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ABSTRACTS FROM THE INTERNATIONAL WORKSHOP ON CHEMICAL SCIENCE AND PHARMACEUTICAL RESEARCH (CPSR2014) BEIJING, 2014 001 A CHEMICAL REACTION INVOLVING THE INTERACTION OF HYPOCRELLIN B AND GELATIN AS A FORMATION OF CYSTEINE-SUBSTITUTED DERIVATIVE

003 THE EFFECT OF RUYANNEIXIAO CREAM ON PTEN AND P21 EXPRESSION IN RAT MAMMARY PRECANCEROUS LESIONS

Liu W., Pan Q.S., Zhang J.C., Chen X.L., Zhang P.

Ma M.1, Li D.H.1, Liao R.1, Zhang G.J.2, Tan B.Z.1, Ma Y.3, Zhang S.Y.1, Liu Y.B.1

School of Science, Honghe University, Mengzi, Yunnan, China Background: Hypocrellin B (HB) is a kind of potential photodynamic drug. The aim of this study is to better understand the interaction of HB and gelatin as a formation of cysteine-substituted derivative. Methods: A concentrated solution of HB in dimethylsulfoxide (DMSO) was added slowly into the gelatin aqueous solution in micro liter quantities and mixed quickly by shaking. Results: By reaction of HB with Tyep II gelatin, the maximum absorption wavelength was red-shifted with appearance of an isosbestic point at around 480 nm, and the fluorescence was quenched almost completely. The interaction of HB with the cysteine-deficient Type I gelatin resembled the reaction for HB binding to the hydrophobic area of bio-molecules. Conclusions: A chemical derivative, cysteine-S-HB, was formed via reaction of HB with Type II gelatin. The Type II gelatin does not possess a hydrophobic area for binding of HB whereas the Type I gelatin does, which implies that type I gelatin is a proper choice as a drug carrier of HB while type II gelatin isn’t. Acknowledgements: Supported by a project grant from National Natural Science Foundation of China (Grand No.61361002 and 21366011).

002 THE COATING OF MICROEMULSIONS IMPROVES THE STABILITY OF FUNCTIONAL PIGMENT NANOPARTICLES Lu Z.F., Ban J.F., Xie Q.C., Liang Z.F., Deng G.H., Wen Y.Q., Shen L., Huang X., Fang R.H., Chen Y.Z. Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China Aims: Lycopene is an unsaturated fat-soluble hydrocarbon in the carotenoid family. The way to increase the solubility of unstable substances has been focused in recent years. In our previous studies, we found that nanoparticles were coated by the oil phase in the microemulsion system (NPs-SEs), and this system was found to both increase the stability of the drug and improve drug loading. In this study we aim to prepare the NPs-SEs and characterize their properties. Methods: High pressure homogenization method was employed to prepare the NPs-SEs and their properties including size, Zeta potential and drug loading capacity of lycopene were characterized. Results: The results showed that the NPs-SEs were formed with the drug loading as 1 mgmL1, particle size as (181  0.5)nm, Zeta potential as(-69.27  0.38)mV and pH value as (7.21  0.1), respectively. Conclusions: The method is feasible and the NPs-SEs possess stable properties. This study provides a new method to apply fat-soluble and unstable substances.

1 Department of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, China; 2The School Outpatient Department, the First Affiliated Hospital of Jinan University, Guangzhou, China; 3Bio-engineering institute of Jinan University, Guangzhou, China

