IUBMB Life最新文献

{"title":"Future Prospects of Imatinib in Advanced Pulmonary Hypertension Management","authors":"Federica Davì,&nbsp;Stella Mangione,&nbsp;Antonella Iaconis,&nbsp;Tiziana Genovese,&nbsp;Nicla Tranchida,&nbsp;Salvatore Cuzzocrea","doi":"10.1002/iub.70098","DOIUrl":"10.1002/iub.70098","url":null,"abstract":"<p>Pulmonary arterial hypertension (PAH) is a severe, progressive disease characterized by elevated pulmonary arterial pressure and increased vascular resistance. This hemodynamic strain forces the right ventricle to pump against a high-pressure system, ultimately leading to right-sided heart failure and death. The pathogenesis of PAH involves a complex interplay of vasoconstriction, chronic inflammation, and pathological remodeling of the pulmonary vessel walls—specifically hypertrophy of the smooth muscle and intimal layers—driven by molecular imbalances and genetic predispositions. Current FDA-approved therapies primarily manage symptoms through vasodilation but fail to directly target the underlying vascular remodeling. Imatinib, a tyrosine kinase inhibitor originally developed for oncological indications, has emerged as a potential disease-modifying agent for PAH. By inhibiting platelet-derived growth factor receptors (PDGFR), imatinib targets the aberrant proliferation of smooth muscle cells, offering a mechanism to potentially reverse or arrest vascular remodeling. Clinical trials, including the IMPRES study, have demonstrated encouraging hemodynamic improvements in patients with severe PAH refractory to standard therapies. However, systemic safety concerns and dose-dependent adverse reactions have limited its clinical approval. This review examines the pharmacological rationale for imatinib, its impact on vascular structure, and the safety signals observed in long-term studies. Furthermore, it discusses emerging strategies, such as inhaled formulations and pharmacogenetic approaches (e.g., the PIPAH study), aimed at enhancing the efficacy-to-safety ratio of kinase inhibitors to improve long-term outcomes for patients with PAH.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148095261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OTUD1 Relieves Coxsackievirus-Induced Ferroptosis and Inflammation in Myocardial Cells by Stabilizing NRF2 and Inhibiting NF-κB Signaling","authors":"Yanfei Chen,&nbsp;Jingxuan Xiong,&nbsp;Yang Xiao,&nbsp;Bin Li,&nbsp;Zhongjian Su,&nbsp;Li Jiang,&nbsp;Xing Zhang","doi":"10.1002/iub.70094","DOIUrl":"10.1002/iub.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Viral myocarditis (VMC) is a common inflammatory myocardial disease in children and is associated with heart failure and sudden cardiac death. Coxsackievirus B3 (CVB3) is the most common pathogen, and inflammation and ferroptosis are the key pathological events of CVB3-induced myocarditis. Studies indicate that the deubiquitinase OTUD1 is involved in cardiac inflammation and ferroptosis, but its role in CVB3-induced myocardial inflammation and ferroptosis remains unclear. Therefore, this study aimed to investigate the function and mechanism of OTUD1 in inflammation and ferroptosis in myocardial cells in the context of CVB3 infection. Mice and H9c2 cells infected with the CVB3 strain were used to construct in vivo and in vitro CVB3 myocarditis models. The inflammatory cytokines IL-1β, IL-6, and TNF-α; Fe²⁺; MDA; SOD; and the myocardial injury markers CK-MB and cTnI were detected using assay kits. Cell viability was measured by a CCK-8 assay, myocardial injury was evaluated by HE staining, and the expression of key proteins was detected by western blotting, immunohistochemistry, and immunofluorescence. After CVB3 infection, heart tissue was damaged; the levels of CK-MB and cTnI increased; the viability of H9c2 cells decreased; the levels of IL-1β, IL-6, TNF-α, Fe²⁺, MDA, and ROS increased; the level of SOD decreased; and the expression of the ferroptosis-related proteins GPX4 and SLC7A11 decreased. Second, CVB3 infection also repressed OTUD1 expression in mouse heart tissues and H9c2 cells. Importantly, the above effects of CVB3 were partially attenuated by overexpression of OTUD1, indicating that OTUD1 can inhibit CVB3-induced myocardial ferroptosis and inflammation. In addition, CVB3 infection also repressed the expression of NRF2 in vivo and in vitro and promoted the activation of NF-κB signaling. A mechanistic study revealed that OTUD1 could relieve CVB3-induced inflammation and ferroptosis by stabilizing NRF2 expression and inhibiting NF-κB signaling activation. Our study revealed the potential of OTUD1 to ameliorate inflammation and ferroptosis in myocardial cells induced by CVB3 infection, providing a potential intervention target for the treatment of VMC.