Mediators of Inflammation最新文献

{"title":"Correlation between the Systemic Immunoinflammatory Index and Platelet–Lymphocyte Ratio in Patients with Adenomyosis","authors":"Yan Dong, YaHui Chen, YaNan Wang, Lin Wang, Yan Zhou, Mei Xue, Lin Sun","doi":"10.1155/2024/9977750","DOIUrl":"https://doi.org/10.1155/2024/9977750","url":null,"abstract":"<i>Background</i>. The chronic inflammatory immune response is a significant factor in the pathogenesis of benign gynecological diseases. The systemic immunoinflammatory index (SII) and the platelet-to-lymphocyte ratio (PLR) are commonly available biomarkers of inflammation. However, evidence of the relationship between SII and PLR in patients with adenomyosis is limited. This study aimed to investigate the relationship between SII and PLR in patients with adenomyosis. <i>Methods</i>. This cross-sectional study included 483 patients with adenomyosis who were first diagnosed at our institution between January 2019 and December 2021. Basic patient clinical information and inflammatory factors were collected for univariate analysis, smoothed curve fitting, and multivariate segmented linear regression. <i>Results</i>. The results of the univariate analysis showed a significant positive correlation between PLR levels and SII (<span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"></path></g></svg><span></span><span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 28.182 9.2729\" width=\"28.182pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,44.605,0)\"></path></g></svg>).</span></span> In addition, a nonlinear relationship between PLR and SII was tested using a smoothed curve fit after adjusting for potential confounders. Multiple segmented linear regression models showed a significant relationship between SII and PLR in both SII < 1,326.47 (<i>β</i> 0.14, 95% CI: 0.12, 0.16; <span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-81\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"><use xlink:href=\"#g117-91\"></use></g></svg><span></span><span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 34.445 9.2729\" width=\"34.445pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"><use xlink:href=\"#g113-47\"></use></g><g transform=\"matrix(.013,0,0,-0.013,32.12","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"262 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139482014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PLCG2 and IFNAR1: The Potential Biomarkers Mediated by Immune Infiltration and Osteoclast Differentiation of Ankylosing Spondylitis in the Peripheral Blood","authors":"Bo Han, Qiaobo Xie, Weishi Liang, Peng Yin, Xianjun Qu, Yong Hai","doi":"10.1155/2024/3358184","DOIUrl":"https://doi.org/10.1155/2024/3358184","url":null,"abstract":"<i>Objectives</i>. Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by chronic spinal inflammation, arthritis, gut inflammation, and enthesitis. We aimed to identify the key biomarkers related to immune infiltration and osteoclast differentiation in the pathological process of AS by bioinformatic methods. <i>Methods</i>. GSE25101 from the Gene Expression Omnibus was used to obtain AS-associated microarray datasets. We performed bioinformatics analysis using R software to validate different expression levels. The purpose of the GO and KEGG enrichment analyses of DEGs was to exclude key genes. Using weighted correlation network analysis (WGCNA), we examined all expression profile data and identified differentially expressed genes. The objective was to investigate the interaction between genetic and clinical features and to identify the essential relationships underlying coexpression modules. The CIBERSORT method was used to make a comparison of the immune infiltration in whole blood between the AS group and the control group. The WGCNA R program from Bioconductor was used to identify hub genes. RNA extraction reverse transcription and quantitative polymerase chain reaction were conducted in the peripheral blood collected from six AS patients and six health volunteers matched by age and sex. <i>Results</i>. 