Hui Tang, Dan Li, Jing Peng, Weitao Yang, Xian Zhang, Hanmei Li
Objective. 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. Methods. 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. Results. 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 Bacteroides, Akkermansia, Eubacterium_coprostanoligenes_group, Phascolarctobacterium, Parasutterella, Odoribacter, Lachnospiraceae_UCG_010, and Dielma 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 (Tyzzerella), 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. Conclusion. Metabolites (METHIONINE, alanine) as well as microbiota (Tyzzerella) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR.
{"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}
CuiPing Pan, ChunXiang Zhang, YiJie Li, Jie Cao, ShiWei Liang, HaiCheng Fang, Ying Liu
Background. 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. Methods. 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-κB signaling pathway-related proteins were detected by western blot (WB). An enzyme-linked immunosorbent assay was used to measure TNF-α and IL-6 secretion. Results. In vitro experiments demonstrated that EsA not only promoted the apoptosis of inflammatory cells but also reduced the secretion of TNF-α and IL-6 in a dose-dependent manner. Additionally, it inhibited the activation of the NF-κB signaling pathway by decreasing the expression of phosphorylated-p65(p-p65) and elevating the expression of IκBα. Similarly, in vivo experiments using a rat AP model showed that EsA inhibited the expression of p-p65 elevating the expression of IκBα 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. Conclusion. 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.
背景。急性胰腺炎（AP）是临床上常见的急腹症，是指胰腺自身消化酶异常激活引起的水肿、出血甚至坏死的炎症反应综合征。肠道损伤可发生在 AP 的早期，表现为肠黏膜屏障功能受损、肠黏膜炎症反应等。它可导致肠道细菌和内毒素转运，进一步加重 AP 的病情。因此，在 AP 早期积极保护肠黏膜屏障，控制肠道炎症进展，改善肠道动力，对改善 AP 的预后具有重要作用。研究方法用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑（MTT）和流式细胞术分别检测用商陆皂苷甲（EsA）和/或脂多糖处理的 RAW264.7 细胞的活力和凋亡。免疫印迹（WB）法检测凋亡相关蛋白和 NF-κB 信号通路相关蛋白的表达。酶联免疫吸附试验用于检测 TNF-α 和 IL-6 的分泌。结果体外实验表明，Esa 不仅能促进炎症细胞的凋亡，还能以剂量依赖的方式减少 TNF-α 和 IL-6 的分泌。此外，它还通过降低磷酸化-p65（p-p65）的表达和提高 IκBα 的表达来抑制 NF-κB 信号通路的激活。同样，使用大鼠 AP 模型进行的体内实验表明，Esa 可抑制 p-p65 的表达，提高大鼠 AP 模型肠道组织中 IκBα 的表达，促进体内实验中肠粘膜炎症细胞的凋亡，同时改善胰腺和肠道组织的病理结果。结论我们的研究结果表明，EsA 可以减轻大鼠 AP 模型的肠道炎症，EsA 可能是治疗 AP 肠道炎症和进一步阻止 AP 进展的候选药物。
{"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}
Xiu Liu, Chuchu Zhang, Jiajia Ren, Guorong Deng, Xi Xu, Jueheng Liu, Xiaoming Gao, Ruohan Li, Jiamei Li, Gang Wang
<i>Background</i>. 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. <i>Materials and Methods</i>. Datasets of plasma MPO levels were from the Folkersen et al. study (<i>n</i> = 21,758) and INTERVAL study (<i>n</i> = 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 <i>Q</i> 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. <i>Results</i>. We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011–1.274; <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)"></path></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"></path></g></svg>)</span></span> and LRTI (ICU) (OR = 1.323; 95% CI = 1.006–1.739; <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)"><use xlink:href="#g113-81"></use></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"></use></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)"><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
{"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":"<i>Background</i>. 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. <i>Materials and Methods</i>. Datasets of plasma MPO levels were from the Folkersen et al. study (<i>n</i> = 21,758) and INTERVAL study (<i>n</i> = 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 <i>Q</i> 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. <i>Results</i>. We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011–1.274; <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)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,44.605,0)\"></path></g></svg>)</span></span> and LRTI (ICU) (OR = 1.323; 95% CI = 1.006–1.739; <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)\"><use xlink:href=\"#g113-81\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"><use xlink:href=\"#g117-34\"></use></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)\"><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","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}
Xiaomin Zhang, Zhiqi Chen, Yi Xiang, Yiquan Zhou, Molian Tang, Jun Cai, Xinyi Xu, Hongyuan Cui, Yi Feng, Renying Xu
Objective. The association between vitamin D status and inflammation remains unclear in hospitalized patients. Materials and Methods. 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 (<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. Results. 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 <60 ml/min/1.73 m2, those whose daily calorie intake <1,000 kcal, and those who were recruited from Xin Hua hospital) generated similar results. Conclusions. 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.
