Mediators of Inflammation最新文献

{"title":"Pharmacological Effects and Pharmacokinetic Profiles of Dehydroandrographolide.","authors":"Chenggang Xu, Yu Shen, Lina Zhang, Feng Wang, Shuting Xiang","doi":"10.1155/mi/4123997","DOIUrl":"10.1155/mi/4123997","url":null,"abstract":"<p><p>Dehydroandrographolide (Deh) is one of the main active ingredients of the traditional Chinese medicine <i>Andrographis paniculata</i>. In recent years, its pharmacological research has made remarkable progress in the fields of antibacterial, anti-inflammatory, antitumor, and antiviral therapies. As a traditional herbal medicine, <i>Andrographis paniculata</i> has long been used in the clinical treatment of infectious diseases, immune disorders, and liver injury. Deh, the plant's core active molecule, has demonstrated therapeutic potential beyond that of its source, owing to its distinctive chemical structure and multitarget mechanism of action. Studies have shown that Deh not only inhibits inflammatory responses by regulating NF-κB, Nrf2, and other related pathways but also induces apoptosis and cycle blockade in tumor cells and exerts antiviral effects by interfering with the viral replication cycle. In this review, we systematically summarized the diverse pharmacological activities of Deh and its molecular mechanisms, drawing attention to its potential role in the treatment of inflammation-related diseases. We hope this work will serve as a theoretical reference for designing innovative drugs based on natural products and encourage the clinical translation of <i>Andrographis paniculata</i>'s active ingredients.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4123997"},"PeriodicalIF":4.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753781","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":"Based on Proteomics Data Revealing the Potential of Traditional Chinese Medicine in Treating Irritable Bowel Syndrome.","authors":"Yizhan Wu, Fei Guo, Xiaoxia Xu, Ya Liu, Jiangwei Liu","doi":"10.1155/mi/7748351","DOIUrl":"10.1155/mi/7748351","url":null,"abstract":"<p><p><b>Introduction:</b> Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Despite its high prevalence, the etiology of IBS remains elusive, and there is an unmet need for targeted therapeutic interventions. <b>Material and Methods:</b> We initiated our study by conducting a causal analysis of proteomics data from 2941 proteins associated with IBS. Following this, we performed enrichment analysis to identify pathways and processes that may be implicated in the etiology of IBS. Subsequently, we utilized network pharmacology to explore the active compounds in traditional Chinese medicine that target the core proteins identified in our analysis. Molecular docking and molecular dynamics (MD) simulation are used to assess the stability of compound-protein binding. <b>Results:</b> Our research has identified 169 proteins that have a positive causal relationship with IBS. We found that pathways linked to viruses, immune cells, and cytokines might play a role in IBS. Two traditional Chinese medicines, Phellodendri Amurensis Cortex (PAC) and Achyranthis Bidentatae Radix (ABR), showed potential in treating IBS, possibly through active compounds like quercetin, berberine, and evodiamine, targeting proteins Tumor Protein p53 (TP53), 5'(3')-Deoxyribonuclease (NT5E), Jun Proto-Oncogene (JUN), and major histocompatibility complex (MHC), Class II Invariant Chain (CD74). Additionally, we conducted molecular docking and MD simulations, and the results indicated that each protein has good binding stability with its corresponding compound. <b>Conclusion:</b> These findings not only deepen our understanding of the pathophysiological mechanisms of IBS but also indicate potential molecular targets for the development of innovative treatment strategies while highlighting the broad application prospects of traditional Chinese medicine in the field of IBS treatment.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7748351"},"PeriodicalIF":4.