Experimental cell research最新文献

{"title":"SOCS1 orchestrates ferroptotic renal injury via GPX4 ubiquitination in hyperuricemia","authors":"Renzhong Zhang,&nbsp;Xu Fu,&nbsp;Xiaoli Zhao,&nbsp;Ke Wang","doi":"10.1016/j.yexcr.2025.114774","DOIUrl":"10.1016/j.yexcr.2025.114774","url":null,"abstract":"<div><div>Hyperuricemia (HUA)-induced renal injury involves elusive molecular mechanisms. This study uncovers suppressor of cytokine signaling 1 (SOCS1) as a pivotal mediator of hyperuricemic nephropathy through ferroptosis regulation. In a murine HUA model, we observed significantly elevated serum uric acid, impaired renal function, heightened inflammation, and activated ferroptosis. <em>In vitro</em> studies using uric acid-treated renal tubular cells demonstrated that SOCS1 deficiency alleviated ferroptotic cell death, reduced inflammatory responses, and preserved mitochondrial integrity. Mechanistically, SOCS1 directly interacts with glutathione peroxidase 4 (GPX4) to promote its ubiquitin-dependent proteasomal degradation, as validated by co-immunoprecipitation and protein stability assays. Crucially, pharmacological induction of ferroptosis abolished the protective effects of SOCS1 knockdown, while GPX4 inhibition counteracted its anti-ferroptotic function. <em>In vivo</em> delivery of renal-targeted SOCS1 shRNA <em>via</em> AAV9 vectors attenuated hyperuricemic nephropathy, ameliorating histological damage and suppressing both ferroptosis and inflammation. Our findings establish a pathogenic axis wherein SOCS1 drives hyperuricemic renal injury by facilitating GPX4 ubiquitination and subsequent ferroptosis activation, highlighting this pathway as a promising therapeutic target.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114774"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174398","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":"Human trophoblast stem cell-differentiated syncytiotrophoblasts as a model for hypoxia-enhanced secretion of the anti-angiogenic factor sFLT1","authors":"Tadashi Sasagawa,&nbsp;Masabumi Shibuya","doi":"10.1016/j.yexcr.2025.114773","DOIUrl":"10.1016/j.yexcr.2025.114773","url":null,"abstract":"<div><div>Preeclampsia (PE) is a major disease in the field of obstetrics. Onset and progression of PE are associated with abnormally high serum levels of soluble fms-like tyrosine kinase-1 (sFLT1), an anti-angiogenic factor primarily secreted by syncytiotrophoblasts (STBs) present in the placenta. Although a cell-based assay using primary human trophoblasts has been developed to identify compounds that inhibit sFLT1 secretion, routine application of this assay is limited owing to the complexity of isolating these cells from the placenta and their inability to be passaged. Recently, human trophoblast stem cell (hTSC) lines that can differentiate into STBs and extravillous trophoblasts have been established. Their high proliferative ability allows for obtaining sufficient STBs for drug screening. In the present study, we investigated whether hTSC-differentiated STBs (dSTBs) exhibit enhanced secretion of sFLT1 under hypoxic conditions, similar to primary trophoblasts. Hypoxic stimulation significantly increased sFLT1 secretion by the dSTBs. This response was markedly inhibited by small interfering RNAs targeting the hypoxia-inducible factor (HIF)-2α and HIF-1β, as well as by the HIF-2α inhibitor, belzutifan. These findings suggest that the dSTBs described above are a practical and scalable alternative to primary trophoblasts for drug screening in PE treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114773"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174428","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 time course analysis of the electrophysiological and gene expression properties during differentiation of hair cell-like cells in culture","authors":"Ali Asghar Peyvandi ,&nbsp;Shima Davoudi ,&nbsp;Narges Bazgir ,&nbsp;Mahyar Janahmadi ,&nbsp;Hamid Norioun ,&nbsp;Shahrokh Khoshsirat ,&nbsp;Somayeh Niknazar","doi":"10.1016/j.yexcr.2025.114775","DOIUrl":"10.1016/j.yexcr.2025.114775","url":null,"abstract":"<div><div>Bone marrow-derived mesenchymal stromal cells (BMSCs) are multipotent cells that have attracted considerable attention in regenerative medicine. Current in vitro test focus on biochemical assays of hair cell-like cells (HCLCs) derived from BMSCs