Journal of Inflammation Research最新文献

{"title":"Noninvasive Quantitative Evaluation of Proliferative Lupus Nephritis Based on Ultrasonic Viscoelastic Imaging.","authors":"Han Yuan, Yuanyuan Chen, Liyan Wei, Xinhong Liao, Yong Gao","doi":"10.2147/JIR.S505223","DOIUrl":"10.2147/JIR.S505223","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the role of ultrasonic viscoelastic imaging in predicting proliferative lupus nephritis (PLN).</p><p><strong>Methods: </strong>We prospectively used ultrasonic viscoelastic imaging to evaluate 143 patients with lupus nephritis (LN), who underwent kidney biopsies from May 2023 to June 2024. Sixty healthy volunteers served as the control group. Patients were categorized as 90 cases of PLN, and 53 cases of nonproliferative lupus nephritis (nPLN). Ultrasonic viscoelastic imaging was employed to quantitatively analyze kidney cortex elasticity (Emean), viscosity coefficient (Vmean) and dispersion coefficient (Dmean). Semi-quantitative assessment of the lesion tissues was conducted based on the activity index and chronic index scoring system established by the National Institutes of Health (NIH) in 2018. The relationship among clinicopathological, conventional ultrasound factors and viscoelastic parameters was evaluated.</p><p><strong>Results: </strong>Viscoelastic parameters (Emean, Vmean, and Dmean) significantly differed among the healthy control, PLN, and nPLN groups (all <i>p</i> < 0.05). The viscoelastic parameters (Emean, Vmean, and Dmean) of the PLN and nPLN groups exceeded those of the control group. Vmean and Dmean were considerably greater in the PLN group than in the nPLN group (<i>p</i> < 0.05). Vmean (OR 89.49, <i>p</i> = 0.002), serum creatinine (Scr) (OR 110.57, <i>p</i> = 0.024), and anti-dsDNA (OR 1.0, <i>p</i> = 0.015) were significant predictors of PLN. The combined model's area under curve (AUC) for predicting PLN was 0.83, better than any single indicator (<i>p</i> < 0.05). The peak systolic velocity (PSV) of the interlobar artery was determining factor of Emean (<i>p</i> < 0.05). The estimated glomerular filtration rate (eGFR), activity index, and body mass index (BMI) were determining factors of Dmean, while activity index was the determining factor of Vmean (<i>p</i> < 0.05). Correlation analysis reveals a positive correlation between Vmean and both the activity index and the chronicity index (<i>r</i> = 0.57 and <i>r</i> = 0.34, respectively, <i>p</i> < 0.05), as well as between Dmean and both the activity index and the chronicity index (<i>r</i> = 0.43 and <i>r</i> = 0.20, respectively, <i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>As a noninvasive examination method, ultrasonic viscoelastic imaging is beneficial for identifying PLN.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3269-3281"},"PeriodicalIF":4.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596928","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":"miR-6089 Alleviates Inflammation and Cell Apoptosis Through Modulating the TLR4 Pathway in Mite-Sensitized Allergic Rhinitis.","authors":"Chang-Yu Qiu, Jia-Xin Bi, Xin-Yan Cui, Ruo-Xi Chen, Zheng Luan, Yun Guo, Mei-Ping Lu, Ling Li, Lei Cheng","doi":"10.2147/JIR.S497005","DOIUrl":"10.2147/JIR.S497005","url":null,"abstract":"<p><strong>Purpose: </strong>Allergic rhinitis (AR), a chronic inflammatory disease of nasal mucosa, is considered as a classic Th2-mediated disease. We aimed to elucidate the molecular mechanisms and therapeutic potential of microRNAs (miRNAs) in AR.</p><p><strong>Methods: </strong>Nasal mucosa was collected from patients with mite-sensitized AR and non-allergic controls for miRNA and mRNA sequencing. miRNA expression was profiled. GO and KEGG enrichment analyses were conducted. Luciferase reporter assay was implemented to identify potential targets of candidate miRNAs. An AR cell model was established through lipopolysaccharide (LPS) exposure. miR-6089 was overexpressed or downregulated to characterize its roles in the proliferation and apoptosis of human nasal epithelial cells (HNEpC). The relationship between miR-6089 and toll-like receptor 4 (TLR4) was described. PCR and ELISA were applied to quantify the expression levels of miRNAs and mRNAs.