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Smad7基因沉默对细胞增殖的影响

Smad7基因沉默对细胞增殖的影响

引用

中国药理学会毒理专业委员会第十次学术会议

作者：霍艳英王莹张开泰王莉项晓琼胡迎春徐勤枝李刚米粲吴德昌军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室军事医学科学院放射医学研究所四室

目的:Smads蛋白家族在转化生长因子β(transforming growth factor-βs,TGF-βs)家族信号通路中发挥不同的作用,参与调控细胞的增殖、转化和凋亡。其中,Smad7具有与其它信号分子不同的负性调控作用,Smad7功能紊乱是TGF-β信号通路紊乱... 详细信息

目的:Smads蛋白家族在转化生长因子β(transforming growth factor-βs,TGF-βs)家族信号通路中发挥不同的作用,参与调控细胞的增殖、转化和凋亡。其中,Smad7具有与其它信号分子不同的负性调控作用,Smad7功能紊乱是TGF-β信号通路紊乱的机制之一。本研究旨在探讨Smad7基因沉默对细胞恶性转化进程的影响。方法:利用RNAi技术,设计并合成了针对Smad7基因的SiRNAs,用基因转染的方法瞬时转染BEP2D和BERP35T2细胞系,用Northern blot法检测RNAi效应。在此基础上,用MTT法检测Smad7基因沉默后对细胞增殖能力的影响和对TGF-β1介导的生长抑制效应的影响,并用流式细胞技术检测Smad7基因沉默后对细胞凋亡有无影响。结果:对永生化及恶性转化的人支气管上皮细胞系BEP2D和BERFJ5T2,RNAi能明显抑制Smad7基因的表达;Smad7基因沉默细胞的增殖能力明显低于对照,同时,TGF-β1对Smad7基因沉默细胞的生长抑制作用增强;Smad7基因沉默对该细胞系的凋亡无明显影响。结论:Smad7基因沉默后,该基因对TGF-β信号通路的抑制作用消失,使TGF-β1介导的对细胞的生长抑制作用恢复,细胞增殖能力减弱。

关键词：基因沉默细胞增殖能力 TGF Smad7

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Safety,tolerability and pharmacokinetic study of recombinant human parathyroid hormone in healthy male Chinese subjects

Safety,tolerability and pharmacokinetic study of recombinant...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： LI Wei-yong LI Qian QIAO Jian DENG Jun-gang ZHANG Ying Institute of Clinic Pharmacy,Union Hospital Affiliated to Tongji Medical College,Huazhong University of Science & Technology,Wuhan 430022,Hubei,China

AIM:To determine the safety,tolerability and pharmaco- kinetic parameters of a new drug recombinant human para- thyroid hormone [rhPTH（1-84）] in healthy male Chinese subjects. METHODS:Thirty-six healthy male volunteers were ran- domly divided into 3 *** volunteers in these groups received single subcutaneous injection of rhPTH（1- 84）in a dosage of 1,2 and 4 μg/kg *** samples were obtained before and after administration with- in 24 *** rhPTH concentrations in serum were de- termined by enzyme linked immunosorbent assay （ELISA）.The pharmacokinetic parameters determined with use of standard noncompartmental analysis were the maximum serum concentration(C),the time to attain that concentration(t),and the area under the serum concentration-time curve up to 24 hours(AUC)and up to infinity(AUC).Dose proportionality of phar- maeokinetic parameters(AUC,Cof every volunteer of each dosage and AUC was computed from log transformed data)and was examined by mean of analysis of variance （ANOVA）using SPSS software *** the study, subjects' symptoms,objective signs,and vital signs,in- cluding blood pressure,heart rate,respiratory rate and body temperature,were checked and 12-lead electrocar- diography was recorded before and after drug administration within 24 *** laboratory tests,including hema- tology,blood biochemistry,serum electrolyte,and urinal- ysis,were performed before and after drug administration within at 24 hours. RESULTS:The specificity,sensitivity,linear range, precision and accuracy of the method were all satisfied for the determination of rhPTH in *** serum concen- tration-time curve of most volunteers clearly exhibited a double-peak profile,with the first peak appearing approxi- mately 10 to 30 minutes and the second peak appearing ap- proximately 1.5 to 2 hours after subcutaneous injection of the *** concentrations of all subjects 24 hours after dosing in the three groups almost returned to physio- logic p

