Journal of Inflammation Research最新文献

{"title":"The Use of Montelukast in Pediatric Asthma and Anti-Inflammatory Effects - Easy Choice or a Balancing Act?","authors":"Aleksander Adamiec, Katarzyna Karwowska, Katarzyna Moliszewska, Karolina Dumycz, Wojciech Feleszko","doi":"10.2147/JIR.S604913","DOIUrl":"https://doi.org/10.2147/JIR.S604913","url":null,"abstract":"<p><p>Montelukast is a selective cysteinyl leukotriene receptor 1 antagonist with an established, though nuanced, role in the management of asthma and allergic rhinitis. By inhibiting leukotriene-mediated signaling, montelukast targets a pathway involved in bronchoconstriction, mucus secretion, vascular permeability, eosinophil recruitment, cytokine release, and airway remodeling. Available evidence indicates that montelukast may reduce several markers of allergic inflammation, including fractional exhaled nitric oxide, peripheral and tissue eosinophilia, eosinophil-derived mediators, adhesion molecules, selected cytokines, and markers related to airway remodeling. These effects are most consistently demonstrated in asthma and allergic rhinitis, while evidence in chronic urticaria, atopic dermatitis, and other inflammatory conditions remains limited or exploratory. Montelukast's once-daily oral administration and age-adjusted pediatric formulations make it a practical option in selected children, particularly when inhaled therapy is difficult or adherence is problematic. However, montelukast should not be regarded as a direct substitute for corticosteroid-based anti-inflammatory therapy. Current evidence and guideline positioning support its use mainly as an add-on controller, or an alternative when more efficacious treatment is contraindicated. The benefit-risk balance is further shaped by concerns regarding neuropsychiatric adverse events, especially in children, although evidence remains heterogeneous. Current data show no increased risk of severe, diagnostically coded neuropsychiatric events, yet milder sleep-related and behavioral symptoms are consistently reported, so that caution and active monitoring remain warranted. Overall, montelukast remains a biologically plausible and clinically useful therapy, but its value depends on appropriate patient selection and realistic expectations of its anti-inflammatory potential.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"604913"},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Inflammation in Osteoarthritis Pain: A Phenotype-Driven Approach.","authors":"Wei Zheng, Chuan Huang, Shen Liu, Kai Fu","doi":"10.2147/JIR.S614867","DOIUrl":"https://doi.org/10.2147/JIR.S614867","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a chronic joint disease marked by the progressive loss of articular cartilage and associated inflammatory processes, which can lead to significant pain and disability. However, the heterogeneous nature of OA has limited the effectiveness of many anti-inflammatory interventions, highlighting the need for phenotype-driven therapeutic strategies.</p><p><strong>Methods: </strong>This narrative review was conducted by searching PubMed, Web of Science, and Google Scholar from inception to June 2025. Predefined keywords included \"osteoarthritis\", \"inflammation\", \"pain\", \"synovitis\", \"effusion\", \"treatment\", \"therapy\" and \"clinical trials\". Additional relevant publications were identified through citation tracking of the included papers.</p><p><strong>Results: </strong>Our analysis of recent randomized clinical trials (RCTs) reveals a clear divergence in therapeutic efficacy, while targeted biologics (eg, TNF-α inhibitors like adalimumab and IL-1 blockers such as lutikizumab) have largely failed to meet primary pain endpoints in unselected populations, broad-spectrum immunomodulators like methotrexate (MTX) show significant promise, particularly in reducing pain and stiffness for the inflammatory phenotype. Furthermore, emerging evidence suggests that intra-articular (IA) treatments and phenotype-driven stratifications are essential to overcoming the current \"one-size-fits-all\" failure in OA drug development.</p><p><strong>Conclusion: </strong>The central message of this review is that the inconsistent efficacy of anti-inflammatory therapies in OA reflects a patient-selection problem more than a failed target: agents tested in unselected populations, including most anti-cytokine biologics, have not relieved pain, whereas signals emerge for MTX in patients with an inflammatory phenotype. Stratifying patients by imaging-defined synovitis or effusion and inflammatory biomarkers is therefore the key unmet need, and phenotype-driven trial design-rather than new molecular targets alone-offers the most promising path to effective inflammation-targeted treatment of OA pain.