BioFactors最新文献

{"title":"VGLL3 Regulates DAPK2-Mediated Autophagy During Osteoblast Differentiation","authors":"Yuhan He,&nbsp;Ziyi Wang,&nbsp;Yao Weng,&nbsp;Heriati Sitosari,&nbsp;Yilin Zheng,&nbsp;Yaxin Qu,&nbsp;Mika Ikegame,&nbsp;Hirohiko Okamura","doi":"10.1002/biof.70104","DOIUrl":"10.1002/biof.70104","url":null,"abstract":"<p>Vestigial-like family member 3 (VGLL3), a transcriptional cofactor of the TEA domain family, has been previously identified as a regulator of osteoblast differentiation. Building upon our previous findings, we investigated VGLL3 function in MC3T3-E1 osteoblasts using an integrated approach combining transcriptomic analysis and functional assays to identify its downstream effectors and explore associated autophagy mechanisms. RNA-seq analysis of Vgll3-knockdown (shVgll3) cells identified death-associated protein kinase 2 (DAPK2), a regulator of autophagy, as a downstream effector. Autophagic activity was examined using transmission electron microscopy and western blot analysis of LC3-II and p62 proteins. The effects of Dapk2 knockdown (shDapk2) on osteoblast differentiation were evaluated using qPCR, western blotting, alkaline phosphatase staining, and Alizarin Red staining. Rapamycin treatment was used to determine whether pharmacologic activation of autophagy could restore osteoblast function. Vgll3 knockdown significantly suppressed autophagic flux, as evidenced by fewer autophagic vacuoles, decreased LC3-II accumulation, and increased p62 expression. A comparable reduction in autophagic activity was observed in shDapk2 cells and was accompanied by impaired osteoblast differentiation. Rapamycin treatment partially restored autophagy and osteogenic differentiation in Vgll3-deficient cells. Finally, overexpression of DAPK2 partially rescued autophagic activity and osteogenic differentiation in shVgll3 cells, supporting its role as a key downstream functional effector. FOXM1 was further implicated as a potential transcriptional regulator contributing to DAPK2 expression. Collectively, our findings suggest that VGLL3 may influence osteogenic differentiation in osteoblasts, potentially involving DAPK2-associated autophagy.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761206","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 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097892","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 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148095884","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 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148095885","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":"Dengue Virus Capsid Protein Interaction With Nucleic Acids","authors":"Nelly M. Silva,&nbsp;Ana S. Martins,&nbsp;Nina E. Karguth,&nbsp;Maria J. Sarmento,&nbsp;Francisco J. Enguita,&nbsp;Roland G. Huber,&nbsp;Ivo C. Martins,&nbsp;Nuno C. Santos","doi":"10.1002/biof.70105","DOIUrl":"10.1002/biof.70105","url":null,"abstract":"<p>Dengue virus (DENV) transmission has greatly increased in the last decade, partly due to the geographical expansion of <i>Aedes</i> spp. mosquitoes. These arthropods are now found even in temperate climates, including Europe, where outbreaks have occurred. A better understanding of the life cycle is essential, as it may enable the development of specific treatments or therapies, which are currently lacking. Recent breakthroughs concerning the viral capsid (C) protein structure and function are encouraging. It is now clear that the C protein binds both to host lipid droplets and to the viral genome—interactions crucial for viral encapsidation and replication. Here, we investigate how DENV C associates with the viral genome. Using DENV C and single-stranded DNA sequences analogous to relevant genomic regions, we biophysically characterize their interaction. A decrease in fluorescence intensity and lifetime, as well as changes in the protein secondary structure, were observed upon interacting with single-stranded DNA. These results are consistent with molecular condensation, supporting a possible liquid–liquid phase separation contributing to DENV C–nucleic acid complex formation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761167","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":"Mechanism of YTHDF2-Mediated Epigenetic Modification in the Proliferation and Invasion of Renal Cell Carcinoma Cells","authors":"Xiaomeng Zhang,&nbsp;Yan Zhang,&nbsp;Xin Yang,&nbsp;Ye Fan,&nbsp;Yingying Zhu","doi":"10.1002/biof.70099","DOIUrl":"10.1002/biof.70099","url":null,"abstract":"<div>\u0000 \u0000 <p>Renal cell carcinoma (RCC) ranks as the most prevalent form of urogenital cancer. This research aims to investigate the role of YTHDF2 in the RCC progression and identify new therapeutic targets for RCC. YTHDF2, E2F2, and CORO6 were assayed via qRT-PCR and Western blot. YTHDF2 was downregulated in RCC cells, while E2F2 and CORO6 were upregulated. After overexpressing YTHDF2 in RCC cells, cell viability, proliferation, invasion, and migration were measured. m6A levels were assessed. The binding of YTHDF2 to E2F2 was detected. The E2F2 mRNA stability was detected. The binding of E2F2 to the CORO6 promoter was analyzed. Overexpression of E2F2 or CORO6 was combined with YTHDF2 overexpression to validate the mechanism. Tumor growth and metastasis were observed. Results confirmed that YTHDF2 overexpression decreased cell proliferation, invasion, and migration. YTHDF2 bound to the m6A sites on E2F2 mRNA, promoted E2F2 degradation, and inhibited E2F2 expression. E2F2 bound to the CORO6 promoter to enhance CORO6 expression. Overexpression of E2F2 or CORO6 partially reversed the suppressive effects of YTHDF2 overexpression on RCC cell proliferation and invasion. YTHDF2 overexpression suppressed tumor growth and metastasis. In conclusion, YTHDF2 overexpression suppresses RCC progression by inhibiting E2F2 expression and reducing CORO6 expression via m6A modification.