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Resveratrol promotes the differentiation of human umbilical cord mesenchymal stem cells into esophageal fibroblasts via AKT signaling pathway 白藜芦醇通过 AKT 信号通路促进人脐带间充质干细胞向食管成纤维细胞分化
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-30 DOI: 10.1177/03946320241249397
Xiujing Chen, Zihao Sun, Qian Wu, Lijuan Shao, Jiaxin Bei, Yiguang Lin, Hongjie Chen, Size Chen
Objectives: Resveratrol has been implicated in the differentiation and development of human umbilical cord mesenchymal stem cells. The differentiation of into esophageal fibroblasts is a promising strategy for esophageal tissue engineering. However, the pharmacological effect and underlying mechanism of resveratrol on human umbilical cord mesenchymal stem cells differentiation are unknown. Here, we investigated the effects and mechanism of resveratrol on the differentiation of human umbilical cord mesenchymal stem cells. Methods: Using a transwell-membrane coculture system to culture human umbilical cord mesenchymal stem cells and esophageal fibroblasts, we examined how resveratrol act on the differentiation of human umbilical cord mesenchymal stem cells. Immunocytochemistry, Sirius red staining, quantitative real-time PCR, and Western blotting were performed to examine collagen synthesis and possible signaling pathways in human umbilical cord mesenchymal stem cells. Results: We found that resveratrol promoted collagen synthesis and AKT phosphorylation. However, co-treatment of cells with resveratrol and the PI3K inhibitor LY294002 inhibited collagen synthesis and AKT phosphorylation. We demonstrated that resveratrol down-regulated the expression of IL-6, TGF-β, caspase-9, and Bax by activating the AKT pathway in human umbilical cord mesenchymal stem cell. Furthermore, resveratrol inhibited phosphorylated NF-ĸB in human umbilical cord mesenchymal stem cells. Conclusion: Our data suggest that resveratrol promotes the differentiation of human umbilical cord mesenchymal stem cells into fibroblasts. The underlying mechanism is associated with the downregulation of IL-6 and TGF-β via the AKT pathway and by inhibiting the NF-ĸB pathway. Resveratrol may be useful for esophageal tissue engineering.
目的白藜芦醇与人脐带间充质干细胞的分化和发育有关。将其分化为食管成纤维细胞是食管组织工程的一种有前途的策略。然而,白藜芦醇对人脐带间充质干细胞分化的药理作用和内在机制尚不清楚。在此,我们研究了白藜芦醇对人脐带间充质干细胞分化的影响和机制。研究方法采用跨孔-膜共培养系统培养人脐带间充质干细胞和食管成纤维细胞,研究白藜芦醇对人脐带间充质干细胞分化的作用。我们采用免疫细胞化学、天狼星红染色、定量实时 PCR 和 Western 印迹技术研究了人脐带间充质干细胞中胶原蛋白的合成和可能的信号通路。结果我们发现白藜芦醇能促进胶原蛋白合成和AKT磷酸化。然而,用白藜芦醇和 PI3K 抑制剂 LY294002 共同处理细胞会抑制胶原合成和 AKT 磷酸化。我们证实,白藜芦醇通过激活人脐带间充质干细胞的 AKT 通路,下调了 IL-6、TGF-β、caspase-9 和 Bax 的表达。此外,白藜芦醇还能抑制人脐带间充质干细胞中磷酸化的 NF-ĸB。结论我们的数据表明,白藜芦醇能促进人脐带间充质干细胞向成纤维细胞分化。其基本机制与通过 AKT 途径和抑制 NF-ĸB 途径下调 IL-6 和 TGF-β 有关。白藜芦醇可用于食管组织工程。
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引用次数: 0
A novel immune cell signature for predicting glioblastoma after radiotherapy prognosis and guiding therapy 用于预测放疗后胶质母细胞瘤预后和指导治疗的新型免疫细胞特征
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-30 DOI: 10.1177/03946320241249395
Rong Huang, Xiaoxu Lu, Xueming Sun, Hui Wu
Background: Glioblastoma, a highly aggressive brain tumor, poses a significant clinical challenge, particularly in the context of radiotherapy. In this study, we aimed to explore infiltrating immune cells and identify immune-related genes associated with glioblastoma radiotherapy prognosis. Subsequently, we constructed a signature based on these genes to discern differences in molecular and tumor microenvironment immune characteristics, ultimately informing potential therapeutic strategies for patients with varying risk profiles. Methods: We leveraged UCSC Xena and CGGA gene expression profiles from post-radiotherapy glioblastoma as verification cohorts. Infiltration ratios were stratified into high and low groups based on the