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Metallothionein Genes in the Nematode Caenorhabditis elegans and Metal Inducibility in Mammalian Culture Cells

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Biomedical and Environmental sciences 1994年第3期7卷 222-231页

作者： FUMIHIKO KUGAWA HIROKO YAMAMOTO SHIGEHIRO OSADA MASATADA AOKI MASAYOSHI IMAGAWA AND TSUTOMU NISHIHARA (college of Pharmacy, Nihon university, 7-7-1 Narashino-dai, Funabashi,Chiba 2.4 and Faculty of{2. sciences, Osaka university,1-6 Yama college of Pharmacy Nihon University Chiba Japan.

Genomic DNAs of metallothionein Ⅰ and Ⅱ in Caenorhabditis elegans (CeMT-Ⅰand CeMT-Ⅱ) were isolated by YAC library/polytene filter hybridization followed by subcloning of corresponding cosmid clones. Both genes are mapped at chromosome V. Although the similarities of 5'-flanking regions and coding regions have shown only 55-58%, the introns are split at the same position in both genes, indicating that these two genes are originally from the same gene. While several metal responsive elements are conserved among eukaryotes, only one metal responsive element was found in the promoter region in CeMT-Ⅱ and not in CeMT-Ⅰ. Indced, neither of 5'-flanking regions of CeMT-Ⅰ nor CeMT-Ⅱ connected to chloramphenicol acetyltransferase reporter gene is responsive to heavy metals in mammalian culture cells by transient transfection analysis. These results would suggest that the metal regulatory factors in *** might be different from those conserved in invertebrates and vertebrates, although the MTs in C elegans revealed the similarities to mammalian MTs in several points

关键词： MT gene Metallothionein Genes in the Nematode Caenorhabditis elegans and Metal Inducibility in Mammalian Culture Cells

Predictive model of blood-brain barrier penetration of organic compounds

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Acta Pharmacologica Sinica 2005年第4期26卷 500-512页

作者： Xiao-lei MA Cheng CHEN Jie YANG~2.State Key Laboratory of pharmaceutical Biotechnology,School of Life Science,Nanjing university,Nanjing 2.0093,China State Key Laboratory of pharmaceutical Biotechnology School of Life Science Nanjing University Nanjing China

Aim:To build up a theoretical model of organic compounds for the prediction ofthe activity of small molecules through the blood-brain barrier(BBB)in ***:A training set of 37 structurally diverse compounds was used toconstruct quantitative structure-activity relationship(QSAR)***-lecular and intramolecular solute descriptors were calculated using molecularmechanics,molecular dynamics simulations,quantum chemistry and so *** models were optimized using multidimensional linear regression fitting andstepwise method.A test set of 8 compounds was evaluated using the models aspart of a validation ***:Significant QSAR models(R=0.955,s=0.2.2.of the BBB penetration of organic compounds were *** penetrationwas found to depend upon the polar surface area,the octanol/water partitioncoefficient,Balaban Index,the strength of a small molecule to combine with themembrane-water complex,and the changeability of the structure of a solute-mem-brane-water ***:The QSAR models indicate that the distribu-tion of organic molecules through BBB is not only influenced by organic solutesthemselves,but also relates to the properties of the solute-membrane-water complex,that is,interactions of the molecule with the phospholipid-rich regions of cellularmembranes.

关键词： blood-brain barrier quantitative structureactivity relationship theoretical models

Expression pattern of antibacterial genes in the Musca domestica

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Science China(Life sciences) 2009年第9期52卷 823-830页

作者： WANG Yan1,JIN XiaoBao1,ZHU JiaYong1,ZENG AiHua2.CHU FuJiang1,YANG XiaoRong1 & MA Yan1 1 Institute of Pathogen Biology and Department of Pathogen Biology,Guangdong pharmaceutical university,Guangzhou 510006,China 2.Department of Pharmacology,Guangdong pharmaceutical university,Guangzhou 510006,China Institute of Pathogen Biology and Department of Pathogen Biology Guangdong Pharmaceutical University Guangzhou China Department of Pharmacology Guangdong Pharmaceutical University Guangzhou China

