Experimental cell research最新文献

{"title":"Activation of STING sensitizes melanoma cells to radiation through ROS-induced NLRP3","authors":"Jiajia Wang ,&nbsp;Shaokai Tang ,&nbsp;Tingyi Yang ,&nbsp;Fenghao Geng ,&nbsp;Xiaoyou Tang ,&nbsp;Rui Xia ,&nbsp;Xin Zhang ,&nbsp;Hao Bai ,&nbsp;Hai Xiong ,&nbsp;Daojiang Yu ,&nbsp;Shuyu Zhang","doi":"10.1016/j.yexcr.2025.114811","DOIUrl":"10.1016/j.yexcr.2025.114811","url":null,"abstract":"<div><h3>Background</h3><div>Melanoma is an aggressive malignancy with one of the highest mortality rates among skin cancers. Radiotherapy is a common treatment modality, but radioresistance remains a significant challenge. The stimulator of interferon genes (STING) pathway has been implicated in antitumor immunity and cancer treatment, yet its role in melanoma radiosensitivity is poorly understood.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the role of STING in enhancing the radiosensitivity of cutaneous melanoma cells and to explore the underlying mechanisms involving reactive oxygen species (ROS) and the NLRP3 inflammasome.</div></div><div><h3>Methods</h3><div>Using TCGA database analysis, we examined the correlation between cGAS-STING pathway expression and melanoma patient survival. In vitro experiments were conducted on A375 and B16F10 melanoma cell lines, where STING was overexpressed or activated using the STING agonist cGAMP. Cell viability, apoptosis, ROS levels, and NLRP3/ASC complex activity were assessed following radiation treatment. In vivo studies involved tumor-bearing mice treated with cGAMP and radiation to evaluate tumor growth and survival.</div></div><div><h3>Results</h3><div>High expression of cGAS and STING was associated with improved survival in melanoma patients. STING overexpression or cGAMP treatment significantly reduced cell viability, increased ROS levels, and enhanced apoptosis in irradiated melanoma cells. Mechanistically, the activation of STING elevated NLRP3/ASC complex activity, and the NLRP3 inhibitor CY-09 reversed the radiosensitization effects. In vivo, cGAMP combined with radiation suppressed tumor growth and improved survival in melanoma-bearing mice.</div></div><div><h3>Conclusion</h3><div>STING enhances radiosensitivity of melanoma through ROS-NLRP3 axis, and combining STING agonists with radiotherapy may be a new strategy to overcome radioresistance.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114811"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414065","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":"Bone marrow mesenchymal stem cell-derived exosomes HADH alleviate vitiligo by activating the Nrf2/HO-1 pathway","authors":"Shiyang Tang ,&nbsp;Xin Li ,&nbsp;Jianyuan Xi","doi":"10.1016/j.yexcr.2025.114798","DOIUrl":"10.1016/j.yexcr.2025.114798","url":null,"abstract":"<div><h3>Background</h3><div>Vitiligo is a chronic skin disorder that significantly impairs patients' quality of life. Exosomes (Exos) have been reported to hold therapeutic promise for vitiligo. This study aimed to investigate the molecular mechanism by which bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) ameliorate vitiligo.</div></div><div><h3>Methods</h3><div><em>In vitro</em> vitiligo cell model was established by hydrogen peroxide (H₂O₂)-induced melanocytes. A mouse model of vitiligo was also established. Immunofluorescence, cell counting kit-8, 2′,7′-dichlorofluorescein diacetate, enzyme linked immunosorbent assay, flow cytometry, real-time quantitative PCR, western blotting, hematoxylin-eosin, Masson-Fontana, and immunohistochemistry staining experiments were elucidated to explore the molecular mechanism of BMSC-Exos in relieving vitiligo.</div></div><div><h3>Results</h3><div>H₂O₂ treatment reduce the cell viability, superoxide dismutase and catalase activities, and promote reactive oxygen species production, pyroptosis, the expression of NLRP3, ASC, IL-1β and IL-18 proteins in melanocytes. BMSC-Exos treatment effectively counteracted these detrimental effects. Knockdown of exosomal HADH derived from BMSC enhanced H₂O₂-induced oxidative stress and pyroptosis in melanocytes. Mechanistically, BMSC-Exos attenuated H₂O₂-induced oxidative stress and pyroptosis by mediating HADH delivery to activate the Nrf2/HO-1 pathway. Moreover, these results were further confirmed by experiments in a mouse model of vitiligo.</div></div><div><h3>Conclusion</h3><div>BMSC-Exos can alleviate vitiligo by delivering HADH to activate the Nrf2/HO-1 pathway. This study provides insights for exploring new treatments for vitiligo.