</p><p><strong>Results: </strong>A total of 28 miRNAs and 172 mRNAs were identified to be differently expressed in the nasal mucosa of patients with AR compared to controls. The KEGG enrichment analysis showed that TLR signaling pathway, NF-κB signaling pathway, IL-17 signaling pathway and other pathways were significantly enriched in these differentially expressed RNAs. As shown by PCR results, the expression of miR-6089 decreased, and that of TLR4, IL-6, IL-8, and TSLP increased significantly in the nasal mucosa from patients with AR. Dual-luciferase reporter assay showed that miR-6089 directly bound to TLR4. miR-6089 could increase the viability, inhibit apoptosis, and relieve inflammatory response in LPS-induced HNEpC. Furthermore, miR-6089 could regulate the expression of TLR4, IL-6, IL-8, and TSLP in the LPS-induced HNEpC.</p><p><strong>Conclusion: </strong>miR-6089 can alleviate LPS-induced inflammatory response via targeting TLR4 and may serve as a therapeutic target in the treatment of mite-sensitized AR.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3243-3254"},"PeriodicalIF":4.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596922","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":"Adenosine A2A Receptor Activation Alleviated Disease of Mice with Systemic <i>Candida albicans</i> Infection by Regulating Macrophage Function.","authors":"Xia-Nan Wu, Ke Dong, Yan Liu, Lan Yang, Jing Zhang, Ming Yang, Zhao-Wei Gao","doi":"10.2147/JIR.S501546","DOIUrl":"10.2147/JIR.S501546","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence of candidemia, mediated by systemic <i>Candida albicans</i> (<i>C. albicans</i>) infection, was increasing. It is an urgent need to understand the underlying disease mechanisms to identify new therapeutic targets. This study aimed to investigate the roles of adenosine-adenosine receptor signal in systemic <i>C. albicans</i> infection.</p><p><strong>Methods: </strong>The candidemia mice models (named CA mice) were established by tail intravenous injection of <i>C. albicans</i>. CA Mice were treated with NECA (a metabolically stable adenosine analogue) or agonists targeting different adenosine receptors (A1R, A2AR, A2BR and A3R). The survival rate, renal fungal load and tissue damage were investigated. Bone marrow-derived macrophages (BMDM) were isolated and cultured to investigate the effects of NECA and adenosine receptor agonist on phagocytosis, killing function and polarization of macrophages.</p><p><strong>Results: </strong>In CA mice, we observed that NECA and A2AR agonist treatment significantly alleviated the sepsis score and increased the survival rate. Moreover, the renal injury and fungal load were reduced by NECA and A2AR agonist treatment. However, the other adenosine receptors (ie, A1R, A2BR and A3R) activation have no effect on survival and tissue damage of CA mice. A2AR activation could reduce macrophage infiltration in kidney and the production of inflammatory cytokine IL-6 in CA mice. Moreover, adenosine-A2AR signaling activation could enhance antifungal capacity of macrophages and promoted macrophage polarization toward the M2 subtype.</p><p><strong>Conclusion: </strong>Activation of adenosine-A2AR axis promoted macrophage M2 polarization, enhanced host defense against systemic <i>C. albicans</i> infection, and alleviated candidiasis. A2AR activation could be considered as a potential therapeutic strategy in candidemia.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3283-3294"},"PeriodicalIF":4.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596855","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":"Recurrence of Rosacea Induced by Compound Vitamin Tablets: A Case Report.","authors":"Hui-Shang Feng, Wan-Tong Zhang, Zi-Ye Xi, Guo-Dong Hua, Chun-Miao Xue, Ling-Ling Li, Shuang-Qing Qu, Li-Li Zhao, Tai Zhang, Bao-Chen Zhu, Yuan-Wen Li","doi":"10.2147/JIR.S507861","DOIUrl":"10.2147/JIR.S507861","url":null,"abstract":"<p><p>We present a case of rosacea recurrence in a 37-year-old woman associated with the intake of compound vitamin tablets during the preconception period, with a Naranjo score of 7. These tablets, commonly used for nutritional supplementation to prevent anemia, contain a variety of vitamins, minerals, and