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OBJECTIVE：To study the effects of shikonin on autophagy and apoptosis of human colon cancer HCT 116 cells. METHODS：After treating HCT 116 cells for 48 h with shikonin at 0（blank control ）10，20，40 μg/mL，MTT method was used to detect inhibitory rate of cell proliferation. Flow cytometry was used to detect cell apoptosis rate. RT-qPCR assay and Western blotting were respectively used to detect mRNA and protein expressions of microtubule associated protein light chain 3（LC3）and autophagy-related protein Beclin- 1 and p 62. RESULTS ：Compared with blank control ，after treated with 10，20，40 μ g/mL shikonin for 48 h，proliferation inhibitory rate and apoptosis rate of HCT 116 cells were increased significantly （P＜0.05 or P＜ 0.01）. After treated with 10，20，40 μg/mL shikonin for 48 h，mRNA and protein expressions of LC 3，Beclin-1 and p 62 in HCT116 cells were increased to different extents ；except that mRNA expression of LC 3 was not increased significantly after treated with 10 μg/mL shikonin，the difference were statistically significant in other indexes ，compared with blank control （P＜0.05 or P＜0.01）. CONCLUSIONS ：Shikonin can induce the apoptosis of human colon cancer HCT 116 cells and activate its autophagy pathway.
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Objective:To assess the influence of glimepiride on the plasma concentrations and antihypertensive effects of losartan and its active metabolite losartan carboxylic acid(E-3174) in the patients with type 2 diabetes mellitus and hypertension. Methods:Pragmatic randomized controlled trial was used in the clinical study. Forty-five patients were enrolled and randomized into glimepiride group and the control group. Losartan was used as the antihypertensive drug in the two groups. After two-week interference,the plasma concentrations of losartan and its active metabolite E-3174 were determined using an LC-MS/MS method and the reduction of hyperten-sion was measured. Results:The plasma trough concentrations of losartan in glimepiride group was not higher than those in the control group,and those of E-3174 in glimepiride group was not lower than those in the control group. Additionally,the reduction of hyperten-sion was similar in the two groups. Conclusion: Glimepiride does not influence the plasma concentrations and the antihypertensive effects of losartan and its active metabolite E-3174 in the patients with type 2 diabetes mellitus and hypertension, suggesting no drug-drug interactions between them. Owing to the small sample,large clinical trial should be performed to confirm the above conclusion.
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Objective:To systematically review the influence of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitors in the treatment of peptic ulcer in Chinese subjects. Methods:Such databases as SinoMed, CNKI, WanFang data, CQVIP, PubMed and Embase were electronically searched for the clinical studies on CYP2C19 genetic polymorphisms, proton pump inhibitors and peptic ulcer. According to the inclusion and exclusion criteria, the literatures were screened out, the data were extracted, and the methodological quality of the included studies was also examined. Meta-analysis was then performed using RevMan 5. 3 and Stata 13. 0 software. Results: A total of 8 studies involving 1197 Chinese subjects were included. The results of meta-analysis showed that CYP2C19 genetic polymorphism of patients was significantly associated with the healing rate of peptic ulcer treated with proton pump in-hibitors. No thinking about the type of proton pump inhibitors, the peptic ulcer healing rate for extensive metabolizer ( EM) phenotype was remarkably lower than that for intermediate metabolizer (IM) phenotype (OR=0. 63, 95％CI:0. 46-0. 86, P0. 05). Subgroup analysis further showed that only in omeprazole treatment, the peptic ulcer healing rate for EM phenotype was remarkably lower than that for IM phenotype (OR=0. 59, 95％CI:0. 36-0. 97, P<0. 05), or PM phenotype (OR=0. 29, 95％CI:0. 13-0. 62, P<0. 05), respectively. However, no differ-ence was found between IM and PM phenotype. The similar trends were not showed in the other proton pump inhibitors, including rabe-prazole, esomeprazole and ilaprazole. Conclusion:CYP2C19 genetic polymorphism only affects the efficacy of omeprazole for the thera-py of peptic ulcer, while shows no influence on the efficacy of the other proton pump inhibitors in Chinese subjects. Therefore, patients with peptic ulcer should receive genetic testing of CYP2C19 polymorphisms before the use of omeprazole.
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OBJECTIVE:To systematically evaluate the relationship of multi-drug resistance gene MDR1 C3435T gene polymor-phism with therapeutic efficacy of proton pump inhibitors (PPIs)-based triple therapy for Helicobacter pylori eradication. METH-ODS:Retrieved from PubMed,EMBbase,CBM,CJFD,Wanfang database and VIP,clinical studies about MDR1 C3435T gene polymorphism and PPIs-based triple therapy for the eradication of H. pylori infection were collected. Meta-analysis was performed by using Rev Man 5.3 statistical software after data extraction and quality evaluation by using STREGA statement. RESULTS:A to-tal of 7 studies were included,involving 1019 patients. The results of MDR1 C3435T genotyping in patients were classified as wild homozygote genotype(CC),mutant heterozygous genotype(CT)and mutant homozygote genotype(TT). The results of Me-ta-analysis showed that there was no statistical significance in the eradication rate of H. pylori among CC,CT and TT groups of MDR1 C3435T gene polymorphism [CC vs. CT:OR=0.99,95%CI(0.69,1.42) ,P=0.95;CC vs.TT:OR=1.44,95%CI(0.66, 3.15),P=0.36;CT vs.TT:OR=1.54,95%CI(0.86,2.73),P=0.14]. Subgroup analysis showed the eradication rate of H. pylori in CT genotype group was higher than that in TT genotype group among Asian population [OR=2.35,95%CI(1.53,3.62),P<0.001]. CONCLUSIONS:MDR1 C3435T gene polymorphism basically do not affect therapeutic efficacy of PPIs-based triple thera-py for H. pylori eradication. For Asian population,gene detection is useful for the treatment.
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Aim To investigate whether rosuvastatin induced reduction of atherosclerotic plaque was related to the expression of Sialyltransferase ( ST6 Gal-Ⅰ) in ApoE-/ - mice. Methods Six-weeks old ApoE-/ -mice fed with high fat were divided randomly into three groups: baseline group ( n=12 ) , control group ( n=12 ) and rosuvastatin group ( n =12 ) . Sixteen weeks later, control group was sacrificed. Serum and aortic intima were saved. Control group and rosuvastatin group were fed for seven weeks continually. Concentra-tions of serum lipids(TC, TG, LDL and HDL) were analyzed. Sections from the aortic root were examined by Hematoxylin-Eosin( HE) staining. The size of ath-erosclerotic lesion in each section was evaluated. Ex-pression of ST6 Gal-Ⅰ in aortic intima was detected by immunohistochemistry. Results Plasma TG and LDL-C, plaque areas and intimal thickness of control group were significant higher than those of baseline group ( P<0. 05 ) . Those results indicated that the AS model was successfully constructed. After seven weeks, the plaque areas and concentrations of serum lipids of rosu-vastatin group were obviously smaller than those of con-trol group(P<0. 05). The expression of ST6Gal-Ⅰin aortic root was decreased in control group compared to the baseline, and which was increased in control group compared to the rosuvastatin group. Conclusion Ro-suvastatin could inhibit the progression of atherosclero-sis, which might be related to the expression of ST6Gal-Ⅰ in aortic root.