International Journal of Biological Sciences最新文献

{"title":"Decoding Vascular Senescence: Cellular Insights and Therapeutic Strategies.","authors":"Mengyuan Gao, Chongjin Zhong, Jiajia Shen, Sainan Peng, Xue Zhou, Qiuhong Shen, Cheng Qian, Xinming Yang, Yuxuan Gong, Kang Zhang, Yin Lu, Xiaodong Shu, Yang Zhao","doi":"10.7150/ijbs.133661","DOIUrl":"10.7150/ijbs.133661","url":null,"abstract":"<p><p>Vascular aging is a dynamic biological process contributing to systemic organismal decay. This review elucidates the heterogeneous cellular phenotypes and microenvironmental remodeling across macrovascular and microvascular beds. These multifaceted pathological shifts are integrated into a unified tripartite framework of twelve hallmarks of vascular aging. These specific molecular dimensions ultimately dictate the clinical divergence between early vascular aging (EVA) and the supernormal vascular aging (SUPERNOVA) phenotype. Furthermore, vascular aging serves as a primary key driver of distant organ dysfunction. Based on these mechanistic insights, we summarize current behavioral and pharmacological senotherapeutic strategies targeting aged blood vessels. This systematic analysis provides critical benchmarks for deciphering vascular senescence and promoting healthy longevity.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7686-7713"},"PeriodicalIF":11.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomilin Rewires mTOR-Driven Immunometabolism via DDIT4 to Restrain Psoriasis.","authors":"Ha Eun Kim, Seung Taek Lee, Hee-Suk Park, Hyun-Su Lee, Jong Yeong Lee, Dae-Ki Kim, Si-Gyun Roh, Kyung-Hwa Nam, Sang-Hyun Kim, Jin Kyeong Choi","doi":"10.7150/ijbs.133330","DOIUrl":"10.7150/ijbs.133330","url":null,"abstract":"<p><p>Nomilin, a citrus-derived limonoid belonging to the tetranortriterpenoid family, has been reported to exert anti-inflammatory and antioxidant effects; however, its therapeutic relevance and underlying mechanisms in psoriasis remain unclear. Here, we investigated the effects of nomilin in 12-O-tetradecanoylphorbol-13-acetate (TPA)- and imiquimod (IMQ)-induced psoriasis-like mouse models, IL-17A-stimulated primary human keratinocytes, Th17-polarized CD4⁺ T cells, and peripheral blood mononuclear cells (PBMCs) from patients with psoriasis. Nomilin markedly alleviated epidermal hyperplasia and inflammatory symptoms, suppressed pro-inflammatory cytokines and psoriasis-associated mediators, and reduced the expansion of inflammatory myeloid and Th1/Th17 cells in lesional skin. Mechanistically, nomilin decreased glucose uptake, glycolytic activity, oxidative phosphorylation, mitochondrial mass, and mitochondrial ROS production, thereby preventing metabolic overactivation and mitochondrial dysfunction. At the molecular level, nomilin upregulated DDIT4 and inhibited mTOR signaling, as evidenced by reduced phosphorylation of mTOR, RAPTOR, p70S6K, and 4EBP1. Genetic silencing of DDIT4 abrogated the anti-inflammatory and metabolic effects of nomilin in keratinocytes, while skin-specific DDIT4 knockdown markedly attenuated its therapeutic efficacy <i>in vivo</i>, demonstrating an essential role for DDIT4 in nomilin-mediated mTOR suppression. Furthermore, molecular docking and cellular thermal shift assay (CETSA) analyses revealed a direct interaction between nomilin and DDIT4. In addition, nomilin suppressed Th17 differentiation and reduced TNF-α-, IFN-γ-, and IL-17A-producing CD4⁺ T cells in PBMCs from patients with psoriasis. Collectively, these findings identify nomilin as a modulator of the DDIT4-mTOR axis that alleviates psoriasis-like inflammation through the rewiring of pathogenic immunometabolic programs and highlight its potential as a therapeutic strategy for psoriasis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7512-7532"},"PeriodicalIF":11.