associated with changes in electrophysiological properties. HCLCs were produced from BMSCs by culturing BMSCs with B27, EGF, FGF, and IGF-1. RNA Sequencing studies, immunocytochemistry (ICC) and double immunofluorescence staining were used to test hair cell-associated markers on day 17 and 21–26. Next, we performed whole-cell patch-clamp recording by utilizing current- and voltage-clamp techniques to assess changes in membrane potential and ionic currents during differentiation. Immunostaining assay reveals significant expression of myosin VIIA and SOX2 in cultured hair cells on day 21–26. We have also found 8 enhanced transcripts in differentiated cell genes (Wnt7a, Mgat5b, Myo7a, Pou4f3, SOX2, Atoh1, Map2k3, Actin) using RNA Sequencing. Electrophysiological results indicate that cells undergoing differentiation had an average resting membrane potential (RMP) of −11.93 ± 0.89 mV on day 17 and −58.96 ± 1.10 mV on days 21–26. Differentiated HCLCs displayed a mean resting membrane resistance of 171.66 ± 29.12 MΩ, membrane time constant of 10.73 ± 0.45 ms and membrane capacitance of 0.0625 ± 0.0087 pF, following 21–26 days in culture. Our results also showed cultured HCLCs express transcriptomic profile of this cell type. These findings indicate that alterations in RMP may serve as a valuable indicator for distinguishing HCLCs differentiation potential from BMSCs.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114775"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185141","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":"Extracellular-vesicle-mediated NLRP3 signaling in cancer","authors":"Harish C. Chandramoorthy ,&nbsp;Raed Obaid Saleh ,&nbsp;Viralkumar Mandaliya ,&nbsp;Roopashree R ,&nbsp;Hanen Mahmod Hulail ,&nbsp;Subasini Uthirapathy ,&nbsp;Renu Arya ,&nbsp;Deepak Nathiya ,&nbsp;Dina M.R. AlKhafaf","doi":"10.1016/j.yexcr.2025.114778","DOIUrl":"10.1016/j.yexcr.2025.114778","url":null,"abstract":"<div><div>The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has recently been characterized as a major player in cancer-related inflammation, tumor progression, immune modulation, and metastasis. The role of extracellular vesicles (EVs), such as exosomes and microvesicles, as active carriers of NLRP3 signaling components is increasingly being recognized, as they modulate the tumor microenvironment as well as distant tissues primed for metastasis. This study will address the diverse roles of EV-mediated NLRP3 signaling in cancer immunopathogenesis, with a particular emphasis on its role in establishing a pre-metastatic niche and immune evasion. Tumor-derived EVs that include NLRP3 as cargo can reprogram stroma and immune cells at secondary sites in the body to support a metabolic role associated with metastatic colonization. While tumor-derived EVs promote extracellular matrix remodeling, angiogenesis, and the recruitment of immune-suppressive cells, this cascade of processes permits the development of a permissive niche for metastatic colonization, and simultaneously impairs anti-tumor immune surveillance. The provided EV-mediated crosstalk also enables tumor cells to evade immune detection through the downregulation of antigen-presenting cells and the activation of immune-suppressive pathways via NLRP3-dependent mechanisms. The molecular mechanisms underlying EV-driven inflammasome signaling could pave the way for the identification of a novel and specific biomarker, in which its modulation could potentially affect the immune system in the tumor microenvironment (TME) and participate in cancer immunopathogenesis. This review highlights the need to dissect further the interactions and context-specific roles of EV-NLRP3 across cancers to identify new therapeutic strategies for preventing metastasis and enhancing immune therapies.