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"614867"},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164522","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":"Ferroptosis Profiling of Outcome-Associated Monocyte Subsets and the Potential Regulatory Role of LDHA in Early Sepsis.","authors":"Xiaoye Wang, Dan Liu, Si Li, Kun Wang","doi":"10.2147/JIR.S633372","DOIUrl":"https://doi.org/10.2147/JIR.S633372","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis carries high morbidity and mortality, and early precise intervention is critical for improving outcomes. The heterogeneity of circulating immune cells, particularly at the monocyte subset level, remains a major barrier to early risk stratification. This study aimed to identify prognosis-associated monocyte subsets and their key regulators in early sepsis, providing potential clues for early prognostic assessment and targeted intervention.</p><p><strong>Methods: </strong>We analyzed single-cell transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from patients with early sepsis and healthy controls in the GSE167363 dataset to define myeloid subsets associated with clinical outcomes. Core regulatory molecules were prioritized by intersecting differentially expressed genes (DEGs) with cell death-related gene sets, and their expression patterns were examined in bulk transcriptomic cohorts. The lead candidate was further evaluated through in vitro functional experiments and in vivo survival studies using the cecal ligation and puncture (CLP) mouse model.</p><p><strong>Results: </strong>A transitional monocyte subset defined by high <i>CD14</i> and modest <i>FCGR3A</i> expression, positioned at the intermediate node of monocyte differentiation, was markedly depleted in sepsis non-survivors. Gene Set Enrichment Analysis (GSEA) revealed ferroptosis as the predominant cell death modality in this subset among non-survivors. Lactate dehydrogenase A (LDHA) was pinpointed as a core regulatory molecule, and its differential expression was validated in independent bulk transcriptomic cohorts. In vitro assays confirmed that LDHA inhibition attenuated ferroptosis in THP-1-derived macrophages. Consistently, both myeloid-specific <i>Ldha</i> conditional knockout (cKO) and pharmacological inhibition of LDHA markedly improved the 7-day survival of CLP-induced septic mice.</p><p><strong>Conclusion: </strong>This study identifies an outcome-associated monocyte subset with a ferroptosis signature in early sepsis and suggests a potential regulatory role for LDHA in monocyte ferroptosis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"633372"},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166620","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":"Medicinal and Edible Plant-Derived Exosome-Like Nanovesicles: Promising Therapeutics and Drug Delivery Nanoplatforms.","authors":"Likang Liu, Fuji Yang, Yongmin Yan, Shihui Li","doi":"10.2147/JIR.S624415","DOIUrl":"https://doi.org/10.2147/JIR.S624415","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Medicinal and edible plant-derived exosome-like nanovesicles (MEPELNVs) have attracted considerable attention as naturally derived immunomodulatory nanoplatforms for inflammatory disease intervention, owing to their excellent biocompatibility, low immunogenicity, and abundant bioactive cargoes capable of regulating immune responses. While recent reviews have broadly surveyed plant-derived exosome-like nanovesicles (PELNVs) across diverse botanical sources or focused on general isolation technologies and drug delivery applications, a systematic synthesis that specifically centers on medicinal and edible plants and integrates isolation methodology with immunomodulatory functionality remains lacking. This review addresses this gap by concentrating on the unique dual identity of MEPELNVs that combines validated pharmacological heritage from traditional medicine with the safety profile of dietary sources, and examines how their immunomodulatory potential is shaped by upstream preparation techniques. As research has progressed, techniques for isolating and preparing these extracellular vesicles have diversified; however, significant challenges remain in improving purity, optimizing yield, and preserving their immunomodulatory and anti-inflammatory biological functions. This review comprehensively surveys current mainstream isolation and preparation methods, analyzes how each technique impacts vesicle integrity and immune-regulatory