Journal of Inflammation Research最新文献

{"title":"Identification of Biomarkers for Sepsis-Induced Acute Lung Injury Through Bioinformatics and Machine Learning Approaches, with Experimental Validation.","authors":"Yannian Luo, Juan Xu, Nannan He, Wen Cao","doi":"10.2147/JIR.S539899","DOIUrl":"https://doi.org/10.2147/JIR.S539899","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced acute lung injury (ALI) remains a life-threatening condition due to the lack of reliable early diagnostic biomarkers. Machine learning offers powerful tools for analyzing high-dimensional gene expression data and identifying potential biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>Five datasets (GSE10474, GSE32707, GSE66890, GSE10361, GSE3037) were obtained from the GEO database. After assessment and normalization, GSE10474, GSE32707, and GSE66890 were combined as a training set to identify differentially expressed genes (DEGs). DEGs were intersected with genes from key modules identified by weighted gene co-expression network analysis (WGCNA), yielding 213 overlapping genes. These were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Eight machine learning algorithms (RF, SVM, GLM, GBM, KNN, NNET, LASSO, DT) were used to develop diagnostic models, which were validated on GSE10361 and GSE3037. Model performance was evaluated using a nomogram, calibration curves, and decision curve analysis (DCA). Immune and inflammatory states were assessed using the CIBERSORT algorithm. Potential therapeutic compounds were identified through the DSigDB database via the Enrichr platform. Molecular docking and molecular dynamics simulations examined interactions between Resveratrol and selected targets. In vitro experiments validated these findings.</p><p><strong>Results: </strong>A total of 213 candidate genes were identified by intersecting DEGs with WGCNA-derived MEblue module genes. GO and KEGG analyses indicated associations with immune activation and bacterial infection. Four key genes (DDAH2, PNPLA2, STXBP2, TCN1) were selected using eight machine learning algorithms. The diagnostic model showed good performance via nomogram, calibration curve, and DCA. Molecular docking revealed stable binding of Resveratrol to these genes. In vitro, Resveratrol pretreatment alleviated LPS-induced ALI by modulating the core genes.</p><p><strong>Conclusion: </strong>The four genes may serve as diagnostic biomarkers for sepsis-ALI. Resveratrol represents a potential therapeutic strategy by targeting these genes.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13635-13650"},"PeriodicalIF":4.1,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258248","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":"Kimura Disease: Retrospective Analysis of 53 Cases and Three Mepolizumab-Responsive Cases.","authors":"Wenjiao Zhu, Lei Zhang, Jing Zhang, Wei Wang, Ye Xiang, Dingxian He, Jing Shi, Yiran Liang, Yuanping Shi, Xianhui Ning, Meiling Jin, Ling Ye","doi":"10.2147/JIR.S538560","DOIUrl":"https://doi.org/10.2147/JIR.S538560","url":null,"abstract":"<p><strong>Background: </strong>Kimura disease (KD) is a rare, chronic lymphoproliferative disorder, which is believed to be driven by a Th2 immune response, though its exact pathogenesis remains unclear. Despite various treatment approaches, no standardized therapy has been established. This study investigated the clinical features of 53 KD patients and evaluated the therapeutic potential of mepolizumab in three cases.</p><p><strong>Methods: </strong>A retrospective age-stratified analysis was performed on 53 patients diagnosed with KD at two tertiary medical centers in China, covering the period from January 2014 to December 2024. We also provided an in-depth case series of three patients who received mepolizumab treatment.</p><p><strong>Results: </strong>This study included 53 KD patients, predominantly male (88.7%) with a mean age of 41 years. The median time from symptom onset to diagnosis was 24 months, and the median lesion diameter was 3.0 cm. Pruritus was present in 52.8% of patients, with frequency increasing with age (P=0.015). Coexisting conditions included IgG4-related disease (11.3%), asthma (9.4%), and thrombotic events (9.4%). Lesions were bilateral in 66.0% and primarily located in the head and neck region (83.0%). Average eosinophil count was 2.09 × 10⁹/L, and mean serum IgE level was 1069 IU/mL. Surgical excision (62.3%) is the most common initial treatment approach, followed by corticosteroids (15.1%). The overall recurrence rate is 60.4%. In the case series, three patients treated with different doses of mepolizumab showed favorable responses, including lymph nodes shrink, symptom control and eosinophil reduction.