Mediators of Inflammation最新文献

{"title":"Caffeine Acts as an Agonist of Siglec-6, Inhibits MRGPRX2-Triggered Mast Cell Degranulation and Anaphylactoid Reactions.","authors":"Yuanyuan Ding, Na Wang, Chenrui Zhao, Hongfen Du, Yujuan Yuan, Tao Zhang, Hongli An","doi":"10.1155/mi/9580121","DOIUrl":"10.1155/mi/9580121","url":null,"abstract":"<p><p><b>Background:</b> Mast cells (MCs) are effectors of anaphylactoid reactions. Mas-related G-protein-coupled receptor X2 (MRGPRX2) receptor mediates the direct activation of MCs in anaphylactoid disease. Siglec-6 negatively regulates MC activation and is a promising target in the development of antianaphylactoid reaction drugs. While caffeine exhibits an inhibitory effect against anaphylactic shock, the molecular mechanisms underlying these activities remain unknown. <b>Objectives:</b> Our objective was to investigate the inhibitory effect of caffeine and its underlying molecular mechanism in MRPGRX2-induced MC activation and anaphylactoid reactions. <b>Methods:</b> Local and systemic anaphylactoid reactions in mice and in vitro MC activation experiments were conducted to investigate the effects of caffeine on anaphylactoid reactions. Molecular docking and surface plasmon resonance (SPR) experiments were used to predict and verify the molecular target of caffeine activity. siRNA silencing and western blot analyses were utilized to investigate the molecular mechanisms underlying caffeine activity. <b>Results:</b> Caffeine inhibited local and systemic anaphylactoid reactions in mice and attenuated MRGPRX2-induced MC activation. Release of β-hexosaminidase, histamine, and Ca²⁺ in siRNA-Siglec-6-laboratory allergic disease 2 (LAD2) cells was significantly higher than in NC-LAD2 cells. The binding affinity between caffeine and Siglec-6 protein is with a calculated <i>K</i> _D of 1.76 × 10^-7 mol/L. Caffeine increased Siglec-6 expression, phosphorylation of SHP-1, and dephosphorylation of PLC-γ1, IP3R, and ERK1/2 in the MRGPRX2 signaling pathway. Western blot demonstrated that phosphorylated SHP-1 (p-SHP-1) protein levels showed no increase, and MRGPRX2, phosphorylated PLCγ1 (p-PLCγ1), and phosphorylated ERK1/2 (p-ERK1/2) were abolished with caffeine treatment in Siglec-6-knockdown cells than in NC-knockdown cells. Caffeine suppressed the m-3M3FBS-induced upregulation of p-PLCγ1 and p-ERK1/2 levels. <b>Conclusions:</b> We have demonstrated that caffeine is an agonist of Siglec-6 and that subsequent activation of the ITIM motif of Siglec-6 phosphorylates SHP-1. This arrests MRGPRX2/PLC-γ1/IP3R signal transduction, thereby attenuating anaphylactoid reactions, including anaphylactic shock.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9580121"},"PeriodicalIF":4.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics Integration and Machine Learning Reveal Colony Stimulating Factor 3 Receptor as a Key Gene and Therapeutic Target in Crohn's Disease.","authors":"Peihong Li, Hongyi Hu, Lujia Yang, Linda Zhong, Boyun Sun, Chaoqun Bao","doi":"10.1155/mi/1619237","DOIUrl":"10.1155/mi/1619237","url":null,"abstract":"<p><p>Crohn's disease (CD) is a chronic inflammatory disease characterized by complex immune dysregulation in which the identification of key molecular drivers is critical for the advancement of diagnostic and therapeutic approaches. In this study, we integrated transcriptomic data from multiple cohorts and applied three machine learning algorithms-Random forest, support vector machine recursive feature elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO)-to robustly identify key gene, converging on CSF3R as a top candidate. Mendelian randomization (MR) analysis supported a causal role of CSF3R in CD pathogenesis (OR = 1.400, 95% CI: 1.022-1.917). Enrichment analysis revealed its association with cytokine-receptor interactions and the JAK-STAT pathway. Single-cell RNA sequencing and immune infiltration analyses demonstrated elevated CSF3R expression in neutrophils, implicating it in neutrophil-mediated inflammation. Experimental validation using intestinal biopsies from CD patients and healthy controls (HCs) confirmed significantly upregulated CSF3R expression at both mRNA and protein levels, as shown by quantitative reverse transcription PCR (qPCR), western blot, and immunohistochemistry. Double immunofluorescence further revealed strong colocalization of CSF3R with the neutrophil marker CD66b, supporting its functional association with neutrophil infiltration. Moreover, molecular docking indicated high binding affinity between CSF3R and several therapeutic agents, including methotrexate and aspirin. Diagnostic performance assessments yielded high AUC values (0.823-0.938) across multiple datasets. Collectively, these findings highlight CSF3R as a robust diagnostic gene and promising therapeutic target in CD, offering mechanistic insights and opportunities for precision medicine.