Cell Death Discovery最新文献_第3页

Metabolic interplay between exogenous cystine and glutamine dependence in triple-negative breast cancer. 三阴性乳腺癌中外源性胱氨酸和谷氨酰胺依赖之间的代谢相互作用。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02714-3

Ziqian Ge, Martina Wallace, Rory Turner, Maureen Yin, Mary F Rooney, Richard K Porter

{"title":"Metabolic interplay between exogenous cystine and glutamine dependence in triple-negative breast cancer.","authors":"Ziqian Ge, Martina Wallace, Rory Turner, Maureen Yin, Mary F Rooney, Richard K Porter","doi":"10.1038/s41420-025-02714-3","DOIUrl":"10.1038/s41420-025-02714-3","url":null,"abstract":"Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by high recurrence rates and limited treatment options due to the absence of hormone receptors. Despite advancements in breast cancer research, effective therapies for TNBC remain inadequate, highlighting the need to elucidate subtype-specific metabolic vulnerabilities. TNBC cells exhibit a strong dependence on the exogenous amino acids cystine and glutamine, yet the interplay between these metabolic dependencies remains poorly understood. Here, we demonstrate that TNBC cells exhibit sensitivity to individual nutrient deprivation but can survive dual cystine and glutamine deprivation via distinct mechanisms. Exogenous glutamine primarily fuels glutamine anaplerosis, supporting TNBC cell proliferation. Notably, when exogenous glutamine is absent, restricted cystine uptake restores intracellular glutamate levels, fulfilling metabolic demands and sustaining TNBC cell growth. Under cystine deprivation, inhibition of glutaminolysis rescues TNBC cells by mitigating lipid peroxidation and reducing ROS production, whereas supplementation with the TCA cycle intermediates ɑ-ketoglutarate (ɑ-KG) and succinate induces profound cell death in both TNBC and luminal breast cancer cells under glutaminolysis blockade. Collectively, these findings highlight the metabolic interdependence of glutamine and cystine in TNBC, providing mechanistic insights into potential metabolic-targeted and dietary interventions for TNBC therapy.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"430"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238148","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}

引用次数: 0

IL-21-dependent Ly6C⁺Ly6G⁺CD4⁺ T cells found in lung enhance macrophages function against Actinobacillus pleuropneumoniae infection in mice. 小鼠肺中发现il -21依赖性Ly6C+Ly6G+CD4+ T细胞增强巨噬细胞抗胸膜肺炎放线杆菌感染的功能。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02742-z

Chuntong Bao, Xuan Jiang, Yanyan Tian, Wenjing Wang, Jiameng Xiao, Baijun Liu, Peiru Chen, Ziheng Li, Jiuyan Li, Junhui Zhu, Tamim Abdelaal, Dexi Chen, Na Li, Liancheng Lei

{"title":"IL-21-dependent Ly6C+Ly6G+CD4+ T cells found in lung enhance macrophages function against Actinobacillus pleuropneumoniae infection in mice.","authors":"Chuntong Bao, Xuan Jiang, Yanyan Tian, Wenjing Wang, Jiameng Xiao, Baijun Liu, Peiru Chen, Ziheng Li, Jiuyan Li, Junhui Zhu, Tamim Abdelaal, Dexi Chen, Na Li, Liancheng Lei","doi":"10.1038/s41420-025-02742-z","DOIUrl":"10.1038/s41420-025-02742-z","url":null,"abstract":"IL-21/IL-21R signaling is crucial in various immune diseases and cellular development, however, its role in bacterial pneumonia remains unclear. Here, IL-21R knockout (IL-21R-/-) mice were more susceptible to Actinobacillus pleuropneumoniae (APP) than wild-type (WT) mice. High-dimensional mass cytometry analysis revealed that IL-21R deficiency inhibited neutrophil activation, decreased the numbers of monocytes and proinflammatory macrophages, and augmented the defective CD3low T cells in the lungs. Intracellular cytokine staining showed decreased IFN-γ/TNF-α/IL-6 production in IL-21R-/- mice, particularly in CD8⁺ T cells. Furthermore, a previously unrecognized Ly6C+Ly6G+CD4+ T cell subset emerged only in the lungs of WT mice post-APP infection, which was in an activated status with stronger secretion capacities of IL-10, IL-21, granzyme B, and perforin by flow cytometry. These cells polarized macrophages into M2- or M1- phenotype without/with infection, respectively, and enhanced proliferation, phagocytosis, and macrophage extracellular traps/ROS-mediated bactericidal activity of macrophages against-APP, Klebsiella pneumoniae, or Escherichia coli infection. Thus, our study demonstrated that IL-21 drives the differentiation of neutrophils, monocytes, and macrophages into pro-inflammatory subsets. IL-21-induced Ly6C+Ly6G+CD4+ T cells cooperate with macrophages to enhance bacterial clearance, providing a promising target for preventing bacterial pneumonia.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"440"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238205","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}

