Genes & Diseases最新文献_第4页

Amylin exacerbates tau pathology in the visual cortex of diabetic mice by impairing lysosomal activity 胰淀素通过损害溶酶体活性加剧了糖尿病小鼠视觉皮层的tau病理

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-18 DOI: 10.1016/j.gendis.2025.101602

Daniel Moreira-Silva , Melike Yuksel , Moorthi Ponnusamy , Mitchell T. Hansen , Joseph D. McMillan , Sneha Geethakrishnan , Shuai Wang , Lisa A. Collier , Gopal Thinakaran

{"title":"Amylin exacerbates tau pathology in the visual cortex of diabetic mice by impairing lysosomal activity","authors":"Daniel Moreira-Silva , Melike Yuksel , Moorthi Ponnusamy , Mitchell T. Hansen , Joseph D. McMillan , Sneha Geethakrishnan , Shuai Wang , Lisa A. Collier , Gopal Thinakaran","doi":"10.1016/j.gendis.2025.101602","DOIUrl":"10.1016/j.gendis.2025.101602","url":null,"abstract":"<div><div>The aggregation of the peptide hormone amylin in the pancreas is a pathological hallmark of type-2 diabetes. Additionally, amylin can form aggregates in the brain, promoting β-amyloid deposition and tau phosphorylation in Alzheimer's disease. The cross-seeding between amylin and tau exacerbates tau pathology spread and synaptic loss, leading to neurodegeneration and cognitive deficits. Given the link between lysosomal dysfunction and tauopathy in the brain and amylin aggregation in the pancreas, we hypothesized that amylin could potentially worsen tau pathology in diabetic mice. We administered streptozotocin and/or amylin peripherally to the PS19 model of tauopathy at 3 months and characterized them at 6 months of age. We found that streptozotocin diminished body weight gain, increased blood glucose levels, worsened motor performance, and improved fear-conditioned memory in PS19 mice. Both amylin and streptozotocin administration prompted the emergence of tau pathology in the pancreas, which coincided with a decrease in the number of lysosomes in pancreatic islets. Mice treated with amylin and streptozotocin also developed robust tau pathology concomitant with lowering lysosomal cathepsin D levels in the visual cortex. These findings suggest that in diabetic mice, amylin administration diminished pancreatic lysosomes, possibly increasing the number of amylin aggregates that reached the brain and contributing to the worsening of tau pathology due to lysosomal impairment in the visual cortex. The outcome of our research enhances the understanding of the cellular pathways by which amylin may serve as a link between the pancreas-brain axis during diabetes, influencing the risk of developing tau pathology.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101602"},"PeriodicalIF":6.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322051","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

Chlorpyrifos induces spermatogenic dysfunction via ferroptosis in Sertoli cells 毒死蜱通过支持细胞的铁下垂诱导生精功能障碍

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-14 DOI: 10.1016/j.gendis.2025.101601

Yan Fu , Xu Huang , Siyuan Wang , Qitong Guo , Yuhao Wu , Xiangqin Zheng , Junke Wang , Shengde Wu , Lianju Shen , Guanghui Wei

{"title":"Chlorpyrifos induces spermatogenic dysfunction via ferroptosis in Sertoli cells","authors":"Yan Fu , Xu Huang , Siyuan Wang , Qitong Guo , Yuhao Wu , Xiangqin Zheng , Junke Wang , Shengde Wu , Lianju Shen , Guanghui Wei","doi":"10.1016/j.gendis.2025.101601","DOIUrl":"10.1016/j.gendis.2025.101601","url":null,"abstract":"<div><div>Chlorpyrifos (CPF), a widely used organophosphate pesticide, accumulates in the environment and affects human health. Its neurotoxicity has been extensively studied, and recent research has revealed that it can also lead to abnormal spermatogenesis. However, the factors and molecular mechanisms involved remain unclear. In this study, male Sprague–Dawley rats were gavaged with different concentrations of CPF for 30 days, resulting in a disrupted blood-testis barrier (BTB) and abnormal spermatogenesis. RNA sequencing analysis of Sertoli cells, the primary components of the BTB and key targets of environmental toxins, revealed that ferroptosis-related genes were predominantly among the differentially expressed genes. The expression of ferroptosis-related markers was up-regulated, malondialdehyde and Fe<sup>2+</sup> levels were elevated, and glutathione levels were reduced in CPF-exposed testicular tissue and its metabolite TCP-exposed Sertoli cells, confirming that CPF exposure triggered ferroptosis in testes and Sertoli cells. Moreover, treatment with ferrostatin-1, a ferroptosis inhibitor, restored Sertoli cell junctional function. Given the important roles of clockophagy and the HIF-1α pathway in ferroptosis, we investigated the activity of clockophagy in testes and Sertoli cells. Unexpectedly, clockophagy activity was found to be enhanced by the significantly reduced expression levels of ARNTL and HIF-1α following CPF and TCP exposure. Notably, <em>Arntl</em> knockdown impaired Sertoli cell junctional function. Collectively, these findings strongly indicate that CPF induces ferroptosis in Sertoli cells through activating clockophagy, resulting in the decreased expression of HIF-1α and BTB-associated proteins; this ultimately leads to the disruption of BTB integrity and spermatogenesis dysfunction.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101601"},"PeriodicalIF":6.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366327","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

