Liver-Derived Cell Transfection Model Efficacy for HBV Genotype B Replication/Transcription Is Determined by Complex Host Transcription Factor Network.

Background: Interaction between host transcription factors (TFs) and the viral genome is fundamental for hepatitis B virus (HBV) gene expression regulation. Additionally, the distinct interaction of the TFs' network with the HBV genome determines the regulatory effect outcome. Hence, different HBV genotypes and their variants may display different viral replication/transcription regulation.

The biochemistry and cell biology of aging: metabolic regulation through mitochondrial signaling.

Cellular and organ metabolism affects organismal lifespan. Aging is characterized by increased risks for metabolic disorders, with age-associated degenerative diseases exhibiting varying degrees of mitochondrial dysfunction. The traditional view of the role of mitochondria generated reactive oxygen species (ROS) in cellular aging, assumed to be causative and simply detrimental for a long time now, is in need of reassessment.

In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression.

Piperine, a major component of black pepper, is used as spice and nutrient enhancer. The purpose of the present study was to evaluate the effects of acute and prolonged piperine exposure on cellular P-gp expression and function in vitro and in vivo. Piperine at concentrations ranging from 10 to 100 microM, determined by MTT assay to be non-cytotoxic, was observed to inhibit P-gp mediated efflux transport of [(3)H]-digoxin across L-MDR1 and Caco-2 cell monolayers.

Induction of human sulfotransferase 1A3 (SULT1A3) by glucocorticoids.

Sulfotransferases (SULTs) play an important role in the detoxification and bioactivation of endogenous compounds and xenobiotics. Studies on rat sulfotransferases had shown that SULT genes, like cytochrome P450 genes, can be regulated by ligands that bind nuclear receptors. For human SULT genes, the regulation of human SULT2A1 expression is currently the best characterized.

Inhibition of enterovirus 71 in virus-infected mice by RNA interference.

Enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD) in young children. It is often associated with neurological complications and has caused high mortality levels in recent outbreaks in the Asia Pacific region. Currently, there is no effective antiviral therapy against EV71 infections.

Control of quorum sensing by a Burkholderia pseudomallei multidrug efflux pump.

The Burkholderia pseudomallei KHW quorum-sensing systems produced N-octanoyl-homoserine lactone, N-decanoyl-homoserine lactone, N-(3-hydroxy)-octanoyl-homoserine lactone, N-(3-hydroxy)-decanoyl-homoserine lactone, N-(3-oxo)-decanoyl-homoserine lactone, and N-(3-oxo)-tetradecanoyl-homoserine lactone. The extracellular secretion of these acyl-homoserine lactones is dependent absolutely on the function of the B. pseudomallei BpeAB-OprB efflux pump.

Traceless solid-phase synthesis and biological evaluation of purine analogs as inhibitors of multidrug resistance protein 4.

The traceless solid-phase syntheses of 6-oxopurines and pyrazolo[3,4-d]pyrimidines are presented. The effects of these compounds on multidrug resistance protein 4 (MRP4/ABCC4) facilitated efflux was examined. Four of the compounds, 7b, 7c, 15a, and 17e, were active in inhibiting MRP4-mediated efflux of the bimane-glutathione conjugate.

Enhanced potency and efficacy of 29-mer shRNAs in inhibition of Enterovirus 71.

Enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD) in young children. It has been associated with severe neurological complications and has caused significant mortalities in large-scale outbreaks in Asia. In this study, we demonstrated an enhanced silencing of EV71 through the use of chemically synthesized 29-mer shRNAs.

Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats.

The aim of this study was to evaluate whether curcumin could modulate P-glycoprotein (P-gp) and CYP3A expression, and in turn modify the pharmacokinetic profiles of P-gp and CYP3A substrates in male Sprague-Dawley rats. Intragastric gavage of the rats with 60 mg/kg curcumin for 4 consecutive days led to a down-regulation of the intestinal P-gp level. There was a concomitant upregulation of hepatic P-gp level, but the renal P-gp level was unaffected.

Effects of capsaicin on P-gp function and expression in Caco-2 cells.

Capsaicin is the pungent component of hot chilli, a popular spice in many populations. The aim of the present study was to evaluate the chronicity and reversibility of the modulating effect of capsaicin on both the P-gp expression and activity in the Caco-2 cell monolayers. Capsaicin at concentrations ranging from 10 to 100 microM, which were found to be non-cytotoxic towards the Caco-2 cells, were observed to inhibit P-gp mediated efflux transport of [3H]-digoxin in the cells.

Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents.

Current treatments for chronic hepatitis B virus (HBV) infection include the use of interferon-alpha and of nucleoside analogs lamivudine, adefovir and entecavir. However, the use of interferon-alpha has many side effects while that of nucleosidic inhibitors can lead to the emergence of resistant viruses. Hence, new drugs for the treatment of HBV infection are still highly desired.

Expression patterns of cytokine, growth factor and cell cycle-related genes after partial hepatectomy in rats with thioacetamide-induced cirrhosis.

Aim: To examine the differences in the responses of normal and cirrhotic livers to partial hepatectomy in relation to the factors influencing liver regeneration.

Methods: Cirrhosis was induced in rats by administration of thioacetamide. Untreated rats were used as controls.

Topotecan is a substrate for multidrug resistance associated protein 4.

Topotecan (TPT) is a semisynthetic water-soluble derivative of camptothecin (CPT) used as second-line therapy in patients with metastatic ovarian carcinoma, small cell lung cancer, and other malignancies. However, both dose-limiting toxicity and tumor resistance hinder the clinical use of TPT. The mechanisms for resistance to TPT are not fully defined, but increased efflux of the drug by multiple drug transporters including P-glycoprotein (PgP), multidrug resistance associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) from tumor cells has been highly implicated.

Are in vitro hepatitis B core promoter mutations important for clinical alterations in viral load?

In vitro studies of HBV core promoter mutations in hepatoma cell lines suggest that some mutations in core promoter transcription factor binding sites result in reduced core promoter activity and viral replication. We sought to validate this hypothesis using clinical samples with viral load differences before and after HBeAg seroconversion. A consensus sequence for transcription factor binding sites/regulatory regions was constructed based on published studies.

Human multidrug resistance associated protein 4 confers resistance to camptothecins.

Purpose: The multidrug resistance associated protein (MRP) 4 is a member of the adenosine triphosphate (ATP)-binding cassette transporter family. Camptothecins (CPTs) have shown substantial anticancer activity against a broad spectrum of tumors by inhibiting DNA topoisomerase I, but tumor resistance is one of the major reasons for therapeutic failure. P-glycoprotein, breast cancer resistance protein, MRP1, and MRP2 have been implicated in resistance to various CPTs including CPT-11 (irinotecan), SN-38 (the active metabolite of CPT-11), and topotecan.

RNA interference against enterovirus 71 infection.

Enterovirus 71 (EV71) is a highly infectious major causative agent of hand, foot, and mouth disease (HFMD) which could lead to severe neurological complications. There is currently no effective therapy against EV71. In this study, RNA interference (RNAi) is employed as a therapeutic approach for specific viral inhibition.

Intracellular inhibition of hepatitis B virus S gene expression by chimeric DNA-RNA phosphorothioate minimized ribozyme.

Chronic hepatitis B virus (HBV) infection is a major problem in Asia. Current therapies for chronic hepatitis B have limited efficacy. The successful use of ribozymes for intracellular inhibition of HBV gene expression was recently reported.