Mediators of Inflammation最新文献

{"title":"Correlation of the Expression Profile of Peripheral Leukocyte and Liver Tissue Immune Markers With Serum Liver Injury Indices in Children With Biliary Atresia.","authors":"Anna Helmin-Basa, Izabela Kubiszewska, Joanna B Trojanek, Małgorzata Wiese-Szadkowska, Maria Janowska, Zbigniew Kułaga, Joanna Pawłowska, Jacek Michałkiewicz","doi":"10.1155/mi/9889239","DOIUrl":"https://doi.org/10.1155/mi/9889239","url":null,"abstract":"<p><p>The aim of the study was to find associations between the levels of liver injury serum markers and the selected liver, peripheral leukocytes, and plasma immune characteristics in biliary atresia (BA) children. Twenty-five newly diagnosed BA children aged 4-30 weeks and 12 age-matched controls were included (for leukocytes characteristics) and 19 BA children and 11 controls (for liver studies). The frequencies of T helper 1 (Th1), Th2, Th17, Th17.1 cells as well as numbers of regulatory T (Treg), B cell subsets, and matrix metalloproteinase -2 and -9 (MMP-2 and MMP-9) expressing leukocytes in the whole blood were evaluated by flow cytometry. Plasma concentrations of tissue inhibitors of metalloproteinase (TIMP)-1, -2, MMP-9, interleukin-17A (IL-17A) and IL-6 were assessed by enzyme-linked immunosorbent assay (ELISA). The leukocyte and liver expression of the retinoic acid receptor-related orphan nuclear receptor gamma (<i>RORγT</i>), fork-head winged helix transcription factor P3 (<i>FoxP3</i>), transforming growth factor beta (<i>TGF-β</i>), interleukin-17A (<i>IL-17A</i>), <i>IL-6</i>, <i>IL-1β</i>, <i>IL-21</i>, interleukin 1 receptor antagonist (<i>IL-1Ra)</i>, <i>MMP-2</i>, <i>MMP-9</i>, <i>MMP-12</i> (liver only), <i>TIMP-1</i>, <i>TIMP-2</i>, T-box transcription factor expressed in T cells, also called TBX21 (<i>T-bet</i>), GATA-binding protein 3 (<i>GATA3</i>), and C-type lectin (<i>CD161</i>) mRNA were determined by real time RT-PCR (reverse-transcription polymerase chain reaction). The BA patients were characterized by increased frequencies of peripheral \"suppressor\" glycoprotein-A repetitions predominant protein (GARP)<sup>+</sup>latency-associated peptide (LAP)<sup>+</sup>Treg and activated Treg cells as well as MMP-2 and MMP-9 bearing lymphocytes, elevated plasma TIMP-1 levels, increased leukocyte expression of <i>MMP-9</i>, <i>TIMP-1</i>, <i>TIMP-2</i>, <i>IL-6</i>, and <i>TGF-β</i>, and decreased leukocyte expression of IL-21 and T-bet, increased liver expression of <i>FoxP3</i>, <i>TIMP-1</i>, and decreased liver expression of <i>IL-1β</i> and <i>MMP-2</i>. The following correlations were found between serum markers of liver injury and leukocyte and liver immune characteristics: (a) hemoglobin (Hb) levels correlated negatively with frequency of peripheral \"suppressor\" GARP<sup>+</sup>LAP<sup>+</sup> Tregs; (b) aspartate aminotransferase (AST) levels correlated positively with frequency of the peripheral Th17.1 subset and expression of leukocyte <i>FoxP3</i>, (c) gamma glutamyltransferase (GGT) levels correlated positively with the peripheral memory B cells frequencies, the leukocyte <i>IL-6</i> and <i>TIMP-1</i> gene expression, (d) alanine aminotransferase (ALT) serum levels correlated positively with the naïve B cell frequency and liver <i>TIMP-2</i> expression, (e) total bilirubin (Bil) levels correlated positively with the leukocyte <i>MMP-9</i>, the plasma IL-6 levels, and the liver <i>TIMP-2</i> gene expression, (f) dir","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9889239"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004346","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 Sleep Disorder and Female Infertility: A Mediation Analysis of Inflammatory and Oxidative Markers.","authors":"Qiaorui Yang, Jinfu Zhang, Zhenliang Fan","doi":"10.1155/mi/4572392","DOIUrl":"https://doi.org/10.1155/mi/4572392","url":null,"abstract":"<p><p><b>Background:</b> Sleep disorder in women of reproductive age may contribute to infertility development, but there is a lack of substantial evidence linking sleep disorder to inflammation and oxidative stress, and the subsequent risk of infertility. <b>Methods:</b> A total of 2365 women aged 18-45 years from the National Health and Nutrition Examination Survey (NHANES) were included in this analysis. Sleep disorder and infertility were assessed according to NHANES questionnaire data module. Inflammatory and oxidative biomarkers such as high-sensitivity C-reactive protein (hs-CRP), white blood cell (WBC), gamma-glutamyl transpeptidase (GGT), albumin, ferritin, and