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

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,{2.,wuhan 43002..china 2.0} of Anesthesia,union hospital,Tongji Medical College,{2.,wuhan 43002..china 3department of general surgery,union hospital,Tongji Medical College,{2.,wuhan 43002..china 1. department of Emergency Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China2. Department of Anesthesia Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China3. Department of General Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 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

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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, {2. 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, {2. 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 {2.} surgery, {2. Affiliated to huazhong university of science and technology, wuhan 430022, china 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 {2. Union Hospital Affiliated to Huazhong University of Science and Technology Wuhan 430022 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-2.3580 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

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NMDA and AMPA receptors mediate intracellular calcium increase in rat cortical astrocytes

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Acta Pharmacologica Sinica 2004年第6期25卷 12-18页

作者： Bo HU, Sheng-gang SUN2. E-tang TONGNeurology department, union hospital, Tongji College, {2., wuhan 430022. china Neurology department Union Hospital Tongji College Huazhong University of Science and Technology Wuhan 430022 China

AIM: To study the effect of glutamate on the intracellular calcium signal of pure cultured rat astrocytes and the roleof N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) re-ceptors in the procedure. METHODS: The fluorescence of calcium was measured by Fura-2.AM (F345/F380).RESULTS: L-Glutamate induced [Ca2.]i increase in most of the cells in concentration- and time-dependent *** 50 mmol/L induced the fluorescence increase by almost three to four times, while the effect of AMPA 50mmol/L was just half of that of D-(-)-2.amino-5-phosphonopentanoic acid (D-AP-5; a selective antagonist of theNMDA receptor). 6-Cyano-7-nitroquinoxaline-2.3-dione (CNQX, a selective antagonist of the AMPA receptor)abolished the effects of NMDA and AMPA, respectively. D-AP-5 and CNQX simultaneously or respectively attenu-ated the effect of L-glutamate at different degrees, but could not abolish it entirely. CONCLUSION: Glutamatemodulated intracellular Ca2. of pure cultured rat astrocytes through different pathways. The activation of NMDAand AMPA receptors took part in the complex mechanisms.

关键词： glutamate astrocytes NMDA receptors AMPA receptors calcium

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Expression and signifi cance of TLR4 and HIF-1α in pancreatic ductal adenocarcinoma

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World Journal of Gastroenterology 2010年第23期16卷 2881-2888页

作者： Jian-Jun Zhang,He-Shui Wu,Lin Wang,Yuan Tian,Jing-Hui Zhang,Hai-Long Wu department of Pancreatic surgery,{2.,Tongji Medical College,huazhong university of science and technology,wuhan 430022.Hubei Province,china department of Pediatrics,{2.,Tongji Medical College,huazhong university of science and technology,wuhan 430022.Hubei Province,china Laboratory of general surgery,{2.,Tongji Medical College,huazhong university of science and technology,wuhan 430022.Hubei Province,china department of Pancreatic surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 Hubei Province China. heshuiwu@***

AIM:To investigate the expression of toll-like receptor(TLR) 4,nuclear factor-κB(NF-κB) p65 and hypoxiainducible transcription factor 1α(HIF-1α) in pancreatic ductal adenocarcinoma and their clinical ***:The mRNA of TLR4 and HIF-1α were investigated by real-time polymerase chain reaction in 30 cases of pancreatic ductal adenocarcinoma and its adjacent tissues,and expression of TLR4,NF-κB p65 and HIF-1α protein were detected by immunohistochemistry in 65 cases of pancreatic ductal adenocarcinoma tissues and 38 cases of corresponding adjacent *** relationship between TLR4 or HIF-1α and pathologic features,as well as the association between TLR4 and HIF-1α,were also ***-Meier method was used to assess the impact of expression of TLR4 and HIF-1α on survival of patients with pancreatic ***:The relative quantif ication of TLR4 and HIF-1α mRNA in tumor tissues was 0.81±0.10 and 0.87±0.11,respectively,signif icantly higher than that in adjacent tissues(0.81±0.10 vs 0.70±0.16,P=0.002.0.87±0.11 vs 0.68±0.13,P=0.000).The protein expression of TLR4,NF-κB p65 and HIF-1α in tumor tissues was 69.2.%,66.15% and 70.80%,respectively,being signif icantly higher than that in adjacent normal tissues(69.2.% vs 39.50%,P=0.003;66.15% vs 31.58%,P=0.001;70.80% vs 36.80%,P=0.001).There was no signif icant correlation between TLR4 or HIF-1α expression and the age,gender,tumor location,the degree of tumor differentiation in the patients(P>0.05).However,there was signif icant correlation between the expression of TLR4 or HIF-1α and tumor size,lymph node metastasis,venous invasion and clinical staging(P<0.05).The expression of TLR4 and HIF-1α had a signif icant impact on survival of patients with pancreatic ***:TLR4,NF-κB p65 and HIF-1α are overexpressed in pancreatic adenocarcinoma,TLR4 may be partly involved in up-regulating HIF-1α,and both synergestically promote development of pancreatic adenocarcinoma.