125 DEGs were identified, consisting of 36 upregulated and 89 downregulated genes that are involved in the cell cycle and replication processes. In the WGCNA, modules of MCODE with different algorithms were used to find 33 key genes that were related to each other in a strong way. Immune infiltration analysis found that naive CD4+ T cells and monocytes may be involved in the process of AS. PLCG2 and IFNAR1 genes were obtained by screening genes meeting the conditions of immune cell infiltration and osteoclast differentiation in AS patients among IGF2R, GRN, SH2D1A, LILRB3, IFNAR1, PLCG2, and TNFRSF1B. The results demonstrated that the levels of PLCG2 mRNA expression in AS were considerably higher than those in healthy individuals (<span><svg height=\"8.8423pt\" style=\"vertical-align:-0.2064009pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 8.8423\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"></path></g></svg><span></span><span><svg height=\"8.8423pt\" style=\"vertical-align:-0.2064009pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 28.182 8.8423\" width=\"28.182pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,44.60","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"30 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139105207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Silymarin in Mitigating Inflammation and Cognitive Impairment Induced by Ovariectomy in Wistar Rats","authors":"Razieh Moalefshahri, Hossein Javid, Fatemeh Gheybi, Somaye Fallahnezhad, Seyed Isaac Hashemy","doi":"10.1155/2023/6639533","DOIUrl":"https://doi.org/10.1155/2023/6639533","url":null,"abstract":"<i>Background</i>. Silymarin, a polyphenolic flavonoid found in milk thistle, has been used to treat liver and brain injuries in humans and animals. The study aims to investigate the protective effects of silymarin on spatial and passive avoidance memory, oxidative stress, and inflammatory factors in the brain and liver tissues of ovariectomized (OVX) Wistar rats. <i>Methods</i>. The study involved 30 female Wistar rats divided into control, sham, and three silymarin-treated groups. After ovariectomy, rats underwent CT scan, and some of them were administered silymarin via gavage for 2 months. Memory and learning were assessed using Morris water maze and shuttle box tests. Brain and liver tissues were analyzed for inflammatory factors (IL-1<i>β</i>, TNF<i>α</i>, and IL-6) and oxidative stress markers (CAT, SOD, and MDA) after sacrifice. <i>Results</i>. Silymarin improved spatial memory and fear learning compared to the sham group (<span><svg height=\"9.75571pt\" style=\"vertical-align:-1.11981pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.75571\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"></path></g></svg><span></span><svg height=\"9.75571pt\" style=\"vertical-align:-1.11981pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 21.918 9.75571\" width=\"21.918pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"></path></g></svg></span> to <span><svg height=\"9.75571pt\" style=\"vertical-align:-1.11981pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.75571\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-81\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"><use xlink:href=\"#g117-93\"></use></g></svg><span></span><span><svg height=\"9.75571pt\" style=\"vertical-align:-1.11981pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 28.182 9.75571\" width=\"28.182pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"><use xlink:href=\"#g113-47\"></use></g><g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,44.605,0)\"></path></g></svg>).</span></span> It also significantly reduced IL-1<i>β</i>, TNF-<i>α</i>, and IL-6 levels in the cortex, hippocampus, and liver (<span><svg height=\"9.75571pt\" style=\"vertical-align:-1.11981pt\"","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"32 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key Cell Types and Biomarkers in Heart Failure Identified through Analysis of Single-Cell and Bulk RNA Sequencing Data","authors":"Ying Kong, Ning Yang, Zhiqing Luo, Ruiting Huang, Quhuan Li","doi":"10.1155/2023/8384882","DOIUrl":"https://doi.org/10.1155/2023/8384882","url":null,"abstract":"Heart failure (HF) is a complex clinical syndrome resulting from various cardiac diseases and a significant medical issue worldwide. Although the role of inflammation in HF pathogenesis is well-known, the specific cell types and regulatory molecules involved remain poorly understood. Here, we identified key cell types and novel biomarkers via an analysis of single-cell and bulk RNA sequencing data obtained from patients with two major HF types of ischemic cardiomyopathy and dilated cardiomyopathy. Myeloid cells were identified as the primary cell population involved in HF through cellular fraction and gene set enrichment analysis. Additionally, differential analysis of myeloid cells revealed crosstalk between cellular communication and cytokine-regulated immune responses in HF, with the MIF pathway emerging as a crucial immune regulatory pathway. The CD74/CXCR4 receptor complex in myeloid cell subgroup M<i>φ</i>2 was significantly upregulated, potentially acting as a crucial regulator in HF. Upon receiving the MIF signal molecule, the CD74/CXCR4 receptor can activate NF-<i>κ</i>B signaling to produce chemokines and thereby enhance the inflammatory response. CD74 and CXCR4 may serve as biomarkers and treatment targets for HF.