Cell Death Discovery最新文献

{"title":"Beyond the target: new dimensions of antifungal action.","authors":"Marina Campos Rocha, Neta Shlezinger, Jean-Pierre Gangneux, Nicolas Papon","doi":"10.1038/s41420-026-03266-w","DOIUrl":"10.1038/s41420-026-03266-w","url":null,"abstract":"","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547974","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":"Emerging roles of SIRT6 and its modulators in kidney diseases.","authors":"Feihong Ren, Yudian Wang, Yufei Zhang, Liheng Liu, Qi Jin, Liping Yang, Yongli Zhan","doi":"10.1038/s41420-026-03264-y","DOIUrl":"10.1038/s41420-026-03264-y","url":null,"abstract":"<p><p>The global incidence and prevalence of kidney diseases continue to rise, posing a serious public health challenge. SIRT6 is an NAD⁺-dependent histone deacetylase with broad essential regulatory roles across various pathophysiological processes, including DNA repair, chromatin accessibility, telomere stability, and glycolipid metabolism. As an epigenetic regulator specifically expressed in kidney tissues, SIRT6 serves as a central mediator of kidney homeostasis. Notably, accumulating evidence has implicated aberrant SIRT6 expression in the onset and development of various kidney diseases, such as acute kidney injury, diabetic kidney disease, hypertensive nephropathy, renal fibrosis, and renal cell carcinoma. In the present review, we provide an overview of the sirtuin family, systematically characterize the enzymatic activities and critical biological functions of SIRT6, and discuss its molecular mechanisms across various kidney diseases, focusing on its cell type-specific functions. We further summarize the latest research advances in SIRT6-targeted modulators for improving kidney diseases and analyze the challenges associated with their clinical application. Overall, we highlight SIRT6 as a highly promising novel target in the treatment and prevention of kidney diseases, with strong potential for clinical translation.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469274","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":"Correction: NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin.","authors":"Rongchuan Yue, Zaiyong Zheng, Yu Luo, Xiaobo Wang, Mingming Lv, Dan Qin, Qingqing Tan, Yulong Zhang, Tao Wang, Houxiang Hu","doi":"10.1038/s41420-026-03177-w","DOIUrl":"10.1038/s41420-026-03177-w","url":null,"abstract":"","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"12 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454885","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":"Correction: A positive feedback loop between TKT and c-Myc drives TACE resistance in hepatocellular carcinoma.","authors":"Yifu Xiao, Mingyu Liu, Ying Zhou, Yunyuan Bao, Guoqing Zhang, Banglong Xu, Wenjie Zheng, Hui Zhao","doi":"10.1038/s41420-026-03216-6","DOIUrl":"10.1038/s41420-026-03216-6","url":null,"abstract":"","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"12 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454776","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":"Technical and regulatory challenges in cell therapy products: lessons from unsuccessful IND and BLA/NDA approvals.","authors":"Dongmei Han, Jinping Xie, Yufang Shi, Rong Shao","doi":"10.1038/s41420-026-03258-w","DOIUrl":"10.1038/s41420-026-03258-w","url":null,"abstract":"","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454733","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":"Uncovering MYOF as a novel therapeutic target in glioblastoma: mechanistic insights and drug discovery.","authors":"Peiqi Zhao, Zhen Chen, Jiajie Zhu, Zibin Zhang, Zhenqiu Xing, Fan Tang, Kankai Wang, Ying Zhang, Hong Chen, Qichuan Zhuge, Jianjing Yang","doi":"10.1038/s41420-026-03254-0","DOIUrl":"10.1038/s41420-026-03254-0","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common type of primary malignant brain tumor, characterized by a poor prognosis, high recurrence rate, and elevated mortality. In recent years, gene-targeted therapies leveraging small molecule compounds have gained momentum as a promising avenue for GBM intervention. Myoferlin (MYOF), a type II membrane protein of the Ferlin family, has emerged as a key regulator of membrane dynamics-governing processes such as vesicular trafficking, endocytosis, and membrane repair. In this study, we explore the previously uncharted role of MYOF in GBM progression and its potential as a diagnostic and therapeutic target. Our data reveal that silencing MYOF markedly suppresses glioma growth both in vitro and in vivo. Mechanistically, MYOF