Journal of Inflammation Research最新文献

{"title":"White Matter Anomaly Associated Cognitive Impairment During Systemic Inflammation Is Related to CX3CR1 Mediated Microglia-Node Interactions That Impacts the Conductive Function of Axons.","authors":"Xue Shi, Jingdong Zhang, Huangying Zhao, Xinglong Yang, Feng Gao","doi":"10.2147/JIR.S513429","DOIUrl":"10.2147/JIR.S513429","url":null,"abstract":"<p><strong>Background: </strong>The effects of CX3CR1 and CCR2 deficiency on cognition are related to microglia-neuron interactions and synaptic plasticity in the hippocampus. Contact between microglia and Ranvier's nodes has been identified in the brain white matter (WM). We propose that WM anomaly associated cognitive impairment during systemic inflammation is due to the alteration of microglia-node interactions, which impacts the conductive function of axons.</p><p><strong>Methods: </strong>Novel object recognition and Y-maze tests were performed, and the corpus callosum (CC) axon compound action potential (CAP), microglia proportional area, density of microglia-node contact, and infiltrated circulating immune cells were examined in wild-type (WT), CX3CR1, and CCR2 knockout mice before and after systemic lipopolysaccharide (LPS) administration.</p><p><strong>Results: </strong>CX3CR1 deficiency significantly reduced rate of exploring new objects and new paths, decreased CC CAP and microglia-node contact compared with WT mice. CX3CR1 or CCR2 knockout diminished the microglial proportional area. Systemic LPS significantly increased microglial proportional area and immune cell infiltration but decreased time and rate of exploring new objects and new paths, declined CAP, and reduced microglia-node contact in CX3CR1 expressed mice. The absence of CX3CR1 in normal conditions deteriorated cognitive performance and CC WM tract conductive function and reduced microglia density and microglia-node contact chance. However, defects in cognitive performance and CC WM tract conductivity, and disruption of microglia-node contact by systemic LPS were protected by CX3CR1 knockout.</p><p><strong>Conclusion: </strong>CX3CR1 is involved in modulating CC WM microglia-node contact, maintaining the CC WM tract conductive function, and improving cognitive performance. In the context of systemic LPS and associated neuroinflammation, CX3CR1 seems to dominate the disruption of microglia-node communication and CC WM tract conductive function, consequently causing cognitive problem. This may be achieved primarily through CX3CR1 mediated microglia activities and activation and subordinately via the infiltration of CX3CR1^high circulating immune cells into the CC WM tract.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8477-8492"},"PeriodicalIF":4.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540510","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 Association of Polymorphisms in Interleukin-6 (IL-6), Interleukin-10 (IL-10), IL-6 Receptor, and IL-10 Receptor Genes with the Risk of Pediatric Inflammatory Bowel Disease.","authors":"Paulina Krawiec, Monika Lejman, Elżbieta Pac-Kożuchowska","doi":"10.2147/JIR.S524632","DOIUrl":"10.2147/JIR.S524632","url":null,"abstract":"<p><strong>Purpose: </strong>Inflammatory bowel disease (IBD) results from a complex interplay between genetic, immune, and environmental factors. Despite a significant advancement in genetic studies, until now, little is known about genotype-phenotype correlations in children with IBD. Thus, we aimed to evaluate if polymorphisms in the Interleukin-6 (IL-6), Interleukin-10 (IL-10), IL-6 receptor, and IL-10 receptor genes are associated with the risk for pediatric IBD, its phenotype and severity.</p><p><strong>Patients and methods: </strong>We enrolled 50 children with IBD in the study group and 20 healthy children to the control group. Demographic and clinical data of the subjects were collected from available electronic medical records. The DNA was extracted from peripheral blood samples of all individuals. TaqMan^® single nucleotide polymorphism (SNP) genotyping assays were used to detect IL-10 variants RS3024505 and RS1800872, IL-10RA RS3135932, IL-10RB RS2834167, IL-6 RS10499563, and IL-6R RS4537545. A binary logistic regression model was used to evaluate the association between SNP's and the risk of IBD, IBD onset, phenotype, and the need to use of steroids or biologics.</p><p><strong>Results: </strong>There was a significant difference in the genotype distribution of IL-6 RS10499563 between patients with IBD and control group (χ2 = 10.96, p = 0.004). The distribution of genotype CT at IL-6 RS10499563 was higher, whereas the distribution of genotype CC and TT at IL-6 RS10499563 was lower in children compared to controls. There were no significant differences in the distribution of the other SNPs between the study and control groups. We found a significant association between the genotype CT at IL-6 RS10499563 and the risk of ulcerative colitis (OR 13.41; 95% CI: 1.58-114.26; p = 0.02), but not Crohn's disease (OR 7.60; 95% CI: 0.82-70.16; p = 0.07).