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Effects of coffee and caffeine on bladder dysfunction in streptozotocininduced diabetic rats

Acta Pharmacologica Sinica 2006年第8期27卷 1037-1043页

作者： Chao-ran YI~(2,5) Zhong-qing WEI~2 Xiang-lei DENG~4 Ze-yu SUN~2 Xing-rong LI~4 Cheng-gong TIAN~3 ~2department of Urology,~3department of Endocrinology,the affiliated Drum Tower hospital,Nanjing university Medical school,Nanjing 210008,china ~4department of Biochemisto,and Molecular Biology,Medieal College of Southeast university,Nanjing 210009,china department of Urology the Affiliated Drum Tower Hospital Nanjing University Medical School Nanjing China department of Biochemistry and Molecular Biology Medical College of Southeast University Nanjing China department of Endocrinology the Affiliated Drum Tower Hospital Nanjing University Medical School Nanjing China

Aim:To explore the effects and mechanisms of caffeine and coffee on bladderdysfunction in streptozotocin-induced diabetic ***:Sprague-Dawleymale rats were divided randomly into 4 groups:control,diabetes mellitus(DM),DM with coffee treatment,and DM with caffeine *** diabetic rat wasinduced by intraperitoneal injection of streptozotocin(60 mg/kg).After 7 weeks oftreatment with coffee and caffeine,cystometrogram,contractile responses to elec-trical field stimulation(EFS)and acetylcholine(ACh),and cyclic AMP(cAMP)concentration of the bladder body and base were ***:The bladderweight,volume threshold for micturition and post-void residual volume(PVR)inthe diabetic rats were significantly higher compared to those in the control *** or caffeine treatment significantly reduced the bladder weight,bladdercapacity and PVR in the diabetic *** caused significant decreases in cAMPconcentration of the bladder and coffee and caffeine caused upregulation of cAMPcontent in the diabetic *** addition,coffee and caffeine tended to normal-ize the altered detrusor contractile responses to EFS and ACh in the diabetic ***:These results indicate that caffeine and coffee may have beneficialeffects on bladder dysfunction in the early stage of diabetes by increasing cAMPcontent in the lower urinary tract,recovering the micturition reflex and improvingthe detrusor contractility.

关键词： caffeine diabetic mellitus bladder urodynamics muscle contraction cyclic AMP

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Effects of aspirin on number,activity and inducible nitric oxide synthase of endothelial progenitor cells from peripheral blood

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Acta Pharmacologica Sinica 2006年第4期27卷 430-436页

作者： Tu-gang CHEN Jun-zhu CHEN~2 Xu-dong XIE department of Cardiovascular Disease,First affiliated hospital,Medical school of Zhejiang university.Hangzhou 310003,china department of Cardiovascular Disease First Affiliated Hospital Medical School of Zhejiang University Hangzhou China

Aim:To investigate whether aspirin has an influence on endothelial progenitorcells(EPC).Methods:Total mononuclear cells(MNC)were isolated from periph-eral blood by Ficoll density gradient centrifugation,then cells were plated onfibronectin-coated culture *** 7 d of culture,attached cells were stimu-lated with aspirin(to achieve final concentrations of 1,2,5,and 10 retool/L)for 3,6,12,and 24 *** were characterized as adherent cells that were double positivefor 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine low density lipoprotein(DiLDL)uptake and lectin binding by direct fluorescent *** prolifera-tion and migration were assayed using a 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)assay and a modified Boyden chamber assay,*** EPC adhesion assay was performed by replating the EPC onfibronectin-coated dishes,and then adherent cells were *** vitrovasculogenesis activity was assayed by using an in vitro vasculogenesis *** nitric oxide synthase(iNOS)was assayed by Western ***:Incubation of isolated human MNC with aspirin decreased the number of *** also decreased the proliferative,migratory,adhesive,and in vitrovasculogenesis capacity of EPC,and also their iNOS levels in a concentration-and time-dependent ***:Aspirin decreases(1)the number ofEPC;(2)the proliferative,migratory,adhesive and in vitro vasculogenesis capaci-ties of EPC;and(3)iNOS levels in EPC.

