Pub Date : 2025-07-25DOI: 10.1016/j.gendis.2025.101783
Mengling Hu , Xiaoqian Li , Dongsheng Fan , Lu Yu , Fan Ren , Jianming Wu , Jianing Mi , Yang Zheng , Xiaogang Zhou , Dalian Qin , Anguo Wu
{"title":"NAD+ supplementation augments the efficacy of the PARP1 inhibitor PJ34 in a 6-OHDA-induced model of Parkinson’s disease","authors":"Mengling Hu , Xiaoqian Li , Dongsheng Fan , Lu Yu , Fan Ren , Jianming Wu , Jianing Mi , Yang Zheng , Xiaogang Zhou , Dalian Qin , Anguo Wu","doi":"10.1016/j.gendis.2025.101783","DOIUrl":"10.1016/j.gendis.2025.101783","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101783"},"PeriodicalIF":9.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577044","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}
Pub Date : 2025-07-25DOI: 10.1016/j.gendis.2025.101784
Min Luo , Lingjuan Liu , Wenjing Yuan , Junjun Quan , Mi Li , Jie Tian
This work aims to investigate the energy metabolism in mice with restrictive cardiomyopathy induced by cardiac troponin I (cTnI) R193H mutation. Echocardiography was used to monitor cardiac function. ATP content and ATPase activity were detected with relevant kits. The expression levels of GLUT4, FAT/CD36, and PI3K/AKT pathway proteins were detected. Proteomics and phosphorylation omics were used to analyze the differential expression and modification of cardiac proteins and related pathways, respectively. The utilization of cardiac energy substrates was investigated using relevant kits. The isovolumic relaxation time of 4-month-old cTnI193His-M mice was significantly prolonged (P < 0.01); Cardiac ATP content, ATPase activity, and mitochondrial number were significantly increased (P < 0.05, P < 0.01, and P < 0.01, respectively); GLUT4 expression level increased (P < 0.01); the expression level of CD36 decreased (P < 0.01). Proteomic results showed that the glycolytic/gluconeogenic pathway was up-regulated. Phosphorylation omics was enriched in the inositol phosphate metabolism pathway and PI3K/AKT pathway. In conclusion, at the early stage of diastolic dysfunction, cTnI193His-M mice may increase glucose uptake and metabolism through the PI3K/AKT pathway to satisfy the high energy demand, which may contribute to the development of myocardial fibrosis and heart failure.
{"title":"cTnIR193H restrictive cardiomyopathy mice satisfy high-energy metabolic demands through regulating glucose metabolism","authors":"Min Luo , Lingjuan Liu , Wenjing Yuan , Junjun Quan , Mi Li , Jie Tian","doi":"10.1016/j.gendis.2025.101784","DOIUrl":"10.1016/j.gendis.2025.101784","url":null,"abstract":"<div><div>This work aims to investigate the energy metabolism in mice with restrictive cardiomyopathy induced by cardiac troponin I (cTnI) R193H mutation. Echocardiography was used to monitor cardiac function. ATP content and ATPase activity were detected with relevant kits. The expression levels of GLUT4, FAT/CD36, and PI3K/AKT pathway proteins were detected. Proteomics and phosphorylation omics were used to analyze the differential expression and modification of cardiac proteins and related pathways, respectively. The utilization of cardiac energy substrates was investigated using relevant kits. The isovolumic relaxation time of 4-month-old cTnI193His-M mice was significantly prolonged (<em>P</em> < 0.01); Cardiac ATP content, ATPase activity, and mitochondrial number were significantly increased (<em>P</em> < 0.05, <em>P</em> < 0.01, and <em>P</em> < 0.01, respectively); GLUT4 expression level increased (<em>P</em> < 0.01); the expression level of CD36 decreased (<em>P</em> < 0.01). Proteomic results showed that the glycolytic/gluconeogenic pathway was up-regulated. Phosphorylation omics was enriched in the inositol phosphate metabolism pathway and PI3K/AKT pathway. In conclusion, at the early stage of diastolic dysfunction, cTnI193His-M mice may increase glucose uptake and metabolism through the PI3K/AKT pathway to satisfy the high energy demand, which may contribute to the development of myocardial fibrosis and heart failure.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101784"},"PeriodicalIF":9.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680824","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}