total bilirubin were derived from the laboratory data module, and systemic immune inflammation index (SII), and system inflammation response index (SIRI) were calculated based on complete blood cell counts. A sophisticated multistage sampling design and weighted multivariable adjusted regression models were employed to conduct comprehensive analysis. Mediation models were applied to explicate the mediating role of biomarkers of inflammation and oxidative stress. <b>Results:</b> Compared to the noninfertility group, the infertile participants had a higher incidence of sleep disorder (34% vs. 25%, <i>p</i> < 0.05). In models with fully adjusted covariates, sleep disorder was positively associated with infertility risk (OR: 1.58; 95%CI: 1.01-2.50, <i>p</i> < 0.05), particularly in subgroups of individuals aged over 30 years old (OR: 1.75; 95%CI: 1.00-3.04, <i>p</i> < 0.05) or with a body mass index (BMI) ≥ 30 kg/m² (OR:2.05; 95%CI: 1.00-4.22, <i>p</i> < 0.05). In terms of mechanisms, there were significant correlations between inflammatory and oxidative markers and both sleep disorder and infertility. Mediation analysis indicated that hs-CRP, SII, SIRI, GGT, and total bilirubin played a significant mediating role in the relationship between sleep disorder and infertility, accounting for 0.4822%, 6.0515%, 1.2485%, 5.1584%, and 0.4738%, respectively. <b>Conclusions:</b> Sleep disorder is a significant risk factor for infertility, particularly in women aged >30 years or with obesity. Furthermore, the presence of inflammation and oxidative stress status in the body, which also significantly mediate the association between sleep disorder and infertility, can be swiftly and repeatedly identified through blood tests. Sleep, as a modifiable behavioral pattern, can be regarded as a new strategy to cope with infertility.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4572392"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001466","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":"A Predictive Model for Acute Kidney Injury Based on Leukocyte-Related Indicators in Hepatocellular Carcinoma Patients Admitted to the Intensive Care Unit.","authors":"Xiulan Peng, Yahong Cai, Huan Huang, Haifeng Fu, Wei Wu, Lifeng Hong","doi":"10.1155/mi/7110012","DOIUrl":"https://doi.org/10.1155/mi/7110012","url":null,"abstract":"<p><p><b>Background:</b> This study aimed to develop and validate a straightforward clinical risk model utilizing white blood cell (WBC) counts to predict acute kidney injury (AKI) in critically sick patients with hepatocellular carcinoma (HCC). <b>Methods:</b> Data were taken from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database for the training cohort. Data for an internal validation cohort were obtained from the eICU Collaborative Research Database (eICU-CRD), while patients from our hospital were utilized for external validation. A risk model was created utilizing significant indicators identified through multivariate logistic regression, following logistic regression analysis to determine the primary predictors of WBC-related biomarkers for AKI prediction. The Kaplan-Meier curve was employed to evaluate the prognostic efficacy of the new risk model. <b>Results:</b> A total of 1628 critically sick HCC patients were enrolled. Among these, 23 (23.2%) patients at our hospital, 84 (17.9%) patients in the eICU-CRD database, and 379 (35.8%) patients in the MIMIC-IV database developed AKI. A unique risk model was developed based on leukocyte-related indicators following the multivariate logistic regression analysis, incorporating white blood cell to neutrophil ratio (WNR), white blood cell to monocyte ratio (WMR), white blood cell to hemoglobin ratio (WHR), and platelet to lymphocyte ratio (PLR). This risk model exhibited robust predictive capability for AKI, in-hospital mortality, and ICU mortality across the training set, internal validation set, and external validation set. <b>Conclusion:</b> This risk model seems to have practical consequences as an innovative and accessible tool for forecasting the prognosis of critically ill HCC patients, which may, to some degree, aid in identifying equitable risk assessments and treatment strategies.