Journal of Inflammation Research最新文献

{"title":"The Relationship Between Immune-Inflammatory Indexes and the Severity of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: A Cross-Sectional Study at a Tertiary Hospital in China.","authors":"Yifan Wu, Jiayi Sheng, Xinwei Liu, Yongneng Huang, Yuwei Zhang, Ninghan Feng","doi":"10.2147/JIR.S523193","DOIUrl":"10.2147/JIR.S523193","url":null,"abstract":"<p><strong>Purpose: </strong>Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are common urogenital system diseases in elderly men and can cause serious complications when the disease progresses to moderate and severe stages. Early and accurate identification is of great significance for prevention, treatment, and prognosis assessment. However, there is still a lack of effective and simple predictive indicators. This study aims to investigate whether immune-inflammatory markers derived from complete blood count (CBC) exhibit an independent association with the severity of BPH/LUTS.</p><p><strong>Patients and methods: </strong>This study included a total of 698 BPH/LUTS patients who met the inclusion criteria at the Department of Urology, Jiangnan University Medical Center. According to the International Prostate Symptom Score (IPSS) score, patients were divided into a mild group and a moderate-to-severe group. Binary logistic regression analysis was used to explore the association between the severity of BPH/LUTS and the neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory response index (SIRI), and systemic immune-inflammatory index (SII).</p><p><strong>Results: </strong>The median age of the participants was 70.00 (65.00, 75.00) years. After adjusting for confounding factors, the NLR, SIRI, and SII were positively correlated with the severity of BPH/LUTS. Compared with the lowest quartile, the highest quartile of NLR (OR = 6.20 [3.49-11.02]), SIRI (OR = 7.49 [4.15-13.50]), and SII (OR =7.85 [4.73-16.61]) were most significantly associated with the risk of BPH/LUTS aggravation. In subgroups stratified by age, diet, physical activity, cardiovascular disease, and diabetes, NLR, SIRI, and SII were positively correlated with BPH/LUTS severity. In subgroups defined by waist circumference and dyslipidemia, SIRI and SII were positively correlated with BPH/LUTS severity. In the smoking subgroup, only SIRI showed a positive correlation with BPH/LUTS severity.</p><p><strong>Conclusion: </strong>The findings suggest that NLR, SIRI, and SII are affordable and readily available detection methods that can be used as indicators for assessing the severity of BPH/LUTS.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8509-8523"},"PeriodicalIF":4.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540509","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":"Comment on \"Predictive Value of Advanced Lung Cancer Inflammation Index and Development of a Nomogram for Prognosis in Patients with Cervical Cancer Treated with Radiotherapy\" [Letter].","authors":"Kailang Li","doi":"10.2147/JIR.S542961","DOIUrl":"10.2147/JIR.S542961","url":null,"abstract":"","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8525-8526"},"PeriodicalIF":4.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540505","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":"Host Immune Response to <i>Mycobacterium tuberculosis</i> Infection: Implications for Vaccine Development.","authors":"Qianfei Liu, Songnian Que, Yixuan Qiu, Mingxing Tang, Shaohua Liu, Guanteng Yang, Yuxiang Wang, Ang Deng, Xiaojiang Hu, Xuehui Lian, Qile Gao","doi":"10.2147/JIR.S517034","DOIUrl":"10.2147/JIR.S517034","url":null,"abstract":"<p><p>Tuberculosis (TB) is an infectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) infection, including pulmonary tuberculosis and extrapulmonary tuberculosis. About a quarter of the people in the world are infected with TB, but only 5-10% of them will progress to active TB, posing a major challenge to the eradication of TB. The study of the host immune response to <i>Mtb</i> infection is a key aspect of the development of effective vaccines and immunotherapies to eradicate tuberculosis. In this review, we delve into the overview of animal models of TB infection and the host's innate and adaptive immune responses to <i>Mtb</i> infection. We discuss how <i>Mtb</i> is recognized and phagocytosed by macrophages, how it evades immune responses, the recruitment and mobilization of neutrophils and monocytes, the role of natural killer cells during the infection process, how dendritic cells initiate adaptive immunity, the important roles of CD4⁺ T cells and their subtypes in TB infection, how CD8⁺ T cells exert cytotoxic functions, and how B cells produce antibodies and exhibit memory characteristics to eliminate pathogens. Furthermore, we review the tuberculosis vaccines currently entering clinical trials, emphasizing that studying the host's immune responses following <i>Mtb</i> infection is crucial for the development of more effective vaccines, providing a theoretical foundation and direction for the treatment of tuberculosis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8429-8445"},"PeriodicalIF":4.