简介:ThechronicinfectionofhepatitisBvirus(HBV)iscloselyrelatedtotheoccurrenceanddevelopmentofhepatocellularcarcinoma(HCC).AccumulatedevidencehasshownthatHBVXprotein(HBxprotein)isamultifunctionalregulatorwithacrucialroleinhepatocarcinogenesis.However,informationonthemechanismbywhichHBVinducesHCCislacking.ThisreviewfocusesonthepathologicalfunctionsofHBxinHBV-inducedhepatocarcinogenesis.Asatransactivator,HBxcanmodulatenuclearfactorkappa-light-chain-enhancerofactivatedBcells(NF-κB)andtranscriptionfactorAP-2.Moreover,HBxcanaffectregulatorynon-codingRNAs(ncRNAs)includingmicroRNAsandlongncRNAs(lncRNAs),suchasmiRNA-205andhighlyupregulatedinlivercancer(HULC),respectively.HBxisalsoinvolvedinepigeneticmodification,includingmethylationandacetylation.HBxinteractswithvarioussignal-transductionpathways,suchasproteinkinaseB/Akt,Wnt/β-catenin,signaltransducerandactivatoroftranscription,andNF-κBpathways.Moreover,HBxaffectscellularfatebyshiftingthebalancetowardcellsurvival.HBxmayleadtothelossofapoptoticfunctionsordirectlycontributestooncogenesisbyachievingtransformingfunctions,whichinducehepatocarcinogenesis.Additionally,HBxcanmodulateapoptosisandimmuneresponsebydirectorindirectinteractionwithhostfactors.WeconcludethatHBxhastensthedevelopmentofhepatoma.
简介:AbstractBone morphogenetic protein belongs to transcription growth factor superfamily β; bone morphogenetic protein signal pathway regulates cell proliferation, differentiation, and apoptosis among different tissues. Cerebrovascular system supplies sufficient oxygen and blood into brain to maintain its normal function. The disorder of cerebrovascular system will result into serious cerebrovascular diseases, which is gradually becoming a major threat to human health in modern society. In recent decades, many studies have revealed the underlying biology and mechanism of bone morphogenetic protein signal pathway played in cerebrovascular system. This review will discuss the relationship between the two aspects, aiming to provide new perspective for non-invasive treatment and basic research of cerebrovascular diseases.
简介:Glyceraldehyde-3-phosphatedehydrogenase(GAPDH),initiallyidentifiedasaglycolyticenzymeandconsideredasahousekeepinggene,iswidelyusedasaninternalcontrolinexperimentsonproteins,mRNA,andDNA.However,emergingevidenceindicatesthatGAPDHisimplicatedindiversefunctionsindependentofitsroleinenergymetabolism;theexpressionstatusofGAPDHisalsoderegulatedinvariouscancercells.OneofthemostcommoneffectsofGAPDHisitsinconsistentroleinthedeterminationofcancercellfate.Furthermore,studieshavedescribedGAPDHasaregulatorofcelldeath;otherstudieshavesuggestedthatGAPDHparticipatesintumorprogressionandservesasanewtherapeutictarget.However,relatedregulatorymechanismsofitsnumerouscellularfunctionsandderegulatedexpressionlevelsremainunclear.GAPDHistightlyregulatedattranscriptionalandposttranscriptionallevels,whichareinvolvedintheregulationofdiverseGAPDHfunctions.Severalcancer-relatedfactors,suchasinsulin,hypoxiainduciblefactor-1(HIF-1),p53,nitricoxide(NO),andacetylatedhistone,notonlymodulateGAPDHgeneexpressionbutalsoaffectproteinfunctionsviacommonpathways.Moreover,posttranslationalmodifications(PTMs)occurringinGAPDHincancercellsresultinnewactivitiesunrelatedtotheoriginalglycolyticfunctionofGAPDH.Inthisreview,recentfindingsrelatedtoGAPDHtranscriptionalregulationandPTMsaresummarized.MechanismsandpathwaysinvolvedinGAPDHregulationanditsdifferentrolesincancercellsarealsodescribed.
