简介：Theintrinsicgrowthabilityofalltheneuronsdeclinesduringdevelopmentalthoughsomemaygrowbetterthanothers.Numerousintracellularsignalingproteinsandtranscriptionfactorshavebeenshowntoregulatetheintrinsicgrowthcapacityinmatureneurons.Amongthem,PI3kinase/Aktpathwayisimportantforcontrollingaxonelongation.Asanegativeregulatorofthispathway,thetumorsuppressorphosphataseandtensinhomolog(PTEN)appearscriticaltocontroltheregenerativeabilityofyoungandadultneurons.ThisreviewwillfocusonrecentresearchprogressinaxonregenerationandneuralrepairbyPTENinhibitionandtherapeuticpotentialofblockingthisphosphataseforneurologicaldisorders.InhibitionofPTENbydeletioninconditionalknockoutmice,knockdownbyshort-hairpinRNA,orblockadebypharmacologicalapproaches,includingadministrationofselectivePTENantagonistpeptides,stimulatesvariousdegreesofaxonregrowthinjuvenileoradultrodentswithcentralnervoussysteminjuries.Importantly,post-injuryPTENsuppressioncouldenhanceaxonalgrowthandfunctionalrecoveryinadultcentralnervoussystemafterinjury.

简介：Apoptosisisprimarilyexecutedbyactivecaspases,whicharederivedfromtheinactiveprocaspasezymogensthroughproteolyticcleavage.Wedeterminedthecrystalstructuresofacaspasezymogen,procaspase-7,andanactivecaspase-7withoutanyboundinhibitors.Comparedtotheinhibitor-boundcaspase-7,procaspase-7zymogenexhibitssignificantstructuraldifferencessurroundingthecatalyticcleft,whichprecludestheformationofaproductiveconformation.Proteolyticcleavageinbetweenthelargeandsmallsubunitsallowsrearrangementofessentialloopsintheactivesite,primingactivecaspase-7forinhibitor/substratebinding.Strikingly,bindingbyinhibitorscausesa180-degree-flippingoftheN-terminusinthesmallsubunit,whichinteractswithandstabilizesthecatalyticcleft.Theseanalysesrevealthestructuralmechanismsofcaspaseactivationanddemonstratethattheinhibitor/substratebindingisaprocessof

简介：

简介：ToexplorethemechanismoftheinhibitionofHIV-1byMycoplasmafermerttans,culturesupernatantsandthallodicproteinsfromM.fermerttansPG18werepreparedandtheproteincomponentsofthesupernatantswerepurifiedwithhighperformanceliquidchromatography(HPLC).Theinhibitoryactivitiestoreversetranscriptase(RT)andthenucleaseactivitiesweredetected;theinfluenceofM.fermerttansonIL-10secretionbybothnormalandH1V-1infectedhumanPBMCweredetermined,andtheinhibitoryeffectofrhIL-10onH1V-1replicationwasdetectedwithEI,ISAmethod.Theresultsshowedthatthepurifiedproteinswithamolecularweightof67-100kDaor10-25kDashoweda36%or34%inhibitoryac-tivitytoRTandpartialnucleaseactivity.ThethallodicproteincouldinducebothnormalandH1V-1infectedPBMCtosecretIL-10remarkably,andtothelatter,thiseffectwasmoreapparent.WhilerhIL-10couldinhibitreplicationofH1V-1inPB-MCinvitroinadose-dependantmanner.ItconcludesthattheinhibitoryeffectoftheM.fermentansPG18culturesupernatantsonRTandthepromotingeffectofPG18thallodicproteinonIL-10secretioninPBMCexplainthemechanismsofinhibitiontoHIV-1byM.fermentansPG18.

简介：Objective:Toexploretheantitumormechanismsofbifidobacteriaadolescenceinvivo.Methods:Thecontentofextracellularsignalregulatedproteins(ERK)1/2,C-JunN-terminalkinase(JNK),p38,c-fosandc-juninnudemousetransplantedlargebowelcarcinomawasdetectedbyusinglaserconfocalmicroscopy.TheexpressionofNF-kBwasdeterminedbyimmunohistochemistry.Results:Afterthenudemousetransplantedtumorwastreatedwithbifidobacteria,theaveragefluorescentstrengthofERK1/2,JNK,c-fosandc-junwassignificantlylowerthanthatintumorcontrolgroup(P<0.01).Theaveragefluorescentstrengthofp38wasnotobviousdifferenceinthetwogroups(P>0.05).ThepositivecelldensityofNF-kBinlargebowelcarcinomatransplantationtumorsinBifidobacteriuminjectiongroupwasmarkedlylowerthanthatintumorgroup(P<0.01).Conclusion:bifidobacteriaadolescencecouldmarkedlydecreasetheactivityofERK1/2andJNK,theexpressionc-fosandc-jun,andtheactivityofNF-kB.