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114798"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312758","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":"A tRNA-derived fragment tiRNA-Met-CAT-002 induced by myocardial ischemia/reperfusion injury inhibits cardiomyocyte autophagy by regulating Bnip3","authors":"Lang Deng ,&nbsp;Yawen Weng ,&nbsp;Jiahui Lin ,&nbsp;Lingfeng Zhong ,&nbsp;Zhixuan Tang ,&nbsp;Shuang Lin ,&nbsp;Weijian Huang ,&nbsp;Zhenfeng Cheng ,&nbsp;Kongjie Lu ,&nbsp;Bozhi Ye","doi":"10.1016/j.yexcr.2025.114809","DOIUrl":"10.1016/j.yexcr.2025.114809","url":null,"abstract":"<div><div>Myocardial ischemia/reperfusion (I/R) injury is a significant contributor to the development of heart failure. This study investigates the differential expression of tRNA-derived small RNAs (tsRNAs) during I/R and explores their potential functional implications. Through tRF &amp; tiRNA sequencing, we identified 115 tsRNAs exhibiting significant changes in expression following I/R. Notably, tiRNA-Met-CAT-002 was found to be upregulated via the hypoxia/hypoxia-inducible factor 1 subunit α (HIF1α)/angiogenin (ANG) signaling axis. Our findings suggest that Bnip3 represents a crucial target for tiRNA-Met-CAT-002. Mechanistically, mimics of tiRNA-Met-CAT-002 reduced Bnip3 protein expression by directly targeting the 3′ untranslated region (UTR) of its mRNA in a manner resembling microRNA activity. Furthermore, tiRNA-Met-CAT-002 was observed to decrease autophagy levels while enhancing cell viability under hypoxia/reoxygenation (H/R) conditions. In conclusion, this study underscores the substantial role of tsRNAs in the pathophysiology of I/R injury, with tiRNA-Met-CAT-002 potentially serving as a protective factor by attenuating autophagy levels.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114809"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360731","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":"KHSRP protects colorectal cancer cells against ferroptosis by regulating GPX4 expression through interaction with hnRNPM","authors":"Xia Ding ,&nbsp;Ningjing Zhang ,&nbsp;Shuai Zhan ,&nbsp;Wanjing Ding","doi":"10.1016/j.yexcr.2025.114812","DOIUrl":"10.1016/j.yexcr.2025.114812","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent form of programmed cell death driven by the accumulation of lipid peroxides. KHSRP, an RNA-binding protein, is known to orchestrate diverse cellular processes, including cell differentiation, proliferation, and lipid metabolism. However, its potential role in modulating ferroptosis in cancer remains unclear. In this study, we found that elevated KHSRP expression was associated with poor prognosis in colorectal cancer (CRC) patients. Knockdown of KHSRP significantly elevated lipid peroxidation, increased malondialdehyde (MDA) accumulation, and reduced glutathione (GSH) levels, ultimately triggering ferroptosis in CRC cells. Mechanistically, we discovered that KHSRP interacts with the splicing factor hnRNPM, which directly binds to GPX4 mRNA. Critically, hnRNPM overexpression effectively rescued the decrease in GPX4 expression and the ferroptotic phenotype induced by KHSRP knockdown. These results suggest that the KHSRP-hnRNPM complex binds to GPX4 mRNA and acts as a key regulator of its post-transcriptional fate to sustain GPX4 expression. Overall, our results uncover a novel regulatory mechanism whereby high KHSRP expression protects CRC cells from ferroptosis. Targeting the KHSRP–hnRNPM-GPX4 axis to overcome ferroptosis resistance represents a promising therapeutic strategy for CRC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114812"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426534","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":"tsRNA-10105-enriched migrasomes mediate hepatocellular carcinoma immunosuppressive microenvironment by inducing M2 Macrophage polarization","authors":"Limin Pan ,&nbsp;Ruiyao Zhou ,&nbsp;Zhikai Wen ,&nbsp;Yue Lin ,&nbsp;Huixin Cai ,&nbsp;Chengyi Lin ,&nbsp;Xuelong Xu ,&nbsp;Limin Ruan ,&nbsp;Yu Zeng ,&nbsp;Haifeng Zhang ,&nbsp;Yu Zhou ,&nbsp;Xiao Hu","doi":"10.1016/j.yexcr.2025.114729","DOIUrl":"10.1016/j.yexcr.2025.114729","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is characterized by a complex immunosuppressive microenvironment, which significantly influences tumor progression. Migrasomes, newly identified extracellular vesicles, have emerged as a novel mode of intercellular communication. However, their roles in HCC immune microenvironment are rarely studied. Here, we observed migrasome markers and M2 polarization levels in HCC patient tissues using immunofluorescence. Migrasomes were isolated from HCC cells and characterized using electron microscopy, immunofluorescence, and Western