Influences of simulated gastrointestinal environment on physicochemical properties of gold nanoparticles and their implications on intestinal epithelial permeability

Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H₂O₂. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.     

Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

母亲龋易感性与婴儿口腔微生物多样性关系的纵向探究

目的通过检查有龋及无龋母亲的口腔卫生状况,并通过随访收集其婴儿1个月(1月龄)及6个月(6月龄)的唾液样本测序分析,观察母亲患龋情况对其婴儿口腔微生物多样性的影响。方法通过筛查收集1月龄婴儿的唾液样本;于首次采样时记录母亲的口腔卫生状况,根据母亲患龋情况将婴儿分为母亲有龋组(简称有龋组)和母亲无龋组(简称无龋组),跟踪随访至婴儿6个月时再次收集唾液样本。通过高通量测序的方法,分析婴儿不同月龄微生物多样性的变化。结果本研究随访受试者10例(男6例,女4例),其中有龋组7例,无龋组3例,各组间的微生物群落多样性Shannon指数均无显著性差异(P>0.05)。无龋组婴儿1月龄至6月龄时微生物群落的物种组成有较大变化;有龋组婴儿在1月龄和6月龄时组内各样本间物种组成均差异较大;1月龄时两组微生物群落较相似,而至6月龄时两组婴儿唾液的物种组成已开始发生变化。结论有龋组婴儿口腔内菌群多样性总体高于无龋组,在1月龄至6月龄间婴儿口腔内微生物物种的多样性及丰度均有了不同程度的提高。