RESUMO
Although the impact of cigarette smoking on glucose homeostasis has been extensively studied, the results, however, are still not conclusive. We, therefore, conducted a cross-sectional analysis of a non-diabetic Chinese cohort collected by the China Health and Nutrition Survey (CHNS 2009) to comprehensively assess the relationship between smoking, Hemoglobin A1c, ß-cell function and insulin sensitivity. The cohort included a total of 5965 individuals (47.4% male) with a mean age of 49.23 years, and 4140 of which were non-smokers (69.4%), 834 were current light smokers (13.9%) and 991 were current heavy smokers (16.6%). Current smokers were predominantly males (93.6%) with a lower BMI (22.95 versus 23.42 kg/m2). HbA1c levels were dose-dependently increased with smoking exposure (5.39%, 5.42% and 5.45%, respectively, P = 0.007). Non-smokers were served as a referent, the adjusted ORs for type 2 diabetes were 1.12 (P = 0.256, light smokers) and 1.26 (P = 0.014, heavy smokers), indicating a positive relationship between cigarette smoking and incidence of diabetes. HOMA%B was decreased in a dose-responsive manner with cigarette smoking (4.80, 4.79 and 4.76, P = 0.036), suggesting an adverse effect of smoking on ß-cell function. Collectively, cigarette smoking is dose-dependently associated with decreased HOMA%B, and current smokers were clearly in a higher risk for diabetes as manifested by the elevated HbA1c.
RESUMO
The Escherichia coli purine nucleoside phospho-rylase/2-fluoro-2-deoxyadenosine (ePNP/F-dAdo) suicide system has demonstrated a powerful killing and bystander effects on tumor cells. However, several drawbacks to this approach remain to be resolved, such as the side-effects and the low efficiency of ePNP-targeted expression. A human telo-merase reverse transcriptase promoter-driven Semliki Forest virus-based DNA vector (pShT-ePNP) with high expression of the ePNP gene was constructed. Live attenuated Salmonella typhimurium 7207 (SL7207) was used initially as a vehicle to targetly transfer the large alphavirus vector into tumor cells. The in vitro quantitative analysis showed ~2-fold higher green fluorescent protein (GFP) expression for pShT-GFP than for conventional cytomegalovirus (CMV) promoter-mediated eukaryotic expression plasmids such as pIRES-GFP and the targeted expression of the ePNP gene in tumor cells was also detected by RT-PCR. After F-dAdo addition, the enzymatic conversion of F-Ado into 2-fluoroadmine (F-Ade) was tested by HPLC. Cell cytotoxicity assays showed that the significant inhibitory effect of the SL/pShT-ePNP system on tumor cells was dose- and time-dependent. Following oral administration, recombinant bacteria targetly allocated within the solid tumor and the expression of ePNP and GFP genes in vivo were detected by RT-PCR or observed by fluorescence microscopy. SL/pShT-ePNP and F-dAdo were also found to exert powerful therapeutic effects in combination against tumor growth and for prolonging the lifespan of tumor-bearing mice. These findings suggest that the SL/pShT-ePNP system may serve as a powerful strategy for tumor therapy.
