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( Lai Wei ),( Jinlin Hou ),( Yan Luo ),( Jeong Heo ),( Chi-jen Chu ),( Zhongping Duan ),( Mong Cho ),( Jun Cheng ),( Jun Li ),( Jidong Jia ),( Wenjing Lu ),( Linda M Fredrick ),( Tami Pilot-matias ),( 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: HCV genotype 1b is the most common genotype in Asian patients. ONYX-I is a phase 3, randomised, double-blind, placebo-controlled study of the 3-DAA regimen of OBV/PTV/r and DSV in treatment- naive and treatment-experienced non-cirrhotic patients with HCV GT1b infection in China, South Korea and Taiwan. Methods: In this study, the safety/efficacy of OBV/PTV/r + DSV administered for 12 weeks were evaluated in non-cirrhotic Asian patients. Patients in Arm A received active study drug during a 12-week double-blind (DB) period, while patients in Arm B received placebo during the same period followed by an open-label (OL) period in which they received 12 weeks of active study drug. Efficacy was assessed by SVR12 and SVR24. Efficacy and safety were assessed in all patients who received at least one dose of active study drugs. Results: 650 HCV GT1b patients (54% female, 100% Asian, 44% treatment-experienced) were enrolled from China (n=410) South Korea (n=120) and Taiwan (n=120), and randomised 1:1 to Arms A and B. In Arm A, SVR12 and SVR24 rates were 99.5% (183/184) in treatment-naive patients and 100% (141/141) in treatment- experienced patients. Most treatment-emergent adverse events (TEAEs) in patients receiving the active drug were mild in severity. The most common (≥5%) TEAEs in Arm A were upper respiratory tract infection (10.5%), headache (6.2%) and dizziness (5.2%). Seven patients had serious AEs during active treatment (Arm A) and one patient in Arm A discontinued treatment. Conclusions: In non-cirrhotic Asian adults with HCV GT1b-infection, treated with OBV/PTV/r + DSV for 12 weeks, SVR24 rates equalled previously reported SVR12 rates from this study (99.5% of treatment- naive and 100% of treatment-experienced patients), and are consistent with other clinical trials with this drug combination. The treatment was generally well tolerated with mostly mild TEAEs reported.
Qian Zhang,Changpeng Hu,Jingbin Huang,Wuyi Liu,Wenjing Lai,Faning Leng,Qin Tang,Yali Liu,Qing Wang,Min Zhou,Fangfang Sheng,Guobing Li,Rong Zhang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
Dopamine deficiency is mainly caused by apoptosis of dopaminergic nerve cells in the substantia nigra of themidbrain and the striatum and is an important pathologic basis of Parkinson’s disease (PD). Recent research has shownthat dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays a crucial role in dopaminergicnerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Our study showed that Drp1knockdown inhibited aberrant mitochondrial fission and apoptosis. Importantly, we found that ROCK1 was activated inan MPP+-induced PD cell model and that ROCK1 knockdown and the specific ROCK1 activation inhibitor Y-27632blocked Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cells by suppressing Drp1dephosphorylation/activation. Our in vivo study confirmed that Y-27632 significantly improved symptoms in a PDmouse model by inhibiting Drp1-mediated aberrant mitochondrial fission and apoptosis. Collectively, our findingssuggest an important molecular mechanism of PD pathogenesis involving ROCK1-regulated dopaminergic nerve cellapoptosis via the activation of Drp1-induced aberrant mitochondrial fission.