简介：AbstractAnti-influenza drugs are one of the most critical pathways for control of influenza virus infection. Drugs that have been developed or are developing may function via different mechanisms, and so far, inhibitors of influenza virus polymerase are among the most promising types of drugs. Favipiravir and Baloxavir, also named T-705 and Xofluza respectively, have been approved for influenza treatment in Japan and the United States. Favipiravir effectively and selectively inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses while Baloxavir specifically targets the cap-dependent endonuclease PA of influenza viruses. These two drugs have been suggested as the first candidate drugs for influenza infection treatment, especially for strains resistant to other anti-influenza drugs. This review will focus on the pharmaceutical mechanisms and anti-influenza activity of these two drugs.

简介：像成纤维细胞的synoviocytes(FLS)在风湿性关节炎(RA)贡献synovial增生。Smoothened(Smo)是发信号的声音的刺猬(嘘)的一个关键部件并且贡献肿瘤房间增长。这研究的目的是在RAsynoviocyte增长调查Smo的角色。FLS从RAsynovium被孤立。发信号的嘘用一个Smo对手(GDC-0449)和在FLS指向Smo基因的小介入RNA(siRNA)被学习。房间增长被使用kit-8试金和房间周期分发确定，apoptosis被流动cytometry评估。房间周期相关的基因和蛋白质被即时PCR和西方的污点检测。与GDC-0449或Smo-siRNA对待的FLS与控制相比显示出显著地减少的增长(P<；0.05)。有GDC-0449的孵化或有Smo-siRNA的transfection与控制相比导致了G1阶段房间的重要增加(P<；0.05)。房间周期拘捕被cyclinD1和E1mRNA表示的重要增加验证，在在Smo-siRNAtransfected房间的cyclin依赖的kinasep21mRNA表示的减少(P<；0.05)。cyclinD1的蛋白质表示也是在Smo基因以后的downregulated击倒(P<；0.05)。结果建议发信号的嘘以一种Smo依赖的方式在RA-FLSs增长起一个重要作用并且可以贡献synovial增生。指向嘘发信号可以帮助与RA在病人控制联合损坏。

简介：

简介：Anewthermokineticreducedextentmethodforstudyingofthereversiblecompetitiveinhibitionofsinglesubstrateenzyme-catalyzedreactionswasproposedinthispaper.Thereactionthatarginase-catalyzedhydrolysisofL-argininetoL-ornithineandureaandtheinhibitionofthisreactionbytheproduct,L-ornithine,andexogenousL-lysinewerestudiedat37℃in40mmol·L^-1sodiumbarbiturate-HC1buffersolution(pH=9.4).MichealisconstantKmforarginineandmaximumvelocityVmofthereactionweredeterminedtobe5.14mmol·L^-1and1.13×10^-2mmol·L^+1·s^-1,respectively.TheproductinhibitionconstantKpandinhibitoryconstantK1ofL-lysineweredeterminedtobe1.18and5.6mmol.L-l,respectively.Alltheresultshavebetterrepeatabilityandself-consistencyandareinagreementwithliteraturevalues.Thisnewmethodusingmoredirectthermalinformationfromtheprocesswouldgivemorereliablekineticinformationthanthetraditionalinitialratemethod.

简介：

简介：

简介：γ-Aminobutyricacid(GABA)isamajorneurotransmitterandplaysimportantrolesinboththedevelopingandmaturecentralnervoussystem(CNS).OnewaythatGABAcanactisbybindingtofast,ionotropicGABAAreceptorsinneurons.ThebindingofGABAtoGABAAreceptorscausesaconformationalchangethatopensionchannels,

简介：披风房间淋巴瘤(MCL)是B房间non-Hodgkin淋巴瘤的好攻击的histotype。疾病不知道了痊愈，它为新奇治疗学的代理人推动迫切需要。(CRM1)Chromosomal区域维护1可以在人的瘤形成起一个作用并且用作癌症治疗的一个新奇目标。这研究总结MCL致病并且在贡献MCL致病的几条重要发信号小径的规定决定CRM1的参与，包括房间周期前进，DNA损坏反应，phosphoinositidekinase-3，原子factor-B激活，和chromosomal稳定性的小径。现出症状之前的潜的研究也被介绍在vitro并且在vivo在MCL在MCL房间线和主要MCL房间把CRM1地位与正常B房间，以及CRM1抑制的治疗学的效率作比较，它使这些代理人成为新奇MCL治疗的潜在的目标。

