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Table of Content

    28 September 2016, Volume 25 Issue 9
    Cancer prevention by traditional Chinese medicine and plant phytochemicals column
    Prostate cancer and chemoprevention by natural dietary phytochemicals
    Asia Abed Al-Mahmood, Limin Shu, Hyuck Kim, Christina Ramirez, Douglas Pung, Yue Guo, Wenji Li, Ah-Ng Tony Kong
    2016, 25(9):  633-650.  DOI: 10.5246/jcps.2016.09.071
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    Prostate cancer is the second leading cancer among men in the United States. Several studies have correlated the development of prostate cancer with diet and life-style. Therefore, a balanced diet and improved life style might inhibit prostate cancer progression. Cancer chemoprevention has emerged as an important factor in controlling cancer development through natural or synthetic compounds. Oxidative stress is among the factors contributing to prostate cancer development. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) controls detoxifying antioxidant enzymes expression by binding to the antioxidant response element (ARE) in the promoter of these genes to activate their expression. Many natural products can fight oxidative stress and protects cells from DNA damage by activating the Nrf2/ARE pathway. High consumption of fruits and vegetables can reduce disease incidence and invasive tumors.  In this review, the roles of important fruit and vegetable phytochemicals in regulating prostate cancer progression and tumor growth are discussed.  
    Original articles
    The adsorption of cellular proteins affects the uptake and cellular distribution of gold nanoparticles
    Mengmeng Qin, Yifan Li, Bing He, Bei Wei, Wenbing Dai, Hua Zhang, Xueqing Wang, Qiang Zhang
    2016, 25(9):  651-659.  DOI: 10.5246/jcps.2016.09.072
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    Nanotechnology has been widely used in the field of medicine, and it can significantly improve the bioavailability and the target efficiency of medicines. However, after administration, nanomedicines can adsorb biomolecules that can influence their effects. It was reported that the adsorption of plasma proteins can change the surface properties of nanoparticles. When nanoparticles pass through cells, they may carry some cellular proteins out of cells. Currently, it is unclear whether the adsorbed proteins affect the uptake of nanoparticles in the next cell layer. To simplify this complex biological process, BSA-capped gold nanoparticles were prepared and incubated with Caco-2 cell lysate to simulate conditions of transcytosis through epithelial cells. The surface morphology of nanoparticles was examined by TEM. SRB was used to evaluate the cytotoxicity of the nanoparticles. The uptake and cellular distribution of the nanoparticles were detected by ICP-MS and CLSM. The results suggested that the adsorption of cell proteins could enhance the adhesion and uptake of gold nanoparticles. The gold nanoparticles were mainly located in lysosomes, and there were some Lysate-capped AuNPs in the mitochondria whereas no BSA-capped AuNPs appeared there.

    In vitro comparative evaluation of three CLD/siRNA nanoplexes prepared by different processes
    Chong Qiu, Shihe Cui, Jing Sun, Jiancheng Wang
    2016, 25(9):  660-668.  DOI: 10.5246/jcps.2016.09.073
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    In this study, a gemini-like cationic lipid (CLD) was used as the carrier to study the complexation features of CLD/siRNA nanoplexes (CLD/siRNA NPs). Three types of CLD/siRNA nanoplexes (named as AT NPs, HT NPs and MT NPs) were prepared by different processes: AT method (mixing siRNA solution with preformed CLD nanoparticles), HT method (hydrating a CLD thin film with siRNA solution), and MT method (dropping an ethanolic solution of CLD into siRNA solution under sonication). The particle size, zeta potential, morphology, siRNA protection, cytotoxicity, cellular uptake, and targeted mRNA down-regulation were studied. At the optimal N/P ratio of 10, the sizes of the three CLD/siRNA NPs were MT NPs ((222.3±19.1) nm)> HT NPs ((105.7±1.31) nm)>AT NPs ((91.8±1.75) nm). Different nanostructures were formed despite the fact that they were composed of the same components. Furthermore, the TEM images indicated that different morphologies were found in the three NPs, indicating that the nanoplexes were assembled by different mechanisms. Among the three NPs, the cell uptake capacity were as follows: AT NPs>MT NPs>HT NPs, whereas the silencing levels on epidermal growth factor receptor (EGFR) in HeLa cells were MT NPs>AT NPs>HT NPs. Based on the above results, we hypothesized that the different preparation processes resulted in nanostructures with varying biological effects. Therefore, we believe that structural optimization of siRNA nanoplexes is essential in achieving better siRNA encapsulation, protection, and gene silencing efficiency.  