</p><p><strong>Conclusion: </strong>This study provided a comprehensive summary and age-stratified analysis of the clinical characteristics of KD, providing valuable insights into its pathophysiology and potential overlapping mechanisms. Additionally, the study presents clinical cases of three patients treated with mepolizumab, highlighting its potential as a promising therapeutic option for the management of KD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13773-13785"},"PeriodicalIF":4.1,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258189","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":"Prediction of Antibiotic Efficacy in Cerebral Hemorrhage-Associated Pneumonia Using Inflammatory Hematological Indices: A Retrospective Study.","authors":"Xian Wang, Xiong Yang, Yuan Yao, Hang Hu, Yongfeng Zhao, Zhansheng Zhu","doi":"10.2147/JIR.S553806","DOIUrl":"https://doi.org/10.2147/JIR.S553806","url":null,"abstract":"<p><strong>Purpose: </strong>The role of inflammatory response in secondary infections following cerebral hemorrhage has attracted considerable attention. We aimed to explore the associations between inflammatory markers and antibiotic efficacy on the cerebral hemorrhage-associated pneumonia.</p><p><strong>Methods: </strong>We conducted a retrospective study including 200 patients with cerebral hemorrhage-associated pneumonia. In the retrospective study, baseline data, blood cell counts, and C-reactive protein (CRP) were collected. The inflammatory markers including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII) were calculated. The difference between the values at admission and at the time of initial efficacy evaluation was denoted by \"Δ\". These inflammatory markers were examined as potential biomarkers to predict the efficacy of initial antibiotic treatment in finally included patients by univariate analysis and multivariate logistic regression models.</p><p><strong>Results: </strong>In the final analysis, there were 105 cases with effective antibiotic treatment and 95 cases with ineffective antibiotic treatment. At the time of initial efficacy evaluation, there were significant differences in the values of NLR, MLR, PLR, SII, and CRP, P<0.05. Significant differences were also showed in the values of ΔNLR, ΔMLR, and ΔSII, P<0.05. The results of multivariate logistic regression model showed that ΔNLR (OR: 1.260, P=0.016), ΔPLR (OR: 0.985, P=0.008), and CRP (OR: 0.975, P=0.043) at the time of efficacy evaluation were possibly associated with the antibiotic efficacy.</p><p><strong>Conclusion: </strong>ΔNLR, ΔPLR, and CRP at the time of efficacy evaluation appear the promising parameters in guiding antibiotic treatment in patients with cerebral hemorrhage-associated pneumonia. However, large-sample, multicenter external validation studies are still needed.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13763-13772"},"PeriodicalIF":4.1,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258256","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":"Clinical Features, Treatment Effectiveness and Long-Term Outcomes in Children with Moderate-to-Severe Generalized Pustular Psoriasis: A Retrospective Cohort Study.","authors":"Zhiqiang Cao, Bin Peng, Zonghao Li, Ruiqi Li, Ruitao Fan, Baibing Mi, Bingjie Li, Xiangjin Song, Jing Shi, Songmei Geng","doi":"10.2147/JIR.S548192","DOIUrl":"https://doi.org/10.2147/JIR.S548192","url":null,"abstract":"<p><strong>Background: </strong>Generalized pustular psoriasis (GPP) is a rare inflammatory skin disorder, frequently accompanied by systemic inflammatory manifestations. Pediatric GPP presents unique clinical features and requires tailored treatment approaches. However, real-world data on pediatric moderate-to-severe GPP remain limited.</p><p><strong>Objective: </strong>To describe the clinical profiles of pediatric moderate-to-severe GPP, evaluate the effectiveness of various treatments, and their impact on disease recurrence.