median value. Differential gene expression was determined through Limma differential analysis. A signature comprising four genes was constructed, guided by Gene Ontology (GO) functional enrichment results and Kaplan–Meier survival analysis. We evaluated differences in cell infiltration levels, Immune Score, Stromal Score, and ESTIMATE Score and their Pearson correlations with the signature. Spearman’s correlation was computed between the signature and patient drug sensitivity (IC50), predicted using Genomics of Drug Sensitivity in Cancer (GDSC) and CCLE databases. Results: Notably, the infiltration of central memory CD8+T cells exhibited a significant correlation with glioblastoma radiotherapy prognosis. Samples were dichotomized into high- and low-risk groups based on the optimal signature threshold (2.466642). Kaplan–Meier (K-M) survival analysis revealed that the high-risk group experienced a significantly poorer prognosis ( p = .0068), with AUC values exceeding 0.82 at 1, 3, and 5 years, underscoring the robust predictive potential of the signature scoring system. Independent validation sets substantiated the validity of the signature. Statistically significant differences in tumor microenvironments (p < .05) were observed between high- and low-risk groups, and these differences were significantly correlated with the signature ( p < .05). Furthermore, there were significant correlations between high and low-risk groups regarding immune checkpoint expressions, Immune Prognostic Score (IPS), and Tumor Immune Dysfunction and Exclusion (TIDE) scores. Conclusion: The immune cell signature, comprising SDC-1, PLAUR, FN1, and CXCL13, holds promise as a predictive tool for assessing glioblastoma prognosis following radiotherapy. This signature also offers valuable guidance for tailoring treatment strategies, emphasizing its potential clinical relevance in improving patient outcomes.
背景:胶质母细胞瘤是一种侵袭性很强的脑肿瘤,它给临床带来了巨大挑战,尤其是在放疗的情况下。在这项研究中,我们旨在探索浸润的免疫细胞,并确定与胶质母细胞瘤放疗预后相关的免疫相关基因。随后,我们根据这些基因构建了一个特征,以辨别分子和肿瘤微环境免疫特征的差异,最终为不同风险特征的患者提供潜在的治疗策略。研究方法我们利用放疗后胶质母细胞瘤的 UCSC Xena 和 CGGA 基因表达谱作为验证队列。根据中位值将浸润率分为高组和低组。基因表达差异通过 Limma 差异分析确定。在基因本体(GO)功能富集结果和 Kaplan-Meier 生存分析的指导下,构建了由四个基因组成的特征。我们评估了细胞浸润水平、免疫评分、基质评分和ESTIMATE评分的差异及其与特征的皮尔逊相关性。利用癌症药物敏感性基因组学(GDSC)和 CCLE 数据库预测了特征与患者药物敏感性(IC50)之间的斯皮尔曼相关性。结果显示值得注意的是,中心记忆 CD8+T 细胞的浸润与胶质母细胞瘤放疗预后有显著相关性。根据最佳特征阈值(2.466642)将样本分为高危和低危两组。卡普兰-梅耶(K-M)生存分析表明,高风险组的预后明显较差(p = .0068),1、3、5年的AUC值均超过0.82,凸显了特征评分系统强大的预测潜力。独立验证集证实了特征的有效性。在高风险组和低风险组之间观察到了肿瘤微环境的统计学差异(p < .05),这些差异与特征显著相关(p < .05)。此外,高危组和低危组在免疫检查点表达、免疫预后评分(IPS)和肿瘤免疫功能紊乱与排斥(TIDE)评分方面也存在明显相关性。结论由 SDC-1、PLAUR、FN1 和 CXCL13 组成的免疫细胞特征有望成为放疗后评估胶质母细胞瘤预后的预测工具。该特征还为定制治疗策略提供了有价值的指导,强调了其在改善患者预后方面的潜在临床意义。
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引用次数: 0
Clinical role of NDRG2-based methylation status on survival pattern of glioblastoma 基于 NDRG2 的甲基化状态对胶质母细胞瘤生存模式的临床作用
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-30 DOI: 10.1177/03946320241250294
Menha Swellam, Mohamed K. Khalifa, Amira M Nageeb, Lobna Ezz El-Arab, Manal El-Mahdy, Khaled El-Bahy, Magda Sayed Mahmoud
Objectives: Gliobalstoma is the most common primary brain tumor in adults with an extensive genetic and transcriptional heterogeneity, still identification of the role of DNA methylation, as one of epigenetic alterations, is emerged. Authors aimed to study the clinical role of N-myc downstream-regulated gene 2 (NDRG2) –based methylation among GBM patients versus benign neurological diseases (BND), investigate its prognostic role and its relation with survival outcomes. Methods: A total of 78 FFPE specimens were recruited as follows: GBM ( n = 58) and BND ( n = 20) then analyzed for NDRG2 methylation using Methyl II quantitative PCR system. The sensitivity and specificity of methylation was detected using receiver operating