Dan Zhao, Limin Wu, Xinru Fang, Luyao Wang, Qianzhuo Liu, Pengyu Jiang, Zhihui Ji, Nian Zhang, Miaozhu Yin, Hui Han
{"title":"Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease.","authors":"Dan Zhao, Limin Wu, Xinru Fang, Luyao Wang, Qianzhuo Liu, Pengyu Jiang, Zhihui Ji, Nian Zhang, Miaozhu Yin, Hui Han","doi":"10.1016/j.cbi.2024.111060","DOIUrl":"10.1016/j.cbi.2024.111060","url":null,"abstract":"<p><p>Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111060"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Elucidating the Molecular Mechanisms of Pterostilbene Against Cervical Cancer Through an Integrated Bioinformatics and Network Pharmacology Approach","authors":"Xiang Li, Dequan Yu, Qiming Wang, Yating Chen, Hanbing Jiang","doi":"10.1016/j.cbi.2024.111058","DOIUrl":"https://doi.org/10.1016/j.cbi.2024.111058","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":"58 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141039406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elena Navarro-Carrasco, Aurora Campos-Díaz, Eva Monte-Serrano, F. Rolfs, Richard de Goeij-de Haas, T. Pham, S. Piersma, Connie R. Jimenez, Pedro A. Lazo
{"title":"Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin","authors":"Elena Navarro-Carrasco, Aurora Campos-Díaz, Eva Monte-Serrano, F. Rolfs, Richard de Goeij-de Haas, T. Pham, S. Piersma, Connie R. Jimenez, Pedro A. Lazo","doi":"10.1016/j.cbi.2024.110908","DOIUrl":"https://doi.org/10.1016/j.cbi.2024.110908","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":"14 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139873725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rafael Arsuffi-Marcon, Lizandra Gomes Souza, Artur Santos-Miranda, J. Joviano-Santos
{"title":"Neurotoxicity of Pyrethroids in exacerbating neurodegenerative diseases: From animals' models to humans’ studies","authors":"Rafael Arsuffi-Marcon, Lizandra Gomes Souza, Artur Santos-Miranda, J. Joviano-Santos","doi":"10.1016/j.cbi.2024.110911","DOIUrl":"https://doi.org/10.1016/j.cbi.2024.110911","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":"67 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139817040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}