An animal's sex influences the effects of the excipient PEG 400 on the intestinal P-gp protein and mRNA levels, which has implications for oral drug absorption

There is a growing body of evidence which suggests that formerly regarded "inert" pharmaceutical excipients have the potential to influence oral drug bioavailability. The solubilizing agent polyethylene glycol 400 (PEG 400), for instance, has a sex-specific effect on P-glycoprotein (P-gp)-mediated drug bioavailability. We hypothesized that such an effect could be via PEG-induced alteration of P-gp activity and/or expression to different extents in males and females. To test this hypothesis in vivo, we investigated the influence of orally administered PEG 400 on the protein content and mRNA expression of P-gp in different regions of the gastrointestinal tract in male and female rats. Fasted rats received an oral dose of PEG 400 and at different time intervals, rats were sacrificed and their intestines were collected. The P-gp protein and mRNA expression in different intestinal segments (duodenum, jejunum, ileum and colon) were measured by Western blotting and PCR, respectively. It was found that P-gp protein and mRNA levels increased along the gastrointestinal tract in control animals (i.e. without PEG administration), and was higher in males compared to the female rats. The oral administration of PEG 400 decreased the P-gp expression in the jejunum, ileum and colon of males but not in the corresponding segments in females. This sex-dependent influence of PEG 400 on P-gp levels reflects and explains the sex-related effect of PEG 400 on oral absorption of certain drugs. The data further adds to the growing literature on the importance of taking into consideration an individual's sex for optimal drug administration

Lead halide perovskite nanowires stabilized by block copolymers for Langmuir-Blodgett assembly

The rapid development of solar cells based on lead halide perovskites (LHPs) has prompted very active research activities in other closely-related fields. Colloidal nanostructures of such materials display superior optoelectronic properties. Especially, one-dimensional (1D) LHPs nanowires show anisotropic optical properties when they are highly oriented. However, the ionic nature makes them very sensitive to external environment, limiting their large scale practical applications. Here, we introduce an amphiphilic block copolymer, polystyrene-block-poly(4-vinylpyridine) (PS-P4VP), to chemically modify the surface of colloidal CsPbBr3 nanowires. The resulting core-shell nanowires show enhanced photoluminescent emission and good colloidal stability against water. Taking advantage of the stability enhancement, we further applied a modified Langmuir-Blodgett technique to assemble monolayers of highly aligned nanowires, and studied their anisotropic optical properties. [Figure not available: see fulltext.]

P-glycoprotein expression in the gastrointestinal tract of male and female rats is influenced differently by food

The aim of this study was to explore the influence of food on P-glycoprotein (P-gp) relative expression in both male and female rats, and its effect on intestinal permeation of P-gp substrates (ranitidine and ganciclovir) and a P-gp non-substrate (metformin). The intestine of 12 male and 12 female Wistar rats were excised and segmented into the duodenum, jejunum, ileum and colon. P-gp extracted from each segment was then determined via Western-blotting. In male rats, the relative P-gp expression decreased significantly after food intake in all segments of the intestine except in the duodenum. The most notable change was demonstrated in the colon where relative expression decreased from 1.75 ± 0.36 in the fasted-state to 0.31 ± 0.15 in the fed-state. In female rats, a fundamentally different result was observed. Food ingestion resulted in a significant increase in relative P-gp expression in all regions of the intestine except in the colon. The largest difference was observed in the jejunum of the fed-state female rat intestine where P-gp expression was 1.76 ± 0.95 which was a six-fold increase from the fasted state at 0.34 ± 0.13. Intestinal permeation studies in an Ussing chamber showed that both ganciclovir and ranitidine exhibited a sex difference in intestinal permeability in the fasted-state. No sex differences and food effects were observed on metformin small intestine permeability. The permeability results of the three drugs highly supported that there was a sex-related food effect on P-gp function in the small intestine. In summary, the current study reports stark differences between male and female rats at a physiological level relating to P-gp expression and the influence of food

Flux pinning mechanism in BaFe1.9Ni0.1As2 single crystals: Evidence for fluctuation in mean free path induced pinning

The flux pinning mechanism of BaFe1.9Ni0.1As2 superconducting crystals have been investigated systematically by magnetic measurements up to 13 T at various temperatures. The field dependence of the critical current density, Jc, was analysed within the collective pinning model. A remarkably good agreement between the experimental results and theoretical dl pinning curve is obtained, which indicates that pinning in BaFe1.9Ni0.1As2 crystal originates from spatial variation of the mean free path. Moreover, the normalized pinning force density, Fp, curves versus h1/4B/Birr (Birr is the irreversibility field) were scaled using the Dew-Hughes model. Analysis suggests that point pinning alone cannot explain the observed field variation of Fp

