Journal of Inflammation Research最新文献

{"title":"Rat Model of Cystic Neutrophilic Granulomatous Mastitis by Corynebacterium Kroppenstedtii.","authors":"Mengjie Wang, Yifei Zeng, Min Liu, Dongxiao Zhang, Di Zhao, Junyue Wang, Yongxin Liu, Wenjie Zhao","doi":"10.2147/JIR.S500310","DOIUrl":"10.2147/JIR.S500310","url":null,"abstract":"<p><strong>Background: </strong>Cystic neutrophilic granulomatous mastitis (CNGM) poses a significant threat to the physical and mental health of women due to its increasing incidence, complex clinical manifestations. Developing an appropriate animal model will help further study the pathogenesis of CNGM.</p><p><strong>Methods: </strong>Seventy-two rats were randomly assigned to seven groups: group A (n=12, tissue suspension 0.2mL), group B (n=12, 1×10^8 CFU/mL <i>Corynebacterium kroppenstedtii</i> (<i>CK</i>) suspension 0.1mL), group C (n=12, 1×10^9 CFU/mL <i>CK</i> suspension 0.1mL), group D (n=12, tissue suspension 0.1mL + 1×10^8 CFU/mL <i>CK</i> suspension 0.1mL), group E (n=12, tissue suspension 0.1mL + 1×10^9 CFU/mL <i>CK</i> suspension 0.1mL), group F (n=6, phosphate buffer saline solution 0.1mL), and group G (n=6, physiological saline 0.1mL + Complete Freund's adjuvant suspension 0.1mL). Groups A to E constitute the experimental groups with 12 rats each, while groups F and G served as control groups with 6 rats each. Tissue suspension of patients with granulomatous mastitis and different concentrations of <i>CK</i> solution were injected into the fourth pair of mammary glands of rats. Tissue samples were harvested on the 3rd, 7th, and 14th days post-implantation. The breast tissue specimens were stained with HE stain and Gram stain to observe the histopathological characteristics and the presence of Gram-positive bacteria. Bacterial culture was performed to observe the presence of <i>CK</i>. The expression levels of C-reactive protein and interleukin-1 beta were detected.</p><p><strong>Results: </strong>Rats in groups A, D, and E exhibited breast masses with erythema, with some showing ulceration, and granulomatous structures in pathological. Lipid vacuoles and Gram-positive rods observed in groups D and E. Pus cultures from groups D and E showed growth of <i>CK</i>. Histopathology revealed minimal inflammatory cell infiltration and no granulomatous formation in groups B and C. Group F showed no masses or inflammatory cell infiltration. Rats in group G presented with masses without ulceration, only chronic and acute inflammatory cell infiltration in pathological. Levels of C-reactive protein and interleukin-1 beta were significantly elevated in groups A and E at day 14.</p><p><strong>Conclusion: </strong>Components of pathological tissues from granulomatous mastitis patient combined with <i>CK</i> suspension, can successfully induce CNGM in rat models.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1887-1898"},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Core Genes Associated with Sepsis and Systemic Inflammatory Response Syndrome Using Single-Cell Sequencing Technology.","authors":"YuZhou Shen, LingHan Leng, YingChun Hu","doi":"10.2147/JIR.S448900","DOIUrl":"10.2147/JIR.S448900","url":null,"abstract":"<p><strong>Purpose: </strong>As a crucial aspect of emergency critical medicine, sepsis has been in a difficult stage. As its \"preparatory stage\", SIRS has attracted the attention of the medical workers all over the world. The frequency of occurrence is on the rise, but there is a lack of certain indicators for the timely detection and recognition of illnesses.</p><p><strong>Methods: </strong>By virtue of scRNA-seq, this research has analyzed single-cell transcriptome data from samples taken from groups with septic death and systemic inflammatory response syndrome so as to identify the unique markers and patterns in immune response.</p><p><strong>Results: </strong>By revealing the status of twelve cell clusters of four major cell types in blood samples through UMAP cell clustering and the differences of major cell populations between the dead and SIRS patients, the results have elucidated the components of different cells and their marker genes in two disease states, and the response mechanism beneficial to disease diagnosis in blood samples.