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Developing glutamate receptor Aptamers as drug candidates

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Developing glutamate receptor Aptamers as drug candidates

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Li Niu department of Chemistry,and the Center for Neuroscience Research,State university of {2. york(SUny)at Albany, Albany,{2. york,12.2.,usa

＜正＞In finding a new treatment for a number of neurological disorders and diseases,such as epilepsy,stroke and amyotrophic lateral sclerosis（ALS）,one of the potential therapeutic strategies is to develop inhibitors for theα-amino- 3-hydroxy-5-methyl-4-isoxazole propionic acid（AMPA） receptors,a receptor subtype in the glutamate ion channel receptor *** is because excessive activity of AMPA receptors leads to abnormal calcium influx into neurons, which in turn leads to cell *** developing AMPA receptor inhibitors that are both potent and water soluble,we have used systematic evolution of ligands by exponential enrichment（SELEX） and have successfully identified three classes of aptamers with nanomolar affinity against AMPA *** the class of competitive aptamers,we found one aptamer with an IC50 value of 30 nM,rivaling any other exiting AMPA receptor ***,this aptamer is broadly active in all AMPA receptor subunits,but has no unwanted activity in either kainate or NMDA receptors,the two other glutamate receptor *** have also identified two other classes of noncompetitive aptamers that are selective to different conformations of GluR2.a key AMPA receptor subunit that mediates glutamateinduced cell *** class uniquely inhibits the open-channel conformation whereas the other inhibits the closedchannel conformation of *** latter in fact is single-subunit selective aptamer designed to target GluR2.*** turn these aptamers into potentially useful drugs,we have now successfully developed a class of chemically modified aptamers that are highly resistant to ribonucleases so that these aptamers can be tested in *** results demonstrate the possibility of developing RNA aptamers against AMPA receptor channels with nanomolar affinity,excellent water solubility and superior selectivity to AMPA receptors and even to a single AMPA receptor *** aptamers are therefore potential templates for design of better in

关键词： glutamate ion channels RNA aptamers SELEX

PROBABILISTIC HEAVY ION JET RECONSTRUCTION FOR RHIC AND LHC

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PROBABILISTIC HEAVY ION JET RECONSTRUCTION FOR RHIC AND LHC

The 19th International Conference on Ultra-Relativistic Nucleus-Nucleus Collisions

作者： Y. S. Lai department of Physics Columbia university 538 West 12.th Street {2. york ny 1002.-6601 usa

＜正＞Currently, hard scattering processes in heavy ion collisions are studied via single high-pT hadron production and di- or tri-hadron correlations. Both at RHIC and in intermediate pT＜ 50 GeV/c at the LHC, the high multiplicity soft background of heavy ion collisions prevents the use of traditional jet reconstruction algorithms . Hard probes at inter-mediate energies could provide an especially rich insight into the properties of the dense matter, and a full jet reconstruction would provide more

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Adenosine stimulation of basolateral 50 pS potassium channels in the thick ascending limb of the rat kidney:Involvement of protein kinase A and phospholipase A2

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Adenosine stimulation of basolateral 50 pS potassium channel...

中国生理学会第2.届全国会员代表大会暨生理学学术大会

作者： Hong-Yu SUI~1,Li-Jun WANG~1,Shu-Min KONG~1,Wen-Nan LI~1,Peng WU~1,Ming-Xiao WANG~1,Yu-Jie LIU~1,Li GU~1,Li-Li FAN~1,Wen-Hui WANG~2.Rui-Min GU~(1,*) 1 department of Pharmacology,Harbin Medical university,Harbin 150081,China 2.department of Pharmacology,new york Medical college,Valhalla,new york,usa

