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  • 简介:N^6-methyladenosine(m^6A)isanessentialRNAmodificationthatregulateskeycellularprocesses,includingstemcellrenewal,cellulardifferentiation,andresponsetoDNAdamage.Unsurprisingly,aberrantm6Amethylationhasbeenimplicatedinthedevelopmentandmaintenanceofdiversehumancancers.Alteredm6AlevelsaffectRNAprocessing,mRNAdegradation,andtranslationofmRNAsintoproteins,therebydisruptinggeneexpressionregulationandpromotingtumorigenesis.Recentstudieshavereportedthattheabnormalexpressionofm6Aregulatoryenzymesaffectsm6Aabundanceandconsequentlydysregulatestheexpressionoftumorsuppressorgenesandoncogenes,includingMYC,SOCS2,ADAM19,andPTEN.Inthisreview,wediscussthespecificrolesofm6A“writers",“erasers”,and“readers”innormalphysiologyandhowtheiralteredexpressionpromotestumorigenesis.Wealsodescribethepotentialofexploitingtheaberrantexpressionoftheseenzymesforcancerdiagnosis,prognosis,andthedevelopmentofnoveltherapies.

  • 标签: RNA modification N^6-methyladenosine (m^6A) CANCER tumor
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  • 简介:AIM:Toinvestigatewhethergenemethylationintheperitonealfluid(PF)predictsperitonealrecurrenceingastriccancerpatients.METHODS:ThegenemethylationofCHFR(checkpointwithforkheadandringfingerdomains),p16,RUNX3(runt-relatedtranscriptionfactor3),E-cadherin,hMLH1(mutLhomolog1),ABCG2(ATP-bindingcassette,sub-familyG,member2)andBNIP3(BCL2/adenovirusE1B19kDainteractingprotein3)wereanalyzedin80specimensofPFbyquantitativemethylation-specificpolymerasechainr...

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  • 简介:Genestellcellswhattodo,forexample,whentorepairDNAmistakesorwhentodie,andcanbeturnedonorofflikealightswitch.Knowingwhichgenesareswitchedon,orexpressed,isimportantforthetreatmentandmonitoringofdisease.Now,forthefirsttime,Researchersinthelaboratoryof

  • 标签: 基因表达 可视化 MRI DNA 光开关 细胞
  • 简介:TheroleofthetranscriptionfactorNF-κBinshapingthecancermicroenvironmentisbecomingincreasinglyclear.InflammationalterstheactivityofenzymesthatmodulateNF-κBfunction,andcausesextensivechangesingenomicchromatinthatultimatelydrasticallyaltercell-specificgeneexpression.NF-κBregulatestheexpressionofcytokinesandadhesionfactorsthatcontrolinteractionsamongadjacentcells.Assuch,NF-κBfinetunestissuecellularcomposition,aswellastissues'interactionswiththeimmunesystem.Therefore,NF-κBchangesthecellresponsetohormonesandtocontactwithneighboringcells.ActivatingNF-κBconferstranscriptionalandphenotypicplasticitytoacellandtherebyenablesprofoundlocalchangesintissuefunctionandcomposition.ResearchsuggeststhattheregulationofNF-κBtargetgenesisspecificallyalteredincancer.SuchalterationsoccurnotonlyduetomutationsofNF-κBregulatoryproteins,butalsobecauseofchangesintheactivityofspecificproteostaticmodulesandmetabolicpathways.ThisarticledescribesthemolecularmodeofNF-κBregulationwithafewcharacteristicexamplesoftargetgenes.

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  • 简介:ObjectiveToinvestigatethehypermethylationstatusofglutathionetransferaseP1(GSTP1)andE-cadherin(ECAD),TSGs(tumorsuppressorgenes)inourbreastcancersamplesandexploretheircorrelationwithclinicopathologicalfeaturesofcorrespondingcancerpatients.MethodsOnehundredandthirty-sixIDC(invasiveductalcarcinoma)patientswererecruitedforanalysisand16fibroadenomapatientsactedascontrol.DNAextractionandmethylation-specificPCR(MSP)weresubsequentlyperformedprecededbypathologicalexamination.ResultsThepercentageofhypermethylatedGSTP1incarcinomaandfibroadenomagroupswas34.92%and15.79%respectivelyandthepercentageofhypermethylatedECADincarcinomasandfibroadenomaswas18.00%and0.00%respectively.Carcinomahadthehighestpercentageofc-erbB2overexpressionbeing54.55%amongtheclinicopathologicalparameters.ConclusionHypermethylationpatternsarefrequentinIDCandseemtorelatetoc-erbB2overexpression,andsuchepigeneticchangeshouldnotbeneglectedinfibroadenoma.Tumormethylationstatusincancerpatientscanbedeterminedatearlystageanditmaybeareferenceforbettertreatmentplanning.