characteristic (ROC) curve and the relation with clinicopathological criteria for GBM and response to treatment were studied. Survival patterns; progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier analyses. Results: Mean methylation NDRG2 level was significantly increased in GBM patients as compared to BND and its sensitivity and specificity were 96.55% and 95%, respectively with area under curve (AUC) equals 0.973. Among the clinical characteristic factors, mean methylation level reported significant difference with ECOG and tumor site. Survival out comes revealed that NDRG2 methylation increased with worse PFS and OS at significant level (long rank test X 2 = 13.3, p < .0001; and X 2 = 7.1, p = .008, respectively). Conclusion: Current findings highlight the importance of studying DNA methylation of NDRG2 as a key factor to understand the role of epigenetic alterations in GBM.
研究目的胶质母细胞瘤是成人中最常见的原发性脑肿瘤,具有广泛的遗传和转录异质性,而DNA甲基化作为表观遗传学改变之一,其作用仍有待鉴定。作者旨在研究基于 N-myc 下游调控基因 2(NDRG2)的甲基化在 GBM 患者与良性神经系统疾病(BND)患者中的临床作用,调查其预后作用及其与生存结果的关系。研究方法共收集了 78 份 FFPE 标本,具体如下:然后使用 Methyl II 定量 PCR 系统分析 NDRG2 甲基化。利用接收器操作特征曲线(ROC)检测甲基化的敏感性和特异性,并研究甲基化与 GBM 临床病理标准和治疗反应的关系。采用卡普兰-梅耶分析法对生存模式、无进展生存期(PFS)和总生存期(OS)进行了分析。结果与BND相比,GBM患者的平均甲基化NDRG2水平明显升高,其敏感性和特异性分别为96.55%和95%,曲线下面积(AUC)等于0.973。在临床特征因素中,平均甲基化水平与 ECOG 和肿瘤部位有显著差异。存活率结果显示,NDRG2甲基化水平的增加与较差的PFS和OS有显著关系(长秩检验X 2 = 13.3,p < .0001;X 2 = 7.1,p = .008)。结论目前的研究结果凸显了研究 NDRG2 DNA 甲基化的重要性,这是了解表观遗传学改变在 GBM 中的作用的关键因素。
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引用次数: 0
Low-dose metformin suppresses hepatocellular carcinoma metastasis via the AMPK/JNK/IL-8 pathway 小剂量二甲双胍通过 AMPK/JNK/IL-8 通路抑制肝细胞癌转移
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-29 DOI: 10.1177/03946320241249445
Chengwen Zhao, Lu Zheng, Yuting Ma, Yue Zhang, Chanjuan Yue, Feng Gu, Guoping Niu, Yongqiang Chen
Background and objectivesMetformin, an oral hypoglycemic drug, has been suggested to possess antitumour activity in several types of cancers. Additionally, interleukin-8 (IL-8) has been reported to be involved in the development and metastasis of many cancers. However, the effect of metformin on IL-8 expression in hepatocellular carcinoma (HCC) remains unclear. Therefore, this study aimed to investigate whether metformin could inhibit IL-8 expression to exert an inhibitory effect on HCC progression.Materials and methodsThe IL-8 levels were measured in the plasma of 159 HCC patients (86 men, 73 women; average age 56 years) and in the culture supernatant of HCC cells (Hep3B and HuH7) using flow cytometry. In addition, the protein expression levels of IL-8 were also validated by the Human Protein Atlas (HPA) database. The prognostic value of IL-8 was evaluated using the Kaplan–Meier Plotter database. The association between IL-8 expression and immune checkpoints was estimated using the TIMER and The Cancer Genome Atlas (TCGA) databases. What’s more, bioinformatics analysis, western blotting, and transwell assays were conducted to illustrate the molecular mechanism of metformin (≤1 mM) on IL-8 in HCC.ResultsIL-8 expression was found to be increased in the plasma of HCC patients, which is consistent with the expression of IL-8 in HCC cells and tissues. High expression of IL-8 was significantly related to poor prognosis. In addition, IL-8 was positively correlated with immune checkpoints in HCC. Notably, we found that low-dose metformin could inhibit the secretion of IL-8 by HCC cells and the migration of HCC cells. Mechanistically, low-dose metformin significantly suppresses HCC metastasis mainly through the AMPK/JNK/IL-8/MMP9 pathway.ConclusionThe results indicate that low-dose metformin can inhibit HCC metastasis by suppressing IL-8 expression. Targeting the AMPK/JNK/IL-8 axis may be a promising treatment strategy for patients with HCC metastasis.