blot. The effects of migrasomes on macrophage polarization and HCC progression were investigated <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em>. Small RNA-seq was conducted to screen for key tsRNA. We discovered that the levels of the migrasome marker and M2 macrophage marker were elevated in liver tumor tissues. Migrasomes derived from HepG2 induced macrophage M2 polarization, as indicated by the increased expression of M2 polarization marker, and the suppressed expression of M1 polarization marker. Macrophages treated with these migrasomes further stimulated the proliferation, migration, and invasion of malignant cells <em>in</em> <em>vitro</em> and augmented tumor growth and metastasis <em>in</em> <em>vivo</em>. Compared to the healthy individuals, the sera of HCC patients demonstrated elevated expression of tsRNA-10105 in migrasomes. Inhibition of tsRNA-10105 significantly abolished the inducing effect of cancer cell migrasomes on the M2 macrophages polarization. Our findings indicate that migrasome-derived tsRNA-10105 from HCC cells can induce the M2 macrophages polarization, which in turn augments survival and migration of HCC cells. This work provides insights into the mechanisms of the immunosuppressive microenvironment in HCC and offers novel perspectives for the immunotherapy of HCC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114729"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000057","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":"Integrative multi-omics analysis identifies mitochondria- and ferroptosis-related prognostic genes in cervical cancer","authors":"Linlin Jia ,&nbsp;Xinyu Cui ,&nbsp;Xiaoting Li ,&nbsp;Rui Li","doi":"10.1016/j.yexcr.2025.114796","DOIUrl":"10.1016/j.yexcr.2025.114796","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondria and ferroptosis are crucial in tumorigenesis. However, their specific role in cervical cancer (CC) remains unclear. This study aimed to identify and validate prognostic genes linked to mitochondrial function and ferroptosis in CC.</div></div><div><h3>Methods</h3><div>Publicly available datasets were analyzed, including 306 CC tumor samples from The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC), with survival data for 293 samples, a training set of 24 normal and 33 tumor tissues (GSE9750), and a validation set of 300 tumor tissues (GSE44001). Prognostic genes associated with mitochondria-related genes (MRGs) and ferroptosis-related genes (FRGs) were identified through machine learning, univariate Cox regression, Weighted Gene Co-expression Network Analysis (WGCNA), Mendelian randomization (MR), differential expression analysis, and multivariate Cox analysis. A risk model was constructed and validated, with the High-Risk Group (HRG) and Low-Risk Group (LRG) defined by optimal risk score thresholds. Independent prognostic analysis, functional enrichment, immune infiltration profiling, and single-cell resolution studies were conducted to explore the underlying molecular mechanisms. Additionally, gene expression was validated in five paired clinical samples (5 tumor/5 normal tissues) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).</div></div><div><h3>Results</h3><div>HSDL2, AMACR, and CBR3 were identified as prognostic genes. The risk model indicated significantly poorer survival rates in HRG patients (P &lt; 0.05). It demonstrated strong predictive performance, with area under the curve (AUC) values exceeding 0.7 in both the training and validation sets. The risk score, tumor (T) stage, and lymph node (N) stage were identified as independent prognostic factors for a nomogram model (hazard ratio (HR ≠ 1, P &lt; 0.5). Pathways co-enriched by these markers, such as allograft rejection, were investigated. Immune infiltration analysis revealed significant differences between HRG and LRG in M0 macrophages and resting myeloid dendritic cells (mDCs) (P &lt; 0.5). Macrophages and epithelial/cancer cells were identified as key contributors to CC progression, exhibiting 13 and 7 distinct differentiation states, respectively, in pseudo-time analysis. Notably, HSDL2 and CBR3 expression levels were significantly different between normal and CC samples (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>HSDL2, AMACR, and CBR3 were established as prognostic biomarkers for CC. The risk model demonstrated robust predictive accuracy, offering a scientific foundation for clinical prognosis prediction in CC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114796"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312756","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":"Modelling CubAm function