Cell Biology International最新文献

{"title":"Bufalin-Induced Epithelial-to-Mesenchymal Transition in Kidney Epithelial Cells.","authors":"Gabriela Morais de Oliveira Barros, Kayo M Bagri, Claudia Mermelstein, Luis Eduardo M Quintas","doi":"10.1002/cbin.70091","DOIUrl":"https://doi.org/10.1002/cbin.70091","url":null,"abstract":"<p><p>The kidney plays a central role in fluid, electrolyte, and blood pressure regulation, processes tightly coupled to Na⁺/K⁺-ATPase activity. Beyond its canonical transport function, Na⁺/K⁺-ATPase also acts as a signaling receptor for cardiotonic steroids (CTSs) such as bufalin, which have been implicated in fibrosis and epithelial-to-mesenchymal transition (EMT). Here, we investigated the effects of serial passages on porcine kidney epithelial LLC-PK1 cells and their response to the endogenous CTS bufalin. High-passage cells (P > 80) displayed increased proliferation (1.7x), viability (1.5x), and migration (2.2x) compared to low-passage cells (P < 40), concomitant with elevated ERK1/2 phosphorylation (2.5x), while NKA activity and expression remained unchanged. Bufalin treatment (20 nM, 48 h) induced striking morphological changes consistent with EMT in P > 80 cells, including a transition from cuboidal to elongated shapes with cytoplasmic extensions, whereas P < 40 cells were largely resistant. In high-passage cells, bufalin reduced pan-cadherin, E-cadherin, occludin, claudin-1, ZO-1, and ZO-2 expression, with redistribution of adhesion proteins from membrane to cytoplasm. β-catenin and ZEB-1 were excluded from the nucleus, indicating altered transcriptional regulation during EMT. In contrast, low-passage cells exhibited only modest reductions in E-cadherin, claudin-1, and ZEB-1, along with increased ZO-2, and β-catenin expression. For comparison, TGF-β1 induced partial EMT features in bufalin-resistant LLC-PK1 cells, including striking cell elongation, increased vimentin expression, and appearance of E-cadherin aggregates. Together, these results demonstrate that bufalin induces EMT-like changes in LLC-PK1 cells in a passage-dependent manner, possibly through ERK1/2 activation, disruption of intercellular adhesion, and modulation of transcription factor localization. These findings highlight bufalin as a regulator of epithelial plasticity with potential implications for renal pathophysiology.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment, Characterization, and Cryopreservation of Feather Follicle Fibroblast Lines From Hyacinth Macaw (Anodorhynchus hyacinthinus).","authors":"Iara Pastor Martins Nogueira, Rachel Castro Teixeira-Santos, Gustavo Caldeira Cotta, Wanderson Valente, John Lennon Paiva de Coimbra, Heloísa Athaydes Seabra Ferreira, Pedro Pires Goulart Guimarães, Anderson Kenedy Santos, Fernanda Mussi Fontoura, Kefany Rodrigues de Andrade Ramalho, Neiva Maria Robaldo Guedes, Samyra Maria Dos Santos Nassif Lacerda","doi":"10.1002/cbin.70089","DOIUrl":"https://doi.org/10.1002/cbin.70089","url":null,"abstract":"<p><p>Cryopreservation, biobanking, and in vitro propagation of cells from endangered species represent key strategies for advancing biodiversity conservation. The Hyacinth Macaw (Anodorhynchus hyacinthinus), a flagship avian species of the Brazilian Pantanal, is among the critically vulnerable taxa that stand to benefit significantly from such cutting-edge biotechnological interventions. This study developed and validated minimally invasive methods for isolating, culturing, and cryopreserving fibroblasts derived from feather follicles (FFFs) of Hyacinth Macaws. Cells isolated from nestlings under 100 days of age demonstrated superior yields and viability compared to older birds. Two cryopreservation media were tested-Cryomedium 1 (55% DMEM-F12, 35% FBS, 10% DMSO) and Cryomedium 2 (90% FBS, 10% DMSO)-with Cryomedium 1 proving more effective in maintaining FFFs viability immediately post-thaw. Several culture conditions were evaluated, including conventional plating, drop plating, gelatin coating, and supplementation with RevitaCell and bFGF. The optimal method involved conventional plating on gelatin-coated plates with RevitaCell supplementation during