International Journal of Biological Sciences最新文献

{"title":"O-GlcNAcylated Hsp47 as a predictive biomarker in colorectal cancer: Kaempferol targets OGT-collagen axis for therapeutic intervention.","authors":"Chishun Zhou, Jing Zheng, Zizheng Li, Yu Li, Xin Jin, Yukai Huang, Yuefang Lin, Xinyue Wen, Yin Wang, Jiarun Lin, Ying Wang, Wei Wang, Zhongqiu Liu, Linlin Lu","doi":"10.7150/ijbs.116513","DOIUrl":"10.7150/ijbs.116513","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a highly lethal gastrointestinal malignancy, and its progression is closely related to abnormal protein O-GlcNAcylation modifications, especially during extracellular matrix (ECM) remodeling. Kaempferol is a natural flavonoid with medicinal value that can inhibit CRC progression through various pathways. However, it is unclear whether its mechanism of action involves O-GlcNAc-driven metabolic reprogramming. This study confirmed that kaempferol can significantly inhibit CRC growth both <i>in vitro</i> and <i>in vivo</i> and effectively reduce the overall protein O-GlcNAcylation levels. Mechanistic studies indicate that kaempferol reduces the levels of substrate uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) and downregulates the expression of O-GlcNAc transferase (OGT), thereby decreasing the O-GlcNAcylation levels of proteins. This leads to a reduction in the O-GlcNAc modification of downstream heat shock protein 47 (Hsp47), which in turn affects the expression and intracellular localization of Hsp47, ultimately inhibiting the maturation and secretion of type I collagen, thereby blocking CRC progression. This study reveals a new mechanism by which kaempferol inhibits CRC by targeting the O-GlcNAcylation pathway. The study results suggest that O-GlcNAc-modified Hsp47 could serve as a potential therapeutic target for CRC and propose a treatment strategy guided by flavonoid biomarkers based on the inhibition of the OGT-collagen axis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5586-5608"},"PeriodicalIF":10.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075151","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":"FAM134B in Cellular Homeostasis: Bridging Endoplasmic Reticulum-Phagy to Human Diseases.","authors":"Ning Chen, Jia-Qi Yang, Sen Tong, Lu Xu, Ning Dong, Yao Wu, Yu-Xuan Li, Ren-Qi Yao, Yong-Ming Yao","doi":"10.7150/ijbs.113890","DOIUrl":"10.7150/ijbs.113890","url":null,"abstract":"<p><p>FAM134B, originally characterized as an oncogene in esophageal squamous carcinoma, has also been implicated in the pathogenesis of hereditary sensory and autonomic neuropathy type IIB (HSAN2B). It is recognized as the inaugural endoplasmic reticulum (ER)-phagy receptor in mammals containing an LC3-interacting region, which facilitates its interaction with LC3 and GABARAP proteins in the autophagosome. ER-phagy, a critical process involved in ER quality control, selectively degrades superfluous or damaged ER fragments in lysosomes, thereby maintaining ER and protein homeostasis. This review offers an in-depth analysis of FAM134B's structure, function, and regulation, emphasizing its role in infectious diseases, neuropathies, cancer, metabolic disorders, degenerative conditions, and cardiovascular diseases. The evidence presented highlights the need for further research on FAM134B as a potential therapeutic target in human diseases.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5514-5530"},"PeriodicalIF":10.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074999","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":"DLGAP5 Promotes Acute Liver Injury via Hepatocyte Pyroptosis-Driven Macrophage Metabolic Reprogramming and M1 Polarization.","authors":"Xianzhi Liu, Zhiyuan Chen, Jun Lin, Yifan Lian, Wenxuan Gan, Huajie Liu, Xingxiang Huang, Jiaxin Mei, Tianrong Ma, Zhi Lu, Wei Zeng, Yihang Gong, Shuai Chen, Weiling He","doi":"10.7150/ijbs.118024","DOIUrl":"10.7150/ijbs.118024","url":null,"abstract":"<p><p>Pyroptosis is a novel programmed cell death that exists in inflammatory diseases and methyltransferase-like 3 (METTL3) is a core N6-methyladenosine (m6A) modified methyltransferase that has been shown to regulate cell fate. However, the role of pyroptosis in acute liver injury (ALI) is still unknown and whether it is regulated by m6A modification needs to be elucidated. Here, <i>Mettl3</i> mutant and <i>Nlrp3</i> knockout mouse were constructed, CCl₄- and TAA-induced ALI models were established and primary cells were isolated, and cell pyroptosis and m6A modification were evaluated. We found that hepatocyte pyroptosis is a key characteristic of ALI, and METTL3-mediated m6A modification was upregulated in hepatocytes during ALI. Inhibition of METTL3-mediated m6A modification alleviated hepatocyte pyroptosis and ALI. Through MeRIP-seq analysis and verification, <i>Dlgap5</i> was determined as the target of METTL3-mediated m6A modification, which