and regulation in proximal tubular cells using iPSC-derived kidney organoids","authors":"Carmen Llorens-Cebrià ,&nbsp;Daphne Bouwens ,&nbsp;Max Van Der Velde ,&nbsp;Mónica Duran ,&nbsp;Mireia Salvadó-Pau ,&nbsp;Irene Martínez-Díaz ,&nbsp;Jordi Vilardell-Vilà ,&nbsp;Anna Meseguer ,&nbsp;Rafael Kramann ,&nbsp;Roser Ferrer-Costa ,&nbsp;Maria José Soler ,&nbsp;Joan López-Hellín ,&nbsp;Gerard Cantero-Recasens ,&nbsp;Jitske Jansen ,&nbsp;Conxita Jacobs-Cachá","doi":"10.1016/j.yexcr.2025.114814","DOIUrl":"10.1016/j.yexcr.2025.114814","url":null,"abstract":"<div><div>Idiopathic nephrotic syndrome (INS) associated to focal segmental glomeruloesclerosis or minimal change disease is characterized by the presence of heavy levels of proteinuria. Filtrated proteins are normally actively reabsorbed in the proximal tubule by the megalin-cubilin-amnionless complex, located at the apical membrane of the proximal tubule epithelial cells. Megalin has a transmembrane domain but cubilin needs to interact with amnionless to reach the cell membrane in a complex known as CubAm. While megalin has a wide variety of ligands only a few proteins are exclusively transported by binding CubAm; one of those is Apolipoprotein A-I (ApoA-I). The reabsorption of Apolipoprotein A-I (ApoA-I) seems to be impaired in INS but this aspect of INS is difficult to study due to the low expression of CubAm in cultured proximal tubular cells as well as in other <em>in vitro</em> tubular modelling approaches. Here we show that RPTEC/TERT-1 cells cultured in monolayer barely express cubilin and amnionless proteins. In contrast, proximal tubular cells of induced Pluripotent Stem Cells (iPSCs)-derived kidney organoids showed robust expression of CubAm. In addition, protein overload induced an increase of the number of proximal tubular cells expressing cubilin that is reversed when the stimuli is removed. Finally, exogenously added ApoA-I targets cubilin suggesting that the CubAm complex is functional in our iPSCs-derived kidney organoids. Thus, kidney organoids provide a valuable system for modelling specific aspects of INS, including the impact of protein overload on tubular cells and the CubAm-mediated endocytosis of ApoA-I, which is thought to be impaired in these conditions.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114814"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450909","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":"Developmental delay in DCP2l(3)tb of Drosophila melanogaster is due to disruption in the regulation of ecdysone signaling","authors":"Govind R. Chaudhary,&nbsp;Vaishali Yadav,&nbsp;Jagat Kumar Roy","doi":"10.1016/j.yexcr.2025.114808","DOIUrl":"10.1016/j.yexcr.2025.114808","url":null,"abstract":"<div><div>The balance between mRNA synthesis and degradation plays an important role in gene regulation, their perturbation can lead to deleterious consequences to the cell. In eukaryotes, mRNA is degraded by a decapping protein-2 (DCP2). A hypomorph mutant allele of DCP2, <em>DCP2</em>^{<em>l(3)tb</em>}, identified in our lab, shows delayed moulting, pupariation and absolute lethality in pupal stages. In <em>Drosophila</em>, moulting and pupariation are primarily regulated by ecdysone which is modulated by a few regulators synthesized by the larval brain, some are stimulatory such as Prothoracicotropic hormone (PTTH) and <em>Drosophila</em> insulin-like peptides (Dilps); whereas some are inhibitory, such as Lgr3-expressing neurons. We aimed to investigate the cause of the delay in moulting and pupariation in <em>DCP2</em>^{<em>l(3)tb</em>} homozygous mutants. Through our RNA Seq data, we found downregulated expression of brain-derived neuropeptides such as <em>PTTH</em> and <em>Dilps</em> which were further confirmed and validated through qRT-PCR and semiquantitative PCR. Furthermore, we assessed the mRNA level of <em>Lgr3</em> which was found to be upregulated in the larval CNS of <em>DCP2</em>^{<em>l(3)tb</em>} homozygotes suggesting insufficient production of stimulatory modulators. Further, providing 20H-ecdysone exogenously through diet, curtailed the extended larval life. We propose that the larval CNS of <em>DCP2</em>^{<em>l(3)tb</em>} homozygotes produces insufficient brain-derived neuropeptides to stimulate the prothoracic gland to synthesize the ecdysone required for moulting and metamorphosis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114808"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367741","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 role and mechanism of fatty acid-binding protein 7 in spinal reactive astrocytes in prolonged postoperative pain induced by high-fat