Mediators of Inflammation最新文献

{"title":"Gut Microbiota-Derived Butyric Acid Alleviates Glucocorticoid-Associated Osteonecrosis of the Femoral Head via Modulating Inflammatory Cytokines in Bone Marrow Mesenchymal Stem Cells.","authors":"Shuai He, Hao Chen, Hongzhong Xi, Guangquan Sun, Bin Du, Xin Liu","doi":"10.1155/mi/8742817","DOIUrl":"10.1155/mi/8742817","url":null,"abstract":"<p><p><b>Background:</b> The role of gut microbiota and its metabolites in regulating bone metabolism has been well established, with inflammatory immune responses potentially playing a critical role. Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH), caused by high-dose glucocorticoid use for inflammatory or immune-related diseases, is a prevalent condition of bone metabolic imbalance. However, the regulatory role and mechanisms of gut microbiota and its metabolites in the development and progression of GA-ONFH remain unclear. This study aims to investigate the intervention effects of gut microbiota and its metabolite butyric acid on GA-ONFH through a series of multi-omics <i>in vitro</i> and <i>in vivo</i> experiments. <b>Methods:</b> Sprague Dawley rats were randomly divided into four groups. The gut microbial composition of the groups was analyzed through 16S rDNA sequencing. Targeted metabolomics was employed to assess differences in short-chain fatty acids (SCFAs) among the groups. Butyric acid, identified as a key differential metabolite, was then selected for further exploration of its effects on bone marrow mesenchymal stem cells (BMSCs) and GA-ONFH rat models through <i>in vitro</i> and <i>in vivo</i> experiments. <b>Results:</b> 16S rDNA sequencing revealed alterations in gut microbiota structure in GA-ONFH rats. Micro-CT and HE staining demonstrated that depletion of gut microbiota with broad-spectrum antibiotics prior to GA-ONFH modeling exacerbated the disease's development. In contrast, fecal microbiota transplantation (FMT) was shown to alleviate GA-ONFH progression. Targeted metabolomics indicated that FMT mitigated the reduction in butyric acid levels induced by dexamethasone (DXM). Subsequent <i>in vitro</i> cell experiments confirmed that butyric acid promotes BMSC proliferation, migration, and osteogenic differentiation. RNA sequencing revealed that butyric acid regulates T cell-mediated inflammatory cytokine genes in BMSCs, while Western blot and immunofluorescence assays confirmed that butyric acid modulates the expression of TNF-α and IL-2/IL-4 in BMSCs. Finally, <i>in vivo</i> experiments demonstrated that butyric acid supplementation attenuated the progression of GA-ONFH and improved the expression of inflammation-related cytokines in femoral head tissue. <b>Conclusions:</b> Our study demonstrates that gut microbiota depletion exacerbates GA-ONFH, while FMT restores butyric acid levels and alleviates disease severity. Butyric acid reduced the expression of TNF-α and IL-2 while increasing the level of IL-4 <i>in vivo</i> and <i>in vitro</i>, thereby improving the local inflammatory environment of the femoral head and alleviating the progression of GA-ONFH. These findings highlight that reduction in butyric acid levels due to gut microbiota dysbiosis is a crucial factor in the progression of GA-ONFH.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8742817"},"PeriodicalIF":4.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285400","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":"RETRACTION: Inhibitory Effect of Matrine on Blood-Brain Barrier Disruption for the Treatment of Experimental Autoimmune Encephalomyelitis.","authors":"Mediators Of Inflammation","doi":"10.1155/mi/9829464","DOIUrl":"10.1155/mi/9829464","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1155/2013/736085.].</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9829464"},"PeriodicalIF":4.