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Activation of ERK/CREB pathway in spinal cord contributes to chronic constrictive injury-induced neuropathic pain in rats

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Acta Pharmacologica Sinica 2005年第7期26卷 789-798页

作者： Xue-song SONG~2 Jun-li CAO~(3,4,5) Yan-bing XU~3 Jian-hua HE~3 Li-cai ZHANG~3 Yin-ming ZENG~(3,4)2 Department of Anesthesiology,First Clinical college of N.Bethune Centre of Health Sciences,Jilin University,Changchun 130021,china 3 Department of Anesthesiology,affiliated hospital of xuzhou medical college,xuzhou 221002,china 4 Jiangsu Institute of Anesthesiology,xuzhou 221002,china DepartmentofAnesthesiology FirstClinicalCollegeofN.BethuneCentreofHealthSciencesJilinUniversityChangchun130021China

Aim:To investigate whether activation and translocation of extracellular signal-regulated kinase(ERK)is involved in the induction and maintenance of neuro-pathic pain,and effects of activation and translocation of ERK on expression ofpCREB and Fos in the chronic neuropathic ***:Lumbar intrathecalcatheters were chronically implanted in male Sprague-Dawley *** left sciaticnerve was loosely ligated proximal to the sciatica's trifurcation at approximately 1.0mm intervals with 4-0 silk *** mitogen-activated protein kinase kinase(MEK)inhibitor U0126 or phosphorothioate-modified antisense oligonucleotides(ODN)were intrathecally administered every 12 h,1 d pre-chronic constrictioninjury(CCI)and 3 d *** and mechanical nociceptive thresholdswere assessed with the paw withdrawal latency(PWL)to radiant heat and vonFrey *** expression of pERK,pCREB,and Fos were assessed by bothWestern blotting and immunohistochemical ***:Intrathecal injec-tion of U0126 or ERK antisense ODN significantly attenuated CCI-induced me-chanical allodynia and thermal *** significantly increased the ex-pression of p-ERK-IR neurons in the ipsilateral spinal dorsal horn to injury,not inthe contralateral spinal dorsal *** time courses of pERK expression showedthat the levels of both cytosol and nuclear pERK,but not total ERK,were in-creased at all points after CCI and reached a peak level on postoperative d *** significantly increased the expression of pCREB and ***-CREB-positive neurons were distributed in all laminae of the bilateral spinal cord and Foswas expressed in laminae I and II of the ipsilateral spinal dorsal *** of U0126 or ERK antisense ODN markedly suppressed the increase ofCCI-induced pERK,pCREB and c-Fos expression in the spinal ***:The activation of ERK pathways contributes to neuropathic pain in CCI rats,andthe function of pERK may partly be accomplished via the cAMP

关键词： extracellular signal-regulated kinases cyclic AMP-response DNA-binding protein pain hyperalgesia spinal cord

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Changes in Dietary Patterns and Certain Nutrition-related Diseases in Urban and Rural Residents of Jiangsu Province,china,During the 1990s

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Biomedical and Environmental Sciences 2002年第4期15卷 271-276页

作者： WANG CAN-NAN , LIANG ZHI , WEI PING , LIU PEI , YD JiA-Xr, ZHANG DAN-MEI, AND MA FENG-LOUFaculty of Public Health, xuzhou medical college, xuzhou, Jiangsu 221002, china Bureau ofHealth, Jiangsu Provincial Government, Nanjing, Jiangsu 210008, china Statistical Bureauof Jiangsu Provincial Government Nanjing, Jiangsu 210026, china Health andAnti-epidemic Station of xuzhou, xuzhou. Jiangsu 221002, china ’ School of PublicHealth, Nanjing medical University, Nanjing, Jiangsu 210029, china Faculty of Public Health Xuzhou Medical College 江苏 Xuzhou 221002 Bureau of Health Jiangsu Provincial Government 江苏 Nanjing 210008 Faculty of Public Health Xuzhou Medical Colleg 江苏 Xuzhou 221002 Health and Anti-epidemic Station of xuzhou 江苏 Xuzhou 221002 School of Public Health Nanjing Medical University 江苏 Nanjing 210029