引用次数: 0

The role of CARMA3 in regulating fibrosis to prevent hypertrophic cardiomyopathy. CARMA3在调节纤维化预防肥厚性心肌病中的作用。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02645-z

Yafeng Liu, Ganyi Chen, Yiwei Yao, Yunfei Jiang, Chenghao Wen, Wuwei Wang, Quan Liu, Yide Cao, Fuhua Huang, Wen Chen, Zhibing Qiu

{"title":"The role of CARMA3 in regulating fibrosis to prevent hypertrophic cardiomyopathy.","authors":"Yafeng Liu, Ganyi Chen, Yiwei Yao, Yunfei Jiang, Chenghao Wen, Wuwei Wang, Quan Liu, Yide Cao, Fuhua Huang, Wen Chen, Zhibing Qiu","doi":"10.1038/s41420-025-02645-z","DOIUrl":"10.1038/s41420-025-02645-z","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is characterized by cardiac hypertrophy and fibrosis. To investigate the impact of CARMA3 on fibroblast phenotypic transformation in hypertrophic cardiomyopathy (HCM), the correlation between CARMA3 expression and fibrosis was analyzed in HCM patients. Cardiac function and fibroblast phenotypic transformation were assessed in wild-type and CARMA3-knockout mice subjected to transverse aortic constriction (TAC) or angiotensin II treatment. Additionally, cardiac fibroblasts were screened using flow cytometry and proteomic analysis to identify potential targets. Significant cardiac functional impairment and fibrosis were observed in CARMA3-knockout mice following TAC or angiotensin II treatment. Primary fibroblasts isolated from these mice exhibited increased myofibroblast differentiation, extracellular collagen production, mitochondrial damage, and macrophage inflammation. Elevated STAT1 expression was identified in cardiac fibroblasts from CARMA3-knockout mice through proteomic analysis. Additionally, STAT1 phosphorylation was regulated by CARMA3, and an interaction between CARMA3 and STAT1 was detected in response to pressure overload. In conclusion, CARMA3 may suppress myofibroblast activation by inhibiting STAT1 phosphorylation, thereby improving myocardial fibrosis in pressure overload-induced HCM.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"429"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238159","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}

引用次数: 0

Fra-1 promotes gastric cancer progression by regulating macrophage polarization and transcriptionally activating HMGA2 expression. Fra-1通过调控巨噬细胞极化和转录激活HMGA2表达促进胃癌进展。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02724-1

Feng Zeng, Jiaying Cao, Shan Liao, Yan Chen, Qian He, Yan Lei, Juan Xu, Yanhong Zhou