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7110012"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033539","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":"Exploring the Relationship Between Immune Cells and Chronic Kidney Disease by Mendelian Randomization, Colocalization Analysis, and SMR.","authors":"Huiling Zhu, Chaofan Qin, Si Cheng, Xi Zhang","doi":"10.1155/mi/4279158","DOIUrl":"https://doi.org/10.1155/mi/4279158","url":null,"abstract":"<p><p><b>Background:</b> Chronic kidney disease (CKD) impacts millions of individuals annually. Current research suggests that immune factors played a significant role in CKD. However, the potential causal relationship between them remains unclear. <b>Methods:</b> We conducted a comprehensive Mendelian randomization (MR) analysis to assess the potential causal association between 731 immune cells and CKD. Sensitivity analysis was performed to test for heterogeneity and horizontal pleiotropy, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis, and MR-PRESSO test. The bidirectional MR was utilized to investigate the bidirectional relationship between the immune cells and CKD. Multivariable MR was also conducted to mitigate confounding among immune cells. The colocalization analysis was performed to find the key genes of immune cells. We used the Summary data-based MR (SMR) analysis to generate effect estimates between the cis-eQTL and immune cells. The heterogeneity in dependent instruments (HEIDIs) test was used to test the heterogeneity between dependent instrumental variables. <b>Results:</b> We identified 14 potential pathogenic factors and six potential protective factors through the univariable MR. Moreover, we did not find reverse causation by using the bidirectional MR. We finally identified one risk factor and two protective factors after multivariate MR adjustment for effects between immune cells. CD28 on CD28⁺ CD45RA⁺ CD8⁺ T cell could increase the risk of CKD (Pval: 0.033, OR: 1.112, 95% CI: 1.009-1.227). CD11c on myeloid dendritic cell (DC) could decrease the risk of CKD (Pval: 0.02, OR: 0.854, 95% CI: 0.748-0.975). CD45RA on naive CD4⁺ T cell could decrease the risk of CKD (Pval: 0.026, OR: 0.918, 95% CI: 0.852-0.990). Importantly, we observed no evidence of heterogeneity and pleiotropy, signifying the robustness of our results. <i>BACH2</i> (PPH4.abf = 0.999, P_SMR: <0.001, P_HIEDI: 0.132) and <i>HLA-G</i> (PPH4.abf = 0.990, P_SMR: <0.001, P_HIEDI: 0.141) shared the same variant with CD28 on CD28⁺ CD45RA⁺ CD8⁺ T cell. <i>PAQR9</i> (PPH4.abf = 0.992, P_SMR: <0.001, P_HIEDI: 0.215) shared the same variant with CD11c on myeloid DC. <b>Conclusion:</b> MR identified a potential correlation between CKD and immune cells. Colocalization and SMR found the key genes of immune cells. Our findings offer insights into the prevention and management of CKD. However, further investigation is required to elucidate the precise mechanisms underlying this relationship.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4279158"},"PeriodicalIF":4.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017607","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":"Immune Landscape Variation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Circulation Before and After Plasmapheresis by Single-Cell Transcriptome.","authors":"Youzhou Tang, Qingtai Cao, Jishi Liu, Quan Zhuang","doi":"10.1155/mi/5531382","DOIUrl":"https://doi.org/10.1155/mi/5531382","url":null,"abstract":"<p><p>Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by inflammation and destruction of small blood vessels. AAV could be fatal if left untreated. Prompt diagnosis and treatment are crucial to protect AAV-related organs and tissue. Plasmapheresis, a therapeutic intervention aimed at removing harmful substances from the blood, devotes benefits to AAV treatment. However, the specific immune mechanism underlying its effectiveness remains unclear. In our research, we used single-cell RNA sequencing (scRNA-seq) to study the variation of peripheral blood mononuclear cells (PBMCs) before and after plasmapheresis in AAV patients. From this work, we explored a novel method for monocyte classification. In addition, flow cytometry was used to detect the relationship between the monocyte clusters and AAV activity under the new monocyte clustering method. Our scRNA-seq results revealed significant changes in monocyte clusters following treatment, which could be classified into three clusters (CD14+ monocytes, FCGR1A+ monocytes, and FCGR3A+ monocytes). In addition, our flow cytometry results showed that FCGR3A+ (CD16+) monocytes were positively correlated with AAV activity, whereas FCGR1A+ (CD16-CD64+) monocytes were negatively correlated with AAV activity. This may be related to the different biological effects of CD16 and CD64 on monocytes after interacting with the Fc region of ANCAs. In conclusion, our research sheds light on the immune landscape of AAV before and after plasmapheresis, identifying specific monocyte clusters linked to disease activity. These findings offer insights for novel monitoring methods and therapeutic targets in AAV.