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ZD7288, a selective hyperpolarization-activated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity

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Neural Regeneration Research 2016年第5期11卷 779-786页

作者： Xiao-xue Zhang Xiao-chun Min Xu-lin Xu Min Zheng lian-jun guo Department of Laboratory Medicine Affiliated Pu'ai Hospital Tongji Medical College Huazhong University of Science and Technology Department of Pharmacology School of Basic Medical Sciences Tongji Medical College Huazhong University of Science and Technology School of Biomedical Engineering Hubei University of Science and Technology

The selective hyperpolarization-activated cyclic nucleotide-gated（HCN） channel blocker 4-（N-ethyl-N-phenylamino）-1,2-dimethyl-6-（methylamino） pyrimidinium chloride（ZD7288） blocks the induction of long-term potentiation in the perforant path-CA3 region in rat hippocampus in vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path-CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hippocampal neurons using high performance liquid chromatography, and determined intracellular Ca2＋ concentration（[Ca2＋]i） using Fura-2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspecific HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Furthermore, ZD7288 attenuated glutamate-induced rises in [Ca2＋]i in a concentration-dependent manner and reversed 8-Br-c AMP-mediated facilitation of these glutamate-induced [Ca2＋]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both glutamate release and resultant [Ca2＋]i increases in rat hippocampal neurons.

关键词： nerve regeneration ZD7288 Ih, channels perforant path-CA3 synapse long-term potentiation field excitatory postsynaptic potentials glutamate release neural regeneration

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Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries:in vivo and in vitro neuroprotective effect of antihypertensive DDPH

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Neural Regeneration Research 2015年第4期10卷 589-593页

作者： Li Sun Qin Li Wei-ting Wang Yu-hua Chen lian-jun guo Department of Neurology Wuhan Brain Hospital (General Hospital of the Yangtze River Shipping) Department of Pharmacology Tongji Medical College of Huazhong University of Science and Technology Department of Pharmacology Shanghai First People’s HospitalSchool of MedicineShanghai Jiao Tong University

1-（2,6-Dimethylphenoxy）-2-（3,4-dimethoxyphenylethylamino）-propane hydrochloride （DDPH） is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemiain vivo, and a rabbit model of isolated basilar arteriesin vitro. Our results show that DDPH （10 mg/kg） significantly increased hippocampal blood flowin vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in thein vitro rabbit model. DDPH （3 × 10–5 M） also inhibited histamine-stimulated extracellular calcium inlfux and intracellular calcium release. Our ifndings suggest that DDPH has a vasodilative effect bothin vivo andin vitro, which mediates a neuropro-tective effect on ischemic nerve tissue.

关键词： nerve regeneration DDPH cerebral ischemia hippocampus blood flow isolated basilar artery dose-response curve NSFC grant neural regeneration

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Blockade of HCN2 Channels Provides Neuroprotection Against Ischemic Injury via Accelerating Autophagic Degradation in Hippocampal Neurons

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Neuroscience Bulletin 2020年第8期36卷 875-894页

作者： Cheng Chen Li Liu Ya-Qiao Shu Ping Jing Yun Lu Xiao-Xue Zhang Xian-Gang Zong lian-jun guo Chang-jun Li Department of Pharmacology School of Basic Medical SciencesTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Neurology The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Office of Academic Research The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430030China Department of Clinical Laboratory Wuhan PuAi HospitalWuhan 430033China Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation Wuhan 430030China Center for Integrated Protein Science and Zentrum fur Pharmaforschung Department PharmazieLudwig-Maximilians-Universitat Miinchen80539 MunichGermany