</p><p><strong>Conclusion: </strong>By establishing a theoretical framework centered on cellular and molecular regulation, the study has introduced a novel approach for diagnosing and treating sepsis death group and SIRS patients early, as well as differentiating and preventing these conditions.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1815-1838"},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398333","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":"Quzhou Aurantii Fructus Flavonoids Ameliorate Inflammatory Responses, Intestinal Barrier Dysfunction in DSS-Induced Colitis by Modulating PI3K/AKT Signaling Pathway and Gut Microbiome.","authors":"Haiou Wang, Wenkang Huang, Xiaoya Pan, Meizi Tian, Jiahui Chen, Xiaotong Liu, Qin Li, Jianhua Qi, Yiping Ye, Lijuan Gao","doi":"10.2147/JIR.S500014","DOIUrl":"10.2147/JIR.S500014","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the protective effect and underlying mechanism of Quzhou Aurantii Fructus flavonoids (QAFF) on Ulcerative colitis (UC).</p><p><strong>Methods: </strong>The constituents of QAFF were accurately determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic impacts of QAFF were assessed in dextran sulfate sodium (DSS)-induced UC mice, focusing on the changes in body weight, disease activity index (DAI), colon length, histological assessment of colonic tissues, levels of pro-inflammatory cytokines, and expression of tight junction proteins. Western blotting confirmed key regulatory proteins within the differential signaling pathways, guided by transcriptome analysis. Additionally, the influence of QAFF on the gut microbiome was explored through 16S ribosomal RNA (rRNA) sequencing. The alterations in endogenous metabolites were detected by untargeted metabolomics, and their potential correlation with intestinal flora was then examined utilizing Spearman correlation analysis. Subsequently, the regulation of gut microbiome by QAFF was validated by fecal microbiota transplantation (FMT).</p><p><strong>Results: </strong>Eleven flavonoids, including Naringin and hesperidin, were initially identified from QAFF. In vivo experiments demonstrated that QAFF effectively ameliorated colitis symptoms, reduced IL-6, IL-1β, and TNF-α levels, enhanced intestinal barrier integrity, and downregulated PI3K/AKT pathway activation. Furthermore, QAFF elevated the levels of beneficial bacteria like <i>Lachnospiraceae_NK4A136_group</i> and <i>Alloprevotella</i> and concurrently reduced the pathogenic bacteria such as <i>Escherichia-Shigella, [Eubacterium]_</i>siraeum<i>_group</i>, and <i>Parabacteroides</i>. Metabolomics analysis revealed that 34 endogenous metabolites exhibited significant alterations, predominantly associated with Glycerophospholipid metabolism. These metabolites were significantly correlated with those differential bacteria modulated by QAFF. Lastly, the administration of QAFF via FMT ameliorated the colitis symptoms.</p><p><strong>Conclusion: </strong>QAFF could ameliorate inflammatory responses and intestinal barrier dysfunction in DSS-induced UC mice probably by modulating the PI3K/AKT signaling pathway and gut microbiome, offering promising evidence for the therapeutic potential of QAFF in UC treatment.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1855-1874"},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390364","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":"Role of Aging in Ulcerative Colitis Pathogenesis: A Focus on ETS1 as a Promising Biomarker.","authors":"Man Ni, Weilong Peng, Xiaoguang Wang, Jingui Li","doi":"10.2147/JIR.S504040","DOIUrl":"10.2147/JIR.S504040","url":null,"abstract":"<p><strong>Purpose: </strong>An increasing proportion of the aging population has led to a rapid increase in the number of elderly patients with ulcerative colitis (UC). However, the molecular mechanisms by which aging causes UC remain unclear. In this study, we explored the role of aging-related genes (ARGs) in UC pathogenesis and diagnosis prediction.