Co-first authors: Ma Min, Li Dehui, Liao Rui. They contributed to the work equally and should be regarded as co-first authors. Objective: To investigate the effect of externally applying Ruyanneixiao cream on the expression of PTEN and p21 in the precancerous lesions of breast cancer in the SD rat model. Methods: DMBA combined with estrogen and progesterone was used to induce SD rats to form the precancerous lesions in the breast cancer model. We divided 96 SD rats into 6 groups (16 rats per group): the control group, the model group, the tamoxifen group, the low- dose Ruyanneixiao cream group, the medium- dose Ruyanneixiao cream group, and the high-dose Ruyanneixiao cream group. We processed 8 rats on week 10 and 14 and the p21 and PTEN expression levels in the mammary tissues were determined by using immunohistochemistry and western blot methods. Results: In the control group, the p21 protein level in mammary tissue in the disease model group was higher in week 14 than that in week 10 (P < 0.05 or P < 0.01). The results indicated that the p21 protein expression level increased dynamically as the mammary pathology developed. Furthermore, upon the treatment of tamoxifen cream and Ruyanneixiao cream, the p21 protein levels in the mammary tissue of the low-, medium-, and high-dose Ruyanneixiao cream groups exhibited varying degrees of decreased protein levels (P < 0.05 or P < 0.01) compared to the disease model group. Correspondingly, the expression levels of PTEN were enhanced (P < 0.05 or P < 0.01). Conclusions: Externally application of Ruyanneixiao cream can reduce the incidence of DMBA-induced rat precancerous lesions of breast cancer, possibly through interfering with the expression of PTEN and p21 in the precancerous lesions of breast cancer. Acknowledgements: Supported by China National Foundation of Natural Science (No. 81173265; 81473688); Program for New Century Excellent Talents in University (No. NCET-13-0827); Guangzhou Municipal Planned Science and Technology Project (No. 2014J4100104).

004 PHARMACEUTICAL RESEARCHES ON FENGBINGKANG MIXTURE INCLUDING THE TOLERANCE TO NORMAL ATMOSPHERIC PRESSURE HYPOXIA THE EFFECT OF RESISTANCE TO HIGH AND LOW TEMPERATURE Miao M.S., Qiu P.B., Tang Z.H., Luo K. Henan University of Traditional Chinese Medicine, Henan, China Objective: To develop a pure mixture of Chinese medicine which can treat effectively common honey bee-related infectious diseases,

© 2014 The Authors Basic & Clinical Pharmacology & Toxicology © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Basic & Clinical Pharmacology & Toxicology, 115 (Suppl. 4), 1–10

2 carry outpharmacodynamic studies and preliminary study on Fengbingkang mixture, and investigate reference on the treatment of bee diseases. Method: By optimizing preparation procedure, determination of mixture preparation and quality standards, Fengbingkang mixture normal mellifera hypoxia tolerance, high temperature resistance, and low temperature capability were assessed, this drug was proved to improve the ability of bee intolerance environment. Results: A kind of mixture formulations was successfully prepared, and the quality standards and trial production of a small amount of sample were well determined. Our results show that the mixture can obviously increase the tolerance onthe normal pressure hypoxia environment, high temperature and low temperature environment, and can reduce the recovery time after freezing. Acknowedgements: The research work is supported by the National Natural Science Foundation of China (Grant No.81173474) and the Collaborative Innovation Center for the creation of new Traditional Chinese medicine and genuine regional drug deep processing in Henan University of Traditional Chinese Medicine (2012) 188-2.

005 RESVERATROL ATTENUATES TNF-a-INDUCED INFLAMMATORY REACTION BY UPREGULATING KLF2 IN LATE ENDOTHELIAL PROGENITOR CELLS Chu H.-R., Li H., Zhang J., Liu J.-H., Li W.-P., Cheng M. Medicine Research Center, Weifang Medical College, Weifang, Shandong, China Background: There is increasing evidence suggesting a vital role of tumor necrosis factor alpha (TNF-a) in cardiovascular disease. Resveratrol is a phytochemical with anti-inflammatory properties. Moreover, the transcription factor Kruppel like factor-2 (KLF2) is known to participate in a number of processes during development and disease progression such as endothelial homeostasis, vascular growth/remodeling and inflammation. We hypothesized that resveratrol may prevent the progression of inflammatory reaction caused by TNF-a through upregulation of the KLF2 in late endothelial progenitor cells (EPCs). Methods: EPCs at passages 3~5, namely late EPCs, were pretreated with different concentrations (0~50 lmol/L) of resveratrol for 2 h, and then were incubated with TNF-a (10 ng/ml) for 24 h. Cell proliferation, adhesion, migration, and angiogenesis were assayed with CCK-8, adhesion test, wound healing assay, and Matrigel assay, respectively. The mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) was measured by qRT-PCR assay. NO level in the supernatant was determined by the Griess reaction. In the meantime, gene and protein expression of KLF2 was measured by qRT-PCR and Western-blot. Results: TNF-a treatment remarkably impaired EPCs proliferation, adhesion, migration, and angiogenesis, decreased the secretion of NO and upregulated the expression of ICAM-1 and MCP-1. Moreover, these alterations were linked to a decrease of KLF2 at both mRNA and protein levels. Resveratrol pretreatment effectively counteracted TNF-a induced inflammatory reaction in the late EPCs and reversed decline of KLF2 in a concentration-dependent manner. Conclusion: Resveratrol can reverse the inflammatory reaction, improve the functions caused by TNF-a through regulation of KLF2 in late EPCs. Acknowledgements: This work is supported by the National Natural Science Foundation of China(No.30900290, 31270993); Administration of traditional Chinese Medicine of Shandong Province(2013-239).