关键词： Pancreatic ductal adenocarcinoma Toll-like receptor 4 Nuclear factor-κB p65 Hypoxia-inducible factor 1

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Inhibition of ethanol-induced toxicity by tanshinone ⅡA in PC12.cells

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Acta Pharmacologica Sinica 2006年第6期27卷 659-664页

作者： Xian-fang MENG~2.Xiao-jing ZOU~3 Bin PENG~2.Jing SHI~2.Xin-min GUAN~2.Chun ZHANG~(4,5)2.department of Neurobiology,Tongji Medical College,huazhong university of science and technology,{2. 430030,china 3 department of Anesthesiology,4 department of Nephrology,union hospital,Tongji Medical College,huazhong university of science and technology,wuhan 43002..china department of Neurobiology Tongji Medical College Huazhong University of Science and Technology Wuhan China department of Anesthesiology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To observe the effects of tanshinone IIA(Tan IIA)on the neurotoxicityinduced by ethanol in PC 12.cells and to explore its protective ***:PC 12.ell survival was measured by MTT *** formation of reactive oxygenspecies(ROS)and lactate dehydrogenase(LDH)release were detected by 2.,7′-dichlorofluorescin(DCF)fluorescence and calorimetric method,*** of cell apoptosis was monitored by flow *** expression ofp53 was detected by immuno-fluorescence and flow ***:Ethanolsignificantly impaired the survival of PC12.cells as demonstrated by MTT *** also induced significant ROS formation and increased LDH ***-incubation with Tan IIA in the culture medium significantly reversed these *** caused cell apoptosis and the upregulation of p53 *** anti-apoptosis effects of Tan IIA on ethanol-induced toxicity were accompanied by thedownregulation of pro-apoptotic p53 protein ***:Tan IIAcan protect neurons from apoptosis and might serve as a potential therapeuticdrug for neurological disorders induced by ethanol.

关键词： apoptosis ethanol PC12.cells p53 tanshinone ⅡA

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The characteristics of arc beam shaping in hybrid plasma and laser deposition manufacturing

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science china(Technological sciences) 2006年第2期49卷 238-247页

作者： ZHANG Hai’ou1, QIAN Yingping1,3, WANG Guilan1 & ZHENG Qiguang2.1. School of Material science and technology, {2., wuhan 430074, china 2. Institute of Laser technology and Engineering, {2., wuhan 430074, china 3. Mechanical Engineering College, Hubei university of technology, wuhan 430068, china 1. School of Material science and technology Huazhong University of Science and Technology Wuhan 430074 China 3. Mechanical Engineering College Hubei University of Technology Wuhan 430068 China 2. Institute of Laser technology and Engineering Huazhong University of Science and Technology Wuhan 430074 China

As a new direct metal prototyping technology,the hybrid plasma and laser deposition manufacturing (PLDM) is proposed in this paper. In order to figure out the characteristics of plasma arc beam and mould in the PLDM process of high temperature alloy, the high speed CCD camera is used to obtain the picture around the plasma arc. Afterwards the sketch of picture is clearly obtained. And the effect of laser parameter, such as average power, pulse width, pulse repetition frequency and the angle between laser beam and plasma arc beam on the plasma arc appearance, is studied experimentally. The results show that the modality of plasma arc beam is markedly influenced by laser beam. And the improvements of shape precision and surface state of the layer deposited by PLDM are confirmed.

关键词： plasma hybrid laser, direct deposition, plasma arc beam, molding character, high-temperature alloy.