关键词： aspirin endothelial progenitor cells cell adhesion cell count cell movement cell division physiologic neovascularization

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Tetramethylpyrazine suppresses HIF-1α,TNF-α,and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats

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Acta Pharmacologica Sinica 2007年第3期28卷 327-333页

作者： Yi CHANG~(2,3) George HSIAO~4 Seu-hwa CHEN~4 Yi-cheng CHEN~4 Jiing-han LIN~4 Kuang-hung LIN~4 Duen-suey CHOU~4 Joen-rong SHEU~(4,5)2 department of Anesthesiology,Shin Kong Wu Ho-Su Memorial hospital,Taipei 110,Taiwan,china 3 school of medicine,Fu-Jen Catholic university,Taipei,110,Taiwan,china 4 Graduate Institute of Medical Sciences,Taipei Medical university,Tuipei 110,Taiwan,china department of Anesthesiology Shin Kong Wu Ho-Su Memorial Hospital Taipei China school of medicine Fu-Jen Catholic University Taipei China Graduate Institute of Medical Sciences Taipei Medical University Taipei China

Aim:To examine the detailed mechanisms underlying the inhibitory effect oftetramethylpyrazine(TMPZ)in inflammatory and apoptotic responses inducedby middle cerebral artery occlusion(MCAO)in ***:MCAO-inducedfocal cerebral ischemia in rats was used in this *** hypoxia-induciblefactor-1α(HIF-1α),activation of caspase-3,and TNF-αmRNA transcription inischemic regions were detected by immunoblotting and RT-PCR,***-oxidative activity was investigated using a thiobarbituric acid-reactive sub-stance(TBARS)test in rat brain homogenate ***:We showedthe statistical results of the infarct areas of solvent-and TMPZ(20 mg/kg)-treatedgroups at various distances from the frontal pole in MCAO-induced focal cerebralischemia in *** with TMPZ(20 mg/kg)markedly reduced the infarctarea in all regions,especially in the third to fifth ***-induced focalcerebral ischemia was associated with increases in HIF-lαand the activation ofcaspase-3,as well as TNF-αtranscription in ischemic *** expressionswere markedly inhibited by treatment with TMPZ(20 mg/kg).However,TMPZ(0.5-5mmol/L)did not significantly inhibit TBARS reaction in rat brain ***:The neuroprotective effect of TMPZ may be mediated at least by aportion of the inhibition of HIF-1αand TNF-αactivations,followed by the inhibi-tion of apoptosis formation(active caspase-3),resulting in a reduction in theinfarct volume in ischemia-reperfusion brain ***,TMPZ treatment mayrepresent an ideal approach to lowering the risk of or improving function in is-chemia-reperfusion brain injury-related disorders.

关键词： tetramethylpyrazine middle cerebral artery occlusion HIF-Iα caspase-3 TNF-α thiobarbituric acid-reactive substance

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Quantitative analysis of the ribbon synapse number of cochlear inner hair cells in C57BL/6J mice using the three-dimensional modeling method

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Science china(Life Sciences) 2009年第9期52卷 807-812页

作者： LIU Ke,LI ShuNa & JIANG XueJun department of Otolaryngology,the First affiliated hospital,china Medical university,Shenyang 110001,china department of Otolaryngology the First Affiliated Hospital China Medical University Shenyang China

