Biochimica et biophysica acta. Molecular basis of disease最新文献

{"title":"Mitochondria: An overview of their origin, genome, architecture, and dynamics","authors":"João P. Moura ,&nbsp;Paulo J. Oliveira ,&nbsp;Ana M. Urbano","doi":"10.1016/j.bbadis.2025.167803","DOIUrl":"10.1016/j.bbadis.2025.167803","url":null,"abstract":"<div><div>Mitochondria are traditionally viewed as the powerhouses of eukaryotic cells, i.e., the main providers of the metabolic energy required to maintain their viability and function. However, the role of these ubiquitous intracellular organelles far extends energy generation, encompassing a large suite of functions, which they can adjust to changing physiological conditions. These functions rely on a sophisticated membrane system and complex molecular machineries, most of which imported from the cytosol through intricate transport systems. In turn, mitochondrial plasticity is rooted on mitochondrial biogenesis, mitophagy, fusion, fission, and movement. Dealing with all these aspects and terminology can be daunting for newcomers to the field of mitochondria, even for those with a background in biological sciences. The aim of the present educational article, which is part of a special issue entitled “Mitochondria in aging, cancer and cell death”, is to present these organelles in a simple and concise way. Complex molecular mechanisms are deliberately omitted, as their inclusion would defeat the stated purpose of the article. Also, considering the wide scope of the article, coverage of each topic is necessarily limited, with the reader directed to excellent reviews, in which the different topics are discussed in greater depth than is possible here. In addition, the multiple cell type-specific genotypic and phenotypic differences between mitochondria are largely ignored, focusing instead on the characteristics shared by most of them, with an emphasis on mitochondria from higher eukaryotes. Also ignored are highly degenerate mitochondrion-related organelles, found in various anaerobic microbial eukaryotes lacking canonical mitochondria.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167803"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KBU2046 exerts inhibition on chemokine gradient-mediated motility of esophageal squamous cell carcinoma through reducing integrin expression","authors":"Kexin Li ,&nbsp;Jinxia Chen ,&nbsp;Wendi Li ,&nbsp;Zhenzhen Zhang ,&nbsp;Yongxian Xue ,&nbsp;Yang Zheng ,&nbsp;Ying Zhang ,&nbsp;Cong Zhang ,&nbsp;Raymond Bergan ,&nbsp;Lianmei Zhao","doi":"10.1016/j.bbadis.2025.167800","DOIUrl":"10.1016/j.bbadis.2025.167800","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) cells migrate from their initial site of origin, ultimately forming metastasis and causing death. The selective inhibition of ESCC cell movement has not been possible to date. Here we demonstrate that the small molecule therapeutic agent KBU2046 inhibits the characteristic migration and invasion of ESCC cells induced by chemokine gradients, having no effect on cell proliferation. After demonstrating that KBU2046 inhibits human ESCC metastasis in a murine model, we showed that it doesn't inhibit the <em>in vitro</em> efficacy of chemotherapeutic agents used clinically, going on to demonstrate maintenance of cisplatin efficacy when combined with KBU2046 in a murine model. Mechanistic studies demonstrated that KBU2046 inhibited epidermal growth factor (EGF)-mediated phosphorylation of receptor-interacting serine/threonine protein kinase 1 (RIPK1) on its Ser166 activation motif. RIPK1 was shown to be necessary for KBU2046 efficacy. However, this was shown to be dependent upon cell context, and was also shown to be dependent upon level of RIPK1 expression, both supporting the presence of additional therapeutically sensitive regulatory pathways. Mass spectrometry analysis of ESCC cells demonstrated that KBU2046 selectively altered the expression of proteins involved in cell motility. Integrin αV (ITGAV) is overexpressed in ESCC, was decreased by KBU2046, and its knockdown inhibited ESCC cell migration and invasion, which was necessary for KBU2046 efficacy. We demonstrate that ESCC's motility can be inhibited, and KBU2046 inhibits motility in an Integrin αV-dependent manner, and that combining anti-motility and cytotoxic agents is a high valuable therapeutic strategy for ESCC that should be further developed.