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简介：MutationsinmitochondrialtRNAgeneshavebeenshowntobeassociatedwithmaternallyinheritedsyn-dromicandnon-syndromicdeafness.Amongthose,mutationssuchastRNALeu(UUR)3243A>Gassociatedwithsyndromicdeafnessareoftenpresentinheteroplasmy,andthenon-syndromicdeafness-associatedtRNAmu-tationsincludingtRNASer(UCN)7445A>Gareofteninhomoplasmyorinhighlevelsofheteroplasmy.ThesetRNAmutationsaretheprimaryfactorsunderlyingthedevelopmentofhearingloss.However,othertRNAmutationssuchastRNAThr15927G>AandtRNASer(UCN)7444G>Aareinsufficienttoproduceadeafnessphe-notype,butalwaysactinsynergywiththeprimarymitochondrialDNAmutations,andcanmodulatetheirphenotypicmanifestation.ThesetRNAmutationsmayalterthestructureandfunctionofthecorrespondingmitochondrialtRNAsandcausefailuresintRNAsmetabolism.Thereby,theimpairmentofmitochondrialproteinsynthesisandsubsequentdefectsinrespirationcausedbythesetRNAmutations,resultsinmitochon-drialdysfunctionsandeventuallyleadstothedevelopmentofhearingloss.Here,wesummarizedthedeaf-ness-associatedmitochondrialtRNAmutationsanddiscussedthepathophysiologyofthesemitochondrialtRNAmutations,andwehopethesedatawillprovideafoundationfortheearlydiagnosis,management,andtreatmentofmaternallyinheriteddeafness.

简介：骨头骨折愈合的起始的煽动性的阶段为愈合的过程的结果代表关键步。然而，开始这个煽动性的阶段的机制和在破裂地点在场的有免疫力的房间的功能糟糕被理解。以便在破裂hematoma以内学习早事件，我们建立了一在里面vitro破裂hematoma模型：我们有教养的hematomas在bioenergetically控制的条件下面在vitro在全部的新潮的关节造形术(THA)期间在腿节的截骨术(人工的骨头破裂)期间形成。这个模型允许我们在跟随破裂的早阶段期间监视有免疫力的房间人口，房间幸存和cytokine表示。而且，这个模型使我们能改变bioenergetical条件以便模仿在里面vivo状况，它被假定被组织缺氧描绘并且限制了营养素的数量。用这个模型，我们发现有免疫力的房间经由angiogenic因素，chemoattractants和支持inflammatory分子的表示适应组织缺氧。另外，联合了氧的限制，滋养的供应与myeloid的比较提高了淋巴细胞的选择幸存导出的房间(即，neutrophils)。笔记，非限制的bioenergetical条件没关于cytokine表示或有免疫力的房间子集的不同幸存率显示出任何类似的效果。在结论，我们发现bioenergetical条件在导致骨折愈合的起始的煽动性的阶段的关键因素之中并且因此是为在早破裂hematoma影响有免疫力的房间的幸存和功能的一个关键步骤。

简介：Thedataofdielectricpropertiesofhumantissuesmainlycomefromanimaltissuesorhumancorpseatpresent.Uptonow,therehasnotbeenareportofdielectricpropertiesofhumanlivingliver.Ourobjectiveistostudythedielectricpropertiesofhumanlivingliverandcomparetheresultswiththoseofanimallivingliveraswellasthehumannon-livingliver.Invitromeasurementsoflivingandnon-livingliversfromhumanandrabbitsareshowninthe10Hzto100MHzrange.Analysisoftheconductivity,permittivityandcharacteristicparametersfromthedataweremade.Theconductivityofthreekindsofliverweremarkedlydifferentatlowfrequencyof0.06s/m(livingrabbitliver),0.13s/m(livinghumanliver)and0.24s/m(non-livinghumanliver).TheColeparametersthatbestcharacterizetheliverofhumanandrabbitareR0,fc1,R1,andR∞TheColeparametersthatbestcharacterizethelivingandnonlivingliverofhumanareR0,fc1,ΔR1,ΔR2andR∞.Inconclusion,wecan’tsubstitutethedielectricpropertiesofanimalorhumancorpseliverforthelivinghumanliver.Theresultssuggestthatthedielectricpropertiesoflivinghumantissueshasgreatsignificanceonstudying.