{"title":"Fra-1 promotes gastric cancer progression by regulating macrophage polarization and transcriptionally activating HMGA2 expression.","authors":"Feng Zeng, Jiaying Cao, Shan Liao, Yan Chen, Qian He, Yan Lei, Juan Xu, Yanhong Zhou","doi":"10.1038/s41420-025-02724-1","DOIUrl":"10.1038/s41420-025-02724-1","url":null,"abstract":"Gastric cancer is a common malignant tumour of gastrointestinal tract with high incidence and low early diagnosis rate. Surgery is its main treatment modality, but some patients have poor prognosis. The rise of immunotherapy provides a new therapeutic strategy for gastric cancer treatment. Elucidating the mechanism of action of immune cells in the tumour microenvironment is the cornerstone for developing new tumour immunotherapy strategies. Previous studies have found that Fra-1 is highly expressed in gastric cancer and is closely associated with macrophage polarisation. In order to further elucidate the specific mechanism, this study firstly used in vitro co-culture experiments to verify that the high expression of Fra-1 in gastric cancer cells induced macrophage M2 polarisation; then, whole proteomics combined with in vitro cellular experiments were used to clarify the specific mechanism by which Fra-1 induced macrophage M2 polarisation by regulating HMGA2 expression in gastric cancer cells. Finally, in vivo experiments further elucidated that Fra-1 induces macrophage polarisation in gastric cancer cells and participates in tumourigenesis and development. The aim of this study was to systematically elucidate the role of Fra-1 in the tumour microenvironment and its possible mechanisms, and to provide an experimental basis for the development of immunotherapeutic strategies for gastric cancer.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"433"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238184","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}

引用次数: 0

Exosomal non-coding RNAs: mediators of crosstalk between cancer and cancer stem cells. 外泌体非编码rna：癌症和癌症干细胞间串扰的介质。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02726-z

Shuangmin Wang, Jiaojiao Shu, Nuoxin Wang, Zhixu He

{"title":"Exosomal non-coding RNAs: mediators of crosstalk between cancer and cancer stem cells.","authors":"Shuangmin Wang, Jiaojiao Shu, Nuoxin Wang, Zhixu He","doi":"10.1038/s41420-025-02726-z","DOIUrl":"10.1038/s41420-025-02726-z","url":null,"abstract":"Current advances in oncology have recognized two distinct cell subpopulations in tumors that include (1) a rare subpopulation, cancer stem cells (CSCs), which is considered to be the \"seed\" of the tumor, with therapy-resistant properties and as key drivers of tumor aggressiveness, and (2) the remaining bulk one, non-CSCs, all differentiated from the CSCs. Within the tumor microenvironment (TME), exosomes secreted by either CSCs or non-CSCs, containing multiple biomolecular cargos, mediate communication between both of the tumor cell subpopulations and play a vital role in promoting tumor progression. Specifically, a class of biomolecular cargo, non-coding RNAs (ncRNAs) that do not code for proteins during translation, has recently been highlighted to be a key participant in oncobiological processes. To comprehensively illuminate the mechanism of exosomal ncRNAs in mediating bidirectional communication between CSCs and differentiated tumor cells within the TME, we systematically analyzed the state-of-the-art literature from PubMed on this topic. It is revealed that: (1) Non-CSC exosomal ncRNAs enhance CSC stemness via upregulating stemness marker expression and activating stemness-reinforcing signaling pathways; (2) CSC-derived exosomal ncRNAs reciprocally mediate tumor progression by enhancing stemness, metastasis, angiogenesis, chemoresistance, and immune suppression of non-CSCs; (3) These tumor-derived exosomal ncRNAs possess the potentials as liquid biopsy biomarkers for early metastasis detection, and treatment targets or drug delivery systems for precision cancer therapy. It is therefore concluded that exosomal ncRNAs serve as critical communication bridges within TME, creating a self-reinforcing tumor-promoting loop, and therapeutically targeting exosomal ncRNAs could disrupt the crosstalk between CSCs and non-CSCs to delay the tumor progression. These findings provide a framework for developing combinatorial strategies against therapy-resistant malignancies.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"434"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238202","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}

