Mediators of Inflammation最新文献

{"title":"Salvianolic Acid B Alleviates High Glucose-Induced Vascular Smooth Muscle Cell Inflammation by Upregulating the miR-486a-5p Expression","authors":"Man-Li Zhang, Man-Na Zhang, Hui Chen, Xia Wang, Kun Zhao, Xuan Li, Xuan Song, Fei Tong","doi":"10.1155/2024/4121166","DOIUrl":"https://doi.org/10.1155/2024/4121166","url":null,"abstract":"The macrovascular complications of diabetes cause high mortality and disability in patients with type 2 diabetes mellitus (T2DM). The inflammatory response of vascular smooth muscle cell (VSMC) runs through its pathophysiological process. Salvianolic acid B (Sal B) exhibits beneficial effects on the cardiovascular system. However, its role and mechanism in diabetic vascular inflammatory response remain unclear. In this study, we found that Sal B reduced vascular inflammation in diabetic mice and high glucose- (HG-) induced VSMC inflammation. Subsequently, we found that Sal B reduced HG-induced VSMC inflammation by downregulating FOXO1. Furthermore, miR-486a-5p expression was obviously reduced in HG-treated VSMC. Sal B attenuated HG-induced VSMC inflammation by upregulating miR-486a-5p. Loss- and gain-of-function experiments had proven that the transfection of the miR-486a-5p mimic inhibited HG-induced VSMC inflammation whereas that of the miR-486a-5p inhibitor promoted HG-induced VSMC inflammation, thereby leading to the amelioration of vascular inflammation in the diabetic mice. Furthermore, studies had shown that miR-486a-5p inhibited FOXO1 expression by directly targeting its 3^′-UTR. In conclusion, Sal B alleviates the inflammatory response of VSMC by upregulating miR-486a-5p and aggravating its inhibition of FOXO1 expression. Sal B exerts a significant anti-inflammatory effect in HG-induced VSMC inflammation by modulating the miR-486a-5p/FOXO1 axis.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"215 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139767614","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":"Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study","authors":"Fucun Liu, Juelan Ye, Shouli Wang, Yang Li, Yuhang Yang, Jianru Xiao, Aimin Jiang, Xuhua Lu, Yunli Zhu","doi":"10.1155/2024/3188216","DOIUrl":"https://doi.org/10.1155/2024/3188216","url":null,"abstract":"<i>Background</i>. Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. <i>Methods</i>. We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of <i>CRTAM</i> in RA. In addition, comparisons of diagnostic efficacy and biological roles among <i>CRTAM</i> and other classic biomarkers of RA were also performed. <i>Results</i>. Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including <i>CRTAM</i>, <i>PTTG1IP</i>, <i>ITGB2</i>, and <i>MMP13</i>, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of <i>CRTAM</i> could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including <i>MMP3</i>, <i>S100A8</i>, <i>S100A9</i>, <i>IL6</i>, <i>COMP</i>, <i>LAG3</i>, and <i>ENTPD1</i>. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. <i>Conclusion</i>. <i>CRTAM</i>, <i>PTTG1IP</i>, <i>ITGB2</i>, and <i>MMP13</i> were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, <i>CRTAM</i> might fuel cancer progression through immune signals, especially among RA patients.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"139 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139767858","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":"Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats.","authors":"Shuyu Ge, Zhenghong Guo, Ting Xiao, Pingping Sun, Bo Yang, Yin Ying","doi":"10.1155/2024/5573353","DOIUrl":"10.1155/2024/5573353","url":null,"abstract":"<p><p>As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-<i>β</i> (TGF-<i>β</i>), tumor necrosis factor-<i>α</i> (TNF-<i>α</i>), and interleukin-1<i>β</i> (IL-1<i>β</i>)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (<i>α</i>-smooth muscle actin (<i>α</i>-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and <i>α</i>-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"5573353"},"PeriodicalIF":4.6,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741335","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":"Cryptotanshinone Inhibits Bladder Cancer Cell Malignant Progression in a Lipopolysaccharide-Induced Inflammatory Microenvironment through NLRP3 Inhibition","authors":"Chenye Tang, Xiao Guo, Yu Li, Yongxiang Yi, Zhiling Tang, Qihui Zhang, Bairu Luo, Kean Chen, Ke Liang, Gang Li","doi":"10.1155/2024/8828367","DOIUrl":"https://doi.org/10.1155/2024/8828367","url":null,"abstract":"<i>Background</i>. Bladder cancer (BC) is one of the most common malignancies of the urogenital system. This study assessed the nucleotide-binding oligomerization domain and leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) in BC as well as the effects of cryptotanshinone on changes in BC malignant behaviors and NLRP3 expression under a lipopolysaccharide (LPS)-induced inflammatory microenvironment. <i>Methods</i>. BC tissue specimens from 62 patients were collected for immunohistochemical detection of NLRP3 protein. BC and normal urothelial cell lines were cultured for the detection of NLRP3 mRNA and protein. Then, BC cells were pretreated with LPS to mimic the inflammatory tumor microenvironment. Next, these cells were incubated with a low or high dose of cryptotanshinone to assess its effects on tumor cell malignant behaviors as well as transfected with NLRP3 cDNA to confirm the role of NLRP3 in BC cells <i>in vitro</i>. <i>Results</i>. High NLRP3 expression was associated with larger tumor diameters (&gt;2 cm), muscle invasion, and metastasis. The levels of NLRP3 mRNA and protein were greater in BC cells than in normal urothelial cells. LPS pretreatment significantly promoted NLRP3 and inflammatory cytokine expression in BC cells, and induced cell viability, migration, and invasion. However, cryptotanshinone was able to reduce the LPS-induced increase of NLRP3 and inflammatory cytokine expression as well as the BC cell malignant progression. NLRP3 overexpression using NLRP3 cDNA further promoted BC cell malignant progression after LPS stimulation and reversed cryptotanshinone-reduced LPS-induced BC cell malignant behaviors. <i>Conclusion</i>. NLRP3 might possess oncogenic activity in BC, and the antitumor activity of cryptotanshinone in BC <i>in vitro</i> might be related to its inhibition of NLRP3 expression.