Inflammation Research最新文献

{"title":"The role of absent in melanoma 2 (AIM2) in cardiovascular diseases.","authors":"Jiesong Pan, Yikai Zhao, Maocheng Gu, Shuqin Chen, Yuxiao Wang, Wen Gao, Jian Li","doi":"10.1007/s00011-025-02078-5","DOIUrl":"https://doi.org/10.1007/s00011-025-02078-5","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) are a group of conditions that significantly affect human health and are among the leading causes of death and disability worldwide. Clinical trials and basic research have demonstrated that inflammation plays a pivotal role in the development of CVDs. The inflammasome is a critical component of the innate immune system, involved in various inflammatory responses to pathogens and tissue damage. Absent in melanoma2(AIM2), which belongs to the PYHIN Family, is a receptor for intracellular DNA pattern recognition. AIM2 inflammasomes are implicated in the onset and progression of CVDs, activated in atherosclerotic plaques, aortic aneurysms, and damaged myocardium. This review summarizes recent advances in AIM2 research in CVDs, exploring its interactions with other inflammasomes and emphasizing its central role in immune and inflammatory responses. Specifically, the review summarizes the progress of AIM2 inhibitors, in order to critically evaluate the translational potential of such concepts into clinical practices.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"120"},"PeriodicalIF":5.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sigma-1 receptor activation by PRE-084 attenuates sepsis-associated encephalopathy by targeting microglial p38 MAPK-mediated neuroinflammation and neuronal endoplasmic reticulum stress.","authors":"Xin Zeng, Wen Kang, Qin Zhou, Xia Pan, Long Wang","doi":"10.1007/s00011-025-02086-5","DOIUrl":"https://doi.org/10.1007/s00011-025-02086-5","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-Associated Encephalopathy (SAE) is a severe neurological complication of sepsis, where neuroinflammation plays a critical pathogenic role, leading to cognitive dysfunction. The Sigma-1 receptor (Sigma-1R), a chaperone protein, is implicated in neuroprotection, including the crucial modulation of neuroinflammation and endoplasmic reticulum stress (ERS). This study aimed to investigate the therapeutic potential of the Sigma-1R agonist, PRE-084, in specifically targeting SAE-associated neuroinflammation and its downstream neuropathology.</p><p><strong>Methods: </strong>A cecal ligation and puncture (CLP) murine model of sepsis was established. Mice received the Sigma-1R agonist PRE-084 or saline. Neurological function (SHIRPA), survival rates, and cognitive performance (Morris Water Maze) were assessed. Hippocampal and cortical tissues were analyzed for Sigma-1R expression and localization, ERS markers (BiP, p-eIF2α), synaptic protein levels (PSD95, Synaptophysin), glial cell activation (Iba-1, GFAP), pro-inflammatory cytokine levels (TNF-α, IL-6), and p38 Mitogen-Activated Protein Kinase (p38 MAPK) pathway activation using Western blotting, immunofluorescence, and ELISA.</p><p><strong>Result: </strong>CLP surgery induced neurological deficits, reduced survival, and upregulated neuronal Sigma-1R in the hippocampus. PRE-084 administration significantly improved survival rates, ameliorated neurological impairments, and attenuated cognitive dysfunction in CLP mice. Mechanistically, PRE-084 treatment directly mitigated neuronal CLP-induced ERS (reduced BiP expression and eIF2α phosphorylation) and preserved hippocampal postsynaptic density protein 95 (PSD95) levels. Crucially, these primary neuroprotective effects on neurons translated into a profound suppression of neuroinflammation, evidenced by reduced microglial (Iba-1) and astrocyte (GFAP) activation, decreased brain levels of pro-inflammatory cytokines TNF-α and IL-6, and specific inhibition of microglial p38 MAPK activation. This indicates an indirect but potent anti-inflammatory effect stemming from primary neuronal Sigma-1R engagement.</p><p><strong>Conclusion: </strong>Our findings demonstrate that activation of neuronal Sigma-1R by PRE-084 confers protection against SAE. This protection involves primary mitigation of neuronal ERS, which is pivotal in subsequently dampening the detrimental microglial p38 MAPK-mediated neuroinflammatory cascade. This multifaceted action, culminating in reduced neuroinflammation, improves neurological outcomes and cognitive function. Targeting Sigma-1R to control neuroinflammation offers a promising therapeutic strategy for SAE.