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent protective responses of taurine in ameliorating radiation-induced intestinal injury: gut microbiota reprogramming in males and estrogen-dependent immunity in females.","authors":"Xudong Ding, Jia Du, Zhaoyu Wang, Lu Lu, Saijun Fan","doi":"10.7150/ijbs.137118","DOIUrl":"10.7150/ijbs.137118","url":null,"abstract":"<p><p>Radiation-induced intestinal injury (RIII) limits abdominal and pelvic radiotherapy. Safe and effective radioprotectors that do not protect tumors remain an unmet need. Here, we examined the radioprotective effect of taurine (Tau) in mice subjected to whole-abdominal irradiation (WAI) and whether this effect depends on sex. Tau treatment improved post-irradiation survival, preserved intestinal stem cells, prevented mucosal barrier breakdown, and reduced systemic inflammation. These effects, however, were sex-dependent. In male mice, Tau altered the gut microbiota, increasing <i>Ligilactobacillus</i> abundance and shifting arginine and proline metabolism. In female mice, Tau maintained circulating estrogen levels, which in turn upregulated AICDA expression and enhanced IgA-mediated intestinal immunity. Under the specific dosing regimens and radiation parameters utilized in this study, Tau neither altered baseline tumor progression nor compromised the tumor response to irradiation. We conclude that Tau protects against RIII through sex-specific mechanisms, microbiota reprogramming in males and estrogen-AICDA-IgA signaling in females, without compromising the antitumor efficacy of radiotherapy.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7628-7643"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regenerative extracellular vesicles reshape systemic aging: lessons from antler stem cells.","authors":"Seung-Jae Lee, Jaehoon Bae, Ye Ji Cheon, Eun-Kyung Kim","doi":"10.7150/ijbs.140033","DOIUrl":"10.7150/ijbs.140033","url":null,"abstract":"","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7606-7609"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Microbial Metabolite IDA Sensitizes Tumor Cells to ARF1 Inhibition by Inducing SVIL-dependent Senescence.","authors":"Menglin Huang, Xuan Wang, Yanfeng Jiang, Jincheng Li, Binliu Hu, Yuetong Wang, Steven X Hou","doi":"10.7150/ijbs.133716","DOIUrl":"10.7150/ijbs.133716","url":null,"abstract":"<p><p>While pharmacological inhibition of ARF1 exhibits robust antitumor activity, its therapeutic efficacy is constrained by tissue-specific limitations. To augment the clinical potential of our developed ARF1 inhibitor, DU102, we pursued a strategy of senescence induction. A screen for endogenous senescence-inducing metabolites identified trans-3-indoleacrylic acid (IDA), a microbiota-derived metabolite, as a potent senescence inducer. We demonstrate that IDA acts through targeting supervillin (SVIL), leading to subsequent enhancement of the expression of the senescence-associated enzyme galactosidase beta 1 (GLB1). <i>In vivo</i>, IDA enhanced the antitumor efficacy of DU102 through senescence-dependent sensitization, overcoming tissue-restricted resistance and achieving potent tumor suppression. Further analysis revealed that this combination remodels the tumor microenvironment by coordinately regulating tumor-associated macrophages through different predominant mechanisms: IDA predominantly promotes M1-like polarization via TNFα, whereas ARF1 inhibition primarily drives macrophage expansion through CSF2 upregulation. Our work unveils a novel metabolite-regulated senescence pathway and establishes a rational combination therapy that effectively co-opts tumor-associated macrophages (TAMs) for cancer treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7585-7605"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SH2B3 Promotes PD-L1-Mediated Immune Evasion in Glioblastoma via BRCC3-Dependent IGF2BP2 Stabilization.","authors":"Rongqing Li, Jiahui Wang, Xiangrui Meng, Jiahua Pan, Xin Chen, Xin Pan, Wei Li, Shigang Qiao, Li Qian","doi":"10.7150/ijbs.134558","DOIUrl":"10.7150/ijbs.134558","url":null,"abstract":"<p><p>Glioblastoma (GBM) is characterized by aggressive progression and profound immune evasion, yet the underlying mechanisms remain incompletely understood. Here, we identify the adaptor protein SH2B3 as a critical driver of immune evasion in glioblastoma and show that elevated SH2B3 expression is associated with higher glioma grade and poorer survival in public datasets and clinical data. Although SH2B3 modulation did not significantly affect GBM cell proliferation, migration, or invasion <i>in vitro</i> assays, it significantly altered tumorigenesis <i>in vivo</i>, with overexpression enhancing and knockdown suppressing tumor growth, suggesting that microenvironmental factors may contribute to the <i>in vivo</i> phenotype. We further show that SH2B3 promotes immune evasion at least in part by upregulating PD-L1 expression. Mechanistically, SH2B3 facilitates BRCC3-dependent removal of K63-linked polyubiquitin chains from the m⁶A reader IGF2BP2, thereby stabilizing IGF2BP2 and preventing its autophagy-lysosome-dependent degradation. The stabilized IGF2BP2 then enhances the stability and translation of m⁶A-marked PD-L1 transcripts through m⁶A-dependent transcript recognition. Collectively, our findings reveal a novel SH2B3/BRCC3/IGF2BP2 axis connecting protein deubiquitination and RNA epigenetics to PD-L1-mediated immune evasion, highlighting SH2B3 as a promising therapeutic target for glioblastoma immunotherapy.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7557-7584"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglycemia in Diabetes Drives Hepatic Fibrosis Through the Non-Enzymatic Function of HK2 and AGEs-mediated Matrix Stiffening.","authors":"Chuxin Huang, Jiali Qian, Li Zhang, Ying Liu, Qiwen Zhou, Jiajun Li, Yingying Zhao, Hongmei Yu, Yawen Zhang, Jinya Huang, Miao Li, Ziyu Ren, Zihao Xu, Rui Liu, Xuanchun Wang, Jie Chen, Jiefeng Cui, Yehong Yang","doi":"10.7150/ijbs.130351","DOIUrl":"10.7150/ijbs.130351","url":null,"abstract":"<p><p>Diabetes is implicated in accelerating the progression of hepatic fibrosis, and empagliflozin (an SGLT2 inhibitor) has potential therapeutic effects on diabetic hepatic fibrosis. However, their underlying mechanisms are still largely uncharacterized. In this study, we found that diabetes obviously promoted hepatic fibrosis progression, and empagliflozin intervention effectively impeded this pathological process independent of its hypoglycemic effects. Mechanistically, high glucose stimulation significantly increased HSC activation and its metabolic enzyme HK2 dissociation from mitochondria. The dissociated HK2 interacted with STAT3 to increase its nuclear entry for upregulating HSC activation-associated gene expression. Meanwhile, high glucose stimulation also suppressed KLF4 expression to attenuate its inhibitory effect on STAT3 transcription activation in HSCs. Additionally, high glucose-induced AGEs accumulation resulted in matrix stiffening, which also increased HSC activation. Empagliflozin alleviated hepatic fibrosis progression through decreasing AGEs accumulation and suppressing STAT3 and FOXO1 phosphorylation in HSCs. From the new perspectives of the non-metabolic functions of metabolic enzymes and matrix biomechanics, this study sheds light on a new synergistic regulatory pathway through which diabetes promotes hepatic fibrosis and highlights empagliflozin as a potential therapeutic agent for diabetic hepatic fibrosis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7533-7556"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orthotopic Porcine Liver and Kidney Xenotransplantation as a Step Toward Multi-Organ Replacement.","authors":"Hwijin Kim, Jongwon Byun, Sun-Uk Kim, Taeho Kwon, Kyungjun Uh","doi":"10.7150/ijbs.139541","DOIUrl":"10.7150/ijbs.139541","url":null,"abstract":"","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 13","pages":"7487-7490"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data.","authors":"Zixin Wang, Hanrui Zhang, Liying