Duusslot5851

Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization.

Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization.In this study, three different chitosan, namely carboxymethyl chitosan (CMC), hydroxypropyl chitosan (HPC) and trimethyl chitosan (TMC) were used as cationic materials to prepare tetrandrine lipid nanoparticles (TET-LNPs) for the treatment of glaucoma. In vitro drug release and pre-corneal retention were used to select the optimal chitosan. In vitro drug release curves of three kinds of LNPs showed a sustained release and TMC-TET-LNPs were the slowest. Moreover, compared with CMC-TET-LNPs and HPC-TET-LNPs, TMC-TET-LNPs had longer corneal retention time. Afterwards, the characteristics of TMC-TET-LNPs were investigated. The ocular irritation study revealed no sign of irritation in rabbit eyes. The pharmacokinetic studies showed that the area under the curve of TMC-TET-LNPs was increased by 2.03 times than TET solution (p less then 0.01). find more Furthermore, the drug biofilm interactions were evaluated by molecular dynamics (MD) simulation. In MD simulation, the strong hydrophobic group of TET interacted with the tail of POPC, making it hard to enter the hydrophobic region of the membrane, thereby restricting TET ocular bioavailability. The experiments and MD simulation indicated that TMC-TET-LNPs had great potential for ocular administration and MD simulation could predict transmembrane transport of drugs.P-glycoprotein (P-gp) efflux assay is an integral part of discovery screening, especially for drugs requiring brain penetration as P-gp efflux ratio (ER) inversely correlates with brain exposure. However, significant variability in P-gp ER generated across cell lines can lead to misclassification of a P-gp substrate and subsequently disconnect with brain exposure data. We hypothesized that the ER depends on P-gp protein expression level in the in vitro assay. Quantitative proteomics and immunofluorescence staining were utilized to characterize P-gp protein expression and localization in four recombinant cell lines, over-expressing human or mouse P-gp isoforms, followed by functional evaluation. Efflux data generated in each cell line was compared against available rodent brain distribution data. The results suggested that the cell line with highest P-gp expression (hMDCK-MDR1 sourced from NIH) led to greatest dynamic range for efflux; thus, proving to be the most sensitive model to predict brain penetration. Cell lines with lower P-gp expression exhibited the greatest tendency for compound-dependent in vitro efflux saturation leading to false negative results. Ultimately, P-gp kinetics were characterized using a compartmental model to generate system-independent parameters to resolve such discrepancy. This study highlights the need for careful choice of well characterized P-gp in vitro tools and utility of modeling techniques to enable appropriate interpretation of the data.Monoclonal antibodies requiring higher doses for exerting therapeutic effect but having lower stability, are administered as dilute infusions, or as two (low concentration) injections both resulting in reduced patient compliance. Present research summarizes impact of manufacturing conditions on ultra-high concentration (≥150 mg/mL) IgG1 formulation, which can be administered as one subcutaneous injection. IgG1 was concentrated to ~200 mg/mL using tangential flow filtration (TFF). Alternatively, spray dried (SPD) and spray freeze dried (SFD) IgG1, was reconstituted in 30%v/v propylene glycol to form ultra-high concentration (~200 mg/mL) injectable formulation. Reconstituted, SPD and SFD IgG1 formulations, increased viscosity beyond an acceptable range for subcutaneous injections ( less then 20 cP). Formulations developed by reconstitution of SPD IgG1, demonstrated increase in high and low molecular weight impurities, at accelerated and stressed conditions. Whereas, the stability data suggested reconstituted SFD IgG1 was comparable to control IgG1 formulation concentrated by TFF. Also, formulation of IgG1 diafiltered with proline using TFF, reduce viscosity from ~21.9 cP to ~11 cP at 25 °C and had better stability. Thus, conventional TFF technique stands to be one of the preferred methods for manufacturing of ultra-high concentration IgG1 formulations. Additionally, SFD could be an alternative method for long term storage of IgG1 in a dry powder state.Arbuscular mycorrhizal fungi (AMF) provide a positive effect on antioxidant mechanisms in terrestrial plants under heavy metal stress. This study investigated the effects of AMF on wetland plant (Iris wilsonii) growth and antioxidant response under Cr stress at different water depths. Results showed that AMF inoculated I. wilsonii had higher antioxidant response than non-inoculated controls, with shoot superoxide dismutase (SOD), root SOD, shoot peroxidase (POD), and root POD contents increased by 4.7-39.6%, 7.5-29.5%, 11.2-68.6%, 16.8-50.3%, respectively. Meanwhile, shoot (root) proline, malondialdehyde (MDA) and superoxide anion (O2.-) contents in the AMF inoculated I. wilsonii were 10.2-44.3% (2.8-37.2%), 11.5-35.4% (16.9-28.2), and 14.9-30.5% (-0.9-26.3%) lower than those in the non-inoculated controls, respectively. Besides, AMF improved the growth of I. wilsonii with biomass, height, chlorophyll, K, and P contents in the shoots increased by 10.5-32.5%, 17.4-44.9%, 4.7-37.7%, 12.0-30.7%, 13.5-20.6%, respectively. Moreover, the I. wilsonii tolerance to Cr stress was also enhanced under the water depth of 6-3 cm. Therefore, AMF play an important role in wetland plant growth and antioxidant response under Cr stress, and it can improve wetland plants' tolerance to Cr stress at fluctuating water depth.COVID-19 has been disturbing human society with an intensity never seen since the Influenza epidemic (Spanish flu). COVID-19 and Influenza are both respiratory viruses and, in this study, we explore the relations of COVID-19 and Influenza with atmospheric variables and socio-economic conditions for tropical and subtropical climates in Brazil. Atmospheric variables, mobility, socio-economic conditions and population information were analyzed using a generalized additive model for daily COVID-19 cases from March 1st to May 15th, 2020, and for daily Influenza hospitalizations (2017-2019) in Brazilian states representing tropical and subtropical climates. Our results indicate that temperature combined with humidity are risk factors for COVID-19 and Influenza in both climate regimes, and the minimum temperature was also a risk factor for subtropical climate. Social distancing is a risk factor for COVID-19 in all regions. For Influenza and COVID-19, the highest Relative Risks (RR) generally occurred in 3 days (lag = 3).