activity, and discusses their differential effects on inflammatory mediator release and immune cell functionality. Based on recent preclinical findings, we highlight the potential clinical applications of MEPELNVs in three inflammation-centric areas: first, reprogramming macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes to alleviate chronic inflammation; second, remodeling the tumor immune microenvironment by alleviating PD-L1-mediated immunosuppression; and third, ameliorating metabolic inflammation and promoting immune homeostasis in metabolic diseases. In summary, while MEPELNVs present considerable therapeutic opportunities across anti-inflammatory, anti-tumor, and metabolic disease intervention, their clinical translation is currently hindered by substantial challenges. These include the absence of standardized isolation and quality control protocols, batch-to-batch heterogeneity in vesicle yield and cargo composition, incomplete safety and toxicological profiling, poorly understood cross-kingdom regulatory mechanisms, and underdeveloped regulatory frameworks. This review critically discusses these translational barriers and proposes actionable strategies to overcome them, offering a realistic roadmap from bench to bedside. By comprehensively evaluating existing research progress, this review aims to provide theoretical support and practical technical guidance for advancing the clinical translation of MEPELNVs as novel anti-inflammatory therapeutics, ultimately promoting their bro","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"624415"},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166106","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":"Integrative Transcriptomic and Genetic Analysis Prioritizes IRF1 as a Candidate Regulatory Gene Associated with Ulcerative Colitis.","authors":"Yanyan Wang, Yuehang Chen, Hailin Wu","doi":"10.2147/JIR.S625071","DOIUrl":"10.2147/JIR.S625071","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a complex and incompletely understood pathogenesis. This study aimed to prioritize candidate genes associated with UC and characterize their potential genetic and immune-related molecular context using an integrative transcriptomic and genetic framework.</p><p><strong>Methods: </strong>Bulk transcriptomic analysis was first performed using the discovery cohort GSE87466. After duplicated gene symbols were collapsed by mean expression, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify UC-related candidate genes. Candidate genes for downstream analyses were defined by the overlap between differentially expressed genes and genes within selected WGCNA core modules. An expression quantitative trait locus-based summary-data-based Mendelian randomization (SMR) framework integrating UC genome-wide association study data with blood-derived eQTL data was subsequently applied to prioritize putative gene-disease associations. Functional enrichment analysis, CIBERSORT-based immune infiltration analysis, single-gene gene set enrichment analysis, and single-cell RNA sequencing analyses were performed to characterize the biological context of the prioritized genes. Three independent transcriptomic cohorts were used for external validation, and a small DSS-induced colitis mouse experiment was used for exploratory experimental assessment.</p><p><strong>Results: </strong>eQTL-based SMR analysis identified IRF1 and JAK2 as candidate genes associated with UC susceptibility. IRF1 was prioritized for downstream characterization based on convergent evidence from transcriptomic, immune, single-cell, and experimental analyses. IRF1 expression was associated with multiple CIBERSORT-inferred immune-cell proportions, including positive correlations with M1 macrophages, neutrophils, activated dendritic cells, and T follicular helper cells, and negative correlations with M2 macrophages and activated natural killer cells. Higher IRF1 expression was associated with interferon, NF-κB, and IL-6/JAK/STAT3 signaling pathways. Single-cell analysis showed IRF1 expression across myeloid cells, fibroblasts, endothelial cells, and epithelial cells. DSS-treated mice showed descriptively higher colonic IRF1 protein expression, providing preliminary experimental support consistent with human transcriptomic findings.</p><p><strong>Conclusion: </strong>IRF1 was prioritized as a candidate gene associated with UC and was linked to interferon-related inflammatory pathways and altered immune-cell profiles. These findings provide an integrated framework for further investigation of the potential role of IRF1 in UC. Given the use of blood-derived eQTL data and preliminary animal evidence, the findings should be considered hypothesis-generating and require further functional validation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"625071"},"PeriodicalIF":4.