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"20 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139052961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB2 Deficiency Mitigates Abdominal Aortic Aneurysm by Suppressing Ang-II-Caused Ferroptosis and Inflammation via NF-κβ Pathway","authors":"Hao Wu, Legao Chen, Kaiping Lu, Yi Liu, Weiqin Lu, Jinsong Jiang, Chao Weng","doi":"10.1155/2023/2157355","DOIUrl":"https://doi.org/10.1155/2023/2157355","url":null,"abstract":"<i>Background</i>. Ferroptosis is a new form of cell death, which is closely related to the occurrence of many diseases. Our work focused on the mechanism by which HMGB2 regulate ferroptosis and inflammation in abdominal aortic aneurysm (AAA). <i>Methods</i>. Reverse transcription–quantitative polymerase chain reaction and western blot were utilized to assess HMGB2 levels. CCK-8 and flow cytometry assays were utilized to measure cell viability and apoptosis. We detected reactive oxygen species generation, Fe²⁺ level, and ferroptosis-related protein levels in Ang-II-treated VSMCs, which were typical characteristics of ferroptosis. Finally, the mice model of AAA was established to verify the function of HMGB2 in vivo. <i>Results</i>. Increased HMGB2 level was observed in Ang-II-treated VSMCs and Ang-II-induced mice model. HMGB2 depletion accelerated viability and impeded apoptosis in Ang-II-irritatived VSMCs. Moreover, HMGB2 deficiency neutralized the increase of ROS in VSMCs caused by Ang-II. HMGB2 silencing considerably weakened Ang-II-caused VSMC ferroptosis, as revealed by the decrease of Fe²⁺ level and ACSL4 and COX2 levels and the increase in GPX4 and FTH1 levels. Furthermore, the mitigation effects of shHMGB2 on Ang-II-induced VSMC damage could be counteracted by erastin, a ferroptosis agonist. Mechanically, HMGB2 depletion inactivated the NF-<i>κβ</i> signaling in Ang-II-treated VSMCs. <i>Conclusions</i>. Our work demonstrated that inhibition of HMGB2-regulated ferroptosis and inflammation to protect against AAA via NF-<i>κβ</i> signaling, suggesting that HMGB2 may be a potent therapeutic agent for AAA.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"55 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138742969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD","authors":"Jiahui Lin, Guowei Wang, Sha Cheng, Yanan Hu, Huan Li, Wanjiang Feng, Xiaoming Liu, Canxia Xu","doi":"10.1155/2023/5533444","DOIUrl":"https://doi.org/10.1155/2023/5533444","url":null,"abstract":"<i>Background</i>. Cancer affects millions of people each year and imposes a huge economic and social burden worldwide. Cuproptosis is a recently discovered novel mode of cell death. The exact function of the cuproptosis-related gene dihydrolipoamide dehydrogenase (DLD) and its role in pan-cancer is unknown. <i>Methods</i>. Data were retrieved from the GTEx, TCGA, and multiple online websites. These data were used to assess the expression, prognosis, and diagnostic value of DLD in various tumors. The relationship of DLD with immune microenvironment immunomodulators, immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI), and oncology drug sensitivity was explored by correlation analysis. <i>Results</i>. The mRNA and protein expression of DLD differs in most cancers. Survival analysis showed that DLD was associated with prognosis with KIRC, KIRP, KICH, and UCS. DLD had a strong diagnostic value in KIRC, GBM, PAAD, and LGG (AUC &gt; 0.9). DLD promoter methylation affects the aberrant expression of LIHC, LUSC, PAAD, READ, and THCA. DLD was negatively correlated with stromal score, immune score, and ESTIMATE score in UCEC, TGCT, LUSC, and SARC. In UCS, resting memory CD4 T cells and activated NK cells were significantly correlated with DLD expression. Significant correlations were also observed between DLD expression and immunomodulators, immune checkpoints, TMB, and MSI in various cancers. Importantly, we also identified a number of potential drugs that may target DLD. <i>Conclusion</i>. DLD expression is associated with a variety of tumor prognoses and plays an integral role in tumorigenesis, tumor metabolism, and immunity.