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234509","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":"Trends and Hot Spots of Macrophages Linked to Metabolic Syndrome: A Comprehensive Bibliometric and Visualization Analysis (2014-2024).","authors":"Yuan Zhang, Qiwang He, Xiaoqian Cong, Huazhou Qiu, Chuan Hua","doi":"10.1155/mi/9487093","DOIUrl":"10.1155/mi/9487093","url":null,"abstract":"<p><p><b>Background:</b> Metabolic syndrome (MetS) has been closely associated with macrophages, as evidenced by a substantial body of literature. However, a comprehensive bibliometric analysis of this research domain remains absent. This study aims to systematically assess the current state of research, identify emerging trends, and investigate key hot spots within macrophage-related MetS research from a bibliometric perspective. <b>Methods:</b> Data including 1657 records on macrophages and their association with MetS were retrieved from the Web of Science Core Collection (WoSCC) database, covering the period from 2014 to 2024. The analysis was conducted using VOSviewer (v1.6.20), CiteSpace (v6.3.R1), the R package \"bibliometrix\" (v4.4.1), and Excel 2019. <b>Results:</b> The annual number of publications peaked in 2017, 2018, and 2021, followed by a decline. However, the increasing citation count suggests growing recognition and influence of this research area. The United States and China account for over half of the academic output in this field, with strong collaborative networks positioning them as key contributors to its advancement. Yan Huang emerged as the most prolific author, while Gozal David had the highest co-citation frequency. Frontiers in Immunology was identified as the most active journal in this domain, whereas the Journal of Clinical Investigation recorded the highest citation impact. Keywords such as \"inflammation,\" \"obesity,\" and \"insulin resistance\" appeared most frequently, with \"gut microbiota\" showing the strongest citation bursts. Themes like inflammation, obesity, and expression need sustained attention and resource allocation, while themes such as macrophage activation syndrome, diagnosis, and mutations need a strategic reevaluation. <b>Conclusion:</b> This study systematically evaluates the research landscape, priorities, and emerging trends of macrophages associated with MetS over the last decade, providing an overview of the field and valuable insights for researchers.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9487093"},"PeriodicalIF":4.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199582","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":"IL-13 May Could Enhance the Proliferation and Affect the Differentiation of Nasal Epithelium Basal Cells Through the mTOR/p70S6K1 Pathway in Chronic Rhinosinusitis With Nasal Polyps.","authors":"Ping Li, Tao Li, Jinfeng Luo, Peng Yu, Tao Jiang, Xiangmin Zhou, Liang Yu, Aiping Chen, Yuzhu Wan, Li Shi","doi":"10.1155/mi/8108993","DOIUrl":"10.1155/mi/8108993","url":null,"abstract":"<p><p><b>Background:</b> One of the hallmarks of Chronic rhinosinusitis with nasal polyps (CRSwNP) is the overexpression of IL-13, which may influence the proliferation and differentiation of nasal epithelial basal cells. However, the pathway is not clear enough, and the mTOR/p70S6K1 pathway is related to cell growth. This study was trying to explore if IL-13 could impact nasal epithelial basal cells through the mTOR/p70S6K1 pathway. <b>Methods:</b> PCR, western blot (WB), and immunohistochemistry (IHC) were used to compare the difference between IL-13 and the mTOR/p70S6K1 pathway-related molecules expression level between the healthy control (HC) and CRSwNP groups. WB, 5-ethynyl-2'-deoxyuridine staining, and Immunofluorescent (IF) were performed on human nasal epithelial progenitor cells (HNEPCs) to detect the proliferation ability under the effect of IL-13. In addition, qRT-PCR, WB, and IF were used to detect the differentiation ability with the stimulation of IL-13 in the air-liquid interface (ALI) system. <b>Results:</b> The expression of IL-13, mTOR/p70S6K1-related molecules, and proliferation-related molecules Ki67, CDK2, and cyclin E1 were upregulated in CRSwNP compared to HC. In HNEPCs, IL-13 could stimulate nasal epithelial cells proliferating through the mTOR/p70S6K1 pathway, and this phenomenon could be inhibited when mTOR (with rapamycin) and S6K1 (with PF-4708671) were blocked. In the ALI system, the effect of IL-13 added in the proliferation phase could persist in the proliferation and differentiation stage, affecting the nasal epithelial progenitor/stem cells' irregular differentiation. <b>Conclusion:</b> IL-13 may affect the proliferation and differentiation of nasal epithelial progenitor/stem cells through the mTOR/p70S6K1 pathway, which may affect the development of nasal polyps.