扫码登录小狗阅读
Expression and correlation of Chemerin and FABP4 in peripheral blood of gestational diabetes mellitus patients.
Chemerin 和 FABP4 在妊娠期糖尿病患者外周血中的表达及相关性
- 影响因子:1.24
- DOI:10.3892/etm.2019.8247
- 作者列表:"Wang X","Liu J","Wang D","Zhu H","Kang L","Jiang J
- 发表时间:2020-01-01
Abstract
:Expression and correlation of Chemerin and fatty acid-binding protein 4 (FABP4) in peripheral blood of gestational diabetes mellitus (GDM) patients were investigated. Sixty patients with GDM from March 2018 to March 2019 in the People's Hospital of Zhangqiu Area were selected as the study group (SG) and another 50 healthy pregnant women corresponding to their age and pregnancy were selected as the control group (CG). Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of Chemerin and FABP4 in serum. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of Chemerin and FABP4 in peripheral blood for GDM patients. Pearson's correlation coefficient was used to analyze the correlation between Chemerin and FABP4 and the correlation between Chemerin and inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Expression of Chemerin and FABP4 in peripheral blood of GDM patients were significantly higher than those in CG. The AUC of GDM patients diagnosed with Chemerin and FABP4 in peripheral blood was 0.820 and 0.814, while the AUC of GDM patients diagnosed with Chemerin combined with FABP4 in peripheral blood was 0.904. Expression of inflammatory factors IL-6 and TNF-α in the SG were significantly higher than those in the CG. Chemerin in the SG was positively correlated with FABP4 and positively correlated with inflammatory factors IL-6 and TNF-α. Patients with advanced age (≥35 years), family history of diabetes, hyperlipidemia, high pre-pregnancy BMI, high fasting blood glucose, high Chemerin and high FABP4 expression have high risk of GDM. In conclusion, Chemerin and FABP4 were upregulated in the peripheral blood of GDM patients. There was a positive correlation between the two and a positive correlation with the inflammatory factors IL-6 and TNF-α.
摘要
探讨 Chemerin 和脂肪酸结合蛋白 4 (FABP4) 在妊娠期糖尿病 (GDM) 患者外周血中的表达及相关性。选取 2018年3月至 2019年3月章丘地区人民医院 GDM 患者 60 例为研究组 (SG) 另选取 50 例与年龄和孕期相对应的健康孕妇作为对照组 (CG)。酶联免疫吸附法 (ELISA) 检测血清中 Chemerin 和 FABP4 的表达。采用受试者工作特征 (ROC) 曲线评价外周血 Chemerin 和 FABP4 对 GDM 患者的诊断价值。采用 Pearson's 相关系数分析 Chemerin 与 FABP4 的相关性及与白细胞介素-6 (IL-6) 、肿瘤坏死因子-α (TNF-α) 等炎症因子的相关性。GDM 患者外周血 Chemerin 和 FABP4 的表达显著高于 CG。确诊为 Chemerin 和 FABP4 的 GDM 患者外周血 AUC 为 0.820 和 0.814,而确诊为 Chemerin 联合 FABP4 的 GDM 患者外周血 AUC 为 0.904。SG 中炎症因子 IL-6 和 TNF-α 的表达明显高于 CG。SG 中 Chemerin 与 FABP4 呈正相关,与炎症因子 IL-6 和 TNF-α 呈正相关。高龄 (≥ 35 岁) 、糖尿病家族史、高血脂、孕前 BMI 高、空腹血糖高、 Chemerin 高、 FABP4 高表达的患者有 GDM 的高风险。总之,Chemerin 和 FABP4 在 GDM 患者外周血中表达上调。两者呈正相关,与炎症因子 IL-6 、 TNF-α 呈正相关。
小狗阅读
帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。
METHODS:Aims We aimed to develop a prediction model based on clinical and biochemical variables for gestational diabetes mellitus (GDM) based on the 2013 World Health Organization (WHO) criteria. Methods A total of 1843 women from a Belgian multi-centric prospective cohort study underwent universal screening for GDM. Using multivariable logistic regression analysis, a model to predict GDM was developed based on variables from early pregnancy. The performance of the model was assessed by receiver-operating characteristic (AUC) analysis. To account for over-optimism, an eightfold cross-validation was performed. The accuracy was compared with two validated models (van Leeuwen and Teede). Results A history with a first degree relative with diabetes, a history of smoking before pregnancy, a history of GDM, Asian origin, age, height and BMI were independent predictors for GDM with an AUC of 0.72 [95% confidence interval (CI) 0.69–0.76)]; after cross-validation, the AUC was 0.68 (95% CI 0.64–0.72). Adding biochemical variables, a history of a first degree relative with diabetes, a history of GDM, non-Caucasian origin, age, height, weight, fasting plasma glucose, triglycerides and HbA_1c were independent predictors for GDM, with an AUC of the model of 0.76 (95% CI 0.72–0.79); after cross-validation, the AUC was 0.72 (95% CI 0.66–0.78), compared to an AUC of 0.67 (95% CI 0.63–0.71) using the van Leeuwen model and an AUC of 0.66 (95% CI 0.62–0.70) using the Teede model. Conclusions A model based on easy to use variables in early pregnancy has a moderate accuracy to predict GDM based on the 2013 WHO criteria.
