Cell Biochemistry and Biophysics最新文献

{"title":"A Potentially Protective Role for NRF2 in Endocannabinoid-Mediated Oxidative Stress in Human Coronary Artery Endothelial Cells.","authors":"Michael J Haas, Kareen Champagne, Nidhi Gupta, Andrew Velarde, Maurice Chakour, Johny Alrahal, George Zakour, Anocens Augustin, Arshag D Mooradian","doi":"10.1007/s12013-026-02169-y","DOIUrl":"https://doi.org/10.1007/s12013-026-02169-y","url":null,"abstract":"<p><p>Excess oxidative and endoplasmic reticulum (ER) stress disrupt cellular homeostasis and promote cardiovascular disease (CVD). The endocannabinoids anandamide and 2-arachidonoyl glycerol and the potent cannabinoid Δ9-tetrahydrocannabinol increase oxidative stress and ER stress in endothelial cells. However, it remains unclear whether endocannabinoids have intrinsic capacity to ameliorate oxidative stress. In human coronary artery endothelial cells (HCAEC), anandamide, 2-arachidonoyl glycerol, and tunicamycin increased superoxide generation and nuclear factor erythroid 2-related factor 2 (NRF2) mRNA and NRF2-dependent reporter gene activity. High anandamide, 2-arachidonoyl glycerol, and tunicamycin levels also increased lipid peroxidation. Furthermore, anandamide increased NRF2-responsive hemeoxygenase 1 (HO1), thioredoxin reductase 1 (TRX1), and NAD(P)H dehydrogenase quinone 1 (NQO1) mRNA. This effect was mediated by protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK); PERK silencing utilizing siRNA suppressed NRF2 induction by anandamide and tunicamycin. In contrast, activating transcription factor 6 (ATF6) and inositol requiring enzyme 1α (IRE1α ) silencing had no effect on NRF2 mRNA or NRF2 target gene expression in tunicamycin and anandamide-treated cells. Likewise, the PERK inhibitor GSK2606414 prevented NRF2 induction by anandamide and tunicamycin while treatment with Ceapin A7 (an ATF6 inhibitor) or GSK2850163 (an IRE1α inhibitor) did not. In conclusion, endocannabinoid-related ER stress increased superoxide generation accompanied by compensatory increase in production of antioxidant enzymes thereby highlighting the cross talk between ER stress and oxidative stress.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IER5L Facilitates the Progression of Hormone Receptor-Positive Breast Cancer by Inhibiting HSF1 Phosphorylation in Response to Bevacizumab.","authors":"Wei Jia, Haoqi Wang, Lina Zhang, Lixian Yang, Jingjing Yu, Jinqiang Yang, Cuizhi Geng","doi":"10.1007/s12013-026-02161-6","DOIUrl":"https://doi.org/10.1007/s12013-026-02161-6","url":null,"abstract":"<p><p>As the most frequently diagnosed cancer in women worldwide, breast cancer (BC) exhibits high heterogeneity, with hormone receptor-positive (HR+) tumors accounting for 60%-75% of all clinical BC cases. Despite extensive evaluation of bevacizumab (Bev) across BC subtypes, HR + BC remains a major clinical challenge. Given current therapeutic limitations, exploring Bev-related strategies offers promise for uncovering new vulnerabilities in HR + BC. In this study, treatment of the prototypical HR + BC cell line MCF-7 with Bev led to an enhanced invasive phenotype in these cells. Subsequent mRNA sequencing of MCF-7 cells revealed immediate early response 5-like (IER5L) as an upregulated gene in Bev-treated cells. Clinical analysis demonstrated that IER5L expression was significantly elevated in HR + BC tissue samples and that high IER5L levels were closely correlated with TNM stage. Functional characterization revealed that IER5L overexpression enhanced cell migration and invasion, concomitant with the induction of an epithelial-mesenchymal transition (EMT) phenotype. Furthermore, heat-shock factor 1 (HSF1), a known oncogenic driver, showed a positive correlation with IER5L in BC samples, and both proteins co-localized in the nuclear and cytoplasmic compartments. Mechanistically, IER5L suppressed phosphorylation of HSF1 at serine 307, and a phospho‑defective mutant (S307A) significantly enhanced the migratory and invasive phenotypes of BC cells. Collectively, these findings suggest that IER5L contributes to the malignant progression of HR + BC through modulation of HSF1 phosphorylation, thereby providing a promising therapeutic strategy for HR + BC.