Thermal Contraction of Electrodeposited Bi/BiSb Superlattice Nanowires

The lattice parameter of Bi/BiSb superlattice nanowire (SLNW) has been measured using in situ high-temperature X-ray diffraction method. The single crystalline Bi/BiSb SLNW arrays with different bilayer thicknesses have been fabricated within the porous anodic alumina membranes (AAMs) by a charge-controlled pulse electrodeposition. Different temperature dependences of the lattice parameter and thermal expansion coefficient were found for the SLNWs. It was found that the thermal expansion coefficient of the SLNWs with a large bilayer thickness has weak temperature dependence, and the interface stress and defect are the main factors responsible for the thermal contraction of the SLNWs

Prandial state and biological sex modulate clinically relevant efflux transporters to different extents in Wistar and Sprague Dawley rats

P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) are clinically relevant efflux transporters implicated in the oral absorption of many food and drug substrates. Here, we hypothesised that food intake could influence protein and mRNA intestinal expression of P-gp/abcb1a, BCRP/abcg2, and MRP2/abcc2 differently in male and female Wistar and Sprague Dawley rats. To test this hypothesis, we used enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) to quantify the protein and mRNA intestinal expression of these transporters, respectively. Our study found food and sex differences in P-gp expression, whereby in the fed state P-gp expression decreased in male Wistar rats, but P-gp expression increased in females. In the fed state, BCRP expression increased in both male and female Wistar rats, compared with the fasted state. In contrast, no sex differences or food effect differences were seen in Sprague Dawley rats for P-gp and BCRP expression. On the other hand, in the fed state, MRP2 expression was higher in male and female Wistar and Sprague Dawley rats when compared with the fasted state. Sex differences were also observed in the fasted state. Overall, significant strain differences were reported for P-gp, BCRP and MRP2 expression. Strong to moderate positive linear correlations were found between ELISA and PCR quantification methods. ELISA may be more useful than PCR as it reports protein expression as opposed to transcript expression. Researchers must consider the influence of sex, strain and feeding status in preclinical studies of P-gp, BCRP and MRP2 drug substrates

Exploring the antioxidant stability of sheep bone protein hydrolysate -identification and molecular docking

The aim of this study was to obtain sheep bone protein hydrolysates (SBPHs) with antioxidant activity from sheep bone byproducts and evaluate their stability and processing characteristics under different conditions. Then, the antioxidant peptides were identified and synthesized, and their antioxidant mechanism of action was investigated using molecular docking. The results showed that SBPHs obtained by alkaline protease hydrolysis had high antioxidant capacity and a high proportion of hydrophobic amino acids (41.33%). The antioxidant activity of SBPHs was intolerant to high temperatures and weakly resistant to acids and alkalis. NaCl improved the reducing power, sugars maintained the antioxidant activity, and metal ions reduced the antioxidant activity of SBPHs. SBPHs maintained higher antioxidant activity after simulated gastrointestinal digestion. Three fractions were isolated by ultrafiltration, among which P–I (MW 0.85 were found in P–I. Among the synthesized peptides, VYPFPGPIPN had the strongest antioxidant activity, which was mainly exerted through hydrogen bonding, π-π stacking and π-alkyl bonding with Keap1. This study provides a reference for subsequent studies on the production, storage and antioxidant function utilization of SBPHs

Enhancement of Critical Current Density in low level Al-doped MgB2

Two sets of MgB2 samples doped with up to 5 at. % of Al were prepared in different laboratories using different procedures. Decreases in the a and c lattice parameters were observed with Al doping confirming Al substitution onto the Mg site. The critical temperature (Tc) remained largely unchanged with Al doping. For 1 - 2.5 at.% doping, at 20K the in-field critical current densities (Jc's) were enhanced, particularly at lower fields. At 5K, in-field Jc was markedly improved, e.g. at 5T Jc was enhanced by a factor of 20 for a doping level of 1 at.% Al. The improved Jcs correlate with increased sample resistivity indicative of an increase in the upper critical field, Hc2, through alloying.Comment: 17 pages, 4 figures, to be published in Superconductor Science and Technolog