Mediators of Inflammation最新文献

{"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}

{"title":"Strain-Dependent Differences in Inflammatory/Immune Activity in Cutaneous Wound Tissue Repair in Rats: The Significance of Body Mass/Proneness to Obesity.","authors":"Jelena B Kulas, Aleksandra D Popov Aleksandrov, Dusanka D Popovic, Anastasija Lj Malesevic, Maja M Cakic Milosevic, Milena V Kataranovski, Ivana I Mirkov, Dina M Tucovic","doi":"10.1155/mi/5525557","DOIUrl":"10.1155/mi/5525557","url":null,"abstract":"<p><p>Inflammatory/immune cells and mediators are substantial for wound healing because they orchestrate biological activities in this complex process. Among factors that affect wound healing, obesity, and metabolic diseases are among the most significant, particularly because of a relationship between obesity and a prediabetic state with immune reactivity. Using Dark Agouti (DA) and Albino Oxford (AO) rats, which differ in immune responses as well as in proneness to obesity, we examined the impact of these intrinsic factors on cutaneous wound healing. Dynamics of the process were monitored at days 3, 5, and 7 post-wounding parallel in both rat strains by analysis of selected basic aspects of the wound repair process (cytokine and growth factor responses) in granulation tissue. Strain-related differences in the extent of reduction of the wound area were shown, which coincided with differential proinflammatory and immune-regulatory cytokines, as well as growth factors response in these rats. Some of these differences seem related to their dissimilarities in the proneness to obesity. Results in this study extended so far known differences in inflammatory/immune responses to a variety of stimuli between AO and DA rats and showed, for the first time, immune-based differences in wound healing between rats that differ in body mass (BM) and obesity proneness (under ad libitum feeding conditions with normal rodent chow).</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5525557"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772672","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":"Heterogeneity of Neutrophils and Immunological Function in Neonatal Sepsis: Analysis of Molecular Subtypes Based on Hypoxia-Glycolysis-Lactylation.","authors":"Huabin Wang, Ru Yang, Nan Chen, Xiang Li","doi":"10.1155/mi/5790261","DOIUrl":"10.1155/mi/5790261","url":null,"abstract":"<p><p><b>Objective:</b> Hypoxia-glycolysis-lactylation (HGL) may play a crucial role in neonatal sepsis (NS). This study aims to identify HGL marker genes in NS and explore immune microenvironment among NS subtypes. <b>Materials and Methods:</b> The gene expression dataset GSE69686, comprising 64 NS cases and 85 controls, was selected for analysis. Based on the screened HGL-related marker genes, diagnostic prediction models were constructed using nine machine learning algorithms, and molecular subtypes of NS were identified through consensus clustering. Subsequently, the heterogeneity of biological functions and immune cell infiltration among the different subtypes was analyzed. Finally, the marker genes and lactylation were validated using the GSE25504 dataset, clinical samples, and mouse neutrophil, respectively. <b>Results:</b> MERTK, HK3, PGK1, and STAT3 were identified and validated as marker genes, and the diagnostic prediction model for NS constructed using the support vector machine (SVM) algorithm exhibited optimal predictive performance. Based on gene expression patterns, two distinct NS subtypes were identified. Functional enrichment analysis highlighted significant immune-related pathways, while immune infiltration analysis revealed differences in neutrophil proportions between the subtypes. Furthermore, the expression levels of marker genes were positively correlated with neutrophil infiltration. Importantly, the experimental validation results were consistent with the findings from the bioinformatics analysis. <b>Conclusion:</b> This study identified the distinct NS subtypes and their associated marker genes. These findings will contribute to elucidating the disease's heterogeneity and establishing appropriate personalized therapeutic approaches.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5790261"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772596","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":"Comparative Analysis of Salivary and Serum Inflammatory Mediator Profiles in Patients With Rheumatoid Arthritis and Periodontitis.","authors":"Carina Fei, Kaja Eriksson, Guozhong Fei, Luis Fernando Delgado Zambrano, Shigufta Syed, Caroline Lindström, Martina Ericson, Mehrad Mohammadi, Georgios Tsilingaridis, Amel Guenifi, Rikard Holmdahl, Leif Jansson, Tülay Yucel-Lindberg","doi":"10.1155/mi/7739833","DOIUrl":"10.1155/mi/7739833","url":null,"abstract":"<p><p><b>Background:</b> Periodontitis (PD) and rheumatoid arthritis (RA) are chronic inflammatory conditions, characterized by dysregulated immune response and excessive production of inflammatory mediators. The oral disease PD is triggered by periodontal pathogens, leading to the destruction of tissues surrounding the teeth, whereas RA is a systemic autoimmune disease primarily affecting the joints. The objective of this study was to investigate the prevalence of PD and map the profile of salivary and serum inflammatory mediators of patients with RA, with respect to periodontal severity (PD stage II and PD stage III/IV). <b>Methods:</b> For this cross-sectional cohort study, 62 patients diagnosed with RA were recruited. All participants underwent a full-mouth dental examination. Levels of various inflammatory mediators, including tumor necrosis factor (TNF) superfamily proteins, interferon (IFN) family proteins, regulatory T cell (Treg) cytokines, and matrix metalloproteinases were determined in saliva and serum samples from each participant using a human inflammation multiplex immunoassay panel. <b>Results:</b> In the current RA cohort, all participants were diagnosed with PD, of which 35.5% were classified as PD stage II and 64.5% as PD stages III/IV. Inflammatory mediator levels were significantly higher in both saliva and serum samples from patients with RA and PD stages III/IV, compared to those with RA and stage II within the same cohort. These included higher serum levels of sCD30, IL-10, IL-19, osteopontin and elevated salivary levels of BAFF/TNFSF13B and IFN-<i>α</i>2. Additionally, APRIL/TNFSF13 levels were increased in both saliva and serum. <b>Conclusions:</b> Among the studied patients with RA, the majority exhibited severe PD (stage III/IV), underscoring the importance of periodontal prophylaxis and treatment for this group of patients. Higher levels of inflammatory mediators were observed in both saliva and serum in those with PD stages III/IV, suggesting a potential link between the severity of PD and systemic inflammation in RA. Further research is needed to explore the clinical implications of these findings.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7739833"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730735","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}