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167800"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2i delays c-Myc-induced HCC progression via targeting mTOR","authors":"Huiling Rao ,&nbsp;Xiaotong An ,&nbsp;Xinyang Qu ,&nbsp;Juan Yu ,&nbsp;Jin Xie ,&nbsp;Jing Ke ,&nbsp;Zhixin Liu ,&nbsp;Lei You ,&nbsp;Zhenpeng Qiu ,&nbsp;Lin Tian ,&nbsp;Weixing Du ,&nbsp;Wanrong Li ,&nbsp;Jie Jia ,&nbsp;Danwen Liu ,&nbsp;Shan Li","doi":"10.1016/j.bbadis.2025.167805","DOIUrl":"10.1016/j.bbadis.2025.167805","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) stands as a primary malignant liver tumor characterized by metabolic reprogramming. The oncogene c-Myc exerts substantial influence by driving the transcription of numerous genes. Empagliflozin (EMPA), a sodium-glucose cotransporter-2 inhibitor (SGLT2i), is widely used in the treatment of type 2 diabetes and has recently attracted attention for its potential anti-cancer effects. This study aims to unravel the complex interplay among c-Myc, EMPA, and the mammalian target of rapamycin (mTOR) in HCC development and progression.</div></div><div><h3>Methods</h3><div>HCC induction in mice utilized high-pressure hydrodynamic transfection of the c-Myc plasmid. QPCR and immunohistochemistry experiments were performed to detect the expression of SGLT2 in HCC tissues. In vivo experiments were conducted to corroborate the upregulation of SGLT2 following c-Myc transfection. <em>In invo and vitro</em> investigations were conducted to evaluate the anti-cancer effects of two SGLT2i: EMPA and canagliflozin (CANA). Network pharmacology, molecular docking analyses, CETSA experiments, and additional western blot experiments were used to reveal EMPA's interaction inhibition with mTOR.</div></div><div><h3>Results</h3><div>The study identified an increase in SGLT2 expression in HCC tissues as a result of c-Myc overexpression. In vitro experiments confirmed the upregulation of SGLT2 following c-Myc transfection. Notably, the administration of SGLT2i effectively curtailed liver cancer progression, and reduced hepatic fat accumulation in mice. EMPA exhibited significant suppression of cell proliferation in c-Myc-transfected cells. In vitro experiments unveiled EMPA's interaction and with inhibition the activation of mTOR.</div></div><div><h3>Conclusion</h3><div>Our study highlights EMPA's potential as a therapeutic agent in delaying the development and progression of HCC.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167805"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation-inducing factor-1 ameliorates liver fibrosis through the reversion of activated hepatic stellate cells","authors":"Akira Ooka ,&nbsp;Momoka Yamaguchi ,&nbsp;Kensuke Suzuki ,&nbsp;Shin-ya Saito ,&nbsp;Yukiko K. Kaneko ,&nbsp;Toshihide Kimura ,&nbsp;Tomohisa Ishikawa","doi":"10.1016/j.bbadis.2025.167802","DOIUrl":"10.1016/j.bbadis.2025.167802","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>DIF-1 derived from <em>Dictyostelium discoideum</em> ameliorates liver fibrosis (LF) in mice.</div></span></li><li><span>•</span><span><div>When the LF mouse model was orally administered with DIF-1, decreased expression of <em>Acta2</em>, <em>Col1a1</em>, <em>Pdgfrb</em>, and <em>Timp1</em>, markers of activated hepatic stellate cells (HSCs) and genes related to LF, and increased expression of <em>Lrat</em>, a marker of quiescent HSCs, were observed in the liver tissue.</div></span></li><li><span>•</span><span><div>The treatment of primary cultured mouse activated HSCs with DIF-1 reverted the cell morphology to a quiescent HSC-like shape and significantly reduced the expression of α-smooth muscle actin, a marker of activated HSCs.