简介：观察联系adeno的病毒的向量(AAV)的生长抑制效果的目的调停了在老鼠和它的机制的植入的乳癌上的angiostatin(ANG)基因。方法基因转移技术被用来把AAV-ANG转移到肿瘤。生长曲线被拉观察在老鼠，和免疫植入的乳癌的生长组织化学的方法被用来在在老鼠植入的乳癌的microvesel密度(MVD)上检测angiostatin的效果。结果Angiostatin禁止了在老鼠植入并且减少的乳癌的生长肿瘤的微容器密度。angiostatintransgene的结论表示能压制通过微容器的生长的抑制在老鼠植入的乳癌的生长，angiostatin基因转移技术可能对乳癌是有效的surggesting。

简介：ObjectivesToobservetheeffectsoftelmisartanandrosiglitazoneandexplorethemechanismonearlyatherogenesisinmaleratswithtype2diabetesmellitus.MethodsFortymaleSDratswererandomlyandequallydividedintofourgroups:controlgroup,type2diabetesmellitusgroup,telmisartangroupandrosiglitazonegroup.HighlipidandhighglucosewereusedforinducingDMinSDrats.Theratswereraisedforsixteenweeks.TC,TG,LDL-CandBG,PGIweremeasured.Theaortaewerecollectedforhistopathlogicalandimmunohistochemicalstudies.Immunohisto-chemistrywasusedtoanalyzetheexpressionofPPAR-γ,VCAM-1andICAM-1inthearterialvesselwall.ResultsComparedwiththecontrolgroup,thelevelofTC,TG,LDL-C,andBGinbloodwereincreasedsignificantly(P<0.01)intype2Diabeticgroup.ThetelmisartanandrosiglitazonetreatmentdecreasedbloodTC,TG,LDL-CandBG.TheexpressionofPPAR-γintype2diabeticgroup,telmisartanandrosiglitazonegroupshadsignificantdifferencescomparedwiththecontrolgroup,buttherewasn'tanysignificantdifferences(P>0.05)amongthosethreegroups.ExpressionofVCAM-1,ICAM-1andthemonocytesinfilitratingintotheintimaoftheaortastelmisartanandrosiglitazoregroupwassignificantlylowerthanthoseindiabeticgroup(P<0.01).Theendothelialdamageoftheaortaeintehnisartanandrosiglitazonegroupwaslessseverethanthatindiabetesmellitusgroup.ConclusionTelmisartanandrosiglitazonecanpreventearlyatherogenesisthroughalleviatingthedamagetothearterialwallbyincreasingtheactivationofPPAR-γandinhibitingtheVCAM-1,ICAM-1expressionandthemonocytesinfilitratingintothearterialwall.

简介：Gapinducedpie-pulseinhibition(Gap-PPI)ofacousticstartlereflexhasbeenusedasameasurementoftinnitusinanimalmodels.However,whetherthistestissensitivetodetecttinnitusinhumansisstillunclear.Basedonthetestingprocedureusedinanimalstudies,ahumansubjecttestingmethodwasformulatedandconductedtoinvestigateifasimilarresultcouldbefoundintinnituspatients.Audiologicandtinnitusassessmentsandacousticstartlereflexmeasurementswereperformedonseventinnitussubjectsandnineagematchedsubjectswithouttinnitus.TherewasnosignificantdifferencefoundbetweenthecontrolandtinnitusgroupontheGap-PPlacrossthefrequenciesevaluated.Theamplitudeofthestartleresponseinthetinnitusgroupwithnormalhearingthresholdswassignificantlyhigherthanthecontrolgroupandthosewithtinnitusandhearingloss.Thispreliminaryresultsuggeststhathyperexcitabilityinthecentralauditorysystemmaybeinvolvedintinnitus.Therewasnocorrelationbetweenhearingthresholdsandtheincreasedamplitudeofstartleresponse.