This work studied the transcriptional patterns of three antibacterial genes,attacin,defensin and cecropin,during the development of Musca domestica. Quantitative analysis by real-time PCR was performed on mRNA levels in different development stages and challenged 3rd-instar larva at different time points after challenge of Musca domestica. The results revealed a predominance of the transcripts of all three genes during the 3rd-instar larvae and the adults. In the meanwhile,it revealed the greatest increase in mRNA. The transcript levels increased to 801 times,1009 times and 2.00 times respectively for cecropin,attacin and defensin in 3rd-instar larvae after challenging susceptible bacterium. The results suggested that the transcriptional patterns of Musca domestica antibacterial genes were different during the different growth stages as well as the microbial challenge encountered in 3rd-instar larvae.

关键词： Musca domestica expression pattern attacin defensin cecropin

Permeation-enhancing effects of chitosan formulations on recombinant hirudin-2.by nasal delivery in vitro and in vivo

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Acta Pharmacologica Sinica 2005年第11期26卷 1402-1408页

作者： Yu-jie ZHANG~(1,2., Chang-hua MA,Wan-liang LU, Xuan ZHANG, Xiao-liang WANG, Jian-ning SUN, Qiang ZHANG~(1.3) ~1 School of pharmaceutical sciences, Peking{2. Health Science Center, Beijing 100083, China,~2.Department of Chinese Pharmacy, Beijing{2. of Traditional Chinese Medicine, Beijing 100102. China School of pharmaceutical sciences Peking University Health Science Center Beijing China Department of Chinese Pharmacy Beijing University of Traditional Chinese Medicine Beijing China

Aim: To investigate the enhancing effects of chitosan with or without enhancers on nasal recombinant hirudin-2.(rHV2. delivery in vitro and in vivo, and to evaluate the ciliotoxicity of these formulations. Methods: The permeation-enhancing effect of various chitosan formulations was estimated by using the permeation coefficient of fluorescein isothiocyanate recombinant hirudin-2.(FITC-rHV2. across the excited rabbit nasal epithelium in vitro. The effect was further evaluated by measuring the blood concentration level after nasal absorption of FITC-rHV2.in rats. The mucosal ciliotoxicity of different formulations was evaluated with an in situ toad palate model. Results: Chitosan at a concentration of 0.5% with or without various enhancers significantly increased the permeability coefficient (P) and relative bioavailability (Fr) of FITC-rHV2.compared with the blank control. The addition of 1 % sodium dodecylsulfate, 5% Brij35,5% Tween 80,1.5% menthol, 1% glycyrrhizic acid monoammonium salt (GAM) or 4% Azone into the 0.5% chitosan solution resulted in a further increase in absorption (P<0.05) compared with 0.5% chitosan alone. But co-administration of chitosan with 5% hydroxyl-propyl-beta-cyclodextrin (HP-β-CD), 5% lecithin or 0.1 % ethylenediamine tetraacetic acid (EDTA) was not more effective than using the 0.5% chitosan solution alone. Chitosan alone and with 5% HP-β-CD, 0.1 % EDTA, 1 % GAM or 5%Tween80 was relatively less ciliotoxic. Conclusion: Chitosan with or without some enhancers was able to effectively promote the nasal absorption of recombinant hirudin, while not resulting in severe mucosal ciliotoxicity. A chitosan formulation system would be a useful approach for the nasal delivery of recombinant hirudin.

