Cell Biology and Toxicology最新文献

{"title":"CD44-targeted therapy using mP6/Rg3 micelles inhibits oral cancer stem cell proliferation and migration.","authors":"Sijia Cai, Yuwen Chen, Changyu Chen, Ming Liu","doi":"10.1007/s10565-025-10070-2","DOIUrl":"10.1007/s10565-025-10070-2","url":null,"abstract":"<p><strong>Background: </strong>This study investigates how mP6/Rg3 micelles modulate ABCB1 expression to induce ferroptosis in oral cancer stem cells (CSC) and enhance oral cancer outcomes.</p><p><strong>Methods: </strong>Micelles targeting CD44 peptide P6 were prepared and characterized using TEM and immunofluorescence. Biocompatibility was evaluated through LIVE/DEAD staining and CCK-8 assays. Impact on oral cancer CSC was assessed through in vitro and OSCC mouse model studies using transcriptomic profiling, proteomic analysis, and metabolomic screening.</p><p><strong>Results: </strong>mP6/Rg3 micelles exhibited good biodegradability, inhibiting CSC proliferation and migration. Integrated multi-omics analysis highlighted ABCB1 as a pivotal modulator in OSCC. Functional assays in cell and animal models validated micelles promote ferroptosis in CSC by inhibiting ABCB1, improving OSCC pathology.</p><p><strong>Conclusions: </strong>Targeting ABCB1 with mP6/Rg3 micelles and regulating CD44 presents a promising approach to suppress oral cancer progression by impacting CSC and tumor metabolic pathways. This study offers crucial molecular insights for new therapeutic strategies in oral cancer treatment.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"122"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PTK2 by vaccarin alleviates osteoporosis through inhibiting ferroptosis via modulating P53 acetylation/succinylation.","authors":"Yanna Wang, Changyuan Wang, Ying Gong, Qingchen Li, Mozhen Liu, Huijun Sun","doi":"10.1007/s10565-025-10074-y","DOIUrl":"10.1007/s10565-025-10074-y","url":null,"abstract":"<p><p>Osteoporosis (OP) is a systemic skeletal disorder marked by reduced bone density and deterioration of trabecular microstructure. Recent studies have established ferroptosis as a major contributor to osteoporotic bone loss; however, the specific molecular mechanisms underlying this process remain incompletely understood. In this study, RNA sequencing revealed decreased expression of protein tyrosine kinase 2 (PTK2) in OP, while bioinformatics analyses identified a significant association between PTK2 and the ferroptosis-related gene P53. Mechanistically, lysine acetyltransferase 8 (MOF) acts as a key acetyltransferase for P53 acetylation. We found that PTK2 negatively regulates ferroptosis by competitively binding with MOF, thereby inhibiting both the acetylation and succinylation of P53 at the K120 site. This inhibition restores the transcriptional expression of fibronectin 1 (FN1). Using computer-aided molecular docking, we identified vaccarin-a bioactive small-molecule compound from the Selleck.cn natural product library-as a PTK2-targeting agent. Vaccarin not only suppressed erastin-induced ferroptosis but also enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Finally, we demonstrated that adenoviral overexpression of PTK2 (ADV-PTK2) or treatment with Vaccarin attenuated ovariectomy (OVX)-induced ferroptosis and osteoporosis in mice. These findings highlight PTK2 as a promising therapeutic target for OP and suggest that targeting PTK2-mediated ferroptosis inhibition may offer a novel therapeutic approach for osteoporosis management.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"121"},"PeriodicalIF":5.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asperosaponin VI mitigates mitochondrial dysfunction and chondrocyte apoptosis in osteoarthritis by modulating the AMPK-SIRT3 pathway.","authors":"Jie Qiao, Ruibing Feng, Gongxu Yang, Zhixin Yang, Aoyu Zhang, Feng Xu","doi":"10.1007/s10565-025-10071-1","DOIUrl":"10.1007/s10565-025-10071-1","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the therapeutic potential of Asperosaponin VI (ASA VI) from Clematis chinensis in mitigating osteoarthritis (OA) progression by modulating the AMPK-SIRT3 pathway, specifically addressing ER stress, mitochondrial dysfunction, and chondrocyte apoptosis.