</p><p><strong>Methods: </strong>This retrospective observational study enrolled pediatric moderate-to-severe GPP inpatients in our department from March 2017 to February 2024. Clinical characteristics, treatment regimens, and recurrence were collected and analyzed using electronic medical records and follow-up data.</p><p><strong>Results: </strong>61 pediatric patients were included, with a male-to-female ratio of 1.54: 1, an average age of 10.6±3.2 years. Concomitant symptoms were present in 93.4% of patients, including pruritus, fever, and skin pain. Common comorbidities included hypoproteinemia, anemia, and hyperlipidemia. Over 80% of patients exhibited elevated inflammatory markers, including IL-6, TNF-α. GPP with psoriasis vulgaris (PV) and without PV had similar clinical presentations. Regarding treatment outcomes, compared with traditional drugs, biologics significantly reduced both hospitalization time (6.0 days vs 8.0 days, <i>P</i>=0.002) and pustule clearance time (3.0 days vs 7.0 days, <i>P</i>=0.013), with a lower incidence of adverse events. Post-discharge follow-up data on annual flare indicated the biologics group was associated with fewer annual flares (0 vs 0.3 per person-year, <i>P</i>=0.052) and lower recurrence rate (21.1% vs 60.0%, <i>P</i>=0.034), compared with the traditional drugs group. Furthermore, serum proteomic analysis revealed significantly elevated IL-17 level and activation of the IL-17 signaling pathway in pediatric GPP compared with healthy controls, elucidating the mechanism underlying the high effectiveness of biologic-targeted therapies.</p><p><strong>Conclusion: </strong>For moderate-to-severe pediatric GPP, biologics exhibit faster effectiveness and better safety than traditional systemic drugs. Specifically, biologics can significantly reduce hospitalization time and pustule clearance time, and decrease disease recurrence.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13787-13798"},"PeriodicalIF":4.1,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258192","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":"Age-Stratified Immune-Inflammatory Profiles and Prognostic Implications of Old Patients in the ICU: A Prospective Study.","authors":"Hui Lian, Guangjian Wang, Qing Zhang, Hua Zhao, Xiaoting Wang","doi":"10.2147/JIR.S548582","DOIUrl":"https://doi.org/10.2147/JIR.S548582","url":null,"abstract":"<p><strong>Background: </strong>The aging population has advanced older patients (OPs) in intensive care units (ICUs). Critical illness and aging exacerbate immune-inflammatory dysregulation, impairing immune interactions and worsening prognosis. However, knowledge regarding immune-inflammatory profiles and prognostic implications for OPs, particularly in very old patients (VOPs), remains limited.</p><p><strong>Methods: </strong>This single-center prospective study included patients aged ≥65 with hemodynamically confirmed shock, signifying severe critical illness admitted between August 2023 and February 2025. Demographic, medication, and laboratory data were collected from electronic medical records. The primary endpoint was in-hospital mortality; secondary endpoints included ICU and hospital stay duration. Participants aged 65-74 were young old patients (YOPs), and those aged ≥75 as VOPs. Statistical analysis included χ² for categorical variables, Kolmogorov-Smirnov for non-normal continuous data, Principal component analysis (PCA) for inflammatory states, while generalized additive mixed models for statistical interactions.</p><p><strong>Results: </strong>A total of 537 OPs were admitted, with no significant differences in inflammatory markers between YOPs and VOPs, except fibrinogen. Survivors had higher levels of hypersensitive C-reactive protein (hsCRP). Lymphocyte counts and subtypes were reduced in OPs. VOPs showed higher natural killer cells, CD8+CD38+, and CD8+DR+ counts versus YOPs. The median CD8+DR+ count was 82 in survivors versus 59 in non-survivors. Among VOPs, hsCRP, interleukin-8, and immunoglobulin G showed significant differences. B cell count was lower (median 104 vs 72), and CD8+ T cell activation declined in non-survivors. Mortality was higher in the low inflammatory state group. As B and T cell counts increased, mortality decreased in high inflammatory states. Higher CD8+DR+ counts reduced mortality.