</p><p><strong>Methods: </strong>Gene expression data were obtained from four independent datasets (GSE75214, GSE87466, GSE94648, and GSE169568) in the GEO database, and ARGs were derived from multiple public databases. After identifying UC-related ARGs, consistent clustering was performed to screen aging-related molecular subtypes, followed by the exploration of differences in the immune microenvironment and pathways between distinct subtypes. Next, core module genes were screened using WGCNA and then the hub genes were characterized using LASSO and random forest methods. Besides, the associations between hub genes, immune cells, and key pathways were explored. Finally, the expression levels of key genes were determined in a dextran sulfate sodium (DSS)-induced UC mouse model by qRT-PCR.</p><p><strong>Results: </strong>UC samples were classified into two subtypes (1 and 2), which displayed significant differences in the immune landscape and JAK/STAT signaling pathways. A series of machine learning algorithms was used to screen two feature genes (ETS1 and IL7R) to establish the diagnostic model, which exhibited satisfactory diagnostic efficiency. In addition, these hub genes were closely associated with the infiltration of specific immune cells (such as neutrophils, memory B cells, and M2 macrophages) as well as with the JAK/STAT pathway. Later, experimental validation confirmed that ETS1 expression was markedly increased in a mouse model of UC.</p><p><strong>Conclusion: </strong>Overall, aging, immune dysregulation, and UC process are closely associated. The identified feature genes, particularly ETS1, could serve as novel diagnostic biomarkers for UC. These findings have the potential to enhance the understanding of the age-related mechanisms of UC.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1839-1853"},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390948","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":"RECK as a Potential Crucial Molecule for the Targeted Treatment of Sepsis.","authors":"Yuting Qin, Shuanglin Liao, Jianbo Sun, Huiyun Ye, Jiafu Li, Jiahui Pan, Junbing He, Zhengyuan Xia, Yiming Shao","doi":"10.2147/JIR.S501856","DOIUrl":"10.2147/JIR.S501856","url":null,"abstract":"<p><p>Reversion inducing cysteine rich protein with kazal motifs (RECK), a Kazal motif-containing protein, regulates pro-inflammatory cytokines production, migration of inflammatory cells, vascular endothelial growth factor (VEGF) and Wnt pathways and plays critical roles in septic inflammatory storms and vascular endothelial dysfunction. Recently, RECK has been defined as the negative regulator of adisintegrin and metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs), which are both membrane \"molecular scissors\" and aggravate the poor prognosis of sepsis. To better understand the roles of RECK and the related mechanisms, we make here a systematic and in-depth review of RECK. We first summarize the findings on structural characteristics of RECK protein and the regulation at the transcription, post-transcription, or protein level of RECK. Then, we discuss the roles of RECK in inflammation, infection, and vascular injury by focusing on the RECK function on ADAMs and MMPs, as well as the pathways of VEGF, WNT, angiopoietin, and notch signaling. In conclusion, RECK participation as a guardian in the development of sepsis provides insight into the strategies of precisely intervening in RECK dysregulationfor the treatment of sepsis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1787-1813"},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390849","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":"Elucidating the Role of HIF-1α/YAP Signaling Pathway in Regulating Inflammation in Human Periodontal Stem Cells: An in vitro Study.","authors":"Hui-Wei Zhao, Shu-Tai Liu, Xiang-Jin Wang, Xue-Mei Zhang, Xiang Ma","doi":"10.2147/JIR.S504793","DOIUrl":"10.2147/JIR.S504793","url":null,"abstract":"<p><strong>Background and objective: </strong>Periodontitis is a chronic inflammatory disease caused by dental plaque accumulation, leading to damage of periodontal tissues and potential tooth loss. Understanding the mechanisms of periodontitis, particularly the role of hypoxia in inflammation, is critical for identifying novel therapeutic strategies. This study investigated the effects of the prolyl hydroxylase (PHD) inhibitor DMOG on pro-inflammatory cytokine expression in human periodontal ligament stem cells (hPDLSCs) and examined the involvement of the HIF-1α/YAP signaling path ay in modulating inflammation.