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"117"},"PeriodicalIF":5.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging worlds: a narrative review of IL-17 at the crossroads of inflammation and thrombosis.","authors":"Gustavo Gomes Resende, Lirlândia Pires Sousa, Mauro Martins Teixeira","doi":"10.1007/s00011-025-02081-w","DOIUrl":"https://doi.org/10.1007/s00011-025-02081-w","url":null,"abstract":"<p><p>Interleukin-17 (IL-17) has emerged as a key cytokine at the intersection of inflammation and thrombosis, potentially playing a pivotal role in thromboinflammation. This review explores the mechanistic contributions of IL-17 to endothelial dysfunction, platelet activation, monocytes activation, and neutrophil extracellular trap (NET) formation, which collectively promotes a pro-thrombotic state. We summarize findings from experimental models and clinical studies linking IL-17 to thrombosis in autoimmune diseases, atherosclerosis, and infectious diseases such sepsis and COVID-19. Additionally, we discuss the therapeutic implications of IL-17 inhibition in mitigating thromboinflammatory complications. Understanding the role of IL-17 in this process may provide new avenues for targeted interventions in thromboinflammatory disorders.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"118"},"PeriodicalIF":5.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early hyperferritinemia in polytrauma: a biomarker of systemic inflammation and mortality risk in a multicenter cohort study.","authors":"Shunyao Chen, Teding Chang, Jialiu Luo, Cong Zhang, Peidong Zhang, Shuaipeng Gu, Zhiqiang Lin, Yujie Chen, Youxie Shen, Liming Dong, Qian Wan, Liang He, Yu Lei, Zhibiao Zhang, Kewen Cao, Jiaying Lin, Di Xu, Xiaozhong Zhou, Zengxiang Yang, Deng Chen, Chunqiu Pan, Zhao-Hui Tang","doi":"10.1007/s00011-025-02074-9","DOIUrl":"10.1007/s00011-025-02074-9","url":null,"abstract":"<p><strong>Background: </strong>Severe polytrauma is one of the leading causes of death and disability worldwide. Hyperferritinemia is increasingly recognized as a biomarker of critical illness, yet its prognostic significance in polytrauma remains underexplored. This multicenter study investigates the temporal dynamics of serum ferritin in polytrauma patients and its association with systemic inflammation, organ dysfunction, and mortality.</p><p><strong>Methods: </strong>A prospective observational cohort of 1475 polytrauma patients from four trauma centers was analyzed. Serum ferritin levels were measured on admission day 1 and day 7. Patients were stratified by ferritin thresholds: < 500 ng/ml, 500-999 ng/ml, 1000-2999 ng/ml, and ≥ 3000 ng/ml. Outcomes included mortality, ICU stay, complications, and organ dysfunction. Logistic regression and ROC analyses identified predictive thresholds. A prognostic nomogram integrating Day 1 ferritin, ferritin change (ΔFerritin), inflammatory markers (IL-6, CRP), and clinical scores (SOFA, APACHE II) was developed and internally validated.</p><p><strong>Results: </strong>Hyperferritinemia (≥ 500 ng/mL) occurred in 39.3% of patients, with mortality escalating from 9.2% (ferritin < 500) to 66.7% (ferritin ≥ 3000) (P < 0.001). Day 7 ferritin (> 655 ng/mL) outperformed day 1 levels (AUC 0.807 vs. 0.686) in mortality prediction, with 68.5% sensitivity and 87.8% specificity. Ferritin > 1000 ng/mL emerged as an independent mortality risk factor (OR = 1.91, P = 0.004), correlating with elevated inflammatory hyperferritinemia markers (IL-6, CRP), hepatic/renal dysfunction (AST↑, eGFR↓), and coagulopathy (INR↑). Survivors exhibited a steeper ferritin decline (- 233 vs. -146 ng/mL, P < 0.001), while non-survivors sustained hyperferritinemia. The prognostic nomogram demonstrated strong discriminative ability for in-hospital mortality (AUC = 0.813) and good calibration. Decision curve analysis confirmed significant clinical net benefit across a wide probability threshold range (0.1-0.8).</p><p><strong>Conclusion: </strong>Early hyperferritinemia predicts adverse outcomes in polytrauma, reflecting systemic inflammation and organ failure. Serial ferritin monitoring post-injury enhances risk stratification, offering a pragmatic biomarker for guiding intensive care and targeted interventions.