</p><p><strong>Conclusion: </strong>OPs, especially VOPs, with hemodynamically confirmed shock and critical illness exhibit distinct immune-inflammatory characteristics affecting prognosis. A weakened immune response in low inflammation links to poor outcomes. Enhancing B cell and CD8+DR+ T cell responses may improve prognosis through precise immune regulation in ICU settings.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13727-13743"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251518","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":"Comprehensive Analysis and Experimental Validation of Immune-Related Biomarkers and Immune Microenvironment in Diabetic Nephropathy.","authors":"Weini Zhou, Ziyang Zeng, Xunjia Li, Mei Yang","doi":"10.2147/JIR.S541886","DOIUrl":"https://doi.org/10.2147/JIR.S541886","url":null,"abstract":"<p><strong>Background: </strong>The molecular mechanism of diabetic nephropathy (DN) is still not fully understood. There is ample evidence that the immune system plays a crucial role in the progression of DN. Further exploration of immune-related genes (IRGs) for DN diagnosis is therefore of significant clinical value.</p><p><strong>Methods: </strong>Gene expression data from DN patients were obtained from the GEO database, and a weighted gene co-expression network analysis (WGCNA) was constructed. The overlapping IRGs derived by the least absolute shrinkage and selection operator (LASSO) and recursive feature elimination (RF) algorithms were identified as DN diagnostic biomarkers. A nomogram model was established to evaluate the diagnostic ability of feature biomarkers. The expression levels of the screened IRGs were validated in vitro using qRT-PCR. Type 2 diabetes mellitus (T2DM) mouse model with DN was also established to confirm the consistency with bioinformatic predictions.</p><p><strong>Results: </strong>Three IRG-related DN characteristic diagnostic biomarkers (<i>CCL9, EDN1</i> and <i>HSPA1L</i>) were identified. After verifying the DN diagnostic capability with nomogram model, pathway enrichment analysis, immunoinfiltration characteristics and correlation analysis were used to comprehensively analyze the potential effects of selected IRGs on DN. The differential expressions of screened IRGs were further confirmed by cell line and T2DM mouse model.</p><p><strong>Conclusion: </strong>Our findings nominate <i>CCL9, EDN1</i>, and <i>HSPA1L</i> as key mediators of DN progression and unveil their potential as diagnostic biomarkers. Although prospective validation in human cohorts is a prerequisite for clinical translation, these IRGs represent a compelling foundation for a precision medicine tool. This tool could transform patient management by facilitating pre-symptomatic diagnosis and informing tailored interventions to halt DN development.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13711-13726"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251547","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":"Identification of Mitophagy-Related Genes and Analysis of Immune Infiltration in Atherosclerosis.","authors":"Jiaqi Zhang, Xiting Wang, Xiahuan Chen, Meilin Liu","doi":"10.2147/JIR.S544597","DOIUrl":"https://doi.org/10.2147/JIR.S544597","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is a chronic inflammatory disease involving mitophagy and immune dysregulation. Currently, there is no integrated diagnostic model for autophagy immune genes in mitochondria. This study aimed to identify potential diagnostic markers through integrated bioinformatics and experimental validation.</p><p><strong>Methods: </strong>Two atherosclerosis-related datasets (GSE43292 and GSE100927) were analyzed to identify differentially expressed mitophagy-related genes (MRGs), followed by enrichment analysis. Key genes were screened using LASSO, SVM-RFE, and random forest algorithms. A diagnostic nomogram was constructed and validated by ROC analysis. Immune infiltration was evaluated using CIBERSORT and ssGSEA. GSEA, GSVA, and unsupervised clustering were applied to explore biological pathways and molecular subtypes. qPCR validation was performed in ox-LDL-treated RAW264.7 and THP-1 cells.