Halofuginone protects HUVECs from H2O2-induced injury by modulating VEGF/JNK signaling pathway.

BACKGROUND: Halofuginone, which is the main active ingredient of Dichroa fabrifuga, was used to inhibit the synthesis of type I collagen and played increasingly important roles in tumor therapy. This study aims to investigate the protective effects of halofuginone on human umbilical vein endothelial cells (HUVECs) from H2O2-induced apoptosis and oxidative stress. METHODS: Propidium iodide and Annexin-V double staining assay was used to measure the apoptosis. Cell viability assay, the measurements of reactive oxygen species (ROS) parameters malondialdehyde and superoxide dismutase, western-blot assays, and quantitative PCR were used to elucidate the effects and mechanisms of halofuginone in protecting H2O2-induced injury. RESULTS: The results showed that halofuginone counteracted H2O2-induced cell viability decline and PCNA downregulation. Furthermore, halofuginone decreased ROS levels and protected HUVECs from H2O2-induced apoptosis. In detail, it showed that H2O2 induced a transient activation of Mitogen-activated protein kinases members ERK1/2 and p38, whereas induced a sustained activation of c-Jun N-terminal kinase (JNK), which play dominant roles in triggering apoptosis. Inhibition of JNK activation also inhibited H2O2-mediated apoptosis. Finally, it was shown that halofuginone upregulated VEGF expressions, which functioned by inhibiting sustained JNK activation, thus protecting HUVECs. CONCLUSION: Halofuginone has powerful effects in protecting HUVECs from H2O2-induced apoptosis, via upregulating VEGF and inhibiting overactivated JNK phosphorylation. Halofuginone might be a promising preventive drug for cardiovascular diseases.

Comparison of dabigatran and warfarin used in patients with non-valvular atrial fibrillation: Meta-analysis of random control trial.

BACKGROUND: Dabigatran is a kind of oral anticoagulant and there was little review only about dabigatran and warfarin used in patients with atrial fibrillation. This meta-analysis only assesses the dabigatran and warfarin used in patients with atrial fibrillation. DESIGN: Cochrane Library, PubMed, Clinical Trials.gov, CNKI, and WanFang databases were searched. The primary endpoint was the incidence of stroke and the second endpoints were the incidence of bleeding and embolic events. RESULTS: Six RCTs and 20086 patients were included in our meta-analysis. No significant difference was obtained between 110 mg dabigatran and warfarin on the endpoint of stroke (risk ratio (RR), 0.90; 95% confidence interval [CI], 0.71-1.12; P = .34; I = 0%) and embolic events p (RR, 0.89; 95% CI, 0.71-1.12; P = .32; I = 0%). However, the 110 mg dabigatran associated lower incidence of bleeding (RR, 0.81; 95% CI, 0.69-0.95; P = .01; I = 0%) compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower rate of stroke (RR, 0.96; 95% CI, 0.83-1.12; P = .62; I = 0%) and embolic events (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%) but similar in the incidence of bleeding (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%). CONCLUSION: No significant difference was obtained between 110 mg dabigatran and warfarin in the incidence of stroke and embolic events. However, the 110 mg dabigatran associated lower incidence of bleeding compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower incidence of stroke and embolic events but similar in the incidence of bleeding.

[Heart rate variability in children with beta-thalassemia major].

OBJECTIVE: To study the diagnostic value of heart rate variability (HRV) in heart dysfunction in children with beta-thalassemia major (ß-TM)by examining the changes of HRV in ß-TM children. METHODS: A 24 hours Holter monitoring electrocardiogram (Holter) was performed in 21 children with ß-TM and 15 healthy children (control group). The time domain and frequency domain indexes of HRV in the two groups were compared. The correlation between serum ferritin levels and HRV was evaluated. RESULTS: The time domain indexes SDNN, rMSSD and PNN50 and the frequency domain indexes very low frequency (VLF), low frequency (LF) and high frequency (HF) in the ß-TM group were significantly lower than in the control group (P<0.05). There was no correlation between serum ferritin level and HRV in children with ß-TM. CONCLUSIONS: The autonomic nerve dysfunction exists in children with ß-TM. HRV analysis is useful in the prediction of early cardiac dysfunction in children with ß-TM.