was regulated in an IGF2BP2-dependent manner. Mechanistically, METTL3 can bind to DLGAP5, and then DLGAP5 promoted pyroptosis through NF-κB-dependent NLRP3 inflammasome activation and direct potentiation of inflammasome structure formation and assembly. <i>Mettl3</i> mutation or AT9283-mediated DLGAP5 inhibition alleviated pyroptosis and ALI. The effects of hepatocyte pyroptosis on cell interaction were then explored and we revealed that NLRP3 inflammasome and interleukin releasing by the GSDMD-N-dependent membrane pores from pyroptotic hepatocytes activated macrophage metabolic reprogramming and M1 polarization, further exacerbating ALI. <i>Nlrp3</i> deficiency alleviated ALI by suppressing hepatocyte pyroptosis and blocking communication between macrophages and hepatocytes. Our findings indicate the potential mechanisms of ALI from an intercellular communication perspective, and targeted-inhibition of DLGAP5 and -blockade of hepatocyte-macrophage interaction provide promising strategies for ALI treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5563-5585"},"PeriodicalIF":10.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075045","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":"Activated B cells modulate the maturation of MDSCs via CD36-dependent MHC-II transfer to orchestrate CD4⁺ Th1-dominant antitumor immunity after cryo-thermal therapy.","authors":"Zelu Zhang, Shicheng Wang, Junjun Wang, Yichen Yao, Yuankai Hao, Yue Lou, Ping Liu, Lisa X Xu","doi":"10.7150/ijbs.115232","DOIUrl":"10.7150/ijbs.115232","url":null,"abstract":"<p><p>Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has shown great success in treating various cancer types. However, the therapeutic efficacy of ICIs remains unsatisfactory because of the immunosuppressive tumor microenvironment. Cryo-thermal therapy (CTT), a novel tumor ablation approach developed by our laboratory, transforms the tumor immunosuppressive environment into an immunostimulatory environment by activating both innate and adaptive immunity. CTT promotes the differentiation of myeloid-derived suppressor cells (MDSCs) into mature dendritic cells and macrophages, activates antigen-presenting cells and natural killer (NK) cells, and induces Th1-dominant CD4⁺ T-cell-mediated antitumor immunity in numerous highly metastatic tumor models. However, the role of B cells in CTT-induced antitumor immunity remains unclear despite their critical function in adaptive immunity. Here, <i>in vivo</i> B-cell depletion with anti-CD20 monoclonal antibodies in multiple tumor models revealed that B cells play a crucial role in suppressing tumor metastasis and extending survival. More interestingly, CTT-activated B cells reprogram MDSCs to a mature phenotype through CD36-dependent major histocompatibility complex class II (MHC-II) transfer, resulting in enhanced Th1-dominant CD4⁺ T-cell responses and CD8⁺ T-cell cytotoxicity. These findings reveal a novel mechanism of B-cell-mediated modulation of the tumor microenvironment and provide insights into enhancing the efficacy of immunotherapy strategies.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5547-5562"},"PeriodicalIF":10.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075306","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":"Overcoming Ferroptosis-Induced Exhaustion of NK Cells through Inhibition of the ATF3-Mediated Integrated Stress Response in Ovarian Cancer.","authors":"Tian Chen, Shulin Zhou, Yashuang Zhang, Huangyang Meng, Huixian Miao, Mingming Feng, Yi Jiang, Yicong Wan, Lin Zhang, Wenjun Cheng","doi":"10.7150/ijbs.112615","DOIUrl":"10.7150/ijbs.112615","url":null,"abstract":"<p><p>The absence of cytotoxic effector cells, such as CD8⁺ T cells or Natural Killer (NK) cells, within tumors establishes an immune-cold tumor microenvironment (TME), contributing to poor immunotherapy responses, as observed in ovarian cancer. Although prior studies implicate NK cell exhaustion within the TME related to ferroptosis, the underlying mechanisms remain undefined. This study demonstrates that upon infiltrating the ovarian cancer TME, NK cells activate an integrated stress response (ISR) centered on ATF3. This ATF3-mediated ISR suppresses NRF2 expression, compromising their ability to counteract oxidative stress and ultimately triggering ferroptosis. Critically, we show that co-treatment with the ISR inhibitor ISRIB and NK cells not only prevents NK cell ferroptosis but also synergizes to enhance tumor cell killing. These findings provide novel insights into the mechanisms driving NK cell exhaustion within the TME and identify ISR inhibition as a promising therapeutic target and intervention strategy for developing NK cell-based therapies against ovarian cancer.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5531-5546"},"PeriodicalIF":10.