</p><p><strong>Results: </strong>Thirteen upregulated and six downregulated MRGs were identified. Five hub genes (MNDA, CD163L1, NEXN, TC2N, SLC22A3) demonstrated strong diagnostic performance (AUC > 0.85) and were closely associated with immune cell infiltration; two molecular subtypes with distinct immune profiles were identified; qPCR validation confirmed the differential expression of these genes under inflammatory stimulation.</p><p><strong>Conclusion: </strong>MNDA, CD163L1, NEXN, TC2N, and SLC22A3 may serve as diagnostic biomarkers for atherosclerosis. This five-gene model can stratify patient risk and guide personalized anti-inflammatory/autophagic therapy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13689-13710"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251516","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":"A Nomogram for Early Prediction of Infected Pancreatic Necrosis Based on Contrast-Enhanced CT Radiomics and Inflammatory Indicators.","authors":"Qing Yao, Yue Duan, Chao Jin, Xiang Li, Shiyu Wei, Yinghuan Shi, Yuelang Zhang, Jingyao Zhang, Chang Liu","doi":"10.2147/JIR.S538345","DOIUrl":"https://doi.org/10.2147/JIR.S538345","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to establish a nomogram for early and accurate identification of infected pancreatic necrosis (IPN) among patients with acute necrotizing pancreatitis (ANP) by integrating clinical data and radiomic information from contrast-enhanced computed tomography (CECT).</p><p><strong>Patients and methods: </strong>This retrospective single-center study included 203 ANP patients who underwent CECT. Patients were divided into training (n=142) and test set (n=61). Radiomic features were extracted from CECT images using PyRadiomics. Three machine learning classifiers were employed to construct a radiomic signature. Clinical factors were identified through regression analysis. A combined nomogram was developed using multivariate logistic regression. ROC and calibration curves were plotted to assess the efficacy of the model. Decision curve analysis (DCA) was applied to identify the clinical value and utility.</p><p><strong>Results: </strong>In the training and test set, 56 (39.43%) and 23 (37.70%) patients developed into IPN, respectively. The optimal Rad score was achieved by the LightGBM classifier. APACHE II and MCTSI scores were independent predictors of IPN. The combined clinical-radiomic nomogram achieved the best predictive efficacy, with an AUC of 0.877 in the training set and 0.829 in the test set. The calibration curve proved good accordance, and the decision curve demonstrated great clinical utility.</p><p><strong>Conclusion: </strong>The clinical-radiomic combined nomogram performed well in predicting IPN in patients with ANP. It could potentially serve as a quantitative, non-invasive tool for early IPN prediction in patients with ANP.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13651-13663"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251505","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":"Mechanistic Exploration of Shenling Baizhu Powder in Treating Irinotecan-Associated Diarrhea: A Study Based on Network Pharmacology and Experimental Validation.","authors":"Meng Liu, Ying Xiong, Jun Yuan, Qi Jin, Jin-Cheng Zhang, Run-Jia Shi, Zhi-Qiang Cheng","doi":"10.2147/JIR.S536184","DOIUrl":"https://doi.org/10.2147/JIR.S536184","url":null,"abstract":"<p><strong>Objective: </strong>Irinotecan-associated diarrhea (IAD) is a severe adverse effect that limits its clinical utility in cancer therapy. Shenling Baizhu Powder (SLBZP), a traditional Chinese herbal formula, has shown potential in alleviating chemotherapy-induced gastrointestinal toxicity, but its mechanism against IAD remains unclear. This study integrated network pharmacology and experimental validation to systematically explore the therapeutic mechanisms of SLBZP in IAD.</p><p><strong>Methods: </strong>Network pharmacology approaches were employed to identify bioactive components of SLBZP and their targets using the TCMSP database, while IAD-related targets were retrieved from Genecards. Protein-protein interaction (PPI) analysis and KEGG pathway enrichment were performed to pinpoint core targets and signaling pathways. For in vivo validation, an IAD rat model was established via tail vein injection of irinotecan (150 mg/kg), with SLBZP intervention and Gegen Qinlian Decoction (GGQLD) as a positive control. In vitro, LPS-stimulated NCM460 cells were treated with SLBZP water extract. Mechanistic evaluations were performed using molecular biology techniques, including ELISA, qPCR, and Western blotting, to validate the underlying mechanisms.