Adenosine is the important local active substance in the body and it plays an important role in regulating function of *** the thick ascending limb(TAL),it can inhibit the transportation of *** a 50 pS K channel is the major type of potassium channel in the basolateral membrane of the thick ascending limb,thus we performed patch-clamp technique in cell-attached patches and Western blot technique to study the effect of adenosine on the basolateral 50 pS K channels in the thick ascending limb of the rat ***(10μmol/L) increased the activity of basolateral 50 pS K channels and this effect was mimicked by cyclohexyladenosine(CHA),which is the analog of *** stimulatory effect of CHA is not mediated by protein kinase C-dependent mechanisms,because blocking protein kinase C with Calphostin C did not abolish the stimulatory effect of CHA on the 50 pS K ***,blocking protein kinase A with H8 and blocking phospholipase A with AACOCF abolished the effect of CHA,this suggests that protein kinase A and phospholipase A are responsible for mediating the effect of CHA on the 50 pS K *** addition,CHA(10μmol/L) increased the express of phosphatase-protein kinase A(p-PKA) and decreased the express of phosphatase-phospholipase A(p-PLA).The db-cAMP(cAMP analog) and AACOCF3(antagonist of PLA) increased the activity of basolateral 50 pS K *** indicates that adenosine increased the activity of basolateral 50 pS K channels by stimulating PKA-dependent mechanisms and inhibiting PLA-dependent *** application CHA after blocking the PLA with AACOCF,the express of p-PKA was still *** application CHA after blocking the PKA with H8 did not change the express of *** studies show that stimulation of basolateral 50 pS K channels by CHA is mediated by stimulating PKA,which in turn inhibits PLA in the thick ascending limb of the rat kidney.

关键词： K channel adenosine protein kinase A phospholipase A2 thick ascending limb

Protein tyrosine kinase and PI3-K participate in the inhibitory effect of insulin-like growth factor I on basolateral 10 pS Chloride channels in the thick ascending limb of the rat kidney

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Protein tyrosine kinase and PI3-K participate in the inhibit...

中国生理学会第2.届全国会员代表大会暨生理学学术大会

作者： Li-Jun WANG~1,Shu-Min KONG~1,Wen-Nan LI~1,Hong-Yu SUI~1,Peng WU~1,Ming-Xiao WANG~1,Yu-Jie LIU~1, Li-Li FAN~1,Li GU~1,Wen-Hui WANG~2.Rui-Min GU~(1,*) 1 department of Pharmacology,Harbin Medical university,Harbin 150081,China 2.department of Pharmacology,new york Medical college,Valhalla,new york,usa

＜正＞Insulin-like growth factorⅠ（IGF-I） plays an important role in accelerating protein and carbohydrate metabolism, and affects cell proliferation,differentiation and inhibiting apoptosis in a long *** to IGF-I and IGF-I receptor are distributed in the basolateral and apical membrane of the thick ascending limb,IGF-I could influence sodium chloride （NaCl） transport in this nephron *** a 10 pS Cl channel is the major type of chloride channel in the basolateral membrane of this nephron segment,thus we performed patch-clamp technique in cell-attached patches to study the effect of IGF-I on the basolateral 10 pS Cl channels in the thick ascending limb of the rat *** of IGF-I inhibited the basolateral 10 pS Cl channels,significantly decreased channel activity（a product of channel number and open probability）.The inhibitory effect of IGF-I is not mediated by protein tyrosine phosphatase or phospholipase C-dependent mechanisms,because blocking protein tyrosine phosphatase with phenylarsine oxide or inhibition of phospholipase C with U7312. did not abolish the inhibitory effect of IGF-I on the 10 pS Cl ***,inhibition of protein tyrosine kinase with Herbinmycin A or Genistein or repression of phosphatidylinositol 3-kinase（PI3-K） with Wortmannin abolished the effect of IGF-I,this suggests that protein tyrosine kinase and PI3-K are responsible for mediating the effect of IGF-I on the 10 pS Cl *** studies show that inhibition of basolateral 10 pS Cl channels by IGF-I is mediated by stimulating protein tyrosine kinase,which in turn stimulates PI3-K in the thick ascending limb of the rat kidney.

