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Acta Pharmacologica Sinica 2005年第5期26卷 603-609页

作者： Hong-li LIU~2,Yan CHEN~(2,3),Guo-hui CUI~2,Jian-feng ZHOU~4~2department of Hematology,Union Hospital,tongji medical college.huazhong university of science and technology.wuhan 430022,china.~4department of Hematology.tongji Hospital,tongji medical college.huazhong university of science and technology.wuhan430030,china department of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China department of Hematology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To investigate curcumin(diferuloylmethane)induced apoptosis and its mo-lecular mechanism of action in B-NHL cell line Raji ***:Raji cells werecultured in RPMI-1640 medium and treated with curcumin in different concentra-tions.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium(MTT)assay wasused to detect growth inhibition and Hoechst 33258 staining was used to *** and Western blot were used to detect the ex-pressions of histone deacetylase 1,3,and 8(HDAC 1,HDAC3,and HDACS)andacetylated histone H4(Ac-histone H4)***:Curcumin inhibited theproliferation of B-NHL cell line Raji cells with a 36-h IC50value of 24.1±2.0μmol/*** 33258 staining showed that curcumin could induce Raji cell *** expression levels of HDAC1,HDAC3,and HDAC8 proteins were downregulat-ed following curcumin treatment in Raji cells,whereas Ac-histone H4 protein expres-sion was upregulated after treatment with ***:Curcumin,as anew member of the histone deacetylase inhibitors,can inhibit the expression ofclass I HDACs(HDAC1,HDAC3,and HDAC8),and can increase the expressionof Ac-histone H4 in Raji *** plays an important role in regulatingB-NHL cell line Raji cell proliferation and apoptosis.

关键词： curcumin histone deacetylase acetylated histone H4 Raji

Efficient inhibition of human telomerase activity by antisense oligonucle-otides sensitizes cancer cells to radiotherapy

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Acta Pharmacologica Sinica 2006年第9期27卷 1185-1191页

作者： Xue-mei JI~2 Cong-hua XIE~2 Ming-hao FANG~3 Fu-xiang ZHOU~2 Wen-jie ZHANG~4 Ming-sheng ZHANG~2 Yun-feng ZHOU~(2,5)2 department of Chemotherapy and Radiation Oncology,Zhongnan Hospital,wuhan university,wuhan 430071,china 3 department of Emergency,tongji Hospital,tongji medical college.huazhong university of science and technology.wuhan 430030,china 4 Cancer Research Institute,wuhan university,wuhan 430071,china department of Chemotherapy and Radiation Oncology Zhongnan Hospital Wuhan University Wuhan China department of Emergency Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China Cancer Research Institute Wuhan University Wuhan China

Aim:To investigate the effect of the antisense otigonucleotides（ASODN）spe-cific for human telomerase RNA（hTR）on radio sensitization and proliferationinhibition in human neurogliocytoma cells（U251）.Methods:U251 cells weretransfected with hTR ASODN or nonspecific oligonucleotides（NSODN）.Beforeand after irradiation of60Co-γray,telomerase activity was assayed by telomericrepeat amplification protocol（TRAP-PCR-ELISA）,and DNA damage and repairwere examined by the comet *** classical colony assay was used to plotthe cell-survival curve,to detect the ***:hTR antisense oligo-nucleotides could downregulate the telomerase activity,increase radiation in-duced DNA damage and reduce the subsequent ***,it could in-hibit the proliferation and decrease the D0value which demonstrates ***,telomere length was unchanged over a short period ***:These findings suggest that an ASODN-based strategy may beused to develop telomerase inhibitors,which can efficiently sensitize radiotherapy.

关键词： oligonucleotides,antisense telomerase radiotherapy glioma,astrocytic gene therapy

Hyaluronic acid fragments evoke Kupffer cells via TLR4 signaling pathway

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science china(Life sciences) 2009年第2期52卷 147-154页

作者： ZHANG JinXiang1, WANG Hui2, XIAO Qing3, LIANG HuiFang4, LI ZhuoYa4, JIANG ChunFang1, WU HeShui5 & ZHENG QiChang5 1 department of Emergency Surgery, Union Hospital Affiliated to huazhong university of science and technology, wuhan 430022, china 2 department of medical Genetics, tongji medical college Affiliated to huazhong university of science and technology, wuhan 430030, china 3 department of Ophthalmology, Union Hospital Affiliated to huazhong university of science and technology, wuhan 430022, china 4 department of medical Immunology, tongji medical college Affiliated to huazhong university of science and technology, wuhan 430030, china 5 department of General Surgery, Union Hospital Affiliated to huazhong university of science and technology, wuhan 430022, china department of Emergency Surgery Union Hospital Affiliated to Huazhong University of Science and Technology Wuhan China department of medical Genetics Tongji Medical College Affiliated to Huazhong University of Science and Technology Wuhan China department of Ophthalmology Union Hospital Affiliated to Huazhong University of Science and Technology Wuhan China department of medical Immunology Tongji Medical College Affiliated to Huazhong University of Science and Technology Wuhan China department of General Surgery Union Hospital Affiliated to Huazhong University of Science and Technology Wuhan China