关键词： recombinant human parathyroid hormone tolerability safety pharmacokinetics single dose

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Effects of florfenicol on early cytokine response and survival in a murine septic shock model

Effects of florfenicol on early cytokine response and surviv...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： ZHANG Xue-mei~(1,2) SONG Yu~1 DENG Xu-ming~1 AN Na~1 CI Xin-xin~1 1 Department of Pharmacology,College of Animal Science and Veterinary Medicine,Jilin University,Changchun 130062,Jilin,China 2 Department of Animal Medicine,Agricultural College of Yanbian University,Yanbian 133400,Jilin,China

AIM:To study the effects of florfenicol on early cytokine response and survival in treatment of infected murine in- duced by septic shock. METHODS:The effect of florfenicol on cytokine produc- tion from lipopolysaccharide(LPS)-stimulated macrophag- es was investigated by using a mouse macrophage cell line. The influence of florfenicol on the survival rate of mice in- jected with lethal dose of endotoxin and early cytokine re- sponses in endotoxemia mice were *** serum cytokine productions of mice were determined at different time points. RESULTS:Florfenicol significantly reduced the produc- tions of tumor necrosis factor(TNF)and interleukin-6 (IL-6)in the supernatant of cells as well as slightly atten- uated the secretions of interleukin-1β(IL-1β)and interleu- kin IL-10(IL-10).No significant difference in IL-1β con- centration was observed between florfenicol-treated group and control ***,florfenicol significantly in- creased serum IL-10 concentration of ***,it was found that florfenicol(at the dose of 100 mg/kg)signifi- cantly increased the survival rate of mice compared to the control group after mice were administrated LPS. CONCLUSION:These data indicate that florfenicol can improve survival rate of endotoxemia mice via modulating early cytokine responses and antibiotics mighty be of po- tential usefulness in treatment of bacterial shock.

关键词： florfenicol lipopolysaccharide(LPS) cytokines mice survival rate

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Study on effects of cinobufagin on the immunologic function of mice in vitro

Study on effects of cinobufagin on the immunologic function ...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： SONG Yu~(1,2) JIANG Feng~1 WANG Da-cheng~1 ZHU Tong-fei~1 HAN Xiao-hu~1 ZHAO Wen-jie~2 DENG Xu-ming~1 1 College of Animal Science and Veterinary Medicine,Jilin University,Changchun 130062,Jilin,China 2 National Standard Laboratory of Pharmacology for Traditional Chinese Medicine,Jilin Natural Pharmatech Co.Ltd,Changchun 130012,Jilin,China

AIM:To investigate the immunoregulatory effects of cinobufagin from the chloroform extract of Venenum Bufo- nis,a famous traditional Chinese medicine in vitro. METHODS:Proliferation of the splenic lymphocytes in Balb/c mice was measured by MTT *** metaboilic level and phagotrophic activity of PMΦ were also deter- mined by MTT *** expressions of CD and CD and cell cycle of the splenic lymphocytes were detected by flow Cytometry. RESULTS:Administration of cinobufagin or coadminis- tration with Con A or LPS increased the cell proliferation and the percentage of S phase cells in the splenic lympho- cytes at a dose-dependent manner（P＜0.05 or P＜ 0.01）.Cinobufagin also enhanced the metabolic capability of MTT and the phagocytosis function of PMΦ（P＜0.05 or P＜0.01）.In addition,it was found that the single administration of cinobufagin or coadministration with Con A or LPS also could increase expressions of CD and CD in T lymphocytes（P＜0.05 or P＜0.01）. CONCLUSION:Single administration of cinobufagin or coadministration with Con A or LPS could enhance the re- active ability to the splenic lymphocytes and PMΦ in mice. The data indicate that the immunoregulatory effect of cinobufagin is related to the increased expression of CD and CD in DP（double positive）phenotype and S phase cells of T lymphocytes.