关键词： C1 transport insulin-like growth factor I protein tyrosine kinase phosphatidylinositol 3-kinase thick ascending limb

Urinary Creatinine-Skeletal Muscle Mass Method:A Prediction Equation Based on Computerized Axial Tomography

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Biomedical and Environmental Sciences 1996年第2期9卷 185-190页

作者： ZI-MIAN WANG YUN-GAO SUN AND STEVEN B. HEYMSFIELD (department of Medicine, Obesity Research Center, St. Luke’s-Roosevelt Hospital, Columbia university {2. of Physicians and Surgeons,Amsterdam Ave. 14C new york, N. Y., usa)(Obesity Research Center, We department of Medicine St. Luke's-Roosevelt Hospital Columbia University College of Physicians and Surgeons New York N.Y. USA.

A classic body composition method is estimation of total body skeletal muscle mass (SM, kg) from 2. h urinary creatinine excretion (Cr, g). Two types of prediction equations were suggested: one assumes a constant SM/Cr ratio; and the other assumes a highly variable SM/Cr ratio. We explored these two extreme possibilities by measuring SM with whole-body computerized axial tomography and collecting Cr during meat-free dietary conditions in 12.healthy young men. Prediction equations were developed in the men that fit these two equation types, SM = 2..8×Cr (SD and CV of SM/Cr ratio, 1.3 kg and 6.0%,respectively) and SM = 18.9 × Cr + 4.1 (r = 0.92. p = 2.55 × 10-5, and SEE = 1.9 kg). The validity of each model is reviewed. This is the first investigation of Cr-SM method using modern techniques for quantifying total body SM mass

关键词： Mass Cr body SM Urinary Creatinine-Skeletal Muscle Mass Method

Protective effect of liver ischemic preconditioning on rat hepatocytes

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Science China(Life Sciences) 2009年第9期52卷 836-840页

作者： FU JianZhu1,2.WANG Yu1,ZHANG LiJun2.& YU ZeLi2.1 department of General Surgery,Beijing Friendship Hospital,Capital Medical university,Beijing 100050,China 2.department of General Surgery,Beijing Tongren Hospital,Capital Medical university,Beijing 100730,China department of General Surgery Beijing Friendship Hospital Capital Medical University Beijing China department of General Surgery Beijing Tongren Hospital Capital Medical University Beijing China

Ischemic preconditioning (IPC) protects liver graft function following ischemia in liver transplantation and liver resection. The aim of this study was to assess the advantages and any potential disadvantages of liver IPC prior to isolation for rat hepatocytes during isolation and cryopreservation. After isolating and thawing the cryopreserved hepatocytes after 14 and 2. d,cell viability,efficiency,and lactate dehydrogenase (LDH) levels in preserve solution were examined for every group. Groups treated with IPC had better cell viability determination,assessment of plating efficiency and lactate dehydrogenase (LDH) assay than Group without IPC,suggesting that IPC prior to isolation may have a significant protective effect on hepatocytes subjected to isolation and short period cryopreservation.

关键词： liver ischemic preconditioning hepatocytes cryopreservation

Hydrogen Peroxide Stimulates the Ca2.-activated Big-conductance K Channels(BK) through cGMP Signaling Pathway in Cultured Human Endothelial Cells

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Hydrogen Peroxide Stimulates the Ca2+-activated Big-conducta...

2.08心血管药理学术研讨会

作者： De-Li Dong~1 Peng Yue~1 Bao-Feng Yang~1 Wen-Hui Wang~2.1 department of Pharmacology,Harbin Medical university,Harbin 150086,China 2.department of Pharmacology new york Medical college,Valhalla,ny 10595

We used the whole cell patch-clamp technique to examine the effect of hydrogen peroxide(HO) on the Ca-activated BK channels in human endothelial *** confirmed the previous finding that a 2.0 pS BK channel activity was...