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075128","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":"PGK1 Regulates Oxidative Stress in Gestational Diabetes Mellitus through the Estradiol-Keap1-Nrf2 Pathway.","authors":"You Peng, Hengli Zhao, Jun Chen, Chi Chiu Wang, Tao Zhang, Tsz Ching Yeung, Haotong Ouyang, Jiayu Zhu, Xiangli Chen, Meng Li, Haoyue Hu, Mei Zhong","doi":"10.7150/ijbs.113728","DOIUrl":"10.7150/ijbs.113728","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM), the most common pregnancy-related metabolic disorder, is characterized by exacerbated oxidative stress (OS). The inhibition of phosphoglycerate kinase 1 (PGK1), the first ATP-generating enzyme in the glycolytic pathway, activates Keap1-Nrf2 antioxidant pathways and reduces OS. However, the detailed roles of PGK1 in GDM remain unexplored. Disruption of pro-oxidant/antioxidant homeostasis was observed in the placentas of GDM patients. PGK1 was significantly upregulated in both human GDM placentas and streptozotocin (STZ)-induced model mice. Pharmacological inhibition of PGK1 <i>in vivo</i> ameliorated placental dysfunction, attenuated excessive ROS production, and improved pregnancy outcomes. Lentivirus-mediated PGK1 knockdown in HTR8/SVneo trophoblasts increased Nrf2-dependent antioxidant protein expression while reducing ROS generation. Mechanistically, PGK1 inhibition elevated estradiol levels, facilitating Keap1 dimerization, and this dimerization destabilized the Keap1-Nrf2 complex, enabling Nrf2 accumulation and antioxidant activation. Exogenous estradiol supplementation recapitulated the effect of inhibiting PGK1 by enhancing Keap1 dimer formation, effectively mitigating placental OS and adverse pregnancy phenotypes in GDM models. This study elucidates the critical role of PGK1 in restoring redox homeostasis through the estradiol-Keap1-Nrf2 axis in the pathogenesis of GDM. PGK1/estradiol crosstalk represents a druggable target, and pharmacological PGK1 inhibition has translational potential for mitigating oxidative stress-related pregnancy complications.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5496-5513"},"PeriodicalIF":10.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075088","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":"WTAP Maintains Alternative Activation of Macrophages by Promoting IDH1-Mediated α-ketoglutarate Production.","authors":"Qianqian Xu, Jing Zhang, Yuan Zou, Longmin Chen, Fei Sun, Xi Luo, Ting Wang, Yang Li, Shu Zhang, Fei Xiong, Qilin Yu, Ping Yang, Quan Gong, Shi-Wei Liu, Cong-Yi Wang","doi":"10.7150/ijbs.115672","DOIUrl":"10.7150/ijbs.115672","url":null,"abstract":"<p><p><b>Background</b>: <i>N</i> ⁶-methyladenosine (m⁶A) modification plays a crucial role in various physiological processes by regulating mRNA biology. However, the exact impact of m⁶A modification on macrophages in adipose tissues under obese settings remains to be further elucidated. <b>Methods</b>: We established macrophage-specific <i>Wtap</i>-deficient mice to explore the effects of <i>Wtap</i> on obesity and metabolic disorders induced by high-fat diet (HFD) in mice. The molecular targets were explored by MeRIP-qPCR, and the metabolomic assays were performed to detect the alteration of relevant metabolites. <b>Results</b>: Wilms tumor 1-associated protein (WTAP), one of the m⁶A \"writers\", was downregulated in adipose tissue macrophages (ATMs) from obese individuals and negatively correlated with clinical metabolic traits. Depletion of <i>Wtap</i> in mouse macrophages exacerbated the metabolic consequences of high-fat diet (HFD) induced obesity. Additionally, energy expenditure and adipose beiging were considerably lower in <i>Wtap</i>-deficient mice in response to cold exposure. Mechanistic study revealed that WTAP-mediated m⁶A modification of isocitrate dehydrogenase 1 (<i>Idh1</i>) transcripts enhanced its stability and translation in macrophages leading to α-ketoglutarate (α-KG) production. Alpha-KG further supported alternative activation of macrophages by metabolic reprogramming. <b>Conclusions</b>: Our data support that <i>Wtap</i> modulates HFD-induced macrophages through interfering with the IDH1-α-KG axis, and highlight the importance of WTAP-mediated m⁶A modification in maintaining alternative macrophage activation, proposing potential targets for the regulation of obesity and related metabolic diseases.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5428-5443"},"PeriodicalIF":10.