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic and Apoptotic Effects of Sultamicillin and Cefuroxime Axetil and Their Potential Transformation Products in RTG-2 Fish Gonad Cells.","authors":"Enes Tuzcuoglu, Muammer Kirici","doi":"10.1007/s12013-026-02163-4","DOIUrl":"https://doi.org/10.1007/s12013-026-02163-4","url":null,"abstract":"<p><p>Sultamicillin and cefuroxime axetil are orally administered prodrugs that have been detected in aquatic environments, yet limited information is available regarding the cellular responses associated with their exposure in fish models. This study evaluated cytotoxic and apoptosis-related cellular responses following in vitro exposure to sultamicillin and cefuroxime axetil in the rainbow trout gonad cell line (RTG-2). Cell viability was assessed after 48 h exposure to concentrations ranging from 3.125 to 100 µM using the WST-1 assay, and IC₅₀ values were determined. The calculated IC₅₀ values were 22.80 ± 1.72 µM for sultamicillin and 31.33 ± 0.95 µM for cefuroxime axetil. Apoptosis-related responses were evaluated by Western blot analysis of p53 and BCL2 proteins. Exposure under the present experimental conditions was associated with increased p53 expression and decreased BCL2 expression, indicating activation of apoptosis-related pathways. Molecular docking analysis predicted stable interactions of both compounds with p53 and BCL2, with sultamicillin exhibiting stronger predicted binding affinities than cefuroxime axetil. Overall, the findings demonstrate that exposure to sultamicillin and cefuroxime axetil under the present in vitro conditions is associated with reduced cell viability and apoptosis-related protein alterations in RTG-2 cells. Because both compounds are prodrugs that may undergo hydrolysis or transformation during incubation, the observed biological responses should be interpreted as effects associated with the exposure conditions rather than as evidence of the intrinsic toxicity of the intact parent compounds. These findings provide baseline information for future mechanistic studies and environmental risk assessment of antibiotic-related contaminants in aquatic ecosystems.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Nrf2/TNF-α and TLR4/TGF-β1 Signaling Pathways by Nigella Sativa Oil and Echinacea Purpurea Extract Attenuates Cyclosporine A-Induced Nephrotoxicity and Immunotoxicity.","authors":"Eman M Abdel-Maksoud, Mohamed A Lebda, Hanaa Tharwat, Yasser El-Sayed, Aml E Hashem","doi":"10.1007/s12013-026-02167-0","DOIUrl":"https://doi.org/10.1007/s12013-026-02167-0","url":null,"abstract":"<p><p>Cyclosporine A (CSA), a critical immunosuppressant, induces nephrotoxicity through oxidative stress and inflammatory pathways, limiting its clinical utility. Natural compounds like Nigella sativa oil (NSO) and Echinacea purpurea extract (EPE) possess antioxidant and immunomodulatory properties, but their combined mechanistic action against CSA toxicity is unexplored. This study investigated the protective mechanisms of NSO and EPE, individually and in combination, against CSA-induced renal and immunological toxicity in rats. Fifty male Wistar rats were divided into five groups (n = 10/group): Control, CSA (cyclosporine A, 15 mg/kg/day, i.p.), CSA + NSO (Nigella sativa oil, 200 mg/kg/day, p.o.), CSA + EPE (Echinacea purpurea extract, 200 mg/kg/day, p.o.), and CSA + NSO+EPE (100 mg/kg/day each, p.o.). After 30 days, renal and bone marrow tissues were analyzed for oxidative stress and redox status markers (malondialdehyde, MDA; reduced glutathione, GSH; oxidized glutathione, GSSG) and the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), alongside the pro-inflammatory mediator TNF-α (tumor necrosis factor-alpha). Gene expression of renal injury biomarkers (Tlr4, toll-like receptor 4; Tgfb1, transforming growth factor-β1; Lcn2, lipocalin-2; Kim1, kidney injury molecule-1) and bone marrow immunomodulatory cytokines (Il2, interleukin-2; Il6, interleukin-6; Il17a, interleukin-17 A; Ifng, interferon-γ) was also assessed. Serum hepatic (AST, aspartate aminotransferase; ALT, alanine aminotransferase) and renal (creatinine, urea) function parameters, along with hematological parameters, were also evaluated. CSA significantly (p < 0.05) induced oxidative stress (↑MDA, ↑GSSG; ↓GSH, ↓Nrf2) and inflammation (↑TNF-α) in kidney and bone marrow. It upregulated renal pro-fibrotic and injury genes (Tlr4, ~ 2.9-fold; Tgfb1, ~ 4.9-fold; Lipocalin-2, ~ 3.9-fold; Kim1, ~ 4.3-fold) and severely downregulated bone marrow cytokines (Il2, Il6, Il17a, Ifng; up to ~ 80%). Co-treatment with NSO and EPE, particularly in combination, potently reversed these effects. The combination therapy most