简介：

简介：AIMToinvestigatetheeffectofgingeroloncolonicmotilityandtheactionofL-typecalciumchannelcurrentsinthisprocess.METHODS：ThedistalcolonwascutalongthemesentericborderandcleanedwithCa^2＋-freephysiologicalsalinesolution.MusclestripswereremovedandplacedinCa^2＋-freephysiologicalsalinesolution,whichwasoxygenatedcontinuously.Longitudinalsmoothmusclesampleswerepreparedbycuttingalongthemusclestripsandwerethenplacedinachamber.Mechanicalcontractileactivitiesofisolatedcolonicsegmentsinratswererecordedbya4-channelphysiograph.Colonsmoothmusclecellsweredissociatedbyenzymaticdigestion.L-typecalciumcurrentswererecordedusingtheconventionalwhole-cellpatch-clamptechnique.RESULTS：Gingerolinhibitedthespontaneouscontractionofcoloniclongitudinalsmoothmuscleinadose-dependentmannerwithinhibitionpercentagesof13.3%±4.1%,43.4%±3.9%,78.2%±3.6%and80.5%±4.5%at25μmol/L,50μmol/L,75μmol/Land100μmol/L,respectively（P〈0.01）.Nifedipine,anL-typecalciumchannelblocker,diminishedtheinhibitionofcolonicmotilitybygingerol.GingerolinhibitedL-typecalciumchannelcurrentsincoloniclongitudinalmyocytesofrats.Ata75μmol/Lconcentrationofgingerol,thepercentageofgingerolinducedinhibitionwasdiminishedbynifedipinefrom77.1%±4.2%to42.6%±3.6%（P〈0.01）.GingerolsuppressedIBainadose-dependentmanner,andtheinhibitionrateswere22.7%±2.38%,35.77%±3.14%,49.78%±3.48%and53.78%±4.16%ofcontrolat0mV,respectively,atconcentrationsof25μmol/L,50μmol/L,75μmol/Land100μmol/L（P〈0.01）.Thesteady-stateactivationcurvewasshiftedtotherightbytreatmentwithgingerol.Thevalueofhalfactivationwas-14.23±1.12mVinthecontrolgroupand-10.56±1.04mVinthe75μmol/Lgroup（P〈0.05）withslopefactors,Ks,of7.16±0.84and7.02±0.93（P〈0.05）inthecontroland75μmol/Lgroups,respectively.However,thesteady-st

简介：Objective:Totesttheeffectsofsalidrosideonformationandgrowthofgliomatogetherwithtumormicroenvironment.Methods:SalidrosideextractedfromRhodiolaroseawaspurifiedandtreatedonhumangliomacellsU251attheconcentrationof20μg/mL.3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazoliumbromide(MTT)assayforcytotoxicityandflowcytometry(FCM)forcellcycleanalysiswereperformed.Thenforinvivostudy,xenotransplantationtumormodelinnudemicewasgeneratedandtreatedwithsalidrosideattheconcentrationof50mg/kg.dfortotally20d.Bodyweightandtumorsizeweredetectedevery2dafterthetreatment.Thelevelsof8-isoprostane,superoxidedismutase(SOD)andmalondialdehyde(MDA),specialmarkersforoxidativestress,weredetectedwhileimmunofluoresencestainingwasperformedforastrocytedetection.Results:Forinvitrostudy,salidrosidecoulddecreasetheviabilityofhumangliomacellsU251andthegrowthofU251cellsatG0/G1checkpointduringthecellcycle.Forinvivostudy,salidrosidecouldalsoinhibitthegrowthofhumangliomatissueinnudemice.Thebodyweightofthesenudemicetreatedwithsalidrosidedidnotdecreaseasquicklyascontrolgroup.Inthetumorxenotransplantationnudemicemodel,micewerefoundofinhibitionofoxidativestressbydetectionofbiomarkers.Furthermore,overgrowthofastrocytesduetothestimulationofoxidativestressinthecortexofbrainwasinhibitedafterthetreatmentofsalidroside.Conclusions:Salidrosidecouldinhibittheformationandgrowthofgliomabothinvivoandinvitroandimprovethetumormicroenvironmentviainhibitionofoxidativestressandastrocytes.

简介：organophosphorus杀虫剂(OP)的主要毒性是neurotoxicity，它被acetylcholinesterase的抑制引起。OP也在抗体生产，IL-2生产，T房间增长，CD5房间的减少，和CD26房间和自身抗体的增加上包括效果影响有免疫力的回答。然而，有很少报纸，调查漂亮房间的cytolytic活动的导致OP的抑制的机制。这研究考察生来的杀手(NK)的活动的导致OP的抑制的新机制，激活lymphokine的杀手(LAK)和细胞毒素的T淋巴细胞(CTL)。NK，LAK和CTL由二主要机制在肿瘤或感染病毒的目标房间导致房间死亡。第一机制是由exocytosis包含perforin，granzymes，和granulysin杀死目标房间的cytolytic小粒的直接版本，它被称为小粒exocytosis小径。第二机制被船边交货调停!igand(Fas-L)/Fas小径。迄今为止，OP由至少下列三机制禁止NK，LAK和CTL活动，这被报导了：1)OP由禁止granzymes的活动，并且由减少损害NK，LAK和CTL房间的小粒exocytosis小径perforin，granzymeA和granulysin的细胞内部的水平，被导致NK房间并且由禁止perforin的mRNA的抄本的degranulation调停，granzymeA和granulysin；2)OP在NK房间的小粒exocytosis小径不在哪个工作损害NK，LAK和CTL房间的FasL/Fas小径，由使用perforin大美人老鼠调查了并且仅仅FasL/Fas小径仍然保持功能；3)OP导致有免疫力的房间的apoptosis。