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540507","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":"IFNα/JAK/STAT1 Axis-Induced FBXO4 Modulates Muscle Cell Differentiation via β-Catenin Degradation in Dermatomyositis.","authors":"Liguo Yin, Hanbo Yang, Min Fu, Yanyan Bai, Naiwen Hu, Hongsheng Sun","doi":"10.2147/JIR.S506056","DOIUrl":"10.2147/JIR.S506056","url":null,"abstract":"<p><strong>Purpose: </strong>Dermatomyositis (DM) is an inflammatory myopathy characterized by chronic muscle inflammation and damage. Although the pathogenesis of DM has been widely reported to be related to chronic inflammation, the role of ubiquitin E3 ligases in DM remains unclear. In the current study, we aimed to investigate the biological roles of ubiquitin E3 ligase in DM.</p><p><strong>Methods: </strong>Deseq2 was used to screen the differential express genes in DM public datasets. Quantitative real time PCR and Western blot were used to examine the mRNA and protein levels. Co-immunoprecipitation assays were used to investigate the protein interactions between proteins. Dual-luciferase reporter assays were applied to investigate the regulation between transcription factors and targets.</p><p><strong>Results: </strong>In the current study, we screened public DM-related datasets and focused on ubiquitin-proteasome-related enzymes. Ultimately, we identified the ubiquitin E3 ligase FBXO4. FBXO4 was significantly upregulated in DM muscle tissues compared to normal controls. In human muscle cells (LHCN-M2), FBXO4 knockout led to significant upregulation of genes related to muscle cell differentiation and significant downregulation of genes enriched in cell cycle pathways, as revealed by RNA-seq. These results suggest that FBXO4 knockout promotes muscle cell differentiation. Mechanistic studies showed that FBXO4 ubiquitinates and degrades β-catenin, thereby inhibiting the Wnt/β-catenin signaling pathway and suppressing muscle cell differentiation. On the other hand, FBXO4 may promote muscle cell apoptosis in DM by degrading MCL1. Additionally, we found that FBXO4 is regulated by the IFNα/JAK/STAT1 signaling pathway in DM and identified FBXO4 as a direct target of STAT1.</p><p><strong>Conclusion: </strong>In conclusion, our findings suggest that IFNα/JAK/STAT1 signaling pathway elevates the expression of FBXO4 in DM and then it contributes to muscle atrophy by inhibiting differentiation and promoting apoptosis. Targeting FBXO4 may offer a novel therapeutic approach for DM.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8527-8539"},"PeriodicalIF":4.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540508","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":"Decrease of Resolvin D1 and E1 in Patients with Chronic Epilepsy, Implicating Dysfunction of Neuroinflammation Resolution.","authors":"Hanli Li, Zhong Dong, Yujing Yang, Qibing Sun, Fengqing Lu, Ran Li, Weifeng Zhou, Wei Gui, Rupan Gao, Yu Wang","doi":"10.2147/JIR.S521679","DOIUrl":"10.2147/JIR.S521679","url":null,"abstract":"<p><strong>Objective: </strong>Inflammation resolution is mediated by specialized pro-resolving lipid mediators (SPMs). It's of high interest to understand the alterations of SPMs in chronic epilepsy.</p><p><strong>Methods: </strong>Sixty-five patients with chronic epilepsy, 43 healthy controls and 43 patients with non-inflammatory neurological disorders were enrolled in this study. Plasma and cerebrospinal fluid (CSF) levels of SPMs were measured using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Moreover, Resolvin D1 (RvD1) and resolvin E1 (RvE1), as well as pro-inflammatory factors were analyzed by enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>LC-MS-MS found several lipid mediators were altered, especially plasma (<i>P</i> = 0.014) and CSF (<i>P</i> = 0.010) RvE1 levels were decreased in patients with chronic epilepsy. Furthermore, ELISA results showed that in plasma and CSF, RvD1 and RvE1 levels were both lower in patients with chronic epilepsy, while pro-inflammatory factors were higher than in controls. Moreover, plasma RvE1 level was independently negatively associated with the National Hospital Seizure Severity Scale scores (Β = -0.00636, <i>P <</i> 0.001). While plasma RvD1 level was correlated with Mini-Mental State Examination scores (R = 0.284, <i>P</i> = 0.022).</p><p><strong>Conclusion: </strong>This study demonstrated decreased levels of RvD1 and RvE1 both in plasma and CSF in patients with chronic epilepsy, suggesting impaired resolution of inflammation in chronic epilepsy. Targeting RvD1 and RvE1 may be a novel direction worthy of further research in the treatment of chronic epilepsy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8541-8551"},"PeriodicalIF":4.