</p><p><strong>Methods: </strong>In vitro studies were conducted using tert-Butyl hydroperoxide (TBHP)-treated chondrocytes to evaluate the effects of ASA VI on apoptosis, extracellular matrix (ECM) degradation, and mitochondrial function. In vivo studies were performed using a Destabilization of the Medial Meniscus (DMM) rat model to assess cartilage protection and joint integrity. Key molecular markers of ER stress (GRP78, CHOP, ATF4) and mitochondrial biogenesis (PGC-1α, TFAM, NRF-2) were analyzed through Western blotting and PCR. Histological assessments, including Safranin O and H&E staining, were used to evaluate joint architecture and cartilage degradation, while Osteoarthritis Research Society International (OARSI) scores quantified the extent of cartilage destruction.</p><p><strong>Results: </strong>ASA VI treatment significantly enhanced chondrocyte viability and reduced apoptosis, as evidenced by a decrease in TUNEL-positive cells. It also preserved cartilage matrix integrity by upregulating Collagen II and Aggrecan, while reducing MMP-13 expression. Mechanistic studies revealed that ASA VI activates the AMPK-SIRT3 pathway, reducing ER stress and enhancing mitochondrial biogenesis, as indicated by increased PGC-1α, TFAM, and NRF-2 expression. Improvements in mitochondrial function were confirmed by increased ATP production and the preservation of mitochondrial membrane potential. In the DMM rat model, ASA VI treatment led to a significant reduction in cartilage degradation and OARSI scores, with histological analysis confirming improved joint architecture. Molecular analysis further validated the reduction in ER stress markers, linking these improvements to the activation of the AMPK-SIRT3 pathway.</p><p><strong>Conclusion: </strong>ASA VI from Clematis chinensis offers a promising therapeutic approach for OA by leveraging the AMPK-SIRT3 pathway to alleviate ER stress and mitochondrial dysfunction. This comprehensive protective mechanism contributes to reduced chondrocyte apoptosis and preserved cartilage integrity, highlighting ASA VI's potential as a novel disease-modifying agent in OA management.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"120"},"PeriodicalIF":5.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intersection of ferroptosis and nanomaterials brings benefits to breast cancer.","authors":"Jian Gao, Ningye Ma, Sha Ni, Xue Han","doi":"10.1007/s10565-025-10067-x","DOIUrl":"10.1007/s10565-025-10067-x","url":null,"abstract":"<p><p>Breast cancer (BC) is the most frequently diagnosed malignancy among women worldwide, with a high incidence and mortality rate. Despite advances in treatment, approximately 10%-15% of patients with BC still face recurrence. Therefore, improving BC therapy remains a significant challenge. In this article, we provide a detailed overview, categorizing and elaborating the developments of current research progress on nanodrug delivery systems based on ferroptosis for BC treatment. By increasing the iron content in BC cells and inhibiting the defense system against ferroptosis, the accumulation of lipid peroxides is promoted, and ferroptosis is induced in BC cells. In addition to directly targeting tumor cells, nanodrug delivery systems can remodel the tumor microenvironment, inhibit BC primary growth, and prevent distant metastasis. These nanomaterials, after drug loading and modification, possess characteristics such as smart activation, controlled release, specific targeting, good biocompatibility, and long circulation time, thereby enhancing the efficacy of BC treatment. We also classify and discuss the mechanisms and advantages of different types of nanomaterials. Finally, we discuss how multifunctional nanosystems can sensitize ferroptosis when combined with radiotherapy, chemotherapy, immunotherapy, and phototherapy to achieve synergistic effects in BC treatment. This work reveals the potential of ferroptosis-based nanomaterials in overcoming BC, analyzes the limitations of the clinical application and proposes possible solutions, offering a promising direction for future treatment strategies.