8 research outputs found
Determination of bupropion and hydroxybupropion by LC-MS/MS in rat and its application to assessment of CYP2B6 activity
A selective and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for quantitation of bupropion (BUP) and its metabolite hydroxybupropion (HBUP) in rat plasma and urine using carbamazepine as an internal standard. Chromatographic separation was achieved on a SB-C18 column at 30 °C, using the gradient elution of 0.1 % formic acid in water and acetonitrile. Calibration plots were linear over range of 10-2000 ng/mL for BUP and 5-1000 ng/mL for HBUP in rat plasma. The intra- and inter-run relative standard deviations of the assay were less than 10 % for both BUP and HBUP. The effects of tolbutamide on cytochrome P450-mediated metabolism of BUP were studied by the validated method above. The results revealed that tolbutamide had signigicantly decreased the rate of BUP hydroxylation.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Efficacy and Safety of Wei Bi Mei, a Chinese Herb Compound, as an Alternative to Bismuth for Eradication of Helicobacter pylori
Bismuth-containing quadruple therapy has been recommended as the first line of treatment in areas of high clarithromycin or metronidazole resistance. However, safety concerns of bismuth agents have long been raised. We first assessed the efficacy and safety of Wei Bi Mei granules, which are bismuth compounds consisting of three synthetic drugs and five medicinal herbs, compared to bismuth aluminate and colloidal bismuth subcitrate (CBS) in H. pylori-infected mouse model. We then used atomic fluorescence spectroscopy and autometallography to measure the accumulation of three bismuth agents in the brain, heart, liver, and kidneys in adult Sprague-Dawley rats. We also evaluated the safety of bismuth agents by conducting clinical biochemistry tests in blood samples of experimental animals. Wei Bi Mei granules exhibited the highest efficacy of anti-H. pylori activity and yielded the lowest bismuth accumulation when compared to CBS and bismuth aluminate. Our findings show that Wei Bi Mei granules are a safe Chinese medicinal herb with potent anti-H. pylori activity and can be considered as an alternative to current bismuth compounds. Thus, Wei Bi Mei granules merit further evaluation, particularly with regard to efficacy and safety when they are combined with other H. pylori eradication medications in the clinical setting
Integration of multiomic annotation data to prioritize and characterize inflammation and immune-related risk variants in squamous cell lung cancer
Clinical trial results have recently demonstrated that inhibiting inflammation by targeting the interleukin-1β pathway can offer a significant reduction in lung cancer incidence and mortality, highlighting a pressing and unmet need to understand the benefits of inflammation-focused lung cancer therapies at the genetic level. While numerous genome-wide association studies (GWAS) have explored the genetic etiology of lung cancer, there remains a large gap between the type of information that may be gleaned from an association study and the depth of understanding necessary to explain and drive translational findings. Thus, in this work we jointly model and integrate extensive multi-omics data sources, utilizing a total of 40 genome-wide functional annotations that augment previously published results from the International Lung Cancer Consortium (ILCCO) GWAS, to prioritize and characterize single nucleotide polymorphisms (SNPs) that increase risk of squamous cell lung cancer through the inflammatory and immune responses. Our work bridges the gap between correlative analysis and translational follow-up research, refining GWAS association measures in an interpretable and systematic manner. In particular, re-analysis of the ILCCO data highlights the impact of highly-associated SNPs from nuclear factor-κB signaling pathway genes as well as major histocompatibility complex mediated variation in immune responses. One consequence of prioritizing likely functional SNPs is the pruning of variants that might be selected for follow-up work by over an order of magnitude, from potentially tens of thousands to hundreds. The strategies we introduce provide informative and interpretable approaches for incorporating extensive genome-wide annotation data in analysis of genetic association studies
Resveratrol ameliorates triglyceride accumulation through FXR deacetylation in high glucose-treated HepG2 cells