</p><p><strong>Materials and methods: </strong>hPDLSCs were cultured and treated with lipopolysaccharide (LPS) to induce inflammation, followed by DMOG treatment. Cell proliferation was assessed using the CCK-8 assay, while ELISA and RT-qPCR evaluated the expression levels of HIF-1α, IL-1β, TNF-α, and YAP. YAP expression was knocked down using siRNA transfection to examine its effects on inflammatory cytokines.</p><p><strong>Results: </strong>DMOG significantly increased HIF-1α expression while reducing IL-1β and TNF-α levels in LPS-treated hPDLSCs. 0.1 mmol/L DMOG inhibited cell proliferation after 72 hours (P < 0.001). ELISA results showed that HIF-1α concentrations in the LPS + DMOG group were significantly higher than in the LPS group (P < 0.01), while IL-1β and TNF-α levels were significantly reduced (P < 0.01). RT-qPCR confirmed these trends, showing reduced mRNA levels of IL-1β and TNF-α and increased YAP expression in the LPS + DMOG group (P < 0.0001). YAP knockdown via siRNA transfection reversed these effects, increasing IL-1β and TNF-α levels (P < 0.01) while significantly reducing HIF-1α expression (P < 0.05).</p><p><strong>Conclusion: </strong>This study demonstrated that DMOG reduces inflammatory cytokine expression in hPDLSCs by stabilizing HIF-1α and activating the YAP signaling pathway. These findings provide a mechanistic basis for targeting the HIF-1α/YAP axis to control periodontal inflammation and support the potential of PHD inhibitors as therapeutic agents for periodontitis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1875-1886"},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391100","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":"Remote Continuous Microinjury-Triggered Cytokines Facilitate Severe Diabetic Foot Ulcer Healing via the Ras/Raf/MEK/ERK Pathway.","authors":"Xiajie Huang, Jie Liu, Xiaomei Wu, Yangzhou Mo, Xiping Luo, Yongge Yang, Chaoquan Yang, Xinyun Liang, Rongyuan Liang, Yeping Chen, Zezhen Fan, William Lu, Yan Chen, Qikai Hua","doi":"10.2147/JIR.S493505","DOIUrl":"10.2147/JIR.S493505","url":null,"abstract":"<p><strong>Purpose: </strong>Microinjury can trigger in situ tissue repair. Bone transport consists of continuous microinjuries/microfracture and induces bone formation and angiogenesis. Tibial cortex transverse transport (TTT) was found to promote angiogenesis at the foot and the healing of diabetic foot ulcers (DFUs). However, the underlying mechanism remains largely unknown.</p><p><strong>Methods: </strong>We divided 72 Sprague-Dawley rats with DFUs into the control, sham, and TTT groups. Wound measurement and histology were performed to evaluate the wound healing processes. Enzyme-linked immunosorbent assay, flow cytometry, immunohistochemistry, and Western Blot were used to assess angiogenesis and the activity of endothelial progenitor cells (EPCs) and the Ras/Raf/MEK/ERK signaling pathway.</p><p><strong>Results: </strong>We found accelerated wound healing, improved epidermal continuity, and increased dermal thickness in the TTT group than the control and the sham groups. Higher levels of serum TGF-β1, PDGF-BB, and VEGF were detected in the TTT group. These changes were in parallel with the expression of TGF-β1, PDGF-BB, and VEGF in the foot wounds and the frequency of EPCs in both bone marrow and peripheral circulation, which implied that the secreted TGF-β1, PDGF-BB, and VEGF promote proliferation and migration of EPCs to the foot wounds. The expression of CD31⁺ cells, SMA-α⁺ cells, and the Ras/Raf/MEK/ERK pathway was higher in the TTT group than in the control and sham groups.</p><p><strong>Conclusion: </strong>The findings showed that TTT enhanced the production of growth factors that in turn activated EPC proliferation and migration through the Ras/Raf/MEK/ERK pathway, ultimately contributing to angiogenesis and DFU healing. Based on these findings, we proposed a theory that remote continuous microinjuries can trigger the repair of target tissues (ie, microinjury-induced remote repair, MIRR). Future studies are needed to validate this theory.