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"1619237"},"PeriodicalIF":4.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoration of Immune Homeostasis: The Role of miR-30b-5p and Notch Signaling in Uveitis After Treatment With Longdan Xiegan Decoction.","authors":"Yan Qiu, Xuewei Yin, Lijie Guo, Baojian Wang, Miao Zhang, Shuqin Xu, Huixia Wei, Bin Liu, Yane Gao, Hongsheng Bi, Dadong Guo","doi":"10.1155/mi/8824838","DOIUrl":"10.1155/mi/8824838","url":null,"abstract":"<p><p>Uveitis is an inflammatory eye disease, and Longdan Xiegan Decoction (LXD) has been used to treat uveitis. However, the underlying mechanisms have not fully been addressed. The present study aimed to provide new insights into LXD ameliorating inflammatory response of experimental autoimmune uveitis (EAU) and regulating T helper (Th) cell differentiation via the interaction between microRNA (miRNA) and mRNA. The hub genes, corresponding miRNAs, and bioactive substances from the LXD formula that are involved in ameliorating uveitis were identified through the network pharmacology analysis. We investigated the efficacy of LXD on the pathogenesis of EAU in vivo using the Genesis-D camera and histopathological examination, and confirmed the inhibitory effect of miR-30b-5p on the Notch signaling pathway in vitro. The analysis results indicated that T-cell lineage commitment and the Notch signaling pathway activation are the primary inflammatory process associated with the therapeutic effects of LXD on uveitis. Further predictions revealed the miRNA-mRNA interactions between miR-30b-5p and the mRNAs associated with Notch1 and DLL4. The pathogenesis of uveitis involves elevated Notch1, DLL4, IL-17A, and RORγt, and decreased levels of miR-30b-5p. LXD can enhance miR-30b-5p expression, inhibit Notch signaling activation, and suppress the commitment of uveitogenic T-cell lineages. Additionally, it downregulates proinflammatory cytokines while upregulating antiinflammatory cytokines, thereby promoting the the expansion of Treg and Th2 cell lineages, and restoring the ratios of Th1/Th2 and Th17/Treg cells. Reduced expression of miR-30b-5p contributes to the pathogenesis of uveitis. LXD exhibited an inhibitory effect on Notch signaling activation through the miR-30b-5p upregulation and the regulation of the balance between Th1/Th2 and Th17/Treg cell differentiation, ultimately facilitating the treatment of uveitis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8824838"},"PeriodicalIF":4.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Neutrophil-to-Lymphocyte Ratio, Atherogenic Index of Plasma, and Cardiovascular Disease Incidence.","authors":"Hongxin Cheng, Wen Zhong, Hanbin Li, Lu Wang, Chengqi He, Liyi Huang, Chenying Fu, Quan Wei","doi":"10.1155/mi/3302911","DOIUrl":"10.1155/mi/3302911","url":null,"abstract":"<p><p><b>Background:</b> With the incidence of cardiovascular disease (CVD) escalating annually, the significance of investigating the correlation between inflammatory markers and lipid-related indices, notably the neutrophil-to-lymphocyte ratio (NLR) and atherogenic index of plasma (AIP), is increasingly paramount. This study aimed to elucidate the distinct and combined roles of NLR and AIP concerning the incidence of CVD. <b>Methods:</b> Diagnoses of CVD were established based on self-reported standardized medical condition questionnaires from participants. NLR was computed by dividing the peripheral blood neutrophil count by the lymphocyte count. AIP was calculated as log [triglyceride (TG, mg/dL)/high-density lipoprotein cholesterol (HDL-C, mg/dL)]. The study's primary outcome was the incidence of CVD. To ensure the reliability and accuracy of the results, the analysis incorporated sample weights and complex survey designs. <b>Results:</b> The final analysis