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"119"},"PeriodicalIF":5.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of novel Phosphodiesterase-4 inhibitors in the treatment of psoriasis.","authors":"Amirreza Fakhri Baghdad Abad, Nazila Heidari, Zahra Lotfi, Amirhossein Heidari","doi":"10.1007/s00011-025-02073-w","DOIUrl":"https://doi.org/10.1007/s00011-025-02073-w","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic immune-mediated skin disease that significantly impacts patients' quality of life due to its physical, psychological, and systemic burden. Phosphodiesterase-4 (PDE-4) plays a pivotal role in the inflammatory cascade of the disease through the modulation of intracellular cyclic adenosine monophosphate (cAMP) levels. This systematic review evaluates current evidence on the clinical efficacy and safety of novel PDE-4 inhibitors in the treatment of psoriasis.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science databases through January 18th, 2025, to identify clinical studies evaluating PDE-4 inhibitors in patients with psoriasis. Methodological quality and risk of bias were assessed using the National Institutes of Health (NIH) quality assessment tool and the Murad et al.quality assessment tool.</p><p><strong>Results: </strong>Out of 1,942 related studies, twelve studies with 642 patients met our inclusion criteria. Among oral PDE-4 inhibitors, oral roflumilast demonstrated consistent improvements in the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI), as well as patient-reported outcomes, in cases with moderate to severe plaque psoriasis. Gastrointestinal symptoms were the most common adverse events. Similarly, orismilast and ME3183 also demonstrated significant PASI reductions and favorable tolerability, while topical agents like crisaborole and PF-07038124 showed a rapid localized response in patients suffering from mild to moderate psoriasis, with minimal adverse effects in sensitive areas, including the face and intertriginous regions.</p><p><strong>Conclusion: </strong>PDE-4 inhibitors, both oral and topical, demonstrate promising efficacy and acceptable safety profiles in the treatment of psoriasis. To confirm their long-term benefits and improve clinical use, larger-scale studies with longer follow-up and a wider range of patients are required.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"116"},"PeriodicalIF":5.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of sepsis on bone marrow mesenchymal stem cells and its implications for hematopoiesis and immunosuppression.","authors":"Thatiana Correa de Melo, Suely Kunimi Kubo Ariga, Thais Martins de Lima, Debora Levy, Sérgio Paulo Bydlowski, Francisco Garcia Soriano","doi":"10.1007/s00011-025-02083-8","DOIUrl":"https://doi.org/10.1007/s00011-025-02083-8","url":null,"abstract":"<p><strong>Objective and design: </strong>Septic patients often exhibit disruption of the normal hematopoiesis, leading to hematological abnormalities such as anaemia, leukopenia, and thrombocytopenia. We hypothesized that sepsis-induced changes in bone marrow mesenchymal stromal cells (BM-MSCs) contribute to the abnormal hematopoiesis observed in these patients.</p><p><strong>Material and methods: </strong>We established lineages of BM-MSCs from male BALB/c mice collected 8 h after the sham (MSC-CT) or cecal ligation and puncture surgery (MSC-Sepsis). We evaluated BM-MSCs proliferation, plasticity, and immunomodulatory properties.</p><p><strong>Results: </strong>No differences in multipotency or immunophenotypic profiles were detected between the MSC-CT and MSC-Sepsis groups. However, MSC plasticity was clearly affected by sepsis, as osteoblast differentiation was impaired in MSC-Sepsis. Since differentiation capacity is closed linked to mitochondrial dynamics and function, we assessed mitochondrial health and found that MSC-Sepsis presented depolarized mitochondria. The photoelectron micrographs supported these findings, as MSC-Sepsis presented higher number of small mitochondria around the nuclei and deformed cristae in the mitochondria. Additionally, cytokine array analysis revealed a marked reduction in the expression of several cytokines and chemokines in MSC-Sepsis.</p><p><strong>Conclusion: </strong>Our findings demonstrate that sepsis induces several functional alterations in MSC that may impair bone marrow homeostasis and contribute to both the acute immune response and long-term complications in sepsis survivors.