effectively normalized oxidative balance, suppressed TNF-α, enhanced Nrf2, mitigated the expression of renal injury genes, and significantly restored the expression of key bone marrow cytokines towards control levels, concurrently improving serum creatinine, urea, and hematological profiles. NSO and EPE confer protection against CSA toxicity through a multi-mechanistic approach: potentiation of the Nrf2 antioxidant pathway and concomitant suppression of TLR4-mediated inflammatory and TGF-β1-driven fibrotic signaling. Their combination offers a superior therapeutic strategy to harness CSA's immunosuppressive benefits while alleviating its detrimental renal and immunological side effects.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence as a Discovery Engine for Routine Molecular Techniques: Extracting Biological Insight from Western Blotting, ELISA, Immunostaining, and Immunoprecipitation.","authors":"Rawan Almazari, Ejlal Abu-El-Rub, Ayman Alzu'bi","doi":"10.1007/s12013-026-02171-4","DOIUrl":"https://doi.org/10.1007/s12013-026-02171-4","url":null,"abstract":"<p><p>Artificial intelligence (AI) is transforming how routine molecular techniques are interpreted, moving beyond traditional statistics such as band intensity, protein concentration, and visual scoring. This review examines how AI enhances the analytical capacity of four widely used methods: Western blotting, ELISA, Immunostaining, and Immunoprecipitation-Mass Spectrometry (IP-MS). Unlike conventional approaches that analyze each measurement in isolation, AI detects hidden relationships across multiple signals, integrates temporal and spatial information, and reconstructs coherent biological pathways from fragmented experimental data. It extracts detailed features from Western blot images, identifies interaction patterns in ELISA datasets, quantifies protein localization in stained tissues, and builds reliable protein-protein interaction networks from IP-MS experiments. Beyond data analysis, AI guides experimental design, generates testable novel hypotheses, and facilitates translation of molecular findings into clinical applications. Despite challenges related to data quality, model interpretability, and validation, AI is increasingly positioned as a complementary tool that works alongside human expertise. By converting routine laboratory assays into innovative, comprehensive discoveries, AI accelerates mechanistic understanding and bridges the gap between basic molecular biology and precision medicine. This review provides an informative overview of these applications and discusses future directions and limitations for AI-driven molecular research.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-Dependent Hepatic Alterations Following Glyphosate Exposure in Female Wistar Rats: Oxidative Stress, Intracellular Cyclic Nucleotide Alterations, Apoptosis, and VEGF.","authors":"Gul Sahika Gokdemir, Sevda Canbay Durmaz, Selim Demirtaş, Nazan Baksi, Mehmet Tahir Gokdemir","doi":"10.1007/s12013-026-02159-0","DOIUrl":"https://doi.org/10.1007/s12013-026-02159-0","url":null,"abstract":"<p><p>Glyphosate-based herbicides (GBHs) are widely used worldwide. Increasing evidence has raised concerns about their hepatotoxic effects. While oxidative stress, inflammation, and apoptosis contribute to glyphosate-induced liver damage, the roles of intracellular cyclic nucleotides and vascular endothelial growth factor (VEGF) are not fully understood. This study investigated the dose-dependent effects of glyphosate on liver function, oxidative status, intracellular cyclic nucleotides, inflammatory mediators, apoptotic markers, and VEGF in adult female Wistar rats. Twenty-eight female Wistar rats were randomly assigned to four groups (n = 7/group) and administered orally either distilled water (control) or glyphosate at doses of 250, 500, or 1000 mg/kg/day for 30 days. Serum aminotransferase activities and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), caspase-3, VEGF, Bax/Bcl-2 immunoreactivity, and histopathological changes were evaluated. Dose-response relationships were assessed using polynomial trend analysis. Glyphosate exposure caused dose-dependent increases in AST, TOS, OSI, TNF-α, IL-1β, caspase-3, VEGF, and the Bax/Bcl-2 ratio, accompanied by decreases in TAS, cAMP, and cGMP, as well as progressive histopathological changes. Polynomial trend analysis showed significant linear dose-response relationships for all biomarkers, while OSI, caspase-3, VEGF, and the Bax/Bcl-2 ratio showed significant deviations from linearity at higher glyphosate doses. These findings suggest that glyphosate-induced hepatotoxicity is associated with coordinated alterations in oxidative status, intracellular cyclic nucleotide homeostasis, inflammatory responses, apoptosis, and hepatic VEGF levels.