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753780","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":"G Protein-Coupled Receptor 30 Attenuates Neuronal Pyroptosis Induced by Subarachnoid Hemorrhage.","authors":"Jun Peng, Xiqi Hu, Jun He, Ying Xia","doi":"10.1155/mi/3585885","DOIUrl":"10.1155/mi/3585885","url":null,"abstract":"<p><p><b>Background:</b> Pyroptosis is implicated as a pathogenic mechanism in early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study aimed to investigate the regulatory role of G protein-coupled receptor 30 (GPR30) in neuronal pyroptosis during SAH. <b>Methods:</b> SAH was induced in rats via intravascular perforation and hemin-treated neurons modeled SAH in vitro. GPR30 agonist G1 and antagonist G15 were administered to assess functional impacts. Neurological deficits (Garcia score), SAH severity, and cerebral edema (brain water content) were evaluated. Pyroptotic markers (cleaved caspase-1, gasdermin D (GSDMD)-N, interleukin (IL)-1β, and IL-18) were quantified. Inflammasome activation (NLRC4 and IFI16) and Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling were analyzed via immunofluorescence (IF) and immunoblotting. The TLR4 antagonist LPS-RS (lipopolysaccharide from <i>Rhodobacter sphaeroides</i>) was applied to validate pathway involvement. <b>Results:</b> GPR30 expression increased post-SAH. G15 exacerbated hemorrhage severity, neurological deficits, and cerebral edema, whereas G1 modestly attenuated SAH. G15 upregulated pyroptotic markers, enhanced neuronal pyroptosis, and activated NLRC4/IFI16 inflammasomes. Concurrently, G15 stimulated TLR4/MyD88 expression and NF-κB phosphorylation. Conversely, G1 suppressed pyroptosis, inactivated inflammasomes, and inhibited TLR4/NF-κB signaling. LPS-RS cotreatment reversed G15-induced pyroptotic and inflammatory cascades. <b>Conclusion:</b> GPR30 mitigates NLRC4- and IFI16-driven neuronal pyroptosis in SAH by modulating TLR4/NF-κB signaling. Pharmacological targeting of GPR30 represents a promising therapeutic strategy to ameliorate SAH-associated brain injury.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"3585885"},"PeriodicalIF":4.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732104","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":"RETRACTION: lncRNA SNHG14 Plays a Role in Sepsis-Induced Acute Kidney Injury by Regulating miR-93.","authors":"Mediators Of Inflammation","doi":"10.1155/mi/9875328","DOIUrl":"10.1155/mi/9875328","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1155/2021/5318369.].</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9875328"},"PeriodicalIF":4.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732105","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":"The Negative Feedback of the Glutamine/Prostatitis Loop Identified Among 1400 Metabolites and Prostatitis via Mendelian Randomization.","authors":"Yi Wang, Hao Ji, Yingfei Chen, Bingye Zhu, Yongming Peng, Qianwei Xing","doi":"10.1155/mi/9648279","DOIUrl":"10.1155/mi/9648279","url":null,"abstract":"<p><p><b>Background:</b> Prostatitis remains a clinically tricky problem due to its enigmatic etiologies, low cure rates, and relatively high recurrence rates. Therefore, we first employed Mendelian randomization to disclose the causal relationships among 1400 metabolites and prostatitis for a better understanding of the etiologies of prostatitis and thus identifying effective therapeutic targets. <b>Methods:</b> Prostatitis or metabolite-related data were derived from the online FinnGen or genome-wide association study (GWAS) Catalog datasets. Two-sample Mendelian randomization was employed, and sensitivity analyses, including heterogeneity, pleiotropy, and leave-one-out analysis, were applied to evaluate its stability. <b>Results:</b> Four potentially metabolic etiologies were identified for prostatitis, including glutamine degradant levels, adenosine 5'-monophosphate (AMP)-inosine 5'-monophosphate (IMP) ratio, glycolithocholate-glycolithocholate sulfate ratio, and AMP-citrate ratio. Therein, genetic susceptibility to the glutamine degradant levels, the AMP-IMP ratio, or the glycolithocholate-glycolithocholate sulfate ratio could decrease, while the AMP to citrate ratio might increase the risks