Administration of Ticagrelor and Double-Dose Clopidogrel Based on Platelet Reactivity Determined by VerifyNow-P2Y12 for Chinese Subjects After Elective PCI.

Previous studies have identified high on treatment platelet reactivity (HTPR) as a potent factor predicting ischemic events for patients with coronary heart disease. We assessed the efficacy and safety of ticagrelor (90 mg twice-daily) and double-dose of clopidogrel (150 mg once-daily) among Chinese patients for elective percutaneous coronary intervention. We enrolled 40 patients with HTPR from among 317 patients with non-ST-segment elevation acute coronary syndromes after a successful elective percutaneous coronary intervention (PCI). Platelet reactivity was measured by VerifyNow P2Y12 assay. Platelet reactivity was significantly lower for both groups when compared with baseline platelet reactivity after medication adjustment (all P < 0.001). The mean platelet reactivity units (PRU) was significantly lower for the ticagrelor group compared with that of the clopidogrel group over time (all P < 0.001). The differences in the rate of sustained HTPR at different time points between the two groups were significant (2 hours: 0% versus 60%; 8 hours: 5.6% versus 50%; 24 hours: 5.9% versus 43.8%, all P < 0.05). Genetic variation of CYP2C19*2 had no impact on PRU means or rate of HTPR in the ticagrelor group (P > 0.05). During the 30-day follow-up, no MACE occurred in any patient, and the overall risk of bleeding showed no difference between the two groups (35% versus 21%, P = 0.48). Our results suggest that ticagrelor may achieve a more rapid and greater platelet inhibition than double-dose clopidogrel. Further studies are still needed to assess the differences in efficacy and safety between ticagrelor and double-dose clopidogrel administration for Chinese patients post elective PCI.

Effects of tea intake on blood pressure: a meta-analysis of randomised controlled trials.

The effect of tea intake on blood pressure (BP) is controversial. We performed a meta-analysis of randomised controlled trials to determine the changes in systolic and diastolic BP due to the intake of black and green tea. A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Controlled Trials Register up to May 2014. The weighted mean difference was calculated for net changes in systolic and diastolic BP using fixed-effects or random-effects models. Previously defined subgroup analyses were performed to explore the influence of study characteristics. A total of twenty-five eligible studies with 1476 subjects were selected. The acute intake of tea had no effects on systolic and diastolic BP. However, after long-term tea intake, the pooled mean systolic and diastolic BP were lower by - 1·8 (95 % CI - 2·4, - 1·1) and - 1·4 (95 % CI - 2·2, - 0·6) mmHg, respectively. When stratified by type of tea, green tea significantly reduced systolic BP by 2·1 (95 % CI - 2·9, - 1·2) mmHg and decreased diastolic BP by 1·7 (95 % CI - 2·9, - 0·5) mmHg, and black tea showed a reduction in systolic BP of 1·4 (95 % CI - 2·4, - 0·4) mmHg and a decrease in diastolic BP of 1·1 (95 % CI - 1·9, - 0·2) mmHg. The subgroup analyses showed that the BP-lowering effect was apparent in subjects who consumed tea more than 12 weeks (systolic BP - 2·6 (95 % CI - 3·5, - 1·7) mmHg and diastolic BP - 2·2 (95 % CI - 3·0, - 1·3) mmHg, both P< 0·001). The present findings suggest that long-term ( ≥ 12 weeks) ingestion of tea could result in a significant reduction in systolic and diastolic BP.

Effects of lipophilic statins for heart failure: a meta-analysis of 13 randomised controlled trials.

BACKGROUND: The effects of lipophilic statins in heart failure (HF) were controversial. The goal of the present study was to systematically review all randomised controlled trials evaluating the effects of lipophilic statins in patients with HF. METHODS: We performed a comprehensive literature search to identify eligible trials that prospectively randomised patients with HF to lipophilic statins or control. Primary end points were all-cause mortality, cardiovascular mortality, hospitalisation for worsening HF, left ventricular ejection fraction (LVEF), and low-density lipoprotein cholesterol. Risk ratios (RRs) and Weighted mean differences (WMDs) were calculated using fixed-effects models or random-effects models. RESULTS: A total of 13 randomised trials with 1,532 subjects were included in this analysis. Ten trials randomised patients to atorvastatin, two to simvastatin, and one to pitavastatin. Overall, lipophilic statins significantly decreased all-cause mortality (RR 0.53, P<0.001), cardiovascular mortality (RR 0.66, P=0.04), and hospitalisation for worsening HF (RR 0.60, P<0.001). Subgroup analyses showed that the effects of lipophilic statins in HF were not modified by age, baseline LVEF, and cause of HF. In addition, patients randomised to lipophilic statins had a significant increase in LVEF (WMD 3.91%, P<0.001) and decrease in low-density lipoprotein cholesterol (WMD 0.90 mmol/L, P<0.001). CONCLUSIONS: It appears that further studies are needed to determine if lipophilic statins are beneficial for HF patients.

Ganoderic acid T improves the radiosensitivity of HeLa cells via converting apoptosis to necroptosis.