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"168 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138508436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Inflammatory Cytokine Levels in Hepatic and Jugular Veins of Patients with Cirrhosis","authors":"Leonard Kaps, Carolina Medina-Montano, Matthias Bros, Stephan Grabbe, Simon Johannes Gairing, Eva M. Schleicher, Stephan Gehring, Jörn M. Schattenberg, Peter R. Galle, Marcus-Alexander Wörns, Michael Nagel, Christian Labenz","doi":"10.1155/2023/9930902","DOIUrl":"https://doi.org/10.1155/2023/9930902","url":null,"abstract":"<i>Background</i>. Systemic inflammation with elevated inflammatory cytokines is a hallmark in patients with cirrhosis and the main driver of decompensation. There is insufficient data on whether inflammatory cytokine levels differ between hepatic and jugular veins, which may have implications for further immunological studies. <i>Methods</i>. Blood from the hepatic and jugular veins of 40 patients with cirrhosis was collected during hepatic venous pressure gradient (HVPG) measurements. Serum levels of 13 inflammatory cytokines (IL-1<i>β</i>, Int-<i>α</i>2, Int-<i>γ</i>, TNF-<i>α</i>, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33) were quantified by cytometric bead array. <i>Results</i>. Cytokine levels of IFN-<i>α</i>2, IFN-<i>γ</i>, TNF-<i>α</i>, IL-6, IL-8, IL-10, IL-17A, IL-18, IL-23, and IL-33 were significantly elevated in patients with decompensated cirrhosis compared to patients with compensated cirrhosis. When comparing patients with clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) to patients without CSPH, there were significantly enhanced serum levels of IL-6 and IL-18 in the former group. There was no significant difference between cytokine serum levels between blood obtained from the jugular versus hepatic veins. Even in subgroup analyses stratified for an early cirrhosis stage (Child-Pugh (CP) A) or more decompensated stages (CP B/C), cytokine levels were similar. <i>Conclusion</i>. Cytokine levels increase with decompensation and increasing portal hypertension in patients with cirrhosis. There is no relevant difference in cytokine levels between hepatic and jugular blood in patients with cirrhosis.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"295 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138508389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abdominal Aortic Occlusion and the Inflammatory Effects in Heart and Brain","authors":"Jun Xu, Sijie Li, Alexandra Wehbe, Xunming Ji, Yong Yang, Yu Yang, Linhui Qin, Feng-Yong Liu, Yuchuan Ding, Changhong Ren","doi":"10.1155/2023/2730841","DOIUrl":"https://doi.org/10.1155/2023/2730841","url":null,"abstract":"Background. Abdominal aortic occlusion (AAO) occurs frequently and causes ischemia/reperfusion (I/R) injury to distant organs. In this study, we aimed to investigate whether AAO induced I/R injury and subsequent damage in cardiac and neurologic tissue. We also aimed to investigate the how length of ischemic time in AAO influences reactive oxygen species (ROS) production and inflammatory marker levels in the heart, brain, and serum. Methods. Sixty male C57BL/6 mice were used in this study. The mice were randomly divided into either sham group or AAO group. The AAO group was further subdivided into 1–4 hr groups of aortic occlusion times. The infrarenal abdominal aorta was clamped for 1–4 hr depending on the AAO group and was then reperfused for 24 hr after clamp removal. Serum, hippocampus, and left ventricle tissue samples were then subjected to biochemical and histopathological analyses. Results. AAO-induced I/R injury had no effect on cell necrosis, cell apoptosis, or ROS production. However, serum and hippocampus levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) increased in AAO groups when compared to sham group. Superoxide dismutase and total antioxidant capacity decreased in the serum, hippocampus, and left ventricle. In the serum, AAO increased the level of inducible nitric oxide synthase (iNOS) and decreased the levels of anti-inflammatory factors (such as arginase-1), transforming growth factor- β1 (TGF-β1), interleukin 4 (IL-4), and interleukin 10 (IL-10). In the hippocampus, AAO increased the levels of tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), IL-4, and IL-6, and decreased the level of TGF-β1. In the left ventricle, AAO increased the level of iNOS and decreased the levels of TGF-β1, IL-4, and IL-10. Conclusions. AAO did not induce cell necrosis or apoptosis in cardiac or neurologic tissue, but it can cause inflammation in the serum, brain, and heart.