the first 24 h post-thaw. Additionally, two different culture media were tested, with KAV-1 emerging as the best option for the long-term propagation of Hyacinth Macaw fibroblasts. After some passages, FFFs maintained a stable karyotype of 2n = 70, expressed classical fibroblast markers such as Vim, Fap, Acta2, Col1a1, Col1a2, synthesized vimentin and Type I collagen in the cytoplasm, and were confirmed to be free of mycoplasma contamination. We successfully established the first primary fibroblast cell lines derived from the Hyacinth Macaw and demonstrated their efficient responsiveness to lipid nanoparticle-mediated transfection and exogenous gene expression, representing a significant advancement toward the development of somatic reprogramming strategies. These experiments enabled the optimization of protocols for cell collection, cryopreservation, in vitro propagation, and inducing sustained heterologous expression, thereby laying a valuable foundation for the future generation of induced pluripotent stem cells (iPSCs) to support ex situ conservation efforts for this endangered species.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esculetin Attenuates Doxorubicin-Induced Cardiotoxicity via Modulation of Apoptotic and Mitochondrial Gene Expression Networks.","authors":"Yeliz Demir, Hamid Ceylan, Medine Sibel Karağaç, Cüneyt Türkeş, Melike Karaman, Şükrü Beydemir","doi":"10.1002/cbin.70086","DOIUrl":"https://doi.org/10.1002/cbin.70086","url":null,"abstract":"<p><p>Doxorubicin (DOX), although widely used as a potent chemotherapeutic agent, is limited by its dose-dependent cardiotoxicity. Esculetin (E), a naturally occurring coumarin derivative, has been reported to exert antioxidant and anti-apoptotic effects in various tissues. This study aimed to evaluate the cardioprotective effects of esculetin against DOX-induced cardiac injury in rats by examining changes in the expression of genes related to apoptosis, oxidative stress, and mitochondrial function. Male Wistar rats were randomly assigned into six groups (Control, DOX, E50, E100, DOX + E50, DOX + E100). Cardiotoxicity was induced by administering DOX was administered as six intraperitoneal injections of 5 mg/kg each over 14 days (cumulative dose = 30 mg/kg). Serum cardiac markers (CK-MB, LDH, and cTn-I) were measured, and cardiac tissues were subjected to histopathological examination and RT-qPCR analysis for target gene expression. In addition, hierarchical clustering heatmap was employed to evaluate multidimensional gene expression patterns across groups. DOX treatment significantly elevated serum cardiac injury markers and upregulated pro-apoptotic genes (Casp3, Casp9, Anf, Bnp, β-Mhc), while downregulating genes associated with mitochondrial biogenesis (Pgc1α) and antioxidant response (Foxo1, Cox2). These findings suggest esculetin as a potential adjunctive candidate for cardioprotection during DOX chemotherapy. However, given the absence of protein-level validation, further studies are warranted to confirm whether the observed gene expression changes translate into corresponding alterations at the protein level.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vinpocetine Overcomes Paclitaxel Resistance in a Triple-Negative Breast Cancer Cell Line.","authors":"Hsiao-Hui Kuo, Chien-Wei Huang, Wei-Rou Chiang, Ling-Huei Yih","doi":"10.1002/cbin.70088","DOIUrl":"https://doi.org/10.1002/cbin.70088","url":null,"abstract":"<p><p>Paclitaxel is a first-line treatment for triple-negative breast cancer (TNBC), but its efficacy is commonly limited by tumor-cell resistance. Vinpocetine is a well-tolerated dietary supplement with pleiotropic cellular effects, including potential anti-tumor activity. In this study, we tested whether and how vinpocetine might enhance the sensitivity of TNBC cells to paclitaxel. A paclitaxel-resistant TNBC cell line (T50RN) was established by incubating MDA-MB-231 cells with escalating concentrations of paclitaxel (0.5-50 nM). The effects of vinpocetine on T50RN cell sensitivity to paclitaxel were examined. T50RN cells were significantly more resistant to paclitaxel than the parental MDA-MB-231 cells. Vinpocetine