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    15 January 2015, Volume 24 Issue 1
    Review
    Environment-responsive drug delivery systems for targeted cancer therapy
    Chunmei Peng, Jie Shen, Weiyue Lu
    2015, 24(1):  1-11.  DOI: 10.5246/jcps.2015.01.001
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    In order to deliver and/or release anti-cancer therapeutics at the tumor sites, novel environment-responsive drug deliverysystems are designed to specifically respond to tumor microenvironment (such as low pH and hypoxia). Due to their extraordinary advantages, these environment-responsive drug delivery systems can improve antitumor efficacy, and most importantly, they can decrease toxicity associated with the anti-cancer therapeutics. This review highlights different mechanisms of environment-responsive drug delivery systems and their applications for targeted cancer therapy.

    Original articles
    Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma
    Sujit Nair, Celine Liew, Tin-Oo Khor, Li Cai, Ah-Ng Tony Kong
    2015, 24(1):  12-27.  DOI: 10.5246/jcps.2015.01.002
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    The incidence of prostate cancer is rising in the Asia-Pacific region as well as other countries. Androgen-ablation therapy is clinically useful in the androgen-dependent phenotype; however, many patients progress to hormone refractory prostate cancer that is difficult to treat and needs newer interventions that are more effective. The objective of this study was to determine functionally-relevant biological networks, to appreciate the potential crosstalk between signaling members, and to identify biomarker signatures in prostate cancer. We used microarray analyses to identify key genes that were upregulated or down regulated at least five-fold in human prostate cancer and constructed canonical interaction networks that are important in prostate cancer through metabolomics analyses. Our prostate cancer network architecture revealed several key biomarkers including ERK1/2, JNK, p38, MEK, PI3K, NFκB, AP-1, 14-3-3, VEGF, PDGF, Rb, WNT8A, WNT10A, CD44, ESR2, FSH and LH. Furthermore, the top ten transcription factors identified by TFBS-association signature analysis in the regulatory elements of co-regulated biomarkers were delineated, which may crosstalk with upstream or downstream genes elicited in our network architecture. Taken together, our results demonstrate that the regulatory interaction networks in prostate cancer provide a universal view of crosstalk between important biomarkers, i.e., key players in the pathogenesis of this disease. This will facilitate more rapid screening of functional biomarkers in early/intermediate drug discovery.

    Vanadium regulates HSP60-induced IL-6 release from RAW264.7 cells in a dose-dependent manner
    Wei Guo, Xiaoda Yang
    2015, 24(1):  28-33.  DOI: 10.5246/jcps.2015.01.003
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    Vanadium compounds are promising anti-diabetic agents. However, the underlying mechanisms have not been fully elucidated. Inflammation and auto-immune disorders play important roles in the progresses of both type I and type II diabetes, in which heat shock protein 60 (HSP60) is an important endogenous inflammatory mediator. In the present work, we investigated the effects of vanadium compounds (vanadyl sulfate and sodium metavanadate) on the IL-6 production in RAW264.7 cells upon HSP60 stimulation. Our data revealed that both vanadyl ions regulated the IL-6 expression in a concentration-dependent manner. However, the two common NF-κB and PPAR-γ signal pathways were not involved in this process. Further works are needed to elucidate the underlying mechanism and significance of the immuno-modification actions for the pharmacological applications of anti-diabetic vanadium compounds.