trace elements. Despite their widespread use, reports of such supplements causing rosacea recurrence are rare. In this case, the patient experienced a recurrence of facial redness, stinging, and burning after taking the tablets on two separate occasions. Skin dermatoscopy, VISIA imaging, Clinician's Erythema Assessment (CEA), Investigator's Global Assessment (IGA), and Visual Analogue Scale (VAS) all confirmed the recurrence of rosacea. Given her intention to conceive, symptomatic treatment with emollient and reparative dressings was administered. The patient's symptoms gradually resolved after discontinuing the medication, with no recurrence observed during follow-up visits. Women with a history of rosacea should avoid these tablets during preconception, pregnancy, and lactation to prevent recurrence and should choose supplements carefully to minimize the risk of rosacea flare-ups.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3311-3319"},"PeriodicalIF":4.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597025","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 Effect of Acupuncture on the Morphology and Neural Coding Damage of the Central Amygdala in Mice with Chronic Inflammatory Pain and Depression.","authors":"Cui Ma, Ren-Zhen Zhang, Hong-Yu Lu, Ting-Ting Dou, Li Li, Xing-Ke Yan","doi":"10.2147/JIR.S501170","DOIUrl":"10.2147/JIR.S501170","url":null,"abstract":"<p><strong>Purpose: </strong>Observing the effects and roles of acupuncture on the morphology and neural coding damage of central amygdala (CeA) neurons in chronic inflammatory pain with depression (CIPD) mice and exploring the central nervous mechanism of acupuncture intervention in CIPD.</p><p><strong>Methods: </strong>A CIPD model was established by injecting Complete Freund's Adjuvant (CFA) into the left hind foot. Using paw withdrawal latency (PWLs), forced swimming, and open field tests, 40 mice with successfully replicated models were selected and randomly divided into a model group, acupuncture group, and sham acupuncture group, with 12 mice in each group. After treatment, Nissl staining was used to observe the morphology of CeA neurons and the number of Nissl bodies. In vivo multi-channel recordings measured the spontaneous firing frequency, waveform amplitude, inter-spike interval (ISI), and power spectral density (PSD) of CeA neurons.</p><p><strong>Results: </strong>The PWLs in the model and sham acupuncture groups were shortened, the activity time and distance in the central region were reduced, and the forced swimming immobility time increased. The arrangement of CeA neurons is sparse, neurons are damaged, and the number of Nissl bodies is reduced; CeA neurons exhibit abnormal changes in spatiotemporal patterns, with a decrease in spontaneous discharge frequency, discharge amplitude, PSD, and an increase in ISI. The acupuncture group showed prolonged PWLs, increased activity time and distance in the central region, and decreased immobility during forced swimming. The loss of CeA neurons decreased, the cells were arranged neatly, the nucleoli were evident, and the number of Nissl bodies increased. The damage to CeA neural coding was significantly improved, with increased spontaneous discharge frequency, discharge amplitude, PSD, and shortened ISI.</p><p><strong>Conclusion: </strong>Acupuncture may alleviate pain and depressive-like behaviors in CIPD mice and reduce neuronal damage, possibly through mechanisms related to improving the spatiotemporal characteristics of neural coding impairments in the CeA brain region.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3255-3268"},"PeriodicalIF":4.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597026","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":"Association Between Uric Acid to High-Density Lipoprotein Cholesterol Ratio and Abdominal Aortic Aneurysm: A Single-Center Retrospective Study.","authors":"Da Lu, Ke Si, Guijun Huo","doi":"10.2147/JIR.S508355","DOIUrl":"10.2147/JIR.S508355","url":null,"abstract":"<p><strong>Objective: </strong>Uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) has been recognized as a novel biomarker for evaluating inflammatory and anti-inflammatory interaction. However, it is not known whether UHR is related to abdominal aortic aneurysm (AAA). The current research aims to explore the potential role of UHR in predicting AAA.