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Convergence analysis for general linear methods applied to stiff delay differential equations

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Progress in Natural science:Materials International 2002年第6期12卷 16-22页

作者： ZHANG Chengjian(department of Mathematics, huazhong university of science and technology, {2. 430074, china) huazhong Univ Sci & Technol Dept Math Wuhan 430074 Peoples R China

For Runge-Kutta methods applied to stiff delay differential equations (DDEs), the concept of D-convergence was proposed, which is an extension to that of B-convergence in ordinary differential equations (ODEs) . In this paper, D-convergence of general linear methods is discussed and the previous related results are improved. Some order results to determine D-convergence of the methods are obtained.

关键词： D-convergence general linear methods stiff delay differential equations.

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Antioxidative effect of propofol during cardiopulmonary bypass in adults

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Acta Pharmacologica Sinica 2004年第3期25卷 80-86页

作者： Shi-hai ZHANG2.Shou-yong WANG,Shang-long YAO department of Anesthesiology,union hospital,Tongji MedicalCollege,{2. universityof science & technology,wuhan 43002..china department of Anesthesiology Union Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan 430022 China

AIM: To investigate the antioxidative potential of propofol (an intravenous anesthetic with a chemical structure similarto phenol-basedfree radicalscavengers suchas vitaminE) during cardiopulmonary bypass(CPB). METHODS: Thirty adult patients referred for elective cardiac procedure with CPB were included and randomly allocated to a propofol group or a control group. Patients in the propofol group received propofol (0.1 mg·kg-1·min-1) intrave- nously for anesthesia maintenance, whereas those allocated to the control group received fentanyl 10 μg/kg intrave- nously and inhaled enflurane (1 %-1.5 %). Blood samples were collected at 7 time points: before the start of CPB, at 30 and 60 min of CPB, at the conclusion of CPB, 10 min after the administration of protamine, and 12.and 2. h after the cessation of CPB. Plasma levels of free F2.isoprostanes (sensitive markers of free radicals production) and complement C5a were determined by mass-spectrometricassay and enzyme immunoassay, respectively. Neu- trophil adhesion to endothelial cells was observed at ×2.0 magnificationunder a light microscope. RESULTS: Levels of F2.isoprostanes, complement C5a and neutrophil adhesion rate increased significantly during and after CPB in both groups. There were significantly higher levels of F2.isoprostanes, C5a, and more neutrophils adhering to endothelial cells in the control group than those in the propofol group, respectively. CONCLUSION: Cardio- pulmonary bypass is associated with a great production of damaging free radicals. Propofol may be beneficial both as an anesthetic and as a potent free radical scavenger in patients presenting pathologies associated with free radical reactions during CPB.

关键词： propofol cardiopulmonary bypass free radicals F2.isoprostanes complement 5a

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The Study on BCR/ABL Fusion Gene in Adult Acute Lymphoblastic Leukemia

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wuhan university Journal of Natural {2.s 2001年第3期6卷 742-746页

作者： Li Hui yu 1,2.,Zuo Guo Lin 1, ,Zuo Ping 2.1.College of Life science, wuhan {2.,wuhan 430072.china 2.union hospital,Tongji Medical College,huazhong university of science and technology,wuhan 43002..china wuhan university College of Life Science Wuhan China (GRID:grid.49470.3e) (ISNI:***) huazhong university of science and technology Union Hospital Tongji Medical College Wuhan China (GRID:grid.33199.31) (ISNI:***) wuhan university College of Life Science Wuhan China (GRID:grid.49470.3e) (ISNI:***) huazhong university of science and technology Union Hospital Tongji Medical College Wuhan China (GRID:grid.33199.31) (ISNI:***)

In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 2. patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT-PCR. The results showed that 9 cases (31.2.%) were BCR/ABL positive, and expressed P2.0 subtype. Among them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p0.05). The induction failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis.

关键词： Key words BCR/ABL gene acute lymphoblastic leukemia nested RT PCR

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D-CONVERGENCE AND STABILITY OF A CLASS OF LINEAR MULTISTEP METHODS FOR NONLINEAR DDES

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Journal of Computational Mathematics 2000年第2期18卷 199-206页

作者： Cheng-jian Zhang Xiao-xin Liao (department of Mathematics, huazhong university of science and technology, {2. 430074, china) 华中科技大学湖北武汉 430074

Presents information on a study which dealt with the error behavior and the stability analysis of a class of linear multistep methods with the Lagrangian interpolation as applied to the nonlinear delay differential eq... 详细信息

关键词： D-convergence stability multistep methods nonlinear DDEs

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