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"115"},"PeriodicalIF":5.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Miconazole attenuates LPS-induced lung inflammation by modulating alveolar macrophage polarization via promoting lipid metabolic reprogramming.","authors":"Huanwen Wu, Qijiang Zhao, Liangliang Dong, Yuxin Wu, Chengzhi Zheng, Tongquan Wu, Daqing Ma, Yicheng Xie, Yingshuo Wang","doi":"10.1007/s00011-025-02082-9","DOIUrl":"https://doi.org/10.1007/s00011-025-02082-9","url":null,"abstract":"<p><strong>Objective: </strong>Pulmonary inflammation is closely associated with macrophage polarization and lipid metabolic reprogramming. Miconazole (MCZ), traditionally used as an antifungal agent, exhibits emerging anti-inflammatory potential, yet its underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>A mouse model of lipopolysaccharide (LPS)-induced lung inflammation was employed to evaluate MCZ's anti-inflammatory efficacy. In vivo inflammatory cell infiltration, cytokine expression (IL-6, IL-1β, TNF-α), and lung histopathology were assessed. Single-cell RNA sequencing (scRNA-seq) characterized alveolar macrophage subpopulations and associated lipid metabolism pathways. In vitro experiments with bone marrow-derived macrophages (BMDM) validated the changes of macrophage polarization.</p><p><strong>Results: </strong>MCZ treatment significantly alleviated lung inflammation by decreasing inflammatory cell infiltration and suppressing pro-inflammatory cytokines. ScRNA-seq analysis revealed subcluster of Itgam (Cd11b) negative, Mrc1, Marco, and Lgals3 high AMs, MCZ decreased the proportions of pro-inflammatory neutrophils and macrophages, and promoted the phenotypic shift of alveolar macrophages from a pro-inflammatory subtype (AM1) to an anti-inflammatory subtype (AM2). Further cell-cell communication analysis showed that MCZ suppressed interactions between AM1 alveolar macrophages and neutrophils via TNF-TNFR, CCL3/5-CCR1, and CXCL1-CXCR2 signaling pathways. Mechanistically, MCZ inhibited lipid synthesis in AM1 alveolar macrophages while enhancing lipid catabolism in AM2 alveolar macrophages. In vitro studies using BMDM further confirmed that MCZ inhibited LPS-induced macrophage M1 polarization and lipid droplet accumulation marked by perilipin 3 (PLIN3), while promoting IL-4/IL-13-induced M2 polarization.</p><p><strong>Conclusion: </strong>MCZ exerts therapeutic effects against pulmonary inflammation primarily by modulating macrophage polarization through lipid metabolic reprogramming, highlighting its promise as a novel therapeutic approach for inflammatory lung diseases.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"113"},"PeriodicalIF":5.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.","authors":"Yuanyuan Jin, Yuchang Liu, Ao Ge, Yang Yu, Ying Wan, Chunhong Li, Chunxiang Zhang","doi":"10.1007/s00011-025-02079-4","DOIUrl":"https://doi.org/10.1007/s00011-025-02079-4","url":null,"abstract":"<p><strong>Background: </strong>Due to population aging and a wide range of risk factors, coupled with the limited regenerative capacity of the myocardium, the prevention and treatment of cardiovascular diseases remain challenging.</p><p><strong>Methods: </strong>This review evaluates cardiac reprogramming as an innovative approach to directly convert fibroblasts into functional cardiomyocytes through genetic or pharmacological means. We focus on its application in myocardial infarction, ischemia-reperfusion injury, and heart failure, and discuss strategies for improving reprogramming efficiency and recent advances in nanomaterial-assisted delivery.</p><p><strong>Results: </strong>Cardiac reprogramming shows potential in reducing fibrosis and restoring function, with efficiency improved through novel delivery systems and optimized protocols.</p><p><strong>Conclusion: </strong>This technology represents a promising strategy for cardiac regeneration, future work should focus on optimizing reprogramming protocols and developing clinically viable delivery systems to accelerate therapeutic translation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"114"},"PeriodicalIF":5.