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136852","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":"Transcriptomic Identification and Validation of NDUFS2 in Acute Rat TMJ Synovitis and Its Functional Role in LPS-Induced Synovial Fibroblast Inflammation.","authors":"Jinghan Li, Jingpeng Zuo, Jianduan Liang, Changbin Zhang, Tao Xie, Feifei Xie, Yinzi Xin, Wei Wang","doi":"10.2147/JIR.S614759","DOIUrl":"10.2147/JIR.S614759","url":null,"abstract":"<p><strong>Purpose: </strong>Temporomandibular joint (TMJ) synovitis persistently drives TMJ osteoarthritis (TMJOA) progression. Aberrant reactive oxygen species (ROS) accumulation triggers chronic oxidative stress, amplifying synovial inflammation. This study aimed to identify candidate ROS-related genes through transcriptomic screening and explore their potential functional involvement in TMJ synovitis.</p><p><strong>Methods: </strong>Acute TMJ synovitis was induced in male Sprague-Dawley rats via intra-articular injection of Complete Freund's Adjuvant (CFA). RNA sequencing of inflamed and normal synovial tissues was performed to screen target genes by intersecting differentially expressed genes (DEGs) with ROS-related genes (ROS-RGs). The expression of the candidate gene was validated in vivo and in vitro, and in vitro functional assays were performed using lipopolysaccharide (LPS)-induced synovial fibroblasts (SFs). The functions of NDUFS2 were assessed via siRNA knockdown or plasmid overexpression, supplemented by rescue experiments using the mitochondria-targeted antioxidant Mito-TEMPO. Intracellular ROS, mitochondrial ROS (mtROS), mitochondrial membrane potential (ΔΨm), and pro-inflammatory markers (MMP13, IL-1β, TNF-α) were evaluated.</p><p><strong>Results: </strong>NDUFS2 was identified as a candidate ROS-related gene through transcriptomic screening, and Gene Set Enrichment Analysis (GSEA) linked it to signaling pathways including oxidative phosphorylation. NDUFS2 was markedly upregulated in inflamed TMJ synovial tissues and LPS-stimulated SFs. In the LPS-induced model, NDUFS2 knockdown attenuated ROS/mtROS accumulation, partially restored ΔΨm, and reduced pro-inflammatory marker expression, whereas NDUFS2 overexpression could increase ROS/mtROS levels, reduce ΔΨm, and elevate pro-inflammatory marker expression. Furthermore, rescue experiments demonstrated that scavenging mtROS with Mito-TEMPO reversed NDUFS2-mediated oxidative stress and inflammation.</p><p><strong>Conclusion: </strong>Our findings identify NDUFS2 as a key ROS-related gene associated with acute TMJ synovitis through transcriptomic screening. In vitro evidence indicates that NDUFS2 modulates inflammatory responses in synovial fibroblasts via mtROS-mediated mitochondrial oxidative stress. These findings provide an experimental basis for further exploration of TMJ synovitis pathogenesis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"614759"},"PeriodicalIF":4.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110844","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":"Soluble Epoxide Hydrolase in Inflammatory and Immune Diseases: A Bibliometric and Visualization Analysis in 2000-2025.","authors":"Tian Han, Zhen Yang, Weiye Zhang, Wen Hou, Zhongyang Shen","doi":"10.2147/JIR.S621758","DOIUrl":"https://doi.org/10.2147/JIR.S621758","url":null,"abstract":"<p><strong>Background: </strong>Soluble epoxide hydrolase (sEH) is extensively involved in the pathophysiological processes of inflammatory and immune diseases. This study aims to systematically analyze the current research status, cooperation networks, and evolutionary trends in this field using bibliometric methods to provide a reference for future basic research and clinical translation.</p><p><strong>Methods: </strong>Articles and reviews related to sEH, inflammation, and immunity published from January 1, 2000, to December 31, 2025, were retrieved from the Web of Science (WoS) and Scopus databases. VOSviewer, CiteSpace, and the bibliometrix package in R were utilized to perform visualization analysis of publication volume, distribution of countries and institutions, core authors, highly cited publications, and keywords.