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Prevention of pathological change and cognitive degeneration of Tg2576 mice by inoculating Aβ_(1-15) vaccine

Science china(Life Sciences) 2008年第8期51卷 743-750页

作者： HU JinJia1, LI GuoYing2, WANG HuaQiao3, LIN Xian3 & YAO ZhiBin3 1 department of anatomy, Medical College of Shanghai Jiao Tong university, Shanghai 200025, china 2 department of anatomy, Preclinical College, Guangdong university of Pharmacy, guangzhou 510006, china 3 department of anatomy, zhongshan school of medicine, sun yat-sen university, guangzhou 510080, china department of anatomy Medical College of Shanghai Jiao Tong University Shanghai China department of anatomy Preclinical College Guangdong University of Pharmacy Guangzhou China department of anatomy Zhongshan School of Medicine Sun Yat-sen University Guangzhou China

This study aims to discuss the effect of preventing pathological changes and cognitive degeneration of Tg2576 mice by inoculating the subunit fragment of Aβ ***-two Tg2576 mice were randomly divided into four groups, each having eight mice:Group I, the control group, inoculated with adjuvants;Group II, the Aβ42 group, inoculated with Aβ42 vaccine;Group Ⅲ, the Aβ1―15 group, inoculated with Aβ1―15 vaccine;and Group IV, the Aβ36―42 group, inoculated with Aβ36―42 *** titer of the serum anti-body against Aβ42(Group II) was significantly higher than that of the control group(Group I), and a low level of antibodies could be detected in the brain homogenate in the three vaccine-inoculated *** water maze test showed that the Aβ42 group, Aβ1―15 group and Aβ36―42 group were obviously im-proved compared with the control *** cultured splenocytes sampled from each group were induced by Con A or their respective antigens, and the cell proliferation of the three vaccine-inoculated groups was significantly higher than that of the control *** the Aβ42 group, IL2 and IFN-γ were relatively low and IL4 and IL10 were relatively *** contrast, IL4 and IL10 were much higher in the Aβ1―15 group and IL2 and IFN-γ were much higher in the Aβ36―42 *** immunohistochemical test showed a large number of senile plaques in the brain cortex and hippocampus of the mice in the con-trol group, no senile plaque in the brain of the Aβ1―15 group and Aβ42 group mice, and a small number of senile plaques in the brain of the Aβ36―42 group *** results suggest that the subunit fragment of Aβ1―15 vaccine could prevent not only cognitive and behavioral degeneration but also Aβ deposition and formation of senile plaques in Tg2576 mice.

关键词： Alzheimer’s disease β-amyloid peptide vaccine Tg2576 mice senile plaque

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Non-invasive Prenatal Gene Diagnosis: Progress through Cell-free Fetal DNA and RNA in Maternal Plasma and Urine

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中山大学学报（医学科学版） 2008年第S2期29卷 140-142页

作者： GUO Xun-yang, GUO Yi-bin ( department of Medical Genetics, zhongshan school of medicine, sun yat-sen university, guangzhou 510080, china )

Non-invasive prenatal gene diagnosis has been developed rapidly in the recent years, and numerous medical researchers are focusing on it. Such techniques could not only achieve prenatal diagnosis accurately, but also prevent tangential illness in fetuses and thus, reduce the incidence of diseases. Moreover, it is non-invasive prenatal gene diagnosis that prevents potential threaten and danger to both mothers and fetuses. Therefore, it is welcomed by clinical gynecologist and obstetrian, researchers of medical genetics, and especially, pregnancies. This review article touches briefly on the advanced development of using cell-free DNA, RNA in maternal plasma and urine for non-invasive prenatal gene diagnosis.