Objective To investigate into the changes of dietary patterns and their impacts on health of urban and rural residents in Jiangsu Province, china during the 1990s. Methods On the basis of the results of food consumption survey, the calorie intake was calculated according to the balanced diet method and the quality of diet was assessed by scores of desirable dietary pattern (DDP). Results It was found that food consumption and dietary patterns changed remarkably during the 1990s. Grain consumption was decreasing year by year, but the consumption of animal food was markedly increasing. Although the score of desirable dietary pattern (DDP) in urban residents was more than 90, the deducted score due to over-consumption of animal food increased. The mortality from infectious diseases evidently decreased in the whole province, while the death rates of some chronic diseases, such as diabetes, hypertension, colorectal cancer and breast cancer, were increasing rapidly in urban areas. Conclusions Sufficient attention should be paid to the negative effects of change in dietary patterns on people's health, especially in the urban residents.

关键词： Dietary patterns Nutrition-related diseases

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Comparative Study on 4 EIA Kits for Screening Antibody to Hepatitis C Virus in Pooled Sera

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Biomedical and Environmental Sciences 1998年第1期11卷 75-80页

作者： LIU PEI SHI ZHI-XU ZHANG YAN-CHAO AND ZHANG XIN-YING (Deportment of Public Health, twrtment of Infectious Disease,xuzhou medical college xuzhou Red Cross BloodService, xuzhou, Jiangsu, china) Department of Public Health Xuzhou Medical College Jiangsu China.

Four enzyme immunoassay (EIA) test kits, 1 Canadian product and 3 Chinese products,were used in the comparative study. Each pool consisted of 5 sera, and the 5 single sera were tested as controls. The tests were carried out according to the instructions, keeping the same dilution of each serum in single and pool samples. It was found that with the Canadian kit,the positive and negative results of opled sera had no difference from that of the controls (P>0. 10). In the case of Chinese Yali and Kehua kits, the positive results of pooled sera showed no difference from the controls (P >0. 10), but the optical density (OD) of negative opls were increased (P < 0. 01 ), though quite distant from the cut-off values. In the case of Changzheng kit, the OD of opitive opls were significantly lower than those of the controls (P < 0. 05 ), and weak positive samples missed the detection. However this problem could be overcome by blocking the microwells beforehand. Our experiment demonstrate that not all EIA test kits are suitable for screening opls for antithey to hepatitis C virus, and that it is important to assess the sensitivity of the EIA kit to be used for this purpose.

关键词： EIA Comparative Study on 4 EIA Kits for Screening Antibody to Hepatitis C Virus in Pooled Sera

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Inhibition of Proliferation and Induction of Apoptosis in Human Renal Carcinoma Cells by Anti-telomerase Small Interfering RNAs

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Acta Biochimica et Biophysica Sinica 2006年第7期38卷 500-506页

作者： Jun-Nian ZHENG~(1,3#*)Ya-Feng SUN~(2#)Dong-Sheng PEI~2 Jun-Jie LIU~1 Jia-Cun CHEN~1 Wang LI~1 Xiao-Qing SUN~1 Qi-Duo SHI~3 Rui-Fa HAN~3 Teng-Xiang MA~3 1 laboratory of Urology,affiliated hospital of xuzhou medical college,xuzhou 221002,china 2 Research center for Biochemistry and Molecular Biology,xuzhou medical college,xuzhou 221002,china 3 Institute of Urology,Tianjin medical University,Tianjin 300070,china laboratoryofUrology AffiliatedHospitalofXuzhouMedicalCollegeXuzhou221002China ResearchcenterforBiochemist'ryandMolecularBiology XuzhouMedicalCollegeXuzhou221002China

Telomerase is an attractive molecular target for cancer therapy because it is present in mostmalignant cells but is undetectable in most normal somatic *** telomerase consists of two subunits,an RNA component(hTR)and a human telomerase reverse transcriptase component(hTERT).Smallinterfering RNA(siRNA),one kind of RNA interferences,has been demonstrated to be an effective methodto inhibit target gene expression in human *** investigated the effects of siRNA targeting at both hTRand hTERT mRNA on the inhibition of telomerase activity in human renal carcinoma cells(HRCCs).Theproliferation and apoptosis of HRCCs were *** treatment of HRCCs using hTR and hTERTsiRNAs resulted in significant decrease of hTR mRNA,hTERT mRNA and hTERT *** siRNA canalso inhibit the telomerase activity and the proliferation of ***,they can induce apoptotic celldeath in a dose-dependent *** these findings,we propose that the inhibition of telomerase activityusing siRNA targeting hTR and hTERT might be a rational approach in renal cancer therapy.