关键词： nasal absorption hirudin chitosan formulation permeability bioavailability enhancer: ciliotoxicity

Doxepin protects cultured neurons against oxidative stress-induced injury

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Acta Pharmacologica Sinica 2004年第3期25卷 43-46页

作者： Bian-sheng JI,He JI1,Guo-qing LIU2.Department of Pharmacology,China pharmaceutical university,Nanjing 2.0009 1Department of Medicine,Henan university,Kaifeng 475001,China Department of Pharmacology China Pharmaceutical University Nanjing 210009 Department of Mecine Henan University Kaifeng 475001

AIM: To investigate protective effects of doxepin (Dox) on cultured neuronal injury induced by oxidative stress. METHODS: Cytotoxicities of glutamate (Glu 0.5 mmol/L, 15 min), sodium dithionite (0.5 mmol/L, 2. h) or hemo- globin (Hb100 mg/L,2. h)and the protective effects of Dox were observed. RESULTS: Exposure of cultured neurons to Glu, sodium dithionite and Hb developed a neurotoxicity expressed in the thiazol blue tetrazolium bro- mide (MTT) assay, the increase of lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) content and intracellular [Ca2.]i accumulation, as well as the decrease of superoxide dismutase (SOD) activity. DOX 1-100 nmol/L significantly inhibited all above changes. CONCLUSION: Dox protects cultured neurons against oxidative stress-induced injury by suppressing intracellular [Ca2.]iaccumulation, decreasing lipid peroxide generation and stimulating antioxidant enzyme.

关键词： doxepin ischemia glutamic acid hemoglobins neurons

Protective effects of cariporide on endothelial dysfunction induced by high glucose

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Acta Pharmacologica Sinica 2005年第3期26卷 329-333页

作者： Shuang-xi WANG Xiao-ming XIONG Tao SONG Li-ying LIU~2.Department of Pharmacology,pharmaceutical college,Central South Universi~ Changsha 410078,China Department of Pharmacology Pharmaceutical College Central South University Changsha China

Aim:To explore the effects of cariporide,a selective sodium-hydrogen antiporterinhibitor,on endothelial dysfunction induced by high ***:Acetyl-choline (ACh)-induced endothelium-dependent relaxation (EDR),sodium nitro-prusside (SNP)-induced endothelium-independent relaxation and biochemical pa-rameters including malondialdehyde (MDA),superoxide dismutase (SOD),andnitric oxide (NO) were measured in rat isolated ***:A 6-h incubationof aortic rings with high glucose (44 mmol/L) resulted in a significant inhibitionof EDR,but had no effects on endothelium-independent *** the 6-hincubation of aortic rings in the co-presence of cariporide (0.01,0.1,and 1 μmol/L)with high glucose,cariporide prevented the inhibition of EDR caused by highglucose in concentration-dependent ***,high glucose decreasedSOD activity and contents of NO,and increased MDA concentration in *** (1 μmol/L) significantly resisted the decrease of NO contentand SOD activity,and elevation of MDA concentration caused by high glucose inaortic *** (44 mmol/L) or cariporide (1 μmol/L) alone had no ef-fect on EDR,endothelium-independent relaxation and biochemical ***:Cariporide significantly prevented endothelial dysfunction inducedby high *** mechanisms of endothelial dysfunction induced by highglucose may involve the activation of sodium-hydrogen antiporter and the gen-eration of oxygen-free radicals,but it is not related to the change of osmolarity.

关键词： sodium-hydrogen antiporter endothelium glucose nitric oxide malondialdehyde superoxide dismutase

Intramolecular aromatic-ring stacking interaction of ternary Zn(UTP)L^(2.) complexes

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Chinese Science Bulletin 1997年第14期42卷 1172-1175页

作者： LE Xueyi, WU Fuhai, SONG Fenyun and Jl Liangnian1.Department of Chemistry, Zhongshan university, Guangzhou 5102.5, China State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of sciences, Lanzhou 730000, China 2. Department of Hygienics, Guangdong{2. School, Guangzhou 5102.4, China Department of Chemistry Zhongshan University Guangzhou China State Key Laboratory for Oxo Synthesis and Selective Oxidation Lanzhou Institute of Chemical Physics Chinese Academy of Sciences Lanzhou China Department of Hygienics Guangdong Pharmaceutical School Guangzhou China

THE mechanism of the action of the classic platinum antitumor drugs can be interpreted accord-ing to their bidentate, bifunctional interaction with the DNA of the tumor cell, resulting in in-hibition of the DNA replication. Recently, it was found that a new class of compounds withthe general formula cis-[Pt（NH3）2./sub>（N-het）Cl]Cl（N-het is a heteroaromatic N-base like pyri-dine） show effective antitumor activities. However, two possible mechanisms of action

关键词： stacking interaction ternary complexes heteroaromatic N-bases UTP4- stability constants.

Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2.2.)

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Chinese Journal of Cancer Research 2024年第3期36卷 240-256页

作者： Zaiwei Song Dan Jiang Lingling Yu Yixuan Chen Daobin Zhou Yue Li Depei Wu Lingli Zhang Liyan Miao Jun Ma Jun Zhu Hongmei Jing Rongsheng Zhao the Steering Committee,the Consensus Panel and the Evidence Synthesis Group Evidence-based Pharmacy Professional Committee of Chinese pharmaceutical Association(CPA) Hospital Pharmacy Professional Committee of Chinese pharmaceutical Association(CPA) Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society(CPS) Expert Committee on Lymphoma of Chinese Society of Clinical Oncology(CSCO) Expert Committee on Leukemia of Chinese Society of Clinical Oncology(CSCO) Society of Integrative Cardio-Oncology of China Anti-Cancer Association(CACA) Chinese Society of Hematology of Chinese Medical Association(CMA) Hospital Pharmacy Professional Committee of Cross-Straits Medicine Exchange Association(SMEA) Department of Pharmacy Peking University Third HospitalBeijing 100191China Institute for Drug Evaluation Peking University Health Science CenterBeijing 100191China Therapeutic Drug Monitoring and Clinical Toxicology Center Peking UniversityBeijing 100191China Department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Hematology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of Cardiology the First Affiliated HospitalHarbin Medical UniversityHarbin 150001China Department of Hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Pharmacy Evidence-based Pharmacy CenterWest China Second HospitalSichuan UniversityChengdu 610041China Department of Pharmacy the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Hematology and Oncology Harbin Institute of Hematology and OncologyHarbin 150010China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of LymphomaPeking University Cancer Hospital&InstituteBeijing 100142China Department of Hematology Peking University Third HospitalBeijing 100191China 不详

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell ***,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased *** evidence-based expert consensus was formulated using an evidence-based approach and the Delphi *** Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,*** consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special *** multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

关键词： Consensus BTK inhibitors safety adverse drug events drug-drug interactions

Immobilized enzyme reactors in HPLC and its application in inhibitor screening:A review

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Journal of pharmaceutical Analysis 2012年第2期2卷 83-89页

作者： Si-Meng Fang a,Hai-Na Wang a,Zhong-Xi Zhao b,Wei-Hong Wang a,n a School of pharmaceutical sciences,Shandong{2.,Ji’nan,China b School of pharmaceutical sciences and Center for pharmaceutical Research & Drug Delivery Systems,Shandong{2.,Ji’nan,China School of pharmaceutical sciences Shandong University Ji'nan China. School of pharmaceutical sciences and Center for pharmaceutical Research & Drug Delivery Systems Shandong University Ji'nan China.

This paper sets out to summarize the literatures based on immobilized enzyme bio-chromatography and its application in inhibitors screening in the last *** order to screen enzyme inhibitors from a mass of compounds in preliminary screening,multi-pore materials with good biocompatibility are used for the supports of immobilizing enzymes,and then the immobilized enzyme reactor applied as the immobilized enzyme stationary phase in ***,a technology platform of high throughput screening is gradually established to screen the enzyme inhibitors as new anti-tumor ***,we briefly summarize the selective methods of supports,immobilization techniques,co-immobilized enzymes system and the screening model.

关键词： Immobilized enzyme reactors (IMERs) Molecular bio-chromatography Screening enzyme inhibitors