itself was slightly cytotoxic to cells but considerably enhanced paclitaxel sensitivity in T50RN cells. Expression of PDE1C, a target of vinpocetine, was elevated in T50RN cells. Depletion of PDE1C moderately enhanced paclitaxel sensitivity of T50RN cells, suggesting that PDE1C overexpression might contribute to paclitaxel resistance. In addition, vinpocetine induced microtubule stabilization and significantly enhanced paclitaxel-induced microtubule stabilization. However, vinpocetine could still enhance paclitaxel sensitivity in PDE1C-depleted T50RN cells, indicating that vinpocetine also acts through factor(s) other than PDE1C. P-gp expression and activity were elevated in T50RN cells, and inhibition of P-gp sensitized T50RN cells to paclitaxel. Vinpocetine functionally disrupted P-gp in T50RN cells and further enhanced the death of P-gp-inhibited paclitaxel-treated T50RN cells. Thus, our results revealed that vinpocetine may act on P-gp and PDE1C to facilitate paclitaxel accumulation and paclitaxel-induced stabilization of microtubules in T50RN cells, thereby enhancing the antimitotic effects of paclitaxel and disrupting paclitaxel-resistance mechanisms.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matter of Fat: Cancer-Associated Adipocytes as Mediators of Tumor Progression and Immune Evasion.","authors":"Niti Sureka, Shikhar Chohan, Samreen Zaheer, Durre Aden, Sana Ahuja, Amit H Agravat, Seema Goel, Jaseem Hassan, Laltlanzovi Chawgthu, Hage Nobin, Sufian Zaheer","doi":"10.1002/cbin.70085","DOIUrl":"https://doi.org/10.1002/cbin.70085","url":null,"abstract":"<p><p>Peritumoral adipocytes that exhibit changes in their phenotype and distinct biological characteristics, such as reduced expression of mature adipocyte differentiation markers, increased secretion of adipocyte-derived factors, and facilitation of metabolic reprogramming in cancer cells, are referred to as cancer-associated adipocytes (CAAs). CAAs are increasingly recognized as important contributors to tumor initiation, progression, and metastasis within the tumor microenvironment (TME). Found predominantly in fat-rich tissues such as breast, ovarian, colorectal, and pancreatic cancers, CAAs undergo significant functional changes when exposed to cancer cells. These changes include lipid transfer to cancer cells, secretion of pro-inflammatory cytokines, and remodeling of the extracellular matrix, all of which enhance cancer cell survival, proliferation, and invasion. The TME, composed of various non-cancerous cells, extracellular matrix components, and signaling molecules, plays a dynamic role in influencing tumor behavior and treatment response. CAAs engage in a reciprocal interaction with cancer cells, transforming from normal adipocytes to tumor-promoting cells while simultaneously driving cancer aggressiveness. Understanding the mechanisms through which CAAs contribute to cancer progression offers promising avenues for novel therapeutic strategies targeting the TME to combat cancer more effectively.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytogenotoxic Evaluation of Lercanidipine Hydrochloride in Human Lymphocytes Using Micronucleus, Chromosome Abnormalities, and Molecular Docking Assays.","authors":"İbrahim Halil Kenger, Ahmet Kardöl, Ahmet Kayraldiz, Mehmet Tahir Hüsunet, Tuğçe Nur Yilmaz","doi":"10.1002/cbin.70083","DOIUrl":"https://doi.org/10.1002/cbin.70083","url":null,"abstract":"<p><p>This study evaluated the cytotoxic and genotoxic potential of lercanidipine hydrochloride (LHC) on human peripheral lymphocytes using in vitro and in silico approaches. The micronucleus (MN) test revealed a significant, dose-dependent increase in MNs, particularly after 24-h treatment (***p < 0.001), which suggests potential DNA damage. However, the chromosome aberration (CA) test did not yield statistically significant results, although a dose-related upward trend was observed. A substantial reduction in both the mitotic index (MI) and the nuclear division index (NDI) was observed at all concentrations (**p < 0.01, ***p < 0.001), indicating strong cytotoxic effects. In silico molecular docking analysis revealed that the ligand (LHC) binds to the minor groove of B-DNA with a binding energy of -7.7 kcal/mol, forming non-covalent interactions similar to those of the known minor groove binder Netropsin (-8.14 kcal/mol). By contrast, the positive control, mitomycin C (MMC), binds to the major groove via intercalation, forming covalent cross-links, with a binding energy of -5.45 kcal/mol. Although LHC's minor groove binding suggests a potential preference for AT-rich regions, its sequence specificity remains unconfirmed. Overall, these findings suggest that LHC primarily exhibits cytotoxic effects (e.g., inhibition of DNA replication or transcription), with only limited and preliminary evidence of genotoxic potential. Further studies are needed to elucidate the safety of LHC and its DNA interaction mechanisms.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tauroursodeoxycholic Acid Mitigates Inflammation, ER Stress, and Apoptosis in Experimental Endotoxin-Induced Uveitis: In Vivo and In Vitro Evidence.","authors":"Yusuf Samet Atlıhan, Aleyna Öztüzün Ün, Hazal Tuzcu Balaban, Esma Kırımlıoğlu, Cumhur İbrahim Başsorgun, Mehmet Erkan Doğan, Mutay Aslan","doi":"10.1002/cbin.70084","DOIUrl":"https://doi.org/10.1002/cbin.70084","url":null,"abstract":"<p><p>Endotoxin-induced uveitis (EIU) is a well-established model for acute ocular inflammation and mimics aspects of human uveitis. Tauroursodeoxycholic acid (TUDCA), a bile acid with known anti-inflammatory and cytoprotective properties, may attenuate retinal injury by targeting endoplasmic reticulum (ER) stress and apoptosis. This study investigates the protective effects of TUDCA in both in vivo and in vitro EIU models. EIU was induced in male Wistar rats by intravitreal injection of lipopolysaccharide (LPS), with or without prior intraperitoneal TUDCA administration. ARPE-19 cells were used to model retinal pigment epithelial stress in vitro. Ocular inflammation was assessed clinically and histologically. Immunostaining and immunofluorescence quantified ER stress marker Glucose-Regulated Protein 78 (GRP78), caspase-3, caspase-12, and apoptosis. Caspase-3 activity and TUNEL assays evaluated apoptotic response. TUDCA pretreatment significantly reduced LPS-induced ocular inflammation and retinal thickening in rats. In ARPE-19 cells, TUDCA restored LPS-compromised viability and mitigated morphological damage. Both models showed reduced expression of GRP78, caspase-3, and caspase-12 following TUDCA administration. TUNEL and caspase-3 activity assays confirmed that TUDCA decreased apoptosis in retinal tissues and cultured cells. The findings demonstrate that TUDCA effectively suppresses ER stress and apoptosis pathways activated during endotoxin-induced retinal inflammation. Its dual anti-inflammatory and cytoprotective actions support its therapeutic potential in acute ocular inflammatory conditions. TUDCA attenuates clinical, histological, and molecular manifestations of LPS-induced uveitis, highlighting its promise as a candidate for adjunctive therapy in inflammatory retinal diseases.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Cryptochromes in Chronic Diseases.","authors":"Takuro Toda, Tsuyoshi Hirota","doi":"10.1002/cbin.70087","DOIUrl":"https://doi.org/10.1002/cbin.70087","url":null,"abstract":"<p><p>The circadian clock generates 24-h molecular rhythms through transcription-translation negative feedback loops (TTFLs) and regulates daily physiological processes such as sleep-wake cycles, body temperature, hormone secretion, metabolism, and immune function. Cryptochromes (CRY1 and CRY2) are essential components of the mammalian circadian clock as the transcriptional repressors in TTFLs. Disruption of the circadian clock by shiftwork or mutations of clock genes disturbs daily physiological rhythms and poses serious risks to human health. Misregulations of CRY in humans and mice induce chronic diseases such as diabetes mellitus, sleep disorders, inflammatory diseases, and cancers. Chemical biology approaches have been applied to further elucidate molecular mechanisms of the circadian clock and to treat chronic diseases. The chemicals enable dose-dependent and reversible manipulation, forming the basis of drug development. Since 2012, about a dozen small-molecule compounds targeting CRY have been discovered, enabling the control of CRY functions. This review summarizes the roles of CRY in chronic diseases and introduces therapeutic approaches using CRY-targeting compounds. A deeper understanding of the pathology of chronic diseases and the effects of CRY-targeting compounds may lead to new circadian clock-based strategies for clinical advances.