Pub Date : 2025-07-24DOI: 10.1016/j.gendis.2025.101779
Yao Lin , Yaxin Chen , Dandan Xiong , Jing Huang , Hongmo Liu , Yawen Qi , Jinfeng Chen , Jun Meng , Yueqi Li , Jingyuan Yang , Yi Bao , Wenxing Li , Li Yang , Sanqi An
{"title":"Unveiling the roles of SPP1+ macrophage and IGFBP2+ fibroblast in lung adenosquamous carcinoma through single-cell analysis","authors":"Yao Lin , Yaxin Chen , Dandan Xiong , Jing Huang , Hongmo Liu , Yawen Qi , Jinfeng Chen , Jun Meng , Yueqi Li , Jingyuan Yang , Yi Bao , Wenxing Li , Li Yang , Sanqi An","doi":"10.1016/j.gendis.2025.101779","DOIUrl":"10.1016/j.gendis.2025.101779","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 1","pages":"Article 101779"},"PeriodicalIF":9.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046867","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}
Pub Date : 2025-07-24DOI: 10.1016/j.gendis.2025.101778
Jie Liu , Xiao Han , Fan-Li Sun , Xue Wang , Lin Wang , Yan-Qiu Zhao , Wen-Jing Liu , Bing-Hua Jiang
{"title":"METTL3 in Cr (VI)-induced carcinogenesis and CXCL6 expression associated with lung cancer development","authors":"Jie Liu , Xiao Han , Fan-Li Sun , Xue Wang , Lin Wang , Yan-Qiu Zhao , Wen-Jing Liu , Bing-Hua Jiang","doi":"10.1016/j.gendis.2025.101778","DOIUrl":"10.1016/j.gendis.2025.101778","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101778"},"PeriodicalIF":9.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577038","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}
Pub Date : 2025-07-23DOI: 10.1016/j.gendis.2025.101777
Chang Liu , Hongyan Yuan , Jindie Huang , Shidian Ran , Xiaorui Wei , Xingrui Yan , Linyu Xue , Tong-Chuan He , Yuxin Zhang , Mengqin Gu , Si Wu , Fugui Zhang , Wenping Luo , Hongmei Zhang
Tooth formation is a highly orchestrated process that precisely regulates the size and shape of the tooth. During typical tooth development, Hertwig's epithelial root sheath (HERS) interacts with mesenchymal cells to direct the elongation of the tooth root and the deposition of dentin and cementum, thereby contributing to the formation of a fully developed tooth root. BMP9, a member of the BMP family, plays a significant role in growth, development, and cell differentiation. However, the precise function of BMP9 in dental root development remains unclear, particularly regarding its influence on HERS and odontoblasts. In this study, we utilized a mouse molar model to investigate the role of BMP9 signaling in tooth root development. The tooth formation of Bmp9 knockout (Bmp9-KO) mice and wild-type (WT) littermates was compared. Our findings revealed that Bmp9-KO mice exhibited shorter mandibular first molar roots, wider apical foramina, and thinner dentin compared with WT mice by micro-CT and hematoxylin-eosin staining analysis. Additionally, the results of immunohistochemistry and quantitative PCR indicated that in the absence of Bmp9, odontoblast differentiation and secretory function were compromised. Furthermore, Bmp9 ablation resulted in reduced cell proliferation and increased intercellular junctions within HERS, subsequently impacting root dentin formation and apical foramen closure. This study offers new insights into the regulatory role of BMP9 signaling in odontoblast and HERS function, highlighting its significance in root development and providing potential avenues for future research in tooth root regeneration.