</p><p><strong>Results: </strong>Network pharmacology analysis revealed that SLBZP exerted therapeutic effects against IAD by closely interacting with multiple inflammatory-related targets and pathways. In vivo studies demonstrated that SLBZP significantly ameliorated diarrhea severity, improved histopathological manifestations in intestinal tissues, and suppressed the expression of key inflammatory cytokines (TNF-α, IL-6, and IL-1β). Mechanistically, SLBZP inhibited the aberrant activation of inflammatory signaling pathways, including PI3K/AKT, MAPK, and NF-κB. Consistent findings were observed in vitro, where SLBZP water extract attenuated inflammatory responses in LPS-stimulated NCM460 cells.</p><p><strong>Conclusion: </strong>Integrated network pharmacology analysis and experimental validation demonstrate that SLBZP alleviates IAD primarily by suppressing intestinal inflammatory responses, providing mechanistic evidence to support its clinical application in managing chemotherapy-induced intestinal toxicity.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13745-13761"},"PeriodicalIF":4.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251596","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":"Low-Intensity Pulsed Ultrasound Promotes a Treg-Like Phenotype and Suppresses a Th17-Like Phenotype in CD4⁺ T Cells via YAP/TAZ Activation in vitro.","authors":"Renli Yang, Xirui Zhang, Yanjun Zhang, Yi Man, Xingmei Yang","doi":"10.2147/JIR.S548291","DOIUrl":"10.2147/JIR.S548291","url":null,"abstract":"<p><strong>Introduction: </strong>CD4⁺ T cell subpopulations, particularly T helper 17 (Th17) and regulatory T (Treg) cells, exhibit antagonistic functions and play essential roles in inflammatory responses. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are critical modulators of cell proliferation and differentiation. Low-intensity pulsed ultrasound (LIPUS) has been shown to regulate YAP/TAZ activity, but its role in Th17/Treg balance remains unclear.</p><p><strong>Methods: </strong>CD4⁺ T cells were purified from rat peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting (MACS). The cells were then treated with low-intensity pulsed ultrasound (LIPUS) at a set of parameters (1.0 MHz, 20 mW/cm², 20% duty cycle, 2h/day for 3 days) optimized based on preliminary proliferation and apoptosis assays. The effects of LIPUS on the expression of key functional markers (Foxp3 for Treg-like cells and IL-17A for Th17-like cells) were evaluated by flow cytometry, quantitative PCR, and ELISA. The activation and subcellular localization of YAP/TAZ were examined using immunofluorescence staining. Furthermore, siRNA-mediated knockdown was performed to investigate the functional involvement of YAP/TAZ in the LIPUS-mediated effects.</p><p><strong>Results: </strong>LIPUS treatment significantly increased the frequency of Foxp3-expressing cells while decreasing the frequency of IL-17A-producing cells. Additionally, LIPUS promoted the activation and nuclear translocation of YAP and TAZ, as evidenced by enhanced protein expression and a shift in subcellular localization. siRNA-mediated knockdown of YAP/TAZ attenuated the LIPUS-induced increase in Foxp3⁺ cells and potentiated the population of IL-17A⁺ cells. Importantly, LIPUS treatment effectively rescued the expression patterns of these functional markers following YAP/TAZ inhibition.</p><p><strong>Discussion: </strong>Our findings demonstrate that LIPUS promotes a Treg-like phenotype and suppresses a Th17-like phenotype in CD4⁺ T cells, a process that is mediated, at least in part, by the activation of the YAP/TAZ signaling pathway. This immunomodulatory effect suggests that LIPUS could be explored as a novel non-invasive strategy for managing autoimmune diseases and chronic inflammatory conditions associated with an imbalance in T cell responses.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13593-13608"},"PeriodicalIF":4.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244588","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}