knockdown disrupts the nuclear translocation of phosphorylated STAT3 (P-STAT3), a critical oncogenic signaling event. Notably, we identified Entacapone (ENT), a small molecule capable of targeting MYOF, which significantly impedes glioma development across experimental models. These findings position MYOF as a novel molecular lever in GBM pathogenesis and highlight ENT as a potential therapeutic agent that exerts anti-glioma effects by blocking MYOF-mediated P-STAT3 nuclear import. The diagram illustrates a novel regulatory mechanism of IL-6/STAT3 signaling involving MYOF. Upon IL-6 stimulation, STAT3 undergoes phosphorylation. MYOF then binds to phosphorylated STAT3 and facilitates its translocation into the nucleus to regulate target gene expression. The compound ENT acts as a targeted inhibitor of this process by binding to MYOF, thereby blocking the nuclear transport of phosphorylated STAT3 and suppressing downstream signaling.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444695","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":"Piceatannol as a safe senotherapeutic: ameliorating senescence-associated markers in a radiation-induced murine model.","authors":"Alessia Ambrosino, Claudia Moriello, Nicola Alessio, Domenico Aprile, Salvatore Cappabianca, Nicolamaria Tarantino, Gianfranco Peluso, Giovanni Di Bernardo, Umberto Galderisi","doi":"10.1038/s41420-026-03253-1","DOIUrl":"10.1038/s41420-026-03253-1","url":null,"abstract":"<p><p>Cellular senescence is a key driver of age-associated tissue dysfunction through the secretion of pro-inflammatory and pro-senescent factors (SASP). Among these, insulin-like growth factor binding proteins (IGFBPs) have emerged as causal mediators of senescence propagation. Piceatannol (PCT), a naturally occurring stilbene and resveratrol metabolite with superior pharmacokinetic properties, exhibits senomorphic activity in vitro, but its in vivo senotherapeutic potential remains poorly defined. We established a murine model of mild aging using sublethal X-ray irradiation, in which organ function remains largely preserved but molecular and cellular hallmarks of aging, such as senescent cell accumulation, SASP factor elevation, tissue remodeling, and low-grade inflammation, are detectable. This controlled model mimics the early stage of aging seen in many healthy middle-aged individuals, particularly prevalent in Western societies, and provides a relevant platform for testing preventive senotherapeutics. Mice were treated with oral PCT at a human-translatable dose and evaluated for behavioral performance, circulating SASP factors, tissue senescence, inflammation and fibrosis. PCT significantly improved motor coordination and spatial memory while reducing systemic inflammation and circulating SASP factors, including the senescence-propagating IGFBPs IGFBP4, IGFBP5, and IGFBP7. In kidney and heart, the organs most affected by radiation-induced aging, PCT reduced senescent cell burden, CD68⁺ inflammatory foci, fibrotic remodeling, and the senescence markers P53 and P21. PCT also preserved mesenchymal stromal cell clonogenic capacity. These multi-organ benefits were achieved without detectable toxicity in healthy animals. Our findings position PCT as a promising, safe, nutritionally derived senotherapeutic candidate for delaying aging-associated deterioration. This mild aging model, capturing preclinical senescence without overt organ failure, may accelerate the development of interventions aimed at preserving health span in middle-aged populations.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444662","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":"KIF14 silencing suppresses cell proliferation and enhances chemosensitivity by modulating 53BP1 nucleocytoplasmic shuttling in non-WNT/non-SHH medulloblastoma.","authors":"Huangyi Fang, Tao Xu, Wei Wen, Shixuan Xiang, Yusong Zhang, Donghao Qin, Anjie Lu, Yutuo Zheng, Lizhong Wang, Regina Chizi Tunje, Zejiang Hong, Siyu Wang, Xiufeng Huang, Hansong Sheng, Jian Lin","doi":"10.1038/s41420-026-03252-2","DOIUrl":"10.1038/s41420-026-03252-2","url":null,"abstract":"<p><p>Medulloblastoma (MB) is the most common malignant pediatric brain tumor. The non-WNT/non-SHH subtypes (Groups 3 and 4) exhibit high genetic heterogeneity and limited therapeutic options. Kinesin family member 14 (KIF14) is selectively expressed during nervous system development. However, its role in non-WNT/non-SHH MB remains poorly understood. In this study, analysis of the GEO database revealed that high KIF14 expression correlates with poor prognosis