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond a Surface Marker: The Multifaceted Role of CD38 in Metabolic Disruption and Tumor Progression.","authors":"Özlem Coşkun","doi":"10.1007/s12013-026-02133-w","DOIUrl":"https://doi.org/10.1007/s12013-026-02133-w","url":null,"abstract":"<p><p>CD38 is a type II transmembrane glycoprotein and serves as the primary ectoenzyme responsible for regulating cellular nicotinamide adenine dinucleotide (NAD⁺⁾ levels in mammalian tissues. Initially identified as a lymphocyte activation marker, recent research has revealed its significant role in immunosuppression within oncological processes, NAD⁺ depletion associated with aging, and exosomal signaling. This review provides a comprehensive analysis of the enzymatic functions of CD38, its pathophysiological impacts on both hematological and solid tumors, and the mechanisms of resistance that emerge against anti-CD38 therapies. Furthermore, the potential of CD38 as an exosomal biomarker in liquid biopsy procedures and its function as a \"metabolic resetter\" for promoting healthy aging are explored.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-Lipoic Acid Attenuates Fibrotic and Inflammatory Dermal Remodelling in a Bleomycin-Induced Skin Model.","authors":"Nese Colcimen, Seda Keskin, Mehmet Hafit Bayir","doi":"10.1007/s12013-026-02151-8","DOIUrl":"https://doi.org/10.1007/s12013-026-02151-8","url":null,"abstract":"<p><p>Bleomycin (BLM) is a widely used chemotherapeutic agent associated with cutaneous toxicity characterised by inflammation, oxidative stress, and progressive fibrosis. However, effective strategies to mitigate these adverse tissue responses remain limited. This study aimed to evaluate potential protective effects of alpha-lipoic acid (ALA) against the BLM-induced skin model, focusing on fibrotic, inflammatory, and proliferative alterations. Thirty adult Wistar albino rats were randomly assigned to four groups: Control, ALA, BLM, and BLM + ALA. BLM (30 mg/m²) was administered intramuscularly on Days 1, 8, and 15, whereas ALA (50 mg/kg/day, subcutaneously) was administered once daily from Days 1-14. Skin tissues were collected immediately after the final scheduled treatment on Day 15 for histopathological and immunohistochemical analyses. Histopathological evaluation was performed using H&E, Masson's trichrome, and Toluidine blue staining. Immunohistochemical staining was conducted to evaluate the expression levels of collagen types I and III, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), caspase-1, and the proliferation marker Ki-67, followed by quantitative image analysis. BLM exposure resulted in marked epidermal thickening, inflammatory cell infiltration, increased collagen deposition, and elevated mast cell density compared with controls. These histopathological alterations were significantly attenuated in the BLM + ALA group. Consistently, BLM significantly increased the expression of collagen I/III, IL-6, iNOS, caspase-1, and Ki-67, whereas ALA treatment significantly reduced these elevations. Overall, ALA attenuated BLM-induced dermal alterations. ALA treatment was associated with reduced collagen deposition and decreased IL-6, iNOS, caspase-1, and Ki-67 immunoreactivity in the experimental skin model. Further mechanistic studies are required to establish the causal relationships underlying these observations.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necrosis by Sodium Overload: Mechanisms, Pathophysiological Roles, and Therapeutic Prospects of a Novel Form of Regulated Cell Death.","authors":"Teng Qi, Pei-Lin Xie, Ting-Xuan Huang, Jin-Suo Xiao, Ling-Jun Yao","doi":"10.1007/s12013-026-02157-2","DOIUrl":"https://doi.org/10.1007/s12013-026-02157-2","url":null,"abstract":"<p><p>Sodium ion (Na⁺), the predominant cation in the extracellular space, is essential for maintaining fundamental cellular activities via preservation of the transmembrane Na⁺ gradient. While intracellular Ca²⁺ overload has long been recognized as the core driver of cell injury and death, accumulating evidence indicates that Na⁺ overload, defined as abnormal