</div></span></li></ul></div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167802"},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrical stimulation promotes peripheral nerve regeneration by upregulating glycolysis and oxidative phosphorylation","authors":"Nannan Zhang ,&nbsp;Xiaoying Yao ,&nbsp;Qingqing Zhang ,&nbsp;Chuanji Zhang ,&nbsp;Qian Zheng ,&nbsp;Yuzhong Wang ,&nbsp;Fangzhen Shan","doi":"10.1016/j.bbadis.2025.167804","DOIUrl":"10.1016/j.bbadis.2025.167804","url":null,"abstract":"<div><div>Peripheral nerve injury (PNI) frequently results in motor and sensory dysfunction due to the limited regenerative capacity of axonal neurons and Schwann cells. Electrical stimulation (ES) has emerged as a promising strategy to enhance nerve regeneration; however, the underlying mechanisms, particularly those related to energy metabolism, remain poorly understood. This study aimed to investigate whether ES could promote nerve regeneration in a mouse model of PNI by modulating energy metabolism. ES was applied to the gastrocnemius and posterior thigh muscles post-sciatic nerve injury. Motor functional recovery was evaluated using gait analysis and electrophysiological test. Molecular and cellular changes in the distal nerve stumps were evaluated through Western blot and immunofluorescence staining. Nerve regeneration was assessed by neurostructural protein staining and nerve ultrastructure visualized by transmission electron microscopy. Our findings indicate that ES significantly accelerated both morphological and functional recovery following PNI. Specifically, ES upregulated energy metabolism in the sciatic nerve post-PNI by enhancing glucose uptake, glycolysis, and oxidative phosphorylation. Furthermore, ES increased the expression of neurotrophic factors and modulated the AMPK/mTOR/p70S6K signaling pathway, which are crucial for cellular metabolism and nerve regeneration. Collectively, these findings underscore the critical role of ES in modulating energy metabolism to support nerve regeneration, highlighting its potential as a clinical strategy for treating peripheral neuropathy.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167804"},"PeriodicalIF":4.2,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keloid vasculature reacts to intralesional injection therapies but does not predict the response to treatment: Biopsies from double-blinded, randomized, controlled trial","authors":"Tuomas Komulainen ,&nbsp;Kristiina E. Hietanen ,&nbsp;Teemu Tolonen ,&nbsp;Seppo Parkkila ,&nbsp;Ilkka S. Kaartinen ,&nbsp;Tero A.H. Järvinen","doi":"10.1016/j.bbadis.2025.167790","DOIUrl":"10.1016/j.bbadis.2025.167790","url":null,"abstract":"<div><div>Keloids are benign fibroproliferative skin scars that expand beyond the original wound site. Hypoxia and angiogenesis are thought to drive pathological scar formation in keloids. We utilized biopsies collected before, during and after the double-blinded randomized controlled trial (RCT) comparing the intralesional treatments of 5-fluorouracil and triamcinolone injections in 48 human keloids. We could not detect any cells expressing the hypoxia markers (carbonic anhydrase 9 and hypoxia-inducible factor 1α) in the three distinct regions of keloid dermis. The amount of epidermal hypoxia could not predict the response to treatment. The middle dermis of the patients obtaining a clinical response to the intralesional injections showed significant increase in mature blood vessels and in lymphatics after the treatment. Our study does not support hypoxia being the driver behind keloid formation but demonstrates that the patients obtaining a response to intralesional therapies develop more blood vessels and lymphatics in the middle dermis of the keloids during the treatment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167790"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628419","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":"Activation, interaction and intimation of Nrf2 pathway and their mutational studies