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1755-1772"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390942","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":"Erbin Regulates Tissue Factors Through Ras/Raf Pathway in Coagulation Disorders in Sepsis.","authors":"Cheng Yang, Chuntian Lei, Guoqing Jing, Yun Xia, Huimin Zhou, Die Wu, Jing Zuo, Hailong Gong, Xing Wang, Yingyue Dong, Delida Aidebaike, Xiaojing Wu, Xuemin Song","doi":"10.2147/JIR.S493093","DOIUrl":"10.2147/JIR.S493093","url":null,"abstract":"<p><strong>Background: </strong>Sepsis, as a clinically critical disease, usually induces coagulation disorders. It has been reported that ERBB2 Interacting Protein (Erbin) is involved in the development of various inflammatory diseases, and macrophages are involved in the regulation of coagulation disorders in sepsis. However, the role of Erbin in coagulation disorders in sepsis and the relationship between Erbin and macrophage regulation of coagulation function are still unclear.</p><p><strong>Methods: </strong>At the cellular level, macrophages were treated with lipopolysaccharide (LPS) or MEK inhibitor (PD98059), protein expression levels were detected by Western blot, co-immunoprecipitation (Co-IP), and immunofluorescence, mRNA expression levels were detected by quantitative real-time polymerase chain reaction (qPCR), and the concentration of tissue factor (TF) in cell supernatant was detected by enzyme linked immunosorbent assay (ELISA). At the animal level, the cecal ligation and perforation (CLP) model was constructed in mice, and the inflammatory response and coagulation disorder of mice were observed by hematoxylin-eosin (HE) staining, immunohistochemistry, ELISA, and automatic hemagglutination analyzer. The protein and mRNA expression level were detected by Western blot and qPCR. Pearson linear correlation analysis was used to analyze the correlation between the inflammation index and the coagulation function index.</p><p><strong>Results: </strong>We confirmed that the Erbin is involved in the regulation of coagulation function by macrophages and plays a role in the coagulation disorder of sepsis. In vivo studies have shown that mice with Erbin deletion have more obvious enhanced coagulation function, and in vitro studies have shown that Erbin knockout mediated macrophage secretion of TF by activating the Ras/Raf pathway.</p><p><strong>Conclusion: </strong>Erbin reduces the coagulation activation by inhibiting TF release from macrophages.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1739-1754"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391101","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":"Prominence of Microbiota to Predict Fibrous Stenosis in Crohn's Disease.","authors":"Xue Yang, Yan Pan, Cai-Ping Gao, Hang Li, Ying-Hui Zhang, Chun-Li Huang, Lu Cao, Shi-Yu Xiao, Zhou Zhou","doi":"10.2147/JIR.S480473","DOIUrl":"10.2147/JIR.S480473","url":null,"abstract":"<p><strong>Purpose: </strong>Intestinal fibrous stenosis due to Crohn's disease (CD) is highly prevalent. Although several clinical risk factors for fibrous stenosis have been identified, such as perianal fistulizing disease, small bowel disease location, and deep mucosal ulceration, predicting fibrous stenosis remains challenging. The intestinal microbiota plays a crucial role in the development and progression of CD. However, its role in intestinal fibrous stenosis is poorly understood. Leveraging a single-center cross-sectional study, we aimed to investigate the role of fecal microbiota in CD-associated fibrous stenosis.</p><p><strong>Methods: </strong>Using metagenomic analysis, we examined the differences in fecal microbiota between CD patients with intestinal fibrous stenosis and those without stenosis. We identified specific microbiota and assessed their predictive accuracy for intestinal fibrous stenosis. Additionally, we explored functional differences in intestinal microbiota between the two groups.