intracellular Na⁺ accumulation, may act as an independent trigger of irreversible cellular damage, rather than merely a preceding event or concomitant phenomenon of Ca²⁺ overload. In 2025, the term Necrosis by Na⁺ Overload (NECSO) was first coined to describe a novel form of regulated necrosis directly triggered by sustained and excessive Na⁺ influx, which is primarily mediated by the transient receptor potential melastatin 4 (TRPM4) channel. Distinct from apoptosis and other established forms of regulated cell death, NECSO is characterized by early cellular and organellar swelling, mitochondrial energy metabolism collapse, ionic homeostasis disruption, and eventual loss of plasma membrane integrity, without the hallmark features of caspase activation and chromatin condensation. The core execution pathway of NECSO involves TRPM4-mediated Na⁺ influx, subsequent mitochondrial Na⁺ accumulation, impaired tricarboxylic acid cycle and oxidative phosphorylation, and catastrophic cellular energy depletion, which further aggravates Na⁺ overload via inhibition of Na⁺/K⁺-ATPase and forms a fatal vicious cycle. In pathophysiological contexts, NECSO serves as a central mediator of myocardial injury in ischemia-reperfusion, and is also implicated in the progression of heart failure and neuronal death in stroke. In cancer biology, NECSO and its core mediator TRPM4 exhibit highly tissue-specific dual roles, acting as either oncogenic drivers or tumor suppressors in different cancer types. Meanwhile, NECSO-related genes have shown promising potential as diagnostic and prognostic biomarkers, as well as predictors of therapeutic response to chemotherapy and immunotherapy across multiple malignancies. Targeted strategies against NECSO, including direct modulation of TRPM4 activity, intervention of Na⁺ homeostasis, and combination therapeutic regimens, have exhibited favorable efficacy in preclinical models of cardiovascular diseases and cancer. This review systematically summarizes the definition, core molecular mechanisms, and pathophysiological functions of NECSO, discusses the application value of NECSO-related biomarkers, and outlines current challenges and future directions in this emerging field, to provide a novel perspective for the development of therapeutic strategies against major human diseases.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vestitol Ameliorates Ferroptosis-Associated Features and Osteoarthritis Progression Through Modulation of the GSK3B/Nrf2/GPX4 Pathway.","authors":"Tingting Wang, Yongxiang Liu","doi":"10.1007/s12013-026-02166-1","DOIUrl":"https://doi.org/10.1007/s12013-026-02166-1","url":null,"abstract":"<p><p>This study aimed to investigate whether vestitol ameliorates osteoarthritis (OA) and the mechanisms involved. We employed destabilization of the medial meniscus (DMM)-constructed OA mouse model and IL-1β-induced chondrocyte model to evaluate vestitol's effects on OA. In vivo, pathological alterations in cartilage tissues were assessed via safranin O and H&E staining. In vitro, chondrocyte viability and apoptosis were detected utilizing CCK-8 and flow cytometry. Vestitol's mechanisms in OA were explored using network pharmacology analysis. Factors related to extracellular matrix (ECM) degeneration, inflammation, oxidative stress, ferroptosis, and pathway were checked using western blot, RT-qPCR, immunohistochemistry, and corresponding commercial reagent kits. In OA mice model, vestitol decreased cartilage destruction and OARSI score. Vestitol enhanced the levels of COL2A1, Aggrecan, SOD, FTH1, but reduced the levels of MMP-13, ADAMTS5, IL-6, IL-1β, COX-2, TNF-α, MDA, Fe²⁺, ROS, ACSL4 and 4-HNE. In IL-1β-induced chondrocyte model, vestitol enhanced cell viability and inhibited cell apoptosis. The changes in indicators related to ECM degradation, inflammation, oxidative stress, and ferroptosis were consistent with in vivo experiments. Moreover, vestitol increased p-GSK3B (Ser9), Nrf2, and GPX4 levels both in vivo and in vitro. The inhibition of vestitol on chondrocyte apoptosis, ECM degradation, inflammation, and ferroptosis-associated features was reversed by GSK3B activation. Vestitol mitigates OA by suppressing chondrocyte apoptosis, ECM degradation, inflammation, and ferroptosis-associated features, with pharmacological evidence implicating the PI3K/AKT/GSK3B axis and downstream modulation of the Nrf2/GPX4 pathway.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}