causing Nrf2 associated cancer","authors":"Mridul Sahu,&nbsp;Utkarsh Jain","doi":"10.1016/j.bbadis.2025.167764","DOIUrl":"10.1016/j.bbadis.2025.167764","url":null,"abstract":"<div><div>Responses against infection trigger several signaling pathways that lead to the production of cytokines, these cytokines release ROS and RNS, damaging DNA and proteins turn into various diseases including cancer. To combat these harmful cytokines, the Nrf2 pathway is activated. The gene NFE2L2 encodes Nrf2, which is divided into seven conserved domains (Neh1–7). The DLG and ETGE motifs, conserved sequences of amino acid in the Neh2 domain of Nrf2, bind to the BTB domain of Keap1. BTB domain promotes Keap1's homodimerization resulting in Cul3 recruitment providing scaffold formation to E2 ubiquitin ligase to form ubiquitin complex. Under normal conditions, this complex regularly degrades Nrf2. However, once the cell is exposed to oxidative stress by ROS interaction with Keap1 resulting in conformational changes that stabilize the Nrf2. Nrf2 further concentrates on the nucleus where it binds with the transcriptional factor to perform the desired genes transcription for synthesizing SOD, GSH, CAT, and various other proteins which reduce the ROS levels preventing certain diseases. To prevent cells from oxidative stress, molecular hydrogen activates the Nrf2 pathway. To activate the Nrf2 pathway, molecular hydrogen oxidizes the iron porphyrin which acts as an electrophile and interacts with Keap1's cysteine residue.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167764"},"PeriodicalIF":4.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine RNA modification in stomach carcinoma: Novel insights into mechanisms and implications for diagnosis and treatment","authors":"Zhengmao Lu ,&nbsp;Zhaojie Lyu ,&nbsp;Peixin Dong ,&nbsp;Yunmei Liu ,&nbsp;Lei Huang","doi":"10.1016/j.bbadis.2025.167793","DOIUrl":"10.1016/j.bbadis.2025.167793","url":null,"abstract":"<div><div>N6-methyladenosine (m⁶A) RNA methylation is crucially involved in the genesis and advancement of gastric cancer (GC) by controlling various pathobiological aspects including gene expression, signal transduction, metabolism, cell death, epithelial-mesenchymal transition, angiogenesis, and exosome function. Despite its importance, the exact mechanisms by which m⁶A modification influences GC biology remain inadequately explored. This review consolidates the latest advances in uncovering the mechanisms and diverse roles of m⁶A in GC and proposes new research and translational directions. Key regulators (writers, readers, and erasers) of m⁶A, such as METTL3/14/16 and WTAP, significantly affect cancer progression, anticancer immune response, and treatment outcomes. m⁶A modification also impacts immune cell infiltration and the tumor microenvironment, highlighting its potential as a diagnostic and prognostic marker. Interactions between m⁶A methylation and non-coding RNAs offer further novel insights into GC development and therapeutic targets. Targeting m⁶A regulators could enhance immunotherapy response, overcome treatment resistance, and improve oncological and clinical outcomes. Models based on m⁶A can precisely predict treatment response and prognosis in GC. Additional investigation is needed to fully understand the mechanisms of m⁶A methylation and its potential clinical applications and relevance (e.g., as precise markers for early detection, prediction of outcome, and response to therapy and as therapeutic targets) in GC. Future research should focus on in vivo studies, potential clinical trials, and the examination of m⁶A modification in other types of cancers.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167793"},"PeriodicalIF":4.