Mediators of Inflammation最新文献

{"title":"Electroacupuncture Improves Cardiac Function via Inhibiting Sympathetic Remodeling Mediated by Promoting Macrophage M2 Polarization in Myocardial Infarction Mice.","authors":"Rou Peng, Junjing Shi, Minjiao Jiang, Danying Qian, Yuhang Yan, Hua Bai, Meiling Yu, Xin Cao, Shuping Fu, Shengfeng Lu","doi":"10.1155/2024/8237681","DOIUrl":"10.1155/2024/8237681","url":null,"abstract":"<p><p>Electroacupuncture (EA) at the Neiguan acupoint (PC6) has shown significant cardioprotective effects. Sympathetic nerves play an important role in maintaining cardiac function after myocardial infarction (MI). Previous studies have found that EA treatment may improve cardiac function by modulating sympathetic remodeling after MI. However, the mechanism in how EA affects sympathetic remodeling and improves cardiac function remains unclear. The aim of this study is to investigate the cardioprotective mechanism of EA after myocardial ischemic injury by improving sympathetic remodeling and promoting macrophage M2 polarization. We established a mouse model of MI by occluding coronary arteries in male C57/BL6 mice. EA treatment was performed at the PC6 with current intensity (1 mA) and frequency (2/15 Hz). Cardiac function was evaluated using echocardiography. Heart rate variability in mice was assessed via standard electrocardiography. Myocardial fibrosis was evaluated by Sirius red staining. Levels of inflammatory factors were assessed using RT-qPCR. Sympathetic nerve remodeling was assessed through ELISA, western blotting, immunohistochemistry, and immunofluorescence staining. Macrophage polarization was evaluated using flow cytometry. Our results indicated that cardiac systolic function improved significantly after EA treatment, with an increase in fractional shortening and ejection fraction. Myocardial fibrosis was significantly mitigated in the EA group. The sympathetic nerve marker tyrosine hydroxylase and the nerve sprouting marker growth-associated Protein 43 were significantly reduced in the EA group, indicating that sympathetic remodeling was significantly reduced. EA treatment also promoted macrophage M2 polarization, reduced levels of inflammatory factors TNF-<i>α</i>, IL-1<i>β</i>, and IL-6, and decreased macrophage-associated nerve growth factor in myocardial tissue. To sum up, our results suggest that EA at PC6 attenuates sympathetic remodeling after MI to promote macrophage M2 polarization and improve cardiac function.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"8237681"},"PeriodicalIF":4.4,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555213","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":"Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis.","authors":"Baoren Zhang, Chenglu Sun, Yanglin Zhu, Hong Qin, Dejun Kong, Jingyi Zhang, Bo Shao, Xiang Li, Shaohua Ren, Hongda Wang, Jingpeng Hao, Hao Wang","doi":"10.1155/2024/3282679","DOIUrl":"10.1155/2024/3282679","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic intestinal inflammatory disease with complex etiology. Interleukin-35 (IL-35), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably expressing IL-35 which enables the cytokines to reach the diseased mucosa, and explored whether upregulation of T-cell protein tyrosine phosphatase (TCPTP) in macrophages is involved in the mechanisms of IL-35-mediated attenuation of UC. After the successful construction of engineered bacteria expressing IL-35, a colitis model was successfully induced by giving BALB/c mice a solution containing 3% dextran sulfate sodium (DSS). Mice were treated with Pichia/IL-35, empty plasmid-transformed Pichia (Pichia/0), or PBS by gavage, respectively. The expression of TCPTP in macrophages (RAW264.7, BMDMs) and intestinal tissues after IL-35 treatment was detected. After administration of Pichia/IL-35, the mice showed significant improvement in weight loss, bloody stools, and shortened colon. Colon pathology also showed that the inflammatory condition of mice in the Pichia/IL-35 treatment group was alleviated. Notably, Pichia/IL-35 treatment not only increases local M2 macrophages but also decreases the expression of inflammatory cytokine IL-6 in the colon. With Pichia/IL-35 treatment, the proportion of M1 macrophages, Th17, and Th1 cells in mouse MLNs were markedly decreased, while Tregs were significantly increased. <i>In vitro</i> experiments, IL-35 significantly promoted the expression of TCPTP in macrophages stimulated with LPS. Similarly, the mice in the Pichia/IL-35 group also expressed more TCPTP than that of the untreated group and the Pichia/0 group.