Kupffer cells, expressing toll-like receptor 4 (TLR4), play a central role in hepatic ischemia/reperfusion (I/R) injury. Hyaluronic acid (HA) fragments, degradative products of high-molecular-weight HA (HMW-HA), acquire the ability to activate immune cells under inflammatory conditions. Here we inves- tigated whether HA fragments could activate Kupffer cells and analyzed the underlying mechanism. Kupffer cells were isolated from wild-type mice (WT, C3H/HeN) and TLR4 mutant mice (C3H/HeJ) and HA fragments were produced by the methods of enzyme digestion and chromatography. Then Kupffer cells were stimulated by HA fragments or other control stimuli. The activation of Kupffer cells was estimated as the release of pro-inflammatory cytokines. The activation of p38 MAPK pathway of Kupffer cells was checked and blocking experiments were done as well. The results indicated that HA fragments acquired the ability to activate Kupffer cells in vitro, which was TLR4 dependent and not due to contamination of lipopolysaccharide. Experiments of p38 MAPK kinase inhibition by SB-203580 verified p38 MAPK was required in HA fragments induced Kupffer cells activation. This suggests that HA fragments, degradative products of one of the major glycosaminoglycans of the extracellular matrix, play critical roles in Kupffer cell activation mediated by TLR4 signaling pathway, which is, at least partially, de- pendent on p38 MAPK activation.

关键词： Kupffer cells hyaluronic acid fragments toll-like receptor 4 p38 MAPK lipoplysaccharide reperfusion injury liver

Prolonged Alzheimer-like Tau Hyperphosphorylation Induced by Simultaneous Inhibition of Phosphoinositol-3 Kinase and Protein Kinase C in N2a cells

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Acta Biochimica et Biophysica Sinica 2005年第5期37卷 349-354页

作者： Guo-Gang XU Yan-Qiu DENG Shi-Jie LIU Hong-Lian LI Jian-Zhi WANG department of Pothophysiology,Institute of Neuroscience,tongji medical college, huazhong university of science and technology, wuhan 430030, china department of Pathophysiology Institute of Neuroscience Tongji Medical College Huazhong University of Science and TechnologyWuhan 430030 China

Co-injection of wortmannin（inhibitor of phosphatidylinositol-3 kinase,PI3K）and GF109203X（inhibitor of protein kinase C,PKC）into the rat brain was found to induce spatial memory deficiency andenhance tau hyperphosphorylation in the hippocampus of rat *** establish a cell model with durativeAlzheimer-like tau hyperphosphorylation in this study,we treated N2a neuroblastoma cells with wortmanninand GF109203X separately and simultaneously,and measured the glycogen synthase kinase 3（GSK-3）activity by γ-（32）P-labeling and the level of tau phosphorylation by Western *** was found that theapplication of wortmannin alone only transitorily increased the activity of GSK-3（about 1 h）and the level oftau hyperphosphorylation at Ser396/Ser404 and Ser199/Ser202 sites（no longer than 3 h）;however,a prolongedand intense activation of GSK-3（over 12 h）and enhanced tan hyperphosphorylation（about 24 h）wereobserved when these two selective kinase inhibitors were applied *** conclude that the simultaneousinhibition of PI3K and PKC can induce GSK-3 overactivation,and further strengthen and prolong the Alzheimer-like tau hyperphosphorylation in N2a cells,suggesting the establishment of a cell model with early pathologicalevents of Alzheimer’s disease.