</p><p><strong>Conclusion: </strong>In this study, we found a significant association between the genotype CT at IL-6 RS10499563 and the risk of ulcerative colitis in children.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8389-8397"},"PeriodicalIF":4.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528298","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":"NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy: Pathogenic Mechanisms and Therapeutic Targets.","authors":"Yichao Chen, Riqiu Chen, Xiaozhen Ji, Zhifu Zeng, Changrong Guan","doi":"10.2147/JIR.S524246","DOIUrl":"10.2147/JIR.S524246","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a prevalent microangiopathic manifestation of diabetes mellitus (DM) and a pathological sequela of chronic glycemic disorders, characterized by several pathological features including glomerulosclerosis, podocyte loss, tubular epithelial atrophy and abnormal extracellular matrix accumulation. A growing body of research has underscored that chronic inflammatory microenvironments play a central role in the progression of DN. Pyroptosis, a newly defined form of programmed inflammatory necrosis, operates through the following molecular mechanism: inflammasome activation, gasdermin D (GSDMD)-mediated plasma membrane perforation and pro-inflammatory mediator release. Pyroptosis is triggered by the activation of the NOD-like receptor 3 (NLRP3) inflammasome. Classical (caspase-1) or non-classical (caspase-4/5/11) pathways activate pyroptosis by cleaving GSDMD, inducing enzymatic fragmentation of the GSDMD protein. GSDMD-N-terminal domain oligomerizes to form transmembrane pores, which further disrupt cellular osmotic homeostasis as well as membrane integrity. Inflammatory cascades are triggered when IL-1 and IL-18 are released as a result of subsequent cell lysis. This review systematically elucidates the pathobiological interplay between pyroptosis regulatory networks and the pathogenesis of DN and summarizes potential therapeutic compounds that mitigate pyroptosis by inhibiting NLRP3 inflammasome activation or blocking GSDMD pore formation. Preclinical studies suggest that targeting pyroptosis-related signaling molecules including NLRP3, caspase-1 and GSDMD may alleviate renal injury by suppressing inflammation-driven fibrosis and ameliorating glomerular dysfunction. Current studies emphasize that regulating pyroptosis mechanisms could slow DN progression, providing novel insights into the development of nephroprotective strategies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8399-8418"},"PeriodicalIF":4.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528295","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":"Diagnostic and Predictive Values of Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Sepsis: A Multi-Center Prospective Clinical Study.","authors":"Kaifei Wang, Youchen Zhang, Lei Sang, Ye Hu, Longxiang Su, Sheling Xie, Kun Xiao, Jianqiao Xu, Jiang Wang, Fei Xie, Guangfa Zhu, Shihui Fu, Lixin Xie","doi":"10.2147/JIR.S519333","DOIUrl":"10.2147/JIR.S519333","url":null,"abstract":"<p><strong>Objective: </strong>To determine diagnostic values of serum and urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in sepsis including septic shock and their predictive values for clinical prognosis and sepsis-associated acute kidney injury (AKI).</p><p><strong>Methods: </strong>A multi-center prospective research method was used to enroll patients with sepsis.</p><p><strong>Results: </strong>A total of 586 cases were studied, including 238 patients with sepsis and 348 healthy individuals. In the sepsis group, 84 patients (35.3%) were diagnosed with septic shock, and 93 patients (38.1%) were diagnosed with AKI. The area under the Receiver Operating Characteristic curve (AUC) for diagnosing sepsis was 0.892 (0.862-0.922). When the cut-off value was 295 pg/mL, the sensitivity was 76.8%, and the specificity was 89.1%. The AUC for predicting AKI was 0.803 (0.739-0.866). When the cut-off value was 485 pg/mL, the sensitivity was 88.4%, and the specificity was 65.8%.</p><p><strong>Conclusion: </strong>sTREM-1 is a good indicator for the diagnosis of sepsis and septic shock and significantly correlated with clinical prognosis and sepsis-associated AKI in patients with sepsis. Diagnostic and predictive values of sTREM-1 may be related to inflammatory storm mediated by TREM-1. Further mechanistic explanation or preliminary evidence in combination with clinical study with more patients will benefit for supporting diagnostic and predictive utilities of sTREM-1 in sepsis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8419-8427"},"PeriodicalIF":4.