Blandputnam5074

Furthermore, the specific transport pathways of bile acid in enterocytes are described and the recent finding of lymphatic delivery of bile acid-containing nanocarriers is discussed.The technology of directing nanoparticles to specific locations in the body continues to be an area of great interest in a myriad of research fields. In the present study, we have developed nanoparticles and a method that allows the nanoparticles to move to specific sites by simultaneously utilizing the homing ability and magnetism of stem cells. Polymeric clustered SPIO (PCS) nanoparticles are composed of a superparamagnetic iron oxide nanoparticle (SPION) cluster core coated with poly lactic-co-glycolic acid (PLGA) and labeled with the fluorescent dye Cy5.5 for tracking. PCS is designed to be internalized by stem cells via endocytosis and then moved to the desired subcellular location through magnetism. Here, we investigated the interactions between SPIONs and mesenchymal stem cells (MSCs), including their absorption mechanism and subcellular localization. Exposure to the nanoparticles at 40 μg/mL for over 96 h did not affect cell survival or differentiation. We used a variety of endocytosis inhibitors and identified the potential cellular internalization pathway of SPIONs to be clathrin-mediated endocytosis. Antibodies to organelles were used to accumulate lysosomes through early and late endosomes. PCS at 40 μg/mL was internalized and stored without significant deleterious effects on stem cells, indicating that MSCs can act as an effective nanoparticle carrier. These findings also demonstrate the successful localization of the novel particles using magnetic attraction.p53 is a tumor suppressor protein with a very low content in the basal condition, but the content rapidly rises during stress conditions including ischemia-reperfusion. An increase in p53 content increases cardiac injury during ischemia-reperfusion. Since mitochondrial damage plays a key role in cardiac injury during ischemia-reperfusion, we asked if genetic ablation of p53 decreases cardiac injury by protecting mitochondria. Isolated, perfused hearts from cardiac specific p53 deletion or wild type underwent 25 min global ischemia at 37 °C and 60 min reperfusion. Angiogenesis inhibitor At the end of reperfusion, hearts were harvested for infarct size measurement. In separate groups, cardiac mitochondria were isolated at 30 min reperfusion. Time control hearts were buffer-perfused without ischemia. Compared to wild type, deletion of p53 improved cardiac functional recovery and decreased infarct size following ischemia-reperfusion. Oxidative phosphorylation was improved in p53 deletion mitochondria following ischemia-reperfusion compve stress and calpain activation during ischemia-reperfusion.Breast cancer as one of the most prevalent cancers has high morbidity and mortality. Very low-density lipoprotein receptor (VLDLR) is a multifunctional receptor which plays a principal role in the tumor development through affecting cell metastasis and proliferation. The VLDLR as a target for miRNA-4465 and miRNA-1297 was predicted using bioinformatics analysis. Tissue specimens of malignant (n = 50), benign (n = 35) and corresponding normal breast (n = 20) were considered to evaluate the expression of VLDLR using RT-qPCR and western blotting. The VLDL cholesterol (VLDL-C) levels were quantified using a colorimetric assay. The relative VLDLR expression was found in the malignant tumors, which was significantly lower than that in the normal tissues (P0.05). The expression levels of VLDLR in E+P-H- (ER+,PR-,HER2-) tumors were higher than those in other subtypes (P less then 0.05). Furthermore, a negative correlation was found between the VLDLR expression level and the Ki 67% score. These data revealed that the lower expression of VLDLR mediated by the high expression levels of miRNA-4465 may be involved in the development of breast cancer. These results might provide some evidence for the effect of VLDLR on the breast cancer.The biosynthesis of berberine alkaloids is thought to begin with the demethylation of berberine followed by methylation reactions to generate other type berberine alkaloids. This seemingly expeditious way to access berberine alkaloids has been stagnated for over half a century due to certain vexing synthetic problems, such as low isolated yield, complex operations and toxic reagents. We further investigated this bioinspired semi-synthesis strategy and significantly improved the synthetic efficacy, by providing a practical synthetic process for demethyleneberberine (DMB), columbamine and palmatine. Furthermore, we found that DMB (IC50, 9.06 μM) inhibited the activity of monoamine oxidase B (MAO-B), an enzyme that deaminates dopamine and is particularly involved in the pathology of Parkinson's disease. Besides, columbamine was able to decrease MAO-B activity by approximately 40%. These findings provide perquisites for further in vivo investigation to confirm the therapeutic potentiality of berberine alkaloids, DMB in particular.The molecular mechanism responsible for hyperphosphorylated tau accumulation in dendrites of Alzheimer's disease (AD) neurons has not been fully clarified. Recently, we reported that tau mRNA is distributed into dendrites, and that translation and phosphorylation of tau protein are immediately enhanced in response to glutamatergic stimulation. Here, we focused on dendritic glycogen synthase kinase 3β (GSK3β), a key enzyme for tau phosphorylation, and investigated the mechanism responsible for the neural stimulation-induced hyperphosphorylation of the newly translated dendritic tau protein. We found that GSK3β mRNA was also distributed into dendrites of cultured hippocampal neurons, and that a glutamate-dependent slight increase of translation occurred in a short time. Concomitantly, dephosphorylation at the Ser9 residue of the preexisting GSK3β, which reactivates this kinase, was strongly induced without an increase of its phosphatase PP1 or a decrease of the PP1 inhibitor I-2. Instead, I-2 phosphorylation was observed, suggesting disinhibition of PP1. This glutamate-dependent phosphorylation of I-2 and the dephosphorylation of preexisting GSK3β were abolished in the presence of GSK3β inhibitors. Interestingly, translational obstruction of GSK3β mRNA also canceled these reactions. These results indicate that dendrites exhibit a glutamate-responsive cycle for amplification of reactivated preexisting GSK3β operating via PP1 disinhibition, whose activation requires neural activity-dependent translation of dendritic GSK3β mRNA. This would explain why a slight increase of dendritic GSK3β is sufficient to trigger hyperphosphorylation of significantly increased tau protein.