</p><p><strong>Results: </strong>A total of 2240 publications were included in this study. The annual publication volume exhibited a steady upward trend, reaching a periodic peak in 2021. The United States ranked first globally in publication volume (908 publications). The University of California was the most contributing institution, and its scholar, Bruce Hammock, held a core position in both publication volume and academic impact. PNAS was the most cited journal in this field. Current research frontiers focus on pharmacodynamics, molecular docking, protein mechanisms, lipid chromatography mass spectrometry, and clinical translation studies.</p><p><strong>Conclusion: </strong>This study presents the first systematic knowledge map of sEH in inflammatory and immune diseases. sEH inhibitors have emerged as highly promising targets for anti-inflammatory and immunomodulatory therapy. Clinical translation will be the key development direction for this field in the future.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"621758"},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110834","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":"TUDCA-3S is Associated with Acute Pancreatitis Severity and Pro-Inflammatory Macrophage Activation Involving S100A8/IL-17 Signaling.","authors":"Linfeng Yang, Duan Yan, Jun Yu, Yi Liu, Yiming Zhang, Pengsheng Yi, Dawei Deng","doi":"10.2147/JIR.S620803","DOIUrl":"https://doi.org/10.2147/JIR.S620803","url":null,"abstract":"<p><strong>Objective: </strong>Early identification of patients at risk of severe acute pancreatitis (SAP) remains challenging, and the contribution of sulfated bile-acid metabolites to AP-associated inflammatory responses remains incompletely understood. This study investigated the association between serum TUDCA-3S and AP severity and explored its effects on inflammatory macrophage activation in vitro.</p><p><strong>Methods: </strong>The study cohort comprised 100 patients with acute pancreatitis (AP) and 50 healthy controls. Serum TUDCA-3S levels were quantified using targeted metabolomics, and associations with disease severity and receiver operating characteristic (ROC) performance were evaluated. An LPS-stimulated RAW264.7 inflammatory macrophage model was used to examine cellular responses associated with TUDCA-3S exposure. Flow cytometry, RT-qPCR, Western blotting, transcriptomics, untargeted metabolomics, lipidomics, and S100A8 knockdown were used for further characterization.</p><p><strong>Results: </strong>Serum TUDCA-3S levels differed significantly among the study groups, with the highest median level observed in patients with SAP. TUDCA-3S distinguished AP patients from healthy controls with an AUC of 0.873. However, its performance for severity discrimination was substantially lower, with an AUC of 0.534 for MAP versus MSAP and 0.714 for MAP/MSAP versus SAP. In LPS-stimulated RAW264.7 macrophages, TUDCA-3S exposure was associated with enhanced M1-related inflammatory features and increased S100A8 and IL-17A expression. S100A8 knockdown attenuated M1-associated markers and IL-17A expression. Transcriptomic, untargeted metabolomic, and lipidomic analyses further identified inflammatory and lipid-metabolic changes associated with TUDCA-3S exposure.</p><p><strong>Conclusion: </strong>Serum TUDCA-3S is associated with AP and disease severity, although its discriminatory performance across AP severity categories is limited to moderate. The in vitro findings support an association between TUDCA-3S exposure and pro-inflammatory macrophage features involving S100A8-associated IL-17A signaling and metabolic remodeling. These findings are exploratory and require independent clinical and experimental validation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"620803"},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110913","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":"Integrated Single-Cell and Bulk RNA Sequencing Reveals Inflammatory Microenvironment and Glycolysis-Driven Epithelial Proliferation in Benign Prostatic Hyperplasia.","authors":"Jianchao Ge, Wei Jiao, Wandong Yu, Guowei Shi, Xilong Wang, Jun Zhang","doi":"10.2147/JIR.S636515","DOIUrl":"https://doi.org/10.2147/JIR.S636515","url":null,"abstract":"<p><strong>Background: </strong>Benign prostatic hyperplasia (BPH) is a prevalent condition and a leading cause of urinary dysfunction in middle-aged and elderly men. The hyperplasia of prostate stromal and epithelial cells enlarges the prostate, compressing the bladder outlet and resulting in obstructive symptoms. However, the crosstalk between the inflammatory microenvironment and metabolic alterations in BPH remains poorly understood.