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SYNTHESIS　AND　ANTICHOLINERGIC　ACTIVITIES　OF　6，11－DIHYDRODIBENZ［b，e］OXEPIN　AND　6，11－DIHYDRODIBENZO［b，e］THIEPIN　HYDROXYCARBOXYLATES

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Chinese Chemical Letters 1996年第2期7卷 115-118页

作者： Shou Hai GAO Liu Hong YUN(institute of Pharmacology and Toxicology,academy of military medical sciences,beijing 100850) Inst. of Pharmacology and Toxicology Academy of Military Medical Sciences Beijing 100850 China

New tricyclic hydroxycarboxylates-dibenz[b,e]oxepin and dibenzo[b,e]thiepin hydroxycarboxylates (7) were synthesized by modifying the structures of xanthene compounds. The pharmacological results showed the antagonistic activities of these tricyclic compounds were all decreased at different levels after this modification, but they exhibited more selective action on the central nicotinic receptor. Especially, the compounds containing sulfur atom almost have no action on the muscarinic receptors, they were still quite potent to the central niacinic receptor.

关键词： 3-QUINUCLIDINYL BENZILATE

A novel erythroid differentiation related gene EDRF2 inhibited α-globin gene expression in K562 cells

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Chinese Science Bulletin 2002年第5期47卷 398-402页

作者： WANG Duncheng, YANG Xiaoming & SHEN Beifeninstitute of Basic medical sciences, institute of Radiation Medicine sciences, academy of military sciences, beijing 100850, China institute of Basic medical sciences Institute of Radiation Medicine Sciences Academy of Military Sciences Beijing China

In previous studies, we found that EDRF2 was an erythroid differentiation related factor, whose expression was markedly upregulated during erythroid differentiation. It suggested that this factor played a role in erythropoiesis. By using rapid amplification of cDNA ends technology, we cloned EDRF2 gene 5’-and 3’-cDNA ends successfully. Transfection and Northern blot analysis demonstrated that EDRF2 inhibited mRNA expression of a-globin gene, while did not regulate γ-globin gene expression. Gel shift assay confirmed that DNA-binding activity of erythroid specific transcription factors GATA-1, NF-E2 and AP1 was not affected by either forced overexpression or artificial down-regulation of EDRF2 gene in K562 cells. However, we detected that the negative regulator of expression of GATA-1 transcription factor was increased in EDRF2 overexpressed K562 cells. These results strongly suggested that EDRF2 was involved in a-globin gene expression and erythroid differentiation and served as a negative regulator of

关键词： globin gene erythroid specific transcription factors leucine zipper RACE EMSA.

Effects of Aging and advanced Glycation on Gene Expression in Cerebrum and Spleen of Mice

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Biomedical and Environmental sciences 2003年第4期16卷 323-332页

作者： YUE-XIN LIANG, ZHEN WANG, DIAN-DONG LI, JIAN-MIN JIANG,AND RONG-GUANG SHAOinstitute of Medicinal biotechnology, Chinese academy of medical sciences and Peking Union medical College, beijing 100050, China institute of Medicinal biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College 北京 100050

Objective To analyze the effects of aging or advanced glycation on gene expression in the cerebrum and spleen of female C57BL/6J mice. Methods The gene expression profile was determined by using cDNA expression arrays containing 588 cDNA. Results Aging and advanced glycation resulted in differential gene expression patterns of cerebrum and spleen compared with young mice. Among the 80 genes detected in cerebrum, 43 exhibited a change in mRNA ratios with aging or treatment. Thirty-four changes (79%) were common in aged and D-galactose treated mice, whereas the cerebrum from aged and AGE-lysine treated mice showed common changes in expression of 38 genes (88%). Of the 86 genes detected in spleen, 29 (34%) displayed an age-related decrease in expression, whereas 3 (3%) displayed an increase in expression levels with aging. Eighteen genes from the detectable genes exhibited expression changes in both cerebrum and spleen of mice. Conclusions The gene expression profiles of D-galactose and AGE-lysine treated mice resemble those of aged mice. Use of cDNA hybridization arrays may provide a promising tool to explore the mechanism of aging at a molecular level.

关键词： Aging Galactose advanced glycation Gene expression DNA microarrays Cerebrum Spleen

Peptidergic innervation of human esophageal and cardiac carcinoma

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World Journal of Gastroenterology 2003年第3期9卷 399-403页

作者： Shuang-Hong Lü Yan Zhou Hai-Ping Que Shao-Jun Liu Department of Neurobiology, institute of Basic medical sciences, academy of military medical sciences, beijing 100850, China Department of Neurobiology Institute of Basic Medical Sciences Academy of Military Medical Sciences Beijing 100850 China.