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148085189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"POBS Relieves Antigen-Induced Experimental Sjögren's Disease by Regulating B Lymphocyte Subsets via CXCL13/CXCR5 Signaling Pathway","authors":"Xiaosheng Lei,&nbsp;Na Li,&nbsp;Qiaolin Zhang,&nbsp;Meng Yang,&nbsp;Yuhao Xuan,&nbsp;Qi Liu,&nbsp;Xiaoyun Chen,&nbsp;Wei Wei,&nbsp;Ruilin Li,&nbsp;Huaxun Wu","doi":"10.1002/iub.70095","DOIUrl":"10.1002/iub.70095","url":null,"abstract":"<div>\u0000 \u0000 <p>Sjögren's Disease (SjD) is an autoimmune disorder characterized by lymphocyte infiltration into exocrine glands, leading to dry eyes and mouth. Its pathogenesis involves B cell hyperactivity and type I interferon activation. CXCL13 promotes B cell migration and ectopic germinal center formation in target tissues. This study investigated whether paeoniflorin-6′-O-benzene sulfonate (POBS) alleviates Experimental Sjögren's Disease (ESjD) by modulating B cell subsets via the CXCL13/CXCR5 pathway. Altered B cell subsets were observed in SjD patient blood and labial glands, suggesting memory B cell migration. In SG-protein immunised ESjD mice, POBS reduced lymphocyte infiltration in submandibular glands, suppressed splenic B cell activation, and modulated peripheral B cell subpopulations. POBS also downregulated CXCL13 and CXCR5 expression. These results demonstrate that POBS attenuates gland damage and immune infiltration by regulating B cells via CXCL13/CXCR5, indicating its therapeutic potential for SjD.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148080839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148064035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148064191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALG8-Driven Metabolic Reprogramming in Polycystic Kidney Disease: A Systematic Synthesis of Evidence Linking Glycosylation Defects to Metabolic Signaling","authors":"Xiaoran Wang,&nbsp;Zhili Huang,&nbsp;Wen Zhang","doi":"10.1002/iub.70091","DOIUrl":"10.1002/iub.70091","url":null,"abstract":"<div>\u0000 \u0000 <p>Endoplasmic reticulum glycosyltransferase ALG8 controls metabolic fate in autosomal dominant polycystic kidney disease (ADPKD). In this paper, we summarize human genetics, cell-based, and organ-based evidence to investigate whether ALG8 variants affect cyst initiation and metabolic states of ADPKD. Population screening showed ALG8 variant enrichment in ADPKD cohorts (OR = 9.75, P0.001); loss-of-function alleles interact with PKD1 mutations to accelerate cystogenesis. ALG8 deficiency leads to metabolic collapse by several mechanisms. Impaired polycystin-1 glycosylation disrupts ER-to-cilium trafficking, prevents PC1/PC2 complex assembly, and impedes calcium-dependent ATP production. Deficient LRP6 glycosylation activates Wnt/−catenin signaling. This shifts metabolism toward aerobic glycolysis, leading to Warburg-like reprogramming seen in malignancy. Single cell analysis showed ALG8 deficient cystic epithelium has tumor-like metabolic signatures, such as increased glucose uptake, suppressed oxidative phosphorylation, and glutamine dependence. Chemical chaperones that restore folding capacity or glycosylation inhibitors that lower anabolic demand both suppressed cyst formation in ALG8/PKD1-deficient organoids. The connection from ALG8 loss to “oncogenic-like” metabolism remains incomplete. Study-to-study variability in model system, genotype, and endpoint still limits cross-cohort comparison. This dual vulnerability—of protein folding and glycosylation—is due to the fragile metabolic balance in cystogenesis. These results recast ADPKD as a metabolic disorder where glycosylation defects link ciliary dysfunction to oncogenic transformation. We focus on three areas: (i) convergence with multiple lines of evidence, (ii) disagreement, and (iii) testable predictions for future studies and trials. The overlap between cystogenic and tumorigenic metabolic programs suggests cancer metabolic inhibitors may be reused for ADPKD in near-term translation. By defining ALG8 as a metabolic checkpoint in polycystic disease, we uncover targets at the glycosylation–metabolism interface.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148075241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}