</p><p><strong>Methods: </strong>In this study, 303 AAA patients and 408 normal subjects were retrospectively analyzed. The relationship between UHR and AAA was evaluated using Logistic regression models. Receiver operating characteristic (ROC) curves and restricted cubic spline (RCS) analysis were employed to elucidate the detailed association between UHR and AAA.</p><p><strong>Results: </strong>UHR value in the AAA group was significantly higher than that in the normal group, and UHA was an independent risk factor for AAA. After adjusting for covariates, each 1-unit increase in UHR was associated with a 12% rise in AAA risk (OR: 1.12, 95% CI: 1.03, 1.21). ROC value of UHR was 0.847 (95% CI, 0.811~0.887, P < 0.05), and the optimal critical value of UHR was 17.2%. The incidence of AAA in the UHR≥17.2% group was significantly higher than that in the UHR < 17.2% group. RCS curves revealed a significant nonlinear relationship between UHR and AAA events (p-value < 0.001, p-nonlinear = 0.002).</p><p><strong>Conclusion: </strong>This study demonstrates that UHR levels are significantly linked to increased AAA risk, which can be widely used as an indicator for dynamic screening of AAA.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3217-3226"},"PeriodicalIF":4.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586075","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 Anoikis-Related Genes in Driving Immune-Inflammatory Responses in Ulcerative Colitis Based on Bioinformatics Analysis and Machine Learning.","authors":"Wenxiu Diao, Xu Huang, Wensha Huang, Jing Jiang, Wentao Li, He Liu, Bo Yan, Lei Shen","doi":"10.2147/JIR.S509659","DOIUrl":"10.2147/JIR.S509659","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a challenging chronic intestinal inflammation. Anoikis, a type of programmed cell death triggered by detachment from the extracellular matrix, is crucial in various physiological and pathological contexts. This study aims to explore the biological and clinical implications of anoikis-related genes (ARGs) in UC.</p><p><strong>Methods: </strong>Gene expression microarrays from normal and UC mucosal tissues focused on ARGs. Differentially expressed genes (DEGs) related to anoikis in UC were identified. Weighted gene co-expression network analysis (WGCNA) screened UC-related module genes. GO, KEGG, GSEA, and GSVA analyses were used to uncover mechanisms. Machine learning identified hub ARG-DEGs highly correlated with UC, and diagnostic nomograms assessed their diagnostic potential. The CIBERSORT algorithm analyzed changes in the UC immune microenvironment related to hub UC-ARGs. Potential drugs, miRNAs, and transcription factors (TFs) interacting with these hub UC-ARGs were investigated, and animal experiments verified their expression.</p><p><strong>Results: </strong>49 ARG-DEGs were identified, mainly linked to the PI3K-AKT signaling pathway, inflammatory signal regulation, and extracellular matrix (ECM)-receptor interactions. Notably, CDH3 and SERPINA1 showed significant diagnostic potential for UC, confirmed by the Wilcoxon rank-sum test, independent validation sets, Western blot, and immunohistochemical staining. Significant variations in immune cell infiltration and activation within UC samples correlated with hub UC-ARGs were observed using the CIBERSORT algorithm.</p><p><strong>Conclusion: </strong>Anoikis may drive UC progression by initiating an immune inflammatory response. CDH3 and SERPINA1 are promising biomarkers and therapeutic targets for UC.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3227-3242"},"PeriodicalIF":4.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586081","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":"Dynamic Inflammatory and Nutritional Profiles in Preoperative Risk Stratification for Elderly Patients [Letter].","authors":"Si-Jia Liu, Zi-Heng Li, Xi-Cai Liang, Jun-Tong Liu","doi":"10.2147/JIR.S522902","DOIUrl":"10.2147/JIR.S522902","url":null,"abstract":"","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3215-3216"},"PeriodicalIF":4.