in patients with non-WNT/non-SHH MB. Silencing KIF14 in MB cells impaired cytokinesis, leading to p53-mediated cell cycle arrest and apoptosis. Mechanistically, KIF14 knockdown disrupted the nucleocytoplasmic shuttling of the p53-binding protein 53BP1, resulting in its nuclear accumulation. This shift inhibited homologous recombination (HR)-mediated repair of DNA double-stranded breaks (DSBs), thereby enhancing cisplatin-induced DNA damage. In vitro experiments and intracranial orthotopic xenograft models confirmed that KIF14 silencing potentiates the antitumor efficacy of cisplatin treatment. Overall, these findings highlight the critical role of KIF14 in promoting cell proliferation and DNA repair in non-WNT/non-SHH MB and suggest that targeting KIF14 may represent a novel therapeutic strategy to enhance the efficacy of DNA-damaging agents in this challenging MB subtype.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444646","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":"Placenta models for HIV-1-ART-nicotine comorbidity research: advances and remaining challenges.","authors":"Sandip Godse, Aditya N Bade","doi":"10.1038/s41420-026-03249-x","DOIUrl":"10.1038/s41420-026-03249-x","url":null,"abstract":"<p><p>Worldwide implementation of antiretroviral therapy (ART) for pregnant women living with human immunodeficiency virus type-1 (HIV-1) has markedly reduced mother-to-child HIV-1 transmission rate to less than one percent. Despite this benefit, adverse pregnancy outcomes remain a major concern. Placental deficits induced by antiretroviral drugs (ARVs) are increasingly recognized as a potential causative factor. Additionally, comorbid effects of substance use on placenta cannot be overstated. Addictive substances are commonly used by people living with HIV-1 (PLWH). However, globally, nicotine exposure through smoking or tobacco use remains a major comorbidity in PLWH. Yet, to date, whether and how, HIV-1, ARVs, and nicotine together exacerbate adverse effects on placenta and affect birth outcomes is unknown. Due to ethical concerns and impracticality of obtaining placenta tissues at different stages of pregnancy, appropriate experimental models that closely recapitulate in vivo placenta physiology are essential to define how HIV-1, ART, and nicotine independently or collectively affect placental development and functions. Herein, we provide a comprehensive review of the experimental placenta models that have been or are yet to be utilized to study placental comorbid pathobiology induced by HIV-1 infection, ART, and/or nicotine exposure. We emphasize how each model is used (or underused) to interrogate infection biology, pharmacokinetic profile, and toxico-pharmacologic mechanisms. Moreover, key limitations associated with each placenta model and necessary improvements for investigating HIV-1 and associated comorbidity are highlighted. Overall, this review seeks to educate both clinical and basic scientists on advances made, and remaining challenges in understanding comorbid effects of HIV-1-ART-nicotine on pregnancy outcomes using experimental placenta models.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435280","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":"PRMT6 acts as a pro-angiogenic factor in colorectal cancer.","authors":"Haifeng Han, Xin Zhang, Mingxin Jin, Yali Chu, Fengjun Liu, Hui Qu, Cheng Chen","doi":"10.1038/s41420-026-03256-y","DOIUrl":"10.1038/s41420-026-03256-y","url":null,"abstract":"<p><p>The progression of colorectal cancer (CRC) is highly dependent on tumor angiogenesis, a process primarily regulated by hypoxia-inducible factor HIF-1α. This study focuses on the mechanistic role of protein arginine methyltransferase 6 (PRMT6) in CRC angiogenesis and reveals that PRMT6 is significantly overexpressed in CRC tissues, stabilizing HIF-1α via the autophagy-lysosome pathway. Specifically, PRMT6 catalyzes the asymmetric dimethylation of HIF-1α at arginine 463, which disrupts its interaction with the autophagy-related protein TAX1BP1, thereby preventing its degradation. In vivo experiments demonstrate that PRMT6 silencing reduces HIF-1α stability, decreases vascular endothelial growth factor A (VEGFA) expression, and markedly suppresses tumor angiogenesis and growth. This study identifies the PRMT6-HIF-1α axis as a novel therapeutic target for CRC and suggests that targeting this pathway may facilitate the development of precision anti-angiogenic therapies.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419055","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}