diet","authors":"Han Zheng ,&nbsp;Xiao Zhang ,&nbsp;Mei Li ,&nbsp;Yu Wang ,&nbsp;Shufen Guo ,&nbsp;Ming Jiang ,&nbsp;Rui Xu ,&nbsp;Yulin Huang ,&nbsp;Zhengliang Ma","doi":"10.1016/j.yexcr.2025.114801","DOIUrl":"10.1016/j.yexcr.2025.114801","url":null,"abstract":"<div><div>Obesity markedly exacerbates nociceptive sensitivity and substantially compromises the quality of life of affected people. Astrocytes orchestrate metabolic regulation and homeostatic maintenance in the central nervous system. Notably, fatty acid binding protein 7 (FABP7) is highly expressed in astrocytes that governs intracellular fatty acid uptake and transport. While systemic hyperlipidemia is pathognomonic of obesity, the mechanistic contribution of FABP7 in astrocytes to obesity-associated pain pathophysiology remains poorly characterized. The present study established a model of high-fat diet (HFD)-induced obesity combined with a standardized hind paw surgical incision paradigm, aiming to unveil the role of astrocytic FABP7 in HFD-induced chronic pain. Furthermore, an <em>in vitro</em> high-fat environment was induced by palmitic acid (PA),aiming to investigate the molecular mechanisms by which primary astrocytes were activated into the A1 phenotype to mediate neuroinflammation. FABP7 was overexpressed in the spinal dorsal of HFD mice. The activation of A1-type astrocytes and neuroinflammation cascades involving elevated iNOS eventually resulted in mechanical allodynia in HFD mice. Pharmacological inhibition of FABP7 <em>via</em> an intraperitoneal administration of SBFI-26 (20 mg/kg) significantly attenuated the paw withdrawal mechanical threshold and inhibited the A1-type astrocytes activation. PA-induced high-fat conditions promoted lipid droplet accumulation and upregulated FABP7 in astrocytes. Pharmacological inhibition of FABP7 using SBFI-26 (100 μmol/L) significantly suppressed the neurotoxic C3-positive A1 astrocyte phenotype, reduced intracellular lipid droplet accumulation, thereby inhibiting the activation of A1-type astrocytes and alleviating neuroinflammation. Overall, FABP7-mediated astrocytic reprogramming was a critical nexus bridging obesity with chronic pain. A1-astrocyte polarization initiated neuroinflammatory amplification, forming a feedforward loop perpetuating central sensitization. Our findings are expected to offer a viable target for metabolic pain management.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114801"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388196","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":"Molecular mechanisms of cuproptosis in osteoarthritis: Pathways, crosstalk, and therapeutic opportunities","authors":"Yanyang Shen ,&nbsp;Mingdong Liu ,&nbsp;Benson O.A. Botchway ,&nbsp;Yong Zhang ,&nbsp;Xuehong Liu","doi":"10.1016/j.yexcr.2025.114800","DOIUrl":"10.1016/j.yexcr.2025.114800","url":null,"abstract":"<div><div>Osteoarthritis (OA), the most prevalent degenerative joint disorder worldwide, continues to impose significant personal and societal burdens due to the absence of effective disease-modifying therapies. Recent advances in metallobiology have identified cuproptosis, a copper (Cu)-dependent regulated cell death pathway, as a potential driver of OA pathogenesis. In OA, dysregulated Cu homeostasis has been linked to oxidative stress, inflammatory signalling activation, mitochondrial dysfunction, and direct chondrocyte injury. Mechanistically, Cu²⁺ overload promotes aggregation of lipoylated tricarboxylic acid (TCA) cycle enzymes and destabilisation of iron–sulfur clusters, thereby impairing mitochondrial integrity and cellular metabolism. Emerging evidence also highlights extensive crosstalk between cuproptosis and ferroptosis, mediated largely by glutathione depletion and glutathione peroxidase 4 (GPX4) dysfunction, which amplifies oxidative damage in joint tissues. This review synthesises current evidence on Cu metabolism, the regulation and function of cuproptosis-related genes (CRGs), and their roles in immune infiltration, inflammatory signalling, and cartilage degeneration in OA. We further examine the interplay between cuproptosis and ferroptosis, and critically evaluate therapeutic strategies, including Cu chelation, antioxidant reinforcement, and pathway modulation, that may offer disease-modifying potential. By integrating these mechanistic insights, we aim to define new translational opportunities for OA management and outline priority areas for future research.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114800"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344447","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}