In the central nervous system,hyperpolarizationactivated cyclic nucleotide-gated(HCN)channels are essential to maintain normal neuronal *** studies have shown that HCN channels may be involved in the pathological process of ischemic brain injury,but the mechanisms remain *** is activated in cerebral ischemia,but its role in cell death/survival remains *** this study,our results showed that the HCN channel blocker ZD7288 remarkably decreased the percentage of apoptotic neurons and corrected the excessive autophagy induced by oxygen-glucose deprivation followed by reperfusion(OGD/R)in hippocampal HT22 ***,in the OGD/R group,p-mTOR,p-ULK1(Ser757),and p62 were significantly decreased,while p-ULK1(Ser317),atg5,and beclin1 were remarkably ***7288 did not change the expression of p-ULK1(Ser757),ULK1(Ser317),p62,Beclin1,and atg5,which are involved in regulating autophagosome ***,we found that OGD/R induced a significant increase in Cathepsin D expression,but not *** with ZD7288 at 10μmol/L in the OGD/R group did not change the expression of cathepsin D and ***,chloroquine(CQ),which decreases autophagosome-lysosome fusion,eliminated the correction of excessive autophagy and neuroprotection by ***,shRNA knockdown of HCN2 channels significantly reduced the accumulation of LC3-Ⅱand increased neuron survival in the OGD/R and transient global cerebral ischemia(TGCI)models,and CQ also eliminated the effects of ***,we found that the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes decreased in Con-shRNAtransfected HT22 neurons exposed to OGD/R or *** HCN2-shRNA-transfected HT22 neurons,the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes increased under OGD/R;however,the percentage was significantly decreased by the addition of CQ to HCN2-shRNA-transfected HT22 *** present re

关键词： HCN2 channel Autophagy Neuroprotection Oxygen-glucose deprivation/reperfusion Transient global cerebral ischemia

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Degration of Partially Stabilized Zirconia Ceramics underan Applied Stress

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Journal of Wuhan University of Technology(Materials Science) 2003年第1期18卷 17-19页

作者：沈强 WuhanUniversityofTechnology

Partially stabilized zirconia ceramics were sintered using fine powder of ZrO 2 3mol%Y 2O 3 prepared by the chemical co precipitation *** tetragonal to monoclinic phase transformation in ZrO 2 ceramics during the aging in boiling water and the effect of an applied stress of 100MPa were mainly *** degradation of ZrO 2 ceramics is considered to be caused by the reaction between Y 2O 3 and H 2O,which leads to a decreasing in the stability of tetragonal phase of ZrO *** is found that the tensile stress improves the driving force of the phase transformation and accelerates the degradation while the compressive stress has no obvious effect on the degradation.

关键词： degradation partially stabilized zirconia applied stress

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A study of ion exchange selectivity coefficient by cyclic voltammetric measurement

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Chinese Journal of Chemistry 1991年第4期9卷 315-321页

作者： DONG,Shao-jun lian,guo-Hua Laboratory of Electroanalytical Chemistry,Changchun Institute of Applied Chemistry,Academia Sinica,Changchun 130022 Laboratory of Electroanalytical Chemistry Changchun Institute of Applied Chemistry Academia Sinica Changchun 130022

An equation to express ion exchange selectivity coefficient was derived and used for cal- culating that of PPY film with the results obtained by cyclic voltamrnetric *** film was synthesized by electrochemical method in aqueous solution using K_4Fc(CN)_6 as supporting electrolyte, and the anions were doped into the *** exchange behaviour of doped Fe(CN)_6^(3-/4-)in the PPY film with Cl^-,NO_3^- or F^- ions in solution has been studied,and the corresponding ion exchange selec- tivity coefficients were determined.

关键词： CN A study of ion exchange selectivity coefficient by cyclic voltammetric measurement

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P11 The Other Form of PBL： Small Group Discussion in Pharmacology Teaching

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中国药理通讯 2006年第2期23卷 20-21页

作者： lian-jun guo Rong Ma Fang Wang Jian-guo Chen Department of Pharmacology Tongji Medical College Huazhong University of Science and Technology. Wuhan 430030 China

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Evaluation of neointimal coverage in patients with coronary artery aneurysm formation after drug-eluting stent implantation by optical coherence tomography

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Chinese Medical Journal 2013年第11期126卷 2092-2097页

作者： TIAN Feng CHEN Yun-dai CHEN lian SUN Zhi-jun guo jun JIN Qin-hua LIU Chang-N WANG Jin-da LIU Hong-bin Department of Cardiology Chinese People's Liberation ArmyGeneral Hospital Beijing 100853 China