关键词： hTERT hTR telomerase siRNA renal cell carcinoma proliferation apoptosis

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Treatment with Vector-expressed Small Hairpin RNAs against Ki67 RNA-induced Cell Growth Inhibition and Apoptosis in Human Renal Carcinoma Cells

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Acta Biochimica et Biophysica Sinica 2006年第4期38卷 254-261页

作者： Jun-Nian ZHENG~(1,3*) Ya-Feng SUN~(2#) Dong-Sheng PEI~2 Jun-Jie LIU~1 Teng-Xiang MA~3 Rui-Fa HAN~3 Wang LI~1 Dian-Bao ZHENG~1 Jia-Cun CHEN~1 Xiao-Qing SUN~1 1 laboratory of Urology,affiliated hospital of xuzhou medical college,xuzhou 221002,china 2 Research center for Biochemistry and Molecular Biology,xuzhou medical college,xuzhou 221002,china 3 Institute of Urology,medical University of Tianjin,Tianjin 300211,china laboratoryofUrology AffiliatedHospitalofXuzhouMedicalCollegeXuzhou221002China ResearchcenterforBiochemistryandMolecularBiology XuzhouMedicalCollegeXuzhou221002China InstituteofUrology MedicalUniversityofTianjin

Short hairpin RNAs (shRNAs) transcribed *** polymerase Ⅲ promoters can triggersequence-selective gene silencing in mammalian *** virtue of their excellent function in knocking downexpression of cancer-associated genes,shRNAs could be used as new therapeutic agents for *** of Ki67 in renal cancer has been correlated to a more aggressive tumor phenotype,inhibitionof Ki67 protein expression by means of shRNAs seems to be a promising approach for the therapy of *** this study,we constructed an expression plasmid encoding shRNAs against the Ki67 gene,namedpSilencerKi67,and transfected it into human renal carcinoma *** pSilencerKi67 was shown to signifi-cantly knock down the expression of the Ki67 gene in human renal carcinoma cells,resulting in inhibitingproliferation and inducing apoptotic cell death that can be maintained for at least *** findings offer thepromise of using vector-based shRNAs against Ki67 in renal cancer gene therapy.

关键词： Ki67 gene shRNAs renal cell carcinoma proliferation apoptosis

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Ohmefentanyl stereoisomers induce changes of CREB phosphorylation in hippocampus of mice in conditioned place preference paradigm

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Cell Research 2003年第1期13卷 29-34页

作者： CAN GAO, Li WEI CHEN, JIE CHEN, XUE JUN XU, ZHI QIANG CHISecond Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, chinaResearch center for Biochemistry and Molecular Biology, xuzhou medical college, xuzhou, Jiangsu 221002, china Second Department of Pharmacology Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

The present study was designed to determine the changes of phosphorylation of cAMP- response element binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204) in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204 displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for a long time without affecting total CREB protein levels. The effect of F9204 was similar to morphine which effect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitive N-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phosphorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also the phosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterations in the phosphorylation of CREB be relevant to opiates signaling and the development of opiates depende

关键词： cAMP-response element binding protein (CREB) ohmefentanyl stereo isomers opiates hippocampus conditioned place preference (CPP).