The use of natural substances derived from traditional Chinese medicine and natural plants as safe radiosensitizing adjuvants is a new trend for cancer radiotherapy. Ganoderma lucidum has been used as a traditional Chinese medicine with a history of more than 2000 years. Ganoderic acid T (GAT) is a typical triterpene of G. lucidum, which has strong cytotoxicity to cancer cells, but whether it has radiation sensitization effect has not been explored. In this work, we treated the HeLa cells with different concentrations of GAT before exposure to gamma-ray radiation and investigated its influence on the radiosensitivity. The cell viability, apoptosis rate, necoptosis rate, intracellular ATP level, cell cycle, the amount of H2AX and 53BP1, reactive oxygen species, and mitochondrial membrane potential were examined. Apoptotic, necroptotic, and autophagic biomarker proteins, including caspase 8, cytochrome c, caspase 3, RIPK, MLKL, P62, and LC3, were analyzed. As a result, we confirmed that with treatment of GAT, the gamma-ray radiation induced both apoptosis and necroptosis in HeLa cells, and with increase of GAT, the percentage ratio of necroptosis was increased. The involved pathways and mechanisms were also explored and discussed.

Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in ESCC cells.

ETHNOPHAMACOLOGICAL RELEVANCE: Ganoderma lucidum has been used as a medicinal mushroom for more than 2000 years in China. Ganoderic acid D (GAD) as a representative active triterpenoid from Ganoderma lucidum is known to possess anticancer activity. However, the mechanism involved in its anticancer cell process is still largely elusive. AIM OF THE STUDY: Our study aimed to investigate the anticancer effects of GAD on the esophageal squamous cell carcinoma (ESCC) cells and the underlying mechanisms at the cell level. MATERIALS AND METHODS: EC9706 and Eca109 cells were treated with GAD (0, 10, 20, 40 µM) for 24 h. The cell viability, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis rate, caspase-3 activity, autophagic flux, lysosomal function were examined. Cell cycle, apoptotic, autophagy and mTOR signal pathway related proteins such as P53, Cyclin B1, CytoC, PARP, Beclin-1, P62, LC3, PI3K, AKT and mTOR were analyzed by Western blot approach. RESULTS: GAD inhibited cell proliferation and induced both apoptosis and autophagic cell death. In particular, we found that in the early stage of the autophagic process, GAD could initiate and enhance the autophagy signal while in the late stage it on the contrary could block the autophagic flux by impairing the autophagosome-lysosome fusion and inhibited the lysosomal degradation. Besides the autophagic cell death, GAD also induced the apoptosis mediated by caspase-related process in parallel. The mechanism involved for the synergistic apoptotic and autophagic cell death was also explored. We found that GAD down-regulated the expression of PI3K, AKT and mTOR phosphorylated proteins in the mTOR signaling pathway which thus led to the synergistic effect on apoptosis and autophagic cell death in the ESCC cells. CONCLUSIONS: In summary, this study has documented that GAD may inhibit cell proliferation through the mTOR pathway in ESCC cells, and induce synergistic apoptosis and autophagic cell death by disrupting the autophagic flux. This work therefore also suggests that GAD may be used as an efficient anticancer adjuvant for ESCC cancer therapy.

Molecular cloning and functional characterisation of the tomato E3 ubiquitin ligase SlBAH1 gene.

Emerging evidence suggests that E3 ligases play critical roles in diverse biological processes, including pathogen resistance in plants. In the present study, an ubiquitin ligase gene (SlBAH1) was cloned from a tomato plant, and the functions of the gene were studied. The SlBAH1 gene contained 1002 nucleotides and encodes a protein with 333 amino acids. The SlBAH1 protein contains a SPX domain and a RING domain. SlBAH1 displayed E3 ubiquitin ligase activity in vitro. SlBAH1 was shown to localise in the nucleus, cytoplasm and plasma membrane by a subcellular localisation assay. The expression of SlBAH1 was induced by various hormones and Botrytis cinerea Pers. treatment. SlBAH1-silencing in plants obtained by virus-induced gene silencing (VIGS) technology enhanced resistance to B. cinerea, and the expression of pathogenesis-related (PR) genes, including PR1, PR2, PR4, PR5, and PR7, was significantly increased. These results indicate that the SlBAH1-dependent activation of defence-related genes played a key role in the enhanced fungal resistance observed in the SlBAH1-silenced plants and may be related to the SA-dependent and JA-dependent signalling pathways.

Meta-analysis of the effect of statins on mortality in patients with preserved ejection fraction.

