;Li Xu ,&nbsp;Yating Wang ,&nbsp;Yunfei An ,&nbsp;Yupeng Cun ,&nbsp;Xuemei Tang","doi":"10.1016/j.gendis.2025.101577","DOIUrl":"10.1016/j.gendis.2025.101577","url":null,"abstract":"<div><div>The study aimed to analyze the single-cell transcriptomes of immune cells in juvenile idiopathic arthritis (JIA) patients to understand the cellular heterogeneity within the immune system. Peripheral blood samples from fourteen JIA patients and four healthy individuals were subjected to single-cell RNA sequencing. Various subtypes of JIA were included in the patient cohort. Functional analyses, such as pseudotime trajectories and cell communication studies, were conducted to uncover immune cell changes in JIA patients. Results showed disrupted interferon and acute inflammatory responses in most cell types of JIA patients, with particularly intense responses in systemic JIA (sJIA) patients versus non-sJIA patients. Pseudotime analysis of CD4⁺ T, CD8⁺ T, B, and myeloid cells revealed that the functions of each cytokine production, cytotoxicity, and the processing and presentation of antigens were progressively strengthened, while the regulation of nuclear factor kappa B (NF-κB)-related pathways was weaker in CD4⁺ T and CD8⁺ T cells than in non-JIA. Reclustering analysis of myeloid cells highlighted interferon-related functions predominantly in non-classical monocytes of sJIA patients. Additionally, cell communication analysis identified unique ligand–receptor pairs in sJIA, suggesting potential roles in disease progression. In conclusion, interferon disorders are evident across various immune cell types in JIA patients, with stronger responses observed in sJIA patients. The ligand–receptor pairs involving migration inhibitory factor (MIF) and CXCR7/CD44 may contribute to differing joint symptoms between sJIA and non-sJIA patients. Moreover, non-classical monocytes and the CXCR2 receptor in MIF signaling may play crucial roles in sJIA progression.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101577"},"PeriodicalIF":6.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321991","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}

{"title":"Elucidating the pathogenesis of bladder cancer through single-cell chromatin accessibility and DNA methylation analysis","authors":"Yu Xiao ,&nbsp;Lingao Ju ,&nbsp;Gang Wang ,&nbsp;Wan Jin ,&nbsp;Hongwei Peng ,&nbsp;Zongning Zhou ,&nbsp;Mengxue Yu ,&nbsp;Yi Zhang ,&nbsp;Kaiyu Qian ,&nbsp;Xinghuan Wang","doi":"10.1016/j.gendis.2025.101578","DOIUrl":"10.1016/j.gendis.2025.101578","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101578"},"PeriodicalIF":6.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904209","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}

{"title":"Crowdedness imposes stress on tumor metastasis in Drosophila melanogaster","authors":"Wenzhe Li ,&nbsp;Zhiyuan Zhang ,&nbsp;Lealia Li Xiong ,&nbsp;Huiyi Yu ,&nbsp;Jiuhong Huang ,&nbsp;Ruixiu Cao ,&nbsp;Lei Xue","doi":"10.1016/j.gendis.2025.101574","DOIUrl":"10.1016/j.gendis.2025.101574","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101574"},"PeriodicalIF":6.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178523","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}

{"title":"Clinical impact of the TPM1 p.Tyr221Cys variant causing hypertrophic cardiomyopathy","authors":"Alessio Marinelli ,&nbsp;Giuliana Longo ,&nbsp;Vincenzo Cirigliano ,&nbsp;Esther Campopiano ,&nbsp;Clementina Dugo ,&nbsp;Luca Ghiselli ,&nbsp;Andrea Chiampan ,&nbsp;Gianluca Ferri ,&nbsp;Alessandro Costa ,&nbsp;Stefano Bonapace ,&nbsp;Laura Lanzoni ,&nbsp;Giulio Molon","doi":"10.1016/j.gendis.2025.101575","DOIUrl":"10.1016/j.gendis.2025.101575","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101575"},"PeriodicalIF":6.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166624","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}

{"title":"New genetic insights into HIV-associated neurocognitive disorder and Alzheimer's disease","authors":"Hai Duc Nguyen ,&nbsp;Woong-Ki Kim","doi":"10.1016/j.gendis.2025.101576","DOIUrl":"10.1016/j.gendis.2025.101576","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101576"},"PeriodicalIF":6.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941795","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}

{"title":"Single-cell transcriptome analysis of in vivo and in vitro human pancreas development","authors":"Xiaofei Zhang ,&nbsp;Hongyan Yi ,&nbsp;Zhuo Ma ,&nbsp;Yinsuo Zhao ,&nbsp;Yanlin Ma ,&nbsp;Eli Song ,&nbsp;Tao Xu","doi":"10.1016/j.gendis.2025.101573","DOIUrl":"10.1016/j.gendis.2025.101573","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 6","pages":"Article 101573"},"PeriodicalIF":6.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679530","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}