    Cheminformatics analysis of the Chinese National Compound Library of Peking University
    Jianxing Hu, Chuanyu Lv, Zhenming Liu, Liangren Zhang
    2016, 25(9):  669-675.  DOI: 10.5246/jcps.2016.09.074
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    The Chinese National Compound Library of Peking University (PKU-CNCL) is a new high-throughput screening collection aimed at driving precompetitive drug discovery and target validation, and is one of satellite libraries of the Chinese National Compound Library (CNCL). It is a chemical database containing binding, functional, and ADMET information for a large number of drug-like bioactive compounds. These data are manually abstracted from the primary literature on a regular basis, and further curated and standardized to maximize their quality and utility across a wide range of chemical biology and drug-discovery research problems. Currently, the database contains 54 000 bioactivity measurements for more than 100 000 compounds. Access, data downloads, and web services are available at: http://www.pkucncl.cn.

    Selective determination of tenofovir in human plasma by LC-MS-MS method
    Xiang Xie, Rui Zhou, Peigen Zhou, Peng Yu, Feng Gao
    2016, 25(9):  676-682.  DOI: 10.5246/jcps.2016.09.075
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    In the present study, we developed and validated a selective, specific and sensitive liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS/MS) method for the determination of tenofovir in human plasma. Entecavir was used as an internal standard, and plasma samples were prepared by solid-phase extraction performed on Phenomenex Strata cartridges (30 mg). The mobile phase consisted of 10 mM ammonium acetate in water and methanol (60:40, v/v). The chromatographic separation was performed isocratically on a Phenomenex C18 (4.6 mm×150 mm, 5 μm), and analytes were analyzed in multiple reaction monitoring (MRM) mode with positive electrospray ionization (ESI) interface using the respective [M+H]+ ions, m/z 288.2→m/z 176.1 for tenofovir and m/z 278.1→m/z 152 for entecavir. The calibration curve (r2 = 0.9962) of tenofovir was established within the range of 4.096–1000 μg/L. The intra- and inter-day precisions were less than 10%. This validated method was successfully applied to a pharmacokinetic study in 12 healthy Chinese volunteers after the oral administration of tenofovir disoproxil fumarate.

    The effect of polymorphisms in STX4 on Warfarin dosage in Chinese cardiovascular disease patients
    Yatong Zhang, Xi Liang, Fan Dong, Zihui Zheng, Xin Hu
    2016, 25(9):  683-689.  DOI: 10.5246/jcps.2016.09.076
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    VKORC1 and CYP2C9 have been shown to be strongly associated with Warfarin dosing. However, it is still unclear whether other common genetic variants also contribute to the variation in Warfarin dosing. In the present study, we aim to investigate possible effects of single nucleotide polymorphisms (SNPs) in other candidate genes (CYP4F2, CACNA1C and STX4), as well as several factors, on stable daily Warfarin dosage (DWMD) in Chinese cardiovascular disease patients. 207 cardiovascular disease patients treated with Warfarin were recruited from Beijing Hospital. DNA was extracted from the blood samples collected one day after Warfarin administration. Nine SNPs (i.e. rs9923231, rs9934438, rs7294, rs1799853, rs1057910, rs4086116, rs2108622, rs216013 and rs10871454 in five genes (i.e. VKORC1, CYP2C9, CYP4F2, CACNA1C and STX4) were analyzed using ligase detection reactions (LDR). Univariate analyses and multiple linear regression analyses were performed to analyze the associations between SNPs and other factors (i.e. body surface area (BSA), Statin medication) and DWMD. Four SNPs (i.e. rs9923231, rs9934438, rs7294 in VKORC1 and rs10871454 in STX4) had significant statistically effects on DWMD. The multiple linear regression model showed that rs10871454 in STX4, BSA, statin medication, and rs1057910 in CYP2C9 were the significant independent covariates of DWMD. SNP (rs10871454) in STX4 had the strongest effect on Warfarin dosing among the examined candidate genes, indicating that it might serve as a key genetic factor for prediciting the Warfarin maintenance dose in Chinese patients.

