Search

Renal cell carcinoma (RCC) is a common malignant tumour affecting the urinary system, and multidrug resistance is one of the major reasons why chemotherapy for this type of cancer often fails. Previous studies have shown that loss of the human organic cation transporter OCT2 is the main factor contributing to oxaliplatin resistance in RCC, and that DNA hypermethylation and histone methylation play important roles in the transcriptional repression of OCT2 in RCC. In this study, we found that histone acetylation also regulates OCT2 repression in RCC and elucidated the underlying mechanisms. In normal renal cells, HDAC7 combines with MYC at the OCT2 promoter, resulting in a decrease in free HDAC7, which in turn increases the levels of H3K18ac and H3K27ac at the OCT2 promotor and activates OCT2 expression. In RCC cells, however, the interaction between HDAC7 and MYC does not occur, which leads a high abundance of HDAC7 and low levels of H3K18ac and H3K27ac at the OCT2 promoter, thereby resulting in the inhibition of OCT2 transcription. We found that combined treatment using the DNA methylation inhibitor decitabine and the histone deacetylase inhibitor vorinostat significantly increased the expression of OCT2 in RCC cell lines, which sensitized these cells to oxaliplatin. We accordingly propose that the combination of anticancer agents and epigenetic drugs can provide a novel chemotherapeutic regimen. [ABSTRACT FROM AUTHOR]

Multi-view texture classification is a very challenging task since the view-point variation often leads to the inconsistent local texton patterns. Existing studies focus on the extraction of scale, rotation or affine invariant representations by some specially designed invariant measurements or local descriptors. Differently, in this paper, we propose another framework for multi-view texture classification. A number of synthetic images are hierarchically created to enlarge the training dataset to cover the possible variations of different view-points. Then, a classifier based on random forests is trained based on these synthetic images. In the classification stage, we also create synthetic images for each testing image, and the synthetic images are classified with the pre-trained classifier. The final decision for this testing image is made by the majority voting of the classification results of all these synthetic images. The classification performance is evaluated on the UIUC texture dataset. Our method achieves the classification rate of 99.21 %, which is higher than most of the state-of-the-arts. [ABSTRACT FROM AUTHOR]

1. Cell models expressing human drug transporters and enzymes are useful tools to understand the process of drug dispositionin vitro. However, no study on transfected cells stably co-expressing human organic anion transporter 1 (hOAT1) and/or human cytochrome P450 1A2 (hCYP1A2) is available. In this study, cell models stably expressing hOAT1 and/or hCYP1A2 were established, and were used to investigate the interactions of ingredients of herbal medicines (IHMs) with hOAT1 and/or hCYP1A2. 2. The MDCK cells were stable transfected with recombinant plasmids expressing hOAT1 and/or hCYP1A2. Cellular uptake assay and CYP450 activity assay showed that the transfected cells were available. A marked high expression of hOAT1 and hCYP1A2 mRNA was also validated by quantitative RT-PCR. Totally 6 IHMs which significantly inhibited the activity of hOAT1 were screened out by employing hOAT1 expressing cells. The contribution of hOAT1 and hCYP1A2 to the toxicity of aristolochic acid I (AAI) was further determined. Compared to mock cells, all transfected cells showed a decrease in viability after being treated with AAI. 3. A method to establish transfected cell expressing drug metabolism enzymes and/or transporters was provided in our study. Three IHMs (dihydrotanshinone I, cryptotanshinone, and tanshinone I) were confirmed as novel inhibitors of hOAT1. Furthermore, a synergistic effect of hOAT1 and hCYP1A2 on AAI-induced toxicity was also observed in this investigation. [ABSTRACT FROM AUTHOR]

This article will report about a study that investigated how a group of elementary school teachers responded to a professional development training on Science and Technology as demonstrated in their perceived preparedness and comfort with teaching science, and their subsequent implementation with K-4 students. The results from the study may help K-4 teachers in schools and teacher education programs better understand how to prepare teachers to learn about Science and to integrate technology into their practice with K-4 students accordingly. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression. [ABSTRACT FROM AUTHOR]

1. In this article, metabolites of ginkgolic acid (GA) (15:1) in rats plasma, bile, urine and faeces after oral administration have been investigated for the first time by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) with the aid of on-line hydrogen/deuterium (H/D) exchange technique and β-glucuronidase hydrolysis experiments. 2. After oral administration of GA (15:1, M0) to rats at a dose of 10 mg/kg, it was found that metabolites M1-M5 together with parent compound (M0) existed in rat plasma; parent compound (M0) and metabolites M2-M5 were observed in rat bile, and parent compound (M0) with metabolites M1 and M2 were discovered in rat faeces, and there was no parent compound and metabolite detectable in rat urine. 3. Two oxidative metabolites of GA (15:1, M0) were identified as 2-hydroxy-6-(pentadec-8-enyl-10-hydroxy) benzoic acid (M1) and 2-hydroxy-6-(pentadec-8-enyl-11-hydroxy-13-carbonyl) benzoic acid (M2), respectively. Metabolites M3, M4 and M5 were identified as the mono-glucuronic acid conjugates of parent compound (M0), M1 and M2, respectively. 4. The results indicated that M1 and M2 with parent compound (M0) were mainly eliminated in faeces and three glucuronide metabolites (M3, M4 and M5) excreted in bile as the predominant forms after oral administration of GA (15:1) to rats. [ABSTRACT FROM AUTHOR]