引用次数: 0

Tracking NF-kB activity across steady-state neutrophil maturation. 中性粒细胞成熟过程中NF-kB活性的追踪。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02737-w

Nathan E Jeffries, Daniel J Floyd, Shenglin Mei, David B Sykes, Michael K Mansour

引用次数: 0

Biomolecular condensates in lung cancer: from molecular mechanisms to therapeutic targeting. 肺癌的生物分子凝聚：从分子机制到治疗靶向。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02735-y

Nannan Wang, Qianqian Liu, Lingrui Shang, Tongran Zhang, Tao Xu, Shangbang Gao, Lihua Chen, Huisheng Liu

{"title":"Biomolecular condensates in lung cancer: from molecular mechanisms to therapeutic targeting.","authors":"Nannan Wang, Qianqian Liu, Lingrui Shang, Tongran Zhang, Tao Xu, Shangbang Gao, Lihua Chen, Huisheng Liu","doi":"10.1038/s41420-025-02735-y","DOIUrl":"10.1038/s41420-025-02735-y","url":null,"abstract":"Lung cancer constitutes a globally prevalent malignancy with high morbidity and mortality, imposing a substantial burden on public health systems worldwide. Growing evidence indicates that the initiation and progression of lung cancer involve multiple biological processes. Liquid-liquid phase separation (LLPS), a fundamental mechanism orchestrating diverse cellular biochemical events, has been increasingly implicated in lung cancer pathogenesis, particularly in tumorigenesis and chemoresistance. These findings unveil promising opportunities for pharmacological intervention through condensate-targeting therapeutics. Herein, we review the composition, regulatory mechanisms, and functional roles of biomolecular condensates in lung cancer progression. We further explore their potential applications in diagnosis, therapeutic strategies, and drug development, while addressing the current challenges and future research directions in this field. Elucidating the mechanistic interplay between phase separation and lung carcinogenesis holds significant promise for advancing novel therapeutic avenues in precision oncology.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"425"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238095","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}

引用次数: 0

Targeting the redox-programmed cell death axis in breast cancer: from molecular mechanisms to therapeutic resistance. 乳腺癌中的氧化还原程序性细胞死亡轴：从分子机制到治疗耐药性

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02743-y

Yiqiao Wen, Zhixuan Lin, Zhongwei Jiang, Yang Li, Tianyi Wu

{"title":"Targeting the redox-programmed cell death axis in breast cancer: from molecular mechanisms to therapeutic resistance.","authors":"Yiqiao Wen, Zhixuan Lin, Zhongwei Jiang, Yang Li, Tianyi Wu","doi":"10.1038/s41420-025-02743-y","DOIUrl":"10.1038/s41420-025-02743-y","url":null,"abstract":"Breast cancer, the most prevalent malignancy among females, threatens public health worldwide. Patients with breast cancer need personalised treatment strategies on the basis of their distinct molecular characteristics due to the unique epidemiological patterns and high heterogeneity of breast cancer, which limits therapeutic efficacy and poses significant challenges to current treatments. The underlying reasons may involve complex interactions and alterations in various cell death pathways. Currently, most studies and therapeutic agents focus on a single type of cell death, whereas opportunities related to other cell death pathways are typically overlooked. Therefore, identifying the predominant type of cell death, understanding the transitions between different cell death modalities during treatment, and developing novel therapies are crucial. In this review, we summarise the dynamic balance between reactive oxygen species (ROS) production and clearance, as well as the characteristics of various forms of cell death induced by ROS, including pyroptosis, apoptosis, necroptosis, autophagy, ferroptosis, cuproptosis, disulfidoptosis, oxeiptosis, and epigenetic regulation of these types of cell death. Additionally, we explored a novel cell death pathway called PANoptosis. This review sheds new light on the treatment of breast cancer from the perspective of nanotechnology and the development of combination therapies.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"441"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238136","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}

