Genes & Diseases最新文献_第10页

Preclinical ex vivo IL2RG gene therapy using autologous hematopoietic stem cells as an effective and safe treatment for X-linked severe combined immunodeficiency disease 使用自体造血干细胞的临床前体外IL2RG基因治疗作为x连锁严重联合免疫缺陷疾病的有效和安全治疗

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-11-06 DOI: 10.1016/j.gendis.2024.101445

Mingfeng Hu , Qiling Xu , Fang Zhang , Karen F. Buckland , Yelei Gao , Weixia Du , Yuan Ding , Lina Zhou , Xiulian Sun , Lijia Ma , Zhiyong Zhang , Xuemei Tang , Xiaodong Zhao , Adrian J. Thrasher , Yunfei An

{"title":"Preclinical ex vivo IL2RG gene therapy using autologous hematopoietic stem cells as an effective and safe treatment for X-linked severe combined immunodeficiency disease","authors":"Mingfeng Hu , Qiling Xu , Fang Zhang , Karen F. Buckland , Yelei Gao , Weixia Du , Yuan Ding , Lina Zhou , Xiulian Sun , Lijia Ma , Zhiyong Zhang , Xuemei Tang , Xiaodong Zhao , Adrian J. Thrasher , Yunfei An","doi":"10.1016/j.gendis.2024.101445","DOIUrl":"10.1016/j.gendis.2024.101445","url":null,"abstract":"<div><div>X-linked severe combined immunodeficiency disease (X-SCID) is a rare inherited disease caused by mutations in the interleukin 2 receptor subunit gamma gene (<em>IL2RG</em>), which encodes the common γ chain protein, a subunit of the receptor for lymphocytes. X-SCID is characterized by profound defects in T-cell, B-cell, and natural killer cell function. Here, we report a Chinese cohort of nine X-SCID patients with six novel <em>IL2RG</em> mutations. Among those, the two adolescent patients with an atypical immunotype were confirmed by further analyzing IL-2-JAK-STAT5 signaling, T cell proliferation, and T cell receptor excision circles (Trecs). Interestingly, Bacillus Calmette-Guérin (BCG) disease occurred commonly in this cohort. Although allogeneic hematopoietic stem-cell transplantation is curative for the disease, it is not available to all patients due to the lack of suitable matched donors. Autologous gene therapy using a self-inactivating lentiviral vector (SIN-LV) technology has provided an alternative therapy for such mono-genetic diseases. Here, we performed the pre-clinical studies to assess our SIN-LV carrying <em>IL2RG</em> on human ED7R cells deficient in <em>IL2RG</em> and CD34<sup>+</sup> stem cells derived from the bone marrow of a healthy donor and a patient with X-SCID. This work is done complied with the established “Good Manufacturing Practice” (GMP) used in the clinical trials. In addition, a safety study is performed using the transduced CD34<sup>+</sup> cells implanted into the axilla of nude mice <em>in vivo</em>. Overall, our studies have demonstrated the efficiency and safety of SIN-IL2RG-LV, which paves the way for conducting X-SCID gene therapy clinical trials in China in the near future.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 3","pages":"Article 101445"},"PeriodicalIF":6.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478554","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}

引用次数: 0

The genomic and epigenomic landscape of iridocorneal endothelial syndrome 虹膜角膜内皮综合征的基因组和表观基因组景观

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-11-06 DOI: 10.1016/j.gendis.2024.101448

Yaoming Liu , Gen Li , Jiaxuan Jiang , Sujie Fan , Lan Lu , Ting Wang , Guigang Li , Wenzong Zhou , Xuequn Liu , Yingjie Li , Hong Sun , Liang Liang , Yuhong Tang , Yang Chen , Jianjun Gu , Fei Li , Xiuli Fang , Tao Sun , Aiguo Lv , Yayi Wang , Xiulan Zhang