{"title":"Bmp9 modulates cell proliferation and intercellular junctions in HERS during tooth root development","authors":"Chang Liu , Hongyan Yuan , Jindie Huang , Shidian Ran , Xiaorui Wei , Xingrui Yan , Linyu Xue , Tong-Chuan He , Yuxin Zhang , Mengqin Gu , Si Wu , Fugui Zhang , Wenping Luo , Hongmei Zhang","doi":"10.1016/j.gendis.2025.101777","DOIUrl":"10.1016/j.gendis.2025.101777","url":null,"abstract":"<div><div>Tooth formation is a highly orchestrated process that precisely regulates the size and shape of the tooth. During typical tooth development, Hertwig's epithelial root sheath (HERS) interacts with mesenchymal cells to direct the elongation of the tooth root and the deposition of dentin and cementum, thereby contributing to the formation of a fully developed tooth root. BMP9, a member of the BMP family, plays a significant role in growth, development, and cell differentiation. However, the precise function of BMP9 in dental root development remains unclear, particularly regarding its influence on HERS and odontoblasts. In this study, we utilized a mouse molar model to investigate the role of BMP9 signaling in tooth root development. The tooth formation of <em>Bmp9</em> knockout (<em>Bmp9</em>-KO) mice and wild-type (WT) littermates was compared. Our findings revealed that <em>Bmp9</em>-KO mice exhibited shorter mandibular first molar roots, wider apical foramina, and thinner dentin compared with WT mice by micro-CT and hematoxylin-eosin staining analysis. Additionally, the results of immunohistochemistry and quantitative PCR indicated that in the absence of <em>Bmp9</em>, odontoblast differentiation and secretory function were compromised. Furthermore, <em>Bmp9</em> ablation resulted in reduced cell proliferation and increased intercellular junctions within HERS, subsequently impacting root dentin formation and apical foramen closure. This study offers new insights into the regulatory role of BMP9 signaling in odontoblast and HERS function, highlighting its significance in root development and providing potential avenues for future research in tooth root regeneration.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 1","pages":"Article 101777"},"PeriodicalIF":9.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145320680","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}
Pub Date : 2025-07-16DOI: 10.1016/j.gendis.2025.101773
Longjun Yang, Qiang Ding, Xiaoyu Ji, Panpan Lu, Mei Liu
Leucine-rich repeat containing 8A (LRRC8A) is a member of the LRRC8 family, exhibiting broad expression across various tissues and cells in vertebrates. Like other LRRC8 family members, LRRC8A contributes to the formation of volume-regulated anion channels (VRACs), which are crucial for regulating cell volume and maintaining homeostasis. LRRC8A participates in diverse signaling pathways. Multiple studies have validated the links between LRRC8A dysregulation and neurological disorders, metabolic ailments, and tumors. This review provides a comprehensive overview of the regulatory mechanisms of LRRC8A in these pathologies. The primary goal was to assess the potential of LRRC8A as a therapeutic target for treating diseases and address key unresolved issues.
{"title":"LRRC8A: A multifaceted regulator in cancer, neurological disorders, metabolic diseases and immune modulation","authors":"Longjun Yang, Qiang Ding, Xiaoyu Ji, Panpan Lu, Mei Liu","doi":"10.1016/j.gendis.2025.101773","DOIUrl":"10.1016/j.gendis.2025.101773","url":null,"abstract":"<div><div>Leucine-rich repeat containing 8A (LRRC8A) is a member of the LRRC8 family, exhibiting broad expression across various tissues and cells in vertebrates. Like other LRRC8 family members, LRRC8A contributes to the formation of volume-regulated anion channels (VRACs), which are crucial for regulating cell volume and maintaining homeostasis. LRRC8A participates in diverse signaling pathways. Multiple studies have validated the links between LRRC8A dysregulation and neurological disorders, metabolic ailments, and tumors. This review provides a comprehensive overview of the regulatory mechanisms of LRRC8A in these pathologies. The primary goal was to assess the potential of LRRC8A as a therapeutic target for treating diseases and address key unresolved issues.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101773"},"PeriodicalIF":9.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680823","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}
Pub Date : 2025-07-14DOI: 10.1016/j.gendis.2025.101771
Chenhe Liu , Shijiang Wang , Xin Zhang , Yifan Han , Min Tan , Jiehou Fan , Jing Du , Yubo Fan , Xinbin Zhao
Tumor cell invasion is the key driver of metastatic dissemination, resulting in the development and progression of metastatic tumors at secondary sites, and remains the major cause of cancer-related death. Recent studies suggest that, in addition to protease-mediated degradation and chemotaxis-stimulated migration, tumor invasion is significantly influenced by physical surroundings. How tumor cells decode information about their shape deformation under mechanical stress and adapt their dynamic behavior to escape the confined regions remains largely unknown. This review highlights recent findings that illustrate mechanical cues in confined tumor microenvironment contribute to tumor progression. We also systematically discuss the role of compression-induced deformation in cell membrane topology and cytoskeletal remodeling, as well as its biophysical mechanisms in regulating tumor invasion from a biomechanical perspective.