No therapy has been shown to improve survival rate in heart failure with preserved ejection fraction (HFPEF). Recent observational studies of the association between statin use and the risk of mortality in HFPEF have shown mixed results. The goal of the present study was to systematically review all published observational studies evaluating the effect of statins on the risk of mortality in HFPEF. A literature search in the PubMed and EMBASE databases was undertaken through December of 2013. Combined relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. A total of 11 eligible studies with 17,985 patients with HFPEF were included in the analysis. Statin use was associated with a 40% lower risk of mortality (RR 0.60, 95% CI 0.49 to 0.74, p<0.001). Stratification of studies by controlled or uncontrolled confounding factors affected the final estimate (confounder-controlled RR 0.63, 95% CI 0.51 to 0.77, p<0.001 and confounder-uncontrolled RR 0.49, 95% CI 0.24 to 1.01, p=0.053). Furthermore, sensitivity analysis confirmed the stability of the results. Cumulative meta-analysis showed an obvious trend of reduction in mortality rates in statin users from 2005 to 2013. In conclusion, our meta-analysis supports the hypothesis that statin therapy may be associated with improved survival rates in patients with HFPEF. Nevertheless, randomized controlled trials are needed to confirm the efficacy of statins in HFPEF.

Meta-analysis of nonsteroidal anti-inflammatory drug use and risk of atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. The goal of the present study was to quantify the association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of AF incidence. MEDLINE and EMBASE were searched for studies that reported risk of AF associated with nonaspirin NSAID use. Combined relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Stratified meta-analyses were used to discern which patients were at the highest risk of AF due to NSAID use. Five studies were identified that met the inclusion criteria, 3 of which additionally reported specifically on the association between selective NSAIDs and risk of AF. Overall, NSAID use was associated with a 12% increased risk for AF incidence (RR 1.12, 95% CI 1.06 to 1.18). The association was found to be apparent among new users (RR 1.53, 95% CI 1.37 to 1.70). The increased risk of AF might be explained by the occurrence of chronic heart failure and kidney disease. In addition, use of selective NSAIDs was still related to an increased risk of AF (RR 1.24, 95% CI 1.18 to 1.30). Sensitivity analyses found results to be robust. In conclusion, use of nonaspirin NSAIDs was associated with an increased risk of incident AF. The association was found to be apparent for new users, with a 53% increase in risk. These findings suggest that AF needs to be added to the cardiovascular risks to be considered when prescribing NSAIDs.

Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.

BACKGROUND: The effect of green tea catechins (GTCs) with or without caffeine on glycemic control is controversial. OBJECTIVE: We aimed to identify and quantify the effects of GTCs or GTC-caffeine mixtures on glucose metabolism in adults. DESIGN: A comprehensive literature search was conducted to identify relevant trials of GTCs with or without caffeine on markers of glycemic control [fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (Hb A1c), and homeostatic model assessment of insulin resistance (HOMA-IR)]. Weighted mean differences were calculated for net changes by using fixed-effects models. Prespecified subgroup analyses were performed to explore the influence of covariates on net changes in FBG and FBI concentrations. RESULTS: Twenty-two eligible randomized controlled trials with 1584 subjects were identified. Pooled analyses showed that FBG (-1.48 mg/dL; 95% CI: -2.57, -0.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 µU/mL; 95% CI: -0.36, 0.45 µU/mL), Hb A1c (-0.04%; 95% CI: -0.15, 0.08%), and HOMA-IR (-0.05; 95% CI: -0.37, 0.26) did not. Subgroup analyses indicated that the glucose-lowering effect was apparent when the duration of follow-up was over a median of 12 wk. Overall, no significant heterogeneity was detected for FBG, FBI, Hb A1c, or HOMA-IR. CONCLUSIONS: The meta-analysis showed that the administration of GTCs with or without caffeine resulted in a significant reduction in FBG. The limited data available on GTCs did not support a positive effect on FBI, Hb A1c, or HOMA-IR. Thus, more large and well-designed trials are needed in the future. This trial was registered at http://www.crd.york.ac.uk/prospero as CRD42012002139.

Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials.

BACKGROUND: The effect of green tea beverage and green tea extract on lipid changes is controversial. OBJECTIVE: We aimed to identify and quantify the effect of green tea and its extract on total cholesterol (TC), LDL cholesterol, and HDL cholesterol. DESIGN: We performed a comprehensive literature search to identify relevant trials of green tea beverages and extracts on lipid profiles in adults. Weighted mean differences were calculated for net changes in lipid concentrations by using fixed-effects or random-effects models. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted. RESULTS: Fourteen eligible randomized controlled trials with 1136 subjects were enrolled in our current meta-analysis. Green tea consumption significantly lowered the TC concentration by 7.20 mg/dL (95% CI: -8.19, -6.21 mg/dL; P < 0.001) and significantly lowered the LDL-cholesterol concentration by 2.19 mg/dL (95% CI: -3.16, -1.21 mg/dL; P < 0.001). The mean change in blood HDL-cholesterol concentration was not significant. Subgroup and sensitivity analyses showed that these changes were not influenced by the type of intervention, treatment dose of green tea catechins, study duration, individual health status, or quality of the study. Overall, no significant heterogeneity was detected for TC, LDL cholesterol, and HDL cholesterol; and results were reported on the basis of fixed-effects models. CONCLUSION: The analysis of eligible studies showed that the administration of green tea beverages or extracts resulted in significant reductions in serum TC and LDL-cholesterol concentrations, but no effect on HDL cholesterol was observed.