    Targeting glioblastoma cancer stem cell marker CD133 by heptapeptide-modified DSPE-PEG micelles
    Jingda Wang, Bing He, Wenbing Dai, Xueqing Wang, Jiancheng Wang, Xuan Zhang, Qiang Zhang
    2015, 24(1):  34-39.  DOI: 10.5246/jcps.2015.01.004
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    Cancer stem cells have become the new target of chemotherapy with specific cell marker. CD133 is shown to be highly expressed in glioma cancer stem cells. In this study, a drug delivery system is designed to target CD133 by a seven amino acid peptide (TR peptide), which is capable to specifically bind to CD133. First, TR was conjugated to DSPE-PEG and coumarin-6 was loaded into the DSPE-PEG micelles. Then fluorescence-activated cell sorting (FACS) and tumorsphere culture were conductedto isolate cancer stem cells in C6 cells. The enhanced uptake of micelles was observed by confocal microscopy and flow cytometry,suggesting that TR peptide-modified micelles may exhibit better anti-cancer efficacy by targeting CD133+ glioma stem cells. In conclusion, TR peptide-modified micelles may provide new strategy to achieve enhanced specificity to CD133+ glioma stem cells.

    Centrifugation-assisted preparation and thermostability of Form I clopidogrel hydrogen sulfate
    Ju Ao, Haitao Gao, Xiaoping Tang, Lan Zhou, Guoqing Zhang
    2015, 24(1):  40-46.  DOI: 10.5246/jcps.2015.01.005
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    Of all reported polymorphs of clopidogrel hydrogen sulfate, Form I is difficult to produce and store owing to its poor thermostability. It is reported that Form I can spontaneously transform into Form II at high temperature and humidity. In this study, high purity Form I of clopidogrel hydrogen sulfate with good thermodynamic stability was prepared by a centrifugation-assisted recrystallization technology. The resultant product was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscope (SEM). The results showed that the crystallinity and crystallite size of the Form I prepared by the centrifugation-assisted recrystallization method were larger than those obtained by conventional anti-solvent recrystallization methods. Long-term thermostability testing demonstrated that the improved product can keep stable crystal structure even at high temperature and humidity.

    Complexation of poorly aqueous soluble drug risperidone with hydroxypropyl-β-cyclodextrin enhances its dissolution
    Weina Ma, Fugen Gu, Yi Wang, Gendalai Meng, Chunzhi Wu
    2015, 24(1):  47-53.  DOI: 10.5246/jcps.2015.01.006
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    In the present study, we investigated the complexation of risperidonewith hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous solution due to the poor water solubility and low oral bioavailability of risperidone in humans. The effect of temperature on the complexation was examined, and thermodynamic parameters of the complexation process, such as Gibbs free energy changeG), enthalpy change (ΔH) and entropy change (ΔS),were also explored. Meantime, the solid dispersion of risperidonewith HP-β-CD was prepared and confirmed by Fourier IR spectroscopy and X-ray diffractometry. The experimental results suggested that the complex of the drugwith HP-β-CD at a molar ratio of 1:1 could form in aqueous solution, and the complexation was an endothermic and entropy-driven process. The risperidone-HP-β-CD solid dispersion exhibited a remarkable improvement in the dissolution rate of the drug.This might be attributed to the amorphous state, the enhanced wettability as well as the complex formation of the drug with HP-β-CD in aqueous solution.

    Effects of Salvia miltiorrhiza injectional powder on the development of liver fibrosis initiated by dimethylnitrosamine in rats
    Yingfan Yang, Yi Sun, Xin Zhao, Xiyuan Zheng, Xiaoping Pu
    2015, 24(1):  54-62.  DOI: 10.5246/jcps.2015.01.007
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    Salvia miltiorrhiza (Sm) is a traditional herbal medicine with multiple effects on various diseases. Its water-soluble parts have been used to produce injectional powder. In this study, liver fibrosis rats were induced by intraperitoneal injection of dimethylnitrosamine for 3 consecutive days per week for 4 weeks. After 2 weeks, rats in the positive drug group were subcutaneously injected with 8×105 IU/kg IFNα2b, while the Sm treatment groups were intraperitoneally injected with 50, 100 and 200 mg/kg solution of Sm injectional powder, respectively, for 6 days per week for 4 weeks. The results showed that either IFNα2b or the Sm injectional powder significantly increased the body weight and liver to spleen ratio, and three doses of the powder brought down the spleen index. Serum analysis showed that both IFNα2b and the Sm powder reduced levels of alanine transaminase and total bilirubin, while only 100 and 200 mg/kg of the Sm powder ameliorated aspartate transaminase and albumin levels. In the collagen examination, reduced hyaluronic acid and procollagen type III levels, less fibrous hyperplasia and collagen deposits, and improved hepatocyte states were clearly observed in rats treated with either IFNα2b or Sm injectional powder. In addition, the mechanism of action of the Sm powder was also studied. Immunohistochemical staining showed that IFNα2b and Sm injectional powder significantly down-regulated the expression of transforming growth factor-β1 (TGF-β1) and platelet derived growth factor (PDGF). In conclusion, Sm injectional powder has protective effects on dimethylnitrosamine-initiated liver fibrosis in rats, and the mechanism may include the down-regulation of TGF-β1 and PDGF.