included 13,184 individuals. Higher levels of NLR and AIP were independently associated with CVD. After adjusting for all variables, compared to Q1 of AIP or NLR, Q4 of AIP (OR 1.54, 95% CI: 1.19-1.98) and NLR (OR 1.54, 95% CI: 1.19-1.98) was significantly associated with CVD. The joint effects showed that participants with higher levels of NLR and AIP had a significantly higher OR of 1.41(1.06, 1.87). The combination of NLR and AIP has better predictive efficacy (AUC: 0.629) for CVD than alone. <b>Conclusion:</b> This cohort suggests combined effects between the NLR and AIP on CVD. Our findings provide clinical implications for monitoring and managing NLR and AIP levels to mitigate the development of CVD.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"3302911"},"PeriodicalIF":4.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep Patterns and Cardiovascular Disease Risk: Investigating the Mediating Role of Inflammatory Markers in a Large NHANES Adult Population.","authors":"Xinru Guo, Shiting Mi, Lin Zhao, Tielong Chen","doi":"10.1155/mi/3250786","DOIUrl":"10.1155/mi/3250786","url":null,"abstract":"<p><p><b>Purpose:</b> Inflammation plays a central role in the occurrence and progression of cardiovascular disease (CVD). However, the intricate relationships between sleep patterns, inflammatory markers, and CVD risk remain insufficiently understood. This study aims to explore these associations, with a specific focus on the mediating role of inflammatory markers and their nonlinear effects. <b>Methods:</b> This study used a multiethnic adult population (<i>N</i> = 8752) from the National Health and Nutrition Examination Survey (NHANES) database (four data cycles from 2005-2006, 2007-2008, 2015-2016, and March 2017-2020). Multivariate logistic regression assessed the effects of sleep patterns and inflammatory markers on CVD risk. Furthermore, the mediating effects of the neutrophil-platelet ratio (NPR) and the systemic immune-inflammation index (SII) were assessed. Binary logistic regression was utilized to analyze the correlations between quartile groupings of inflammatory markers (SII and NPR) and CVD, as well as its specific types. The nonlinear relationship between inflammatory markers and CVD risk was explored using a generalized additive model (GAM). <b>Results:</b> Trouble sleep pattern significantly increased the risk of CVD (odds ratio [OR] = 2.7558, 95% confidence interval [CI]: 1.9019, 3.9931, <i>p</i>  < 0.0001). Mediation analyses showed NPR mediated 17.38% and SII mediated 3.27% of the association. GAM showed that NPR (<i>p</i>-trend < 0.0001) and SII (<i>p</i>-trend = 0.001) had a significant inverted \"U\" shaped relationship with CVD risk, with higher inflammation increasing CVD risk up to a point, after which the risk decreased. <b>Conclusion:</b> Trouble sleep pattern significantly increased CVD risk, NPR and SII partially mediated the relationship between sleep patterns and CVD risk, and the nonlinear relationship with CVD risk suggests a bi-directional mechanism for the regulation of inflammatory markers. These findings offer new insights for inflammatory interventions and sleep health management in CVD prevention.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"3250786"},"PeriodicalIF":4.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC.","authors":"Bokang Yan, Jiaxing Guo, Meiyuan Huang, Zhecheng Li, Jingyue Sun, Hailong Tan, Weiwei Lai, Shi Chang","doi":"10.1155/mi/5576056","DOIUrl":"https://doi.org/10.1155/mi/5576056","url":null,"abstract":"<p><p>G protein-coupled receptor 34 (GPR34) is an orphan receptor within the G protein-coupled receptor (GPCR) superfamily, and its specific role in anaplastic thyroid carcinoma (ATC) remains to be elucidated. In this study, we observed that GPR34 was aberrantly upregulated in ATC and the deletion of GPR34 inhibited tumor progression both in vivo and in vitro. Additionally, suppression of GPR34 promoted ferroptosis in ATC cells. We further identified USP8 as a deubiquitinase (DUB) for GPR34, and the effects induced by GPR34 deletion were reversible through USP8 overexpression. Moreover, targeting USP8 with the inhibitor DUB-IN-3 effectively restrained ATC growth. Together, the present study revealed the role of GPR34 in ATC progression and ferroptosis, discovered its corresponding DUBs, and proposed GPR34 as a promising target for ATC therapy.