Inhibition Mechanism of Novel Pyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives Against Proliferation of A549 and H322 Cancer Cells.

OBJECTIVE: To explore the inhibition mechanism and safety of pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives against proliferation of human lung cancer A549 cells, H322 cells, and human umbilical vein endothelial cell (HUVEC). METHODS: Cells were treated with 40 Μmol/L of the ppo3a, ppo3b, ppo3i, and 0.1% DMSO (control) for 48 hours, respectively. Apoptosis was determined by Hoechst 33258 staining assay in H322 and A549 cells. Cell cycle distribution was determined by flow cytometry analysis in A549 cell. LC3-II, p53, and heat shock protein (HSP) 70 protein levels were detected by Western blotting in A549 cells treated with ppo3b for 48 hours. The morphology and viability of HUVEC were observed by inverted microscope and sulforhodamine B (SRB) assay. RESULTS: Ppo3a, ppo3b, and ppo3i significantly induced apoptosis in H322 and A549 cells. A strong G1-phase arrest was concomitant with the growth inhibitory effect on A549 cells. Ppo3b effectively elevated the p53 protein level, but significantly reduced the HSP70 protein level. There were no significantly inhibitory effect on the morphology and viability of HUVEC when treated with ppo3a, ppo3b, and ppo3i. CONCLUSIONS: ppo3a, ppo3b, and ppo3i could inhibit H322 proliferation through apoptosis and inhibit A549 through apoptosis and G1-phase arrest. The protein p53 and HSP70 might involve in the inhibition effects. These derivatives might be a clue to find effective and safe drug for lung cancers.

[Study on the relations between overweight, obesity, blood pressures, serum lipids and glucose in schoolchildren of Shijiazhunag].

OBJECTIVE: To explore the clustering character of overweight and obesity with multiple cardiovascular disease risk factors such as blood pressure, serum lipids and glucose, and to provide evidence for intervention in childhood. METHODS: A cross-sectional study was conducted on 913 children aged 7-13 years in urban area of Shijiazhuang. Measurements included height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and serum glucose (GLU). RESULTS: Overall prevalence rate of overweight and obesity was 29.24% (boys: 34.98% vs. girls: 24.23%). When compared with normal children, children with overweight or obesity had significantly higher levels of SBP, DBP, TC, TG but low HDL-C. The prevalence rates of high SBP, DBP, TC, TG, GLU and low HDL-C in overweight and obese children were higher than in normal children. After adjusted for gender and age, the odds ratios of overweight and obese children for high SBP, DBP, TC, TG, GLU and low HDL-C were 6.77, 3.22, 2.55, 6.42, 3.85 and 2.94 (95% CI: 4.15-11.04, 1.38-7.49, 1.59-4.11, 3.46-11.92, 1.69-8.78 and 1.83-4.73), respectively. Odds ratios of overweight and obese children holding any one, two or three of the selected six risk factors appeared to be 2.74, 13.15 and 15.33 (95% CI : 1.92-3.92, 6.69-25.87 and 4.17-56.39), respectively. CONCLUSION: Childhood overweight and obesity increased the clustering of children's risk factors on cardiovascular diseases, as well as increasing the risk of children acquiring multiple cardiovascular disease risk factors. Controlling overweight and obesity would help early prevention on children from getting cardiovascular diseases.