{"title":"Exogenous pyruvate is therapeutic against colitis by targeting cytosolic phospholipase A2","authors":"Sadaf Hasan ,&nbsp;Nabil Ghani ,&nbsp;Xiangli Zhao ,&nbsp;Julia Good ,&nbsp;Chuan-ju Liu","doi":"10.1016/j.gendis.2025.101571","DOIUrl":"10.1016/j.gendis.2025.101571","url":null,"abstract":"<div><div>Ulcerative colitis is an idiopathic, chronic inflammatory bowel disease. Its pathogenesis is multifactorial involving inflammation and immune dysregulation. Proinflammatory TNFα/NFκB signaling is believed to play a cardinal role in ulcerative colitis. Growing evidence indicates the molecular interactions between the cellular metabolites and different phases of inflammation. This study aims to identify the metabolites that can inhibit TNFα/NFκB signaling and are potentially therapeutic against various TNFα-associated inflammatory diseases, particularly inflammatory bowel diseases. We performed <em>in vitro</em> and <em>in vivo</em> screening of cellular metabolites to inhibit TNFα/NFκB signaling. Multiple confirmation assays, including NFκB translocation, quantitative real-time PCR, ELISA, immunofluorescence staining, and RNA sequencing analysis were executed. Drug affinity-responsive target stability assay with proteomics was utilized for target identification. cPLA2 ablated mice with dextran sodium sulfate-induced colitis were employed to assess pyruvate's dependence on its molecular target in attenuating ulcerative colitis pathogenesis. Metabolite screening and subsequent validation with multiple approaches led to the isolation of pyruvate, a glycolytic metabolite, and a critical node in several metabolic pathways, as a novel inhibitor of TNFα/NFκB signaling. Importantly, pyruvate suppressed inflammation, preserved colonic histology, maintained tight junction proteins, and regulated permeability in the ulcerative colitis model. Additionally, cPLA2 was identified as a previously unknown target of pyruvate and pyruvate largely lost its therapeutic effects against ulcerative colitis in cPLA2-deficient mice. Conclusively, this study not only unveils pyruvate as an antagonist of TNFα/NFκB signaling and therapeutic intervention against colitis but also provides mechanistic insight into the mode of action of pyruvate.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101571"},"PeriodicalIF":6.9,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322050","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}

{"title":"Dysfunction of PDE4DIP contributes to LVNC development by regulating cell polarity, skeleton, and energy metabolism via Rho-ROCK pathway","authors":"Wuxia Gu ,&nbsp;Hongyan Li ,&nbsp;Wenjing Yuan ,&nbsp;Xiaoqiong Fu ,&nbsp;Rui Wang ,&nbsp;Xiaohui Xu ,&nbsp;Xuemei Liao ,&nbsp;LingJuan Liu ,&nbsp;Bo Pan ,&nbsp;Jie Tian ,&nbsp;Haixin Yuan ,&nbsp;Yi Huang ,&nbsp;Tiewei Lu","doi":"10.1016/j.gendis.2025.101568","DOIUrl":"10.1016/j.gendis.2025.101568","url":null,"abstract":"<div><div>Left ventricular non-compaction (LVNC), is a hereditary cardiomyopathy with limited treatments. Our previous study linked phosphodiesterase 4D interacting protein (PDE4DIP) to LVNC development. To explore the functional role of PDE4DIP activation in regulating cell polarity, skeleton, and energy metabolism, and to elucidate its mechanisms driving LVNC development, bioinformatics analysis was performed to compare its expression in LVNC patients and normal subjects. Overexpression and knockdown of PDE4DIP were constructed in H9C2 cells and neonatal Sprague–Dawley rat primary cardiomyocytes, respectively. Electron microscopy, MitoTracker-Green staining, and an ATP kit were employed to assess mitochondria's morphology and functional status. Real-time quantitative PCR, western blotting, and immunofluorescence assays were employed to detect the expression of cell polarity-, skeleton-, and Rho-ROCK signaling-related genes and proteins. Cell scratching and CCK-8 assays were employed to detect cell migration and proliferation abilities of H9C2, respectively. We found that PDE4DIP expression was increased in the LVNC-derived human-induced pluripotent stem cell-derived cardiomyocytes compared with normal subjects. Furthermore, overexpression of PDE4DIP induced cytoskeletal disorganization, decreased ATP content and cell migration, and increased cell proliferation and mitochondrial vacuolation. Moreover, the knockdown of PDE4DIP promoted cytoskeleton formation and contributed to increased ATP content and elevated cell migration. Mechanically, overexpression of PDE4DIP inhibited cell polarity-, skeleton-, and Rho-ROCK signaling-related genes and proteins, which could be increased by knockdown of PDE4DIP, suggesting that a critical regulation of PDE4DIP to Rho-ROCK pathway. This discovery suggests that PDE4DIP contributes to the development of LVNC by regulating cell polarity, skeleton, and energy metabolism through the Rho-ROCK pathway.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101568"},"PeriodicalIF":6.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331141","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}

{"title":"Gut microbiome–metabolome–ionome network spectrum mapping of colorectal cancer","authors":"Xi Yang ,&nbsp;Yin Jin ,&nbsp;Yinhang Wu ,&nbsp;Feng Zhou ,&nbsp;Zhanbo Qu ,&nbsp;Qing Zhou ,&nbsp;Jiaying He ,&nbsp;Ye Tao ,&nbsp;Jing Zhuang ,&nbsp;Shuwen Han","doi":"10.1016/j.gendis.2025.101566","DOIUrl":"10.1016/j.gendis.2025.101566","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 1","pages":"Article 101566"},"PeriodicalIF":9.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046871","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}

{"title":"Identification and functional analysis of CCN6 variants in progressive pseudorheumatoid dysplasia: Exploring the potential role of ferroptosis and apoptosis in chondrocytes","authors":"Yueyang Sheng ,&nbsp;Shan Li ,&nbsp;Ying Wang ,&nbsp;XinYu Wang ,&nbsp;Yanzhuo Zhang ,&nbsp;Chengai Wu ,&nbsp;Xu Jiang","doi":"10.1016/j.gendis.2025.101564","DOIUrl":"10.1016/j.gendis.2025.101564","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 1","pages":"Article 101564"},"PeriodicalIF":9.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026670","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}