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial activation is inhibited by selective anti-seizure medications.","authors":"Robert Jürgen Platow, Sabrina Pommer, Julia Brauer, Yanyan Wang, Shyamala Mani, Angela M Kaindl","doi":"10.1007/s00011-025-02076-7","DOIUrl":"https://doi.org/10.1007/s00011-025-02076-7","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the anti-inflammatory properties of anti-seizure medications (ASMs) administered to patients with drug-resistant epilepsy (DRE) and the role of sodium channels in microglial activation.</p><p><strong>Material: </strong>Primary microglia monocultures from mice brains.</p><p><strong>Treatment: </strong>Microglia were activated with 10 μg/mL lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) and pre- (45 min ASM then 2 h ASM plus stimulus) or post- (2 h stimulus then 24 h only ASM) treated with ASMs. Microglia were treated with cannabidiol (10 μM), stiripentol (250 μM), fenfluramine (50 μM), phenytoin (8 and 40 μM), cenobamate (300 and 900 μM), or the small molecule sodium channel blocker GS967 (10 and 30 μM). The sodium channel modulators tetrodotoxin (1 μM), µ-conotoxin KIIIA (1 μM), and β-pompilidotoxin (0.5 μM) were also applied.</p><p><strong>Methods: </strong>Microglia activation was quantified through measurements of Ptgs2 (Cox2), Tnf-α, and Ifn-β induction by RT-qPCR and of cell morphology by immunocytochemistry. Expression of sodium channels in microglia was studied using PCR, RT-qPCR, immunohisto- and immunocytochemistry. Mann Whitney test and the Kruskal-Wallis test with Dunn's multiple comparisons post-test were used.</p><p><strong>Results: </strong>ASMs have a differential effect on microglial activation. Uniquely, cenobamate inhibited the induction of Ifn-β and made the cells less amoeboid. The voltage gated sodium channel Na_v1.2 is expressed by microglial cells and its expression levels change with microglial inflammatory response. Toxins that block sodium channels modulated microglial activation.</p><p><strong>Conclusions: </strong>ASMs, applied to patients with DRE, have a differential ability to reduce microglial activation and pro-inflammatory microglial morphology in vitro. Moreover, sodium channel blockage modulates inflammation through microglia activation. Taken together these results suggest, that further investigation of patient's immune response to ASMs could be important.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"112"},"PeriodicalIF":5.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KIAA1429 Silencing ameliorates osteosarcoma progression through promoting ferroptosis via Nrf2/NQO1 axis.","authors":"Cheng Xie, Yihui Xiao, Lubing Yang, Jiaquan Luo","doi":"10.1007/s00011-025-02080-x","DOIUrl":"https://doi.org/10.1007/s00011-025-02080-x","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is the most common primary malignant bone tumor. Recent insights into ferroptosis have opened new avenues for OS therapy. However, the role of KIAA1429 in regulating ferroptosis and its underlying mechanisms in OS remain unclear.</p><p><strong>Methods: </strong>The effects of KIAA1429 silencing on ferroptosis were evaluated in OS cells treated with erastin alone or in combination with ferrostatin-1 (Fer-1), as well as in an OS mouse model administered sulfasalazine (SAS). Methylation sites on the Nrf2 and NQO1 transcripts were predicted using the SRAMP database and subsequently validated by MeRIP-qPCR. Furthermore, RTA-408 was employed to further investigate the impact of KIAA1429 knockdown on the Nrf2/NQO1 signaling pathway in OS cells.</p><p><strong>Results: </strong>KIAA1429 silencing reduced cell viability and increased the expression of ferroptosis-related markers in erastin-treated OS cells, and these effects were reversed by Fer-1. Knockdown of KIAA1429 further enhanced SAS-induced ferroptosis and suppression of xenograft tumor growth. MeRIP-qPCR and dual-luciferase reporter assays demonstrated that KIAA1429 directly regulated Nrf2 via m6A-dependent modification of its 3'UTR. KIAA1429 depletion inhibited viability, migration, and invasion and promoted apoptosis of MG-63 and U2OS cells through suppression of the Nrf2/NQO1 signaling.</p><p><strong>Conclusion: </strong>KIAA1429 silencing facilitates ferroptosis, thereby delaying OS progression, potentially through modulation of the Nrf2/NQO1 signaling pathway.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"111"},"PeriodicalIF":5.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}