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2024 ","pages":"3282679"},"PeriodicalIF":4.4,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498369","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":"What Are the Reliable Plasma Biomarkers for Mild Cognitive Impairment? A Clinical 4D Proteomics Study and Validation","authors":"Zhitao Hou, Ailin Sun, Yan Li, Xiaochen Song, Shu Liu, Xinying Hu, Yihan Luan, Huibo Guan, Changyuan He, Yuefeng Sun, Jing Chen","doi":"10.1155/2024/7709277","DOIUrl":"https://doi.org/10.1155/2024/7709277","url":null,"abstract":"&lt;i&gt;Objective&lt;/i&gt;. At present, Alzheimer’s disease (AD) lacks effective treatment means, and early diagnosis and intervention are the keys to treatment. Therefore, for mild cognitive impairment (MCI) and AD patients, blood sample analysis using the 4D nonstandard (label-free) proteomic in-depth quantitative analysis, looking for specific protein marker expression differences, is important. These marker levels change as AD progresses, and the analysis of these biomarkers changes with this method, which has the potential to show the degree of disease progression and can be used for the diagnosis and preventive treatment of MCI and AD. &lt;i&gt;Materials and Methods&lt;/i&gt;. Patients were recruited according to the inclusion and exclusion criteria and divided into three groups according to scale scores. Elderly patients diagnosed with AD were selected as the AD group (&lt;i&gt;n&lt;/i&gt; = 9). Patients diagnosed with MCI were classified into the MCI group (&lt;i&gt;n&lt;/i&gt; = 10). Cognitively healthy elderly patients were included in the normal cognition control group (&lt;i&gt;n&lt;/i&gt; = 10). Patients’ blood samples were used for 4D label-free proteomic in-depth quantitative analysis to identify potential blood biomarkers. The sample size of each group was expanded (&lt;i&gt;n&lt;/i&gt; = 30), and the selected biomarkers were verified by enzyme-linked immunosorbent assay (ELISA) to verify the accuracy of the proteomic prediction. &lt;i&gt;Results&lt;/i&gt;. Six specific blood markers, namely, APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8, were detected by 4D label-free proteomic quantitative analysis. These markers showed a statistically significant upregulation trend in the MCI and AD groups compared with the normal cognition control group (&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 21.918 9.2729\" 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;&lt;/span&gt; ELISA results showed that the levels of these six proteins in the MCI group were significantly higher than those in the normal cognition control group, and the levels of these six proteins in the AD group were significantly higher than those in the MCI group (&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:xlin","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"49 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141170134","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":"Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression","authors":"Li Xiang, Wenxu Pan, Huan Chen, Wenjun Du, Shuping Xie, Xinhua Liang, Fangying Yang, Rongwei Niu, Canxin Huang, Minan Luo, Yuxin Xu, Lanlan Geng, Sitang Gong, Wanfu Xu, Junhong Zhao","doi":"10.1155/2024/7524314","DOIUrl":"https://doi.org/10.1155/2024/7524314","url":null,"abstract":"<i>Objective</i>. Microfold cells (M cells) are specific intestinal epithelial cells for monitoring and transcytosis of antigens, microorganisms, and pathogens in the intestine. However, the mechanism for M-cell development remained elusive. <i>Materials and Methods</i>. Real-time polymerase chain reaction, immunofluorescence, and western blotting were performed to analyze the effect of sorbitol-regulated M-cell differentiation <i>in