{"title":"The genomic and epigenomic landscape of iridocorneal endothelial syndrome","authors":"Yaoming Liu , Gen Li , Jiaxuan Jiang , Sujie Fan , Lan Lu , Ting Wang , Guigang Li , Wenzong Zhou , Xuequn Liu , Yingjie Li , Hong Sun , Liang Liang , Yuhong Tang , Yang Chen , Jianjun Gu , Fei Li , Xiuli Fang , Tao Sun , Aiguo Lv , Yayi Wang , Xiulan Zhang","doi":"10.1016/j.gendis.2024.101448","DOIUrl":"10.1016/j.gendis.2024.101448","url":null,"abstract":"<div><div>Iridocorneal endothelial (ICE) syndrome is a rare, irreversibly blinding eye disease with an unknown etiology. Understanding its genomic and epigenomic landscape could aid in developing etiology-based therapies. In this study, we recruited 99 ICE patients and performed whole-genome sequencing (WGS) on 51 and genome-wide DNA methylation profiling on 48 of them. We conducted mutational burden testing on genes and noncoding regulatory regions, comparing the ICE cohort with control groups (9197 East Asians from the gnomAD database and 350 normal Chinese from our in-house cohort). Copy number variation (CNV) analysis and differential methylation of regions were also explored. We identified RP1L1 (27/51, 53%) with a significantly higher coding-altering mutational burden in the ICE cohort (p < 8.3×10<sup>−7</sup>), with mutations predominantly at chr8:10467637 (hg19). Additionally, 41 regions with significant CNVs were identified, including two regions at chr19:15783859-15791329 (hg19) and chr3:75786061-75790887 (hg19), showing copy number loss in 39 and 19 patients, respectively. We also identified 2,717 differentially methylated regions (DMRs), with hypomethylation prevalent in ICE syndrome (91.9% of DMRs). Among these, 45 recurrent hypomethylated regions (HMRs) in more than 10% of ICE patients showed differential methylation compared to normal controls. This study presents the first comprehensive genomic and epigenomic characterization of ICE syndrome, offering insights into its underlying etiology.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 3","pages":"Article 101448"},"PeriodicalIF":6.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511451","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}

引用次数: 0

Molecular mechanism of tumor-infiltrating immune cells regulating endometrial carcinoma 肿瘤浸润性免疫细胞调控子宫内膜癌的分子机制

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-11-05 DOI: 10.1016/j.gendis.2024.101442

Silu Ding , Yingying Hao , Yue Qi , Heng Wei , Jin Zhang , Hui Li

{"title":"Molecular mechanism of tumor-infiltrating immune cells regulating endometrial carcinoma","authors":"Silu Ding , Yingying Hao , Yue Qi , Heng Wei , Jin Zhang , Hui Li","doi":"10.1016/j.gendis.2024.101442","DOIUrl":"10.1016/j.gendis.2024.101442","url":null,"abstract":"<div><div>Endometrial carcinoma (EC) is a prevalent gynecological cancer, and its interaction with the immune system is pivotal in cancer progression. This comprehensive review explores the molecular mechanisms involved in the regulation of EC by tumor-infiltrating immune cells. This review discusses the composition and functions of various immune cell types within the tumor microenvironment, including T cells, B cells, macrophages, and natural killer cells, and elucidates their specific roles in cancer control. It also delves into the immune evasion strategies employed by EC cells, with a specific focus on immune checkpoint pathways and their influence on tumor development. Signaling pathways, cytokines, and chemokines mediating immune responses within the tumor microenvironment are also detailed. Furthermore, clinical implications and therapeutic strategies, such as immunotherapies, are also reviewed, and relevant clinical trials are discussed. Additionally, this review discusses the existing gaps in our knowledge, suggests potential avenues for future research, and emphasizes the significance of understanding these mechanisms for enhanced EC treatment. This review provides an exhaustive overview of the current knowledge, supporting the ongoing quest for more effective therapeutic interventions on EC.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 3","pages":"Article 101442"},"PeriodicalIF":6.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464628","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}

引用次数: 0

CRISPR/Cas9 screening reveals Zfp607b as a novel transcription factor regulating myogenesis CRISPR/Cas9筛选显示Zfp607b是一种新的调节肌肉发生的转录因子

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-10-30 DOI: 10.1016/j.gendis.2024.101444

Siyuan Liu , Wei Wang , Zishuai Wang , Chao Yan , Guohao Han , Weiwei Liu , Yuxing Huang , Wangchang Li , Shengsong Xie , Zhonglin Tang

引用次数: 0

Characterization of a novel HIV-1 second-generation circulating recombinant form (CRF144_07C) in Ganzhou, China 中国赣州一种新的HIV-1第二代循环重组形式（CRF144_07C）的特征

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-10-30 DOI: 10.1016/j.gendis.2024.101443

Xiaoyi Zhang , Hongmin Cao , Yating Chen , Chaoxian Lian , Ting Zeng , Junjie Liu , Junzhi Su , Qian Gao , Fengxiu Zhu , Yuning Zhang , Dandan Huang , Yanheng Zhou , Xin Chen