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5576056"},"PeriodicalIF":4.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Aster spathulifolius</i> Maxim. Alleviates Primary Dysmenorrhea in a Mouse Model by Modulating Myometrial Contractions via NF-κB/COX-2 Pathway Inhibition.","authors":"Min-Soo Kim, Kang-In Lee, Heung Joo Yuk, Yousang Jo, Hyungjun Kim, Ki-Sun Park","doi":"10.1155/mi/1654087","DOIUrl":"https://doi.org/10.1155/mi/1654087","url":null,"abstract":"<p><p>Primary dysmenorrhea (PD) is characterized by excessive uterine contraction and ischemic vasoconstriction, primarily driven by elevated levels of prostaglandins (PGs; PGF2α) and inflammatory mediators. Nonsteroidal antiinflammatory drugs (NSAIDs) remain the standard treatment for PD; however, their associated adverse effects necessitate the use of alternative therapeutic strategies. <i>Aster spathulifolius</i> Maxim. is a perennial herb native to the coastal regions of Korea, that exhibits antiviral, anticancer, and antidiabetic effects. In this study, we investigated the potential of <i>Aster spathulifolius</i> Maxim. extract (PDR97) to alleviate PD in both animal models and human uterine smooth muscle cells (HUtSMCs). Our findings demonstrated that PDR97 significantly reduced pain-related responses and restored uterine morphology in PD-induced mice. Mechanistically, PDR97 suppressed the expression of uterine contraction-related proteins, decreased NF-κB phosphorylation, and downregulated the expression of proinflammatory cytokines. Furthermore, PDR97 effectively inhibited PGF2α- and interleukin-1β (IL-1β)-induced reactive oxygen species (ROS) production in both the PD mouse model and HUtSMCs, exhibiting potent antioxidant properties. Notably, PDR97 modulated NF-κB signaling-a key regulatory pathway associated with uterine contraction and pain relief-and its antioxidant effects contributed to the suppression of inflammatory and oxidative stress-mediated signaling. Collectively, these findings highlight the potential of PDR97 as a promising natural therapeutic agent for PD, with potential applications in other gynecological disorders associated with inflammation and oxidative stress.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"1654087"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Ifitm1 as a Pivotal Gene in Mouse Spinal Cord Injury Using Comprehensive Machine Learning Algorithms.","authors":"Yu Yao, Kun Xi, Shaohu Xu, Feiyu Zhang, Liang Chen","doi":"10.1155/mi/6149780","DOIUrl":"10.1155/mi/6149780","url":null,"abstract":"<p><p><b>Background:</b> Spinal cord injury (SCI) functions as a medical condition leading to substantial motor and neurological system deteriorations. Researchers must understand the molecular mechanisms of this disease because it serves as a foundation for creating therapeutic solutions. <b>Methods:</b> This study analyzed the single-cell dataset GSE189070 and microarray datasets GSE47681, GSE92657, and GSE93561 retrieved from the GEO database. Using R packages \"Seurat\" and \"Celldex,\" we identified and annotated cell clusters in single-cell data. Combined microarray datasets underwent differential expression analysis, WGCNA, and machine learning to identify key hub genes. Immune cell associations were assessed using Cibersort, while the connection map (CMap) database was employed to predict small-molecule drugs targeting the identified genes. Experimental validation confirmed findings. <b>Results:</b> In datasets involving single cells, granulocyte subpopulations denote unique cellular populations related to SCI. The high-dimensional weighted gene co-expression network analysis (hdWGCNA) algorithm pinpointed crucial modules linked to granulocyte subgroups, particularly from the black, green, and yellow modules. In the SCI cohort, Ifitm1 emerged as a potential hub gene. Importantly, Ifitm1 shows a significant positive correlation with M1 macrophages. Utilizing the CMap database along with molecular docking investigations, the small-molecule drug NVP-AUY922, which interacts with Ifitm1, was discovered. Experimental assessments revealed that Ifitm1 is linked to macrophage inflammation following SCI. <b>Conclusion:</b> This study revealed the importance of granulocyte subsets and Ifitm1 in SCI, proposed Ifitm1 as a potential therapeutic target, and provided new insights into the molecular mechanisms of SCI.