vivo</i> and <i>in vitro</i>, and luciferase and chromatin Immunoprecipitation were used to reveal the mechanism through which sorbitol-modulated M-cell differentiation. <i>Results</i>. Herein, in comparison to the mannitol group (control group), we found that intestinal M-cell development was inhibited in response to sorbitol treatment as evidenced by impaired enteroids accompanying with decreased early differentiation marker Annexin 5, Marcksl1, Spib, sox8, and mature M-cell marker glycoprotein 2 expression, which was attributed to downregulation of receptor activator of nuclear factor kappa-В ligand (RANKL) expression <i>in vivo</i> and <i>in vitro</i>. Mechanically, in the M-cell model, sorbitol stimulation caused a significant upregulation of phosphodiesterase 4 (PDE4) phosphorylation, leading to decreased protein kinase A (PKA)/cAMP-response element binding protein (CREB) activation, which further resulted in CREB retention in cytosolic and attenuated CREB binds to RANKL promoter to inhibit RANKL expression. Interestingly, endogenous PKA interacted with CREB, and this interaction was destroyed by sorbitol stimulation. Most importantly, inhibition of PDE4 by dipyridamole could rescue the inhibitory effect of sorbitol on intestinal enteroids and M-cell differentiation and mature <i>in vivo</i> and <i>in vitro</i>. <i>Conclusion</i>. These findings suggested that sorbitol suppressed intestinal enteroids and M-cell differentiation and matured through PDE4-mediated RANKL expression; targeting to inhibit PDE4 was sufficient to induce M-cell development.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"73 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834834","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":"Impact of Preoperative Neutrophil to Prealbumin Ratio Index (NPRI) on Short-Term Complications and Long-Term Prognosis in Patients Undergoing Laparoscopic Radical Surgery for Colorectal Cancer","authors":"Wenliang Jiang, Yong Xia, Yujun Liu, Shaoqi Cheng, Wenya Wang, Zhenghui Guan, Hongmei Dou, Changhe Zhang, Honggang Wang","doi":"10.1155/2024/4465592","DOIUrl":"https://doi.org/10.1155/2024/4465592","url":null,"abstract":"<i>Objective</i>. This study aims to evaluate the impact and predictive value of the preoperative NPRI on short-term complications and long-term prognosis in patients undergoing laparoscopic radical surgery for colorectal cCancer (CRC). <i>Methods</i>. A total of 302 eligible CRC patients were included, assessing five inflammation—and nutrition-related markers and various clinical features for their predictive impact on postoperative outcomes. Emphasis was on the novel indicator NPRI to elucidate its prognostic and predictive value for perioperative risks. <i>Results</i>. Multivariate logistic regression analysis identified a history of abdominal surgery, prolonged surgical duration, CEA levels ≥5 ng/mL, and NPRI ≥ 3.94 × 10⁻² as independent risk factors for postoperative complications in CRC patients. The Clavien–-Dindo complication grading system highlighted the close association between preoperative NPRI and both common and severe complications. Multivariate analysis also identified a history of abdominal surgery, tumor diameter ≥5 cm, poorly differentiated or undifferentiated tumors, and NPRI ≥ 2.87 × 10⁻² as independent risk factors for shortened overall survival (OS). Additionally, a history of abdominal surgery, tumor maximum diameter ≥5 cm, tumor differentiation as poor/undifferentiated, NPRI ≥ 2.87 × 10⁻², and TNM Stage III were determined as independent risk factors for shortened disease-free survival (DFS). Survival curve results showed significantly higher 5-year OS and DFS in the low NPRI group compared to the high NPRI group. The incorporation of NPRI into nomograms for OS and DFS, validated through calibration and decision curve analyses, attested to the excellent accuracy and practicality of these models. <i>Conclusion</i>. Preoperative NPRI independently predicts short-term complications and long-term prognosis in patients undergoing laparoscopic colorectal cancer surgery, enhancing predictive accuracy when incorporated into nomograms for patient survival.