引用次数: 0

OSdream: An online survival and differential analysis tool of recurrence and metastasis of pan-cancers OSdream：泛癌复发和转移的在线生存和差异分析工具

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-10-30 DOI: 10.1016/j.gendis.2024.101446

Huimin Li , Qiang Wang , Yunyi Liu , Lin Chen , Qiwei Zhao , Longxiang Xie , Lu Zhang , Zhongyi Yan , Guosen Zhang , Yali Han , Wan Zhu , Xiangqian Guo

引用次数: 0

Inflammatory transcriptomic signatures and cell type compositions in inflamed and non-inflamed colonic mucosa of ulcerative colitis 溃疡性结肠炎炎症和非炎症结肠黏膜的炎症转录组特征和细胞类型组成

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-10-30 DOI: 10.1016/j.gendis.2024.101447

Eun Mi Song , Jahanzeb Saqib , Yang Hee Joo , Zehra Ramsha , Chang Mo Moon , Sung-Ae Jung , Junil Kim

引用次数: 0

Ce6-GFFY is a novel photosensitizer for colorectal cancer therapy Ce6-GFFY是一种用于结直肠癌治疗的新型光敏剂。

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-10-28 DOI: 10.1016/j.gendis.2024.101441

Wei Qiao , Shuxin Li , Linna Luo , Meiling Chen , Xiaobin Zheng , Jiacong Ye , Zhaohui Liang , Qiaoli Wang , Ting Hu , Ling Zhou , Jing Wang , Xiaosong Ge , Guokai Feng , Fang Hu , Rongbin Liu , Jianjun Li , Jie Yang

{"title":"Ce6-GFFY is a novel photosensitizer for colorectal cancer therapy","authors":"Wei Qiao , Shuxin Li , Linna Luo , Meiling Chen , Xiaobin Zheng , Jiacong Ye , Zhaohui Liang , Qiaoli Wang , Ting Hu , Ling Zhou , Jing Wang , Xiaosong Ge , Guokai Feng , Fang Hu , Rongbin Liu , Jianjun Li , Jie Yang","doi":"10.1016/j.gendis.2024.101441","DOIUrl":"10.1016/j.gendis.2024.101441","url":null,"abstract":"<div><div>Photodynamic therapy is an “old” strategy for cancer therapy featuring clinical safety and rapid working, but suitable photosensitizers for colorectal cancer therapy remain lacking. This study synthesized a novel photosensitizer termed Ce6-GFFY based on a self-assembling peptide GFFY and a photo-responsive molecule chlorin e6 (Ce6). Ce6-GFFY forms macroparticles with a diameter of ∼160 nm and possesses a half-life of 10 h, as well as an ideal tumor-targeting ability in mouse models. Ce6-GFFY effectively penetrates cells and generates numerous reactive oxygen species upon 660 nm laser irradiation. The reactive oxygen species promotes the accumulation of cytotoxic T cells and decrease of myeloid-derived suppressor cells in the tumor microenvironment through immunogenic cell death, thus prohibiting the growth of both primary and metastatic tumors after once treatment. This study not only provides a strategy for photosensitizer development but also confirms a promising application of Ce6-GFFY for colorectal cancer therapy.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 2","pages":"Article 101441"},"PeriodicalIF":6.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932871","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}

引用次数: 0

AUTS2 expression within mammalian lineage: A predictor of neural networks involved in autism spectrum disorders 哺乳动物谱系中的AUTS2表达：自闭症谱系障碍中涉及的神经网络的预测因子。

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-10-19 DOI: 10.1016/j.gendis.2024.101440

Aude-Marie Lepagnol-Bestel , Yann Loe-Mie , Mounia Bensaid , Michel Simonneau

引用次数: 0

lncRNA POU3F3 promotes osteosarcoma progression through GPX4-modulated ferroptosis by interaction with IGF2BP2 to facilitate NRF2 mRNA stability lncRNA POU3F3通过与IGF2BP2相互作用促进NRF2 mRNA的稳定性，通过gpx4调节的铁凋亡促进骨肉瘤的进展

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-10-12 DOI: 10.1016/j.gendis.2024.101439

Suyang Xu , Yingjie Zhou , Ma Wan , Yikang Bi , Pengcheng Liu , Zixiang Li , Yafeng Xu , Hao Fang , Hai Hu , Chongshan Yang , Shenghui Lan

引用次数: 0