目的。住院患者的维生素 D 状态与炎症之间的关系仍不明确。材料和方法。我们根据两家教学医院的实际数据开展了本研究。在入院后 2 天内评估血清维生素 D 水平（通过 25- 羟基维生素 D 评估）。所有患者被进一步分为三组：缺乏（12 毫微克/毫升）、不足（12-20 毫微克/毫升）和充足（≥20 毫微克/毫升）。此外，还测量了白细胞（WBC）计数、血清 C 反应蛋白（CRP）水平和降钙素原，用于评估炎症情况。其他潜在的协变量均来自医疗记录。计算夏尔森合并症指数（CCI）以评估疾病的严重程度。研究结果共纳入 35528 名住院成年患者（男性 21171 人，女性 14357 人）。平均年龄和体重指数分别为 57.5 ± 16.2 岁和 23.4 ± 3.7 kg/m2，维生素 D 中等水平为 16.1 纳克/毫升（四分位数间距：11.4 纳克/毫升，21.6 纳克/毫升），CCI 中位数为 1 点（四分位数间距：0 点，2 点）。缺乏和不足的发生率分别为 28.0% 和 40.5%。多变量线性回归模型显示，血清维生素 D 水平与白细胞和 CRP 显著相关，但与降钙素原无关。维生素 D 每增加一个标准差（≈7.4 纳克/毫升），WBC 就会减少 0.13 × 109/毫升（95% CI：0.2 × 109/毫升，0.06 × 109/毫升），CRP 减少 0.62 毫克/升（95% CI：0.88 毫克/升，0.37 毫克/升）。亚组分析和敏感性分析（排除 eGFR <60 ml/min/1.73 m2 者、每日热量摄入 <1,000 kcal 者和从新华医院招募者）得出了相似的结果。结论在住院的成年患者中，维生素 D 缺乏和不足的情况非常普遍。然而，由于这些结果在所有住院病人中的代表性有限，因此在解释这些结果时应谨慎。维生素 D 水平低与炎症生物标志物有关，这为早期干预以降低感染风险提供了证据。
{"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 (<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/m<sup>2</sup>, 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 × 10<sup>9</sup>/mL (95% CI: 0.2 × 10<sup>9</sup>/mL, 0.06 × 10<sup>9</sup>/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 <60 ml/min/1.73 m<sup>2</sup>, those whose daily calorie intake <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}
Wenbing Su, Meifen Lv, Dayu Wang, Yinghong He, Hui Han, Yu Zhang, Xiuying Zhang, Shaokun Lv, Liqing Yao
<i>Background</i>. 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 <i>Salvia miltiorrhiza</i>, 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. <i>Methods</i>. 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 <i>in vitro</i> 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, <i>in vivo</i> and <i>in vitro</i>. 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. <i>Results</i>. 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<i>β</i>, IL-6, TNF-<i>α</i>, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. <i>In vitro</i> 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
{"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":"<i>Background</i>. 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 <i>Salvia miltiorrhiza</i>, 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. <i>Methods</i>. 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 <i>in vitro</i> 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, <i>in vivo</i> and <i>in vitro</i>. 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. <i>Results</i>. 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<i>β</i>, IL-6, TNF-<i>α</i>, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. <i>In vitro</i> 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}
Atherosclerosis is a leading cause of death in the world. A significant body of evidence suggests that inflammation and various players are implicated and have pivotal roles in the formation of atherosclerotic plaques. Toll-like receptor 4 (TLR4) is linked with different stages of atherosclerosis. This receptor is highly expressed in the endothelial cells (ECs) and atherosclerotic plaques. TLR4 activation can lead to the production of inflammatory cytokines and related responses. Lectin-like oxidized low-density lipoprotein-1 (LOX-1), an integral membrane glycoprotein with widespread expression on the ECs, is involved in atherosclerosis and has some common pathways with TLR4 in atherosclerotic lesions. In addition, proprotein convertase subtilisin/kexin type9 (PCSK9), which is a regulatory enzyme with different roles in cholesterol uptake, is implicated in atherosclerosis. At present, TLR4, PCSK9, and LOX-1 are increasingly acknowledged as key players in the pathogenesis of atherosclerotic cardiovascular diseases. Herein, we presented the current evidence on the structure, functions, and roles of TLR4, PCSK9, and LOX-1 in atherosclerosis.