关键词： Venenum Bufonis Cinobufagin lymphocytes peritoneal macrophage CD4 CD8 S phase

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In vitro pharmacokinetics and pharmacodynamics of Ievofloxacin against plasmid-mediated quinolone resistant Escherichia coli

In vitro pharmacokinetics and pharmacodynamics of Ievofloxac...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： XU Jun-fang WU Xiao-jie WANG Ming-hua XU Xiao-gang WANG Ming-gui ZHANG Jing.Institute of Antibiotics,Huashan Hospital,Fudan University,Shanghai 200040,China

AIM:Bacterial resistance to quinolones has traditionally mediated by alteration of the quinolone targets and/or over- production of efflux ***,a new mechanism, the plasmid-mediated quinolone resistance named qnr,has been *** and its homologus are widely distribut- ed among gram-negative *** presence of qnr only slightly elevates the resistance level,however it facili- tates the selection of highly resistant *** our study, we examined the probable influence of such phenomenon to the clinical regimens of levofloxacin. METHODS:In-vitro hollow fiber infection model simu- lating oral two-compartment pharmacokinetic model was es- *** the model,bacteria was incubated in the pe- ripheral compartment without‘washout effect’.We de- signed two therapeutic regimens of levofloxacin,including 500 mg qd（peak 5.12 mg/L;half-time 6.9 h）and 700 mg qd（peak 9.46 mg/L;half-time 6.9 h）for 3 days against *** J53 and *** 650,which carrying qnr positive plasmid. RESULTS:Although 500 mg qd regimen could decrease the bacteria density of *** 650 at the beginning, the bacteria population bounced back when the drug con- centration was drecreased below 2 mg/L,and the regrowth bacteria had higher MICs than the parental strains.700 mg qd for 3 days could inhibit the outgrowth of *** 650 all the *** J53 was well inhibited by both the mentioned therapeutic *** sequencing found the mutations in QRDR of *** 650. CONCLUSION:We conclude that 500 mg qd which is the most popular regimen is at risk of selecting resistant mutations and treatment failure while treating the infections caused by qnr positive ***,and 750 mg qd might be *** vivo pharmacodynamic studies to support our findings are warranted.

关键词： levofloxacin pharmacokinetics and pharmacodynamics plasmid-mediated quinulone resistance

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Pharmacokinetics of theophylline in patients with COPD and its interference factors

Pharmacokinetics of theophylline in patients with COPD and i...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： LIU Xiao-ming Department of Pharmacy,the First Affiliate Hospital of Hebei North University,Zhangjiakou 075000,Hebei,China

AIM:To study the pharmacokinetics of theophylline in patients with chronic obstructive pulmonary diseases （COPD）and its interference factors. METHODS:Serum theophylline concentrations in 9 pa- tients with COPD after oral administration of theophylline （200 mg,tid）for 5 consecutive days or combining with nifedipine（10 mg,tid）for 5 consecutive days were deter- mined by high performance liquid chromatography（HPLC） with ultraviolet spectrophotometry. RESULTS:The pharmacokinetics of theophylline in COPD patients was one-compartment model after oral ad- ministration of theophylline（200 mg,tid）for 5 consecu- tive *** significant difference in individual variation on phannacokinetics of theophylline was observed in this *** volume of distribution（V）was（0.50± 0.21）L/kg,the elimination half-life(t)was（5.4± 1.3）h and clearance（CL）was（0.07±0.03） L·h·kgin the patients with *** was no significant difference in V,t,and CL between COPD patients and healthy volunteers（P＞0.05）.The values of k and Cl were faster and twas shorter in the middle- aged patients than those in old COPD patients（P＜ 0.05）.After administration of nifedipine for 5 consecutive days,the mean serum theophylline concentration de- creased by（1.8±2.0）mg/*** Cand AUC were,Iower than those obtained before nifedipine[（12±6） vs（10±5）mg/L,（82±52）vs（62±39）mg·L·h, P＜0.05 ],*** this study,the mean serum concentration of theophylline determined by UV method was significantly lower than that by HPLC [△C=（-0.6 ±1.6）mg/L,n=123,P＜0.05].However,the phar- macokinetic parameters of theophylline determined by the two methods were no difference（P＞0.05）.In addition, the results showed that there was no significant change in theophyiline recovery,in pure serum of theophylline and mixture serum of theophylline and CTRX. CONCLUSION:The pathological state of COPD appears not to affect the pharmacokinetic profiles in middle-aged patients with *** is not necessary to change the ther- apeutic combination wi

