Elevation of Glucose 6-Phosphate Dehydrogenase Activity Induced by Amplified Insulin Response in Low Glutathione Levels in Rat Liver

Weanling male Wistar rats were fed on a 10% soybean protein isolate (SPI) diet for 3 weeks with or without supplementing 0.3% sulfur-containing amino acids (SAA; methionine or cystine) to examine relationship between glutathione (GSH) levels and activities of NADPH-producing enzymes, glucose 6-phosphate dehydrogenase (G6PD) and malic enzyme (ME), in the liver. Of rats on the 10% SPI diet, GSH levels were lower and the enzyme activities were higher than of those fed on an SAA-supplemented diet. Despite the lower GSH level, γ-glutamylcysteine synthetase (γ-GCS) activity was higher in the 10% SPI group than other groups. Examination of mRNAs of G6PD and ME suggested that the GSH-suppressing effect on enzyme induction occurred prior to and/or at transcriptional levels. Gel electrophoresis of G6PD indicated that low GSH status caused a decrease in reduced form and an increase in oxidized form of the enzyme, suggesting an accelerated turnover rate of the enzyme. In primary cultured hepatocytes, insulin response to induce G6PD activity was augmented in low GSH levels manipulated in the presence of buthionine sulfoximine. These findings indicated that elevation of the G6PD activity in low GSH levels was caused by amplified insulin response for expression of the enzyme and accelerated turnover rate of the enzyme molecule

Mixed HCV Infection of Genotype 1B and Other Genotypes Influences Non-response during Daclatasvir + Asunaprevir Combination Therapy

Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing. HCV genotypes were determined by PCR with genotype-specific primers targeting HCV core and NS5B regions. SVR was achieved in 91.1% of patients. Female sex, age > 70 years, and RAVs were significantly associated with non-SVR (p<0.01 for all). Propensity score-matching results among the patients without RAVs regarding sex, age, and fibrosis revealed that mixed HCV infection determined by HCV NS5B genotyping showed significantly lower SVR rates than 1B-mono infection (p=0.02). Female sex and RAVs were significant factors associated with treatment failure of this combination therapy for patients with HCV serogroup 1 infection. Mixed HCV infection other than 1B-mono infection would be useful for predicting treatment failure

Magnetically Responsive Assemblies of Polymer-Brush-Decorated Nanoparticle Clusters That Exhibit Structural Color

The development of new magnetic materials for applications such as magnetic-driven drug delivery, next-generation display materials, and magnetic resonance imaging is an important objective. To that end, we synthesized monodispersed, magnetically responsive particles grafted with well-defined polymer brushes and investigated the formation of their ordered arrays in organic solvents in response to a magnetic field. To achieve this, we prepared monodispersed magnetic nanoparticle clusters (MNCs) composed of large numbers of superparamagnetic ferrite ZnFe₂O₄ nanoparticles. The MNCs were subsequently coated with thin silica layers through the hydrolysis of tetraethoxysilane. The colloidal particles were surface-modified with initiating groups for atom transfer radical polymerization (ATRP) using a triethoxysilane derivative with an ATRP initiation site. To demonstrate the ability of the synthesized particles to produce well-defined polymer brushes on their surfaces, the ATRP-initiator-functionalized silica-coated MNCs were subjected to surface-initiated ATRP with methyl methacrylate. This polymerization proceeded in a living fashion to produce graft polymers with targeted molar masses and narrow molar mass distributions. The average graft density was determined to be 0.65 chains/nm², which confirms the formation of concentrated polymer brushes on the MNCs. The hybrid particles were analyzed by dynamic light scattering and transmission electron microscopy techniques, which revealed excellent uniformity and solvent dispersibility. A suspension of the polymer-brush-decorated MNCs in acetone quickly developed intense structural color in response to approaching a magnet that depended on the strength of the magnetic field