  • 标签: 乳腺癌 临床 治疗 疗效
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  • 简介:Thematrixmetalloproteinases(MMPs)areafamilyofzine-dependentendopeptidasesthatplayakeyroleinbothnormalandpathologicalprocessesinvolvingtissueremodelingevents.Theexpressionoftheseproteolyticenzymesishighlyregulatedbyabalancebetweenextracellularmatrix(ECM)depositionanditsdegradation,andiscontrolledbygrowthfactors,cytokines,hormones,aswellasinteractionswiththeECMmacromolecules.Furthermore,theactivityoftheMMPsisregulatedbytheirnaturalendogenousinhibitors,whicharemembersofthetissueinhibitorofmetalloproteinases(TIMP)family.Inthenormalmammarygland,MMPsareexpressedduringductaldevelopment,lobulo-alveolardevelopmentinpregnancyandinvolutionafterlactation.Underpathologicalconditions,suchastumorigenesis,thedysregulatedexpressionofMMPsplayaroleintumorinitiation,progressionandmalignantconversionaswellasfacilitatinginvasionandmetastasisofmalignantcellsthroughdegradationoftheECMandbasementmembranes.

  • 标签: 基质金属蛋白酶 乳腺 ECM 基因表达 胞外基质 肿瘤侵袭
  • 简介:AIM:ToscreenmicroRNAs(miRNAs)andsetuptargetmiRNAsinpterygium.METHODS:PrimaryfibroblastswereisolatedfrompterygiumandTenon’scapsuleandcultured.ImmunocytochemicalanalysisandWesternblottingwereperformedtoconfirmthecultureoffibroblasts.Inall,1733miRNAswerescreenedinthefirststepbyusingGeneChip?miRNA3.0Array.SpecificmiRNAsinvolvedinthepathogenesisofpterygiumweresubsequentlydeterminedusingthefollowingcriteria:1)highreproducibilityinarepetitivetest;2)baselogvalueof>7.0forbothcontrolandpterygialfibroblasts;and3)logratioof>1.0betweenpterygialfibroblastsandcontrolfibroblasts.RESULTS:Primaryscreeningshowedthat887/1733miRNAswereup-regulatedand846/1733miRNAsweredown-regulatedinpterygialfibroblastscomparedwiththoseincontrolfibroblasts.Ofthe1733miRNAsscreened,4miRNAs,namely,miRNA-143a-3p,miRNA-181a-2-3p,miRNA-377-5pandmiRNA-411a-5p,mettheabove-mentionedcriteria.Primaryscreeningshowedthatthese4miRNAswereup-regulatedinpterygialfibroblastscomparedwithcontrolfibroblastsandthatmiRNA-143a-3phadthehighestmeanratiocomparedwiththemiRNAsincontrolfibroblasts.CONCLUSION:miRNA-143a-3p,miRNA-181a-2-3p,miRNA-377-5pandmiRNA-411a-5pareup-regulatedinpterygialfibroblastscomparedwithcontrolfibroblasts,suggestingtheirinvolvementinthepathogenesisofpterygium.