简介:Numerouscellularfunctionsoccurinspatiallyandtemporallyconfinedregions.Recentstudieshaveshownthatmembrane-lessorganellesandcompartmentsinthecellareassembledvialiquid-liquidphaseseparation(LLPS).InvitroLLPSassaysusingrecombinantexpressedandpurifiedproteinsarenecessaryforustofurtherunderstandhowtheassemblyofphase-separatedcompartmentsisregulatedincells.However;uniformstandardsandprotocolsarelackingfortheseinvitrostudies.Here,wedescribeastep-by-stepprotocolcommonlyusedtoinvestigateinvitroLLPSusingpurifiedproteins.Thisprotocolincludesexpressionandpurificationofthestudiedproteins,inductionofLLPSofthepurifiedproteins,andstudiesofthebiophysicalpropertiesoftheliquiddropletsformedbyLLPS.TheseprotocolscanbeeasilyfollowedbyresearcherstoinvestigatetheLLPSbehaviorsofproteinsofinterest.
简介:Anewmethodwasdescribedforusingarecurrentneuralnetworkwithbiasunitstopredictcontactmapsinproteins.Themaininputstotheneuralnetworkincluderesiduespairwise,residueclassificationaccordingtohydrophobicity,polar,acidic,basicandsecondarystructureinformationandresidueseparationbetweentworesidues.Inourwork,adatasetwasusedwhichwascomposedof53globulinproteinsofknown3Dstructure.Anaveragepredictiveaccuracyof0.29wasobtained.Ourresultsdemonstratetheviabilityoftheapproachforpredictingcontactmaps.
简介:Theadenomatoidodontogenictumorischaracterizedbytheformationofduct-likestructuresandappearanceofeosinophilicmaterials.Eosinophilicmaterialsshowamorphousmassordropletsamongtheepithelialcells.Intheduct-likestructures,itshowsathinlayerofbasementmembranel...
简介:由使用DDRT-PCR和EST片断结扎,新奇老鼠胸腺复杂物联系了基因Rwddl被识别。读的框架编码了在N终点包含了一个RWD领域的243氨基酸残余的蛋白质。在胸腺的Rwddl表示在年老、氧化地强调的鼠标被减少。在thymocytes和thymic广泛地被表示被发现上皮的房间。Rwddl的表示水平能影响雄激素受体(AR)的transactivation活动在短暂地transfectedthymic上皮的房间。然而,没有直接相互作用能被荧光回声精力转移检测(烦恼)分析。在结论,Rwddl是胸腺复杂物可以间接地影响AR发信号的相关蛋白质小径。细胞与分子的免疫学。2008;5(4):279-285。
简介:BackgroundTheprognosticvalueofserumC-reactiveprotein(CRP)inpatientswithinfectiveendocarditis(IE)isnotwellelucidated.ThisstudyaimedtoevaluatetheusefulnessofCRPinpredictingtheoutcomeofIE.MethodsTwohundredninty-sixpatientsfrom2009to2012intheDepartmentofCardiologyatGuangdongGeneralHospitalwerescreenedanddividedintosurgicalandconventionaltreatmentgroups.CRP,whitebloodcell(WBC),erythrocytesedimentationrate(ESR)andotherclinicaldatawereobtainedwithfollow-upfor12months.ResultsTwohundredthirty-sixpatientswereassignedtoreceivesurgerytreatmentwhile60patientsreceivedconventionaltreatment.Inthesurgerygroup,thelevelofCRPinthedeathpatientswassignificantlyhigherthanthatinthesurvivalpatients(P<0.001).TheareaunderthecurveofROCwasabout0.749(SE0.064,P=0.005,95%CI,0.624-0.874)andthecut-offpointofCRPwas23.8mg/L.Inconventionalgroup,therewassignificantdifferencebetweendeathandsurvival(P<0.001).TheareaunderthecurveofROCwasabout0.701(SE0.095,P=0.032,95%CI,0.515-0.888)andthecut-offpointsofCRPwas65.6mg/L.TherewerenosignificantdifferencesinWBCandESRbetweensurgeryandconventionalgroups.ConclusionAmoreaggressivesurgicalinterventionresultsinabetteroutcomeoverconventionaltreatmentandCRPcouldbeservedasapredictivemarkerforadverseoutcomeinIEpatients.