背景和目的二甲双胍是一种口服降糖药,被认为对多种癌症具有抗肿瘤活性。此外,有报道称白细胞介素-8(IL-8)参与了多种癌症的发展和转移。然而,二甲双胍对肝细胞癌(HCC)中 IL-8 表达的影响仍不清楚。因此,本研究旨在探讨二甲双胍是否能抑制 IL-8 的表达,从而对 HCC 的进展产生抑制作用。材料和方法 使用流式细胞术检测了 159 例 HCC 患者(86 例男性,73 例女性;平均年龄 56 岁)血浆中的 IL-8 水平以及 HCC 细胞(Hep3B 和 HuH7)培养上清液中的 IL-8 水平。此外,人类蛋白质图谱(HPA)数据库也验证了 IL-8 的蛋白质表达水平。使用 Kaplan-Meier Plotter 数据库评估了 IL-8 的预后价值。IL-8的表达与免疫检查点之间的关联则通过TIMER和癌症基因组图谱(TCGA)数据库进行了评估。此外,研究人员还进行了生物信息学分析、Western 印迹和跨孔实验,以说明二甲双胍(≤1 mM)对 HCC 中 IL-8 的分子机制。结果发现,HCC 患者血浆中 IL-8 表达增加,这与 HCC 细胞和组织中 IL-8 的表达一致。IL-8 的高表达与预后不良明显相关。此外,IL-8 与 HCC 中的免疫检查点呈正相关。值得注意的是,我们发现小剂量二甲双胍可抑制HCC细胞分泌IL-8,并抑制HCC细胞的迁移。从机理上讲,小剂量二甲双胍主要通过AMPK/JNK/IL-8/MMP9途径显著抑制HCC转移。针对AMPK/JNK/IL-8轴可能是治疗HCC转移患者的一种有前景的策略。
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引用次数: 0
Macrophage-derived exosomal miRNA-141 triggers endothelial cell pyroptosis by targeting NLRP3 to accelerate sepsis progression 巨噬细胞源性外泌体miRNA-141通过靶向NLRP3引发内皮细胞脓毒症,加速脓毒症进展
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-23 DOI: 10.1177/03946320241234736
Feng Zhan, Jun Zhang, Ping He, Wenteng Chen, Yanhong Ouyang
Sepsis, critical condition marked by severe organ dysfunction from uncontrolled infection, involves the endothelium significantly. Macrophages, through paracrine actions, play a vital role in sepsis, but their mechanisms in sepsis pathogenesis remain elusive. Objective: We aimed to explore how macrophage-derived exosomes with low miR-141 expression promote pyroptosis in endothelial cells (ECs). Exosomes from THP-1 cell supernatant were isolated and characterized. The effects of miR-141 mimic/inhibitor on apoptosis, proliferation, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed using flow cytometry, CCK-8, and transwell assays. Key pyroptosis-related proteins, including caspase-1, IL-18, IL-1β, NLR Family Pyrin Domain Containing 3 (NLRP3), ASC, and cleaved-GSDMD, were analyzed via Western blot. The interaction between miR-141 and NLRP3 was studied using RNAhybrid v2.2 and dual-Luciferase reporter assays. The mRNA and protein level of NLRP3 after exosomal miR-141 inhibitor treatment was detected by qPCR and Western blot, respectively. Exosomes were successfully isolated. miR-141 mimic reduced cell death and pyroptosis-related protein expression in HUVECs, while the inhibitor had opposite effects, increasing cell death, and enhancing pyroptosis protein expression. Additionally, macrophage-derived exosomal miR-141 inhibitor increased cell death and pyroptosis-related proteins in HUVECs. miR-141 inhibits NLRP3 transcription. Macrophages facilitate sepsis progression by secreting miR-141 decreased exosomes to activate NLRP3-mediated pyroptosis in ECs, which could be a potentially valuable target of sepsis therapy.