{"title":"The biomechanical signature of tumor invasion","authors":"Chenhe Liu , Shijiang Wang , Xin Zhang , Yifan Han , Min Tan , Jiehou Fan , Jing Du , Yubo Fan , Xinbin Zhao","doi":"10.1016/j.gendis.2025.101771","DOIUrl":"10.1016/j.gendis.2025.101771","url":null,"abstract":"<div><div>Tumor cell invasion is the key driver of metastatic dissemination, resulting in the development and progression of metastatic tumors at secondary sites, and remains the major cause of cancer-related death. Recent studies suggest that, in addition to protease-mediated degradation and chemotaxis-stimulated migration, tumor invasion is significantly influenced by physical surroundings. How tumor cells decode information about their shape deformation under mechanical stress and adapt their dynamic behavior to escape the confined regions remains largely unknown. This review highlights recent findings that illustrate mechanical cues in confined tumor microenvironment contribute to tumor progression. We also systematically discuss the role of compression-induced deformation in cell membrane topology and cytoskeletal remodeling, as well as its biophysical mechanisms in regulating tumor invasion from a biomechanical perspective.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 1","pages":"Article 101771"},"PeriodicalIF":9.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321367","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}
Pub Date : 2025-07-14DOI: 10.1016/j.gendis.2025.101772
Wenxin Zhang , Peiwen Wang , Guiqiang Yuan , Fusheng Liu , Guishan Jin , Junwen Zhang
Lipid metabolic reprogramming has emerged as a hallmark in cancer research, especially that of fatty acids (FAs). It promotes the effective utilization of the limited nutrients in the tumor microenvironment (TME) by the cells and has considerably been associated with immune escape. Tumor cells exhibit enhanced FA uptake, synthesis, and oxidation for metabolic adaptation, and non-tumor cells also undergo FA metabolic remolding in the TME. Owing to the essential role of FA metabolism in TME, the associated critical enzymes may be targeted for developing novel therapeutic approaches. This review aims to comprehensively summarize the FA metabolic landscapes in various cancers and FA-related molecular changes, FA metabolic reprogramming in different cells in the TME to identify potential targets, and FA-related cell interactions and underlying mechanisms in the TME. The findings of this study may provide insights into exploring the intricate FA metabolism–TME adaptation interplay to uncover potential metabolic targets of therapeutic significance for combinatorial strategies and enhancing immunotherapy.
{"title":"Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects","authors":"Wenxin Zhang , Peiwen Wang , Guiqiang Yuan , Fusheng Liu , Guishan Jin , Junwen Zhang","doi":"10.1016/j.gendis.2025.101772","DOIUrl":"10.1016/j.gendis.2025.101772","url":null,"abstract":"<div><div>Lipid metabolic reprogramming has emerged as a hallmark in cancer research, especially that of fatty acids (FAs). It promotes the effective utilization of the limited nutrients in the tumor microenvironment (TME) by the cells and has considerably been associated with immune escape. Tumor cells exhibit enhanced FA uptake, synthesis, and oxidation for metabolic adaptation, and non-tumor cells also undergo FA metabolic remolding in the TME. Owing to the essential role of FA metabolism in TME, the associated critical enzymes may be targeted for developing novel therapeutic approaches. This review aims to comprehensively summarize the FA metabolic landscapes in various cancers and FA-related molecular changes, FA metabolic reprogramming in different cells in the TME to identify potential targets, and FA-related cell interactions and underlying mechanisms in the TME. The findings of this study may provide insights into exploring the intricate FA metabolism–TME adaptation interplay to uncover potential metabolic targets of therapeutic significance for combinatorial strategies and enhancing immunotherapy.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101772"},"PeriodicalIF":9.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074388","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}
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