006 MILDRONATE VERSUS LEVOCARNITINE IN PATIENTS WITH ISCHEMIC HEART DISEASE: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, NON-INFERIORITY TRIAL Shu M.Q.1, Song Z.Y.1, Jing T.1, Zhang Q.1, Song Y.M.2, Zhang Y.2, Yang C.M.3, Zhang H.3, Yin Y.H.4, Liu D.4, Hao Y.M.5, Liu F.5, Zheng Q.6, Xiao J.F.6, Li X.T.7, Fu H.7, Chen Y.8, She B.R.8 1 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China; 2Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China; 3Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China; 4Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; 5Department of Cardiology, The Second Affiliated Hospital of Hebei Medical University, Hebei, China; 6Department of Cardiology, Harrison International Peach Hospita, Hebei, China; 7 Department of Cardiology, the Forth Affiliated Hospital of Hebei Medical University, Hebei, China; 8Department of Cardiology, Henan Provincial People Hospital, Henan, China

Background: In addition to the standard therapy, mildronate and levocarnitine are the potential treatments for patients with ischemic heart disease (IHD). In this study, we aim to compare the efficacy and safety of these drugs. Methods: In this study, a parallel, randomized, double-blind, non-inferiority trial was conducted using patients aged 35 years to 85 years with a confirmed diagnosis of IHD according to the American College of Physicians. Between Aug, 2007, and Sept. 2011, patients at 8 Chinese centers were randomly allocated by a computer-generated randomization sequence to receive either intravenously guttae (iv gtt) of 0.1 mg per kg mildronate or levocarnitine for 10 days. Both patients and investigators were masked to study the treatment. The primary outcome indicated that there was a change in ventricular wall motion score index(VMI)from the baseline. Analyses were done by per protocol population and intention-to-treat. This trial is approved by the State Food and Drug Administration (NO. 2004L01635). Results: Two hundred thirty-one patients were randomly assigned, among of which, 115 patients were allocated to receive mildronate and 116 patients to receive levocarnitine. At day 10, reduction in VMI from baseline occurred in mildronate (1.30  0.44 to 1.28  0.43, P = 0.4035) and levocarnitine (1.33  0.43 to 1.25  0.37, P = 0.0005). Other parameters had also been improved, i.e. left ventricular ejection fraction (LVEF) in mildronate (from 58.78  11.82 to 60.46  12.08, P = 0.0254) and levocarnitine (from 60.28  11.46 to 61.56  10.89, P = 0.1084), left ventricular end-diastolic diameter (LVD) in mildronate (from 49.37  9.32 to 49.31  9.54, P = 0.9370) and levocarnitine (from 48.76  8.86 to 47.74  7.52, P = 0.0845), left ventricular fraction shortening (FS) in mildronate (from 32.61  8.67 to 33.34  9.00, P = 0.2170) and levocarnitine (from 32.83  7.77 to 33.88  8.10, P = 0.0201), stroke Volume (SV) in mildronate (from 73.68  23.02 to 75.19  24.62, P = 0.2085) and levocarnitine (from 71.27  20.26 to 71.95  18.71, P = 0.6264) and cardiac output (CO) in mildronate (from 5054.55  1689.95 to 5109.59  1682.65, P = 0.3233) and levocarnitine (from 4990.71  1694.15 to 4884.72  1652.86, P = 0.5197). Incidence of adverse events were similar in the mildronate (7.83%; n = 9) and levocarnitine (11.21%, n = 13). Conclusions: Intravenously guttae of mildronate are non-inferior to levocarnitine. Our findings lend support to the use of mildronate for IHD. Acknowledgements: Supported by a project grant from Changchun Xiangtong Pharmaceutical Co. Ltd. (Jilin Province, China).