of prostatitis. Moreover, two potential metabolic phenotypes of prostatitis were also identified, containing glutamine degradant levels and histidine betaine (hercynine) levels, indicating that genetic susceptibility to prostatitis could increase the risks of these two metabolites. Interestingly, we unexpectedly identified the negative feedback of the glutamine/prostatitis loop, showing that not only genetic susceptibility to glutamine degradant levels could decrease the risks of prostatitis but also genetic susceptibility to prostatitis could increase the risks of glutamine degradant levels. <b>Conclusion:</b> Four metabolic etiologies, two metabolic phenotypes, and the glutamine/prostatitis negative feedback loop were first identified by us for prostatitis in the European population to better understand its etiologies and offer novel treatment targets.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9648279"},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690706","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":"Association of Albumin-Bilirubin (ALBI) Grade With 28-Day All-Cause Mortality in Patients With Acute Respiratory Distress Syndrome: A Retrospective Analysis of the MIMIC-IV Database.","authors":"Weixiao Chen, Qingzhou Chen, Zhiwei Tang, Zhibo Li, Weiyan Chen, Xuming Xiong, Deliang Wen, Zhenhui Zhang","doi":"10.1155/mi/9930648","DOIUrl":"10.1155/mi/9930648","url":null,"abstract":"<p><p>The albumin-bilirubin (ALBI) grade, a validated prognostic tool in cancers such as hepatocellular carcinoma, has not been evaluated in acute respiratory distress syndrome (ARDS). This retrospective cohort study, utilizing data from the MIMIC-IV (v3.0) database, aimed to assess ALBI's predictive value for 28-day all-cause mortality in 338 adult ARDS patients admitted to the ICU. Patients were stratified into survivors (209 cases) and nonsurvivors (129 cases), with a 28-day mortality rate of 38.2%. Multivariable Cox regression identified ALBI as an independent predictor of 28-day mortality (HR = 1.46, 95% CI: 1.09-1.95, <i>p</i>=0.011). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 61.1% (95% CI: 54.7%-67.4%) with an optimal ALBI cutoff of -1.681; Kaplan-Meier (KM) survival curves confirmed significantly higher mortality in patients with ALBI ≥-1.681 versus ALBI <-1.681 (<i>p</i>=0.0098). Subgroup analyses revealed no significant interactions between ALBI and clinical variables (interaction <i>p</i>: 0.672-0.85). These findings demonstrate ALBI's utility as a novel, independent prognostic marker for short-term mortality risk in ARDS patients.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9930648"},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682745","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":"Integrating GEO Database, Mendelian Randomization, and Molecular Docking to Identify HLA-C as a Potential Therapeutic Target for Periodontitis.","authors":"ChengJi Shi, Xinyi Ou, LiJuan Huang, XiaoXu Lei, ShuHao Xu, Menglu Ou, Wei Li, Xi Zhao","doi":"10.1155/mi/9163431","DOIUrl":"10.1155/mi/9163431","url":null,"abstract":"<p><p><b>Background:</b> Periodontitis is a chronic inflammatory disease that leads to the destruction of periodontal tissues, ultimately resulting in tooth loss. Current treatments primarily focus on mitigating inflammation and alleviating symptoms, but they often lack specificity. This study aims to explore the molecular mechanisms of periodontitis using gene expression databases (GEOs) and bioinformatics methods, combined with Mendelian randomization (MR) analysis, to identify key therapeutic targets. <b>Methods:</b> This study analyzed GSE10334 microarray data to identify differentially expressed genes (DEGs) in periodontitis using R. Weighted gene co-expression network analysis (WGCNA) identified key gene modules and enrichment analysis revealed functional pathways. Immune infiltration was assessed with CIBERSORT and MR explored human leukocyte antigen C's (HLA-C's) role. Single-cell analysis using Seurat identified cell types and CellChat mapped cell communication. Molecular docking (MD) and molecular dynamic simulations were used