败血症是一种因感染失控而导致器官功能严重失调的危重病,严重影响内皮细胞。巨噬细胞通过旁分泌作用在败血症中发挥着重要作用,但其在败血症发病机制中的作用机制仍不明确。研究目的我们旨在探索低 miR-141 表达的巨噬细胞衍生外泌体如何促进内皮细胞(ECs)的脓毒症。我们从 THP-1 细胞上清液中分离并鉴定了外泌体。使用流式细胞仪、CCK-8和透孔试验评估了miR-141模拟物/抑制剂对人脐静脉内皮细胞(HUVECs)凋亡、增殖和侵袭的影响。通过 Western 印迹分析了关键的热蛋白相关蛋白,包括 caspase-1、IL-18、IL-1β、NLR 家族含吡啶域 3(NLRP3)、ASC 和裂解-GSDMD。利用 RNAhybrid v2.2 和双荧光素酶报告实验研究了 miR-141 和 NLRP3 之间的相互作用。通过 qPCR 和 Western 印迹分别检测了外泌体 miR-141 抑制剂处理后 NLRP3 的 mRNA 和蛋白水平。miR-141模拟物减少了HUVECs的细胞死亡和热蛋白相关蛋白的表达,而抑制剂则产生了相反的效果,增加了细胞死亡和热蛋白表达。此外,巨噬细胞衍生的外泌体 miR-141 抑制剂增加了 HUVECs 中的细胞死亡和热蛋白相关蛋白的表达。巨噬细胞通过分泌减少的外泌体miR-141来激活NLRP3介导的ECs脓毒症,从而促进脓毒症的进展,这可能是脓毒症治疗的一个有价值的靶点。
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引用次数: 0
Effect of overweight/obesity on relationship between fractional exhaled nitric oxide and airway hyperresponsiveness in Chinese elderly patients with asthma 超重/肥胖对中国老年哮喘患者呼出一氧化氮分数与气道高反应性关系的影响
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-22 DOI: 10.1177/03946320241246713
Fengjia Chen, Yangli Liu, Long-hua Sun, Zhimin Zeng, Xinyan Huang
Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model’s R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.
目的:这项回顾性研究探讨了超重和肥胖状态对老年哮喘患者肺功能、气道炎症标志物和气道反应性的影响。研究方法本研究通过回顾性研究确定了在 2015 年 12 月至 2020 年 6 月期间完成支气管激发试验(BPT)或支气管扩张试验(BDT)和分数呼出一氧化氮(FeNO)试验的 65 岁以上哮喘患者。根据体重指数将所有患者分为超重/肥胖组和非肥胖组。肺功能测试(PFT)和 FeNO 测量分别根据 2014 年《中国肺功能测试国家指南》建议和美国胸科学会/欧洲呼吸学会建议完成。结果共发现 136 名患者,平均年龄(71.2±5.40)岁。平均体重指数为(23.8±3.63),而 FeNO 值为(42.3±38.4)十亿分之一(ppb)。非肥胖组的 FeNO 值为 48.8 ± 43.1 ppb,相比之下,超重/肥胖组的 FeNO 值明显较低,为 35.4 ± 31.4 ppb。超重/肥胖组和非肥胖组(共 96 名患者)气道高反应性的比例没有明显差异。多元线性回归分析确定了 FeNO 与导致 FEV1 下降 20% 的刺激浓度(PC20)之间的反相关性,但排除了与年龄和体重指数之间的显著关系。模型的 R 值为 0.289,P 值为 0.045。结论根据我们的研究结果,超重/肥胖的中国汉族老年哮喘患者的 FeNO 水平低于非肥胖者。此外,老年哮喘患者的 FeNO 水平与 PC20 呈反相关。
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引用次数: 0
The Nose and Paranasal Sinuses 鼻子和副鼻窦
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-04-13 DOI: 10.1177/03946320100230s101
A. Varricchio, F. Avvisati, A.M. Varricchio, G. Tortoriello, G. Ciprandi
The airways should be considered as a functional unit. Indeed, disorders involving the upper respiratory tract (URT) spread to the lower respiratory tract (LRT). Modern functional anatomy divides U...