In mammals,the ribbon synapses of cochlear inner hair cells are a synaptic structure of the first sensory nerve in the pathway of acoustical signal transmission to the acoustic center,and it is directly involved in voice coding and neurotransmitter release. It is difficult to quantitatively analyze the ribbon synaptic number only using an electron microscope,because the ribbon synaptic number is relatively limited and their location is deep. In this study,the specific presynaptic structure-RIBEYE,and non-specific postsynaptic structure-GluR 2 & 3 in C57BL/6J mouse basilar membrane samples were treated by immunofluorescent labeling. Serial section was performed on the samples using a laser scanning confocal microscope,and then the serial sections were used to build three-dimensional models using 3DS MAX software. Each fluorescein color pair indicates one synapse,so the number of ribbon synapses of inner hair cells is obtained. The spatial distribution and the number of ribbon synapses of cochlear inner hair cells were clearly shown in this experiment,and the mean number of ribbon synapses per inner hair cell was 16.10±1.03. Our results have demonstrated the number of ribbon synapses is accurately calculated by double immunofluorescent labeling to presynaptic and postsynaptic structures,serial sections obtained using a laser scanning confocal microscope,and three-dimensional modeling obtained using 3DS MAX software. The method above is feasible and has important significance for further exploring the mechanism of sensorineural deafness.

关键词： inner hair cells Ribbon synapses laser scanning confocal microscope three-dimensional modeling

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AICAR inhibits proliferation and induced S-phase arrest,and promotes apoptosis in CaSki cells

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Acta Pharmacologica Sinica 2007年第12期28卷 1984-1990页

作者： Tong-ju GUAN~2,Feng-jin QIN~3,Jian-hai DU~4,Li Geng~3,You-yi ZHANG~(4,5),Min LI~(2,5)~2 Institute of Pathology,The school of Basic medicine,Lanzhou university,Lanzhou 730000,china ~3 department of Gynaecology andObstetrics,Peking university Third hospital,Beijing 100083,china ~4 Institute of Vascular medicine,Peking university Third hospital andKey Laboratory of Molecular Cardiovascular Sciences Ministry of Education,Beijing 100083,china Institute of Pathology The School of Basic Medicine Lanzhou University Lanzhou China department of Gynaecology and Obstetrics Peking University Third Hospital Beijing China Institute of Vascular medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing China

Aim:The aim of the present study was to determine the effect of 5-aminoimidazole-4-carboxamide-ribonucleoside （AICAR） on proliferation,cell cycle,and apoptosisin the human epithelial cervical cancer cell line CaSki ***:Cell countand 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay were usedto determine cell proliferation and *** 33258 staining was con-ducted to distinguish the apoptotic *** cycle and Annexin-V/propidiumiodide staining were analyzed by fluorescence-activated cell sorting （FACS）.AWestern blot assay was used to evaluate the expression of AKT （also known asprotein kinase B）,mammalian target of rapamycin （mTOR）,p53,and extracellularsignal-regulated kinase （ERK）.Results:AICAR （500 μmol/L） significantly inhibi-ted the proliferation of CaSki cells treated for 24,48,and 72 h as determined by *** cells at the G1and G2phases were dramatically decreased while cells atthe S phase were increased in response to AICAR treatment for 24,48,and 72 *** MTT assay showed less viable cells and Hoechst fluorescent staining showedmore apoptotic cells upon AICAR *** results of the Annexin-Vstaining demonstrated a time-dependent increase of apoptosis in cells treatedwith AICAR for 24,36,and 48 ***,AICAR activated caspase-3 in atime-dependent *** was also found that AICAR inhibited the phosphory-lation of AKT and mTOR,which are important kinases regulating cell growth *** stimulation obviously increased the expression of the tumorsuppressor p53 and the phosphorylation of ***:AICAR inhibitedproliferation and induced S phase arrest and promoted apoptosis in CaSki cells,which might be mediated by the downregulation of the AKT/mTOR pathway andthe upregulation of the p53/ERK pathway.