    Effect of Curcuma longa L. extract on the AP1 expression in rat cochlear fibroblasts under noise conditions
    Tengku Siti Hajar Haryuna, Ramsi Lutan, Faathir Agung Ainul Taufika, Ratna Anggraeni, Tengku Siti Harilza Zubaidah
    2016, 25(9):  690-694.  DOI: 10.5246/jcps.2016.09.077
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    Noise-induced cellular stress can cause damage to fibroblasts within the cochlear supporting tissues and lateral wall. In the present study, we aimed to evaluate the role of curcumin as the safe and effective therapeutic agent in the prevention and treatment of this condition according to the expression of activator protein-1 (AP1). A total of 24 Rattus norvegicus were randomly divided into four groups (n = 6). Group 1: control; group 2: noise (+); group 3: noise (+), 50 mg/day curcumin (+); group 4: noise (+), 100 mg/day curcumin (+). All groups (except for group 1) were subjected to a sound pressure level (SPL) of 100 dB for 2 h/day during 2 weeks. Curcumin used in this study was derived from Curcuma longa L. (Turmeric), and it was orally administered for 2 weeks. All samples were immunohistochemistrically examined for the expression of AP1 in cochlear fibroblasts. The results showed that there were significant differences for the AP1 expression (P<0.05) among all groups, except for between groups 1 and 3, or between groups 1 and 4. Our data proved that curcumin was potentially effective in the prevention and treatment of damage of fibroblasts within the cochlear supporting tissues and lateral wall due to the decreased AP1 expression following noise exposure.

    Drug administration column
    Regulation of online pharmacies in China: the current situation and suggested improvements
    Menglu Qi, Bo Gao, Fei Wang, Bin Jiang
    2016, 25(9):  695-699.  DOI: 10.5246/jcps.2016.09.078
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    Through literature research, expert investigation, and stakeholder interviews, this article summarizes related regulation policies and industry developments of China’s online pharmacies. Based on the main problems, suggestions to improve the regulatory policies of online pharmacies in China were put forward regarding prescriptions, pharmaceutical services, medical insurance, and drug delivery.          

    Short communication
    A new homoisoflavone compound as a potent antibacterial agent from Aspidistra typica Baill.
    Xiaoxia Liang, Lingxi Kong, Min He
    2016, 25(9):  700-703.  DOI: 10.5246/jcps.2016.09.079
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    A novel homoisoflavone typicalvone A (1), together with two known compounds, n-heneicosane and p-hydroxy benzoic acid, were isolated from Aspidistra typica Baill. The structure of the new compound was elucidated by sepctral techniques, viz. 1D, 2D NMR spectra and HR-ESI-MS. Compared with berberine hydrochloride, typicalvone A showed moderate anti-bacterial activities, especially against the Gram-negative Paeudomonas aeruginosa ATCC-9027 and Escherichia coli ATCC-25922, with MBC values of 1000 and 500 µg/mL, respectively. In addition, it exhibited weak inhibitory activities against the tumour cells.

    Other
    The 4th Cancer Chemoprevention Symposium, Beijing 2016—Cancer Chemoprevention by Dietary Phytochemicals and Traditional Chinese Medicines
    Simin Yang, Siwang Yu
    2016, 25(9):  704-706. 
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    On July 30–31, 2016, the 4th Cancer Chemoprevention Symposium, co-hosted by Peking University School of Pharmaceutical Sciences (PKUSPS) and the State Key Laboratory of Natural and Biomimetic Drugs (SKLNBD), and exclusively sponsored by Shenzhen Fushan Biotech Co. Ltd., was successfully held in Peking University Health Science Center (PKUHSC), to promote the academic communications among cancer chemoprevention researchers both in China and internationally, and to discuss the future direction of cancer chemoprevention studies in China. Cancer chemoprevention refers to the strategy to block, delay or reverse the process of carcinogenesis by using of natural or synthetic chemicals, and has attracted more and more research interests. China is facing a serious challenge from cancers, and has made significant contributions to cancer prevention research worldwide. “To cure the disease before it happens” has been a motto of traditional Chinese medicine for thousands of years, however, the chemoprevention studies in China are still lagging behind the needs of cancer control and international research community. To promote cancer chemoprevention researches in China, PKUSPS has organized the 1st and 2nd Cancer Chemoprevention Symposia in 2010 and 2012, respectively; the 3rd one was hosted by Jiangsu Academy of Traditional Chinese Medicine in Nanjing, 2014. PKUSPS also organized the 471st Xiangshan Science Conference of “Frontiers in Cancer Chemoprevention” in 2013, and the National Natural Science Foundation of China (NSFC) has set up a study section of “cancer chemoprevention” in 2012, and called a strategic symposium on “tumor chemoprevention” in 2016.