BioFactors最新文献

{"title":"ANXA5: A Multi-Omics-Derived, UPR-Associated Dual-Function Biomarker for Prognosis and Immunotherapy Response Prediction in Glioma","authors":"Jiachong Wang,&nbsp;Haijun Guo,&nbsp;Wei Zheng,&nbsp;Maximo Lin,&nbsp;Chunyuan Zhang,&nbsp;Biying Zeng,&nbsp;Duorong Wu,&nbsp;Zigui Chen,&nbsp;Changfeng Miao,&nbsp;Chunhai Tang,&nbsp;Qisheng Luo","doi":"10.1002/biof.70092","DOIUrl":"10.1002/biof.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioma, a highly aggressive brain cancer, thrives in an immunosuppressive tumor microenvironment (TME). The Unfolded Protein Response (UPR) is a key adaptive stress pathway implicated in therapy resistance. To discover clinically actionable biomarkers, we employed an integrated multi-omics strategy, combining single-cell and bulk transcriptomic data from multiple glioma cohorts. Using hdWGCNA network analysis, we identified a UPR-associated gene module that defined two molecular subtypes with stark survival differences. Through a rigorous machine learning pipeline (Random Survival Forest, LASSO, and CoxBoost), ANXA5 emerged as the central prognostic gene. High ANXA5 expression consistently predicted poorer overall survival across eight independent datasets, validating its robust prognostic value. Functionally, ANXA5 was linked to extracellular matrix remodeling and immune modulation. Multi-omics profiling revealed that ANXA5-high gliomas exhibit a T-cell-inflamed yet immunosuppressive TME, characterized by elevated immune checkpoint expression. Crucially, ANXA5 demonstrated strong predictive power for response to immune checkpoint blockade (ICB), showing significant correlation with nine established immunotherapy response signatures and accurately discriminating responders from non-responders in six independent ICB-treated clinical cohorts (AUC: 0.65–0.78). Genomic analysis associated ANXA5 expression with distinct mutation patterns (EGFR/PTEN vs. IDH1/TP53). In vitro knockdown of ANXA5 confirmed its oncogenic role, as it suppressed glioma cell proliferation and invasion. Our study establishes ANXA5 as a prime example of a translatable biomarker discovered through multi-omics integration. It functions dually as a prognostic indicator and a predictive biomarker for immunotherapy, offering a tangible framework for patient stratification and personalized therapeutic strategies in glioma, thereby bridging a critical gap toward clinical translation.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472575","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":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148071352","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":"Elesclomol Promotes oxLDL-Mediated Foam Cell Formation and Cuproptosis in Macrophages","authors":"Daming Jiang,&nbsp;Yigong Zhang","doi":"10.1002/biof.70091","DOIUrl":"10.1002/biof.70091","url":null,"abstract":"<div>\u0000 \u0000 <p>The formation of macrophage-derived foam cells is a critical factor in the development of atherosclerotic lesions. However, the mechanisms through which the cuproptosis pathway contributes to macrophage foam cell formation remain unclear. This study aimed to investigate the role and mechanisms of the cuproptosis inducer Elesclomol in atherosclerosis. Macrophages were exposed to ox-LDL to establish a foam cell model. Subsequently, CCK8, oil red O staining, and Western blot were used to investigate foam cell formation and the cuproptosis pathway in macrophages. Furthermore, proteomics analysis was employed to explore the molecular mechanisms underlying the effects of Elesclomol. The results demonstrated that Elesclomol promoted foam cell formation by increasing lipid accumulation in ox-LDL-treated macrophages, which was attributed to the inhibition of cholesterol efflux mediated by ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1). Additionally, Elesclomol enhanced the cuproptosis pathway in macrophages, leading to increased intracellular ROS accumulation and consequent cell death. Mechanistically, the cytotoxic effects of Elesclomol were mediated through activation of the mitogen-activated protein kinase (MAPK) pathway and upregulation of metallothionein 2A (MT2A). Collectively, these findings underscore the critical role of cuproptosis in the pathogenesis of atherosclerosis and suggest that targeting this pathway may represent a promising therapeutic strategy for the disease.