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114778"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206082","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 glutaminase C, a splice variant of glutaminase 1, suppresses smooth muscle cell phenotypic modulation and neointimal hyperplasia","authors":"Ankan Sarkar ,&nbsp;Bhavneesh Kumar ,&nbsp;Ashok K. Yadav,&nbsp;Sandip V. Pawar,&nbsp;Kanwaljit Chopra,&nbsp;Manish Jain","doi":"10.1016/j.yexcr.2025.114777","DOIUrl":"10.1016/j.yexcr.2025.114777","url":null,"abstract":"<div><div>Smooth muscle cell (SMC) phenotypic modulation plays a pivotal role in vascular proliferative disorders. During proliferation, SMCs utilize glutamine to fulfill their energy, biosynthesis, and redox needs. Glutaminase C (GAC), a splice variant of glutaminase (<em>GLS</em>), catalyzes the hydrolysis of glutamine to glutamate, which is ultimately used in the TCA cycle. Although GAC is known to stimulate the proliferation of human cancer cells, endothelial cells, and fibroblasts, its role in SMC proliferation and neointimal hyperplasia remains elusive. This study explores the role of the therapeutic potential of targeting GAC during SMC proliferation and neointimal hyperplasia. To assess the role of GAC on the proliferation of SMCs, murine aortic SMCs were treated with CB-839 (selectively inhibits GAC activity; 10 μM) for 60 min. SMCs were stimulated with Platelet-Derived Growth Factor-BB (PDGF-BB; 20 ng/ml) for 24 h. Using Western blotting and immunofluorescence, we report that GAC expression was significantly higher in SMCs stimulated by PDGF-BB and in the neointima of wire-injured mice as compared to the control. Deprivation of glutamine in the media impeded the proliferation and migration of SMCs. Pretreatment of SMCs with GAC inhibitor reduces PDGF-BB-induced SMC migration, proliferation, and phenotypic switching. GAC inhibition was associated with decreased phosphorylation of ERK and mTOR. GAC translocated to mitochondria and induced oxidative stress. The perivascular application of a GAC inhibitor attenuated injury-induced neointimal hyperplasia. The present study demonstrates that targeting glutamine metabolism by inhibiting GAC reduces SMC proliferation and may be a potential target for reducing neointimal hyperplasia.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114777"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185201","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":"Downregulation of heat shock protein 90 alpha family class A member 1 inhibits necroptosis in cardiac microvascular endothelial cells and alleviates sepsis-induced cardiomyopathy","authors":"Zhen Fan,&nbsp;Jinzhong Dong,&nbsp;Yuanyuan Zhao,&nbsp;Jihui Ye,&nbsp;Jianhua Zhu,&nbsp;Danhui Li","doi":"10.1016/j.yexcr.2025.114757","DOIUrl":"10.1016/j.yexcr.2025.114757","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Sepsis-induced cardiomyopathy (SIC) is a disease of cardiac dysfunction caused by sepsis and represents one of the most serious complications of sepsis. Cardiac microvascular endothelial cells (CMECs) play an important role in supporting and nourishing cardiomyocytes (CMs) and blood vessels. SIC may cause injury to CMECs, thereby accelerating the disease progression. In addition, heat shock protein 90 alpha (HSP90α) is encoded by heat shock protein 90 alpha family class A member 1 (HSP90AA1). As a stress-responsive molecule, HSP90α exhibits markedly elevated expression under pathological conditions such as inflammation, ischemia, and hypoxia. Furthermore, HSP90α plays a crucial role in disease progression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;Using mice as models, this study aims to investigate the effects of Hsp90AA1 (the mouse ortholog of human HSP90AA1) on the function and necroptosis of mouse cardiac microvascular endothelial cells (MCMECs), and to clarify whether Hsp90AA1 is involved in the pathological process of SIC through the nuclear factor-kappa B (NF-κB) signaling pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Heterogeneity of capillary endothelial cells (Cap ECs) in SIC was analyzed via single-cell RNA sequencing (scRNA-seq), followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Sepsis models were established both &lt;em&gt;in vitro&lt;/em&gt; and &lt;em&gt;in vivo&lt;/em&gt; by inducing MCMECs with lipopolysaccharide (LPS) and performing cecal ligation and puncture (CLP) surgery on mice, respectively. Cell viability was detected by cell counting kit-8 (CCK-8). Hsp90aa1 expression was detected by Western blot. Phosphorylated receptor-interacting protein kinase 3 (p-RIPK3), phosphorylated mixed lineage kinase domain-like pseudokinase (p-MLKL), and phosphorylated nuclear factor-kappa B p65 subunit (p-NF-κB p65) expression was detected by immunofluorescence. MCMEC tube formation and migration were separately detected by the tube formation assay and the Transwell migration assay. Serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1) levels in mice were determined by enzyme-linked immunosorbent assay (ELISA). Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured by transthoracic echocardiography (TTE).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;scRNA-seq techniques showed a significant increase in the number of heat shock protein 90 alpha family class A member 1-positive Cap ECs (Hsp90aa1&lt;sup&gt;+&lt;/sup&gt;Cap ECs) in SIC. Additionally, these cells exhibited upregulation of necroptosis and NF-κB signaling pathways. After LPS treatment, MCMEC viability was decreased, and p-RIPK3, p-MLKL, and Hsp90aa1 expression was increased. Whereas, Hsp90aa1 knockdown restored cell viability of LPS-treated cells, decreased p-RIPK3 and p-MLKL expression, and improve","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114757"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085621","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":"Inhibition of USP18 in the presence of IFN-α elevates apoptosis, autophagy, and chemosensitivity of oesophageal cancer cell lines","authors":"M.M. Carey,&nbsp;T.R. O'Donovan,&nbsp;C.M. Coveney,&nbsp;S.L. McKenna","doi":"10.1016/j.yexcr.2025.114768","DOIUrl":"10.1016/j.yexcr.2025.114768","url":null,"abstract":"<div><div>Oesophageal cancer remains a poor-prognosis disease with a five-year survival of 20 %. Chemoresistance poses a significant challenge, and its mechanisms remain unclear. Our previous study found that the ISGylation network is differentially expressed in drug-sensitive and resistant oesophageal cancer cells. ISGylation involves conjugating Interferon-Stimulated Gene 15 (ISG15) to target proteins, regulated by E1, E2, and E3 enzymes, similar to ubiquitin. Ubiquitin Specific Peptidase 18 (USP18) removes ISG15 and negatively regulates the type I interferon (IFN) response. We investigated whether USP18 expression influences the chemosensitivity of two resistant oesophageal cancer cell lines. Treatment with IFN-α ( ± 5-fluorouracil (5-FU) or oxaliplatin) induces ISGylation network proteins, including USP18. ISG15 conjugation is only detected after USP18 depletion with siRNA. Silencing USP18 significantly increased sensitivity to 5-FU and oxaliplatin, inducing extensive apoptosis in both cell lines previously regarded as apoptosis incompetent. USP18 depletion also elevated LC3 II expression and autophagosome formation induced by IFN-α ( ± chemotherapeutic agents), indicative of autophagy. These findings demonstrate that strategies to inhibit USP18 could re-engage cell death signalling and restore sensitivity to chemo-resistant oesophageal cancer cells.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114768"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148624","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":"Suppressor of Tumorigenicity 14 inhibits non-small cell lung cancer cell proliferation by suppressing Transketolase O-GlcNAcylation","authors":"Lei Ji ,&nbsp;Maowei Zhang ,&nbsp;Yanan Liu ,&nbsp;Hui Zhang ,&nbsp;Tao Luo ,&nbsp;Ling Zhao ,&nbsp;Wenhui Zhang ,&nbsp;Bi Chen ,&nbsp;Rui Chen","doi":"10.1016/j.yexcr.2025.114776","DOIUrl":"10.1016/j.yexcr.2025.114776","url":null,"abstract":"<div><div>Suppressor of Tumorigenicity 14 Protein (ST14), a type II transmembrane serine protease, is a well-documented oncogenic driver in multiple malignancies. Paradoxically, its pathobiological functions in non-small cell lung cancer (NSCLC) remain incompletely defined. This study uncovers a previously unrecognized tumor-suppressive role for ST14: we demonstrate that ST14 overexpression significantly suppresses NSCLC cell proliferation <em>in vitro</em> and tumor growth <em>in vivo</em>.</div><div>Mechanistically, we identify a novel ST14-Transketolase (TKT) regulatory axis, in which ST14 modulates cellular metabolism through post-translational modifications. Specifically, we establish the following: (i) TKT physically interacts with O-GlcNAc transferase (OGT) to undergo functional O-GlcNAcylation; (ii) ST14 competitively disrupts the TKT-OGT interaction, thereby ablating TKT O-GlcNAcylation; (iii) Such suppression of TKT glycosylation attenuates glycolytic flux, as evidenced by reduced glucose uptake and lactate production; (iv) The resulting metabolic impairment directly inhibits cellular proliferation. Collectively, these findings provide the first mechanistic evidence that ST14 constrains NSCLC cell proliferation via glycosylation-dependent metabolic reprogramming.