© 2014 The Authors Basic & Clinical Pharmacology & Toxicology © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Basic & Clinical Pharmacology & Toxicology, 115 (Suppl. 4), 1–10

3 007 DETERMINATION AND PHARMACOKINETIC STUDY OF MATRINE-LOADED MICROEMULSION HYDROGEL IN RABBIT PLASMA BY GC-MS METHOD Fu Z., Yuan C., Chen L.-H., Wei H. Pharmaceutical Sciences, Shandong Medical College, Jinan, China Aims: Currently, the common method of delivering matrine is through injection. However, its blood drug concentration (BDC) is not persistant and stable. The objective of this study is to evaluate a new transdermal delivery system of microemulsion-based hydrogel (MBH) of matrine by determining the pharmacokinetics in rabbit plasma. Methods: A sensitive and simple GC-MS method was developed and applied to determine matrine concentration in rabbit plasma. Matrine and n-Tricosane (internal standard) in rabbit plasma were extracted with perchloric acid, and separated on a 5% diphenyl-95% dimethylpolysiloxane capillary column, with helium as the carrier gas. Matrine and n-Tricosane were quantified in the selected ion monitoring (SIM) mode, with the characteristic ions m/z 248.1 and m/z 324.1, respectively. Results: The linear range of the calibration curve for matrine was 32– 800 ng/mL, with a limit of quantification (LOQ) 1 ng/mL. The results of the pharmacokinetics indicated that the plasma elimination half-life of matrine in MBH (6.1 h) was significantly longer than that of commercial matrine injections (2.5 h). BDC by MBH delivery was more persistent than by matrine injection. Conclusions: In this study, a validated GC-MS method was developed to detect matrine at low concentration in rabbit plasma using transdermal delivery of matrine in MBH. Our GC-MS method was successfully applied to determine the pharmacokinetic profile of matrine. The pharmacokinetics study showed that MBH form of matrine prolonged the effective BDC compared with matrine injection.

008 INTAKE OF THE BRANCHED-CHAIN AMINO ACID EXTENDS THE LIFESPAN OF CAENORHABDITIS ELEGANS Wang H.Y., Guo C.L., Tan X.Q., Xuan D.R., Wang J.H., Zhang Z.Z. School of Marine Science and Technology, Harbin Institute of Technology, Weihai, China Aims: In recent years, lots of compounds are reported to be able to extend the lifespan in model organisms. The aim of this study is to test whether branched-chain amino acids (BCAAs, L-valine, L-leucine, Lisoleucine) could prolong the lifespan of Caenorhabditis elegans (C. elegans), and explore the molecular mechanism relying on the ageing-related local gene network (LGN). Methods: After synchronization, adult C. elegans were fed with living E. coli strain OP50 bacteria on nematode growth medium (NGM) agar plates with or without BCAAs. According to the results of lifespan analysis, the group with significantly increased survival was selected for quantitative polymerase chain reaction (qPCR) analysis to measure the expression of genes those are closely related with BCAAs metabolic modules in the LGN. Results: L-valine extended the average lifespan of C. elegans significantly at a low concentration (0.1 9 ; CVal(19)=0.649uM), but the other two amino acids affected lifespan slightly. The 0.1 9 Val impacted on the expression of genes which are functionally related to the metabolic modules of L-valine, L-leucine, and L-isoleucine in the LGN. Conclusions: Our results suggest that L-valine has a favorable effect on anti-ageing in C. elegans. Moreover, the LGN is worthy of further evaluation as a platform exploring molecular mechanisms of lifespan determination.