</p><p><strong>Results: </strong>: Our investigation of fecal samples revealed no significant differences in the gut microbiota structure between patients with fibrous stenosis and those without stenosis in CD. However, taxonomically, we found 70 taxa with significantly different abundance (p < 0.05) between the two groups. Furthermore, LEfSe analysis indicated that <i>g_Bacteroides</i> and <i>g_Enterocloster</i> could predict intestinal fibrous stenosis while <i>p_Actinobacteria, c_Actinomycetia, c_Bacilli, o_Lactobacillales, f_Streptococcaceae</i> and <i>g_Streptococcus</i> could predict CD without stenosis. Functional analysis revealed differential enrichment in five metabolic pathways at the KEGG pathway level in CD patients with fibrous stenosis, including sphingolipid metabolism, lipoic acid metabolism, and biosynthesis of neomycin, kanamycin and gentamicin. In the eggNOG database, we observed differences in four functional categories between the two groups, encompassing cellular process, signaling, and metabolism.</p><p><strong>Conclusion: </strong>Fecal microbiota significantly impacted intestinal fibrous stenosis in CD. Although there were no significant differences in alpha and beta diversities, fibrous stenosis was associated with changes in microbiota composition and function, suggesting the potential of fecal microbiota in predicting CD-associated fibrous stenosis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1413-1423"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390136","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":"Metformin Ameliorates Ulcerative Colitis Through Inhibiting NLRP3 Inflammasome Activation.","authors":"Run Cao, Jing Jing, Yuting Ma, Wenqing Qi, Xinyu Huang, Chaofang Zhang, Zhizhuo Lu, Jiayi He, Guiling Wang, Yuanfang Ma, Hailong Zhang","doi":"10.2147/JIR.S503033","DOIUrl":"10.2147/JIR.S503033","url":null,"abstract":"<p><strong>Purpose: </strong>Metformin (Met) is widely used to treat a variety of diseases, but its role in ulcerative colitis (UC) has not been fully elucidated. This study aimed to clarify the effect of Met on UC, exploring its relationship with NLRP3 inflammasome and elucidating the potential mechanisms.</p><p><strong>Methods: </strong>C57BL/6J mice were administrated with DSS solution to establish UC model. Disease Activity Index (DAI) and hematoxylin and eosin staining (HE) were performed to evaluate the impact of Met on UC model. Enzyme-linked immunosorbent assay (ELISA), Reverse transcription - quantitative polymerase chain reaction (RT-qPCR), Western blotting (WB), immunohistochemistry, and immunofluorescence were used to detect NLRP3 inflammasome activation in vivo. Furthermore, in vitro, bone marrow-derived macrophages (BMDMs) selected to clarify the role of Met on NLRP3 inflammasome activation and the underlying mechanisms.</p><p><strong>Results: </strong>In vivo, Met could significantly inhibit the development of UC, characterized by decreased DAI, increased body weight and colorectal length, and the repair of damaged tissue. Met could also block macrophage infiltration and subsequently reduced the level of IL-1β, NLRP3, and Caspase-1 in the colorectal tissue, which were mainly expressed by macrophages. In addition, the level of IL-1β in serum was remarkedly down-regulated by Met. In vitro, Met could inhibit NLRP3 inflammasome activation and subsequently dampen the maturation of pro-caspase-1 and pro-IL-1β. Moreover, Met could simultaneously suppress the activation of NF-κB/p65 signaling pathway and disrupt the formation of ASC speck. At last, Met exhibited an anti-oxidant effect, along with upregulating the level of UCP2 and NCF1.</p><p><strong>Conclusion: </strong>Met significantly ameliorated UC by inhibiting NLRP3 inflammasome activation in macrophages. The underlying mechanisms not only involved the inhibition of NF-κB signaling pathway activation (first signal), but was also associated with up-regulation of UCP2 and NCF1 levels and thus the repression of ROS generation (second signal).</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1773-1786"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391102","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}