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586080","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":"Osteoclast Activation and Inflammatory Bone Diseases: Focusing on Receptors in Osteoclasts.","authors":"Weijie Zhao, Ji Li, Tian Su, Chuanling Wang, Yonghua Fu, Changjia Li, Pengbing Hua, Xuelong Liang, Yongjun Zhu, Hongwang Cui","doi":"10.2147/JIR.S507269","DOIUrl":"10.2147/JIR.S507269","url":null,"abstract":"<p><p>Bone homeostasis depends on the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. An increasing number of studies have revealed that under inflammatory conditions, osteoclast overactivation is responsible for bone loss in relevant bone diseases. Multiple signaling pathways such as receptor activator of nuclear factor-kappa B ligand (RANKL) signaling are involved in osteoclast activation. These signaling pathways rely on various receptors expressed on the surface of osteoclast progenitor cells (OPCs) or osteoclasts, which are activated by their corresponding ligands and subsequently trigger intracellular signaling. Targeting of these receptors may exert an inhibitory effect on osteoclast activation and inflammatory bone diseases. In this review, we discuss osteoclast activation and receptors involved in this process. The role of these receptors in relevant bone diseases has also been discussed.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3201-3213"},"PeriodicalIF":4.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585944","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":"<i>Saccharomyces boulardii</i> Alleviates Colitis by Regulating FXR-NLRP3 Mediated Macrophage Pyroptosis.","authors":"Lijiao Yang, Wanyu Li, Qianjing Zhao, Qi Mo, Tianyu Liu, Hailong Cao","doi":"10.2147/JIR.S504957","DOIUrl":"10.2147/JIR.S504957","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC), a typical inflammatory bowel disease (IBD), is pathologically defined by mucosal inflammation confined to the colonic mucosa. <i>Saccharomyces boulardii</i> (Sb), a commonly utilized probiotic yeast for managing digestive disorders like UC, has not been thoroughly investigated regarding its precise mechanisms for alleviating colitis. Increasing evidence indicates the involvement of FXR in UC. Meanwhile, the regulatory role of FXR on NLRP3 has garnered increasing attention. This study investigated the therapeutic effects of Sb supernatant (SbS) on colitis and elucidated the role of the FXR-NLRP3 signaling pathway in this process.</p><p><strong>Methods: </strong>A murine model of colitis was established through administration of dextran sulfate sodium (DSS), followed by oral gavage with either SbS or the control Sabouraud dextrose broth (SDB) culture medium. The FXR activation, NLRP3 inflammasome inhibition, and macrophage pyroptosis were evaluated both in vivo and in vitro. The effects of SbS in activating FXR, suppressing NLRP3 inflammasome and alleviating the colitis were assessed.</p><p><strong>Results: </strong>SbS ameliorated symptoms of DSS-induced colitis. Our data demonstrated that SbS elicited activation of FXR and concomitantly suppressed NLRP3 expression within the colonic tissue samples. Additionally, SbS was further observed to suppress the expression of cleaved caspase-1, a key effector protein in pyroptosis process, within the F4/80⁺ macrophage population. Moreover, SbS modulated the expression of genes and proteins associated with pyroptosis, collectively suggesting its potential to ameliorate intestinal pyroptosis, potentially via its direct impact on macrophage. Consistently, SbS ameliorated pyroptosis of macrophages in vitro through activating FXR and inhibiting NLRP3 inflammasome. However, the therapeutic effect of SbS was reversed by the FXR inhibitor, guggulsterone, resulting in increased levels of pyroptosis-related proteins.</p><p><strong>Conclusion: </strong>SbS demonstrated a beneficial effect in alleviating UC by modulating the FXR-NLRP3 signaling pathway, thereby mitigating macrophage pyroptosis. This discovery presents new insights into effects of Sb on alleviating UC.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3161-3176"},"PeriodicalIF":4.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596902","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}