</p><p><strong>Methods: </strong>This study integrated single-cell RNA sequencing and spatial transcriptomics datasets to characterize the biological and metabolic properties of BPH. Analyses were conducted using CellChat, CytoTRACE, Monocle, and SCENIC, alongside functional pathway exploration. The CARD algorithm mapped single-cell clusters onto spatial transcriptomics, enabling subtype-specific investigations of cell dependencies and pathway activities. Bulk RNA sequencing of rat prostate tissues and in vivo experiments were performed to validate these findings.</p><p><strong>Results: </strong>Our analysis revealed a pro-inflammatory microenvironment in BPH, marked by a higher ratio of M1-like macrophages and an enriched cell-cell interaction network that promote disease progression. Significant alterations in epithelial cells were identified, with basal epithelial (BE) cells playing a pivotal role in driving hyperplasia. SCENIC and metabolic pathway analyses demonstrated that glycolysis-mediated BE cell proliferation is a crucial mechanism in BPH progression. Bulk RNA sequencing of rat prostate tissues further confirmed glycolysis pathway enrichment in BPH models. Notably, glycolysis inhibitors demonstrated therapeutic effects from both macroscopic and histological perspectives in BPH rat models.</p><p><strong>Conclusion: </strong>This study provides a comprehensive analysis of the inflammatory microenvironment and metabolic characteristics of BPH and identifies glycolysis-mediated proliferation of basal epithelial cells as a key driver of disease progression. Pharmacological inhibition of glycolysis with 2-deoxy-D-glucose reduced prostate weight, prostate index, epithelial proliferation and M1-like macrophage infiltration in vivo, indicating that targeting glycolytic metabolism is a promising therapeutic strategy for BPH. These findings offer novel insights into BPH pathogenesis and provide a rationale for developing metabolism-directed, and potentially locally delivered, interventions that could benefit patients who respond poorly to current medical therapy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"636515"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110714","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-Based Prediction of 28-Day Mortality in Patients with Sepsis-Induced Cardiomyopathy: An Integrated Analysis of Inflammatory Biomarkers.","authors":"Chun Yang, Jingyu Wang, Jialiang Li, Yangyang Qu, Yao Meng, Hairui Shao, Yao Li, Lei Lyu, Genshan Ma","doi":"10.2147/JIR.S628783","DOIUrl":"https://doi.org/10.2147/JIR.S628783","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced cardiomyopathy (SICM) is a common complication of sepsis and is associated with poor short-term outcomes. However, effective tools for early risk stratification remain limited. This study aimed to develop a machine learning (ML)-based model to predict 28-day mortality in patients with SICM.</p><p><strong>Methods: </strong>A single-center retrospective cohort study was conducted, including 762 patients with SICM admitted to the intensive care unit (ICU). Clinical variables, including inflammatory biomarkers, were collected. The dataset was divided into training and validation sets at a ratio of 7:3. Feature selection was performed using least absolute shrinkage and selection operator (LASSO) regression. Multiple ML algorithms, including Random Forest (RF), Decision Tree (DT), Extreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Logistic Regression (LR), Light Gradient Boosting Machine (LightGBM), and Multilayer Perceptron (MLP), were used to develop prediction models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and Brier score. Shapley Additive Explanations (SHAP) were applied to interpret the model.</p><p><strong>Results: </strong>A total of 762 patients were included, with a 28-day mortality rate of 31.5%. Among all models, RF achieved the best performance (AUC = 0.88) with good calibration (Brier score = 0.149). SHAP analysis identified albumin (ALB), N-terminal pro-B-type natriuretic peptide (NT-proBNP), age, pH (PH), systolic blood pressure (SBP), and neutrophil-to-lymphocyte ratio (NLR) as key predictors of mortality. A web-based interactive nomogram was constructed to generate individualized risk estimates tailored to each patient's clinical profile.</p><p><strong>Conclusion: </strong>The ML-based model demonstrated good predictive performance and interpretability for 28-day mortality in SICM patients. This model may serve as a useful tool for risk stratification and clinical decision-making. Further external validation in multicenter prospective cohorts is required before broader clinical implementation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"628783"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110721","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}