简介：Objective:Toinvestigatetheimpactofbeta-elemeneinjectiononthegrowthandalpha-tubuleofhumanhepatocarcinomaHepG2cells.Methods:CellproliferationwasassessedbyMTTassay.Cellcycledistributionwasdetectedbyflowcytometry(FCM).ThemRNAexpressionofalpha-tubulinwasmeasuredbyRT-PCR.Westernblotanalysiswasusedtodetermineproteinexpressionofalpha-tubulinandthepolymerizationoftubulin.Results:Beta-elemeneinjectioninhibitedHepG2cellsproliferationinadose-andtime-dependentmanner;FCManalysisindicatedbeta-elemeneinjectioninducedcellcyclearrestedatSphase.RT-PCRandwesternblotanalysisshowedthatbeta-elemeneinjectiondown-regulatedalpha-tublinatbothmRNAandproteinlevels,presentingadose-dependentmanner.Moreover,beta-elemeneinjectionreducedthepolymerizationofmicrotubulesinadose-dependentmanner.Conclusions:Beta-elemeneinjectioncaninhibittheproliferationofhepatomaHepG2cellsandinducecellapoptosis,themechanismmightbepartlyrelatedtothedown-regulationofalpha-tubulinandinhibitionofmicrotubularpolymerization.

简介：Hepatocellularcarcinoma(HCC)isoneofthemostdeadlyhumancancers,butitisverydifficulttoestablishananimalmodelbyusingsurgicalspecimens.Inthepresentexperiment,histologicallyintactfreshsurgicalspecimensofHCCweresubcutaneouslytransplantedinnon-obesediabetic/severecombinedimmunodeficienccy(NOD/SCID)mice.Thebiologicalcharacteristicsoftheoriginalandthecorrespondingtransplantedtumorsandcelllineswereinvestigated.Theresultsshowedthat5newanimalmodelsand2primarycelllinesweresuccessfullyestablishedfromsurgicalspecimens.Hematoxylin-eosinstainingshowedthatxenograftsretainedmajorhistologicalfeaturesoftheoriginalsurgicalspecimens.Thetwonewcelllineshadbeencultivatedfor3yearsandsuccessivelypassagedformorethan100passagesinvitro.Themorphologicalcharacteristicsandbiologicfeaturesofthetwocelllinesweregeneticallysimilartotheoriginaltumor.Thesubcutaneoustransplantanimalmodelswithhistologicallyintacttumortissueandprimarycelllinescouldbeusefulforinvivoandinvitrotestingofanti-cancerdrugsandbeidealmodelstostudyvariousbiologicfeaturesofHCC.

简介：Objective:Toidentifydifferentiallyexpressedlongnon-codingRNAs(lncRNAs)involvedinthemetastasisofepithelialovariancancer.Methods:AninvitroinvasionassaywasperformedtovalidatetheinvasivecapabilityofSKOV3andSKOV3.ip1celllines.TotalRNAwasthenextracted,andmicroarrayanalysiswasperformed.Moreover,ninelncRNAswereselectedforvalidationusingRT-qPCR.Results:ComparedwiththeSKOV3cells,theSKOV3.ip1cellssignificantlyimprovedintheinvitroinvasiveactivity.Ofthe4,956lncRNAsdetectedinthemicroarray,583and578lncRNAswereupregulatedanddownregulated,respectively,inSKOV3.ip1cells,comparedwiththeparentalSKOV3cells.SevenoftheanalyzedlncRNAs(MALAT1,H19,UCA1,CCAT1,LOC645249,LOC100128881,andLOC100292680)confirmedthederegulationfoundbymicroarrayanalysis.Conclusion:LncRNAsclustersweredifferentiallyexpressedinovariancancercellswithvaryingmetastaticpotentials.ThisresultindicatesthatsomelncRNAsmightexertapartialorkeyroleinepithelialovariancancermetastasis.FurtherstudiesshouldbeconductedtodeterminetherolesoftheselncRNAsinovariancancermetastasis.

简介：Objective:Earlymetastasisisamajorbiologicalfeatureofpancreaticcancer.ThecurrentstudyexaminedwhethersilencingSlc38a1,ageneinvolvedinenergymetabolism,usingshorthairpinRNA(shRNA)couldinhibitthegrowth,migration,andinvasivenessofpancreaticcancercells.Methods:AseriesofSlc38a1shRNAsweredesignedandclonedintothepGPU6/GFP/Neovectors.AnshRNAwiththemostefficaciousinhibitoryactiononSCL38A1expression(65%inhibition)uponscreeninginDH5αbacteriawasusedtotransfectSW1990humanpancreaticcancercells.Cellgrowth,migration,andinvasivenesswereexaminedusingcellcountingkit-8,BoydenchamberwithoutandwithMatrigel,respectively.Results:TransfectionofSW1990cellswiththeSLCs38A1shRNAsignificantlydecreasedtheproliferation(P<0.0001)andmigratorypotential(by46.7%,P=0.0399)ofthecancercells.Invasiveness,however,wasnotaffected.Conclusions:InhibitingSlc38a1usingshRNAtechnologycoulddecreasethegrowthandmigrationofrepresentativepancreaticcancercells.However,thefactthatinvasivenesswasnotaffectedsuggestedthatSLC38A1isunlikelytoberesponsibleforearlymetastasis.

