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Metabonomic phenotype and identification of “heart blood stasis obstruction pattern” and “qi and yin deficiency pattern” of myocardial ischemia rat models

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Science china(Life Sciences) 2009年第11期52卷 1081-1090页

作者： YAN Bei1, A JiYe1, HAO HaiPing1, WANG GuangJi1, ZHU XuanXuan2, 3. ZHA WeiBin1, LIU LinSheng1, GUAN EnZe3. ZHANG Ying1, GU ShengHua1, HUANG Qing1 & ZHENG YuanTing1 1Key Laboratory of Drug Metabolism and Pharmacokinetics, china pharmaceutical university, Nanjing 210009, china 2Pharmacological Laboratory of Clinical Research institute, Jiangsu Provincial hospital of Traditional Chinese Medicine, Nanjing 210029, china 3.ollege of Pharmacy, Nanjing university of Traditional Chinese Medicine, Nanjing 210029, china 1. Key Laboratory of Drug Metabolism and Pharmacokinetics China Pharmaceutical University Nanjing 210009 China 2. Pharmacological Laboratory of Clinical Research institute Jiangsu Provincial Hospital of Traditional Chinese Medicine Nanjing 210029 China 3. College of Pharmacy Nanjing University of Traditional Chinese Medicine Nanjing 210029 China

The traditional Chinese medicine concepts of "Xinxueyuzuzheng (heart blood stasis obstruction pattern)" and "Qiyinliangxuzheng (qi and yin deficiency pattern)" for myocardial ischemia rat models were constructed in the present study. Endogenous metabolites in rat plasma were analyzed using the GC/TOF-MS-based metabonomic method. Significant metabolic differences were observed between the control and two model groups, and the three groups were distinguished clearly by pattern recognition. Compared with those of the control, the levels of hydroxyproline, threonic acid, glutamine and citric acid were strikingly up or down-regulated in model rats. The metabolites contributing most to the classification between the two "pattern" rats were identified, such as valine, serine, threonine, ornithine, hydroxyproline, lysine, 2-hydroxybutanoic acid, 3.hydroxybutanoic acid, galactofuranose and inositol. These compounds were indicated as the potential biomarkers. The results suggested that the two "patterns" are involved in dysfunction in oxidative stress, energy metabolism and amino acid metabolism. These findings also provided the substantial foundation for exploring the scientific connotation of these two "Zhengxing (pattern types)" of myocardial ischemia, and "Bianzheng (pattern identification)".

关键词： Metabonomics GC/TOF-MS heart blood stasis obstruction pattern qi and yin deficiency pattern myocardial ischemia rat model

Interaction of cellular-localized signature modules in response to prostate cancer

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Progress in Natural Science:Materials International 2007年第11期17卷 1368-1375页

作者： Zhu Jing1, Guo Zheng1,2, Zhang Min2, Yang Da2, Wang Jing2 and Wang Chenguang2(1. School of Life Science and Bioinformatics Centre, university of Electronic Science and Technology of china, Chengdu 610054, china 2. Department of Bioinformatics, Bio-{3. Key Laboratory of Heilongjiang Province, Harbin Medical university, Harbin 150081, china) School of Life Science and Bioinformatics Centre University of Electronic Science and Technology of China Chengdu 610054 China Department of Bioinformatics Bio-Pharmaceutical Key Laboratory of Heilongjiang Province， Harbin Medical University， Harbin 150081 China

Rapid progress in high-throughput biotechnologies (e.g. microarrays) and exponential accumulation of gene functional knowledge makes it promising for systematic understanding of complex human diseases at the functional modules level. Current modular categorizations can be defined and selected more specifically and precisely in terms of both biological processes and cellular locations, aiming at uncovering the modular molecular networks highly relevant to cancers. Based on Gene Ontology, we identifed the functional modules enriched with differentially expressed genes and characterized by biological processes and specific cellular locations. Then, according to the ranking of the disease discriminating abilities of the pre-selected functional modules, we further defined and filtered signature modules which have higher relevance to the cancer under study. Applications of the proposed method to the analysis of a prostate cancer dataset revealed insightful biological modules.

关键词： microarray analysis Gene Ontology classification analysis cellular location functional module

The effects of overexpression of Nurrl on SK-N-SH cells vulnerability to neurotoxin 6-OHDA

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The effects of overexpression of Nurrl on SK-N-SH cells vuln...