    Others
    Information for Authors
    Journal of Chinese Pharmaceutical Sciences
    2015, 24(1):  63-70. 
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    Journal of Chinese Pharmaceutical Sciences Rated "The Excellent International Impact Academic Journals of China, 2014"
    Journal of Chinese Pharmaceutical Sciences
    2015, 24(1):  71-71. 
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    The 2014 Press Conference of the Highest International Impact Academic Journals of China & Annual Report for Impact Factors and International Citation of Chinese Academic Journals” was held in New Tsinghua Auditorium on Dec. 16th, 2014.Liu Binjie, member of National People’s Congress Standing Committee, Chairman of Education, Science, Culture and Public Health Committee and Chairman of the Publishers Association of China was present at the Conference, together with leaders and professionals from Propaganda Department of the CPC Central Committee, Chinese Ministry of Education, China Association for Science and Technology, Chinese Academy of Sciences, Chinese Academy of Social Sciences, Tsinghua University and Peking University,etc. More than 2000 participants gathered, and editors of Journal of Chinese Pharmaceutical Sciences (JCPS) Jian Han and Jingjing Zhang attended the conference.
    Various kinds of reports on the impact of Chinese academic journals published on this conference are conducted by International Academic Literature Evaluation Research Center, which is jointly established by China Academic Journal Electronic Publishing House affiliated to Tsinghua University and Tsinghua University Library. The report is also the third consecutive annual report, attracting widely attention from periodicals and academia both at home and abroad.
    In this Press Conference,Journal of Chinese Pharmaceutical Sciences Rated “The Excellent International Impact Academic Journals of China, 2014”, which is the second time that JCPS rated this award. Under the supporting of China Association for Science and Technology (CAST), Chinese Pharmaceutical Association (CPA), and School of Pharmaceutical Science, Peking University Health Science Center, there has been a significant development in JCPS these years. In 2013, JCPS has received the support of “the International Influence of Chinese Science and Technology Journals Promotion Plan C class”. In 2014, JCPS has also received the support of “Chinese University Quality Science and Technology Journals Project”. In the same year, the Executive Associate Editor-in-Chief of JCPS, associate Prof. Heqing Huang received the award “2014 Excellent Editor-in-Chief of Chinese University Medical Journals”. 
    The Result of "2014 Excellent Articles of Journal of Chinese Pharmaceutical Sciences" is Announced
    Journal of Chinese Pharmaceutical Sciences
    2015, 24(1):  72-72. 
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    Atthe energetic support of scholars and relevant agencies, the result of 2014 Excellent Articles of Journal of Chinese Pharmaceutical Sciences is announced.
    The 2014 Excellent Articles award is under the strict rule of editorial office of Journal of Chinese Pharmaceutical Sciences. Firstly,weidentified 16 candidate from 108 original articles published in our journal 2014. Then, editorial office invited more than 60 experts as evaluation experts. The experts voted to choose 10 excellent articles from the 16 candidate. The titles and authors of 2014 Excellent Articles are as follows.