AIM: To investigate the distribution of neuropeptideimmunoreactive nerve fibers in esophageal and cardiac carcinoma as well as their relationship with tumor cells so as to explore if there is nerve innervation in esophageal and cardiac ***: Esophageal and cardiac carcinoma specimens were collected from surgical operation. One part of them were fixed immediately with 4 % paraformaldehyde and then cut with a cryostat into 40-pm-thick sections to perform immunohistochemical analysis. Antibodies of ten kinds of neuropeptide including calcitonin gene-related peptide (CGRP), galanin (GAL), substance P (SP), etc. were used for immunostaining of nerve fibers. The other part of the tumor specimens were cut into little blocks (1 mm3) and cocultured with chick embryo dorsal root ganglia (DRG) to investigate if the tumor blocks could induce the neurons of DRG to extend processes, so as to probe into the possiblereasons for the nerve fibers growing into tumors. RESULTS: Substantial amounts of neuropeptide including GAL-, NPY-, SP-immunoreactive nerve bundles and scattered nerve fibers were distributed in esophageal and cardiac carcinomas. The scattered nerve fibers waved their way among tumor cells and contacted with tumor cells closely. Some of them even encircled tumor cells. There were many varicosities aligned on the nerve fibers like beads. They were also closely related to tumor cells. In the co-culture group, about 63 %and 67 % of DRG co-cultured with esophageal and cardiac tumor blocks respectively extended enormous processes,especially on the side adjacent to the tumor, whereas in the control group (without tumor blocks), no processes grew ***: Esophageal and cardiac carcinomas may be innervated by peptidergic nerve fibers, and they can induce neurons of DRG to extend processes in vitro.

关键词：肽能神经分布食管癌贲门癌肿瘤基因相关肽肿瘤生物学

Inhibition of acid-induced apoptosis by targeting ASIC1a mRNA with short hairpin RNA

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Acta Pharmacologica Sinica 2007年第10期28卷 1621-1627页

作者： Xie-chuan WENG,Jian-quan ZHENG~2,Qing-e JIN,Xiao-yun MAbeijing institute of Pharmacology and Toxicology,the academy of military medical sciences,beijing 100850,China beijing institute of Pharmacology and Toxicology the Academy of Military Medical Sciences Beijing China

Aim:To study the role of acid-sensing ion channel (ASIC) 1a in the cell death andapoptosis induced by extracellular acid in C6 glioma ***:The stableASIC1a-silenced C6 cell line,built with RNA interference technology,were con-firmed by RT-PCR and Western blot *** cell viability following acidexposure was analyzed with lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) *** apoptoticcells dyed with Annexin-V and propidium iodide were measured with a flowcytometer,while the changes of cell cycle were also ***:Thedownregulation of ASIC1a proteins by stable transfection of short hairpin RNAdecreased the cell death percentage and increased cell viability following acidexposure with LDH and the MTT *** rate of apoptosis was lower in theASIC1a-silenced cell line than that in the wild-type C6 cell *** percentage ofsub-G0cells was lower in the ASIC1a-silenced C6 cells than that in the ***:Extracellular acid induced cell death and apoptosis via ASIC1amechanisms in the C6 glioma cells.

关键词： acid-sensing ion channel RNA interference short hairpin RNA apoptosis

SCUTEBARSATINE　A，　A　NEW　NEOCLERODANE－TYPE　DITERPENOID　ALKALOID　FROM　SCUTELLARIA　BARBATA

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Chinese Chemical Letters 1996年第4期7卷 333-334页

作者： Zhao Quan WANG Feng Ming XU Xian Zhong YAN and Yuan ZHU(Anhui institute of medical sciences, Hefei, 230061)(Instrumental Analysis Center, academy of military sciences, beijing, 100850) Annul institute of medical sciences Hefei 230061 Instrumental Analysis Center Academy of Military Sciences Beijing 100850

A new neoclerodane type diterpenoid alkaloid, scutebarbatine A, was isolated from the whole plants of Scutellaria batoats D. Don. On the basis of the spectral evidence, its structure was proposed as (1). This type of ...