气道应被视为一个功能单位。事实上,上呼吸道(URT)的疾病会扩散到下呼吸道(LRT)。现代功能解剖学将U…
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引用次数: 0
Elevated serum cholesterol levels are associated with proteinuria over 0.5 g/day in premenopausal women with systemic lupus erythematosus 绝经前系统性红斑狼疮妇女血清胆固醇水平升高与蛋白尿超过0.5 g/天相关
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-05-01 DOI: 10.1177/03946320221101287
Haijun Liu, Qianhua Li, Xiu-ning Wei, Jian-da Ma, K. Long, Xia Ouyang, Nemin Liu, Yongsheng Li, L. He, L. Dai, Xiaoyan Cai
Background: Systemic lupus erythematosus (SLE) commonly occurs in premenopausal women and is associated with elevated estrogen levels. Patients with SLE may have abnormal serum triglyceride (TG) levels, and lipid reportedly promotes kidney damage in patients with nephrosis. Since estrogen regulates lipid levels, we investigated the serum lipid levels of premenopausal women with SLE and their relationship with proteinuria. Methods: This cross-sectional study included 123 premenopausal women with SLE (SLE group), who were classified into 24-h urine protein exceeding 0.5 g (24 h-UPRO > 0.5 g, n = 22) and 24 h-UPRO ≤ 0.5 g (n = 101) subgroups, and 100 similarly aged healthy women (control group). Clinical characteristics and biomarker levels were compared between these groups. The associated factors of proteinuria over 0.5 g/day were evaluated using multivariate logistic regression. A receiver operating characteristic (ROC) curve was plotted to assess the cholesterol (CH) cut-off associated with increased development of proteinuria over 0.5 g/day. Results: The SLE group had significantly higher serum TG levels than that of control group. 24 h-UPRO were significantly correlated with serum creatinine, CH, TG, and uric acid levels. Serum CH level was the greatest associated factor for proteinuria over 0.5 g/day. The area under the ROC curve was 0.843, with a CH cut-off of 4.58 mmol/L. Patients with serum CH above 4.58 mmol/L had a higher proportion of type IV LN, but with no statistical difference. Conclusions: In premenopausal SLE patients, serum TG levels were higher than in healthy women, and serum CH levels were the primary associated factor for proteinuria over 0.5 g/day. Proteinura over 0.5 g/day may occur in women with SLE with serum CH levels >4.58 mmol/L. CH levels may be useful for predicting proteinuria.