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6149780"},"PeriodicalIF":4.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota Dysbiosis in Preeclampsia: Mechanisms, Biomarkers, and Probiotic-Based Interventions.","authors":"Yefang Zhao, Bingjie Wang, Xujing Wei, Dengxiang Liu, Ruiping Wang, Huashu Ma, Zongxu Qiao, Nana Kong, Jinhui Feng, Dan Cui, Shaoke Hou, Hongzhen Zhang","doi":"10.1155/mi/3010379","DOIUrl":"10.1155/mi/3010379","url":null,"abstract":"<p><p><b>Background:</b> This study aimed to investigate the impact of fecal microbiota transplantation (FMT) on gut microbiota composition and serum inflammatory factors in a murine model. <b>Methods:</b> Female C57BL/6J mice (<i>n</i> = 60) were divided into four groups: control (Con), negative (Neg), normal transplantation (NT), and preeclampsia transplantation (PET). The Con group received no treatment, while the Neg, NT, and PET groups were administered a triple antibiotic regimen (ampicillin, neomycin sulfate, and metronidazole) for 14 days to deplete gut microbiota. Following antibiotic treatment, FMT was performed: the NT group received fecal microbiota from healthy pregnant women and the PET group received microbiota from severe preeclampsia patients. Fecal samples and serum were collected for 16S rRNA sequencing and inflammatory factor analysis, respectively. <b>Results:</b> Significant differences in gut microbial composition were observed between the PET group and other groups, with enriched taxa such as <i>Coprococcus</i>, <i>Bacillales</i>, and <i>Staphylococcus</i> in the PET group. Conversely, taxa such as <i>Helicobacter</i> and <i>Klebsiella</i> were more abundant in the fecal microbiota of mice in the NT group. Furthermore, serum levels of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were markedly elevated in the PET group compared to the control, negative, and NT groups. Transplantation with fecal bacteria from preeclampsia patients leads to significant alterations in gut microbiota composition and increased serum inflammatory factors levels in mice. <b>Conclusion:</b> These findings provide insights into the relationship between gut microbiota and inflammatory processes in preeclampsia and underscore the potential therapeutic implications of FMT in modulating gut microbiota dysbiosis and inflammatory responses.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"3010379"},"PeriodicalIF":4.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunocytes Mediate the Effects of Gut Microbiome on Inflammatory Bowel Disease: Insights From a Mendelian Randomization Study.","authors":"Linbin He, Jianhui Wei, Ziye Li, Suyan Guo, Shanyu Lin, Tingting Wang, Lizhang Chen","doi":"10.1155/mi/9956259","DOIUrl":"10.1155/mi/9956259","url":null,"abstract":"<p><p>Observational evidence suggests a complex link between gut microbiota and inflammatory bowel disease (IBD). However, the mechanisms underlying this relationship remain unclear. The present Mendelian randomization (MR) study aims to examine the causal relationships between gut microbiome and IBD (including its subtypes), and to explore potential mediating effects of immunocyte. This MR study utilized the latest genome-wide association study data, which includes 412 gut microbiome features from the Dutch Microbiome Project, a meta-analysis of 731 immunocyte traits, and summary data on IBD from the FinnGen database. The two-sample MR was employed to examine the causal associations, with inverse-variance weighted (IVW) as the main statistical method. In addition, two-step MR was used to explore the mediation effect. Our MR analysis identified the causal effects of 13 microbial taxa, 23 microbial-related functional pathways, and 27 immunocyte traits on IBD. Notably, the dTDP-L-rhamnose biosynthesis pathway is the most significant risk factor for both IBD and its subtypes. After rigorous screening, 10 combinations were examined for mediated effects. This study brings valuable evidence for the relationship between gut microbiome and IBD and the mediating role of immunocyte, providing new insights into the identification of biomarkers and interventional targets for IBD.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9956259"},"PeriodicalIF":4.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}