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Table of Content

    28 December 2019, Volume 28 Issue 12
    Original articles
    Synthesis of c-di-GMP analogs modified by ganciclovir and biological activity to induce type I interferon
    Hong Dai, Xiaotong Yu, Zhu Guan, Lihe Zhang, Zhenjun Yang
    2019, 28(12):  825-834.  DOI: 10.5246/jcps.2019.12.078
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    C-di-GMP is one kind of second messengers which plays an important role not only in the regulation of various bacterialphysiological activities but also in the activation of innate immune response to induce type I interferon in mammalian cells. In thisassay, by using one-pot phosphoramidite method, three novel kinds of analogs of c-di-GMP including its phosphorthiates modified by ganciclovir (7a, 7b, 7c) have been designed and synthesized. The immune-stimulatory results of these c-di-GMP analogs in RAW-Lucia ISG cells indicated that they couldn’t induce the release of type I interferon, which demonstrated that the intact structure of ribose moieties is very vital for their bioactivity upon the activation of STING signaling pathway.
    Two glucosylated angucyclines from deep-sea-derived Streptomyces sp. PKU-MA01297
    Xueyang Ma, Guiyang Wang, Zhongyi Zhang, Tongtong Geng, Xiaoxu Sun, Donghui Yang, Xixiang Tang, Ming Ma
    2019, 28(12):  835-842.  DOI: 10.5246/jcps.2019.12.079
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    Angucyclines are aromatic polyketides produced by type II polyketide synthase (PKS) exclusively from actinomycetes. These natural products contain hydrolyzable sugar moieties that attach to various positions of the polyketide skeleton and expand the structural diversity. We here report the isolation of two new angucyclines (1 and 2) from the deep-sea-derived Streptomycessp. PKU-MA01297, which was isolated from a sediment sample collected at a depth of 3202 meters from the Indian Ocean. The structures of the two new compounds were elucidated based on comprehensive methods, including NMR, MS and CD analysis. Compounds 1 and 2 featured a 1-O-β-d-glucopyranosyl moiety that has not been reported for angucyclines. Several biological activity assays, including antibacterial, cytotoxicity and anti-inflammatory assays, were carried out, and compounds 1 and 2 showed no activities. These results set the stage for biosynthetic research and more biological activity assays in the future.
    Comparative study on main compounds in Ginkgo biloba L. base on  mathematical statistics
    Yiyi Zhao, Ruyi Guo, Haili Yin, Xintong Fu, Yougen Chen, Hongzhu Guo
    2019, 28(12):  843-854.  DOI: 10.5246/jcps.2019.12.080
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    In this paper, an HPLC-DAD-ELSD method was developed to determine main 20 components of Ginkgo bilobaL. leaves from different ages and sources, including six flavonol glycosides, five terpene lactones and nine organic acids. Using statistics method and establishing relevant mathematics models, the measured data has proceeded correlation analysis, principal component analysis, and regression statistics and the results showed generality and specific characteristics. We defined p-hydroxybenzoicacid, catechinic, KRcG and ginkgolide A as characteristic indexes representing commonness and speciality of Ginkgo biloba L. leaf. The four characteristic indexes can reflect the quality of Ginkgo biloba L. leaf, and the internal relations between them are significant.The contents of other compounds could define the quantity relation with characteristic markers. It simplified the approach of quality control, and provided a basis for quality control of Ginkgo biloba L.
    Meta-analysis of the effect of statin use and pancreatic cancer risk
    Yao Song, Xiaofei Zhi, Hongyu Zhao, Xingqin Zhou, Wenjuan Chen, Naofumi Mukaida, Qing Lin, Bin Ji
    2019, 28(12):  855-867.  DOI: 10.5246/jcps.2019.12.081
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    Statin has been proposed to have a capacity to reduce the risk of pancreatic cancer, while the obtained results are notconsistent. To gain a clearer picture of the relationship between statin use and pancreatic cancer, the present meta-analysis took into consideration data from eight cohort studies, ten case-control studies and three RCTs.We searched all relevant studies on the effect of statin use on the risk of pancreatic cancer using PubMed, Embase and the Cochrane library database from inception to July 30, 2018. The following search terms were used: (1) statin (“statins”, “statin”, “3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors”, “atorvastatin”, “cerivastatin”, “fluvastatin”, “lovastatin”, “pravastatin”, “rosuvastatin”, “simvastatin”); (2) pancreatic cancer (“cancer”, “neoplasm”, “malignancy”). We manually examined the references of the relevant articles and reviews to identify additional studies. A total of 21studies, published between 2001 and July 2018 and involving 1 148 680 cases and 2 177 842 controls, fulfilled the selection criteria. The pooled results revealed a significant relationship between statin use andpancreatic cancer risk (OR = 0.84, 95% CI 0.72–0.98, P = 0.000, I2= 84.3%). However, lipophilic statins (OR = 1.07, 95% CI 0.97–1.18,P = 0.651, I2= 0.0%) had no significant effect on the risk of pancreatic cancer. In contrast, short-term statin use (OR = 0.72, 95% CI 0.54–0.96, P = 0.000, I2= 80.1%) and long-term statin use (OR = 0.70, 95% CI 0.54–0.92, P = 0.000, I2= 79.8%)significantly reduced pancreatic cancer risk. Notably, the high heterogeneity among the selected studies was eliminated by excluding the three studies that focused on restricted populations. Statin could significantly reduce the risk of pancreatic cancer.
