Paclitaxel and etoposide-loaded Poly (lactic-co-glycolic acid) microspheres fabricated by coaxial electrospraying for dual drug delivery

Abstract

In this study, we fabricated paclitaxel (PTX) and etoposide (ETP) loaded Poly (lactic-co-glycolic acid) (PLGA) microspheres with core–shell structures and particle sizes ranging from 1 to 4?µm by coaxial electrospraying. The microspheres were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM). The drug loading rate and entrapment efficiency of the microspheres were detected by high performance liquid chromatograph (HPLC). Moreover, the drug release profiles and degradation of drug-loaded PLGA microspheres in vitro were investigated, respectively. The distinct layered structure that existed in the manufactured core–shell microspheres can be observed by TEM. The in vitro release profiles indicated that the PLGA/PTX?+?ETP (PLGA/PE) microspheres exhibited the controlled release of two drugs in a sequential manner. Cell Counting Kit-8 was used to detect the toxic and side effects of the microspheres on bone tumor cells. PTX and ETP for combination drug therapy loaded microspheres had more cytotoxic effect on saos-2 osteosarcoma cells than the individual drugs. In conclusion, core–shell PLGA microspheres by electrospraying for combination drug therapy is promising for medicine applications, the PLGA/PE microspheres have some potential for osteosarcoma treatment.     

Determination of plasma antiglycan autoantibodies in patients with IgA nephropathy and the correlation with clinical characteristics

Objective To establish the measurement of IgA1 O-glycan-specific antiglycan autoantibodies in patients with IgA nephropathy (IgAN), and evaluate their role in the development and progression of IgAN. Methods In the IgAN regular follow-up cohort of Peking University Institute of Nephrology from January 2006 to December 2015, 170 patients drawn by stratified randomization were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma galactose-deficient IgA1 (Gd-IgA1) and antiglycan autoantibody (IgG and IgA1). The correlation between antiglycan autoantibodies and clinicopathological parameters was analyzed by linear correlation and multiple linear regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the value of plasma anti glycide antibodies in the diagnosis of IgAN. Results IgG and IgA1 antiglycan autoantibodies that specifically recognized Fab-hinge region (Fab-HR) antigens could be detected in both IgAN and healthy control group. Agglutinin inhibition test showed that the specific antigen epitope was N-acetylgalactosamine (GalNAc) residue exposed to galactose deficiency in IgA1 hinged region. There was no significant difference in the absolute levels of plasma IgG antiglycan autoantibodies between IgAN and healthy controls (P=0.963). After adjustment of the plasma level of IgG, the normalized antiglycan autoantibody (ln[IgG antiglycan antibody/IgG]) in patients with IgAN was significantly higher than that in healthy controls (0.58±0.31 vs 0.37±0.11, P﹤0.01). The normalized level of IgG antiglycan autoantibody in IgAN patients was positively correlated with 24 h urine protein level during renal biopsy (Spearman r=0.183, P﹤0.05), and was also significantly correlated with 24 h urinary protein level after adjusting for baseline clinical and pathological factors (β=0.713, 95%CI 0.323-1.102, P﹤0.01). The area under ROC curve (AUC) of normalized IgG antiglycan autoantibody in the diagnosis of IgAN was 0.764 (95% CI 0.682-0.845, P﹤0.05). Using the cut-off value of 0.396, the sensitivity and specificity of normalized IgG antiglycan autoantibody for IgAN were 0.729 and 0.700 respectively. There was no significant difference in the absolute or normalized levels of IgA1 antiglycan autoantibodies between IgAN patients and healthy controls. Conclusions Gd-IgA1-specific antiglycan autoantibodies can be detected both in IgAN patients and healthy controls. They are elevated in some patients with IgAN and possibly involved in the development of IgAN.     

A Bayesian Meta-analysis Method for Estimating Risk Difference of Rare Events

Bayesian meta-analysis has been more frequently utilized for synthesizing safety and efficacy information to support landmark decision-making due to its flexibility of incorporating prior information and availability of computing software. However, when the outcome is binary and the events are rare, where event counts can be zero, conventional meta-analysis methods including Bayesian methods may not work well. Several methods have been proposed to tackle this issue but the prior knowledge of event rate was not utilized to increase precision of risk difference estimates. To better estimate risk differences, we propose a new Bayesian method, Beta prior BInomial model for Risk Differences (B-BIRD), which takes into account the prior information of rare events. B-BIRD is illustrated using a real data set of 48 clinical trials about a type 2 diabetes drug. In simulation studies, it performs well in low event rate settings.     

Effects of Polystyrene Microplastics on Growth and Toxin Production of Alexandrium pacificum

Microplastics (MP) widely distributed in aquatic environments have adverse effects on aquatic organisms. Currently, the impact of MP on toxigenic red tide microalgae is poorly understood. In this study, the strain of Alexandrium pacificum ATHK, typically producing paralytic shellfish toxins (PST), was selected as the target. Effects of 1 and 0.1 μm polystyrene MP with three concentration gradients (5 mg L⁻¹, 25 mg L⁻¹ and 100 mg L⁻¹) on the growth, chlorophyll a (Chl a), photosynthetic activity (F_v/F_m) and PST production of ATHK were explored. Results showed that the high concentration (100 mg L⁻¹) of 1 μm and 0.1 μm MP significantly inhibited the growth of ATHK, and the inhibition depended on the size and concentration of MP. Contents of Chl a showed an increase with various degrees after MP exposure in all cases. The photosynthesis indicator F_v/F_m of ATHK was significantly inhibited in the first 11 days, then gradually returned to the level of control group at day 13, and finally was gradually inhibited in the 1 μm MP treatments, and promotion or inhibition to some degree also occurred at different periods after exposure to 0.1 μm MP. Overall, both particle sizes of MP at 5 and 25 mg L⁻¹ had no significant effect on cell toxin quota, and the high concentration 100 mg L⁻¹ significantly promoted the PST biosynthesis on the day 7, 11 and 15. No significant difference occurred in the cell toxin quota and the total toxin content in all treatments at the end of the experiment (day 21). All MP treatments did not change the toxin profiles of ATHK, nor did the relative molar percentage of main PST components. The growth of ATHK, Chl a content, F_v/F_m and toxin production were not affected by MP shading. This is the first report on the effects of MP on the PST-producing microalgae, which will improve the understanding of the adverse impact of MP on the growth and toxin production of A. pacificum.     

Normal development of hindgut and anorectum in human embryo

Purpose  

The aim of the present analysis is to examine the morphological changes, the spatiotemporal distribution of apoptosis/proliferation in the human embryonic anorectum, to reveal the normal development of human anorectum, and investigate the possible roles of apoptosis/proliferation during anorectal development.