关键词： chronic obstructive pulmonary diseases theophylline pharmacokinetics interaction HPLC UV

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Plasma level of AcMPAG in renal transplant recipients is related to the polymorphism of UGT2B7 211G＞T

Plasma level of AcMPAG in renal transplant recipients is rel...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： ZHANG Wei-xia~1 CHEN Bing~1 YU Zi-cheng~1 JIN Zhao~1 WANG Xiang-hui~2 CAI Wei-min~1 1 Institute of Clinical Pharmacology,Ruijin Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 200025,China 2 Organ Transplantation Center,Ruijin Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 200025,China

AIM:To clarify whether Mycophenolic acid（MPA）or its metabolite AcMPAG can cause gastrointestinal disturbanc- es,and to explore the effect of UGT2B7 SNP 211G＞T on the pharmacokinetic of AcMPAG. METHODS:Twenty-four renal transplant patients were enrolled in this *** study was per- formed on day 14 after transplantation and symptoms were recorded on the same *** blood samples were collected before dosing and 0.5,1,1.5,2,4,6,8,10 and 12 hours after morning *** concentrations of MPA,MPAG and AcMPAG were detected by HPLC. Genotype of UGT2B7 211G＞T was determined using PCR-RFLP method. RESULTS:No significant difference was observed be- tween patients with and without side effects for AUC of MPA and *** values of AUC/dose of MPA,MPAG and AcMPAG were（39.7±12.3）, （1063.7±646.5）and（10.2±3.0）ng·h·mL·mg in TT genotype group and（42.0±20.0）,（1466.5± 683.3）and（20.7±5.6）ng·h·mL·mgin GG gen- otype group,*** ratio of AUC_(（AcMPAG）(0-12))/ AUC,which was used to describe the change of UGT2B7 enzyme activity,was 0.49±0.20,0.34±0.26 and 0.28±0.14 in recipients with 211GG,GT and TT genotype,respectively（P＜0.05）. CONCLUSION:There was no significant differences in pharmacokinetics of MPA and its metabolites between side effect group and non-side effect *** seems that the polymorphism 211G＞T in the UGT2B7 gene results in the reduction of enzyme acitivity.

关键词： UDP-glucuronosyltransferase 2B7 MPA AcMPAG polymorphism adverse effect

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Association of elF3 p170 expression with chemotherapy response of lung cancer and its effects on cisplatin sensitivity in lung carcinoma cells

Association of elF3 p170 expression with chemotherapy respon...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： SHEN Jie~1 XIE Hai-tang~1 YIN Ji-ye~1 DONG Zi-zheng~2 YANG You-yun~2 ZHOU Hong-hao~1 ZHANG Jing-ting~2 LIU Zhao-qian~1 1 Pharmacogenetics Research Institute,Institute of Clinical Pharmacology,Central South University Hunan 410078,Changsha,China 2 Department of Pharmacology & Toxicology,I.U.Cancer Center,Indiana University School of Medicine,Indiana 46202,Indianapolis,USA

AIM:To evaluate the expression of eukaryotic initiation factors 3(eIF3)subunit 170(eIF3 P170)in lung cancer tissues and its association with chemotherapy response of lung cancer. METHODS:31 paraffin imbedded slices of lung cancer tissue from fiberscope diagnosis,20 samples of benign lung tissues from inflammatory pseudotumor and bronchiec- tasis,and 10 samples of normal lung tissues from surgical operation were *** protein expression of eIF3 p170 in lung-cancer tissues,benign lesion tissues,and normal lung tissues were determined by immunohistoche- mical staining. RESULTS:The positive ratio of eIF3 p170 expression in lung cancer tissues is higher than those in normal and be- nigh tissues,the lung cancer patients with a higher expres- sion level of elF3 p170 seems to be more sensitive to che- ***,we also found that down-regulation of expression of eIF3 p170 could inhibit the growth of human lung adeno-carcinoma cell A549 cells and decrease the sensitivity of A549 to cisplatin. CONCLUSION:Our data suggest that eIF3 p170 may be involved in the pathogenesis of lung cancer and it appears to be associated with chemotherapy response of lung can- cer.