Background The vessel healing in patients with coronary artery aneurysms （CAA） that form after drug-eluting stent （DES） implantation is not clear. This study aims to assess the vessel healing in patients with CAA formation after DES implanation. Methods From june 2008 to August 2011, follow-up coronary angiography was conducted on 1160 patients who underwent percutaneous coronary intervention （PCI）. The average period of follow-up was about （18.95±13.05） months. A total of 175 patients who underwent DES implantation into de novo lesions and who underwent coronary angiography and optical coherence tomography （OCT） examination during follow-up were identified. Patients were divided into the CAA group （n=31） and non-CAA group （n=144） based on the results of the coronary angiography. The cardiac events including angina and acute myocardial infarction were noted; in addition, the neointimal thickness and the frequency of strut malapposition and strut uncoverage were also noted. Results A greater proportion of incomplete neointimal coverage （17.17% vs. 1.90%, P 〈0.001） and strut malapposition （18.20% vs. 1.38%, P 〈0.001） were observed in the CAA group. The neointimal thickness in the CAA group was significantly thinner than that in the non-CAA group （（146.6±94.8） μm vs. （192.5＋97.1）μm, P 〈0.001）, as detected via OCT. Patients with CAA formation had a higher frequency of cardiac events including angina pectoris （25.81% vs. 6.25%, P=0.001） and acute myocardial infarction （9.68% vs. 0.13%, P=0.002） and thrombosis （16.13% vs. 0.69%, P 〈0.001）. The longitudinal length of the CAA in the cardiac event group was significantly longer than in the no cardiac event group （（20.0±9.07） mm vs. （12.05±5.38） ram, P=0.005）. Conclusion CAA formation after DES implantation is frequently associated with cardiac events as a result of stent malapposition and incomplete neointimal coverage.

关键词： optical coherence tomography coronary artery aneurysms drug-eluting stent neointimal coverage

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The Other Form of PBL:Small Group Discussion in Pharmacology Teaching

The Other Form of PBL:Small Group Discussion in Pharmacology...

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Satellite Meeting on Pharmacological Teaching & The 15th World Congress of Pharmacology

作者： lian-jun guo Rong Ma Fang Wang and Jian-guo Chen Department of Pharmacology Tongji Medical College Huazhong University of Science and Technology. Wuhan 430030 China

＜正＞Problem-based learning （ PBL） is now an established method in undergraduate medical education that aims to develop reasoning skills based on clinical problems. PBL is an

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EBT-OP水溶液作为络合滴定指示剂

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理化检验（化学分册） 2001年第1期37卷 40-40,42页

作者：连国军曹建明温州医学院分析中心温州325027

近十几年来，表面活性剂在分析化学中的应用已较为广泛，其中在光度法中应用较多。应用表面活性剂改善金属指示剂的性能也有报道[1]。络黑T(EBT)是络合滴定中较为常用的指示剂之一，改善其指示性能具有普遍的实用意义。

关键词：络合滴定指示剂络黑T 聚乙二醇辛基苯基醚

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Regulation of graphdiyne-based nanozymes with enhanced oxidaselike activity by cobalt and nitrogen codoping

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Nano Research 2025年第1期18卷 21-29页

作者： Jiali Liu Xiaoli Wang Yongfu lian Xue Wang Xiuxiu Wang Xingfa Gao Baoyun Sun Xihong guo CAS Key Laboratory for Biomedical Effects of Nanomaterial&Nanosafety Institute of High Energy PhysicsChinese Academy of ScienceBeijing 100049China Key Laboratory of Functional Inorganic Material Chemistry Ministry of EducationSchool of Chemistry and Materials ScienceHeilongjiang UniversityHarbin 150080China Laboratory of Theoretical and Computational Nanoscience National Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

The development of nanozymes with excellent intrinsic oxidase-like activity and specificity has received increasing ***(GDY)could be a promising choice for designing nanozymes with enhanced oxidase(OXD)-like activity due to its unique structure and ***,Co-N-GDY with high OXD activity but no peroxidase(POD)activity was synthesized by codoping of cobalt(Co)and nitrogen(N)into GDY and compared with other GDY-based nanozymes(including GDY,Co-GDY,and N-GDY).Upon analyzing the doping effect of Co and N on the OXD-like and POD-like activities,we found that the combination of Co and N in GDY played a significant role in enhancing the OXD-like activity,and even reversed the POD-like activity of N-GDY to OXD-like activity of *** electrochemical experiment and the theoretical calculations provided an explanation for the mechanism and showed that the activity was closely linked to the reduction ability of O_(2) or H_(2)O_(2) on the nanozyme substrates,which was determined by the ratedetermining step of the catalytic reaction.

关键词： nanozymes oxidase-like activity graphdiyne heteroatom doping regulation

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