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"15 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140806325","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":"Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction","authors":"Hui Tang, Dan Li, Jing Peng, Weitao Yang, Xian Zhang, Hanmei Li","doi":"10.1155/2024/9986187","DOIUrl":"https://doi.org/10.1155/2024/9986187","url":null,"abstract":"<i>Objective</i>. Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR. <i>Methods</i>. In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status. Umbilical cord blood, maternal serum, feces, and placental tissue samples were collected during delivery. RNA sequencing, 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in umbilical cord blood circulating mRNA, fecal microbiota, and metabolites. RT-qPCR, ELISA, or western blot were used to detect the expression of top 5 differential circulating mRNA in neonatal cord blood, maternal serum, or placental tissue samples. Correlation between differential circulating mRNA, microbiota, and metabolites was analyzed by the Spearman coefficient. <i>Results</i>. The top 5 mRNA genes in FGR were altered with the downregulation of TRIM34, DEFA3, DEFA1B, DEFA1, and QPC, and the upregulation of CHPT1, SMOX, FAM83A, GDF15, and NAPG in newborn umbilical cord blood, maternal serum, and placental tissue. The abundance of <i>Bacteroides</i>, <i>Akkermansia</i>, <i>Eubacterium_coprostanoligenes_group</i>, <i>Phascolarctobacterium</i>, <i>Parasutterella</i>, <i>Odoribacter</i>, <i>Lachnospiraceae_UCG_010</i>, and <i>Dielma</i> were significantly enriched in the FGR group. Metabolites such as aspartic acid, methionine, alanine, L-tryptophan, 3-methyl-2-oxovalerate, and ketoleucine showed notable functional alterations. Spearman correlation analysis indicated that metabolites like methionine and alanine, microbiota (<i>Tyzzerella</i>), and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) might play a role as mediators in the communication between the gut and circulatory system interaction in FGR. <i>Conclusion</i>. Metabolites (METHIONINE, alanine) as well as microbiota (<i>Tyzzerella</i>) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"86 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578091","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":"Studies Related to the Involvement of EsA in Improving Intestinal Inflammation in Acute Pancreatitis via the NF-κB Pathway","authors":"CuiPing Pan, ChunXiang Zhang, YiJie Li, Jie Cao, ShiWei Liang, HaiCheng Fang, Ying Liu","doi":"10.1155/2024/9078794","DOIUrl":"https://doi.org/10.1155/2024/9078794","url":null,"abstract":"<i>Background</i>. Acute pancreatitis (AP) is a clinically frequent acute abdominal condition, which refers to an inflammatory response syndrome of edema, bleeding, and even necrosis caused by abnormal activation of the pancreas’s own digestive enzymes. Intestinal damage can occur early in the course of AP and is manifested by impaired intestinal mucosal barrier function, and inflammatory reactions of the intestinal mucosa, among other factors. It can cause translocation of intestinal bacteria and endotoxins, further aggravating the condition of AP. Therefore, actively protecting the intestinal mucosal barrier, controlling the progression of intestinal inflammation, and improving intestinal dynamics in the early stages of AP play an important role in enhancing the prognosis of AP. <i>Methods</i>. The viability and apoptosis of RAW264.7 cells treated with Esculentoside A (EsA) and/or lipopolysaccharide were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. The expression of apoptosis-related proteins and NF-<i>κ</i>B signaling pathway-related proteins were detected by western blot (WB). An enzyme-linked immunosorbent assay was used to measure TNF-<i>α</i> and IL-6 secretion. <i>Results</i>. In vitro experiments demonstrated that EsA not only promoted the apoptosis of inflammatory cells but also reduced the secretion of TNF-<i>α</i> and IL-6 in a dose-dependent manner. Additionally, it inhibited the activation of the NF-<i>κ</i>B signaling pathway by decreasing the expression of phosphorylated-p65(p-p65) and elevating the expression of I<i>κ</i>B<i>α</i>. Similarly, in vivo experiments using a rat AP model showed that EsA inhibited the expression of p-p65 elevating the expression of I<i>κ</i>B<i>α</i> in the intestinal tissues of the rat AP model and promoting the apoptosis of inflammatory cells in the intestinal mucosa in vivo experiments, while improving the pathological outcome of the pancreatic and intestinal tissues. <i>Conclusion</i>. Our results suggest that EsA can reduce intestinal inflammation in the rat AP model and that EsA may be a candidate for treating intestinal inflammation in AP and further arresting AP progression.