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8108993"},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174091","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":"Baicalin Modulates Glycolysis <i>via</i> the PKC/Raf/MEK/ERK and PI3K/AKT Signaling Pathways to Attenuate IFN-I-Induced Neutrophil NETosis.","authors":"Hong Wei, Dongni Xia, Li Li, Linpan Liang, Lijun Ning, Cuiliu Gan, Ying Wu","doi":"10.1155/mi/8822728","DOIUrl":"10.1155/mi/8822728","url":null,"abstract":"<p><p>Type I interferon (IFN-I), a pivotal component of the host's innate antiviral immune system, can induce the formation of neutrophil extracellular traps (NETs) and facilitate inflammatory responses. Baicalin exhibits a range of pharmacological activities, including anti-inflammatory and immunomodulatory effects. It has been reported that neutrophil glycolysis plays a pivotal role in the formation of NETs and the regulation of inflammatory response in immune modulation, regulated by IFN-I. However, it remains unclear whether baicalin regulates IFN-I-induced NETs formation through glycolysis. In this study, we induced the formation of NETs <i>in vitro</i> using IFN-I and observed that baicalin significantly reduced the formation of IFN-I-induced NETs. Furthermore, baicalin inhibited the production of pro-inflammatory cytokines, specifically interleukin-1 beta (IL-1<i>β</i>) and interleukin-6 (IL-6), as well as the generation of reactive oxygen species (ROS) and chemotactic responses. Our findings further indicated that baicalin could inhibit both lactic acid and ATP levels in IFN-I-induced neutrophils, as well as the expression of glycolytic-related proteins, including HK2, HK3, PKM2, and LDHA. Moreover, following the administration of glycolytic agonists insulin, it was observed that heightened glycolytic activity significantly augmented NETs formation and the release of inflammatory cytokines, potentially regulated by PKC/Raf/MEK/ERK and PI3K/AKT signaling pathways. In conclusion, our findings indicated that baicalin may exert inhibitory effects on IFN-I-induced NETs formation and inflammatory cytokine production by modulating glycolysis, thereby providing further evidence for the potential clinical application of baicalin in the treatment of IFN-I-related inflammatory diseases.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8822728"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150862","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":"IL-6 and Olfactory Dysfunction: Focus on Changes, Effects, and Mechanisms.","authors":"Xiao-Yu Song, Ya-Kui Mou, Han-Rui Wang, Yao Wang, Wan-Chen Liu, Ting Yang, Cai-Yu Sun, Chao Ren, Xi-Cheng Song","doi":"10.1155/mi/5891188","DOIUrl":"10.1155/mi/5891188","url":null,"abstract":"<p><p>The sense of smell is vital for human life and risk identification. Many diseases can cause olfactory disorders, and early identification and intervention of olfactory disorders are crucial. Currently, the diagnosis of olfactory disorders in clinical practice mostly relies on subjective visual analog scale (VAS) evaluations, expensive and complex imaging, and neurophysiological examinations, which lead to poor patient compliance and low completion rates. Therefore, there is an urgent need to identify novel, objective, easily detectable biological indicators. Interleukin-6 (IL-6) is an inflammatory factor that is closely associated with olfactory dysfunction in various diseases. However, the role of IL-6 in the occurrence and development of olfactory disorders is not yet clear, which limits its clinical application. This article reviews the changes and possible mechanisms of IL-6 in various diseases associated with olfactory disorders, with the aim of providing a reference for the clinical application of IL-6 as a biomarker for olfactory disorders and promoting an in-depth exploration of its mechanism in the occurrence and development of olfactory disorders.