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375926","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":"Coenzyme Q10 Mitigates Myocardial Infarction by Modulating HDAC4 O-GlcNAcylation","authors":"Wei Xie,&nbsp;Xiang Gao,&nbsp;Shifei Song,&nbsp;Na Li,&nbsp;Liang Zhao","doi":"10.1002/biof.70085","DOIUrl":"10.1002/biof.70085","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial infarction (MI) is a major cause of mortality. This study explores the cardioprotective effects of Coenzyme Q10 (CoQ10) and its molecular mechanisms in MI. A rat myocardial ischemia–reperfusion model was established, and infarct size was assessed via triphenyl tetrazolium chloride (TTC) staining. Hematoxylin and eosin (H&amp;E) and Masson's staining analyzed histological changes, while terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry assessed apoptosis. Western blot and immunofluorescence evaluated collagen I, collagen III, α-SMA, histone deacetylases (HDACs) (4,5,7,9,11), O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and O-GlcNAcylation. Enzyme-linked immunosorbent assay (ELISA) measured tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-β, suppression of tumorigenicity (ST)-2, galectin (Gal)-3, and growth differentiation factor (GDF)-15, while cell counting kit-8 (CCK-8), EdU, and Transwell migration assays assessed fibroblast proliferation and migration. O-GlcNAcylation of HDAC4 was analyzed using Click-iT labeling and immunoprecipitation. Cycloheximide chase assay and ubiquitination assay detected the impact of O-GlcNAcylation at Ser455 on HDAC4 protein stability. CoQ10 significantly improved cardiac function in rat models, reducing infarct size, apoptosis, fibrosis, and inflammation. CoQ10 treatment in MIRI rats increased ejection fraction (EF) and fractional shortening (FS), reduced infarct volume (TTC staining), and decreased collagen deposition (Masson's, Sirius Red staining). TUNEL and flow cytometry confirmed reduced cardiomyocyte apoptosis, while ELISA showed lower TNF-α, IL-6, and TGF-β, indicating suppressed inflammation. At the molecular level, CoQ10 reduced global O-GlcNAcylation together with decreased OGT and increased OGA expression. Western blot and immunofluorescence confirmed reduced HDAC4 levels, linked to O-GlcNAcylation suppression particularly at Ser455. CoQ10 promoted the degradation of HDAC4 through the precise inhibition of its stabilizing O-GlcNAc modification at Ser455. In vitro, CoQ10 enhanced oxygen–glucose deprivation and reperfusion (OGD/R) cardiomyocyte survival, reduced apoptosis (TUNEL, flow cytometry), and suppressed HDAC4 expression. In fibroblasts, CoQ10 inhibited TGF-β1-induced proliferation/migration (CCK-8, EdU, Transwell assays) and reduced collagen I, collagen III, and α-SMA expression, indicating anti-fibrotic effects. Furthermore, HDAC4 knockdown in vivo improved cardiac function, and in vitro reduced cardiomyocyte apoptosis and fibroblast proliferation/migration, reinforcing HDAC4's role in MI pathology. CoQ10 exerts cardioprotective effects by modulating O-GlcNAc modification and HDAC4 expression.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147363858","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":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066213","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":"ANO6 Confers Paclitaxel Resistance by Targeting Ferroptosis in Cervical Cancer","authors":"Yanming Cao,&nbsp;Yuping peng,&nbsp;Jian Shen","doi":"10.1002/biof.70070","DOIUrl":"10.1002/biof.