关键词： eIF3 p170 lung cancer drug sensitivity A549 cisplatin

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Contrast study on optimizing antibacterial lead compounds from three kinds of derivates in vitro

Contrast study on optimizing antibacterial lead compounds fr...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： LI Juan XIE Hai-tang SUN Rui-yuan TONG Jiu-cui Anhui Provincial Centre for Drug Clinical Evaluation,Yijishan Hospital,Wannan Medical College,Wuhu 241001,Anhui,China

AIM:To choose at least one kind of better derivate from 81 novel compounds for further structure-function relation- ship researches by contrast study on antibacterial activity of three kinds of derivates developed from decanoyl acetalde- hyde,a certain kind of ethnodrug and pure synthetics. METHODS:Three quality control strains,staphylococcus aureus ATCC25923,bacillus coil ATCC25922 and bacillus aeruginosus ATCC27853 were used in the preliminary screening in *** active derivates were selected to carry out the minimal bactericidal concentration test,kill- ing curve test,and the effect of cultivation parameters on minimal inhibitory concentration on clinical separated staphylococcus aureus and *** toxicity test of a few promising derivates were tested preliminarily by intra- gastric administration to mice. RESULTS:There were significant differences of the anti- bacterial activity for the three different kinds of derivatives compared to the quality control *** shown that 15 percent of the 53 compounds developed from decanoyl acetaldehyde had special activity of inhibiting staphylococ- cus aureus *** optimized derivatives had better activity to clinical separated staphylococcus aureus and MRSA compared to the positive control drug decanoyl *** the derivates showed stronger inhibitive action to the staphylococcus aureus in basylous circum- stance than in acid ***,among 20 derivates developed from a certain kind of ethnodrug,there were 90 percents shown fairly strong and broad antibacteri- al activity to staphylococcus aureus ATCC25923 and bacil- lus coil ATCC25922 with high toxicity in *** 8 samples of pure synthetics showed weak antibacterial activ- ity. CONCLUSION:The derivates developed from natural products showed fairly well antibacterial *** the derivates related to decanoyl acetaldehyde had lower toxcity than that of derivates obtained from the *** pure synthetic compounds

关键词： decanoyl acetaldehyde derivate ethnodrug active monome derivate antibacterial primer/derivate in vitro antibacterial activity minimal inhibitory concentration

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Coenzyme Q10 protects human dopaminergic cell line SHSY-5Y against rotenone-induced apoptosis

Coenzyme Q10 protects human dopaminergic cell line SHSY-5Y a...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： DENG Sheng~1 ZHANG Wei~2 YIN Tao~1 TANG Ling~1 DENG Hao~3 1 Department of Pharmacy,Xiangya Hospital,Central South University,Changsha 410008,Hunan,China 2 pharmacogenetics Research Institute,Institute of Clinical Pharmacology,Central South University,Changsha 410078,Hunan,China 3 Medical Experimental Center,The Third Xiangya Hospital,Central South University,Changsha 410013,Hunan,China

AIM:To determine whether the use of an antioxidant re- agent coenzyme Q10 can protect human dopaminergic cell line SHSY-5Y against rotenone-induced apoptosis. METHODS:Cell viability was quantified by 3-(4,5-dim- ethyhhiazol-2-yl)-2,5-diphenyhetrazolium bromide(MTF) assay and the apoptosis induced by rotenone was observed by Hoechst 33342,propidium iodide,and ealcein AM staining in SHSY-5Y cells. RESULTS:Rotenone,a commonly used natural pesti- cide,inhibitor of mitochondrial respiratory chain complex I,was shown to decrease cell viability and induce apopto- sis in SHSY-5Y *** with coenzyme Q10,the electron transporter in the mitochondrial respiratory chain, remarkably increased cell viability as well as significantly reduced the percentage of apoptotic SHSY5Y cells induced by rotenone. CONCLUSION:Coenzyme QI0 has a beneficial effect in protecting against rotenone-indueed apoptosis in SHSY-SY *** results support the hypothesis that coenzyme QI0 is a component of the antioxidant machinery that pro- tects cell membranes from oxidative damage and decreases *** evaluation is required to determine whether the neuroprotective action of coenzyme Q10 can be used for the prevention and therapy of neurodegenerative diseases.

关键词： Coenzyme Q10 rotenone cell viability apoptosis

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