009 TREATMENT OF SPINAL CORD INJURY WITH NEURAL STEM CELLS STABLY EXPRESSING NEUROTROPHIN-3 Teng A.P.1, Xue Y.2, Peng S.Q.3, Cui K.4, Wang Z.D.4, Li P.4, Zhang B.4, Zhao L.J.3, Chen L.3 1 Department of Imaging, China National Heavy Duty Truck Group CO, LTD Hospital, Jinan, China; 2Jinan Child Hospital, Jinan, China; 3 Department of Orthopaedic surgery, Shandong Provincial Hospital, Jinan, China; 4Department of Hepatobiliary Surgery, Shandong Cancer Hospital, Jinan, China

Aims: This study is to investigate the effect of neural stem cells (NSCs) stably transfected with rat neurotrophin (NT)-3 gene on the repair of spinal cord injury (SCI) in a rat model. NSCs were isolated from rats on gestational day 14 by collecting embryonic cortical cells and isolating Nestin positive cells. Methods: Rat NT-3 was transfected into the NSCs. Geneticin418 (G418) was used to screen NT-3-positive cells.. The stable expression of NT-3 protein was confirmed by western blot. The spinal cords of forty female Wistar rats were impacted to induce SCI. After nine days, the rats in experimental group were injected with 5 ll NT-3- overexpressing NSCs (10 000 cells/ll). The rats in control group 1 were injected with 5 ll medium and the rats in control group 2 were injected with 5 ll- untransfected NSCs (10000cells/ll). One week after the transplantation, tilt tests and Basso-Beattie-Bresnahan (BBB) scores were conducted to observe the repair of motor function of rat hind limbs. The transplantation of NT-3-overexpressing NSCs improved the recovery indices of experimental SCI rats. Conclusions: The treatment with NSCs stably expressing NT-3 can significantly repair SCI and improve spinal function, which provides a potentially feasible method to treat SCI in clinic. Acknowledgements: Grant No. Y2007C122 and 2008BS03024 of the Natural Science Foundation of Shandong.

0010 INDOMETHACIN ACCELERATES REENDOTHELIALIZATION IN A RAT CAROTID ARTERIAL INJURY MODEL Li X, Zhang X.Y., Guan X.M., Meng A.X., Cui X.D., Liu J.H., Cheng M. School of Basic Medicine, Weifang Medical College, Weifang, Shandong, China Background: Endothelial progenitor cells (EPCs) play a crucial role in endothelial repair after artery injury. Indomethacin, a non-steroidal anti-inflammatory drug, has been applied clinically to prevent and treat cardiovascular disease. However, little is known about the effects of indomethacin on EPC functions, especially on the reendothelialization capacity of EPCs in vivo. In this study, we investigated the functional influences of indomethacin on late outgrowth EPCs in vitro and the reendothelialization capacity of EPCs in vivo. Methods: EPCs at passages 3–5, namely late outgrowth EPCs (late EPCs), were cultured with different concentrations of indomethacin for 24 h. Cell proliferation, migration, adhesion, tube formation, and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay, wound healing assay, adhesion test, Matrigel assay and fluorescence-activated cell sorting (FACS), respectively, in vitro. Balloon injury was performed by introducing a Fogarty 2F embolectomy catheter to the common carotid through the external carotid of rat. Late EPCs (1 9 106 cells) labeled with CM-Dil were transplanted 3 h after carotid artery injury via tail vein injection. Two weeks after carotid artery injury, the CM-DiI-labeled EPCs incorporated in the injured vessels were quantitatively analyzed by a fluorescent microscope. Evans Blue staining was conducted to assess the carotid endothelial recovery. Results: In vitro, indomethacin treatment augmented late EPCs proliferation, migration, adhesion, and tube formation. FACS assays demonstrated that apoptosis of late EPCs was decreased upon the treatment of indomethacin. Compared with the vehicle, transplantation of late

