BackgroundGlucokinase (GCK) is the key glucose phosphorylation enzyme which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) based on its enzyme function as the first rate-limiting step in the glycolysis pathway and regulates glucose-stimulated insulin secretion. In the past decade, the relationship between GCK and T2D has been reported in various ethnic groups. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis.MethodsDatabases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.ResultsA total of 24 articles involving 88, 229 cases and 210, 239 controls were included. An overall random-effects per-allele OR of 1.06 (95% CI: 1.03–1.09; P<10−4) was found for the GCK −30G>A polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians; whereas no significant associations were found among Asians. In addition, we found that the −30G>A polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. Besides, −30G>A homozygous was found to be significantly associated with increased fasting plasma glucose level with weighted mean difference (WMD) of 0.15 (95%: 0.05–0.24, P = 0.001) compared with G/G genotype.ConclusionsThis meta-analysis demonstrated that the −30G>A polymorphism of GCK is a risk factor associated with increased T2D susceptibility, but these associations vary in different ethnic populations.

To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFβR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS) and disease free survival (DFS) was increased in patients with low TGFβR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFβR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFβR2 is a potential prognostic tumor biomarker for chemotherapy.

Epidemiological data has demonstrated that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 µm (PM2.5) is associated with cancer incidence. However, the precise mechanisms underlying PM2.5-mediated hepatocellular carcinoma cancer (HCC) migration and invasion remain unclear. The aim of the present study was to explore the response of the HCC cell lines HepG2 and HuH-7 to PM2.5 exposure. The results revealed that PM2.5 treatment promoted the migration and invasion of HCC cells, in addition to increasing protein levels of matrix metalloproteinase (MMP)-13. Additionally, PM2.5 induced intracellular reactive oxygen species formation in HCC cells. Further investigation revealed that phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) increased in response to PM2.5 exposure in HCC cells, and the AKT antagonist LY294002 reduced PM2.5-induced migration, invasion and MMP-13 expression. In addition, the data from the present study demonstrated that high concentrations of PM2.5 decreased the proliferation of normal HL7702 hepatocyte cells and promoted apoptosis. These results indicate that the activation of AKT by PM2.5 results in MMP-13 overexpression, and stimulates HCC cell migration and invasion. In conclusion, the results from the present study demonstrate that PM2.5 promotes HCC development and elucidate a potential underlying molecular mechanism for this effect.

Indoleamine 2,3-dioxygenase (IDO) converts tryptophan to l-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, to investigate the effects of IDO in carbon tetrachloride (CCl(4) )-induced hepatitis model, the levels of IDO enzymic activities in the mock group, the control group and the 1-methyl-D-tryptophan (1-MT)-treated group were confirmed by determination of l-kynurenine concentrations. Serum alanine aminotransferase levels in 1-MT-treated rats after CCl(4) injection significantly increased compared with those in mock and control groups. In CCl(4)-induced hepatitis models, tumour necrosis factor-α (TNF-α) is critical in the development of liver injury. The mRNA expression and secretion levels of TNF-α in the liver from 1-MT-treated rats were more enhanced compared with those in the mock and the control groups. Moreover, the levels of cytokine and chemokine from mock, control group and 1-MT-treated rats after treated with CCl(4) were analyzed by ELISA, and the level of interleukin-6 was found to increase in 1-MT-treated rats. It was concluded that the deficiency of IDO exacerbated liver injury in CCl(4)-induced hepatitis and its effect may be connected with TNF-α and interleukin-6.