NKAPL suppresses NSCLC progression by enhancing the protein stability of TRIM21 and further inhibiting the NF-κB signaling pathway NKAPL通过增强TRIM21蛋白稳定性和进一步抑制NF-κB信号通路抑制NSCLC进展

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-11 DOI: 10.1016/j.gendis.2025.101598

Chunhong Li , Qiang Wang , Fengsheng Dai , Xinni Xiang , Lin Yi , Bianfei Shao , Qian Li , Xi Peng , Renyan Li , Fang Luo , Zhongjun Wu , Tingxiu Xiang

{"title":"NKAPL suppresses NSCLC progression by enhancing the protein stability of TRIM21 and further inhibiting the NF-κB signaling pathway","authors":"Chunhong Li , Qiang Wang , Fengsheng Dai , Xinni Xiang , Lin Yi , Bianfei Shao , Qian Li , Xi Peng , Renyan Li , Fang Luo , Zhongjun Wu , Tingxiu Xiang","doi":"10.1016/j.gendis.2025.101598","DOIUrl":"10.1016/j.gendis.2025.101598","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) remains a leading cause of mortality in the clinic. Previous studies have demonstrated that the NF-kappa-B activating protein like (NKAPL) is positively correlated with prognosis in several types of cancers. However, the role of NKAPL in the progression of NSCLC remains unclear. The expression and promoter methylation of NKAPL were examined by real-time PCR, quantitative PCR, and methylation-specific PCR. The functional impacts of NKAPL on NSCLC proliferation were explored by CCK8 assay and colony formation assay. Transwell assay was conducted to investigate the role of NKAPL in NSCLC cell migration and invasion, and the influence on metastasis was verified <em>in vivo</em>. Flow cytometry was exploited to analyze the influence on the cell cycle and apoptosis. The regulatory mechanism of NKAPL was investigated by immunoprecipitation-mass spectrometry, western blotting, immunofluorescence, and immunohistochemistry. NKAPL was down-regulated due to promoter methylation, which was associated with poor prognosis in NSCLC patients, while the up-regulation of NKAPL suppressed NSCLC cell proliferation and metastasis both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, the NF-κB signaling pathway was inhibited because the up-regulation of NKAPL increased the stability and expression of TRIM21. NKAPL suppressed NSCLC cell proliferation and metastasis both <em>in vitro</em> and <em>in vivo</em> by increasing the stability and expression of TRIM21 and subsequently inhibiting the NF-κB signaling pathway.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101598"},"PeriodicalIF":6.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321992","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

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

Corrigendum to “Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia” [Genes & Dis 11 (2024) 413–429] “小鼠肠道Cdc42单基因缺陷导致黏膜炎症，诱发隐窝发育不良”的勘误表[基因与疾病11 (2024)413-429]

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-04 DOI: 10.1016/j.gendis.2025.101579

Dongsheng Zhang , Wenjuan Tang , Haitao Niu , William Tse , Hai-Bin Ruan , Helmut Dolznig , Thomas Knösel , Friedrich KarlHeinz , Madeleine Themanns , Jiang Wang , Mingquan Song , Lee Denson , Lukas Kenner , Richard Moriggl , Yi Zheng , Xiaonan Han

引用次数: 0

Bulk RNA sequencing combined with single-cell RNA sequencing analysis revealed the ferroptosis immune target of osteoarthritis synovial fibroblasts 大量RNA测序结合单细胞RNA测序分析揭示了骨关节炎滑膜成纤维细胞的铁下垂免疫靶点

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-04 DOI: 10.1016/j.gendis.2025.101587

Qian Wu , Liang Zhou , Yuan Xue , Jiaqian Wang

引用次数: 0

Single-cell landscape of immunological responses in patients with juvenile idiopathic arthritis 青少年特发性关节炎患者免疫反应的单细胞景观

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-03 DOI: 10.1016/j.gendis.2025.101577

Yun Liu , Xiwen Luo , Liuqing Yang , Qiang Luo , Xiya Luo , Li Xu , Yating Wang , Yunfei An , Yupeng Cun , Xuemei Tang

{"title":"Single-cell landscape of immunological responses in patients with juvenile idiopathic arthritis","authors":"Yun Liu , Xiwen Luo , Liuqing Yang , Qiang Luo , Xiya Luo , Li Xu , Yating Wang , Yunfei An , Yupeng Cun , 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<sup>+</sup> T, CD8<sup>+</sup> 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<sup>+</sup> T and CD8<sup>+</sup> 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}

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

Crowdedness imposes stress on tumor metastasis in Drosophila melanogaster 拥挤对黑腹果蝇的肿瘤转移有应激作用

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-27 DOI: 10.1016/j.gendis.2025.101574

Wenzhe Li , Zhiyuan Zhang , Lealia Li Xiong , Huiyi Yu , Jiuhong Huang , Ruixiu Cao , Lei Xue

引用次数: 0

Clinical impact of the TPM1 p.Tyr221Cys variant causing hypertrophic cardiomyopathy TPM1 p.Tyr221Cys变异引起肥厚性心肌病的临床影响

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-26 DOI: 10.1016/j.gendis.2025.101575

Alessio Marinelli , Giuliana Longo , Vincenzo Cirigliano , Esther Campopiano , Clementina Dugo , Luca Ghiselli , Andrea Chiampan , Gianluca Ferri , Alessandro Costa , Stefano Bonapace , Laura Lanzoni , Giulio Molon

引用次数: 0