to validate the interaction between the hub target genes and the potential drug. <b>Results:</b> Differential expression analysis identified 167 DEGs in periodontitis. WGCNA revealed a strong association with the blue module. MR analysis confirmed HLA-C as a risk factor. Single-cell RNA sequencing (scRNA-seq) showed elevated plasmablasts and HLA-C expression. MD and molecular dynamic simulation analysis identified metronidazole as a potential drug with stable binding to HLA-C, forming a stable complex with no significant conformational changes during the 100 ns simulation period. <b>Conclusion:</b> This study identifies HLA-C as a potential therapeutic target for periodontitis, with MD studies and molecular dynamic simulations highlighting metronidazole as a potential treatment. These findings provide new insights into periodontitis pathogenesis and potential therapeutic strategies.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9163431"},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682746","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":"The Effects of Probiotic-Prebiotic Use on Acute Inflammatory Parameters in Patients Receiving Pelvic Radiotherapy: A Prospective Multicenter Study.","authors":"Muge Akmansu, Sefika Dincer, Esra Kaytan Saglam, Zuleyha Akgun, Hatice Pasaoglu","doi":"10.1155/mi/1441225","DOIUrl":"10.1155/mi/1441225","url":null,"abstract":"<p><p><b>Background:</b> This is the first prospective clinical study to evaluate the impact of prebiotic and probiotic use on acute radiation-induced pelvic side effects and associated changes in serum cytokine levels in patients with pelvic malignancies. <b>Methods:</b> This multicenter prospective study included 80 patients with pelvic cancers treated at two centers between 2021 and 2023. Patients were divided into three groups: probiotic + prebiotic, prebiotic only, and nonsupplemented. Serum cytokine levels (tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6) and radiation-related side effect scores were assessed at the beginning of pelvic radiotherapy (RT) and again at the fifth week. Based on data normality, the Wilcoxon signed-rank test was used for statistical analysis. <b>Results:</b> According to side effect scores, in the prebiotic-only group, a modest yet statistically significant increase in fecal incontinence (FI; <i>p</i>=0.040) and blood and mucus in the stool (BMS; <i>p</i>=0.049) was observed. Conversely, the probiotic + prebiotic group showed a significant increase in dysuria (<i>p</i>=0.001) and impotence (<i>p</i>=0.016). IL-6 levels significantly increased in the prebiotic-only group (<i>p</i>=0.035), while TNF-α levels rose significantly in the group without any nutritional support (<i>p</i>=0.025). No significant increase in cytokine levels or intestinal side effects was observed in the combined probiotic + prebiotic group (<i>p</i>  > 0.05 for all comparisons). <b>Conclusions:</b> The absence of a rise in cytokine levels and intestinal toxicity in the probiotic + prebiotic group suggests that probiotics may play a role in mitigating radiation-induced intestinal side effects and inflammatory responses.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"1441225"},"PeriodicalIF":4.4,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682747","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":"Lymphocyte-to-Monocyte Ratio and All-Cause Mortality in Populations With Abdominal Aortic Calcification: A Prospective Cohort Study.","authors":"Jingjing Huang, Chunyong Chen","doi":"10.1155/mi/9358261","DOIUrl":"10.1155/mi/9358261","url":null,"abstract":"<p><p><b>Objective:</b> The identification of reliable prognostic markers is essential for the effective management of abdominal aortic calcification (AAC). This research focused on assessing whether the lymphocyte-to-monocyte ratio (LMR) correlates with long-term mortality risk in the AAC population. <b>Methods:</b> This analysis included 888 adults with AAC from National Health and Nutrition Examination Survey (NHANES) 2013-2014. Mortality risk was assessed using Cox proportional hazards models and Kaplan-Meier curves. Nonlinear