关键词： non-invasive prenatal gene diagnosis cell-free fetal DNA and RNA DNA and RNA detection maternal urine maternal plasma

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Spontaneous chiral-symmetry breaking of lattice QCD with massless dynamical quarks

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Science china(Physics,Mechanics & Astronomy) 2007年第1期50卷 6-14页

作者： LUO XiangQian department of Physics,school of Physics and Engineering,sun yat-sen university,guangzhou 510275,china department of Physics School of Physics and Engineering Sun Yat-Sen University Guangzhou China

One of the most challenging issues in QCD is the investigation of spontaneous chiral-symmetry breaking, which is characterized by the non-vanishing chiral condensate when the bare fermion mass is zero. In standard methods of the lattice gauge theory, one has to perform expensive simulations at multiple bare quark masses, and employ some modeled functions to extrapolate the data to the chiral limit. This paper applies the probability distribution function method to computing the chiral condensate in lattice QCD with massless dynamical quarks, without any ambiguous mass extrapolation. The results for staggered quarks indicate that this might be a promising and efficient method for investigating the spontaneous chiral-symmetry breaking in lattice QCD, which deserves further investigation.

关键词： lattice QCD spontaneous chiral-symmetry breaking dynamical quarks

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Microtubule stability and MAP1B upregulation control neuritogenesis in CAD cells

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Acta Pharmacologica Sinica 2006年第9期27卷 1119-1126页

作者： Wen LI~(2,5)Jin-tang XIA~3 Yue FENG~(4,5)2 Laboratory of Surgery,The First Affiliated Hospital,sun yat-sen university,guangzhou 510080,china 3 department of General Surgery,The First People's Hospital of guangzhou,guangzhou 510180,china 4 department of Pharmacology,Emory university school of medicine,USA Laboratory of Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou China department of General Surgery The First People's Hospital of Guangzhou Guangzhou China department of Pharmacology Emory University School of Medicine USA

Aim:To study the role of microtubule dynamics and microtubule associated pro-tein 1B(MAP1B)in regulation of the neurite extension in CAD catecholaminergicneuronal cell ***:The neuritogenesis of the CAD cells was abolishedby inhibiting microtubule polymerization with nocodazole and by blocking micro-tubule depolymerization with ***1B and tubulin protein expression wasdetected by Western *** staining of tubulins was observedby fluorescent and confocal ***:Microtubule dynamics wasessential for CAD neurite *** analysis revealed that neurite exten-sion was much more sensitive to nocodazole than to taxol,suggesting a func-tional requirement for highly active microtubule assembly.A remarkableupregulation of MAP IB protein was detected during neurite extension accompa-nied with increased microtubule ***:Upregulation of MAP1Bleads to the stabilization of newly formed microtubules in the developing neurites,which in turn promotes neurite extension.

关键词： microtubule stability microtubule associated protein 1B neuritogenesis

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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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Activation of PI3-K/Akt pathway for thermal preconditioning to protect cultured cerebellar granule neurons against low potassium-induced apoptosis

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Acta Pharmacologica Sinica 2007年第2期28卷 173-179页

作者： Lin CAO~(2,3) De-xiong CAO~3 Xing-wen SU~2 Li-jun CHEN~2 Ai-lin LIU~2 Wei-jian JIAN~2 Yu-ping WU~2 Peng-xin QIU~2 Guang mei YAN~(2,4)2 department of Pharmacology,zhongshan Medical school,sun yat-sen university,guangzhou 510080,china 3 department of Anesthesiology The Second Affiliated Hospital,sun yat-sen university,guangzhou 510120,china department of Pharmacology Zhongshan Medical School Sun Yat-sen University Guangzhou China department of Anesthesiology The Second Affiliated Hospital Sun Yat-sen University Guangzhou China

Aim:This study was designed to investigate whether the activation of thephosphatidylinositol 3-kinase(PI3-K)/Akt pathway is required for thermal pre-conditioning to protect rat cerebellar granule neurons(CGN)against apoptosisinduced by low potassium,and to explore the possibility of a link between theupregulated heat shock protein(HSP)70 expression and Akt activation in theacquisition of neuroprotection induced by thermal ***:CGN cultured for 8 d in vitro were switched to 5K medium for 24 h after thermalpreconditioning(TP;43.5 ℃ for 90 min,then 37 ℃ for 1 h).To study the role of thePI3-K/Akt pathway,a PI3-K inhibitor,LY294002(20 μmol/L)was added into thecultures 1 h before TP.3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bro-mide(MTT)assay and fluorescein diacetate staining were used to determine *** 33258 staining and agar gel electrophoresis were used to testthe morphological and biological characters of *** blot analysis wasemployed to detect the levels of phospho-Akt,phospho-glycogen synthase ki-nase 3β(GSK3β) Akt,GSK3β,and ***:TP protected CGN againstapoptosis induced by low ***294002 inhibited the neuroprotectiveeffect on CGN induced by *** induced a robust activation of Akt and theinactivation of GSK3β via ***,the activation of the PI3-K/Aktpathway by TP persisted for 24 h in the 5K ***294002(20 μmol/L)failedto inhibit the upregulated HSP70 expression induced by ***:Theactivation of the PI3-K/Akt pathway is required for TP to protect CGN againstapoptosis induced by low potassium,but the neuroprotective effect by Akt acti-vation is not mediated through the downstream induction of HSP70 expression.