{"title":"Atherosclerosis and Toll-Like Receptor4 (TLR4), Lectin-Like Oxidized Low-Density Lipoprotein-1 (LOX-1), and Proprotein Convertase Subtilisin/Kexin Type9 (PCSK9)","authors":"Bahador Bagheri, Zahra Khatibiyan Feyzabadi, Ahmad Nouri, Ali Azadfallah, Mahyar Mahdizade Ari, Maral Hemmati, Mahboubeh Darban, Parisa Alavi Toosi, Seyedeh Zahra Banihashemian","doi":"10.1155/2024/5830491","DOIUrl":"https://doi.org/10.1155/2024/5830491","url":null,"abstract":"Atherosclerosis is a leading cause of death in the world. A significant body of evidence suggests that inflammation and various players are implicated and have pivotal roles in the formation of atherosclerotic plaques. Toll-like receptor 4 (TLR4) is linked with different stages of atherosclerosis. This receptor is highly expressed in the endothelial cells (ECs) and atherosclerotic plaques. TLR4 activation can lead to the production of inflammatory cytokines and related responses. Lectin-like oxidized low-density lipoprotein-1 (LOX-1), an integral membrane glycoprotein with widespread expression on the ECs, is involved in atherosclerosis and has some common pathways with TLR4 in atherosclerotic lesions. In addition, proprotein convertase subtilisin/kexin type9 (PCSK9), which is a regulatory enzyme with different roles in cholesterol uptake, is implicated in atherosclerosis. At present, TLR4, PCSK9, and LOX-1 are increasingly acknowledged as key players in the pathogenesis of atherosclerotic cardiovascular diseases. Herein, we presented the current evidence on the structure, functions, and roles of TLR4, PCSK9, and LOX-1 in atherosclerosis.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"1 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139979201","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}
Zhongjia Jiang, Weiping Zhou, Xing Tian, Peng Zou, Ning Li, Chunmeng Zhang, Yanting Li, Guangyan Liu
Inflammation is a complex host defensive response against various disease-associated pathogens. A baseline extent of inflammation is supposed to be tightly associated with a sequence of immune-modulated processes, resulting in the protection of the host organism against pathogen invasion; however, as a matter of fact is that an uncontrolled inflammatory cascade is the main factor responsible for the host damage, accordingly suggesting a significant and indispensable involvement of negative feedback mechanism in modulation of inflammation. Evidence accumulated so far has supported a repressive effect of the canonical Wnt/β-catenin pathway on microbial-triggered inflammation via diverse mechanisms, although that consequence is dependent on the cellular context, types of stimuli, and cytokine environment. It is of particular interest and importance to comprehend the precise way in which the Wnt/β-catenin pathway is activated, due to its essential anti-inflammatory properties. It is assumed that an inflammatory milieu is necessary for initiating and activating this signaling, implying that Wnt activity is responsible for shielding tissues from overwhelming inflammation, thus sustaining a balanced physiological condition against bacterial infection. This review gathers the recent efforts to elucidate the mechanistic details through how Wnt/β-catenin signaling modulates anti-inflammatory responses in response to bacterial infection and its interactions with other inflammatory signals, which warrants further study for the development of specific interventions for the treatment of inflammatory diseases. Further clinical trials from different disease settings are required.