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"119"},"PeriodicalIF":5.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The SDF-1α/MTDH axis inhibits ferroptosis and promotes the formation of anti-VEGF-resistant choroidal neovascularization by facilitating the nuclear translocation of SREBP1.","authors":"Rong Zou, Xi Zhang, Xiaochan Dai, Yuanzhi Yuan, Jinhui Dai, Fei Yuan","doi":"10.1007/s10565-025-10066-y","DOIUrl":"10.1007/s10565-025-10066-y","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) has been well recognized as the first ranked blinding ocular fundus diseases among older individuals, particularly in developed regions, owing to its progressive nature and high prevalence in aging populations. Anti-vascular endothelial growth factor (VEGF) agents injected into patients' vitreous cavity is the preferred treatment regimen for neovascular AMD. However, many patients exhibit resistance to anti-VEGF treatment, which is an urgent clinical problem. In this study, we treated mouse and endothelial cells with anti-VEGF drug Ranibizumab and stromal cell-derived factor-1α (SDF-1α) and found that ferroptosis was induced by Ranibizumab but inhibited by SDF-1α. SDF-1α inhibited ferroptosis by promoting transport of Sterol regulatory element binding protein 1 (SREBP1) from endoplasmic reticulum (ER) to Golgi transportation and SREBP1 maturation. Furthermore, we found that metadherin (MTDH) mediates SREBP1' s movement from the endoplasmic reticulum (ER) to Golgi apparatus by inhibiting SREBP1 binding to INSIG1/INSIG2. Our study revealed the important role of SDF-1α/MTDH/SREBP1 axis in regulating anti-VEGF treatment resistance in patients with AMD.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"118"},"PeriodicalIF":5.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZMIZ1 lactylation induces tamoxifen resistance in breast cancer through increasing transcriptional activity of Nanog to impact cell stemness and cholesterol uptake.","authors":"Yue Liu, Jingyu Chen, Li Ma, Shu Zhao, Xue Hui, Wenjing Xiong, Shaoqiang Cheng, Yue Zhang","doi":"10.1007/s10565-025-10068-w","DOIUrl":"10.1007/s10565-025-10068-w","url":null,"abstract":"<p><p>Tamoxifen is a critical drug for the treatment of oestrogen receptor (ER)-positive breast cancer (BC), which represents the majority of BC subtypes. However, many BC tumours that initially respond eventually develop acquired Tamoxifen resistance. Bioinformatics analysis was conducted on genes affected by Tamoxifen and upregulated in Tamoxifen-resistant cells to identify the biological processes associated with Tamoxifen resistance. Metabolomics analysis was conducted to identify the metabolites that were altered in BC with tamoxifen resistance. Resistance to Tamoxifen was evaluated by cell viability, proliferation, invasion, and colony formation in vitro, and by tumour growth in vivo. Metabolomic profiling and the detection of relevant enzymes and metabolites corroborated the metabolic reprogramming towards glycolysis in tamoxifen - resistant BC. The produced lactic acid induced the lactylation of ZMIZ1. This post-translational modification at K843 (but not K537) increased protein stability by suppressing SUMOylation and ubiquitination. The elevated total level of ZMIZ1 increased the enrichment of ZMIZ1 binding to Nanog, resulting in increased transcriptional activity of Nanog, including in OCT4 and NPC2 genes. Therefore, it leads to increased stemness and cholesterol accumulation in Tamoxifen-resistant BC. Knockdown of ZMIZ1 impaired Tamoxifen resistance, but this effect was reversed by Nanog overexpression. In summary, this study identified an important mechanism underlying Tamoxifen resistance and revealed a potential association of glucose glycolysis with cholesterol metabolism through the ZMIZ1/Nanog/NPC2 axis.