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5891188"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150868","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 Mechanosensitive PIEZO1 Channel Contributes to the Reaction of RAW264.7 Macrophages to Mechanical Strain.","authors":"Agnes Schröder, Hanna Engelhardt, Andressa Nogueira, Björn Clausen, Christian Kirschneck, Jonathan Jantsch, Peter Proff, Kathrin Renner, Eva Paddenberg-Schubert","doi":"10.1155/mi/9998838","DOIUrl":"10.1155/mi/9998838","url":null,"abstract":"<p><p>The mechanosensitive channel 'piezo type mechanosensitive ion channel component 1' (PIEZO1) plays a regulatory role in the response of periodontal ligament fibroblasts (PDLFs) to the mechanical strain that occurs during orthodontic tooth movement. In addition to PDLFs, immune cells such as macrophages are also exposed to mechanical stimuli. Macrophages respond to mechanical strain with increased expression of inflammatory mediators. The role of PIEZO1 in this response remains elusive. To investigate the effect of PIEZO1 activation, RAW264.7 macrophages were stimulated with the PIEZO1 activator YODA1 without concurrent application of pressure. To further examine the specific role of PIEZO1 during mechanical strain, RAW264.7 macrophages were exposed to mechanical strain without and with simultaneous inhibition of PIEZO1 either by chemical inhibition (GsMTx4) or siRNA silencing. The expression of genes and proteins involved in orthodontic tooth movement was examined by quantitative PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Activation of PIEZO1 by YODA1 or mechanical strain increased the expression of inflammatory cytokines and osteoprotegerin (Opg), which is critically involved in bone remodeling processes. Conversely, inhibition of the PIEZO1 channel attenuates the effects of mechanical stress. In conclusion, our data demonstrate that the PIEZO1 channel is a major contributor to the response of macrophages to mechanical strain encountered during orthodontic tooth movement and affects the expression of inflammatory and bone remodeling factors.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9998838"},"PeriodicalIF":4.4,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150903","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":"Detection of the Prognostic Gene CYB5D2 in Cervical Squamous Epithelial Lesions.","authors":"Yanan Liu, Guoqiang Zhao, Yanqing Kong, Fengyuan Zhou, Tong Zhang, Xiaohang Chen, Haiyan Hu, Fengxiang Wei","doi":"10.1155/mi/2360364","DOIUrl":"10.1155/mi/2360364","url":null,"abstract":"<p><p>CYB5D2 is a novel tumor suppressor gene that exhibits ectopic expression in various tumors. This study explored its significance in cervical cancer screening and prognosis by examining its expression in cervical precancerous lesions and cancer tissues and analyzing follow-up data. CYB5D2 expression was comprehensively assessed in 112 clinical samples, combined with routine cervical cancer screening methods to evaluate its early detection potential. Postoperative survival data from cervical cancer patients were analyzed using Kaplan-Meier curves to examine the association between CYB5D2 protein expression and clinicopathological characteristics, as well as its prognostic implications. Results revealed a progressive downregulation of CYB5D2 expression with advancing cervical lesions. Immunohistochemical detection of CYB5D2 protein outperformed ThinPrep cytology test (TCT), DNA aneuploidy analysis, and HR-HPV E6/E7 mRNA testing (mRNA expression of the E6 and E7 genes in high-risk HPV virus) in diagnosing high-grade squamous intraepithelial lesions (HSIL+) of the cervix. Combined testing of TCT, HR-HPV E6/E7 mRNA, and CYB5D2 achieved 100% sensitivity and negative predictive value for HSIL+. In conclusion, low CYB5D2 expression was identified as an independent risk factor for progression-free survival (PFS) in cervical cancer patients. Incorporating CYB5D2 testing into routine screening protocols for squamous cell lesions, along with TCT and HPV testing, may enhance diagnostic efficiency and provide prognostic value for adverse outcomes.