背景:系统性红斑狼疮(SLE)常见于绝经前妇女,与雌激素水平升高有关。SLE患者可能有异常的血清甘油三酯(TG)水平,据报道,脂质会促进肾病患者的肾脏损害。由于雌激素调节脂质水平,我们研究了绝经前SLE妇女的血脂水平及其与蛋白尿的关系。方法:本横断研究纳入123例绝经前SLE女性(SLE组),分为24 h尿蛋白超过0.5 g (24 h-UPRO低于0.5 g, n = 22)和24 h-UPRO≤0.5 g (n = 101)亚组,以及100例年龄相似的健康女性(对照组)。比较两组的临床特征和生物标志物水平。蛋白尿超过0.5 g/d的相关因素采用多因素logistic回归进行评估。绘制受试者工作特征(ROC)曲线,以评估胆固醇(CH)临界值与蛋白尿发生率超过0.5 g/天相关。结果:SLE组血清TG水平明显高于对照组。24 h-UPRO与血清肌酐、CH、TG、尿酸水平显著相关。血清CH水平是蛋白尿超过0.5 g/d的最大相关因素。ROC曲线下面积为0.843,CH截止值为4.58 mmol/L。血清CH > 4.58 mmol/L的患者发生IV型LN的比例较高,但差异无统计学意义。结论:绝经前SLE患者血清TG水平高于健康女性,血清CH水平是蛋白尿超过0.5 g/d的主要相关因素。蛋白尿超过0.5 g/天可能发生在血清CH水平为bb0 4.58 mmol/L的SLE患者。CH水平可用于预测蛋白尿。
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引用次数: 1
Procollagen C-protease enhancer protein is a prognostic factor for glioma and promotes glioma development by regulating multiple tumor-related pathways and immune microenvironment 前胶原C蛋白酶增强蛋白是神经胶质瘤的预后因子,通过调节多种肿瘤相关途径和免疫微环境促进神经胶质瘤发展
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-05-01 DOI: 10.1177/03946320221104548
Zijun Zhao, Jiahui Zhao, Zairan Wang, Yue Wu, Zhanzhan Zhang, Zihan Song, Jihao Miao, Boheng Liu, Shiyang Zhang, Boyu Sun, Zongmao Zhao
Objectives Glioma is a common type of brain tumor with high incidence and mortality rates. Procollagen C-protease enhancer protein (PCOLCE) has been shown to regulate tumor growth and metastasis in several cancers. However, the role of PCOLCE in glioma is unknown. This study aims to assess the association between PCOLCE and prognosis of glioma, and investigated the potential mechanisms. Methods The prognostic value of PCOLCE was determined using data from nine publicly available glioma cohorts. We also investigated the relationship between PCOLCE and glioma immune microenvironment and predicted response to immunotherapy based on the expression levels of PCOLCE. The potential roles of PCOLCE in glioma were also explored and validated in cell experiment. Results Survival analysis suggested that high-PCOLCE expression was associated with poor prognosis in glioma. Upregulation of PCOLCE enhanced an immune suppressive microenvironment in glioma by regulating immunocyte infiltration and Cancer-Immunity Cycle. Cox and ROC analysis revealed that PCOLCE was a prognostic factor for glioma and could be used to predict survival of the patients. Patients with low-PCOLCE expression were more likely to respond to Immunotherapy with ICI (immune checkpoint inhibitor) and survive longer. Enrichment analysis showed that PCOLCE was associated with multiple tumor-related pathways. Finally, we demonstrated that the knockdown of PCOLCE inhibited glioma development by regulating cell cycle and promoting apoptosis in in vitro experiments. Conclusion PCOLCE promotes glioma progression by regulating multiple tumor-related pathways and immune microenvironment and can be used as a prognostic factor for glioma.
目的胶质瘤是一种常见的脑肿瘤,发病率高,死亡率高。前胶原C蛋白酶增强蛋白(PCOLCE)已被证明可以调节几种癌症的肿瘤生长和转移。然而,PCOLCE在神经胶质瘤中的作用尚不清楚。本研究旨在评估PCOLCE与神经胶质瘤预后之间的关系,并探讨其潜在机制。方法利用9个公开的神经胶质瘤队列的数据来确定PCOLCE的预后价值。我们还研究了PCOLCE与神经胶质瘤免疫微环境之间的关系,并根据PCOLCE的表达水平预测了对免疫疗法的反应。PCOLCE在胶质瘤中的潜在作用也在细胞实验中得到了探索和验证。结果生存分析提示PCOLCE高表达与胶质瘤预后不良有关。PCOLCE的上调通过调节免疫细胞浸润和癌免疫循环增强了胶质瘤的免疫抑制微环境。Cox和ROC分析显示PCOLCE是神经胶质瘤的预后因素,可用于预测患者的生存率。PCOLCE表达低的患者更有可能对ICI(免疫检查点抑制剂)的免疫治疗产生反应,并存活更长时间。富集分析显示PCOLCE与多种肿瘤相关途径有关。最后,我们在体外实验中证明了敲低PCOLCE通过调节细胞周期和促进细胞凋亡来抑制神经胶质瘤的发展。结论PCOLCE通过调节多种肿瘤相关通路和免疫微环境促进胶质瘤的进展,可作为胶质瘤的预后因素。
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引用次数: 1
Association between IL-27p28 gene polymorphisms and susceptibility to allergic rhinitis IL-27p28基因多态性与变应性鼻炎易感性的关系
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-03-01 DOI: 10.1177/03946320221087922
Farzaneh Koohyanizadeh, Seyed Hamidreza Mortazavi, Farhad Salari, Sara Falahi, Alireza Rezaiemanesh, A. Gorgin Karaji