Hepatic lipid accumulation promotes the development of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. Sirt1, an NAD+-dependent histone deacetylase, plays a crucial role in NAFLD pathogenesis by regulating glycolipid metabolism. This study aims to evaluate the hepatoprotective effects and underlying mechanisms of resveratrol in T2DM-induced hepatic lipid accumulation. In vitro analysis of Sirt1 expression was conducted in high glucose (HG) -cultured HepG2 cells. It was observed that resveratrol (20 μM) significantly counteracted the triglyceride deposition and lipid droplet accumulation induced by the silencing of Sirt1. Further mechanistic studies attributed this benefit to the inhibition of FXR acetylation through upregulation of Sirt1. Notably, this hepatoprotective effect was abrogated upon the silencing of FXR. Overall, resveratrol reduced HG-induced lipid deposition by regulating the Sirt1-mediated deacetylation of FXR. The findings support the clinical potential of resveratrol in managing or preventing T2DM-induced hepatic steatosis
A bio-based hyperbranched flame retardant towards the fire-safety and smoke-suppression epoxy composite
The design of fully biological flame retardants is vital for environment-friendly and sustainability development. Herein, a fully biological hyperbranched flame retardant named PA-DAD was synthesized successfully through a simple neutralization reaction between 1,10-Diaminodecane (DAD) and phytic acid (PA). PA-DAD as a kind of reactive flame retardant was subsequently employed to composite with epoxy resin (EP). The obtained EP composite, comprising 25 wt% PA-DAD, exhibited excellent flame resistance with an appreciative limiting oxygen index (LOI) of 28.0%, and a desired V-0 rating of UL-94. The favorable attributes stem from the evident flame-retardant characteristics of PA-DAD, manifesting particularly within the gaseous and condensed phases of combustion. Benefitting from the PA-DAD with the synergetic effect of smoke suppression and flame resistance, the EP/25% PA-DAD composite displayed highlighted reductions both in smoke production and heat release rate. In contrast with neat EP, total smoke production (TSP), peak smoke production release (pSPR), the peak heat release rate (pHRR), and the rate of fire growth (FIGRA) of the EP/25% PA-DAD composite were decreased by 49.5%, 57.0%, 72.2% and 77.8%, respectively. Moreover, the EP/25% PA-DAD composite resulted in well-preserved mechanical properties, especially enhanced toughness, compared with the neat EP. The strategies in our work provided a facile, green, and highly efficient way for fabricating high fire-retardant EP composites
Inhibitory effects of HNF4α on migration/maltransformation of hepatic progenitors: HNF4α-overexpressing hepatic progenitors for liver repopulation
Abstract Background Although they are expandable in vitro, hepatic progenitors are immature cells and share many immunomarkers with hepatocellular carcinoma, raising potential concerns regarding maltransformation after transplantation. This study investigated the effects of hepatic nuclear factor (HNF) 4α on the proliferation, migration, and maltransformation of hepatic progenitors and determined the feasibility of using these manipulated cells for transplantation. Methods The effects of HNF4α on rat hepatic progenitors (i.e. hepatic oval cells) were analyzed by HNF4α overexpression and HNF4α shRNA. Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice injured by carbon chloride (CCl4) were then transplanted with control, HNF4α-overexpressing or HNF4α-suppressing hepatic oval cells. Finally, the engraftment of these cells in the recipient liver was analyzed. Results Rat hepatic progenitors (i.e. hepatic oval cells) expressed HNF4α, although less than that in hepatocytes. When HNF4α was overexpressed in these cells, the proliferation and migration of hepatic oval cells were reduced; but when HNF4α was suppressed by shRNA, the proliferation and migration, and even anchorage-independent growth, of these cells were accelerated. RNA microarray and gene functional analysis revealed that suppressing HNF4α not only impaired many biosynthesis and metabolism pathways of hepatocytes but also increased pathways for cancer. When transplanted into CCl4-injured NOD/SCID mice, few HNF4α-suppressing hepatic oval cells localized into the liver, while control cells and HNF4α-overexpressing cells engrafted into the liver and differentiated into albumin-positive hepatocytes. Interestingly, the hepatocytes derived from HNF4α-overexpressing cells were less migrative and expressed less c-Myc than the cells derived from control cells. Conclusion HNF4α constrains proliferation, migration, and maltransformation of hepatic progenitors, and HNF4α-overexpressing hepatic progenitors serve as an optimal candidate for cell transplantation
Additional file 1: of Inhibitory effects of HNF4Îą on migration/maltransformation of hepatic progenitors: HNF4Îą-overexpressing hepatic progenitors for liver repopulation
Presents supplemental materials and methods. (DOCX 19Â kb