关键词： AICAR proliferation apoptosis CaSki cells

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Antitumor effect of cytosine deaminase/5-fluorocytosine suicide gene therapy system mediated by Bifidobacterium infantis on melanoma

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Acta Pharmacologica Sinica 2005年第5期26卷 629-634页

作者： Cheng YI~2,Ying HUANG~3,Zhi-ying GUO~3,Shu-ren WANG~(3,4) ~2Cancer Center,West china hospital,Sichuan university Chengdu,610041,china ~3department of Pathophysiology,West china school of Preclinical and Forensic medicine,Sichuan university,Chengdu 610041,china Cancer Center West China Hospital Sichuan University Chengdu China department of Pathophysiology West China School of Preclinical and Forensic Medicine Sichuan University Chengdu China

Aim:To construct a Bifidobacterium infantis/CD targeting gene therapy systemand observe the antitumor effect of cytosine deaminase/5-fluorocytosine(CD/5-FC)suicide gene therapy system mediated by Bifidobacterium infantis on mela-noma in vitro and in ***:A recombinant CD/pGEX-1LamdaT plasmidwas transfected into Bifidobacterium infantis by ***-terium infantis transfected by recombinant CD/pGEX-1LamdaT plasmid was in-cubated with 5-FC *** the supernatant fluid was collected andadded to melanoma B 16-F10 cells to observe the killing effect for B 16-F10 *** were inoculated with melanoma B 16-F10 cells to establish animal *** mice were then injected with 5-FC and Bifidobacterium infantis transfectedby recombinant CD/pGEX-1LamdaT ***:Two segments of approxi-mate 4.9 kb and 1.3 kb were extracted from the 6.2 kb recombinant plasmid,whichwere equal to the size of the pGEX-1LamdaT plasmid and CD gene,*** results showed that the full length and sequence of nucleotide acid ofthe inserted gene in extracted recombinant plasmid was completely identical to theCD *** vitro,B16-F10 cells treated by supernatant fluid were remarkablydamaged morphologically,and the cell growth was significantly ***-ments on the mice melanoma model showed that after treatment with a combina-tion of transfected Bifidobacterium infantis and 5-FC,the tumor volume wassignificantly inhibited compared with ***:The foreign gene,CD gene,was correctly inserted into pGEX-1LambdaT plasmid and transferredinto Bifidobacterium ***/5-FC suicide gene therapy system mediated byBifidobacterium infantis demonstrated a good antitumor effect on melanoma invitro and in vivo.

关键词： Bifidobacterium infantis cytosine deaminase gene therapy

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Method for tumor recognition with short dynamic PET images:Theory and simulation study

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Progress in Natural Science:Materials International 2009年第1期19卷 73-77页

作者： Huiting Qiao a,Jing Bai a,Yingmao Chen b,Jiahe Tianb a department of Biomedical Engineering,school of medicine,Tsinghua university,Beijing 100084,china b department of Nuclear medicine,General hospital of PLA,Beijing 100853,china department of Biomedical Engineering School of Medicine Tsinghua University Beijing 100084 China department of Nuclear medicine General Hospital of PLA Beijing 100853 China

A new method was provided in this paper to recognize tumor in PET images automatically and reduce the waiting time of *** on the unsupervised clustering algorithm(ISODATA),this method diagnoses tumor with short dynamic PET *** theoretical basis of this method is that the metabolic characteristics of different tissues,represented by time-activity curve in the region of interest,are *** computer program was developed and validated using simulated dynamic PET data with small tumor in *** study shows that this method could recognize tumor with the short dynamic PET data in 10 min successfully,and this method was not sensitive to initial cluster center.

关键词： Dynamic PET Clustering algorithm Tumor recognition Simulation

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What we know about ST13, a co-factor of heat shock protein, or a tumor suppressor?

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2007年第3期8卷 170-176页

作者： SHI Zheng-zheng, ZHANG Jia-wei, ZHENG Shu (The Second affiliated hospital, Cancer Institute, school of medicine, Zhejiang university, Hangzhou 310009, china) The Second affiliated hospital Cancer Institute School of Medicine Zhejiang University Hangzhou 310009 China.