Preparation of two triflate precursors for O-(2-[^(18)F] fluoroethyl)-L-tyrosine used in positron emission tomography (PET)

中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Yongmei ZHAO~1,Yang LIU~1,Haiyan ZHANG~2,Weihong LI~2,Qunyuan XU~3.1 Key Laboratory for Neurodegenerative Diseases of Ministry of Education,xuanwu hospital,capital Medical university, Beijing {3. 2 Department of Cell Biology,capital Medical university,Beijing 100069 3.Beijing institute for Neuroscience,capital Medical university,Beijing 100069

＜正＞Background Nurr1（nuclear receptor-related factor 1）,a transcription factor of the steriod/thyroxin hormone nuclear receptor superfamily,is highly expressed in mesencephalic dopamine（DA） *** is specifically required for the induction of ventral midbrain DArgic neurons and important for development and survival of mature DArgic neurons,the cells primarily lost in human Parkinson’s disease（PD）.In homozygous Nurr1-deficient mice,DArgic neurons fail to develop in the substantia nigra and ventrotegmental areas but are preserved in other brain *** observations suggest that Nurrl may play an important role in maintaining mature mesencephalic DArgic neuron function and may be one of the potential susceptibility factors for *** To investigate possible correlation between the expression of Nurrl gene and selective cell death of DArgic ***:a human neuroblastoma-derived cell line SK-N-SH which do not express endogenous Nurrl were transfected with the pBK-RSV-Nurr1 plasmid by LipofectAMINE and selected by ***-N-SH and SK-N-SH cells over-expressing Nurrlgene（SK-N-SH/Nurr1） were used as models to investigate the effects of overexpression of Nurrl on SK-N-SH cells vulnerability to neurotoxin ***（1） Nurr1 gene was highly overexpressed in transgenetic SK-N-SH/Nurr1 cells and cell proliferation in SK-N-SH/Nurr1 cells were *** Nurr1-overexpressing cells showed a significantly slow growth rate about（29.6±3.8）%decrease of that in SK-N-SH cells,which was might due to a marginal block in the G0/G1 to S phase transition,indicating Nurrl gene inhibited cell proliferation in SK-N-SH/ Nurrl cells.（2） The cell survival of Nurr1-overexpression SK-N-SH/Nurr1 cells was significantly inhibited by 6-OHDA,and the distribution of both cells at each phase in cell cycle were *** with 50μM6-OHDA changed SK-N-SH/Nurr1 cells morphology within 1 hr,accompanied by retraction of processes,shrinkage of cell body,whereas SK-N-SH c

关键词： Nurr1 Overexpression 6-OHDA Apotosis

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Science china Chemistry 2009年第12期52卷 2195-2199页

作者： LIU ChunYan1,2 & JIANG ShenDe1 1 School of pharmaceutical Science and Technology,Tianjin university,Tianjin 3.0072,china 2 Department of Pharmacy,North china Coal Medical College,Tangshan 063.00,china 1. School of pharmaceutical Science and Technology Tianjin University Tianjin 300072 China 2. Department of Pharmacy North China Coal Medical College Tangshan 063000 China

Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b,are synthesized. The triflate agent,9a or 9b,is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine,protection of the amine group with di-tert-butyl dicarbonate,alkylation with chlorohydrin,and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 3.% and 15%,respectively.

关键词： positron emission tomography triflate L-tyrosine [18F]FET precursor PET imaging

Establishment of a uremic apolipoprotein E knockout mouse model to explore the mechanism of uremic atherosclerosis

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Journal of pharmaceutical Analysis 2010年第2期22卷 111-115页

作者： Yan Shen1,Zu-Yi Yuan2,Yan Xiao3.Li-Jun Wang2,Yue Wu2,Xiao Liang2,Yan Zhao2,Yu-Ling Tian2,Wei-Min Liu2,Tao Chen21. Department of Nephrology,the First Affiliated hospital,Medical School of Xi’an Jiaotong university,Xi’an 710061 2. Department of Cardiology,the First Affiliated hospital,Medical School of Xi’an Jiaotong university,Xi’an 710061 3. Department of Cardiology,Beijing Xishan hospital,Beijing 100144,china. Department of Nephrology First Affiliated Hospital Medical School of Xi'an Jiaotong University Xi'an 710061 China Department of Cardiology First Affiliated Hospital Medical School of Xi'an Jiaotong University Xi'an 710061 China Department of Cardiology Beijing Xishan Hospital Beijing 100144 China