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Detection and quantitation of PS20, a phosphorothioate oligodeoxynucleotides in monkey plasma

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Acta Pharmacologica Sinica 2004年第6期25卷 99-104页

作者： Ming-mei SHANG, Hai-feng SONG2, Xiu-wen LIU, Zhong-ming TANG Department of Pharmacology and Toxicology, the institute of Radiation Medicine, academy of military medical sciences, beijing 100850, China Department of Pharmacology and Toxicology the Institute of Radiation Medicine Academy of Military Medical Sciences 北京 100850

AIM: To establish the method for quantitation of the phosphorothioate oligodeoxynucleotides (S-ODNs) in plasma. METHODS: Two solid-phase extraction columns combined with a strong anion-exchange column were utilized to remove proteins and lipids in plasma, and the salts were removed by a reverse-phase column followed by dialysis with a 2500 Da-cutoff membrane. The concentration of the tested S-ODNs, PS20, and its metabolites extracted from the plasma were determined by the method of non-gel sieving capillary electrophoresis (NGCE) with diode array detection in the presence of internal standard (IS). RESULTS: The method was with good base number specificity. Relative standard deviation % of both intra and inter assay were all less than 10 %, and the total mean recovery was about 91 %. The methodology was successfully used to determine the PK behavior of an anti-tumor antisense S-ODNs in monkeys and identify the metabolites with single base difference. CONCLUSION: The combined method of solid-phase extraction and NGCE could be used to study the pharmacokinetics of S-ODNs, and the main parameters of the methodology met the requirement of PK study.

关键词： antisense oligodeoxyribonucleotides thionucleotides rhesus monkey plasma solid-phase extraction capillary electrophoresis non-gel sieving internal standard

BENZODIAZEPINE RECEPTORS IN ISOLATED ADRENAL GLOMERULOSA CELLS

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Science China Chemistry 1989年第4期32卷 458-467页

作者：宋烈昌周廷冲 institute of Basic medical sciences Academy ot Military Medical Sciences Beijing

In our experiments the isolated rat adrenal glomerulosa cells displayed perlpheral-type benzodiazepine receptors, which could bind to [~3H] PKl1195 with an apparent equilibrium dissociation constant (KD) of 9.4±2.8 nmol/L and a maximal binding capacity (B_(max)) of 5.6q-1.8 pmol/10~6 cells. The effects of five ligands: PKl1195, Ro5--4846, flunitrazepam, diazepam and clonazepam on aldosterone secretion responses of isolated glomerulosa cells to anglotensin Ⅱ or extracellular potassium ions were observed. The logarithm of EO_(50) for these ligands as stimulators was well correlated with the logarithm of their Ki value for [~3H] PK11195 binding, suggesting that the stimulative effects might be mediated by the benzodiazepine receptor in isolated glomerulosa cells.

关键词： adrenal glomerulosa cell aldosterone secretion benzodiazepine receptor.

Ginsenoside Rg1 inhibits proliferation of vascular smooth muscle cells stimulated by tumor necrosis factor-α

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Acta Pharmacologica Sinica 2006年第8期27卷 1000-1006页

作者： Zeng-chun MA Yue GAO~2 Yu-guang WANG Hong-ling TAN Cheng-rong XIAO Sheng-qi WANG institute of Radiation Medicine sciences,academy of military medical sciences,beijing 100850,China institute of Radiation Medicine sciences Academy of Military Medical Sciences Beijing China

Aim:To investigate the proliferation of vascular smooth muscle cells(VSMC)affected by ginsenoside Rg1 and further explore the molecular mechanism ofginsenoside Rg1 using ***:The proliferation of VSMC wasmeasured by MTS assay kit and flow *** alterations were ana-lyzed using two-dimensional electrophoresis and peptide mass *** proteins found in proteomics were confirmed by ***:The proliferation of VSMC was enhanced significantly after tumor necrosis fac-tor-α(TNF-α)treatment,and ginsenoside Rg1 treatment inhibited proliferation ina dose-dependent *** analysis showed 24 protein spots werechanged,including 17 spots that were increased and 7 spots that were *** Rg1 could restore the expression levels of these proteins,at leastpartly,to basic levels of untreated *** expression of G-protein coupledreceptor kinase,protein kinase C(PKC)-ζ,N-ras protein were decreased,whilecycle related protein p21 was increased by ginsenoside Rgl in TNF-α ***:PKC-ζ and p21 pathway might be the mechanism for inhibi-tory effects of ginsenoside Rg1 on proliferation of VSMC.

关键词： cell cycle ginsenoside Rg1 proteomics tumor necrosis factor-α vascular smooth muscle cells