关键词： Alzheimer’s disease(AD) tau glycogen synthase kinase 3(GSK-3) protein kinase C(PKC) phosphatidylinositol-3 kinase(PI3K) N2a cells

Expression of Androgen Receptor in Meningiomas

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Journal of huazhong university of science and technology(medical sciences) 2001年第2期21卷 140-142页

作者：陈坚陈刚 department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan

In order to investigate the expression of androgen receptor in meningiomas and its relation to tumor proliferative potential, we examined the expression of AR and proliferating cell nuclear antigen by avidine biotin complex immunohistochemistry in 39 cases of meningiomas. Of the 39 cases of meningiomas, 20 showed positive AR immunoreactivity. The AR expression positivity rates were 31 % in benign meningiomas, 58 % in atypical meningiomas, 87.5 % in malignant meningiomas, respectively. In addition to the tumor cells, cells of microvascular endothelial proliferation were frequently AR positive. Malignant meningiomas had a significantly higher percentage of AR positive cells compared with atypical and benign meningiomas . The mean proliferating cell nuclear antigen labeling index was significantly higher in the malignant meningiomas when compared with atypical meningiomas and benign meningiomas . AR positive meningiomas had higher PCNA LI than AR negative meningiomas . The expression of AR in tumor tissues was significantly related with PCNA LI. These data indicated that AR in the meningiomas was correlated with histological grade and AR might participate in the growth of these tumors and tumor angiogenesis. The measurement of AR in these tumors may indirectly represent tumor growth potential.

关键词： meningiomas androgen receptor immunohistochemistry proliferating cell nuclear antigen angiogenesis

Effect of amyloid peptides on serum withdrawal-induced cell differentiation and cell viability

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Cell Research 2004年第6期14卷 467-472页

作者： Yi Peng WANG, Ze Fen WANG, Ying Chun ZHANG, Qing TIAN, Jian Zhi WANG department of Pathophysiology, tongji medical college, huazhong university of science and technology, wuhan, 430030, china 1department of Pathophysiology Tongji Medical College Huazhong University of Science and Technology Wuhan China

Abnormal deposition of amyloid-p(Ap) peptides and formation of neuritic plaques are recognized as pathological processes in Alzheimer’s disease (AD) brain. By using amyloid precursor protein (APP) transfected cells, this study aims to investigate the effect of overproduction of Aβ on cell differentiation and cell viability. It was shown that after serum withdrawal, untransfected cell (N2a/Wt) and vector transfected cells (N2a/vector) extended long and branched cell processes, whereas no neurites was induced in wild type APP (N2a/APP695) and Swedish mutant APP (N2a/ APPswe) transfected N2a cells. After differentiation by serum withdrawal, the localization of APP/AP and neurofilament was extended to neurites, whereas those of APP-transfected cells were stillrestricted within the cell body. Levels of both APP and Aβ were significantly higher in N2a/APP695 and N2a/APPswe than in N2a/Wt, as determined by Western blot and Sandwich ELISA, respectively. To further investigate the effect of A0 on the inhibition

关键词： Alzheimer’s disease amyloid β cell differentiation.

The Expression of Cyclins in Neurons of Rats after Focal Cerebral Ischemia

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Journal of huazhong university of science and technology(medical sciences) 2008年第1期28卷 60-64页

作者：陈彬王伟 department of Neurology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The change of the expression of Cyclins in neurons of rats after focal cerebral ischemia was investigated. Ischemia was induced by temporary middle cerebral artery occlusion （MCAO）. The experimental rats induced by MCAO were sacrificed on 7th and 14th day after reperfusion. The brain was taken out at 7th and 14th day after injury, and the expression of Cyclin D1, E, A and B1 in neurons of cerebral cortex or hippocampal CA1 region was detected by immunofluorescence and confocal microscope. The results showed that after MCAO, in the ipsilateral CA1 subfield of hippocampus the expression of Cyclin D1, E, A and B1 in neurons was significantly gradually up-regulated at 7th and 14th day after reperfusion （P〈0.05） as compared with that in control group. In the ipsilateral cerebral cortex the expression of Cyclin D1 and B1 in neurons was notably gradually down-regulated at 7th and 14th day, and that of Cyclin E and A was significantly up-regulated at 14th day after reperfusion as compared with that in control group （all P〈0.05）. It was concluded that there was a differential sensitivity among neurons from different brain regions to ischemic injury. But all of them re-enter into cell cycle after MCAO.