    Quercetin-phospholipids complex solid dispersion and quercetin solid dispersion: preparation and evaluation
    Zhengsheng Liu, Haijun Hao, Mingsong Fan
    2019, 28(12):  868-877.  DOI: 10.5246/jcps.2019.12.082
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    Quercetin (QUE) has many beneficial biological activities and pharmacological actions in vitro. However, its oral bioavailability in vivo was very poor due to poor solubility, and severely restricted its clinical applications. In this study, we preparedquercetin solid dispersion (QUE-SD) and quercetin phospholipids complex solid dispersion (QUE-PC-SD) by a solvent evaporationmethod to improve the absorption of QUE in vivo. The results of XRD of QUE-SD and QUE-PC-SD showed that QUE was dispersed homogeneously in an amorphous or molecular state in QUE-SD and QUE-PC-SD, which could contribute to improve the solubility and dissolution of QUE. The solubility of QUE-SD and QUE-PC-SD was enhanced from (4.03±0.02) μg/mL to (26.91±0.06) μg/mL and (30.65±0.06) μg/mL, respectively. The solubility of QUE-PC-SD was higher than that of QUE-SD. In vitro dissolution study, it was showed that the maximum dissolution of QUE (9.57%) from the QUE-SD and QUE-PC-SD was enhanced to 93.81% and 94.16%, respectively. The results of pharmacokinetic experiment indicated that the QUE-SD and QUE-PC-SD exhibited considerable enhancement in the oral bioavailability. The relative bioavailability of QUE-SD and QUE-PC-SD compared with QUE were 149.49% and 198.32%, respectively. In addition, the relative bioavailability of QUE-PC-SD was also higher than that of QUE-SD. Therefore, in regard to drugs with poor solubility and low permeation, an active constituent-PC-SD system could result to a better absorption and higher bioavailability.
    Retrospect and reflection on the construction of large-scale technology platform of the State Key Laboratory of Natural and Biomimetic Drugs in 2018-2020
    Shuxiang Song
    2019, 28(12):  878-884.  DOI: 10.5246/jcps.2019.12.083
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    The State Key Laboratory of Natural and Biomimetic Drugs was approved for a funding of nearly 100 million yuan specifically aimed at the purchase and maintenance of equipment and instruments from 2018 to 2020, which is a record high. The Laboratory focuses on two major directions of scientific research, the basic scientific problems of drug resistance of complex components of natural products and the key biomimetic scientific problems of endogenous substances therapeutic functions. The selection of scientific instruments and equipment, trial production, upgrading, as well as high level of technical and managementpersonnel allocation and other aspects are critical to meet the development needs of the Key Laboratory and to maintain the advantages and leading role in these two major directions of scientific research.
    Others
    Small molecule, major functions: a new breakthrough in Nitrogenation reaction of Jiao Ning’s research team published in Science
    Shuxiang Song
    2019, 28(12):  885-888. 
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    Small molecule, major functions: a new breakthrough in Nitrogenation reaction of Jiao Ning’s research team published in Science.

    Contents of Volume 28
    Journal of Chinese Pharmaceutical Sciences
    2019, 28(12):  889-901. 
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    Keywords Index of Volume 28
    Journal of Chinese Pharmaceutical Sciences
    2019, 28(12):  902-905. 
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    Author Index of Volume 28
    Journal of Chinese Pharmaceutical Sciences
    2019, 28(12):  906-909. 
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    Acknowledgements
    Journal of Chinese Pharmaceutical Sciences
    2019, 28(12):  910-910. 
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