简介:AIM:Tostudytheformationofintracellularglyceraldehyde-derivedadvancedglycationendproducts(Glycer-AGEs)inthepresenceofhighconcentrationsoffructose.METHODS:CellsofthehumanhepatocytecelllineHep3Bwereincubatedwithorwithoutfructoseforfivedays,andthecorrespondingcelllysateswereseparatedbytwo-dimensionalgradientsodiumdodecylsulfate-polyacrylamidegelelectrophoresis.Glycer-AGEsweredetectedwiththeanti-Glycer-AGEsantibody.Furthermore,theidentificationoftheproteinsthataremodifiedbyglyceraldehydeinthepresenceofhighconcentrationsoffructosewasconductedusingmatrixassistedlaserdesorption/ionizationtime-of-flightmassspectrometry(MALDI-TOF-MS).TheproteinandmRNAlevelsweredeterminedbyWesternblottingandrealtimereversetranscriptionPCR,respectively.RESULTS:Theresultsofthetwo-dimensionalgradientsodiumdodecylsulfate-polyacrylamidegelelectrophoresisindicatedagreateramountofGlycerAGEsinthesampleexposedtohighconcentrationsoffructosethaninthecontrol.ThedetectedGlycerAGEsshowedisoelectricpointsintherangeof8.0-9.0andmolecularweightsintherangeof60-80kDa.TheheterogeneousnuclearribonucleoproteinM(hnRNPM),whichplaysanimportantroleinregulatinggeneexpressionbyprocessingheterogeneousnuclearRNAstoformmaturemRNAs,wasidentifiedasamodifiedproteinusingMALDI-TOF-MS.Increasingtheconcentrationoffructoseinthemediuminducedaconcentration-dependentincreaseinthegeneratedGlycer-AGEs.Furthermore,inanexperimentusingglyceraldehyde,whichisaprecursorofGlycer-AGEs,hnRNPMwasfoundtobemoreeasilyglycatedthantheotherproteins.CONCLUSION:Theresultssuggestthatglyceraldehyde-modifiedhnRNPMaltersgeneexpression.Thischangemaycauseadverseeffectsinhepatocytesandmayserveasatargetfortherapeuticintervention.
简介:Objective:Toinvestigatetheroleandclinicalsignificanceofp16proteininCondylomaAcuminatum(CA)anditscancerization.Methods:Theexpressionofp16proteinwastestedin33CAsamplesand7cancerizedCAsamplesbyimmunohistochemicalassays.Results:Therewasabnormalexpressionofp16proteininCAandcancerizedCA,mainlymajorproteinexpression.Thep16proteinexpresseedindifferentlocationsindifferentcaseswasasfollows:Inbasallayercellsinnormalcuits;inspinouslayer,granularlayerandstratumcorneumlayercellsinCA;inkeratinpearlperipheralandspinouslayercellsincancerizedCA.Conclusion..Therewasmajorexpressionofp16proteininCAandcancerizedCA,andtheseproteinofthetwogroupsmightnotnaturallybethesame.Ourstudyindicatedthatinclinicalpractice,whenmajorp16proteinexpressioninCAoccurs,it'sriskofcancerizationshoudbesuspected.