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Editing for Cystic Fibrosis: Advances and Prospects of CRISPR-Cas9 Therapy.","authors":"Iqra Khurram, Mahmood S Choudhery, Muhammad Usman Ghani, Taqdees Arif, Aiza Naeem, Ruhma Mahmood, Ahmad Niaz, Muhammad Umer Khan","doi":"10.1002/cbin.70082","DOIUrl":"https://doi.org/10.1002/cbin.70082","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is an inherited, autosomal recessive disorder that is caused by mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CFTR maintains the balance between water and salts by transporting chloride ions along various epithelial surfaces. CFTR impairment affects the function of several organs, including the lungs. Newborn screening, prenatal diagnosis, and pharmacological interventions have altered the prevalence and incidence of cystic fibrosis. Although CFTR modulators are a promising treatment option, their ability to target and correct only one mutation at a time restricts their therapeutic potential. The development of genome editing technologies such as Clustered Regularly Interspaced Short Palindromic Repeats-Cas(CRISPR-Cas9) has the potential to correct genetic mutations, including those associated with CF, thereby offering a permanent treatment by fixing the root cause of CF. This article summarizes cystic fibrosis development, prognosis, and diagnosis, as well as possibilities for correcting various types of CFTR gene mutations. The review focuses on the potential of gene editing technologies to repair CFTR mutations and their applications in the advancement of CF treatment.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Malonate as a Succinate Dehydrogenase Inhibitor on Myocardial Ischemia/Reperfusion Injury.","authors":"Amir Modarresi Chahardehi, Reza Arefnezhad, Sajjad Rafei, Alireza Arzhangzadeh, Reza Nasiri, Fatemeh Rezaei-Tazangi, Marziye Ranjbar Tavakoli","doi":"10.1002/cbin.70079","DOIUrl":"https://doi.org/10.1002/cbin.70079","url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion injury (MIRI) continues to provide a serious therapeutic challenge, substantially influencing myocardial infarct size and negative cardiovascular outcomes. Recent research underscores the critical significance of succinate accumulation and its rapid oxidation during reperfusion, initiating the generation of reactive oxygen species (ROS) and mitochondrial impairment. Malonate, a competitive inhibitor of succinate dehydrogenase (SDH), has attracted interest as a cardioprotective drug by reducing ROS production and cellular damage during the first reperfusion. Malonate preferentially accumulates in ischemic tissues via monocarboxylate transporter 1 (MCT1), driven by the acidic conditions of ischemia. This specific dosing prevents SDH, which in turn reduces succinate oxidation and ROS production, protecting mitochondrial integrity and heart function. The effects of malonate on infarct size reduction, left ventricular ejection fraction enhancement, and pro-inflammatory and fibrotic marker mitigation have been demonstrated in preclinical research conducted on animal models. Additionally, acidified malonate formulations improve therapeutic selectivity, providing significant cardioprotection at lower dosages. Notwithstanding encouraging experimental results, clinical validation is crucial to ascertain malonate's translational potential for the treatment of acute myocardial infarction (MI) and post-reperfusion heart failure. This review discusses the pathophysiology of MIRI, the function of SDH, and the mechanism of action of malonate, highlighting its potential as a targeted intervention for MIRI.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}