© 2014 The Authors Basic & Clinical Pharmacology & Toxicology © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Basic & Clinical Pharmacology & Toxicology, 115 (Suppl. 4), 1–10

4 EPCs with or without indomethacin treatment significantly accelerated reendothelialization in vivo. Moreover, transplantation of EPCs with indomethacin treatment further enhanced the reendothelialization capacity compared with EPCs without indomethacin treatment. More indomethacin-treated EPCs were incorporated in the injured vessels compared with EPCs without indomethacin treatment. Conclusions: Our data demonstrated a positive effect of indomethacin on late EPCs. Reendothelialization capacity of EPCs was enhanced by indomethacin in vivo. Indomethacin treatment in EPCs may become a novel therapeutic target for endothelial repair. Acknowledgements: This work is supported by the National Natural Science Foundation of China. No. 30900290, 31270993, Science and technology project of higher education of Shandong Province.No.J14LK59.

0011 AN IMPROVEMENT OF GENE TRANSFECTION AND DELIVERY SYSTEM BASED ON a-CYCLODEXTRINPOLYAMIDOAMINE CONJUGATES

Method: Primary ADSCs were harvested by the enzyme digestion method. The expression of CXCR4 and CXCR7 were detected by flow cytometry and western blot. ADSCs were treated with SDF-1 and neutralized with anti-CXCR4 and/or anti-CXCR7 antibody. The secretion of VEGF, HGF, and b-FGF was determined by ELISA. Human umbilical vein endothelial cells (HUVECs) tube formation assay was performed to examine the effect of SDF-1 and neutralization of CXCR4 and CXCR7 on angiogenesis promoting property of ADSCs. Results: ADSCs were successfully isolated from human liposuction tissue and cultured in vitro. The expression of CXCR4 and CXCR7 significantly decreased during cell culture and increased by SDF-1 stimulation. SDF-1 pretreatment also promoted the secretion of angiogenesis factors including VEGF, HGF, and b-FGF, and enhanced the ability of ADSC-induced tube formation in HUVECs. On the other hand, blocking of CXCR4 and CXCR7 activation inhibited the promotion of angiogenesis property of ADSCs induced by SDF-1. Conclusions: SDF-1 pretreatment increases the expressions of CXCR4 and CXCR7 in ADSCs. In addition, it also promotes the angiogenesis ability of ADSCs through CXCR4, CXCR7 pathways. a These authors contributed equally to this work.

Chen J.H., Qin L.H., Cao D.W., Huang H. Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, Guangzhou, China. Aims: Highly attention has been attracted recently about Polyamidoamines (PAMAMs) due to their special properties in the drug and gene delivery systems, especially the high generation of PAMAMs as the gene vector showing stronger transfection ability compared with the other non-viral carrier materials. The main drawback of these materials is the serious cell toxicity. In order to overcome this problem, a novel gene delivery system was designed in our research group. Methods: PAMAMs are covalently conjugated to a-cyclodextrin (aCD) via amide bonds to obtain the starburst-like cationic polymers (CD-PG2). The chemical structure and composition of CD-PG2 were characterized by H-NMR. The physicochemical and biological properties of CD-PG2/pDNA polyplex were evaluated by agarose gel retardation, stability test against DNase I, MTT assay, DLS measurement, CLSM observation, LDH leakage test, and in vitro cell transfection. Results: CD-PG2 efficiently condensed pDNA into nano-scale particles with a narrow distribution in size, and protest pDNA from DNase I degradation. CD-PG2 showed excellent gene transfection efficiency without serum interference as well as relatively low cytotoxicity, compared with free PET-25K and a commercial reagent Lipofectamine 2000. The cell uptake route analysis showed cellular uptake of CDPG2/pDNA polyplex is mainly through Clathrin-mediated endocytosis (CME) and Caveolae-mediated endocytosis (CvME) routes. Further investigations demonstrated that a-CD regulated CvME pathway to improve the behavior of polyplex transfection. Conclusions: CD-PG2 could be used as a versatile tool for gene transfection and delivery in the future. Acknowledgements: the financial support from the National Nature Science Foundation of the People’s Republic of China (No. 30870618 and 31170918). 0012 SDF-1 PROMOTES ANGIOGENESIS PROPERTY OF ADSCS VIA CXCR4 AND CXCR7 PATHWAYS Liu J.1,a, Li P.H.1,a, Zhang A.J.1,a, Yu Y.2, Wang H.C.3, Li Q.1, Jin P.S.1 1 Department of Plastic Surgery, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; 2Department of Plastic Surgery, 1st Teaching Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China; 3Medical Center of Hip, Luoyang Orthopedic-Traumatological Hospital, luoyang, HenanProvince, China