关键词： cerebral ischemia neuron cell cycle confocal microscope

TLR4 signaling induced TLR2 expression in the process of mimic cerebral ischemia/reperfusion in vitro

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中国科学：生命科学英文版 2010年第2期53卷 223-228页

作者： SUN Peng1,ZHANG Qing2,HAN JiYuan1,TIAN Yuan3 & ZHANG JingHui3 1department of Emergency,Union Hospital,tongji medical college.huazhong university of science and technology.wuhan 430022,china 2department of Anesthesia,Union Hospital,tongji medical college.huazhong university of science and technology.wuhan 430022,china 3department of General Surgery,Union Hospital,tongji medical college.huazhong university of science and technology.wuhan 430022,china department of Emergency Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China department of Anesthesia Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China department of General Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Both TLR4 and TLR2 participated in the mediation of the inflammatory injury in the process of partial cerebral ischemia/***,it still remains unclear whether a crosstalk exists between TLR2 and TLR4 in ischemic cerebral *** the present study,we investigated the effect of TLR4 signaling on TLR2 expression during mimic cerebral I/R in ***-2 cells were cultured and treated with ischemia/reperfusion,then transfected with the plasmid pEGFP-H1/TLR4-siRNA,the plasmid pEGFP-H1/control sequence-siRNA and the blank plasmid,***,the expression of TLR2 and TLR4 mRNA and protein,NF-κB p65 mRNA and supernatant TNF-α level were significantly higher in ischemia/reperfusion treated cells than those lack of ischemia/reperfusion treatment,and as compared with those in ischemia/reperfusion treated cells without transfection,no significant differences about the above mentioned gene and protein expression were found in the blank plasmid tranfected cells and the plasmid pEGFP-H1/control sequence-siRNA transfected cells respectively,while the expression levels in the plasmid pEGFP-H1/TLR4-siRNA transfected cells were significantly ***,in order to determine the effects of pyrrolidinediethyldithiocarbamate (PDTC),an NF-κB inhibitor,on the TLR4-induced TLR2 expression in BV-2 cells treated with ischemia/reperfusion,it was found that TLR4 and TLR2 mRNA expressions in PDTC pretreated cells were significantly lower in comparison with normal saline pretreated cells and non-pretreated *** data suggested that TLR2 activation,signaled by TLR4 and regulated by NF-κB,might be directly involved play an important role in ischemia/reperfusion induced brain damage.

关键词： Toll-like receptor 4 Toll-like receptor 2 cerebral ischemia/reperfusion microglia

Influences of dibutyryl cyclic adenosine monophosphate and forskolin on human sperm motility in vitro

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Asian Journal of Andrology 2003年第2期5卷 113-115页

作者： Ji-Hong LIU, Yang LI, Zheng-Guo CAO, Zhang-Qun YEdepartment of Urology, tongji Hospital, tongji medical college, huazhong university of science and technology.wuhan 430030, china department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Aim: To study the influences of dibutyryl cyclic adenosine monophosphate (dbcAMP) and forskolin on human sperm motility in vitro. Methods: Semen samples, aseptically obtained by masturbation and prepared by swim-up technique from 20 fertile men, were incubated with different concentrations of dbcAMP and forskolin at 37 癈. Measurements were carried out after 10 min, 20 min, 30 min and 60 min incubation. Motility parameters were estimated by using an automatic analyzing system. Results: Treatment with dbcAMP or forskolin resulted in a significant increase in sperm motility and progressive motility. The larger the concentrations of dbcAMP or forskolin, the greater the effect appeared. The straight linear velocity and curvilinear velocity were not affected by both agents. Conclusion: dbcAMP and forskolin increase the motility and progressive motility of human sperm in vitro.

关键词： dibutyryl cyclic AMP forskolin sperm motility

Risk Factors of Learning Disabilities in Chinese Children in wuhan

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Biomedical and Environmental sciences 2003年第4期16卷 392-397页

作者： BIN YAO AND HAN-RONG WUdepartment of Children and Adolescent Health, Maternity and Child Health Care, tongji medical college, huazhong university of science and technology, wuhan 430030, Hubei, china department of Children and Adolescent Health Maternity and Child Health Care Tongji Medical College Huazhong University of Science and Technology 湖北 Wuhan 430030

Objective To investigate prevalence rate of learning disabilities (LD) in Chinese children, and to explore related risk factors, and to provide theoretical basis for preventing such disabilities. Methods One thousand and one hundred fifty one children were randomly selected in primary schools. According to criteria set by ICD-10, 118 children diagnosed as LD were classified into the study group. Four hundred and ninety one children were classified into the normal control group. Five hundred and forty two children were classified into the excellent control group. The study instruments included PRS (The pupil rating scale revised screening for learning disabilities), Conners' children behavior check-list taken by parents and YG-WR character check-list. Results The prevalence rate of LD in Chinese children was 10.3%. Significant differences were observed between LD and normally learning children, and between the LD group and the excellent group, in terms of scores of Conners' behavior check-list (Pchina. LD is resulted from a number of factors. Good studying and living environments should be created for LD children.

关键词： Learning disabilities (LD) Behavior problems Character Children Risk factors