关键词： thermal preconditioning heat cerebellum neurons apoptosis LY294002 phospho Akt phospho-GSK3β HSP70

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PPAR gamma inhibits growth of rat hepatic stellate cells and TGF beta-induced connective tissue growth factor expression

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Acta Pharmacologica Sinica 2006年第6期27卷 715-723页

作者： Kai sun Qian WANG~2 Xiao-hui HUANG department of Hepatobiliary Surgery,the First Affiliated Hospital of sun yat-sen university,guangzhou 510080,china department of Hepatobiliary Surgery the First Affiliated Hospital of Sun Yat-Sen University Guangzhou China

Aim:To investigate the effect of peroxisome proliferator-activated receptor gamma(PPARγ)activation on the growth of rat hepatic stellate cells(HSC)and trans-forming growth factor beta(TGF-β)-induced connective tissue growth factor(CTGF)***:After being treated with various amounts of thePPARγ natural ligand 15-deoxy-A 12,14-prostaglandin J2(15-d-PGJ2)or syntheticligand GW7845,the status of HSC proliferation and apoptosis were detected byMTT assay and flow ***,HSC were treated with PPARγ-specific antagonist GW9662 prior to the addition of 15-d-PGJ2or GW7845 andwere subsequently stimulated with TGF-β*** mRNA and protein levels ofCTGF expression were detected by semi-quantitative RT-PCR and Western blot-ting *** changes in the HSC were observed by ***:15-d-PGJ2and GW7845 markedly inhibited HSC prolifera-tion and induced cell apoptosis in a dose-dependent ***,PPARγligands significantly suppressed TGF-β1-induced CTGF expression(at both tran-scriptional and post-transcriptional levels)in HSC,and the inhibitory effect wasdramatically,if not completely,abolished by pretreatment with GW9662,sug-gesting that the inhibition was indeed mediated by PPARγ.Moreover,morpho-logical observation revealed that PPARγ activation caused obvious changes ofHSC from activated to quiescent ***:The PPARγligand hasa potent inhibitory effect on the growth of HSC and TGF-β1-induced CTGFexpression,which makes it a potential antifibrotic candidate for the treatment andprevention of hepatic fibrosis.

关键词： PPAR gamma transforming growth factor beta connective tissue growth factor hepatic stellate cells

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Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR

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Acta Pharmacologica Sinica 2005年第8期26卷 1009-1016页

作者： Xiao-qing TANG~1, Hu BI~1, Jian-qiang FENG~2, Jian-guo CAO~3 ~1 department of Physiology, Nanhua university, Hengyang 421001, china ~2 department of Physiology, zhongshan Medical College, sun yat sen university, guangzhou 510080, china ~3 Institute of Oncology, Nanhua university, Hengyang 421001, china department of Physiology Nanhua University Hengyang China department of Physiology Zhongshan Medical College Sun Yatsen University Guangzhou China Institute of Oncology Nanhua University Hengyang China