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"117"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epi-nutrients for cancer prevention: Molecular mechanisms and emerging insights.","authors":"Saad Bakrim, Nasreddine El Omari, Ouadie Mohamed El Yaagoubi, Asaad Khalid, Ashraf N Abdalla, Siddiqa M A Hamza, Salma Elhadi Ibrahim, Farah Atifi, Younes Zaid, Abdelhakim Bouyahya, Meriem El Fessikh, Long Chiau Ming, Tarik Aanniz","doi":"10.1007/s10565-025-10054-2","DOIUrl":"10.1007/s10565-025-10054-2","url":null,"abstract":"<p><p>The burgeoning field of epigenetics holds considerable potential in cancer prevention and management, as it targets mechanisms essential to regulating gene expression without altering DNA sequences. Epigenetic processes like DNA methylation, histone modifications, non-coding RNAs, and nucleosome remodelling-play an essential role in cellular differentiation and development, with dysfunction in these pathways often leading to malignancy. Targeting epigenetic regulators, including DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), can suppress cancer cell proliferation, making epigenetics a promising therapeutic frontier. Phytochemicals, natural bioactive compounds predominantly found in vegetables, fruits, and seeds, offer a complementary approach to traditional cancer therapies through their epigenetic influence. These compounds exhibit anti-inflammatory, anti-angiogenic, and antioxidant properties, which modulate pathways and proteins involved in chromatin remodeling and may influence the mammalian epigenome. A diverse spectrum of bioactive dietary ingredients, including curcumin, epigallocatechin-3-gallate (EGCG), genistein, quercetin, resveratrol, and sulforaphane, has gained significant interest for their ability to modulate gene expression and chromatin structure via epigenetic mechanisms. Their potential implications for cancer prevention and their role in regulating key epigenetic genes have been described in numerous investigations. This comprehensive review explores the molecular mechanisms by which dietary bioactive molecules may reverse epigenetic aberrations in cancer cells. It examines the influence of these compounds on DNA methylation, ten-eleven translocation (TET) enzymes, and histone modifications, while discussing their specific molecular targets in various cancer types. Additionally, we highlight the pathways through which these epi-nutrients may impact gene expression and enzyme activities associated with epigenetic regulation, which leads to innovative, diet-based anticancer strategies. Clinical trial number: not applicable.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"116"},"PeriodicalIF":5.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in hybrid hydrogel design for biomedical applications: innovations in drug delivery and tissue engineering for gynecological cancers.","authors":"Hua Chang, Heng Wei, Yue Qi, Silu Ding, Hui Li, Si Si","doi":"10.1007/s10565-025-10064-0","DOIUrl":"10.1007/s10565-025-10064-0","url":null,"abstract":"<p><p>Hybrid hydrogels have emerged as multifunctional biomaterials for targeted drug delivery and tissue engineering in gynecologic oncology. In this review, we summarize recent advances in the design of hybrid hydrogels that combine polymer networks with nanomaterials to achieve tunable stimuli-responsiveness, enhanced mechanical strength, and improved biocompatibility. For example, preclinical studies of folate-conjugated liposomal doxorubicin have demonstrated enhanced accumulation and antitumor efficacy in ovarian cancer models, while growth factor-loaded hydrogel scaffolds have supported endometrial repair in rodent models. We discuss strategies for optimizing drug loading, controlling spatiotemporal release profiles in response to tumor-specific cues (such as pH or enzyme activity), and customizing scaffold architecture for patient-specific regenerative needs. Implementation challenges-including efficient encapsulation of multiple cargos, precise control over degradation rates, and scale-up for clinical manufacturing-are critically examined. Finally, we outline future directions, including multifunctional platforms that integrate real-time monitoring with combined chemo-immunotherapy and approaches to address regulatory and translation hurdles. This evidence-based analysis highlights how hybrid hydrogels can advance precision therapy and regenerative medicine for gynecologic cancers while there is a need for further validation in clinical settings.