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第十五届国际药理学大会

作者： Chen Yuh-Fung Lin Yuh Tzy tsai huei-yann Department of Pharmacology. China Medical University Taichung4042. Departemnt of Nursing Jen - Teh Junior College of MedicineNursing and ManagementMiaoli 35603. Department of Pharmacology China Medical UniversityTaichung4042.

＜正＞ Paeoniflorin （PF）,a principal component from paeony roots, has been used as an antispasmodic and analgesic agent. From our previous study, we found that paeoniflorin showed antinociceptive effect on both the writhing response test and formalin test performed in mice. In the present study, the effect of paeoniflorin on monoamine neurotransmitters and their metabolites was investigated by using HPLC-microdialysis in mice and rats. PF increased norepinephrine （NE） and 3,4-dihydroxyphenylacetic acid （DOPAC） content in cortex, and increased the content of NE and decreased serotonin （5-HT） content in medulla of the homogenized brain tissue. By microdialysis. paeoniflorin increased DOPAC and 5 -hydroxyindoleacetic acid （5 - HIAA） content and increased homovanillic acid （HVA）,DOPAC and 5 - HIAA content in anesthetic rat cortex and striatum,*** turns out that PF could activate the release of monoamines and increase their metabolites in mice and rat brain, which might account for its antinociceptive effects.

关键词： Paeoniflorin Monoamine Levels HPLC-Microdialysis.

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Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats

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Acta Pharmacologica Sinica 2004年第8期 53-56页

作者： Tsung-hsing LEE,Yi-jung tsai,yann-jang CHEN Department of Anesthesiology Department of Biological Sciences "National" Sun Yat-sen University Kaohsiung Chang-Gung Memorial Hospital Center for General Education "National" Yang-Ming University Taipei 833 Taiwan China

AIM: To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats. METHODS: Tail-flick test as pain threshold measurement and intrathecal injection techniques were used. RESULTS: Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5μg/h for 5 d. Co administration of intrathecal roscovitine 1μg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose"Cresponse curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED50 of morphine (dose producing 50 % of the maximum response). CONCLUSION: Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.

关键词： roscovitine cyclin-dependent kinase 5 morphine

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Biological Applications of Silica Based Nanoparticles

Biological Applications of Silica Based Nanoparticles

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第七届全国磷化学化工暨第四届海峡化学生物学、生物技术与医药发展讨论会

作者： Chih-Pin tsai yann Hung Chung-Yuan Mou Department of Chemistry National Taiwan University Taipei Taiwan 106 Department of Chemistry National Taiwan University Taipei Taiwan 106 Department of Chemistry National Taiwan University Taipei Taiwan 106 Center for Condensed Matter Sciences National Taiwan University Taipei Taiwan 106

Silica has great biocompatibility. Core-shell nanoparticles with superparamagnetic iron oxide core and Ru(bpy)3Cl2 containing silica shell have been synthesized and the nanoparticles can serve as dual imaging agents. Mesoporous materials, especially MCM-type silica, have many unique properties, such as ordered porous structure, extremely high surface area (>1000 m2 g-1), large pore volume, and well-defined and tunable pore size (1.5-10 nm). It is proposed that mesoporous materials can act as a convenient reservoir for drugs and biomolecules. At the same time, the extensive internal structure may be utilized for carrying non-releasing molecular imaging agents, such as fluorophore or magnetic resonance imaging (MRI) contrast agent. We have functionalized nano-sized mesoporous silica to be used as fluorescence and MR cell tags. Cellular uptake and the potential of using these nanoparticles as cell markers have been demonstrated.

关键词： Biological Applications of Silica Based Nanoparticles

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Determination of Fragmentation Schemes and Metabolites of Fluorinated Histone Deacetylase Inhibitors for Use as Positron Emission Tomography Imaging Agents Using HPLC-MS/MS

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International Journal of Analytical Mass Spectrometry and Chromatography 2018年第1期6卷 1-19页

作者： Wei-Hsi Chen Yu-Chieh Hsiao Ming-Hsin Li Mu-Chen tsai Chun-Fang Feng Han-Chih Chang Hung-Wen Yu Chyng-yann Shiue Chemistry Division Institute of Nuclear Energy Research Taiwan Isotope Application Division Institute of Nuclear Energy Research Taiwan PET Center Department of Nuclear Medicine National Taiwan University Hospital Taiwan PET Center Department of Nuclear Medicine Tri-Service General Hospital Taiwan

High performance liquid chromatography coupled with tandem mass spectrometry was developed and validated as a method for the analysis of fluorinated histone deacetylase inhibitors (F-HDACi), and then employed to study their metabolism in biosystems. Four HDACi analogs labeled with the positron emission nuclide 18F constitute a group of potential positron emission tomography imaging agents, which were developed by the Institute of Nuclear Energy Research (INER) and coded as INER-1577 #1, #2, #3, and #4 during animal studies for the diagnosis of dementia. The performance of the method was found to be suitable for the determination of analog #3, and it was employed to determine the structures and fragmentation mechanisms of all four analogs and to study the biotransformations of analogs #3 and #4. The results indicated that the method used for the determination of analog #3 was suitable for determining the abundance of the analogs in chemical and biochemical tests with high precision, accuracy, reproducibility, and recovery. Weaknesses in the chemical bonding of the analogs were found to involve the fluoro, dimethylamino, and benzamide groups in a fragmentation mechanism deduced via tandem mass spectrometry. The metabolites of analogs #3 and #4 in rat liver microsomes and rat plasma were also identified to clarify their characteristic behaviors in biosystems. The major product of analogs #3 in liver microsomes was produced by hydroxylation of the benzylic carbon atom, but in rat plasma the metabolites of analog #3 were produced by hydrolysis of the benzamide group to give a diaminobiphenyl compound with the simultaneous replacement of a fluorine atom by a hydroxyl group. The metabolites of analog #4 in liver microsomes were produced by hydroxylation of the benzylic carbon atom and hydrolysis of the benzamide bond. The results of the studies characterized the chemical and biochemical behaviors of the series F-HADCi analogs.

关键词： Histone Deacetylase Inhibitors Positron Emission Tomography Imaging Agent Dementia LC-Tandem MS Fragmentation Mechanism Metabolism Pathways Epigenetics

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Blood DNA methylation markers in prospectively identifiedhepatocellular carcinoma cases and controls from Taiwan

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World Journal of Hepatology 2016年第5期8卷 301-306页

作者： Hui-Chen Wu Jing Shen Hwai-I Yang Wei-yann tsai Chien-Jen Chen Regina M Santella Department of Environmental Health Sciences Mailman School of Public Health of Columbia UniversityNew YorkNY 10032United States Genomics Research Center Academia SinicaTaipei 11529Taiwan Graduate Institute of Clinical Medical Science China Medical UniversityTaichung 40402Taiwan Molecular and Genomic Epidemiology Center China Medical University HospitalTaichung 40402Taiwan Departments of Biostatistics Mailman School of Public Health of Columbia UniversityNew YorkNY 10032United States Department of Statistics National Chen Kung UniversityTainan 70101Taiwan Graduate Institute of Epidemiology and Preventive Medicine College of Public HealthNational Taiwan UniversityTaipei 10617Taiwan Herbert Irving Comprehensive Cancer Center Columbia University Medical CenterNew YorkNY 10032United States

AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarke

关键词： DNA methylation Epigenetics Hepatitis Bvirus Hepatocellular carcinoma White blood cell DNA

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