Aim: To investigate the reversal effects of curcumin on multidrug resistance （MDR） in a resistant human gastric carcinoma cell line. Methods: The cytotoxic effect of vincristine （VCR） was evaluated by MTT assay. The cell apoptosis induced by VCR was determined by propidium iodide （PI）-stained flow cytometry （FCM） and a morphological assay using acridine orange （AO）/ethidium bromide （EB） dual staining. P-glycoprotein （P-gp） function was demonstrated by the accumulation and efflux of rhodamine 123 （Rh123） using FCM. The expression of P-gp and the activation of caspase-3 were measured by FCM using fluorescein isothiocyanate （FITC）-conjugated anti-P-gp and anti-cleaved caspase-3 antibodies, respectively. Results: Curcumin, at concentrations of 5 μmol/L, 10 μmol/L, or 20 μmol/L, had no cytotoxic effect on a parent human gastric carcinoma cell line （SGC7901） or its VCR-resistant variant cell line （SGC7901/VCR）. The VCR-IC50value of the SGC7901/VCR cells was 45 times more than that of the SGC7901ceUs and the SGC7901/VCR cells showed apoptotic resistance to VCR. SGC7901/VCR cells treated with 5 μmol/L, 10μmol/L, or 20 μmol/L curcumin decreased the IC50value of VCR and promoted VCR-mediated apoptosis in a dose-dependent manner. Curcumin （10 μmol/L） increased Rh123 accumulation and inhibited the effiux of Rh123 in SGC7901/VCR cells, but did not change the accumulation and efflux of Rh123 in SGC7901 ceils. P-gp was overexpressed in SGC7901/VCR cells, whereas it was downregulated after a 24-h treatment with curcumin （10 μmol/L）. Resistant cells treated with 1 μmol/L VCR alone showed 77% lower levels of caspase-3 activation relative to SGC7901 cells, but the activation of caspase-3 in the resistant cell line increased by 44% when cells were treated with VCR in combination with curcumin. Conclusion: Curcumin can reverse the MDR of the human gastric carcinoma SGC7901/VCR cell line. This might be associated with decreased P-gp function and expression, and the promotion of caspase-3

关键词： curcumin multidrug resistance apoptosis P-glycoprotein caspase-3

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Proteomics-based Identification of Proteins with Altered Expression Induced by 12-O-Tetradecanoylphorbol 13-acetate In Nasopharyngeal Carcinoma CNE2 Cells

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Acta Biochimica et Biophysica Sinica 2005年第2期37卷 97-106页

作者： Pei-Zhou JIANG Ming GAN Hua HUANG Xin-Ming SHEN Shuang WANG Kai-Tai YAO Cancer Research Institute.Southern Medical university,guangzhou 510515,china department of Histology and Embryology.Southern Medical university,guangzhou 510515,china department of Parasitology,zhongshan Medical College.sun yat-sen university,guangzhou 510080.china Cancer Research Institute Southern Medical UniversityGuangzhou 510515 China department of Histology and Embryology Southern Medical UniversityGuangzhou 510515 China department of Parasitology Zhongshan Medical College SUN Yat-sen UniversityGuangzhou 510080 China

Nasopharyngeal carcinoma(NPC)is a malignancy with high incidence in Southern china andSouth-East *** studies indicate that chemical carcinogen promoters,such as 12-O-tetradecanoylphorbol-13-acetate(TPA),are important ... 详细信息

关键词： 12-O-tetradecanoyl-phorbol-13-acetate nasopharyngeal carcinoma proteomics apoptosis

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Protective effect of membrane cofactor protein against complementdependent injury

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Acta Pharmacologica Sinica 2005年第8期26卷 987-991页

作者： Dong XU, Shou-jian HUANG~1, Jin-qun WANG, Chu-kun WU department of Pharmacology, sun yat-sen Medical College of sun yat-sen university, guangzhou 510080, china department of Pharmacology Sun Yat-Sen Medical College of Sun Yat-Sen University Guangzhou China

Aim: To evaluate the protective role of membrane cofactor protein (MCP CD46) on complement-dependent injury. Methods: MCP was separated by ion exchange chromatography on a DEAE sephadex A-50 column from pig erythrocyte ghosts. Its protective effect was tested in models such as cobra venom factor (CVF)-induced platelet metamorphosis and aggregation, human serum-induced injury in isolated working guinea pig heart and reverse passive Arthus reaction. Results: MCP inhibited CVF-induced platelet metamorphosis with an IC50of 56.7 mg/L±2.6 mg/L, and prevented injury induced by activated complement in isolated working guinea pig hearts. In the rat model of reverse Arthus reaction, MCP relieved the skin lesions induced by immune complexes. Conclusion: MCP has a protective effect against complement-dependent injury.

关键词： CD46 antigen complement heart reverse Arthus reaction

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