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528321","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":"Machine Learning and Experimental Validation Reveal MYH11 as a Novel Prognostic Biomarker and Therapeutic Target in Bladder Cancer.","authors":"Zhiyong Tan, Xiaorong Chen, Shi Fu, Yinglong Huang, Haihao Li, Chen Gong, Dihao Lv, Chadanfeng Yang, Jiansong Wang, Mingxia Ding, Haifeng Wang","doi":"10.2147/JIR.S519719","DOIUrl":"10.2147/JIR.S519719","url":null,"abstract":"<p><strong>Introduction: </strong>Bladder cancer (BCa) is one of the top ten most common cancers, yet its underlying mechanisms remain unclear. This study aimed to explore the potential molecular mechanisms of BCa using multi-omics and single-cell analysis.</p><p><strong>Methods: </strong>First, differential analysis of transcriptome data related to BCa from public databases was performed, and a risk model was then developed using 101 different machine learning algorithms to determine prognostic genes, followed by independent prognostic analysis to construct a nomogram. Immune infiltration analysis was performed to explore the impact of prognostic genes on the tumor microenvironment. Metabolomics, proteomics, and post-translational modification data from BCa tumor and adjacent non-tumor tissues were used to explore the relationships between prognostic genes and various omics levels. Finally, single-cell analysis identified key cells involved in BCa pathogenesis, and in vitro experiments validated the expression and function of key genes.</p><p><strong>Results: </strong>The risk model constructed by 8 prognostic genes identified using 101 algorithms effectively predicted the survival outcomes of BCa patients. Furthermore, risk scores, pathological T stage, and pathological N stage were confirmed as independent prognostic factors for the nomogram construction. Interestingly, high-risk patients showed a significantly lower response to PD-L1 treatment, with higher TIDE scores. Omics analysis revealed a close relationship between prognostic genes and proteomics, metabolomics, and post-translational modifications. Specifically, FLNC and MYH11 may influence BCa progression through phosphorylation and succinylation. Single-cell analysis identified fibroblasts as key cells in BCa. Functional experiments showed that MYH11 knockdown promoted cell proliferation, migration, and invasion.</p><p><strong>Conclusion: </strong>This study identified 8 prognostic genes to construct a risk model, and suggest that MYH11 is a potential diagnostic and prognostic biomarker for BCa.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8357-8387"},"PeriodicalIF":4.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528293","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":"Exploring the Correlation Between Psychological Stress, Anxiety, and Periodontitis Among University Students: A Cross-Sectional Investigation.","authors":"Shuyu Xu, Xuehan Zhang, Ruonan Gong, Xuanzhi Huang, Min Zhang","doi":"10.2147/JIR.S530138","DOIUrl":"10.2147/JIR.S530138","url":null,"abstract":"<p><strong>Objective: </strong>Periodontitis is a prevalent chronic inflammatory disease, with growing evidence suggesting a link to psychological factors such as stress and anxiety. University students, who frequently experience elevated psychological stress, may be particularly susceptible to periodontal issues. This study aimed to examine the relationship between stress levels, anxiety status, and periodontitis in university students, and to assess the potential influence of psychological factors on periodontal health.</p><p><strong>Methods: </strong>The study sample comprised 240 university students. Participants were categorized post hoc according to their periodontal status and psychological assessment scores. Periodontal health was evaluated using the Community Periodontal Index (CPI), while stress and anxiety levels were measured with the Perceived Stress Scale-14 (PSS-14) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. Statistical analyses included chi-square tests and multivariable logistic regression models to examine associations between psychological factors and periodontitis, adjusting for potential confounding variables.</p><p><strong>Results: </strong>Among the participants (mean age: 21.70 ± 3.16 years), 43.3% were diagnosed with periodontitis. The mean age was 21.78 ± 3.32 years in the non-periodontitis group and 21.24 ± 2.06 years in the periodontitis group. Anxiety was prevalent: 33.8% had no anxiety, 30.8% had mild, 22.1% had moderate, and 13.3% had severe anxiety. Reported stress levels were 35.0% normal, 48.8% high, and 16.3% very high. Anxiety levels were significantly associated with an increased risk of periodontitis (<i>P</i> < 0.001). After adjusting for a range of potential confounders, including but not limited to gender, age, education level, smoking, and oral hygiene practices, individuals with mild, moderate, and severe anxiety had 8.391 (95% CI: 2.776-25.362), 11.423 (95% CI: 3.116-41.872), and 46.196 (95% CI: 10.414-204.921) times higher odds of developing periodontitis, respectively, compared to those without anxiety. In contrast, stress levels were not significantly associated with periodontitis after adjustment (<i>P</i> > 0.05).