Seraprevir and sofosbuvir for treatment of chronic hepatitis C virus infection: A single-arm, open-label, phase 3 trial.

BACKGROUND AND AIM: This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis. METHODS: Treatment-naive or interferon-experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12). RESULTS: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post-treatment course and 3 discontinued follow-up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention. CONCLUSIONS: The all-oral, ribavirin-free regimen of seraprevir and sofosbuvir is an effective and well-tolerated treatment option for Chinese patients mono-infected with HCV, including those with a history of interferon treatment.

2-[4-(4-Methylphenylsulfonyl)piperazin-1-yl]-1-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)ethanone.

In the title thienopyridine derivative, C(20)H(25)N(3)O(3)S(2), the piperazine ring exhibits a chair conformation and the tetra-hydro-pyridine ring exhibits a half-chair conformation. The folded conformation of the mol-ecule is defined by the N-C-C-N torsion angle of -70.20 (2) °. Inter-molecular C-H⋯S and C-H⋯O hydrogen bonds help to establish the packing.

Gibberellic acid application on biomass, oxidative stress response, and photosynthesis in spinach (Spinacia oleracea L.) seedlings under copper stress.

The mechanism of Cu tolerance in plants and its control measures are of considerable significance for the remediation of Cu-contaminated soils. Gibberellic acid (GA3) is involved in plant growth and development and in the response to heavy metal stress. In the present study, changes in the biomass, oxidative stress response responses, and photosynthesis of spinach seedlings were examined under Cu stress with exogenous GA3 applied at concentrations of 0, 3, 5, 10, 20, 40, 60, or 80 mg L-1. Under Cu stress, the plant Cu concentration and oxidative damage were greater, photosynthetic parameters and biomass declined, and antioxidant enzyme activities and the proline concentration increased. However, spinach growth did not terminate, indicating that spinach seedlings had strong Cu tolerance. When low concentrations of GA3 (3-5 mg L-1) were added to Cu-stressed spinach seedlings, the damage caused by Cu stress to spinach seedlings was reduced, and the Cu tolerance of spinach seedlings was enhanced, which mainly manifested as reduced oxidation damage, an increased proline concentration, elevated antioxidant enzyme activities, decreased Cu concentration in leaves, and increased Cu concentration in roots, increased photosynthetic parameters, and an increased in the total biomass. In contrast, additions of GA3 at concentrations higher than 40 mg L-1 intensified oxidative damage and decreased the activities of antioxidant enzymes, photosynthetic parameters, and biomass. Additionally, the Cu concentration increased in leaves and decreased Cu concentration in roots, indicating that high concentrations of GA3 aggravated stress damage and severely influenced physiological functions in spinach seedlings. In summary, the application of 3-5 mg L-1 GA3 to spinach seedlings in Cu-contaminated soil can be used to reduce Cu toxicity to plants and increase Cu tolerance.

Mining miRNAs' Expressions in Glioma Based on GEO Database and Their Effects on Biological Functions.

PURPOSE: To mine miR expression in glioma based on the Gene Expression Omnibus (GEO) database and to explore its effects on biological functions. METHODS: Differentially expressed miRs in glioma-related chips were found out based on the GEO database. Fifty patients with glioma treated in our hospital from February 2012 to July 2013 (observation group, OG) and a further 50 healthy people undergoing physical examinations (control group, CG) were enrolled. miR-873-5p expression in serum and in U87, T98G, U251, LN-229, and HEK-293T cells was tested by qRT-PCR. T98G and U251 cells were transfected with miR-873-5p-mimics and miR-NC sequences. The expression in the two cells was also tested by qRT-PCR. The proliferation, invasion, and apoptosis of the transfected cells were, respectively, tested by MTT assay, Transwell, and flow cytometry. The patients were followed up for 5 years to observe their survival. RESULTS: miR-873-5p expression in OG was remarkably higher than that in CG (p < 0.001). miR-873-5p was closely correlated with the tumor diameter, lymph node metastasis, and TNM staging of the patients (p < 0.05). According to the plotted receiver operating characteristic (ROC) curves, the areas under the curves (AUCs) of miR-873-5p for diagnosing the disease, tumor diameter, lymph node metastasis, and TNM staging were 0.842, 0.706, 0.865, and 0.793, respectively. The 5-year and recurrence-free survival rates in the low expression group were lower than those in the high expression group. According to multivariate Cox regression analysis, tumor diameter, lymph node metastasis, and miR-873-5p were independent prognostic factors for the disease. After transfection, compared with those in the miR-NC group, T98G and U251 cells in the miR-873-5p-mimic group had remarkably higher miR-873-5p expression (p < 0.05), remarkably lower proliferation and invasion rates (p < 0.05), and a remarkably higher apoptotic rate (p < 0.05). CONCLUSIONS: miR-873-5p can inhibit glioma cells to proliferate and invade, and promote their apoptosis, so it is expected to become a potential diagnostic index and therapeutic target for glioma.