Tu, Jingjing He, Rong Wang, Yinghong Su, Siwei Tang, Qingfeng Li, Wenzheng Xia, Yashan Gao, Yixuan Zhao, Xin Huang, Tao Zan","doi":"10.7150/ijbs.137778","DOIUrl":"10.7150/ijbs.137778","url":null,"abstract":"<p><p>Pathological cutaneous fibrosis, exemplified by hypertrophic scarring and keloid formation, imposes substantial disease burden through persistent pruritus, pain and contracture-induced functional impairment. While the antifibrotic role of gp130 signaling inhibition has been established in visceral organ fibrosis, its therapeutic efficacy in pathological cutaneous fibrosis remains unexplored. Herein, we investigated the effectiveness of gp130 inhibition on cutaneous fibrosis by leveraging the application of Bazedoxifene, a clinically approved selective estrogen receptor modulator recently identified as a gp130 signaling inhibitor. We demonstrate that gp130 signaling is aberrantly activated in human keloid tissues and fibroblasts. <i>In vitro,</i> Bazedoxifene suppressed the fibroblast activation of disease-derived fibroblasts, featured by attenuated cell migration, myofibroblast differentiation and ECM production. <i>In vivo</i>, Bazedoxifene ameliorated dermal fibrosis and ECM deposition in both bleomycin-induced cutaneous fibrosis and keloid xenograft models. Notably, spatial transcriptomic analysis revealed reduced myofibroblast differentiation within fibrotic regions, providing tissue-level evidence for inhibition of fibroblast activation. Transcriptomic analysis revealed suppression of multiple fibrosis-associated signaling pathways following Bazedoxifene treatment, including the PI3K-AKT-mTOR, JAK-STAT, and MAPK pathways, with the PI3K-AKT-mTOR pathway showing the most prominent inhibition. Collectively, these findings establish Bazedoxifene repurposing as a promising therapeutic strategy for cutaneous fibrosis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7491-7511"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of the Upb1-3-ureidopropionate Pathway Impairs Fatty Acid Metabolism and Exacerbates Acute Kidney Injury.","authors":"Yu Zhang, Jia He, Runxin Zeng, Mingzhu Jiang, Shuang Xu, Yuxian Guo, Yue Zhang, Zhanjun Jia, Ran You, Mengqiu Wu, Aihua Zhang, Mi Bai","doi":"10.7150/ijbs.135329","DOIUrl":"10.7150/ijbs.135329","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a prevalent clinical syndrome associated with high mortality and lacking effective therapies, largely due to incomplete understanding of its pathogenic mechanisms. Proximal tubular epithelial cells (PTECs), with their high metabolic demand, represent the primary targets of injury in AKI. We identified β-ureidopropionase 1 (Upb1), a key enzyme in pyrimidine catabolism, as being specifically enriched in PTECs but markedly downregulated upon AKI. Genetic silencing of Upb1 exacerbated IR-induced AKI. Targeted metabolomics revealed that loss of renal Upb1 drives accumulation of 3-ureidopropionate (3-UPA), a pyrimidine catabolic intermediate. Integrated multi-omics analyses and functional validation demonstrated that 3-UPA impairs fatty acid oxidation through DNMT1-mediated DNA methylation, leading to mitochondrial structural and functional defects. Transcription factor analysis further revealed that myeloid ecotropic viral integration site 1 (Meis1) transcriptionally represses Upb1. Tubule-specific Meis1 overexpression aggravated folic acid (FA)- and ischemia/reperfusion injury (IR)-induced AKI, whereas pharmacological inhibition of Meis1 alleviated tubular damage. Notably, Meis1 overexpression induced marked 3-UPA accumulation, reinforcing its role as an upstream regulator of this metabolic axis. Collectively, these results demonstrate that Meis1/Upb1/3-UPA axis exerted a detrimental role in AKI, and targeting this axis (inhibiting Meis1 or activating Upb1) has therapeutic potential for AKI.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7644-7666"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}