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostaglandin E2 alleviates inflammatory response and lung injury through EP4/cAMP/IKK/NF-κB pathway","authors":"Yelin Tang ,&nbsp;Weiting Pan ,&nbsp;Wenting Ding ,&nbsp;Xingye Pan ,&nbsp;Junyi Zhu ,&nbsp;Huiwen Chen ,&nbsp;Xiaona Zhu ,&nbsp;Jingyi Chen ,&nbsp;Zijun Cheng ,&nbsp;Yali Zhang ,&nbsp;Bing Zhang","doi":"10.1016/j.bbadis.2025.167801","DOIUrl":"10.1016/j.bbadis.2025.167801","url":null,"abstract":"<div><h3>Purpose</h3><div>Prostaglandin E2 (PGE2), a pivotal lipid metabolite, plays a dual role in inflammation, manifesting both pro-inflammatory and anti-inflammatory effects, which are significantly influenced by the cellular microenvironment and receptor subtype. Although recent studies have highlighted the anti-inflammatory potential of PGE2, its role in toll-like receptor (TLR)-associated inflammation and the underlying mechanisms have not fully elucidated. Consequently, the primary aim of this study was to assess the anti-inflammatory efficacy of PGE2 in TLR-related inflammation and to elucidate the associated mechanisms.</div></div><div><h3>Methods</h3><div>In vitro, the anti-inflammatory effect of PGE2 on TLR-related inflammation were investigated by measuring pro-inflammatory cytokine protein and gene levels using ELISA and RT-qPCR, respectively. Western blot analysis was used to explore the corresponding anti-inflammatory signaling pathways. In vivo, the anti-inflammatory effects of PGE2 were further validated using ALI and sepsis models, employing the PGE2 analog 16,16-dimethyl prostaglandin E2 (dmPGE2).</div></div><div><h3>Results</h3><div>The findings revealed that PGE2 inhibited the LPS-induced inflammatory response and activation of the IKK/NF-κB signaling pathway via the EP4 receptor-mediated downstream cAMP/PKA pathway. Additionally, PGE2 analog, dmPGE2, effectively mitigated pathological injury and the inflammatory response in lung tissue of mice subjected to LPS-induced ALI and sepsis. Notably, dmPGE2 suppressed LPS-induced activation of the IKK/NF-κB signaling pathway in lung tissue.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that PGE2 can inhibit the IKK/NF-κB signaling pathway through the EP4/cAMP/PKA pathway, thereby alleviating the LPS-induced inflammatory response and providing a protective effect against LPS-induced ALI and sepsis. Consequently, PGE2 holds promise as a candidate for drug development aimed at preventing ALI and sepsis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167801"},"PeriodicalIF":4.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis, necroptosis, and pyroptosis in calcium oxalate crystal-induced kidney injury","authors":"Kun Tang ,&nbsp;Tao Ye ,&nbsp;Yu He ,&nbsp;Xiaozhuo Ba ,&nbsp;Ding Xia ,&nbsp;Ejun Peng ,&nbsp;Zhiqiang Chen ,&nbsp;Zhangqun Ye ,&nbsp;Xiaoqi Yang","doi":"10.1016/j.bbadis.2025.167791","DOIUrl":"10.1016/j.bbadis.2025.167791","url":null,"abstract":"<div><div>Kidney stones represent a highly prevalent urological disorder worldwide, with high incidence and recurrence rates. Calcium oxalate (CaOx) crystal-induced kidney injury serves as the foundational mechanism for the formation and progression of CaOx stones. Regulated cell death (RCD) such as ferroptosis, necroptosis, and pyroptosis are essential in the pathophysiological process of kidney injury. Ferroptosis, a newly discovered RCD, is characterized by its reliance on iron-mediated lipid peroxidation. Necroptosis, a widely studied programmed necrosis, initiates with a necrotic phenotype that resembles apoptosis in appearance. Pyroptosis, a type of RCD that involves the gasdermin protein, is accompanied by inflammation and immune response. In recent years, increasing amounts of evidence has demonstrated that ferroptosis, necroptosis, and pyroptosis are significant pathophysiological processes involved in CaOx crystal-induced kidney injury. Herein, we summed up the roles of ferroptosis, necroptosis, and pyroptosis in CaOx crystal-induced kidney injury. Furthermore, we delved into the curative potential of ferroptosis, necroptosis, and pyroptosis in CaOx crystal-induced kidney injury.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167791"},"PeriodicalIF":4.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631118","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}