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"1 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578008","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 Causal Relationship between Plasma Myeloperoxidase Levels and Respiratory Tract Infections: A Bidirectional Mendelian Randomization Study","authors":"Xiu Liu, Chuchu Zhang, Jiajia Ren, Guorong Deng, Xi Xu, Jueheng Liu, Xiaoming Gao, Ruohan Li, Jiamei Li, Gang Wang","doi":"10.1155/2024/6626706","DOIUrl":"https://doi.org/10.1155/2024/6626706","url":null,"abstract":"&lt;i&gt;Background&lt;/i&gt;. Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause–effect relation between plasma MPO levels and RTIs. &lt;i&gt;Materials and Methods&lt;/i&gt;. Datasets of plasma MPO levels were from the Folkersen et al. study (&lt;i&gt;n&lt;/i&gt; = 21,758) and INTERVAL study (&lt;i&gt;n&lt;/i&gt; = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane’s &lt;i&gt;Q&lt;/i&gt; test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. &lt;i&gt;Results&lt;/i&gt;. We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011–1.274; &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;/path&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; and LRTI (ICU) (OR = 1.323; 95% CI = 1.006–1.739; &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;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=\"#g117-34\"&gt;&lt;/use&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;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","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"30 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140313865","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 Association between Serum Level of Vitamin D and Inflammatory Biomarkers in Hospitalized Adult Patients: A Cross-Sectional Study Based on Real-World Data","authors":"Xiaomin Zhang, Zhiqi Chen, Yi Xiang, Yiquan Zhou, Molian Tang, Jun Cai, Xinyi Xu, Hongyuan Cui, Yi Feng, Renying Xu","doi":"10.1155/2024/8360538","DOIUrl":"https://doi.org/10.1155/2024/8360538","url":null,"abstract":"<i>Objective</i>. The association between vitamin D status and inflammation remains unclear in hospitalized patients. <i>Materials and Methods</i>. We performed the current study based on real-world data from two teaching hospitals. Serum level of vitamin D (assessed by 25-hydroxyvitamin D) was evaluated within 2 days after admission. All the patients were further classified into three groups: deficiency (&lt;12 ng/mL), insufficiency (12–20 ng/mL), and adequate (≥20 ng/mL). White blood cell (WBC) count, serum level of C-reactive protein (CRP), and procalcitonin were also measured and used to evaluate inflammation. Other potential covariates were abstracted from medical records. Charlson comorbidity index (CCI) was calculated to assess the severity of disease. <i>Results</i>. A total number of 35,528 hospitalized adult patients (21,171 men and 14,357 women) were included. The average age and BMI were 57.5 ± 16.2 years and 23.4 ± 3.7 kg/m², respectively, while medium vitamin D level was 16.1 ng/mL (interquartile range: 11.4 ng/mL, 21.6 ng/mL) and median CCI was one point (interquartile range: 0 point, two points). The prevalence of deficiency and insufficiency was 28.0% and 40.5%. Multivariate linear regression model showed that serum level of vitamin D was significantly associated with WBC and CRP but not associated with procalcitonin. Each standard deviation (≈7.4 ng/mL) increase in vitamin D was associated with a decrease in WBC by 0.13 × 10⁹/mL (95% CI: 0.2 × 10⁹/mL, 0.06 × 10⁹/mL) and 0.62 mg/L (95% CI: 0.88 mg/L, 0.37 mg/L) for CRP. Subgroup analysis and sensitivity analysis (excluding those whose eGFR &lt;60 ml/min/1.73 m², those whose daily calorie intake &lt;1,000 kcal, and those who were recruited from Xin Hua hospital) generated similar results. <i>Conclusions</i>. The deficiency and insufficiency of vitamin D in the hospitalized adult patients was very common. However, the results should be interpreted with caution for limited representation of the whole inpatients. Low level of vitamin D was associated with inflammatory biomarkers, which provide the evidences to early intervention for lower the risk of infection.