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114776"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185150","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":"Tumor cell-derived DNASE2B mediates M2 macrophage infiltration to promote prostate cancer progression through the PSA secretion","authors":"Yulin Dai ,&nbsp;Junkai Xu ,&nbsp;Yunhui Zhao ,&nbsp;Dongdong Ke ,&nbsp;Qing Gao ,&nbsp;Qisong Chen","doi":"10.1016/j.yexcr.2025.114772","DOIUrl":"10.1016/j.yexcr.2025.114772","url":null,"abstract":"<div><div>This study sought to explore the role of DNASE2B (deoxyribonuclease II beta), a gene specifically overexpressed in prostate cancer (PCa) whose mechanism in driving disease progression remains unclear. We analyzed DNASE2B expression in the TCGA database and PCa cell lines/tissues using Western blotting, q-PCR, and immunohistochemistry. Biological functions were assessed via cell scratch, Transwell, and subcutaneous tumor assays. Immune microenvironment changes were investigated using TISCH2, GEO datasets, and Timer2.0. M2 macrophage infiltration was validated via Transwell, orthotopic models, Immunohistochemistry and immunofluorescence and flow cytometry. Downstream targets were identified, and the DNASE2B-PSA relationship was verified using q-PCR, Western blotting, and ELISA. In vivo models explored the mechanism of M2 regulation. Results showed that DNASE2B expression was significantly higher in PCa tissues than in adjacent normal tissues. Silencing DNASE2B in PC3 cells markedly inhibited malignant progression of PCa both in vitro and in vivo. DNASE2B expression was strongly positively correlated with M2 macrophage infiltration, and it indirectly promoted M2 macrophage infiltration and accelerated PCa progression by affecting PSA secretion. In summary, high DNASE2B expression in PCa cells enhances M2 macrophage infiltration by increasing PSA secretion, thereby driving malignant progression of PCa.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114772"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157023","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 mechanism and the main signaling pathways in the development and progression of multiple sclerosis","authors":"Leila Naserpour ,&nbsp;Saeedeh Zare Jalise ,&nbsp;Mohadeseh Khoshandam ,&nbsp;Faezeh Hosseinzadeh","doi":"10.1016/j.yexcr.2025.114769","DOIUrl":"10.1016/j.yexcr.2025.114769","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic, inflammatory central nervous system (CNS) disorder that often leads to significant disability, particularly in younger individuals. Its pathogenesis is thought to involve a complex interplay between genetic predispositions and environmental factors, culminating in CNS inflammation. Despite extensive research, treatment options for MS remain limited and often only partially effective. This review examines key signaling pathways implicated in MS progression, focusing on their potential as therapeutic targets. These pathways include the Fibroblast Growth Factor (FGF)/FGF receptor signaling, MAPK, NF-kB, JAK/STAT, Notch, mTOR, TGF-β, and PI3K/Akt pathways. The FGF pathway, particularly FGF2, plays a pivotal role in myelination and remyelination, while also contributing to neuroinflammation and disease exacerbation. Dysregulated MAPK/ERK signaling in microglia is associated with neurodegeneration, and NF-kB activation in glial cells promotes inflammation and demyelination. The JAK/STAT pathway is crucial for immune response regulation, with its dysregulation being a key factor in MS pathogenesis. Notch signaling regulates oligodendrocyte precursor cell differentiation, offering potential therapeutic advantages. mTOR and TGF-β signaling are essential for oligodendrocyte survival and tissue repair. Finally, the PI3K/Akt pathway is involved in cell survival and immune modulation, with applications in tissue engineering to enhance remyelination. These pathways provide valuable insights into MS mechanisms, highlighting novel therapeutic strategies.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 2","pages":"Article 114769"},"PeriodicalIF":3.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120648","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}