ABSTRACT
BACKGROUND: Adiponectin (ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual's predisposition to metabolic syndrome and type 2 diabetes. Moreover, women with gestational diabetes mellitus (GDM) are at an increased risk of developing type 2 diabetes. Several studies have been conducted previously to assess the association between ADIPOQ polymorphisms and GDM; however, the results of the association are inconclusive. AIM: To quantitatively evaluate the association between ADIPOQ +45T/G, +276G/T, and -11377C/G polymorphisms and the risk of GDM. METHODS: A systematic search of EMBASE, PubMed, CNKI, Web of Science, and WANFANG DATA was conducted up to October 20, 2018. We calculated merged odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed-effects or random-effects model depending on the between-study heterogeneity to evaluate the association between AIDPOQ +45T/G, +276G/T, and -11377C/G polymorphisms and the risk of GDM. Subgroup analysis was performed by ethnicity. Publication and sensitivity bias analyses were performed to test the robustness of the association. All statistical analyses were conducted using Stata12.0. RESULTS: Nine studies of +45T/G included 1024 GDM cases and 1059 controls, five studies of +276G/T included 590 GDM cases and 595 controls, and five studies of -11377C/G included 722 GDM cases and 791 controls. Pooled ORs indicated that +45T/G increased GDM risk in Asians (allelic model: OR = 1.47, 95%CI: 1.27-1.70, P = 0.000; dominant model: OR = 1.54, 95%CI: 1.27-1.85, P = 0.000; recessive model: OR=2.00, 95%CI: 1.43-2.85, P = 0.000), not in South Americans (allelic model: OR = 1.21, 95%CI: 0.68-2.41, P = 0.510; dominant model: OR = 1.13, 95%CI: 0.59-2.15, P = 0.710; recessive model: OR = 2.18, 95%CI: 0.43-11.07, P = 0.350). There were no significant associations between +276G/T (allelic model: OR = 0.88, 95%CI: 0.74-1.05, P = 0.158; dominant model: OR = 0.91, 95%CI: 0.65-1.26, P = 0.561; recessive model: OR = 0.82, 95%CI: 0.64-1.05, P = 0.118) or -11377C/G (allelic model: OR = 0.96, 95%CI: 0.72-1.26, P = 0.750; dominant model: OR = 1.00, 95%CI: 0.73-1.37, P = 0.980; recessive model: OR = 0.90, 95%CI: 0.61-1.32, P = 0.570) and the risk of GDM. CONCLUSION: Our meta-analysis shows the critical role of the ADIPOQ +45T/G polymorphism in GDM, especially in Asians. Studies focused on delineating ethnicity-specific factors with larger sample sizes are needed.
ABSTRACT
AIM: To compare the accuracy of the scoring systems Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease score (MELD), MELD-Na, and MELD to Serum Sodium ratio (MESO) to predict the mortality in decompensated liver cirrhosis. METHODS: The PubMed, Web of Science, Cochrane Library, EMBASE, and Ovid databases were systematically searched from inception to September 2018 for relevant articles, and we evaluated the quality of the included studies. The accuracy of scoring systems was analyzed with Stata 12 and MetaDiSc 1.4. RESULTS: Sixteen studies involving 2337 patients were included. The pooled areas under the summary receiver operating characteristic curves (AUROCs) of CTP, MELD, MELD-Na, and MESO to predict mortality were 0.81, 0.78, 0.85, and 0.86, respectively. Within 3 mo, the AUROCs of CTP, MELD, and MELD-Na in predicting mortality were 0.78, 0.76, and 0.89, respectively. The AUROCs of CTP, MELD, and MELD-Na at 3 mo were 0.86, 0.78, and 0.86, respectively. The AUROCs of CTP, MELD, and MELD-Na at 6 mo were 0.91, 0.83, and 0.90, respectively. The AUROCs of CTP, MELD, and MELD-Na at 12 mo were 0.72, 0.75 and 0.84, respectively. In cirrhotic patients with bleeding, the AUROCs of CTP and MELD were 0.76 and 0.88, respectively. CONCLUSION: MESO has the highest AUROC in all assessed scoring systems. Considering the different time points, MELD-Na has good accuracy in predicting the mortality of decompensated liver cirrhosis. Compared to CTP, MELD is better in predicting variceal bleeding.
ABSTRACT
Protein kinase D (PKD) isoforms are protein kinase C (PKC) effectors in diacylglycerol (DAG)-regulated signaling pathways. Key physiological processes are placed under DAG control by the distinctive substrate specificity and intracellular distribution of PKDs. Comprehension of the roles of PKDs in homeostasis and signal transduction requires further knowledge of regulatory interplay among PKD and PKC isoforms, analysis of PKC-independent PKD activation, and characterization of functions controlled by PKDs in vivo. Caenorhabditis elegans and mammals share conserved signaling mechanisms, molecules, and pathways Thus, characterization of the C. elegans PKDs could yield insights into regulation and functions that apply to all eukaryotic PKDs. C. elegans DKF-1 (D kinase family-1) contains tandem DAG binding (C1) modules, a PH (pleckstrin homology) domain, and a Ser/Thr protein kinase segment, which are homologous with domains in classical PKDs. DKF-1 and PKDs have similar substrate specificities. Phorbol 12-myristate 13-acetate (PMA) switches on DKF-1 catalytic activity in situ by promoting phosphorylation of a single amino acid Thr(588) in the activation loop. DKF-1 phosphorylation and activation are unaffected when PKC activity is eliminated by inhibitors. Both phosphorylation and kinase activity of DKF-1 are extinguished by substituting Ala for Thr(588) or Gln for Lys(455) ("kinase dead") or incubating with protein phosphatase 2C. Thus, DKF-1 is a PMA-activated, PKC-independent D kinase. In vivo, dkf-1 gene promoter activity is evident in neurons. Both dkf-1 gene disruption (null phenotype) and RNA interference-mediated depletion of DKF-1 protein cause lower body paralysis. Targeted DKF-1 expression corrected this locomotory defect in dkf-1 null animals. Supraphysiological expression of DKF-1 limited C. elegans growth to approximately 60% of normal length.