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540506","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":"Mild Chronic Colitis Exacerbates Intracerebral Inflammation in Mice with Parkinson's Disease Through LRRK2-Mediated Regulation of NF-κB Activation and Inhibition of Nrf2.","authors":"Manqi Yang, Linping Ke, Yiman Geng, Piao Hu, Yao Qiu, Ziwen Liu, Xueqin Zhang, Fuxin Wan, Joe Antony Jacob, Jingling Liao","doi":"10.2147/JIR.S526777","DOIUrl":"10.2147/JIR.S526777","url":null,"abstract":"<p><strong>Background and objective: </strong>Inflammatory bowel disease (IBD) is a known risk factor for Parkinson's disease (PD). Leucine-rich repeat kinase 2 (LRRK2), a protein associated with both disease, regulates inflammation in the colon and brain. However, the precise mechanism by which LRRK2 mediates the crosstalk between intestinal inflammation and PD neuropathology remains unclear. This study aims to elucidate how LRRK2 mediates the inflammatory response in both the gut and brain.</p><p><strong>Methods: </strong>A dual-hit (DSS+MPTP) mouse model was established to induce IBD and PD, along with separate single DSS-induced colitis and MPTP-induced PD models. LRRK2 expression was analyzed in the colon and striatum. Intestinal barrier integrity (ZO-1, Occludin), dopaminergic neuron loss and inflammation (TH, Iba-1 staining in SNpc/striatum), NF-κB and Nrf2 pathways activity, and levels of inflammatory cytokines (TNF-α, IL1-β, IL-6 and IL-10) in the colon and striatum was assessed.</p><p><strong>Results: </strong>In the colon, LRRK2 expression was significantly increased in all experimental groups compared to the control, with the highest levels observed in the dual-hit group. The elevated LRRK2 expression correlated with the reduction in ZO-1 and Occludin levels and an increase in inflammatory cytokines IL1-β and TNF-α. A similar pattern of LRRK2 expression was observed in the brain. The dual-hit group exhibited increased Iba-1 expression and a significant loss of dopaminergic neurons. Furthermore, the upregulation of LRRK2 was associated with NF-κB activation and Nrf2 inhibition in the brain.</p><p><strong>Conclusion: </strong>Mild chronic colitis induced by DSS may exacerbate brain inflammation in MPTP-induced PD mice by upregulating LRRK2 expression, leading to NF-κB activation and Nrf2 inhibition. We propose that LRRK2 may play a regulatory role in the NF- κB/Nrf2 interplay in PD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8493-8507"},"PeriodicalIF":4.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553704","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":"Qimai Feiluoping Decoction Inhibits EndMT to Alleviate Pulmonary Fibrosis by Reducing PI3K/AKT/mTOR Pathway-Mediated the Restoration of Autophagy.","authors":"Jing Ma, Lu Ding, Xiaoyu Zang, Yingying Yang, Wei Zhang, Xiangyan Li, Daqing Zhao, Zepeng Zhang, Zeyu Wang, Linhua Zhao, Xiaolin Tong","doi":"10.2147/JIR.S515286","DOIUrl":"10.2147/JIR.S515286","url":null,"abstract":"<p><strong>Purpose: </strong>Pulmonary Fibrosis (PF) is a severe interstitial lung disease currently lacking effective prevention strategies. Endothelial mesenchymal transition (EndMT), a novel mechanism for fibroblast production, is closely associated with PF. The precise mechanisms underlying the contribution of EndMT-derived fibroblasts to PF, however, remain unclear.</p><p><strong>Methods: </strong>Using network pharmacology, molecular docking, and molecular dynamics, we identified the key targets and pathways through which Qimai Feiluoping decoction (QM) combats PF. EndMT and autophagy proteins were quantified in bleomycin (BLM) -induced C57BL/6 mice, human umbilical vein endothelial cells (HUVECs), and zebrafish using Western blotting (WB), quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), immunofluorescence (IF), Transwell migration assays, and transmission electron microscopy (TEM), revealing the targets and pathways through which QM mitigates PF.</p><p><strong>Results: </strong>Network pharmacology, molecular docking, and molecular dynamics suggest that QM combats PF by modulating the PI3K/AKT/mTOR pathway. Observations from the study indicated that QM was found to alleviate EndMT by restoring autophagy, primarily through inhibition of the PI3K/AKT/mTOR signaling pathway in both BLM-induced C57 mice and HUVECs. Supporting evidence from zebrafish models demonstrated that QM not only counteracts EndMT but also improves a range of vascular functional disorders and remodeling issues following EndMT.</p><p><strong>Conclusion: </strong>Our research validates the active compounds, core targets, and signaling pathways through which QM counters PF, providing valuable insights for its therapeutic application in PF management.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8447-8475"},"PeriodicalIF":4.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528296","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":"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}