</p><p><strong>Conclusion: </strong>Anxiety was significantly associated with periodontitis in university students, highlighting the importance of addressing anxiety as part of periodontal disease prevention and management strategies in this population.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8317-8329"},"PeriodicalIF":4.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528292","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":"Thyroid Stimulating Hormone May Facilitates Adipose Tissue Insulin Resistance by Inducing M1 Macrophage Polarization.","authors":"Mengfei Fu, Hanyu Wang, Yuhan Zhang, Liu Yang, Yang Chen, Xiao Chen, Zixuan Wang, Hui Sun","doi":"10.2147/JIR.S522062","DOIUrl":"10.2147/JIR.S522062","url":null,"abstract":"<p><strong>Background: </strong>Recent studies suggest connection between the thyroid stimulating hormone (TSH) and insulin resistance (IR). Adipose tissue is one of insulin's target tissues. However, currently the regulatory mechanism of TSH on the adipose tissue is not fully investigated yet.</p><p><strong>Methods: </strong>We constructed a subclinical hypothyroidism (SCH) mouse model induced by methimazole with elevated TSH levels and then observed its metabolic profile, adipose tissue IR, and the adipose tissue macrophages (ATMs) phenotype. In vitro, we treated RAW264.7 cells and bone marrow-derived macrophages (BMDM) to assess the effect of TSH on macrophage polarization and explore the specific underlying mechanisms.</p><p><strong>Results: </strong>SCH mice exhibited a poorer metabolic profile and an advanced adipose tissue IR. Meanwhile, the number of M1 ATMs was increased in SCH mice adipose tissue. In vitro, TSH induced endoplasmic reticulum stress in macrophages, which activated the GRP78-ATF6-CHOP signaling pathway, and further promoted M1 macrophage polarization. 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum stress inhibitor, corrected the polarization imbalance of ATMs in SCH mice adipose tissue and improved adipose tissue dysfunction and IR.</p><p><strong>Conclusion: </strong>TSH activated endoplasmic reticulum stress in macrophages, which induced the polarization of ATMs toward a pro-inflammatory M1 phenotype and promotes adipose tissue IR. Our findings highlight the possible relationship of TSH with immunity and metabolism.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8331-8343"},"PeriodicalIF":4.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528299","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":"Cytokine Signatures as Biomarkers of Clinical Remission in Rheumatoid Arthritis.","authors":"Wei Su, Yang Xiao, Xiaohong Chen, Yan Wu, Bitao Wu, Qiang Yang, Bi Peng, Jie Tang, Yuwei Yang","doi":"10.2147/JIR.S527601","DOIUrl":"10.2147/JIR.S527601","url":null,"abstract":"<p><strong>Objective: </strong>Variations in cytokine levels have been observed in patients with rheumatoid arthritis (RA), which contribute to immune dysfunction. This study aimed to investigate the potential of intricate cytokine networks for predicting the clinical remission of RA.</p><p><strong>Methods: </strong>In total, 164 patients with RA and 69 healthy individuals were included in this study. We investigated the levels of interleukins (ILs, including IL1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12P70, and IL17), interferons (IFNs, including IFNα and IFNγ), tumor necrosis factor-alpha (TNFα), and immunoinflammatory markers, and subsequently analyzed their association and diagnostic potential in RA remission.</p><p><strong>Results: </strong>In all patients with RA, the prevalence of the release of more than six or seven cytokines was 25.0% or 18.9%, respectively, and presented nearly or the highest consistency with the prevalence of non-remission RA (<i>Kappa</i>=0.678 or 0.682, respectively, <i>P</i><0.001). All the 12 cytokines examined were significantly associated with non-remission of RA in both Spearman correlation analysis (<i>ρ</i>=0.28~0.58, <i>P</i><0.017) and univariate logistic regression analysis (<i>OR</i>=1.005~1.546, all <i>P</i><0.05). However, multivariate analysis identified only IL-6, IL12P70, and TNFα as independently associated with non-remission RA (<i>OR</i>=1.003~1.460, all <i>P</i><0.05). For the diagnosis of clinical remission of RA, the release patterns of these three cytokines yielded areas under the curve of 0.941 and 0.926 in the modeling and validation groups, respectively, with sensitivities of 88.9% and 87.0% and specificities of 87.5% and 87.9%, respectively.</p><p><strong>Conclusion: </strong>Our study suggests that IL6, TNFα, and IL12P70 may plot a cytokine release pattern for non-remission of RA, and are associated with its initiation, progression, and manifestation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8345-8356"},"PeriodicalIF":4.