Objective: To study the effect of SDF-1 on angiogenesis property of Adipose-derived stem cells (ADSCs) and explore the role of CXCR4 and CXCR7 in angiogenesis.

0013 NEUROTRANSMITTERS INHIBIT THE GROWTH OF GLIOBLASTOMA MULTIFORME CELLS IN A DOSAGEDEPENDENT MANNER Kim S.C. Medical School & College of Medicine/Molecular Medicinal Chemistry Lab, WCU Programme, Department of Life Sciences & Biotechnology, Yonsei University, Seoul, Seodaemun-gu, Korea Background: Neurotransmitters derived from the nervous system have been shown to inhibit the growth of normal neurons, and they are expected to have effects on brain related cancer. Methods: Endocrine neurotransmitters were applied to the glioblastoma multiforme cell lines to evaluate their effects on glial cancer. Three concentrations were used for each neurotransmitters, range of dopamine was 1~100 lM, range of synthetic beta - endorphin was 1~10 lM, and range of epinephrine was 1~100 nM. Normal serum concentration was used. Results: Endorphin inhibited cell growth in all ranges (T-test p < 0.01). Dopamine had different effects on cell growth at different concentrations (Student T-test. 0.01 < p < 0.05). We couldn’t detect the effect of epinephrine because the cells were overgrown (p > 0.05). But it increased cell proliferation in all dosages (Chi-square test. p < 0.01). Conclusions: Our study indicates that neurotransmitters have dosagedependent inhibitory effects. Also, this study implies that controlling neurotransmitters can be used as a potential alternative immune therapy inhibiting the growth of fatal glioblastoma cells.

0014 UTILIZATION OF LC FOR THE PHYSICOCHEMICAL AND THERMODYNAMIC CHARACTERIZATIONS OF FORMING CILOSTAZOL INCLUSION COMPLEXES WITH b-CD AND DM-b-CD Wang J.H., Wang X.Z., Li C.H. Chongqing Academy of Animal Sciences, Chongqing, China Aims: In this study, the interactions between cilostazol and two different cyclodextrins (b-CD, DM-b-CD) are elucidated by using LC. Methods: The capacity factors (k) of cilostazol were monitored in the presence of increased concentrations of b-CD or DM-b-CD from the reduction of the retention time (tR). Results: We observed that cilostazol forms a 1:1 inclusion complex with b-cyclodextrin (b-CD) and dimethyl-b-cyclodextrin (DM-b-CD)

© 2014 The Authors Basic & Clinical Pharmacology & Toxicology © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Basic & Clinical Pharmacology & Toxicology, 115 (Suppl. 4), 1–10

5 at 25°C,37°C and 45°C. The interaction of cilostazol with DM-b-CD was more efficient than with b-CD and the highest formation constant (K) was found for DM-b-CD (23.82M1) at 25°C. Moreover, the K values decreased as the system temperature increased. To obtain the information on the mechanism of cilostazol affinity for b-CD and DMb-CD, the thermodynamic parameters of the complexation (DG, DH, and DS) were analyzed. Conclusions: The comparison of the K values obtained from the two different cyclodextrins revealed that the K values of the complexation are dependent on the structure of the host molecule. The change in the thermodynamic parameters suggested that the complexation could proceed spontaneously (DG

Special issue: abstracts from the international workshop on chemical science and pharmaceutical research, 25-28 september 2014, beijing, china.

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