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>Paclitaxel (PTX) resistance limits cervical cancer therapy. Ferroptosis suppression via GPX4 and redox remodeling has emerged as a resistance mechanism, but upstream regulators remain unclear. To determine whether ANO6 drives PTX resistance by inhibiting ferroptosis and to define the ANO6–GPX4 axis mechanistically and therapeutically. Transcriptomic analyses, immunohistochemistry on clinical specimens, and cervical cancer cell models with gain/loss of ANO6 were combined with ferroptosis assays, mitochondrial imaging, apoptosis/viability assays, and Co-IP/CHX chase to assess ANO6–GPX4 interaction and stability. GPX4 transcriptional control was probed by ChIP-qPCR and dual-luciferase. PTX sensitivity was tested in vitro and in xenografts, with or without the ferroptosis inducer RSL3. ANO6 was overexpressed in cervical cancer and associated with worse prognosis. ANO6 knockdown reduced GPX4, SLC7A11, and NRF2, increased ACSL4, elevated lipid peroxidation and iron load, disrupted mitochondrial integrity, and heightened PTX cytotoxicity; ANO6 overexpression had opposite effects. ANO6 physically associated with GPX4 and preserved its protein stability; NRF2 enhanced GPX4 promoter activity, supporting a dual (post-translational/transcriptional) maintenance of GPX4 under ANO6 control. In PTX-resistant cells, ANO6 was upregulated; its depletion restored ferroptosis and PTX sensitivity, whereas GPX4 overexpression rescued resistance. In vivo, ANO6 overexpression promoted tumor growth and PTX resistance, while PTX + RSL3 synergistically suppressed tumors and reversed GPX4-axis signaling. ANO6 confers PTX resistance by sustaining GPX4-dependent ferroptosis evasion and mitochondrial homeostasis. Targeting the ANO-GPX4 axis, alone or combined with ferroptosis induction, may improve chemotherapy sensitivity in cervical cancer.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353596","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":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148064424","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":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148064034","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":"Modulatory Effect of Natural Antioxidants on Tissue Transglutaminase Levels in Olfactory Ensheathing Cells Exposed to Amyloid-β: Integrated Biochemical and Computational Analysis","authors":"Rosalia Pellitteri,&nbsp;Cristina Tomasella,&nbsp;Maria Assunta Chiacchio,&nbsp;Matteo Pappalardo,&nbsp;Laura Legnani,&nbsp;Michela Spatuzza,&nbsp;Alessandro Massaro,&nbsp;Salvatore Guccione,&nbsp;Agatina Campisi","doi":"10.1002/biof.70088","DOIUrl":"10.1002/biof.70088","url":null,"abstract":"<p>Herein, we adopted a dual approach combining molecular modeling and biological studies, in order to assess the interaction between four selected natural antioxidants (NAs; berberine, curcumin, astaxanthin, indicaxanthin) and tissue transglutaminase (TG2) levels both in the absence and in the presence of full native peptide of amyloid-β (Aβ). Docking studies were performed to ascertain the binding affinity of NAs against the TG2 closed, Ca²⁺-bound closed, and open forms. In the biological investigation, the effect of berberine and curcumin treatment on TG2 in Olfactory Ensheathing Cells (OECs) exposed to Aβ(1–42) or to Aβ(25–35), a Aβ toxic fragment, or to reverse-sequence fragment Aβ(35–25), an Aβ not toxic fragment, was tested. In addition, their effect on the percentage of cell viability and cytoskeleton marker (GFAP, vimentin and nestin) levels were evaluated. The role of berberine and curcumin on both endocellular levels of reactive oxygen species (ROS) and apoptotic pathway activation were also assessed. Our findings demonstrate that pretreatment of OECs with these NAs counteracted the Aβ-induced upregulation of TG2, restoring its expression to control levels and preserving its predominant cytosolic localization. Furthermore, antioxidant pretreatment reinstated cell viability, normalized the expression of GFAP, vimentin, and nestin, reduced intracellular ROS accumulation, and prevented activation of the apoptotic cascade. Our findings demonstrate that integrating computational and biological approaches, enhances the identification of potent therapeutic agents and also highlights berberine and curcumin as promising candidates for the development of novel neuroprotective drugs against neurodegenerative disorders, including Alzheimer's disease.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12953212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343588","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":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148095571","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}