METHODS:Leveraging the availability of nationwide electronic health records from over 500,000 pregnancies in Israel, a machine-learning approach offers an alternative means of predicting gestational diabetes at high accuracy in the early stages of pregnancy. Gestational diabetes mellitus (GDM) poses increased risk of short- and long-term complications for mother and offspring^ 1 – 4 . GDM is typically diagnosed at 24–28 weeks of gestation, but earlier detection is desirable as this may prevent or considerably reduce the risk of adverse pregnancy outcomes^ 5 , 6 . Here we used a machine-learning approach to predict GDM on retrospective data of 588,622 pregnancies in Israel for which comprehensive electronic health records were available. Our models predict GDM with high accuracy even at pregnancy initiation (area under the receiver operating curve (auROC) = 0.85), substantially outperforming a baseline risk score (auROC = 0.68). We validated our results on both a future validation set and a geographical validation set from the most populated city in Israel, Jerusalem, thereby emulating real-world performance. Interrogating our model, we uncovered previously unreported risk factors, including results of previous pregnancy glucose challenge tests. Finally, we devised a simpler model based on just nine questions that a patient could answer, with only a modest reduction in accuracy (auROC = 0.80). Overall, our models may allow early-stage intervention in high-risk women, as well as a cost-effective screening approach that could avoid the need for glucose tolerance tests by identifying low-risk women. Future prospective studies and studies on additional populations are needed to assess the real-world clinical utility of the model.
METHODS::Repurposing of currently approved medications is an attractive option for the development of novel treatment strategies against physiological and infectious diseases. The antidiabetic sulfonylurea glyburide has demonstrated off-target capacity to inhibit activation of the NLRP3 inflammasome in a variety of disease models, including vaginal candidiasis, caused primarily by the fungal pathogen Candida albicans Therefore, we sought to determine which of the currently approved sulfonylurea drugs prevent the release of interleukin 1β (IL-1β), a major inflammasome effector, during C. albicans challenge of the human macrophage-like THP1 cell line. Findings revealed that the second-generation antidiabetics (glyburide, glisoxepide, gliquidone, and glimepiride), which exhibit greater antidiabetic efficacy than prior iterations, demonstrated anti-inflammatory effects with various degrees of potency as determined by calculation of 50% inhibitory concentrations (IC50s). These same compounds were also effective in reducing IL-1β release during noninfectious inflammasome activation (e.g., induced by lipopolysaccharide [LPS] plus ATP), suggesting that their anti-inflammatory activity is not specific to C. albicans challenge. Moreover, treatment with sulfonylurea drugs did not impact C. albicans growth and filamentation or THP1 viability. Finally, the use of ECE1 and Candidalysin deletion mutants, along with isogenic NLRP3-/- cells, demonstrated that both Candidalysin and NLRP3 are required for IL-1β secretion, further confirming that sulfonylureas suppress inflammasome signaling. Moreover, challenge of THP1 cells with synthetic Candidalysin peptide demonstrated that this toxin is sufficient to activate the inflammasome. Treatment with the experimental inflammasome inhibitor MCC950 led to similar blockade of IL-1β release, suggesting that Candidalysin-mediated inflammasome activation can be inhibited independently of potassium efflux. Together, these results demonstrate that the second-generation antidiabetic sulfonylureas retain anti-inflammatory activity and may be considered for repurposing against immunopathological diseases, including vaginal candidiasis.