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"300 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138508406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Specific Regulation of Inflammatory Cytokines and Acute-Phase Proteins by the Glucocorticoid Receptor","authors":"Rebecca Winkler, Hong Lu","doi":"10.1155/2023/4399998","DOIUrl":"https://doi.org/10.1155/2023/4399998","url":null,"abstract":"<i>Background</i>. Literature and data mining found abnormal induction of chemokine (C-X-C motif) ligand 1 (CXCL1) and CXCL8 and down-regulation of CXCL2 in inflammatory liver diseases. This study was performed to understand the glucocorticoid receptor’s (GR’s) effects on chemokine and acute-phase protein expression in human liver, in settings of bacterial infection (modeled using LPS) or inflammation (modeled using TNF<i>α</i>). <i>Methods</i>. Primary human hepatocytes (PHH) were treated with combinations of tumor necrosis factor alpha (TNF<i>α</i>), lipopolysaccharide (LPS), and dexamethasone (DEX) for 24 h, following which chemokine mRNA and protein expression were analyzed using qPCR and enzyme-linked immunosorbent assay assays. Dual luciferase assays were performed on transfected cell lines. Mutant CXCL2 promoters were used in dual luciferase assays to identify specific regions of the CXCL2 promoter affected by GR, TNF<i>α</i>, or hepatocyte nuclear factor 4<i>α</i> (HNF4<i>α</i>, a liver-enriched transcription factor). <i>Results</i>. In PHH from donor 1, GR strongly inhibited LPS-induced CXCL1 and CXCL8 translation and transcription, whereas CXCL2 transcription tended to increase with DEX treatment. In PHH from donor 2, DEX treatment inhibited protein expression and secretion of CXCL1 and CXCL8 induced by TNF<i>α</i> and/or LPS, whereas CXCL2 upregulation was largely unaffected by DEX treatment. In nonliver HEK293T cells GR activity inhibited CXCL2 promoter activity. However, in liver-derived HEPG2 cells, GR induced CXCL2 promoter activity. A 407-base pair region upstream of CXCL2 promoter is necessary for full GR functionality in HEPG2 cells. TNF<i>α</i> synergized with HNF4<i>α</i> in inducing CXCL2 promoter activity in HEPG2 cells. <i>Conclusions</i>. GR’s effects on chemokine expression are cell-type specific and chemokine specific. GR down-regulated CXCL1 and CXCL8 in different cell types, whereas the specific activation of CXCL2 in hepatocytes and down-regulation of CXCL2 in nonhepatocytes by GR appears due to cell-specific utilization of CXCL2 promoter. By specifically increasing GR activity in the liver, we may normalize chemokine imbalances and prevent sepsis in inflammatory liver diseases.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"293 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138508390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between the Systemic Immune-Inflammation Index and Thyroid Function in U.S. Adults.","authors":"Xin-Yu Hu, Ying-Chao Liang, Huan-Huan Zhang, Hui-Lin Li, De-Liang Liu","doi":"10.1155/2023/5831858","DOIUrl":"https://doi.org/10.1155/2023/5831858","url":null,"abstract":"<p><strong>Background: </strong>The systemic immune-inflammation index (SII) is used as an indicator of prognosis for a wide range of diseases. Thyroid function has been found to be strongly associated with inflammation. The purpose of this investigation was to analyze the correlation between SII and various thyroid functions.</p><p><strong>Methods: </strong>This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. The association between SII and thyroid function was analyzed using weighted univariate and multivariate linear regression analyses. Subgroup analyses, interaction tests, and weighted restricted cubic spline (RCS) regression analyses were also employed to test this correlation.</p><p><strong>Results: </strong>Of the 6,875 participants (age ≥ 20 years), the mean age was 46.87 ± 0.40 years. The adjusted model showed that lnSII was negatively correlated with FT3 (<i>β</i> = -0.0559, 95% CI -0.1060 to -0.0059,) and FT3/FT4 (<i>β</i> = -0.0920, 95% CI -0.1667 to -0.0173,). There was a positive correlation between lnSII and TT4 (<i>β</i> = 0.1499, 95% CI 0.0722-0.2276,). In subgroup analyses, lnSII still independently affected a wide range of thyroid functions. Weighted RCS analysis showed a nonlinear relationship between FT3 and lnSII.</p><p><strong>Conclusion: </strong>Close relationships exist between SII and a variety of thyroid functions. SII can be used as an indicator to predict thyroid dysfunction. Control of inflammatory activity may be a protective measure against thyroid dysfunction. More large-scale prospective studies are necessary to further explore the correlation between SII and thyroid function and the role of obesity in this.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2023 ","pages":"5831858"},"PeriodicalIF":4.6,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460812","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}