This article is to summarize the molecular and functional analysis of the gene “suppression of tumorigenicity 13” (ST13). ST13 is in fact the gene encoding Hsp70 interacting protein (Hip), a co-factor (co-chaperone) of the 70-kDa heat shock proteins (Hsc/Hsp70). By collaborating with other positive co-factors such as Hsp40 and the Hsp70-Hsp90 organizing protein (Hop), or competing with negative co-factors such as Bcl2-associated athanogen 1 (Bag1), Hip facilitates may facilitate the chaperone function of Hsc/Hsp70 in protein folding and repair, and in controlling the activity of regulatory proteins such as steroid receptors and regulators of proliferation or apoptosis. Although the nomenclature of ST13 implies a role in the suppression of tumorigenicity (ST), to date available experimental data are not sufficient to support its role in cancer development, except for the possible down-regulation of ST13 in gastric and colorectal cancers. Further investigation of this gene at the physiological level would benefit our understanding of diseases such as endocrinological disorders, cancer, and neurodegeneration commonly associated with protein misfolding.

关键词： ST13 Hip p48 Hsc/Hsp70 Heat shock protein Protein folding Steroid receptor Tumorigenicity

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Protective effect of raloxifene on lipopolysaccharide and acid-induced acute lung injury in rats

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Acta Pharmacologica Sinica 2007年第10期28卷 1585-1590页

作者： Guang-ju ZHOU~1,Hong ZHANG~2,Sheng-de ZHI~3,Guo-ping JIANG~1,Jing WANG~2,Mao ZHANG~1,Jian-xin GAN~1,Shao-wenXU~1,Guan-yu JIANG~(1,4)~1 department of Emergency medicine,Second affiliated hospital,Zhejiang university,school of medicine and Research Institute of Emer-gency medicine,Hangzhou 310009,china ~2 department of Nuclear medicine,Second affiliated hospital,Zhejiang university,Hangzhou310009,china ~3 Drug Design and Discovery Center,Shanghai Institute of Materia Medica,Shanghai Institute for Biological Sciences,Chinese Academy of Sciences,Shanghai 201203,china department of Emergency medicine Second Affiliated Hospital Zhejiang University School of Medicine and Research Institute of Emergency Medicine Hangzhou China department of Nuclear medicine Second Affiliated Hospital Zhejiang University Hangzhou China Drug Design and Discovery Center Shanghai Institute of Materia Medica Shanghai Institute for Biological Sciences Chinese Academy of Sciences Shanghai China

Aim:To evaluate the protective effect of oral raloxifene on acute lung ***:Thirty adult,male Sprague-Dawley rats each weighing 180-210 g wereused and divided into 3 groups:the raloxifene-lipopolysaccharide （LPS）-HCl group（n=10）,the LPS-raloxifene-HCl group （n=10）,and the placebo group （n=10）.Allthe rats were injected intraperitoneally （ip） with 5 mg/kg LPS,and raloxifene （30mg/kg） was orally administered 1 h before and 14 h after LPS injection into theraloxifene-LPS-HCl and the LPS-raloxifene-HCl groups,respectively;the placebogroup received *** hours after LPS injection,all the animals wereanesthetized and the femoral artery was *** the rats received a directintratracheal （IT） injection of HCl（pH 1.2;0.5 mL/kg）.The mean arterial pressure（MAP） and blood gas concentrations were *** rats （5 in eachgroup,respectively） underwent a micro positron emission tomography （microPET）scan of the thorax 4 h after HCl *** wet/dry （W/D） weight ratiodetermination and histopathological examination were also ***:The rats in the LPS-raloxifene-HCl group had a lower [18F]fluorodeoxyglucoseuptake compared with the rats in the placebo group （4.67±1.33 vs 9.01±1.58,respectively,P<0.01）.The rats in the LPS-raloxifene-HCl group also had a lowerhistological lung injury score （8.20±1.23 vs 12.6±0.97,respectively,P<0.01） andW/D weight ratio （5.335±0.198 vs 5.886±0.257,respectively,P<0.01） compared tothe placebo *** rats in this group also showed better pulmonary gasexchange and more stable mean arterial pressure （MAP） compared to the ***:Raloxifene provides a significant protective effect on acutelung injury in rats induced first by LPS ip injection and then by HCl IT instillation.