简介：Objective:Fusogenicendogenousretroviralsyncytinplaysanimportantroleintheformationofsyncytiotrophoblastsinhumanplacenta.Apartfromitsexpressioninplacenta,brainandtestis,syncytinhasalsobeenfoundinmanycancers.Althoughsyncytinhasbeenproposedtoserveasapositiveprognosticmarkerinsomecancers,theunderlyingmechanismisunclear.Theaimofthisstudyistoevaluatetheeffectsofsyncytinexpressionontheinvasivephenotypeofmelanomacells.Methods:Theeukaryoticexpressionplasmidforsyncytin-EGFPwasconstructedandtransfectedintoB16F10melanomacells.TheeffectofsyncytinontheinvasionpotentialoftumorcellswasevaluatedinB16F10sublinecellsthatstablyexpressedsyncytin-EGFPfusionproteinorEGFPalone.Results:TheB16F10sublinesthatstablyexpressedsyncytin-EGFPorEGFPalonewereestablishedrespectivelyandconfirmedbyimmunofluorescentandimmunoblottingassay.SyncytinexpressioninB16F10cellswasassociatedwithdecreasedcellproliferation,migrationandinvasion.Multinucleatedgiantcellsthatcontainedasmanyasfivenucleiwereinducedinsyncytin-expressingcells.Inaddition,syncytinexpressiondidnotalterthesensitivityofB16F10cellstotrichosanthin,atoxinthatdamagessyncytiotrophoblastsmoreefficientlythanothertissues.Conclusions:Theseresultssuggestthatsyncytinexpressioninsomecancersmayconfinetheirinvasionpotentialandthusserveasapositiveprognosticfactor.更多还原

简介：高度病原的鸟的流行性感冒H5N1流行病是重要公共健康危险。有哺乳动物的传播活动的遗传上设计的H5N1病毒加亮人的流行性感冒H5N1的潜在的风险流行。响应流行性感冒H5N1病毒理解天生的免疫系统的内在的原则将导致这些潜在地致命的病毒的改进预防和控制。γ；δ；当第一对微生物引起的感染防卫排队并且帮助在病毒的感染的早阶段期间开始适应有免疫力的回答，T房间行动。在这研究，我们调查了γ的分子的机制；δ；响应流行性感冒H5N1病毒的感染的T房间。我们发现从流行性感冒H5N1病毒的三不同紧张导出的recombinant红血球凝聚素(rHA)得到了γ的激活；δ；在外部血mononuclear房间(PBMC)有教养的T房间。两CD69的房间表面表示，γ上的一个早激活标记；δ；interferon-γ的T房间，和生产；(IFN-γ；)显著地被增加。尤其是，rHA导致蛋白质的γ；δ；T房间激活没被TCRγ调停；δ；，NKG2D或模式识别受体(PRR)或NKp46受体。有sialic酸受体的rHA蛋白质的相互作用可以在γ起一个关键作用；δ；T房间激活。我们的数据可以提供卓见进位于γ下面的机制；δ；响应有H5N1病毒的感染的T房间激活。

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简介：像使用费的受体(TLR)是主人防卫系统的哨兵，它认出很多微生物引起的病原体。主机防卫系统可能是低效的或如果由TLR和随后的被触发TLR的cytokine生产的微生物引起的识别是deregulated，煽动性的疾病可以发展。激活抄写因素4(ATF4)，ATF/CREB抄写因素家庭的一个成员，是参予几个pathophysiological过程的一个重要因素。在这份报告，我们发现ATF4也涉及调停TLR的天生的有免疫力的反应，它参予TLR4信号transduction并且调停许多cytokines的分泌物。我们观察到ATF4被激活并且translocates到经由TLR4-MyD88-dependent小径跟随lipopolysaccharide(LPS)刺激的原子核。另外，cytokine数组试金证明某关键煽动性的cytokines例如IL-6，IL-8和RANTES，被ATF4断然调整。我们也证明c6月直接绑在ATF4，从而支持煽动性的cytokines的分泌物。一起拿，这些结果显示ATF4在被触发TLR4的cytokine充当一个积极管理者生产。

简介：2009H1N1流行性感冒流行表明了对人的全球健康威胁的意义。尽管流行H1N1疫苗很快被开发了，被动serotherapy可以在孩子对感染提供优异立即的保护，老、妥协免疫者的病人在流行性感冒期间流行。这里，我们基于使不朽的Epstein-Barr病毒(EBV)使用了新奇策略从个人屏蔽高病毒的抵销monoclonal抗体(MAbs)的外部血记忆B房间与2009流行H1N1疫苗的PANFLU.1种牛痘。通过13090使不朽的记忆B房间的一幅巨大的屏幕，从三的克隆选择了vaccinees，七MAbs与两个高病毒的抵销能力和红血球凝聚抑制(HAI)被识别对2009个流行H1N1病毒的活动。这些MAbs可以与严重呼吸症候群为感染的病人的被动serotherapy治疗有重要临床的含意，特别孩子，老并且immunodeficient个人。我们为从使EBV不朽的外部血记忆B房间产生高亲密关系的MAbs的成功的策略可能也对另外的传染或自体免疫的疾病适用。