简介:Usingatriangularlatticemodeltostudythedesignabilityofproteinfolding,weovercametheparityproblemofpreviouscubiclatticemodelandenumeratedallthesequencesandcompactstructuresonasimpletwo-dimensionaltriangularlatticemodelofsize4+5+6+5+4.Weusedtwotypesofaminoacids,hydrophobicandpolar,tomakeupthesequences,andachieved223+212differentsequencesexcludingthereversesymmetrysequences.Thetotalstringnumberofdistinctcompactstructureswas219,093,excludingreflectionsymmetryintheself-avoidingpathoflength24triangularlatticemodel.Basedonthismodel,weappliedafastsearchalgorithmbyconstructingaclustertree.Thealgorithmdecreasedthecomputationbycomputingtheobjectiveenergyofnon-leafnodes.Theparallelexperimentsprovedthatthefasttreesearchalgorithmyieldedanexponentialspeed-upinthemodelofsize4+5+6+5+4.Designabilityanalysiswasperformedtounderstandthesearchresult.
简介:哺乳动物的精子必须经历一系列生物化学、生理的修正,一起叫的capacitation,在在acrosome反应(AR)以前的女繁殖的道。尽管蛋白质kinases被显示在capacitation和AR期间涉及细胞内部的Ca2+的规定,这些修正的机制很好没被描绘。在现在的评论,我们总结一些涉及capacitation的发信号的事件。在capacitation过程期间,phosphatidyl-inositol-3-kinase(PI3K)是经由一个蛋白质kinaseA(PKA)依赖者的phosphorylated/activated由蛋白质kinaseCα的串联,和downregulated;(PKCα;)。PKCα;在capacitation的开始是活跃的,导致PI3Kinactivation。在capacitation期间,PKCα;象PP1γ一样;2被PKA依赖的机制降级,允许PI3K的激活。PKA的激活主要在capacitation期间取决于酸式碳酸盐依赖者生产的周期的腺苷monophosphate(营地)可溶的adenylylcyclase。PKA的这激活在肌动朊聚合导致增加,必需品为hyperactivated活动性的发展处理,它为成功的授精是必要的。肌动朊聚合被果仁2以二个方法调停:首先,果仁2为phospholipaseD(PLD)激活,和秒充当一个余因子,作为绑并且禁止象gelsolin那样的切断肌动朊的蛋白质的一个分子。gelsolin的酷氨酸phosphorylation为它的inactivation也在由Src家庭kinase(SFK)的capacitation期间是重要的。在AR以前,gelsolin被免除果仁2并且经历dephosphorylation/activation,导致AR,导致快F肌动朊depolymerization。
简介:Thecorona-likespikesorpeplomersonthesurfaceofthevirionunderelectronicmicroscopearethemoststrikingfeaturesofcoronaviruses.TheS(spike)proteinisthelargeststructuralprotein,with1,255aminoacids,intheviralgenome.Itsstructurecanbedividedintothreeregions:alongN-terminalregionintheexte-rior,acharacteristictransmembrane(TM)region,andashortC-terminusintheinteriorofavirion.WedetectedfifteensubstitutionsofnucleotidesbycomparisonswiththeseventeenpublishedSARS-CoVgenomesequences,eight(53.3%)ofwhicharenon-synonymousmutationsleadingtoaminoacidalternationswithpredictedphysiochemicalchanges.ThepossibleantigenicdeterminantsoftheSproteinarepredicted,andtheresultisconfirmedbyELISA(enzyme-linkedimmunosorbentassay)withsynthesizedpeptides.AnotherprofoundfindingisthatthreedisulfidebondsaredefinedattheC-terminuswiththeN-terminusoftheE(envelope)pro-tein,basedonthetypicalsequenceandpositions,thusestablishingthestructuralconnectionwiththesetwoimportantstructuralproteins,ifconfirmed.Phyloge-neticanalysisrevealsseveralconservedregionsthatmightbepotentdrugtargets.