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075236","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":"Therapeutic Activation of PPARα Inhibits Transformed Follicular Lymphoma Tumorigenesis via the FOXM1 Signaling Pathway.","authors":"Dongmei Qin, Hui Zhou, Jie Zhou, Chendi Xie, Shuman Jia, Xingxing Yu, Yan Hong, Li Zhang, Yueting Huang, Yong Zhou, Bing Xu, Jie Zha","doi":"10.7150/ijbs.116437","DOIUrl":"10.7150/ijbs.116437","url":null,"abstract":"<p><p>Transformed follicular lymphoma (t-FL) is a subtype of follicular lymphoma (FL) characterized by aggressive behavior and poor treatment outcomes. Dysregulated glucose uptake and cell cycle disruption have been implicated in t-FL progression. Here, we found that PPARα is frequently low-expressed in transformed follicular lymphoma, and therapeutic activation of PPARα significantly represses the progression of t-FL in cell line-derived xenograft (CDX) and primary t-FL patient-derived xenograft (PDX) models <i>in vivo</i>. Mechanistically, activation of PPARα inhibits t-FL progression mainly through three different signaling pathways as follows: PPARα inhibits glycolysis in t-FL cells by blocking the HIF1α signaling pathway; activation of PPARα induces mitochondria-dependent apoptosis in t-FL cells by disrupting mitochondrial homeostasis; and PPARα transcriptionally inhibits FOXM1 expression, causing the downregulation of its downstream target genes and inducing cell cycle arrest in t-FL cells. Concurrently, knockdown of FOXM1 enhances the sensitivity of t-FL cells to chiglitazar, and overexpression of FOXM1 partially rescued the inhibitory effect of chiglitazar on t-FL cells, highlighting the involvement of the PPARα-FOXM1 axis in the antitumor effects of chiglitazar. These promising preclinical results support further clinical evaluation of chiglitazar as a potential therapeutic option for t-FL patients, providing a novel and effective treatment approach for this aggressive subtype of FL.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5411-5427"},"PeriodicalIF":10.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075277","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":"JPI-547, a Dual Inhibitor of PARP/Tankyrase, Shows Antitumor Activity Against Pancreatic Cancers with Homologous Recombination Repair Deficiency or Wnt-Addiction.","authors":"Kyoung-Seok Oh, Ah-Rong Nam, Ju-Hee Bang, Yoojin Jeong, Sea Young Choo, Hyo Jung Kim, Su In Lee, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh","doi":"10.7150/ijbs.113726","DOIUrl":"10.7150/ijbs.113726","url":null,"abstract":"<p><p>PARP inhibitors have demonstrated antitumor efficacy in solid tumors, including pancreatic ductal adenocarcinoma (PDAC) characterized by homologous recombination deficiency (HRD). The definition of HRD and other potential biomarkers should be further evaluated using PARP inhibitors. JPI-547 is a novel dual inhibitor targeting PARP1/2 and Tankyrase1/2. Herein, we demonstrate the potent antitumor activity of JPI-547 against BRCA2^-/- PDAC cells. JPI-547 outperformed most PARP inhibitors, with a half-maximal inhibitory concentration approximately 10-fold lower than that of olaparib. JPI-547 efficiently trapped PARP1 on the chromatin, disrupted poly-ADP-ribosylation, induced G2/M phase arrest, and triggered apoptosis in PDAC cells. In addition to HRD, we identified Wnt addiction as a predictive factor for JPI-547 activity. PDAC cells reliant on Wnt signaling due to pathogenic RNF43 mutations showed increased susceptibility to JPI-547 without altering homologous recombination repair efficiency. JPI-547 disrupts the Wnt/β-catenin pathway in RNF43-mutated cells and inhibits the oncogenic YAP pathway, highlighting its multifaceted therapeutic potential in PDAC with HRD or Wnt-addiction.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5460-5475"},"PeriodicalIF":10.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075018","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":"Mechanism of Ferroptosis and Its Role in Disease Development.","authors":"Zhangruijian Ye, Bin Xie, Yongguang Tao, Desheng Xiao","doi":"10.7150/ijbs.102859","DOIUrl":"10.7150/ijbs.102859","url":null,"abstract":"<p><p>Ferroptosis is a type of cell death that differs from general forms of cell death such as apoptosis. Iron accumulation and lipid peroxidation are distinct biochemical features of ferroptosis. Accumulation of iron ions in ferrodead cells can increase the probability of the Fenton reaction and produce more reactive oxygen species (ROS). Further, iron ions are cofactors for some intracellular oxidases. ROS, which are normally produced in the mitochondria, attack the phospholipid bilayer of the cell and produce lipid peroxides that ultimately kill the cell. Since the discovery of ferroptosis, its mechanism and relationship with diseases, such as nervous system diseases, tumors, and sepsis has been studied. Controlling disease development by regulating ferroptosis has thus become a popular topic of current research. This article summarizes the recent research progress on the mechanism of ferroptosis and its relationship with diseases. Overall, this study can provide a valuable reference for future ferroptosis studies.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 12","pages":"5328-5360"},"PeriodicalIF":10.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075097","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}