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"115"},"PeriodicalIF":5.3,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-nucleus rna sequencing identifies universal camk1d upregulation and dysregulated c-ltmr subtypes as key drivers of paclitaxel-induced neuropathy.","authors":"Wuping Sun, Rongzhen Li, Xinyi Zhang, Songbin Wu, Yanjun Jiang, Qian Li, Di Cao, Donglin Xiong, Lizu Xiao, Xiaodong Liu","doi":"10.1007/s10565-025-10065-z","DOIUrl":"10.1007/s10565-025-10065-z","url":null,"abstract":"<p><p>Neuropathic pain triggered by chemotherapy poses a significant clinical challenge. Investigating cell type-specific alterations through single-cell transcriptome analysis holds promise in understanding symptom development and pathogenesis. In this study, we performed single nuclei RNA (snRNA) sequencing of dorsal root ganglions (DRG) to explore the molecular mechanism underlying paclitaxel-induced neuropathic pain. Mouse exposed to repeated paclitaxel doses developed persistent pain hypersensitivity lasting at least 21 days. The snRNA sequencing unveiled seven major cell types within DRGs, with neurons further subdivided into 12 distinct subclusters using known markers. Notably, type C low-threshold mechanoreceptors (C_LTMR) exhibited the most pronounced transcriptomic changes post-paclitaxel administration. Differential gene expression and Gene Ontology (GO) analysis highlighted suppressed potassium-related currents, microtubule transport, and mitochondrial functions in C_LTMR following paclitaxel treatment. Pseudo-time analysis uncovered nine distinct states (state 1 to 9) of C_LTMR. State 1 exhibits higher prevalence in paclitaxel-treated mice and altered neurotransmission properties, likely contributing to paclitaxel-induced pain hypersensitivity. Additionally, Camk1d is involved in temperature hyperalgesia in CIPN, a key clinical symptom observed in human patients with CIPN. This comprehensive exploration sheds light on the molecular mechanisms driving paclitaxel-induced neuropathic pain, offering potential avenues for therapeutic intervention.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"114"},"PeriodicalIF":5.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cGAS-STING targeting offers novel therapeutic regimen in sepsis-associated organ dysfunction.","authors":"Tao Yu, Joshua S Fleishman, Hongquan Wang, Xueyan Liu, Liang Huo","doi":"10.1007/s10565-025-10051-5","DOIUrl":"10.1007/s10565-025-10051-5","url":null,"abstract":"<p><p>Sepsis is clinically defined as a life-threatening syndrome characterized by dysregulated host responses to infection, culminating in progressive multi-organ dysfunction. The pathogenesis of sepsis-associated organ dysfunction (SAOD) -manifesting as encephalopathy, cardiomyopathy, acute kidney/liver injury, and respiratory failure-represents the primary determinant of mortality in septic patients. Despite its clinical significance, the molecular mechanisms driving SAOD remain incompletely elucidated. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) axis is a critical innate immune pathway by triggering a type I interferon (IFN-I) response. However, aberrant activation of this axis leads to inflammatory and autoimmune diseases.Emerging evidence implicates hyperactivation of cGAS-STING as a critical mediator of SAOD across multiple organ systems. Notably, pharmacological inhibitors targeting cGAS-STING signaling demonstrate therapeutic promise in preclinical models of sepsis-induced organ injury, attenuating inflammatory cascades and preserving tissue integrity. This review synthesizes current insights into the mechanistic contributions of cGAS-STING signaling to SAOD pathogenesis while critically evaluating novel therapeutic agents-including small -molecule inhibitors, natural compounds, and biologics-that disrupt this pathway to mitigate organ dysfunction. By bridging molecular mechanisms with translational applications, we underscore cGAS-STING inhibition as a paradigm-shifting strategy for addressing the unmet clinical needs in sepsis and SAOD management.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"113"},"PeriodicalIF":5.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}