引用次数: 0

From mechanisms to markers: role of pyroptosis in revolutionizing thyroid cancer care. 从机制到标志物：焦亡在革命性甲状腺癌治疗中的作用。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02741-0

Ningxin Wang, Yuying Chen, Guhan Luo, Dingcun Luo

{"title":"From mechanisms to markers: role of pyroptosis in revolutionizing thyroid cancer care.","authors":"Ningxin Wang, Yuying Chen, Guhan Luo, Dingcun Luo","doi":"10.1038/s41420-025-02741-0","DOIUrl":"10.1038/s41420-025-02741-0","url":null,"abstract":"The global incidence of thyroid cancer, especially papillary thyroid cancer, has increased in recent decades, making it a significant global health issue. Pyroptosis, an important form of programmed cell death, is characterized by pore formation in the cell membrane, membrane rupture, cell swelling, and the subsequent release of cellular contents. Factors released during this process, such as interleukin-1β and interleukin-18, amplify inflammatory effects and trigger immune activation. Increasing evidence indicates that pyroptosis has either tumour-promoting or tumour-suppressing effects at various stages of tumour progression, which has garnered significant attention and warrants further investigation. Thus, harnessing the tumour-inhibitory effects while mitigating the tumour-promoting effects of pyroptosis represents a promising therapeutic strategy for the clinical management of thyroid cancer. Furthermore, pyroptosis-related genes are significantly correlated with the prognosis of thyroid cancer. Therefore, this review provides an overview of the current research regarding the role of pyroptosis in thyroid cancer, focusing on its mechanisms, therapeutic targets, and predictive biomarkers. These findings highlight the importance of pyroptosis in thyroid cancer and offer valuable insights for the development of innovative treatment strategies and accurate prognostic markers.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"439"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238150","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}

引用次数: 0

Research advances on the role of programmed endothelial cell death in sepsis. 内皮细胞程序性死亡在脓毒症中的作用研究进展。

IF 7 2区生物学

Cell Death Discovery Pub Date : 2025-10-06 DOI: 10.1038/s41420-025-02728-x

Yichen Bao, Xingpeng Yang, Pengyue Zhao, Xiaohui Du

{"title":"Research advances on the role of programmed endothelial cell death in sepsis.","authors":"Yichen Bao, Xingpeng Yang, Pengyue Zhao, Xiaohui Du","doi":"10.1038/s41420-025-02728-x","DOIUrl":"10.1038/s41420-025-02728-x","url":null,"abstract":"Sepsis is a life-threatening systemic inflammatory response syndrome triggered by infection, characterized by a dysregulated host immune response to pathogenic organisms and associated with substantial morbidity and mortality. According to the most recent sepsis guidelines, effective monitoring and therapeutic strategies remain insufficient, leading to suboptimal patient outcomes. Endothelial cells (ECs) constitute a critical pathophysiological nexus in sepsis pathogenesis, wherein their dysregulation disrupts both microvascular homeostasis and endothelial barrier competence. During sepsis, aberrant activation of programmed cell death (PCD) pathways in ECs induces both structural and functional disruptions, thereby enhancing vascular permeability, causing hemodynamic instability, promoting systemic circulatory dysfunction, and compromising tissue perfusion. These pathophysiological derangements potentiate a vicious cycle of systemic inflammatory amplification, exacerbate disseminated intravascular coagulation, and culminate in lethal multiple organ dysfunction syndrome. This comprehensive review systematically evaluates contemporary insights into the molecular pathophysiology of PCD pathways in endothelial cells during sepsis, with particular emphasis on their mechanistic interplay and therapeutic implications, providing an in-depth understanding of their contributions to sepsis pathophysiology. Additionally, we explore the potential of key PCD-associated molecules as biomarkers for monitoring and evaluating vascular function and permeability in septic patients. Finally, we discuss the current state of drug development targeting ECs' PCD and their prospective therapeutic implications for sepsis, offering valuable insights for future basic research and clinical applications.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"426"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238178","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}

引用次数: 0