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761177","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":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148091000","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":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148087356","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":"ISG15 Mediates Oxidative Stress Modulation in T2DM Patients by Directly Targeting PIK3R2","authors":"Mei-qi He,&nbsp;Jie Liu,&nbsp;Gao-peng Guan,&nbsp;Hong Liu,&nbsp;Li-ping Luo,&nbsp;Yi-wen Fu,&nbsp;Xin-xing Wan,&nbsp;Ping Jin","doi":"10.1002/biof.70103","DOIUrl":"10.1002/biof.70103","url":null,"abstract":"<div>\u0000 \u0000 <p>Type 2 diabetes (T2DM), a chronic metabolic disorder characterized by pancreatic β-cell dysfunction and insulin resistance, is closely associated with oxidative stress. Interferon-stimulated gene 15 (ISG15), a ubiquitin-like modifier, has been implicated in redox regulation; however, its mechanistic role in T2DM progression remains unclear. To identify novel bio-factors contributing to T2DM, peripheral blood mononuclear cells (PBMCs) and serum samples were collected from T2DM patients and age-/BMI-matched healthy controls to quantify ISG15 expression. Complementary studies utilized a T2DM mouse model to assess β-cell-specific ISG15 expression within pancreatic islets. In parallel, MIN6 pancreatic β-cells were exposed to pathophysiological stressors, including hyperglycemic/hyperlipidemic (HG/PG) conditions and hydrogen peroxide (H₂O₂)-induced oxidative stress, to mimic the diabetic microenvironment. Protein–protein interactions were evaluated, and functional analyses were conducted following ISG15 genetic ablation. The results demonstrated that ISG15 expression was significantly elevated in PBMCs and serum from T2DM patients compared to healthy controls. Similarly, T2DM mouse models exhibited marked upregulation of ISG15 in islet β-cells. In vitro, exposure to HG/PG or H₂O₂ increased ISG15 levels, reduced MIN6 cell viability, and heightened reactive oxygen species (ROS) accumulation. Mechanistic studies revealed that ISG15 directly interacts with the PI3K regulatory subunit PIK3R2, suppressing its activity and thereby disrupting the PI3K/AKT/Nrf2 antioxidant signaling axis. This disruption led to exacerbated oxidative stress. Collectively, these findings indicate that ISG15 acts as a novel mediator of oxidative stress in T2DM by targeting and inhibiting the PIK3R2-dependent PI3K/AKT/Nrf2 pathway. These results uncover a previously unrecognized molecular mechanism driving β-cell dysfunction and identify ISG15 as a potential therapeutic target for mitigating oxidative damage in diabetes.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761235","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":"Phytoestrogenic Isoflavone Formononetin Attenuates Motor Deficits and Mitochondrial Impairment by Regulating SIRT1/PGC-1α/NRF1/TFAM Axis in Parkinson's Disease","authors":"Jasleen Kaur,&nbsp;Saba Naqvi","doi":"10.1002/biof.70098","DOIUrl":"10.1002/biof.70098","url":null,"abstract":"<div>\u0000 \u0000 <p>Parkinson's disease (PD) is a progressive neurodegenerative disorder. An essential early hallmark of PD is disrupted mitochondrial dynamics driven by impaired cellular energy homeostasis. Therapeutic interventions restoring mitochondrial function and biogenesis hold promise for neuroprotection in PD. In the present study, the neuroprotective effects of formononetin (FMN) were evaluated in both MPP⁺-induced SH-SY5Y cells and the MPTP-induced mouse model of Parkinson's disease, using concentrations of 5, 10, 20, and 40 μM in vitro and doses of 25 and 40 mg/kg in vivo. To evaluate its biological activity, we employed western blotting and immunofluorescence assay to quantify the expression of disease-relevant markers. Mitochondrial health was further assessed using Mitotracker, alongside reactive oxygen species (ROS) assessment. Motor behavior and molecular endpoint parameters were also measured. Our results demonstrated that FMN significantly attenuates MPP⁺/MPTP-induced neurotoxicity, improves motor function, and restores the expression of PGC-1α, tyrosine hydroxylase, and key mitochondrial proteins involved in mitochondrial DNA replication. Enhancement of mitochondrial fusion proteins and other transcriptional regulators was also observed in the administered groups. Flow cytometry and imaging analyses confirmed that FMN-mediated PGC-1α activation preserves mitochondrial integrity and reduces oxidative stress. Altogether, these findings provide evidence that formononetin exerts neuroprotective effects in PD by modulating the PGC-1α signaling axis.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721689","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}