Current Issue : April - June Volume : 2019 Issue Number : 2 Articles : 5 Articles
RNA-binding proteins (RBPs) lie at the center of posttranscriptional regulation and the\ndysregulation of RBPs contributes to diabetes. Therefore, the modulation of RBPs is anticipated\nto become a potential therapeutic approach to diabetes. CYC27 is a synthetic derivative of marine\nbromophenol BDB, which is isolated from red alga Rhodomela confervoides. In this study, we found\nthat CYC27 significantly lowered the blood glucose levels of diabetic BKS db mice. Moreover, CYC27\neffectively ameliorated dyslipidemia in BKS db mice by reducing their total serum cholesterol (TC)\nand triglyceride (TG) levels. Furthermore, CYC27 was an insulin-sensitizing agent with increased\ninsulin-stimulated phosphorylation of insulin receptors and relevant downstream factors. Finally, to\nsystemically study the mechanisms of CYC27, label-free quantitative phosphoproteomic analysis was\nperformed to investigate global changes in phosphorylation. Enriched GO annotation showed that\nmost regulated phosphoproteins were related to RNA splicing and RNA processing. Enriched KEGG\nanalysis showed that a spliceosome-associated pathway was the predominant pathway after CYC27\ntreatment. Protein-protein interaction (PPI) analysis showed that CYC27 modulated the process of\nmRNA splicing via phosphorylation of the relevant RBPs, including upregulated Cstf3 and Srrt. Our\nresults suggested that CYC27 treatment exerted promising anti-diabetic effects by sensitizing the\ninsulin signaling pathways and modulating RNA splicing-associated RBPs....
Background: Hyperpigmentation disorders such as post-inflammatory hyperpigmentation are major concerns not\nonly in light-skinned people but also in Asian populations with darker skin. The anti-tyrosinase and immunomodulatory\neffects of sericin have been known for decades. However, the therapeutic effects of sericin on hyperpigmentation\ndisorders have not been well documented.\nMethods: In this study, we used an in vitro model to study the anti-tyrosinase, tolerogenic, and anti-melanogenic\neffects of sericin on Staphylococcus aureus peptidoglycan (PEG)-stimulated melanocytes, dendritic cells (DCs), and\nartificial skin (MelanoDerm). Enzyme-linked immunosorbent assay, conventional and immunolabeled electron\nmicroscopy, and histopathological studies were performed....
Importance\nFor nearly a century, no generic form of insulin has been available in the United States.\nHowever, the first biosimilar insulin, Basaglar, was approved by the U.S. Food and Drug\nAdministration in 2015, and subsequently Admelog and Lusduna in 2017.\nObjective\nTo summarize the scientific evidence comparing the safety, efficacy, pharmacokinetics, and\npharmacodynamics of biosimilar and reference insulin products.\nData sources\nWe conducted a systematic review using PubMed, Cochrane, Embase, Latin America and\nCaribbean Health Sciences, South Asian Database of Controlled Clinical Trials, and\nIndiaMED from their inception through January 14, 2018.\nStudy selection\nWe included randomized controlled trials (RCTs) comparing safety, clinical efficacy, pharmacokinetics\nand pharmacodynamics of any biosimilar insulin with a reference product in\nadults regardless of sample size and location.\nData extraction and synthesis\nTwo researchers independently reviewed all titles, abstracts and text; extracted data; and\nperformed quality assessments.\nMain outcomes and measures\nEfficacy, safety, pharmacokinetics, and pharmacodynamics of biosimilar and reference\ninsulin products\nResults\nOf 6945 articles screened, 11 studies were included in the data synthesis. LY2963016,\nBasalog, Basalin, and MK-1293 were compared to Lantus while SAR342434 was compared\nto Humalog. Three trials enrolled healthy volunteers, five enrolled type 1 diabetics, and two\nenrolled type 2 diabetics. One study enrolled both healthy and type 1 diabetics. Of the\neleven studies, six examined pharmacokinetic and/or pharmacodynamic parameters and\nfive examined clinical efficacy and immunogenicity. All studies included adverse events. All\nPK and/or PD studies showed that comparable parameters of biosimilar and reference products\nwere within the pre-specified equivalence margins. Clinical studies suggested similar\nclinical efficacy and immunogenicity. Adverse events were similar between the groups\nacross all studies.\nConclusions and relevance\nFew published studies have compared biosimilar and reference insulins, though those that\ndid suggest that the biosimilars have comparable safety and clinical efficacy as its reference\nproduct....
Purpose: To compare the pharmacokinetics of APZ001 antibody with those of cetuximab (Erbitux®)\nand to evaluate the toxicology of the former.\nMethods: To evaluate cetuximabâ??s biosimilar APZ001, Crl:CD1(ICR) (CD-1) mice and Macaca\nfascicularis (cynomolgus monkey) were chosen for the studies on acute toxicity, chronic toxicity,\npharmacokinetics in chronic toxicity and immunogenicity toxicity. The study also compared the\npharmacokinetic parameters of APZ001 with those of cetuximab upon single and multiple drug\nadministrations in cynomolgus monkeys.\nResults: Pharmacokinetic parameters including maximum concentration (Cmax) and time to attain\nmaximum drug concentration (Tmax), clearance rate and apparent volume of distribution of APZ001 were\ncompared with those of cetuximab in both single and multiple administration studies. Difference of\npharmacokinetics from weekly administration of APZ001 and cetuximab in cynomolgus monkeys was\ninsignificant (p > 0.05), with relative bioavailability of 116.9 %. Both APZ001-treated and cetuximabtreated\nCD-1 mice showed the same level of food intake and body weight. Hematological and\nserological data were similar from APZ001 antibody and cetuximab treatments, so were the acute and\nchronic toxicity. Weekly transfusion of APZ001 did not alter its pharmacokinetic parameters. The\nadministered drug was hardly detected in the serum in the 31st and 37th week of recovery; no\naccumulation of drug was observed upon withdrawal.\nConclusion: APZ001 has extremely similar characteristics as cetuximab in terms of pharmacokinetics\nand toxicity....
The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs)\nshows great potential for intracellular delivery of DNA. Currently, its application is limited due\nto the potential toxicity and unknown long-term side effects. In this study NPs prepared using a\nbiodegradable polymer, poly(lactic-co-glycolic acid (PLGA) in association with a CPP, was assessed\non two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and\nnormal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular\ninternalization. No effects were observed on the mitochondrial activity and membrane integrity.\nCells exposed to the NPs-DNA-CPP showed low inflammatory response, low levels of apoptosis and\nno activation of caspase-3. Increase in necrotic cells (between 10%-15%) after 24 h of incubation and\nincrease in autophagy, induced by NPs-DNA-CPP, are likely to be related to the lysosomal escape\nmechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs-DNA-CPP\nshowed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential\nantioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for\nintracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be\nconducted in other lung-related systems to better understand its potential effects on the lungs....
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