{"title":"A Protective Role of Canonical Wnt/β-Catenin Pathway in Pathogenic Bacteria-Induced Inflammatory Responses","authors":"Zhongjia Jiang, Weiping Zhou, Xing Tian, Peng Zou, Ning Li, Chunmeng Zhang, Yanting Li, Guangyan Liu","doi":"10.1155/2024/8869510","DOIUrl":"https://doi.org/10.1155/2024/8869510","url":null,"abstract":"Inflammation is a complex host defensive response against various disease-associated pathogens. A baseline extent of inflammation is supposed to be tightly associated with a sequence of immune-modulated processes, resulting in the protection of the host organism against pathogen invasion; however, as a matter of fact is that an uncontrolled inflammatory cascade is the main factor responsible for the host damage, accordingly suggesting a significant and indispensable involvement of negative feedback mechanism in modulation of inflammation. Evidence accumulated so far has supported a repressive effect of the canonical Wnt/<i>β</i>-catenin pathway on microbial-triggered inflammation via diverse mechanisms, although that consequence is dependent on the cellular context, types of stimuli, and cytokine environment. It is of particular interest and importance to comprehend the precise way in which the Wnt/<i>β</i>-catenin pathway is activated, due to its essential anti-inflammatory properties. It is assumed that an inflammatory milieu is necessary for initiating and activating this signaling, implying that Wnt activity is responsible for shielding tissues from overwhelming inflammation, thus sustaining a balanced physiological condition against bacterial infection. This review gathers the recent efforts to elucidate the mechanistic details through how Wnt/<i>β</i>-catenin signaling modulates anti-inflammatory responses in response to bacterial infection and its interactions with other inflammatory signals, which warrants further study for the development of specific interventions for the treatment of inflammatory diseases. Further clinical trials from different disease settings are required.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"23 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139979326","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}
Yi Han, Lei Fu, Yan Kong, Changqing Jiang, Liying Huang, Hualing Zhang
Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action.
{"title":"STEAP3 Affects Ovarian Cancer Progression by Regulating Ferroptosis through the p53/SLC7A11 Pathway","authors":"Yi Han, Lei Fu, Yan Kong, Changqing Jiang, Liying Huang, Hualing Zhang","doi":"10.1155/2024/4048527","DOIUrl":"https://doi.org/10.1155/2024/4048527","url":null,"abstract":"Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"3 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968526","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}
Paulina Hernández-Ruiz, Alma R. Escalona Montaño, Luis M. Amezcua-Guerra, Héctor González-Pacheco, Elena Niccolai, Amedeo Amedei, María M. Aguirre-García
Many attempts have been proposed to evaluate the linkage between the oral–gut–liver axis and the mechanisms related to the diseases’ establishment. One of them is the oral microbiota translocation into the bloodstream, liver, and gut, promoting a host dysbiosis and triggering the presence of some metabolites such as trimethylamine N-oxide (TMAO), known as a risk marker for cardiovascular disease, and especially the myocardial infarction (MI). In the present pilot study, the involvement of oral dysbiosis related to the presence of TMAO has been considered an independent component of the standard risk factors (SRs) in the development of MI, which has not been previously described in human cohorts. A positive and significant correlation of TMAO levels with Porphyromonas was identified; likewise, the increase of the genus Peptidiphaga in patients without SRs was observed. We determined that the presence of SRs does not influence the TMAO concentration in these patients. This report is the first study where the relationship between oral dysbiosis and TMAO is specified in the Mexican population. Our findings provide information on the possible contribution of the oral pathogens associated with gut dysbiosis in the development of MI, although further analysis should be performed.
{"title":"Potential Association of the Oral Microbiome with Trimethylamine N-Oxide Quantification in Mexican Patients with Myocardial Infarction","authors":"Paulina Hernández-Ruiz, Alma R. Escalona Montaño, Luis M. Amezcua-Guerra, Héctor González-Pacheco, Elena Niccolai, Amedeo Amedei, María M. Aguirre-García","doi":"10.1155/2024/3985731","DOIUrl":"https://doi.org/10.1155/2024/3985731","url":null,"abstract":"Many attempts have been proposed to evaluate the linkage between the oral–gut–liver axis and the mechanisms related to the diseases’ establishment. One of them is the oral microbiota translocation into the bloodstream, liver, and gut, promoting a host dysbiosis and triggering the presence of some metabolites such as trimethylamine N-oxide (TMAO), known as a risk marker for cardiovascular disease, and especially the myocardial infarction (MI). In the present pilot study, the involvement of oral dysbiosis related to the presence of TMAO has been considered an independent component of the standard risk factors (SRs) in the development of MI, which has not been previously described in human cohorts. A positive and significant correlation of TMAO levels with <i>Porphyromonas</i> was identified; likewise, the increase of the genus <i>Peptidiphaga</i> in patients without SRs was observed. We determined that the presence of SRs does not influence the TMAO concentration in these patients. This report is the first study where the relationship between oral dysbiosis and TMAO is specified in the Mexican population. Our findings provide information on the possible contribution of the oral pathogens associated with gut dysbiosis in the development of MI, although further analysis should be performed.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"194 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139925945","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}