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5531382"},"PeriodicalIF":4.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017582","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 Crohn's Disease-Related Biomarkers and Pan-Cancer Analysis Based on Machine Learning.","authors":"Tangyu Yuan, Jiayin Xing, Pengtao Liu","doi":"10.1155/mi/6631637","DOIUrl":"https://doi.org/10.1155/mi/6631637","url":null,"abstract":"<p><p><b>Background</b>: In recent years, the incidence of Crohn's disease (CD) has shown a significant global increase, with numerous studies demonstrating its correlation with various cancers. This study aims to identify novel biomarkers for diagnosing CD and explore their potential applications in pan-cancer analysis. <b>Methods</b>: Gene expression profiles were retrieved from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified using the \"limma\" R package. Key biomarkers were selected through an integrative machine learning pipeline combining LASSO regression, neural network modeling, and Support Vector Machine-Recursive Feature Elimination (SVM-RFE). Six hub genes were identified and further validated using the independent dataset GSE169568. To assess the broader relevance of these biomarkers, a standardized pan-cancer dataset from the UCSC database was analyzed to evaluate their associations with 33 cancer types. <b>Results</b>: Among the identified biomarkers, S100 calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8) emerged as key candidates for CD diagnosis, with strong validation in the independent dataset. Notably, S100P displayed significant associations with immune cell infiltration and patient survival outcomes in both liver and lung cancers. These findings suggest that chronic inflammation and immune imbalances in CD may not only contribute to disease progression but also elevate cancer risk. As an inflammation-associated biomarker, S100P holds particular promise for both CD diagnosis and potential cancer risk stratification, especially in liver and lung cancers. <b>Conclusion</b>: Our study highlights S100P and S100A8 as potential diagnostic biomarkers for CD. Moreover, the pan-cancer analysis underscores the broader clinical relevance of S100P, offering new insights into its role in immune modulation and cancer prognosis. These findings provide a valuable foundation for future research into the shared molecular pathways linking chronic inflammatory diseases and cancer development.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6631637"},"PeriodicalIF":4.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11991868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016400","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":"Causal Associations of Inflammatory Cytokines With Osteosarcopenia: Insights From Mendelian Randomization and Single Cell Analysis.","authors":"Zugui Wu, Jiyong Yang, Yue Zhu, Jiao Li, Kang Xu, Yuanlong Li, Guoqing Zhong, Yanfei Xu, Ying Guo, Yu Zhang","doi":"10.1155/mi/6005225","DOIUrl":"https://doi.org/10.1155/mi/6005225","url":null,"abstract":"<p><p><b>Background:</b> Osteosarcopenia, the coexistence of osteoporosis and sarcopenia, poses significant challenges in aging populations due to its dual impact on bone and muscle health. Inflammation, mediated by specific cytokines, is thought to play a crucial role in the development of osteosarcopenia, though the underlying mechanisms are not fully understood. <b>Objective:</b> This study aimed to clarify the causal role of circulating cytokines in the pathogenesis of osteosarcopenia by employing mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to identify cell-specific cytokine expression patterns. The ultimate objective was to uncover potential pathological mechanisms and therapeutic targets for treating osteosarcopenia. <b>Methods:</b> A two-sample MR approach was employed, leveraging publicly available genome-wide association study (GWAS) data from multiple cohorts. A total of 91 circulating cytokines were examined using genetic instruments, and their causal effects on traits related to osteoporosis and sarcopenia were evaluated. Various complementary and sensitivity analyses were performed to ensure robust findings. Additionally, scRNA-seq datasets from human muscle and bone marrow were analyzed to validate the single-cell expression