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"24 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140201529","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":"Tanshinone IIA Alleviates Traumatic Brain Injury by Reducing Ischemia‒Reperfusion via the miR-124-5p/FoxO1 Axis","authors":"Wenbing Su, Meifen Lv, Dayu Wang, Yinghong He, Hui Han, Yu Zhang, Xiuying Zhang, Shaokun Lv, Liqing Yao","doi":"10.1155/2024/7459054","DOIUrl":"https://doi.org/10.1155/2024/7459054","url":null,"abstract":"&lt;i&gt;Background&lt;/i&gt;. Cerebral ischemia–reperfusion injury is a common complication of ischemic stroke that affects the prognosis of patients with ischemic stroke. The lipid-soluble diterpene Tanshinone IIA, which was isolated from &lt;i&gt;Salvia miltiorrhiza&lt;/i&gt;, has been indicated to reduce cerebral ischemic injury. In this study, we investigated the molecular mechanism of Tanshinone IIA in alleviating reperfusion-induced brain injury. &lt;i&gt;Methods&lt;/i&gt;. Middle cerebral artery occlusion animal models were established, and neurological scores, tetrazolium chloride staining, brain volume quantification, wet and dry brain water content measurement, Nissl staining, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription–quantitative polymerase chain reaction were performed. The viability of cells was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays, while cell damage was measured by lactate dehydrogenase release in the &lt;i&gt;in vitro&lt;/i&gt; oxygen glucose deprivation model. In addition, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription–quantitative polymerase chain reaction were used to evaluate the therapeutic effect of Tanshinone IIA on ischemia/reperfusion (I/R) induced brain injury, as well as its effects on the inflammatory response and neuronal apoptosis, &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt;. Furthermore, this study validated the targeting relationship between miR-124-5p and FoxO1 using a dual luciferase assay. Finally, we examined the role of Tanshinone IIA in brain injury from a molecular perspective by inhibiting miR-124-5p or increasing FoxO1 levels. &lt;i&gt;Results&lt;/i&gt;. After treatment with Tanshinone IIA in middle cerebral artery occlusion–reperfusion (MCAO/R) rats, the volume of cerebral infarction was reduced, the water content of the brain was decreased, the nerve function of the rats was significantly improved, and the cell damage was significantly reduced. In addition, Tanshinone IIA effectively inhibited the I/R-induced inflammatory response and neuronal apoptosis, that is, it inhibited the expression of inflammatory cytokines IL-1&lt;i&gt;β&lt;/i&gt;, IL-6, TNF-&lt;i&gt;α&lt;/i&gt;, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. &lt;i&gt;In vitro&lt;/i&gt; oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, Tanshinone IIA also inhibited the expression of inflammatory factors in neuronal cells and inhibited the occurrence of neuronal apoptosis. In addition, Tanshinone IIA promoted the expression of miR-124-5p. Transfection of miR-124-5p mimic has the same therapeutic effect as Tanshinone IIA and positive therapeutic effect on OGD cells, while transfection of miR-124-5p inhibitor has the opposite effect. The targeting of miR-124-5p negatively regulates FoxO1 expression. Inhibition of miR-124-5p or overexpression of FoxO1 can weaken the inhibitory effect of Tanshinone IIA on brain inj","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"22 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140201928","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}