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528320","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":"Exploration and Validation of Key Genes and Immune Infiltration in Alcoholic Hepatitis.","authors":"Yingna Mei, Yitao Zheng, Xingfen Zhang, Ting Hu, Xiaoqing Zheng, Cui Zhang, Qinzhi Deng","doi":"10.2147/JIR.S514515","DOIUrl":"10.2147/JIR.S514515","url":null,"abstract":"<p><strong>Objective: </strong>Apart from alcohol abstinence and glucocorticoids, there is still no effective treatment to improve alcoholic hepatitis, and the specific mechanism of its pathogenesis is still unclear.</p><p><strong>Methods: </strong>We screened the differential genes in GEO alcoholic hepatitis database by differential analysis and screened the eQTL genes that have causal relationship with alcoholic hepatitis by Mendelian randomization analysis. The intersection of differential genes and eQTL genes was used to obtain candidate genes. The candidate genes were then screened out by machine learning, and their expression was further verified in clinical patients and mice with alcoholic hepatitis. Based on key genes, pathway analysis via single-gene GSEA analysis and immune microenvironment analysis via ssGSEA analysis were conducted to explore the relationship between key genes and immune microenvironment. Finally, regulatory relationship between key genes and immune cells was explored based on cell experiments.</p><p><strong>Results: </strong>Based on the GEO Alcoholic hepatitis database (GSE28619 and GSE142530) and Mendelian randomization of eQTL genes, we obtained 17 candidate genes. We then obtained two key genes (CXCL8 and CTNNA1) through lasso and random forest tree algorithms. CXCL8 and CTNNA1 were highly expressed in the alcoholic hepatitis group, which were verified in clinical patients and mice. Through single-gene GSEA analysis, two key genes were identified to be enriched in the antigen presentation pathway. At the same time, the alcoholic hepatitis group had obvious immune infiltration disorder, and two key genes were correlated with immune environment via correlation analysis. B cells and NKT cells exhibited the highest correlation with key genes. In alcoholic hepatitis mice, liver infiltration of B cells and NKT cells was verified. Through cell experiments, ethanol exposure increased CTNNA1 and CXCL8 expression in NKT and B cells, enhancing inflammatory cytokine release and suppressing IgG production, respectively. Silencing CXCL8 and CTNNA1 reversed these effects.</p><p><strong>Conclusion: </strong>These results suggested that CXCL8 and CTNNA1 were potential biomarkers for alcoholic hepatitis, and might be new targets for the treatment of alcoholic hepatitis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8243-8262"},"PeriodicalIF":4.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528291","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":"NLRP3 Inflammasome Activation in Liver Disorders: From Molecular Pathways to Therapeutic Strategies.","authors":"Wenxiang Ma, Yilei Wang, Jinfeng Liu","doi":"10.2147/JIR.S532908","DOIUrl":"10.2147/JIR.S532908","url":null,"abstract":"<p><p>The NOD-like receptor protein 3 (NLRP3) inflammasome, a cytosolic multi-protein complex, detects danger signals released by injured cells and pathogens. It plays a critical role in the pathogenesis of various acute and chronic liver diseases. NLRP3 activation triggers caspase-1-mediated processing and secretion of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Unlike other inflammatory pathways, NLRP3 activation requires two signals, ensuring a tight control over inflammation. Caspase-1 activation further amplifies the response by cleaving IL-1β, a potent pro-inflammatory mediator. Extensive research suggests the NLRP3 inflammasome contributes significantly to hepatocyte injury, immune cell activation, and the perpetuation of inflammatory responses in various human and experimental liver disease models. This review comprehensively examines NLRP3 inflammasome activation and its functional consequences in the context of liver injury and disease progression, including conditions such as alcoholic liver disease (ALD), metabolic dysfunction-associated fatty liver disease (MAFLD), viral hepatitis, hepatic fibrosis, and drug-induced liver injury (DILI). We specifically highlight emerging therapeutic strategies targeting NLRP3 inflammasome that show translational promise in attenuating liver inflammation and fibrosis. This review provides a theoretical framework and reference for the development of novel therapeutics targeting the NLRP3 inflammasome in liver injury and chronic liver diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8277-8294"},"PeriodicalIF":4.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528294","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}