Objective To establish a uremic apoE-/- mouse model to observe serum biochemical parameters and features of aortic root atherosclerosis (AS) in the model. Methods A uremic model was induced surgically in apoE-/- mice: electrocautery of the right kidney at 8 weeks of age and nephrectomy (NX) of the left one 2 weeks later. Control mice were sham-operated. Two weeks after NX,renal functions were detected in the uremic and control mice to evaluate the efficiency of the model. After 10 weeks of NX,blood samples were taken to determine serum biochemical parameters,and aortic root was collected for frozen sections to investigate the lesion features of AS. Results Two weeks after NX,renal functions declined significantly in the uremic mice compared with the control ones,and remained stable 8 weeks later either in males or in females. Ten weeks after NX,serum levels of TCH,TG and LDL-C were dramatically higher in the uremic mice than in the controls,whereas no differences in serum HDL-C or glucose concentration were found between the two groups. Aortic root plaque relative area increased significantly in the uremic mice compared with the controls either in males or in females; more-over,the lesion area was larger in female mice than in male ones. Conclusion We established a uremic apoE-/- mouse model successfully,and this model is characterized by accelerated atherogenesis which is associated with an increase in serum lipid profile. This experimental model can be a useful tool to study the pathogenesis and therapeutic strategies of uremic AS.

关键词： uremia atherosclerosis apoE-/- mouse

Cell cycle-dependent gene networks relevant to cancer

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Progress in Natural Science:Materials International 2008年第8期18卷 945-952页

作者： Yun Xiao a,1, Xia Lia,b,*,1, Yueying Yang a, Yadong Wangc, Shaoqi Rao a,b a College of Bioinformatics Science and Technology, and Bio-pharmaceutical Key Laboratory of Heilongjiang Province and State, Harbin Medical university, Harbin 150086, china b Biomedical Engineering {3. of capital Medical university, Beijing 10004, china c Department of Computer Science, Harbin {3. of Technology, Harbin 150080, china College of Bioinformatics Science and Technology and Bio-pharmaceutical Key Laboratory of Heilongjiang Province and State Harbin Medical University Harbin 150086 China Biomedical Engineering institute of capital Medical university Beijing 10004 China Department of Computer Science Harbin Institute of Technology Harbin 150080 China

The analysis of sophisticated interplays between cell cycle-dependent genes in a disease condition is one of the largely unexplored areas in modern tumor biology research. Many cell cycle-dependent genes are either oncogenes or suppressor genes, or are closely associated with the transition of a cell cycle. However, it is unclear how the complicated relationships between these cell cycle-dependent genes are, especially in cancers. Here, we sought to identify significant expression relationships between cell cycle-dependent genes by analyzing a HeLa microarray dataset using a local alignment algorithm and constructed a gene transcriptional network specific to the cancer by assembling these newly identified gene-gene relationships. We further characterized this global network by partitioning the whole network into several cell cycle phase-specific sub-networks. All generated networks exhibited the power-law node-degree distribution, and the average clustering coefficients of these networks were remarkably higher than those of pure scale-free networks, indicating a property of hierarchical modularity. Based on the known protein-protein interactions and Gene Ontology annotation data, the proteins encoded by cell cycle-dependent interacting genes tended to share the same biological functions or to be involved in the same biological processes, rather than interacting by physical means. Finally, we identified the hub genes related to cancer based on the topological importance that maintain the basic structure of cell cycle-dependent gene networks.

关键词： Cell cycle Microarray HeLa cell Gene network

Overexpression of Nurrl Enhances the Vulnerability of SK-N-SH Cells to Neurotoxin 6-OHDA

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Overexpression of Nurrl Enhances the Vulnerability of SK-N-S...