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CHARACTERISTICS OF LIGNIN REACTIONS IN SODA COOKING OF WHEAT STRAW PART 1 REACTION OF UNCONDENSED LIGNIN

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天津科技大学学报 2004年第A2期19卷 115-118页

作者： HuaminZhai YuanzongLai collegeofChemicalEngineering NanjingForestryUniversityNanjingChina210037 PaperScienceandEngmeeringFaculty stateUniversityofNewYorkCollegeofEnvironmentalScienceandForestrySyracuseNY13210USA

Characteristics of uncondensed lignin reactions in soda cooking of wheat straw were studied. Mild and intense cooking conditions were used to get the pulp sample in which lignin was dissolved physically and the pulp sample in which lignin was dissolved chemically respectively. The pulp samples were analyzed by phenolic group determination, alkaline nitrobenzene oxidation and ozonation method. The results indicated that around 90% of lignin in wheat straw is alkali-soluble at the mild conditions, is basically dissolved physically without chemical change. The phenolic group content was not changed greatly, the nitrobenzene oxidation yield only changed slightly during the mild cooking. The phenolic group content was increased obviously and uncondensed lignin content was decreased very much when the intense cooking conditions were applied and the delignification was over 90%. The lignin structure was changed greatly during this period.

关键词：小麦秸杆木质素反应苏打碱性烹饪不凝结木质素纸浆臭氧分析

Cucurbitacin E inhibits the proliferation of hepatoma cells in vitro and in vivo through induction of G2.M phase arrest

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Cucurbitacin E inhibits the proliferation of hepatoma cells ...

两岸三地药理学与临床药理学术会议

作者： LI Yan-chun~1 MA En-long~1 DENG Yi-hui~2.JING Yong-kui~3 (1. department of Pharmacology, Shenyang Pharmaceutical university, Shenyang 110016, China 2. department of Pharmaceutics, Shenyang Pharmaceutical university, Shenyang 110016, China 3. department of Medicine, Mount Sinai School of Medicine, new york, usa)

Objective Cucurbitacins are the highly oxygenated tetracyclic triterpenes,which are predominant- ly found in the Cucurbitaceae family but are also present in several other families of the plant kingdom.A number of compounds of this group have been investigated for their cytotoxic,hepatoprotective,anti-inflam- matory,cardiovascular and anti-diabetic *** China,the cucurbitacin preparation,which contains mostly cucurbitacin B and cucurbitacin E,has been clinically used for the treatment of the primary liver car- *** has been previously reported that cucurbitacin E could produce cytotoxicity against a variety of cancer cells,and various mechanisms were implicated in its cytotoxic *** present study is to investi- gate the effect of cucurbitacin E on hepatoma cells in vitro and in vivo and to study their potential mecha- nisms of *** The MTT assay was used to assess the viability of human HepG2.and BEL7402.hepatoma cells in vitro after treatment with different concentrations of cucurbitacin *** cell cycle distri- bution was determined by flowcytometric analysis after propidium iodide(PI)*** cell cycle-relat- ed proteins were detected using western blotting *** mouse hepatoma H2. model was built to evaluate the growth inhibitory effect of cucurbitacin E in vivo in *** Our studies found that cu- curbitacin E(10-300 nM)produced anti-proliferative effect on human HepG2.and BEL7402.hepatoma cells in vitro without *** to flowcytometric analysis,cucurbitacin E arrested the cell cycle at G2.M phase in both HepG2.and BEL7402.hepatoma cells after 2. h *** E induced the decrease in the level of CDK1 protein and the increase in the level of p2. protein,but had no effect on the levels of cyclin A,cyclin B1 and Cdc2.C *** in vivo anti-tumor experiment,cucurbitacin E had sig- nificant inhibitory effects on the growth of mouse H2. hepatoma *** Cucurbitacin E inh

关键词： cucurbitacin e hepatoma cells G2.M arrest