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The role of different cues in the brain mechanism on visual spatial attention

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Progress in Natural Science:Materials International 2006年第10期16卷 1045-1050页

作者： SONG Weiqun, LUO Yuejia, CHI Song, JI Xunming, LING Feng, ZHAO Lun, WANG Maobin and SHI Jiannong ( Department of Rehabilitation, Xuanwu hospital, Capital University of medical Science, Beijing 100053, china State Key laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, china School of Psychology, Southwest University, Chongqing 400715, china Key laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, china Department of Neurology, affiliated hospital of Qingdao University, medical college, Qingdao 266003, china Department of Neurology, Xuanwu hospital, Capital University of medical Science, Beijing 100053, china Institute of Linguistics, xuzhou Normal University, xuzhou 221116, china) [a]Department of Rehabilitation Xuanwu Hospital Capital University of medical science Beijing China [b]State Key laboratory of Cognitive Neuroscience and Learning Beijing Normal University Beijing China [c]School of Psychology Southwest University Chongqing China [d]Key laboratory of Mental Health Institute of Psychology Chinese Academy of Science Beijing China [e]Department of Neurology Affiliated Hospital of Qingdao University Medical College Qingdao China [f]Department of Neurology Xuanwu Hospital Capital University of Medical Science Beijing China [g]Institute of Linguistics Xuzhou Normal University Xuzhou China

The visual spatial attention mechanism in the brain was studied in 16 young subjects through the visual search paradigm of precue-target by the event-related potential (ERP) technique, with the attentive ranges cued by different scales of Chinese character and region cues. The results showed that the response time for Chinese character cues was much longer than that for region cues especially for small region cues. With the exterior interferences, the target stimuli recognition under region cues was much quicker than that under Chinese character cues. Compared with that under region cues, targets under Chinese character cues could lead to increase of the posterior P1, decrease of the N1 and increase of the P2. It should also be noted that the differences between region cues and Chinese character cues were affected by the interference types. Under exterior interferences, no significant difference was found between region cues and Chinese character cues; however, it was not the case under the interior interferences. Considering the difference between the exterior interferences and the interior interferences, we could conclude that with the increase of difficulty in target recognition there was obvious difference in the consumption of anterior frontal resources by target stimuli under the two kinds of cues.

关键词： visual spatial attention cue scale event-related potential (ERP) Chinese character cues region cues.

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GABAA receptor partially mediated propofol-induced hyperalgesia at superspinal level and analgesia at spinal cord level in rats

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Acta Pharmacologica Sinica 2004年第12期25卷 53-59页

作者： Qin-yun WANG2,3, Jun-li CAO2, Yin-ming ZENG2, Ti-jun DAI2,4 2Jiangsu Institute of Anesthesiology, Jiangsu Province Key laboratory of Anesthesiology, xuzhou, 221002, china 3Department of Anesthesiology, the1st affiliated hospitalof Soochow University, Suzhou 215006, china Jiangsu Institute of Anesthesiology Jiangsu Province Key Laboratory of Anesthesiology Department of Anesthesiology the 1st Affiliated Hospital of Soochow University

AIM: To observe effects of propofol on nociceptive response at superspinal and spinal level in rats. METHODS: Two hundreds and fifty-eight Sprague-Dawley male rats were randomized into thirty-two groups. Propofol and bicuculline were microinjected into lateral ventricle (icv), ventrolateral periaqueductal gray (vlPAG), intrathecal (ith), and intraperitoneal (ip). The noxious responses were evaluated by hot plate and formalin test. RESULTS: In hot-plate test, systemic and superspinal administration of propofol (40 mg·kg-1 ip, 100 μg in 10 μL, icv, and 4 μg in 0.4 μL vlPAG microinjection) produced hyperalgesia (P4 μL, vlPAG) (P4.8 %, 80.8 %, and 97.4 % at 10, 20, 30 and 40 min by ith bicuculline (P40 mg·kg-1 ip, 4 μg in 0.4 μL, vlPAG) also produced hyperal- gesia (P<0.01). The increased formalin pain scores were antagonized about 57.1 % by bicuculline (10 ng, vlPAG) (P<0.05) at 60 min after formalin injection. The decreased formalin pain scores induced by ith propofol (100 μg in 10 μL) were antagonized about 66.7 % at 30 min by ith bicuculline (P<0.05) after formalin injection. Hyperalgesia produced by ip propofol in both hot plate and formalin test could not be antagonized by vlPAG administration of bicuculline. CONCLUSION: GABAA receptor partly mediated propofol-induced hyperalgesia at superspinal and analgesia at spinal cord in rats.