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"38 5 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139586992","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":"Photoprotective Effects of Epigallocatechin Gallate on Ultraviolet-Induced Zebrafish and Human Skin Fibroblasts Cells","authors":"Jie Zhang, Yahui Xu, Xiyu Ruan, Ting Zhang, Minghui Zi, Qiao Zhang","doi":"10.1155/2024/7887678","DOIUrl":"https://doi.org/10.1155/2024/7887678","url":null,"abstract":"<i>Background</i>. The long-term exposure to ultraviolet radiation (UVR) raises oxidative stress and chronic inflammation levels, which in turn has a series of deleterious effects on skin health, such as sunburn, photoaging, and skin cancer. Hence, our study was determined to investigate the effects and mechanisms of epigallocatechin gallate (EGCG) in zebrafish and human skin fibroblasts (HSF) cells to alleviate ultraviolet-induced photoaging. <i>Methods</i>. The 4 days postfertilization (dpf) zebrafish larvae and HSF cells were treated with 10 J/cm² UVA + 30 mJ/cm² UVB, or 25, or 50 <i>μ</i>M EGCG for 72 hr. The indicators involving in oxidative stress, inflammatory, and photoaging were measured by the kits, ELISA Kits and western blot methods. <i>Results</i>. EGCGs protect against UVR-induced skin damage in zebrafish and HSF cells. EGCG markedly decreased the reactive oxygen species (ROS), malondialdehyde, 8-OHdG levels, increased superoxide dismutase (SOD) activity, and significantly inhibited inflammatory factors levels including tumor necrosis factor-<i>α</i> (TNF-<i>α</i>), interleukin-1<i>α</i> (IL-1<i>α</i>), interleukin-6 (IL-6) in zebrafish, and HSF cells irradiated with UVR. We found that EGCG could reduce UVR-induced p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation and effectively inhibited the activity of the transcriptional factor nuclear factor-<i>κ</i>B (NF-<i>κ</i>B), thereby reducing the protein-1 (AP-1), TNF-<i>α</i>, IL-1<i>α</i>, IL-6, and matrix metalloproteinase-1 (MMP-1) expressions, which are critical mediators of skin aging cascade causing the photoaging. <i>Conclusion</i>. These results validate that EGCG for protection of photoaging in zebrafish and HSF cells induced by UVR, which is closely related to the regulation of p38 MAPK/NF-<i>κ</i>B, AP-1 signaling pathway which relieve oxidative stress, inflammation, and collagen degradation.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"212 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139561339","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":"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":"&lt;i&gt;Background&lt;/i&gt;. 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. &lt;i&gt;Methods&lt;/i&gt;. 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. &lt;i&gt;Results&lt;/i&gt;. The results of the univariate analysis showed a significant positive correlation between PLR levels and SII (&lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,44.605,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;).&lt;/span&gt;&lt;/span&gt; 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 &lt; 1,326.47 (&lt;i&gt;β&lt;/i&gt; 0.14, 95% CI: 0.12, 0.16; &lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;use xlink:href=\"#g113-81\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"&gt;&lt;use xlink:href=\"#g117-91\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"&gt;&lt;use xlink:href=\"#g113-47\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;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":"&lt;i&gt;Objectives&lt;/i&gt;. 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. &lt;i&gt;Methods&lt;/i&gt;. 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. &lt;i&gt;Results&lt;/i&gt;. 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 (&lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;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":"&lt;i&gt;Background&lt;/i&gt;. 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. &lt;i&gt;Methods&lt;/i&gt;. 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&lt;i&gt;β&lt;/i&gt;, TNF&lt;i&gt;α&lt;/i&gt;, and IL-6) and oxidative stress markers (CAT, SOD, and MDA) after sacrifice. &lt;i&gt;Results&lt;/i&gt;. Silymarin improved spatial memory and fear learning compared to the sham group (&lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;/span&gt; to &lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;use xlink:href=\"#g113-81\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"&gt;&lt;use xlink:href=\"#g117-93\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;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\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"&gt;&lt;use xlink:href=\"#g113-47\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,44.605,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;).&lt;/span&gt;&lt;/span&gt; It also significantly reduced IL-1&lt;i&gt;β&lt;/i&gt;, TNF-&lt;i&gt;α&lt;/i&gt;, and IL-6 levels in the cortex, hippocampus, and liver (&lt;span&gt;&lt;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}