  • 标签: MICRORNA PTERYGIUM FIBROBLAST
  • 简介:Objective:ToconstructtherecombinantplasmidcontainingGlycerophosphodiesterphosphodiesterase(Gpd)genefromTreponemapallidumandtransfectitintoHelacellstoexpresstheencodedoutermembraneprotein.Methods:TheGpdgenewasamplifiedfromthegenomicDNAofT.pallidumbypolymerasechainreaction(PCR)andinsertedintocloningvectorpUCm-T.TheinsertedGpdgenewassubclonedintotheappropriatesiteofpcDNA3.1(+)vector.Afteridentificationbysequencingandrestrictiveenzymesdigestion,therecombinantplasmidwastransfectedintoHelacellsusingliposomes.TheexpressedproteinwasidentifiedbyimmunocytochemistryandWesternblot.Results:ThetargetGpdgenesegmentwasapproximately1059bp.TheDNAsequenceoftheGpdgenecontainedinthepcDNA3.1(+)vectorwasconsistentwiththepublishednucleotidesequence.ThehomologyofthenucleotideandputativeaminoacidsequencesoftheGpdgenebetweenT.pallidumsubsp.pallidumNicholsandvariouspathogenictreponemalstrainsrangedfrom98%to100%.ImmunocytochemistryandWesternblotanalysisshowedthattheconstructedGpd-pcDNA3.1(+)vectorexpressedafusionproteinwithacalculatedmolecularmassof41KDainHelacellsandthattheexpressedproteinreactedwiththeserafromsyphilispatients.Conclusion:ThesuccessfulconstructionandexpressionoftheeukaryoticexpressionplasmidoftheGpdgenefromT.pallidumprovideapromisingtooltofurtherstudythebiologicalactivityofT.pallidumanddevelopaDNAvaccineforsyphilis.

  • 标签: 真核细胞 甘油三脂 基因表达 密螺旋体 人宫颈癌传代细胞
  • 简介:Duringtheevolvementofarchitecture,theresearchonarchitecturalformandstructureaswellasdifferentwaystoexpressandrealizearchitecturalthoughtsisconstantlythefocusofmanyarchitects,Thispaperillustratesthemutualinfluenceofthewaysofexpressionanddesignofarchitecturetopeople'sunderstandingofthemeaningofarchitecturethroughoutthehistoryoftheireffortsandexploration.thepaperalsodiscussestheextensiveusageofvirtual-realithapproachthroughcomputertechnology,Itpointsoutthatthetraditionalarchitecturalstandpointwillundergobreakthroughbytheemergenceofnewexpressionanddesignmethod.Inthisway,people'sunderstandingofarchitecturewillbemoreprofoundandlasting.

  • 标签: 建设设计 CAD 虚拟现实 建筑结构 计算机辅助设计
  • 简介:Objective:Toclone,sequenceandexpresstheprimateβ-chemokineRANTESgenes,hRANTESfromH.sapiensandmRANTESfromM.Mulatta,inordertoexplorethepossibilityofAIDSgenetherapy.Methods:hRANTESandmRANTESwereamplifiedbyreversetranscription-polymerasechainreaction(RT-PCR)fromRNAsextractedfromphytoagglutinin(PHA)-activatedperipheralbloodlymphocytes,hRANTESwascloned,sequencedandexpressedinvitro,andmRANTESwasdirectlysequencedforhomologycomparison.Results:Anexpected276bpfragmentwasobtainedinbothamplifications,andsequencedatademonstratedarelativelyhighhomologyamongdifferentcopiesofhRANTES(97%),andhRANTESwasupto95.6%homologoustomRANTES.WhencomparedwithRANTESfromothermammals,hRANTESgaverisetoahomologyrangingfrom77%to86%.TheclonedhRANTESwasexpressedinvitroandapositivesignalofRANTESwasdetectedbydotblotting.Conclusion:Thefull-lengthofhRANTESsequencewassubmittedtoGenBankandhadbeenreleased.OurmRANTESsequenceisfirstreportedandnotyetappearedinGenBank.ThesuccessfulcloningandexpressionofhRANTESwillprovideabasisforAIDSgenetherapyinthefuture.

  • 标签: RANTES基因 基因表达 基因多态性 爱滋病
  • 简介:多字的表情(MWE)在自然语言经常并且不合语法地出现。在免费文章识别MWE是一个很挑战性的问题。这份报纸建议没有知识、无指导、语言无关的多字的表示距离(MED)。新度量标准从一个接受物理原则被导出,从n克测量距离到它的语义,并且超过在二应用的MWE上的另外的最先进的方法:问答和命名实体抽取。

  • 标签: 应用程序 度量 语义距离 自然语言 物理原理 命名实体