关键词： GABA receptors propofol pain ventrolateral periaqueductal gray spinal cord

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Competitive binding of postsynaptic density 95 and Ca2+-calmodulin dependent protein kinase II to N-methyl-D-aspartate receptor subunit 2B in rat brain

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Acta Pharmacologica Sinica 2004年第2期25卷 50-54页

作者： Fan-jie MENG , Jun GUO, Bo SONG, Xue-bo YAN, Guang-yi ZHANG2 Research center of Biochemistry and Molecular Biology, xuzhou medical college, xuzhou 221002, china Research center of Biochemistry and Molecular Biology Xuzhou Medical College Xuzhou 221002 China

AIM: To investigate the interactions among postsynaptic density 95 (PSD-95), Ca2+-calmodulin dependent protein kinase IIα (CaMKIIα), and N-methyl-D-aspartate receptor subunit 2B (NR2B) during ischemia and reperfusion in hippocampus of rats. METHODS: Brain ischemia was induced by four-vessel occlusion procedure in rats. Immu- noprecipitation and immunoblotting were performed to study the interactions and phosphorylation of proteins. The association-dissociation of PSD-95 and CaMKIIα to and from N-methyl-D-aspartate (NMDA) receptor induced by ischemia and reperfusion and the effects of 1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenyl-pip- erazine (KN-62, a selective inhibitor of CaMKII) on these protein interactions were investigated. Coimmuno- precipitation and immunoblotting were performed for the studies of interactions among proteins. RESULTS: The alternations of the binding level of PSD-95 and CaMKIIα to NR2B during ischemia and reperfusion demonstrated the negative correlation to each other. Pre-administration of KN62 through both cerebral ventricles inhibited the 10 min ischemia-induced increase of the binding of PSD-95 to NR2B and, on the contrary, promoted the binding of CaMKIIα to NR2B. CONCLUSION: PSD-95 competes with CaMKII to bind to NR2B during ischemia and reperfusion in rat hippocampus.

关键词： N-methyl-D-aspartate receptors Ca2+-calmodulin dependent protein kinase brain ischemia

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Neuroprotection of selenite against ischemic brain injury through negatively regulating early activation of ASK1/JNK cascade via activation of PI3K/AKT pathway

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Acta Pharmacologica Sinica 2007年第1期28卷 19-27页

作者： Qing WANG Quan-guang ZHANG Dong-na WU Xiao-hui YIN Guang-yi ZHANG~2 Research center for Biochemistry and Molecular Biology,xuzhou medical college,xuzhou 221002,china ResearchcenterforBiochemistryandMolecularBiology XuzhouMedicalCollegeXuzhou221002China

Aim:To investigate whether selenite,a known antioxidant,could decrease theactivation of apoptosis signal regulating kinase 1/c-jun N-terminal kinase(ASK1/JNK)signaling cascade in cerebral ischemia/reperfusion(I/R)by activating thephosphatidylinositol 3-kinase(PI3K)/AKT pathway in rat hippocampi,and theneuroprotective effect of selenite against ischemic injury after 15 min of transientbrain ***:Transient global brain ischemia was induced by4-vessel occlusion into adult male Sprague-Dawley rats weighing 250-300 *** were pretreated only with selenite(0.3 mg/kg dissolved in 0.9% saline)every24 h for 7 d by means of intravenous injection of the tail or combined with LY294002from d 5 by left cerebral ventricle injection before ***:Selenitesignificantly increased AKT 1 activation and decreased the activation of ASK1/JNK cascade via phosphorylating ASK1 at Ser-83 residue by AKT1 during earlyreperfusion after 15 min transient global brain *** the contrary,com-bined pretreatment of the rats with LY294002(a specific PI3K inhibitor)and selen-ite significantly inhibited the effects solely with ***:The activa-tion of the pro-apoptotic ASK1/JNK cascade,which is closely associated withoxidative stress,could be suppressed by selenite through activating the anti-apoptotic PI3K/AKT pathway during early reperfusion after cerebral ischemia inrat hippocampi.

关键词： cerebral ischemia PI3K/AKT ASK1/JNK LY294002 selenite

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