Recombinant expression of rt-PA gene (encoding Reteplase) in gametophytes of the seaweed Laminaria japonica (Laminariales,Phaeophyta)

中国细胞生物学学会第九次会员代表大会暨青年学术大会

作者： Yong-Mei Zhao~1 Yang Liu~1 Hai-Yan Zhang~2 Qun-Yuan Xu~3.1 Key Laboratory for Neurodegenerative Diseases of Ministry of Education,xuanwu hospital of capital Medical university,Beijing {3. 2 Department of Cell Biology,capital Medical university,Beijing 100069 3.Beijing institute for Neuroscience,capital Medical university,Beijing 100069,china

Objectives:To investigate whether overexpression of Nurr1(nuclear receptor-related factor 1)enhances the vulnerability of SK-N-SH ceils to neurotoxin ***1 is a transcription factor of the steriod/thyroxin hormone nucl... 详细信息

关键词： Nurrl overexpression 6-OHDA apotosis

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Science china(Life Sciences) 2008年第12期51卷 1116-1120页

作者： ZHANG YiChen1,2, JIANG Peng1, GAO JiangTao1,3. LIAO JianMin4, SUN ShiJing4, SHEN ZiLong4 & QIN Song1, 1 institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, china 2 College of Chemistry and Life Science, Tianjin Normal university, Tianjin 3.03.7, china 3.Graduate university of Chinese Academy of Sciences, Beijing 100049, china 4 Biotechnology Center, china pharmaceutical university, Nanjing 210009, china institute of Oceanology Chinese Academy of Sciences Qingdao 266071 China College of Chemistry and Life Science Tianjin Normal University Tianjin 300387 China Graduate university of Chinese Academy of Sciences Beijing 100049 China Biotechnology Center China Pharmaceutical University Nanjing 210009 China

The life cycle of seaweed Laminaria japonica involves a generation alternation between diploid sporophyte and haploid gametophte. The expression of foreign genes in sporophte has been proved. In this research, the recombinant expression in gametophyte was investigated by particle bombardment with the rt-PA gene encoding the recombinant human tissue-type plasminogen activator (Reteplase), which is a thrombolytic agent for acute myocardial infarction (AMI). Transgenic gametophytes were selected by their resistance to herbicide phosphiothricin (PPT), and proliferated in an established bubble column photo-bioreactor. According to the results from quantitative ELISA, Southern blotting, and fibrin agarose plate assay (FAPA) for bioactivity, it was showed that the rt-PA gene had been inte-grated into the genome of gametophytes of L. japonica, and the expression product showed the ex-pected bioactivity, implying the proper post-transcript modification in haploid gametophyte.

关键词： Laminaria japonica gametophyte genetic engineering Reteplase rt-PA bioreactor

Binding activity of H-Ras is necessary for in vivo inhibition of ASK1 activity

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Cell Research 2004年第2期14卷 148-154页

作者： Jun DU~(1,2*), Shao Hui CAI~(3.4), Zhe SHI~3. Fumihiko NAGASE~1 ~1Department of Medical Technology, Nagoya university School of Health Sciences, Aichi 461-8673. Japan. ~2School of pharmaceutical Science, Sun Yat-Sen university, Guangzhou, 510089, {3.. ~3.epartment of Immunology, Nagoya university Graduate and Faculty School of Medicine, Aichi, 466-8550, Japan. ~4College of Pharmacy, Jinan university, Guangzhou, 51063., {3.. 2School of pharmaceutical Science Sun Yat-Sen University Guangzhou 510089 China. 4College of Pharmacy Jinan University Guangzhou 510632 China. 3.epartment of Immunology Nagoya University Graduate and Faculty School of Medicine Aichi 466-8550 Japan. 1Department of Medical Technology Nagoya University School of Health Sciences Aichi 461-8673 Japan.

H-Ras is well known as one of the essential components of Ras/Raf/MEK/ERK cascade, which is a critical prosurvival signaling mechanism in most eukaryotic cells. Ras targets Raf/MEK/ERK cascade by integrating and transmitting extracellular signals from growth factor receptors to Raf, leading to the propagation of signals to modulate a serious of cellular survival events. Apoptosis signal-regulating kinasel (ASK1) serves as a general mediator of cell death because it is responsive to a variety of death signals. In this study, we found that H-Ras interacted with ASK1 to cause the inhibition of both ASK1 activity and ASK1-induced apoptosis in vivo, which was reversed only partially by addition of RafS621A, an antagonist of Raf, whereas MEK inhibitor, PD98059, and PI3. inhibitor, LY294002, did not disturb the inhibitory effect of H-Ras on ASK-1-induced apoptosis. Furthermore, by means of immunoprecipitate and kinase assays, we demonstrated that the interaction between H-Ras and ASK1 as well as the inhibition

关键词： H-Ras ASK1 apoptosis binding activity.