关键词： acute lung injury aspiration fluorodeoxyglucose lipopolysaccharide microPET pulmonary edema raloxifene

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Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line

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Acta Pharmacologica Sinica 2007年第11期28卷 1819-1826页

作者： Hong-zhen HU~2,Yue-bo YANG~3,Xiang-dong XU~4,Hong-wei SHEN~5,Yi-min SHU~6,Zi REN~7,Xiao-mao LI~3,Hui-ming SHEN~3,Hai-tao ZENG~(3,8)~2 department of Gynecology and Obstetrics,Yijishan hospital,Wannan Medical College,Wuhu 241001,china ~3 department of Gynecologyand Obstetrics,the Third affiliated hospital,Sun Yat-sen university,Guangzhou 510080,china ~4 department of Surgery,the First affiliatedhospital,Sun Yat-sen university,Guangzhou 510080,china ~2 department of Gynecology and Obstetrics,the First affiliated hospital,SunYat-sen university,Guangzhou 510080.china ~6 department of Obstetrics and Gynecology,IVF Program,Stanford university MedicalCenter,Palo Alto,CA 94304,USA ~7 department of Gynecology and Obstetrics,Guangdong Provincial People's hospital,Guangzhou510080.china department of Gynecology and Obstetrics Yijishan Hospital Wannan Medical College Wuhu China department of Gynecology and Obstetrics the Third Affiliated Hospital Sun Yat-sen University Guangzhou China department of Surgery the First Affiliated Hospital Sun Yat-sen University Guangzhou China department of Gynecology and Obstetrics the First Affiliated Hospital Sun Yat-sen University Guangzhou China department of Obstetrics and Gynecology IVF Program Stanford University Medical Center Palo Alto USA department of Gynecology and Obstetrics Guangdong Provincial People's Hospital Guangzhou China

Aim:To investigate the apoptosis-inducing effect of oridonin,a diterpenoid iso-lated from Rabdosia rubescens,in the human cervical carcinoma HeLa cell ***:A morphological analysis,nuclear condensation,and fragmentation ofchromatin were monitored using Hoechst 33342 *** viability was as-sessed using the 3-(4,5-dimethylthiazol-(2)-yl)-2,5-diphenyl tetrazolium bromide(MTT) *** apoptosis and the apoptosis-related activation in the HeLa cellline were evaluated by flow cytometry and Western ***:Oridoninsuppressed the proliferation of the HeLa cell line in a dose-and *** treatment downregulated the activation of protein kinase B(Akt),the expression of forkhead box class O (FOXO) transcription factor,andglycogen synthase kinase 3 (GSK3).Oridonin also induced the release of cyto-chrome c accompanied by the activation of caspase-3 and poly-adenosine diphos-phate-ribose polymerase *** addition,Z-D(OMe)-E(OMe)-V-D(OMe)-FMK (z-DEVD-fmk),an inhibitor of caspases,prevented caspase-3 activation andabrogated oridonin-induced cell ***,oridonin treatment of the HeLa cellline downregulated the expression of the inhibitor of the apoptosis ***:Our results showed that oridonin-induced apoptosis involved sev-eral molecular *** may suppress constitutively activated targetsof phosphatidylinositol 3-kinase (Akt,FOXO,and GSK3) in the HeLa cell line,inhibiting the proliferation and induction of caspase-dependent apoptosis.

关键词： cervical carcinoma oridonin apoptosis Akt

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