简介:Humanpolymorphonuclearleukocytes(PMN)havebeenreportedtocompletelylackofDNA-dependentproteinkinase(DNA-PK)whichiscomposedofKuproteinandthecatalyticsubunitDNA-PKcs,neededfornonhomologousend-joining(NHEJ)ofDNAdouble-strandbreaks.PromyelocyticHL-60cellsexpressavariantformofKuresultinginenhancedradiationsensitivity.ThisraisesthequestioniflowefficiencyofNHEJ,instrumentalforthecellularrepairofoxidativedamage,isanormalcharacteristicofmyeloiddifferentiation.HereweconfirmedthecompletelackofDNAPKinPMNproteinextracts,andtheexpressionofthetruncatedKu86variantforminHL-60.However,thisdegradationofDNA-PKwasshowntobeduetoaDNA-PK-degradingproteaseinPMNandHL-60.Inaddition,byusingaprotease-resistantwholecellassay,bothKu86andDNA-PKcscouldbedemonstratedinPMN,suggestingthepreviouslyreportedabsenceinPMNofDNA-PKtobeanartefact.ThelevelsofKu86andDNA-PKcsweremuchreducedinPMN,ascomparedwiththatofthelymphocytes,whereasHL-60displayedamarkedlyelevatedDNA-PKconcentration.Inconclusion,ourfindingsprovideevidenceofreduced,notdepletedexpressionofDNA-PKduringthematurestagesofmyeloiddifferentiation.
简介:Identificationofproteinsbymassspectrometry(MS)isanessentialstepinpro-teomicstudiesandistypicallyaccomplishedbyeitherpeptidemassfingerprinting(PMF)oraminoacidsequencingofthepeptide.AlthoughsequenceinformationfromMS/MSanalysiscanbeusedtovalidatePMF-basedproteinidentification,itmaynotbepracticalwhenanalyzingalargenumberofproteinsandwhenhigh-throughputMS/MSinstrumentationisnotreadilyavailable.Atpresent,avastmajorityofproteomicstudiesemployPMF.However,therearehugedisparitiesincriteriausedtoidentifyproteinsusingPMF.Therefore,toreduceincorrectproteinidentificationusingPMF,andalsotoincreaseconfidenceinPMF-basedproteinidentificationwithoutaccompanyingMS/MSanalysis,definitiveguidingprinciplesareessential.Tothisend,weproposeavalue-basedscoringsystemthatprovidesguidanceonevaluatingwhenPMF-basedproteinidentificationcanbedeemedsufficientwithoutaccompanyingaminoacidsequencedatafromMS/MSanalysis.
简介:摘要:目的:通过在Human Protein Atlas数据库中对LILRB2检索来指导后续研究;方法:在数据库中对LILRB2检索获取结果后进行综合分析;结果:LILRB2在表达广泛,并与多种疾病的发病。结论:LILRB2在基于免疫功能的基础上发挥着重要的调控作用,比如参与肿瘤的调控、神经退行性变等。
简介:DEVELOPMENTOFAVERSATILESENSINGMEMBRANEFORIMMUBILIZATIONOFPROTEINANDANEWIMMOBILIZATIONMETHODY.K.Zhou,J.W.Yuan,S.Q.Xu,B.H.Shu(D...
简介:Objective:Toconstructarecombinantplasmidcontainingtheoutermembraneprotein2(Omp2)geneofChlamydiatrachomatisandexpressOmp2inE.coli.Methods:Theomp2geneofC.trachomatisserovarDwasclonedintopQE30vectorfollowingPCRamplificationfromgenomicDNA.E.coliM15transformantswereinducedtoexpressthefusionproteinbyIPTGandtheproductwasidentifiedbySDS-PAGEandWesternblot.Results:ConfirmedbyenzymecleavageanalysisandDNAsequencing,acorrectrecombinantplasmidpQE30/omp2wasconstructed.Thefusionproteinfromthetransformantswasapproximately60kDainsizeinSDS-PAGEanalysis,whichcouldspeciallyreactwithanti-6×HismousemonoclonalIgGantibodies.Conclusion:WesuccessfullyexpressedOmp2inE.coilM15,providinganefficientandsimplesystemforassayingtheimmunologicalpropertiesofOmp2.