Background Interleukin-27 (IL-27) is a cytokine composed of two subunits, EBI3 and p28, which is an important mediator in regulating the differentiation of TCD4 + cells and plays an important role in immune-related disorders. This study aimed to elucidate the potential association of single nucleotide polymorphisms (SNPs) of the IL-27p28 gene with serum IL-27 levels and the risk of allergic rhinitis (AR). Materials and methods The study included 130 patients with AR and 130 healthy individuals. To evaluate the association between IL-27p28 gene SNPs (rs153109 and rs181206) and the risk of AR, the Polymerase chain reaction-restriction fragment length polymorphism method was used. Enzyme-linked immunosorbent assay was also used to determine the serum level of IL-27 in patients with AR and healthy individuals. Results Our results did not show a significant relationship between IL-27p28 gene polymorphisms (rs153109 and rs181206) with the risk of AR and serum IL-27 levels. However, our results indicated that the serum level of IL-27 in patients with AR (342 ± 299 pg/mL) was significantly lower than the healthy controls (455 ± 274 pg/mL) (p = 0.02). Conclusion Our findings suggested that IL-27p28 SNPs (rs181206 and rs153109) are not associated with susceptibility to AR, but decreased serum IL-27 levels may be associated with the development of AR.
白细胞介素-27 (Interleukin-27, IL-27)是一种由EBI3和p28两个亚基组成的细胞因子,是调节TCD4 +细胞分化的重要介质,在免疫相关疾病中起重要作用。本研究旨在阐明IL-27p28基因单核苷酸多态性(snp)与血清IL-27水平和变应性鼻炎(AR)风险之间的潜在关联。材料与方法本研究纳入130例AR患者和130例健康人。为了评估IL-27p28基因snp (rs153109和rs181206)与AR风险的相关性,采用聚合酶链反应-限制性片段长度多态性方法。采用酶联免疫吸附法测定AR患者和健康人血清IL-27水平。结果IL-27p28基因多态性(rs153109和rs181206)与AR风险和血清IL-27水平无显著关系。然而,我们的研究结果显示,AR患者血清IL-27水平(342±299 pg/mL)显著低于健康对照组(455±274 pg/mL) (p = 0.02)。结论IL-27p28 snp (rs181206和rs153109)与AR易感性无关,但血清IL-27水平降低可能与AR的发生有关。
{"title":"Association between IL-27p28 gene polymorphisms and susceptibility to allergic rhinitis","authors":"Farzaneh Koohyanizadeh, Seyed Hamidreza Mortazavi, Farhad Salari, Sara Falahi, Alireza Rezaiemanesh, A. Gorgin Karaji","doi":"10.1177/03946320221087922","DOIUrl":"https://doi.org/10.1177/03946320221087922","url":null,"abstract":"Background Interleukin-27 (IL-27) is a cytokine composed of two subunits, EBI3 and p28, which is an important mediator in regulating the differentiation of TCD4 + cells and plays an important role in immune-related disorders. This study aimed to elucidate the potential association of single nucleotide polymorphisms (SNPs) of the IL-27p28 gene with serum IL-27 levels and the risk of allergic rhinitis (AR). Materials and methods The study included 130 patients with AR and 130 healthy individuals. To evaluate the association between IL-27p28 gene SNPs (rs153109 and rs181206) and the risk of AR, the Polymerase chain reaction-restriction fragment length polymorphism method was used. Enzyme-linked immunosorbent assay was also used to determine the serum level of IL-27 in patients with AR and healthy individuals. Results Our results did not show a significant relationship between IL-27p28 gene polymorphisms (rs153109 and rs181206) with the risk of AR and serum IL-27 levels. However, our results indicated that the serum level of IL-27 in patients with AR (342 ± 299 pg/mL) was significantly lower than the healthy controls (455 ± 274 pg/mL) (p = 0.02). Conclusion Our findings suggested that IL-27p28 SNPs (rs181206 and rs153109) are not associated with susceptibility to AR, but decreased serum IL-27 levels may be associated with the development of AR.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43484265","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}
引用次数: 0
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International Journal of Immunopathology and Pharmacology
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