Julia Salvan da Rosa, Eduarda Talita Bramorski Mohr, Tainá Larissa Lubschinski, Guilherme Nicácio Vieira, Thais Andreia Rossa, Marcus Mandolesi Sá, Eduardo Monguilhott Dalmarco
Traditionally, the treatment of inflammatory conditions has focused on the inhibition of inflammatory mediator production; however, many conditions are refractory to this classical approach. Recently, an alternative has been presented by researchers to solve this problem: The immunomodulation of cells closely related to inflammation. Hence, macrophages, a critical key in both innate and acquired immunity, have been presented as an alternative target for the development of new medicines. In this work, we tested the fluorophenyl-imidazole for its anti-inflammatory activity and possible immunomodulatory effect on RAW 264.7 macrophages. We also evaluated the anti-inflammatory effect of the compound, and the macrophage repolarization to M2 was confirmed by the ability of the compound to reduce the M1 markers TNF-α, IL-6, MCP-1, IL-12p70, IFN-γ, and TLR4, the high levels of p65 phosphorylated, iNOS and COX-2 mRNA expression, and the fact that the compound was not able to induce the production of M1 markers when used in macrophages without lipopolysaccharide (LPS) stimulation. Moreover, fluorophenyl-imidazole had the ability to increase the M2 markers IL-4, IL-13, CD206, apoptosis and phagocytosis levels, arginase-1, and FIZZ-1 mRNA expression before LPS stimulation. Similarly, it was also able to induce the production of these same M2 markers in macrophages without being induced with LPS. These results reinforce the affirmation that the fluorophenyl-imidazole has an important anti-inflammatory effect and demonstrates that this effect is due to immunomodulatory activity, having the ability to trigger a repolarization of macrophages from M1 to M2a. These facts suggest that this molecule could be used as an alternative scaffold for the development of a new medicine to treat inflammatory conditions, where the anti-inflammatory and proregenerative properties of M2a macrophages are desired.
{"title":"Interference in Macrophage Balance (M1/M2): The Mechanism of Action Responsible for the Anti-Inflammatory Effect of a Fluorophenyl-Substituted Imidazole","authors":"Julia Salvan da Rosa, Eduarda Talita Bramorski Mohr, Tainá Larissa Lubschinski, Guilherme Nicácio Vieira, Thais Andreia Rossa, Marcus Mandolesi Sá, Eduardo Monguilhott Dalmarco","doi":"10.1155/2024/9528976","DOIUrl":"https://doi.org/10.1155/2024/9528976","url":null,"abstract":"Traditionally, the treatment of inflammatory conditions has focused on the inhibition of inflammatory mediator production; however, many conditions are refractory to this classical approach. Recently, an alternative has been presented by researchers to solve this problem: The immunomodulation of cells closely related to inflammation. Hence, macrophages, a critical key in both innate and acquired immunity, have been presented as an alternative target for the development of new medicines. In this work, we tested the fluorophenyl-imidazole for its anti-inflammatory activity and possible immunomodulatory effect on RAW 264.7 macrophages. We also evaluated the anti-inflammatory effect of the compound, and the macrophage repolarization to M2 was confirmed by the ability of the compound to reduce the M1 markers TNF-<i>α</i>, IL-6, MCP-1, IL-12p70, IFN-<i>γ</i>, and TLR4, the high levels of p65 phosphorylated, iNOS and COX-2 mRNA expression, and the fact that the compound was not able to induce the production of M1 markers when used in macrophages without lipopolysaccharide (LPS) stimulation. Moreover, fluorophenyl-imidazole had the ability to increase the M2 markers IL-4, IL-13, CD206, apoptosis and phagocytosis levels, arginase-1, and FIZZ-1 mRNA expression before LPS stimulation. Similarly, it was also able to induce the production of these same M2 markers in macrophages without being induced with LPS. These results reinforce the affirmation that the fluorophenyl-imidazole has an important anti-inflammatory effect and demonstrates that this effect is due to immunomodulatory activity, having the ability to trigger a repolarization of macrophages from M1 to M2a. These facts suggest that this molecule could be used as an alternative scaffold for the development of a new medicine to treat inflammatory conditions, where the anti-inflammatory and proregenerative properties of M2a macrophages are desired.","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"18 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139767621","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：