associations between the LMR and mortality were examined with restricted cubic spline (RCS). The predictive ability was evaluated by time-dependent receiver operating characteristic (ROC) analysis. <b>Results:</b> Over median follow-up for 71 months, 145 deaths were recorded. After adjusting for covariates, higher LMR was found to be significantly associated with a reduced risk of all-cause mortality, with a 28% decrease in risk per one-unit increment in LMR (hazard ratio; HR = 0.72, 95% confidence interval (CI): 0.57-0.91, <i>p</i>=0.02). This was consistent across quartiles. A nonlinear relationship was noted; below LMR 4.49, risk decreased (HR = 0.49, 95% CI: 0.40-0.60, <i>p</i> < 0.0001); above it, LMR was not significantly linked to mortality (HR = 1.14, 95% CI: 0.77-1.7, <i>p</i>=0.51). The area under the curve (AUC) for 2-, 4-, and 6-year survival were 0.647, 0.707, and 0.682, respectively. <b>Conclusions:</b> Higher LMR is significantly associated with lower all-cause mortality in individuals with AAC, suggesting its potential utility as a prognostic marker in this population.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9358261"},"PeriodicalIF":4.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675250","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":"HMGB1 Exacerbates Intestinal Barrier Damage by Inducing Ferroptosis Through the TLR4/NF-κB/GPX4 Pathway in Ulcerative Colitis.","authors":"Nannan Zhu, Xiaoyuan Ge, Lixue Zhang, Xinwen Chen, Weizhen Xiang, Qiao Mei","doi":"10.1155/mi/2395557","DOIUrl":"10.1155/mi/2395557","url":null,"abstract":"<p><p><b>Background:</b> Intestinal barrier dysfunction and persistent inflammatory response are key pathophysiologic features of ulcerative colitis (UC). High mobility group box-1 protein (HMGB1), an important inflammatory mediator and immunomodulatory factor, has been shown to be involved in the pathogenesis of UC. However, the association between HMGB1 and intestinal barrier dysfunction is unclear. <b>Methods:</b> In this study, we investigated the mechanism of HMGB1 driving intestinal barrier damage by integrating clinical data, animal models, and cellular experiments in UC. First, HMGB1 levels and its correlation with intestinal barrier protein expression in UC patients were verified based on Gene Expression Omnibus (GEO) dataset GSE75214 analysis and western blotting (WB) assay. Subsequently, colitis was induced in C57BL/6J mice using dextran sodium sulfate (DSS) and intervened with dipotassium glycyrrhizinate (DPG), and the effects of HMGB1 on colonic inflammation, ferroptosis, and intestinal barrier were assessed by histopathological scoring, qRT-PCR, enzyme-linked immunosorbent assay (ELISA), WB assay, immunofluorescence, and transmission electron microscopy (TEM) examination. Lastly, the influence of HMGB1 on ferroptosis-related genes expression, TLR4/NF-κB/GPX4 pathway activation and intestinal barrier damage were revealed by transepithelial electrical resistance (TEER) value measures, FITC-dextran permeability detections, qRT-PCR, and WB assays in vitro Caco-2 cell models. <b>Results:</b> HMGB1 expression was significantly elevated in colonic tissues of UC patients (especially in active stage), and was negatively correlated with barrier protein expression. In DSS-induced colitis mouse model, HMGB1 upregulation accompanied by changes in TLR4, NF-κB, and GPX4 expression and ferroptosis-related genes upregulation, while inhibition of HMGB1 attenuated inflammation, restored barrier function, and reversed ferroptosis. Moreover, cellular experiments further confirmed HMGB1 induced ferroptosis and intestinal barrier damage in Caco-2 cells via the TLR4/NF-κB/GPX4 pathway. <b>Conclusion:</b> Our results suggest that HMGB1 drives ferroptosis through the TLR4/NF-κB/GPX4 signaling pathway, thereby exacerbating intestinal inflammation and barrier damage in UC. Targeting this pathway may provide a novel therapeutic strategy for UC.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2395557"},"PeriodicalIF":4.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675249","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}