profiles of candidate cytokines. <b>Results:</b> MR analysis identified several cytokines with causal effects on osteosarcopenia traits, including LTA, CD40, CXCL6, CXCL10, DNER (delta and notch-like epidermal growth factor-related receptor), and VEGFA (vascular endothelial growth factor A). LTA and CD40 were protective for both bone and muscle, while VEGFA posed a risk. Other cytokines demonstrated opposite effects on bone and muscle. Single cell analysis revealed distinct expression patterns, with LTA highly expressed in lymphocytes, CD40 in immune cells, and VEGFA in various musculoskeletal cell types. Age-related differences in cytokine expression were also noted, with LTA more highly expressed in younger individuals, and VEGFA in older individuals. <b>Conclusion:</b> This study offers preliminary insights into the inflammatory mechanisms potentially driving osteosarcopenia, identifying key cytokines that may be involved in its pathogenesis. By integrating MR and scRNA-seq data, we highlight potential therapeutic targets, though further research is needed to confirm these findings and their implications for musculoskeletal health.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6005225"},"PeriodicalIF":4.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989700","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":"Electroacupuncture Improves Ovarian Function in Rats With <i>Tripterygium</i> Glycoside-Induced Diminished Ovarian Reserve by Promoting the Polarization of M2 Macrophages and Inhibiting Inflammatory Responses.","authors":"Jia Luo, Yantong Qin, Yaoyao Zhu, Yaoli Yin, Meihong Shen","doi":"10.1155/mi/1694470","DOIUrl":"10.1155/mi/1694470","url":null,"abstract":"<p><p>Immunoinflammatory responses and macrophage polarisation are crucial for maintaining ovarian function. Moreover, electroacupuncture (EA) has been shown to protect ovarian function. However, the mechanisms by which EA improves ovarian function, including its effects on immunoinflammatory responses and macrophage polarisation, have not been determined. This study aimed to investigate the protective effects of EA on ovarian function in rats with diminished ovarian reserve (DOR) and to elucidate the regulatory mechanisms underlying inflammation and M1 and M2 macrophage polarisation. DOR models were established through the intragastric administration of 50 mg/kg <i>Tripterygium</i> glycoside suspension (TGs) for 14 consecutive days. The EA group received treatment at 2/100 Hz and 1.0 mA for 10 min using acupoints BL23, CV4 and CV12 for 14 days. Following the intervention, we employed various methodologies, including haematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunohistochemical (IHC) staining, western blotting and quantitative reverse transcriptase-polymerase chain reaction (PCR), to assess ovarian function, inflammatory factors and the expression levels of M1 and M2 macrophage-related factors. EA intervention reduced the oestrous cycle disorder rate in the rats compared with that in the DOR group, leading to an increase in growing follicles, a reduction in atretic follicles (AFs) and an enhancement of both the capillary (Cap) network and corpus luteum (CL) structure. This intervention also resulted in decreased serum levels of follicle-stimulating hormone (FSH), interferon-<i>γ</i> (IFN-<i>γ</i>) and tumour necrosis factor-<i>α</i> (TNF-<i>α</i>), along with increased levels of oestradiol (E₂), interleukin-4 (IL-4) and interleukin-10 (IL-10). Furthermore, the number of M2 macrophages in the spleen increased, which was accompanied by elevated arginase 1 (Arg1) and decreased inducible nitric oxide synthase (iNOS) expression in the ovarian tissues. In summary, EA can restore the impaired ovarian function caused by TGs by promoting M2 macrophage polarisation and inhibiting inflammatory responses.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"1694470"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811754","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":"Mdivi-1 Attenuates Sepsis-Associated Acute Lung Injury by Inhibiting M1 Alveolar Macrophage Polarization and Pyroptosis.","authors":"Xiaoyu Zhang, Hui Fan, Li Su, Yanni Wang, Guozhong Chen","doi":"10.1155/mi/3675276","DOIUrl":"10.1155/mi/3675276","url":null,"abstract":"<p><p><b>Background:</b> Dynamin-related protein 1 (DRP1)-dependent mitochondrial fission is a novel target for mitigating inflammatory diseases. This study aims to explore the effects of the DRP1 inhibitor Mdivi-1 on sepsis-induced acute lung injury (ALI). <b>Methods:</b> C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then treated with or without Mdivi-1 2 h post-injection. RAW264.7 alveolar macrophages were stimulated with LPS and treated with or without NLRP3 inhibitors, Mito-TEMPO, or Mdivi-1. Hematoxylin and eosin (H&E) staining was used to observe pathological changes in lung tissues. The levels of inflammatory cytokines in lung tissue homogenates, serum, and cell culture medium were detected using enzyme-linked immunosorbent assays (ELISA). The mRNA expression of macrophage polarization markers, NLRP3 activation, and phosphorylation status of DRP1 were assessed. Flow cytometry was employed to evaluate the levels of macrophage apoptosis. Immunofluorescence was utilized to detect the levels of in vivo and in vitro macrophage polarization markers. Mitochondrial reactive oxygen species (Mito-ROS) were measured using a Mito-SOX assay kit. <b>Results:</b> Our results suggested that Mdivi-1 reduced lung tissue pathological injury, M1 alveolar macrophage polarization, NLRP3 activation, and DRP1 Ser616 phosphorylation. In vitro, LPS triggered abnormal accumulation of M1 polarization, NLRP3 activation, and excessive increase in Mito-ROS. NLRP3 inhibitors and Mito-TEMPO inhibited M1 alveolar macrophage polarization and pyroptosis-mediated tissue damage. Mito-TEMPO significantly inhibited NLRP3 activation. Furthermore, Mdivi-1 reduced ALI by inhibiting M1 polarization and pyroptosis. The mechanism of Mdivi-1 in reducing M1 alveolar macrophage polarization and pyroptosis may be related to the inhibition of DRP1-mediated mitochondrial fission, thus suppressing the Mito-ROS/NLRP3 pathway. Similar results were observed <i>in vitro</i> by knocking down DRP1. <b>Conclusion:</b> Inhibition of DRP1 by Mdivi-1 alleviates ALI by hindering Mito-ROS/NLRP3-mediated M1 alveolar macrophage polarization and pyroptosis, suggesting that DRP1-dependent mitochondrial fission is a potential therapeutic target for ALI.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"3675276"},"PeriodicalIF":4.4,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803686","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":"Exploring the Relationship Between Immune Cells and Scoliosis by Mendelian Randomization, Colocalization Analysis, and SMR.","authors":"Chaofan Qin, Zhengjian Yan, Qingshuai Yu, Mingxin Chen, Tao Hu, Xin Wang, Bo Lei, Yu Chen, Ke Ma, Zhongliang Deng, Si Cheng","doi":"10.1155/mi/8833556","DOIUrl":"10.1155/mi/8833556","url":null,"abstract":"<p><p><b>Background:</b> Scoliosis is a condition that can have severe consequences for millions of individuals on an annual basis. Current research in this field is increasingly focusing on the role of the immune system in the development of the disease. However, the precise relationship between immunity and scoliosis remains to be fully elucidated. <b>Method:</b> Our investigation involved a comprehensive Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and scoliosis. The comprehensive univariable MR analysis encompassed 731 immune cells to explore their relationship with scoliosis. Cochran's <i>Q</i> test, the leave-one-out test, and MR-Egger intercept analysis were used to assess pleiotropy and heterogeneity. We performed multivariable MR analysis to account for potential confounding factors between the immune cells. The colocalization analysis and summary data-based MR (SMR) analysis were utilized to explore relationship between immune cells and cis-eQTL. <b>Results:</b> Our study identified 13 immune cells that were significantly associated with scoliosis by univariable MR, including four risk factors and nine protective factors for scoliosis. In order to reduce confounding between immune cells, multivariable MR was employed, and it was determined that only six immune cell types had independent effects on scoliosis. <i>SERPINH1</i> shared the same variant with CX3CR1 on CD14- CD16-. <i>FSD1L</i> shared the same variant with CCR2 on CD14- CD16-. <i>SNHG14</i>, <i>SNORA33</i>, <i>NET1</i>, and <i>SNORD100</i> shared the same variant with HLA DR on CD14+ CD16+ monocyte. <b>Conclusion:</b> Our findings suggested a possible link between immune cells and scoliosis and found the key genes for the immune cell, which provides a new direction for further research. However, the specific underlying mechanisms require further investigation in future experiments.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8833556"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772665","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}