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2360364"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110912","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":"Efficacy and Safety of Syk and BTK Inhibitors in Immune Thrombocytopenia: A Comprehensive Review of Emerging Evidence.","authors":"Amirhossein Heidari, Amirhossein Shahbazi Mazid, Mohammad Behroozfar, Negar Ghotbi, Fatemeh Fathabadi, Sara Eghbali, Nazila Heidari","doi":"10.1155/mi/5578929","DOIUrl":"10.1155/mi/5578929","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a reduced platelet count, resulting in bleeding risks and compromised quality of life. Advances in understanding ITP pathogenesis have revealed critical roles for spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) in Fc receptor (FcR)-mediated immune pathways, which are central to autoantibody production and platelet destruction. We sought to evaluate the efficacy and safety of Syk and BTK inhibitors in the management of ITP. PubMed/Medline, Scopus, and Web of Science databases were systematically searched up to July 28, 2024. Clinical studies with available full-text in English were included. Fostamatinib, an FDA-approved Syk inhibitor, has shown efficacy in enhancing platelet counts and reducing bleeding events in refractory ITP patients. Among the newer Syk inhibitors, sovleplenib demonstrated rapid and sustained platelet increases in clinical trials, with an 80% response rate at the 300 mg dosage and a favorable safety profile. Additionally, BTK inhibitors, including rilzabrutinib and orelabrutinib, have shown potential in clinical trials, offering increased platelet stability and favorable safety profiles in ITP cases. Syk and BTK inhibitors hold potential as targeted therapies for refractory ITP, with evidence supporting their ability to improve clinical outcomes and enhance patient quality of life. Continued research is warranted to optimize these therapies and confirm their long-term efficacy and safety in diverse patient populations.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5578929"},"PeriodicalIF":4.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094160","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":"Association of Three Composite Inflammatory and Lipid Metabolism Indicators With Cardiovascular-Kidney-Metabolic Syndrome: A Cross-Sectional Study Based on NHANES 1999-2020.","authors":"Jiayuan Song, Ziyi Xu, Han Yu, Aimin Li, Yiying Liu, Meiying Jin","doi":"10.1155/mi/6691516","DOIUrl":"https://doi.org/10.1155/mi/6691516","url":null,"abstract":"<p><p><b>Background:</b> Various leukocyte-to-high-density lipoprotein cholesterol (HDL-C) ratios, namely the neutrophil to HDL-C ratio (NHR), lymphocyte to HDL-C ratio (LHR), and monocyte to HDL-C ratio (MHR), have been identified as potential inflammatory biomarkers. Despite this, the intricate relationship between these ratios and Cardiovascular-Kidney-Metabolic (CKM) Syndrome has yet to be fully elucidated. This study aims to explore the associations between these white blood cell ratios and the presence of CKM Syndrome. <b>Methods:</b> This cross-sectional retrospective analysis utilized data from 19,534 individuals diagnosed with CKM Syndrome, sourced from the National Health and Nutrition Examination Survey (NHANES) database covering the years 1999-2020. Participants were stratified, and relevant covariates were adjusted during the analysis. Weighted logistic regression models were employed to statistically assess the relationships between the inflammatory markers and the differing stages of CKM Syndrome, with stage 0 serving as the reference point. <b>Results:</b> After adjusting for all the covariates, high levels of three inflammatory indicators were associated with higher odds of having CKM Syndrome stage 1-4, using stage 0 as a reference. When we assessed the associations between inflammatory indicators with stage 3-4 with stage 0-1-2 as the reference group, we found that inflammatory indicators still increased the risk of higher CKM Syndrome stage. The dose-response relationship revealed that the inflammatory indicators increased the risk of higher CKM Syndrome stage. After conducting subgroup analyses, we found that LHR and education, as well as LHR, MHR, and drinking status, had significant interactions. <b>Conclusion:</b> Elevated NHR, LHR, and MHR are significantly associated with an increased risk of CKM Syndrome across stages 1-4.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6691516"},"PeriodicalIF":4.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078994","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}