简介：AbstractBackground:Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer.Methods:By transfection of a 5 hypoxia-responsive element (HRE)/green fluorescent protein (GFP) plasmid, the cell line Ca761-hregfp was established, which emitted green fluorescence triggered by HIF-1α under hypoxia. The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy. We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice. Experiments were conducted on days 4, 9, 15, and 19. For in vivo analysis, Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound (CEUS) and fluorescence imaging (FLI) during tumor development. The tumor size, CEUS peak intensity, and FLI photons were measured to evaluate tumor growth, angiogenesis, and HIF-1α activity, respectively. After each experiment, three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1α activity and the microvessel density (MVD).Results:In vitro, both green fluorescence and HIF-1α expression were detected in Ca761-hre-gfp cells treated with CoCl2, indicating the suitability of the cells to detect HIF-1α activity. In vivo, HIF-1α activity first increased and then decreased, which was significantly correlated with angiogenic changes (r = 0.803, P = 0.005). These changes were confirmed by immunohistochemical staining of HIF-1α and MVD.Conclusions:The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1α activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities. The cell line may be useful for studies of anti-HIF pathway therapies.

简介：Hypoxia-induciblefactor1(HIF-1)attenuatesamyloid-betaproteinneurotoxicityanddecreasesapoptosisinducedbyoxidativestressorhypoxiaincorticalneurons.Inthisstudy,weconstructedarecombinantadeno-associatedvirus(rAAV)vectorexpressingthehumanHIF-1αgene(rAAV-HIF-1α),andtestedtheassumptionthatrAAV-HIF-1αrepresseshippocampalneuronalapoptosisinducedbyamyloid-betaprotein.OurresultsconfirmedthatrAAV-HIF-1αsignificantlyreducesapoptosisinducedbyamyloid-betaproteininprimaryculturedhippocampalneurons.DirectintracerebralrAAV-HIF-1αadministrationalsoinducedrobustandprolongedHIF-1αproductioninrathippocampus.SinglerAAV-HIF-1αadministrationresultedindecreasedapoptosisofhippocampalneuronsinanAlzheimer’sdiseaseratmodelestablishedbyintracerebroventricularinjectionofaggregatedamyloid-betaprotein(25–35).OurinvitroandinvivofindingsdemonstratethatHIF-1haspotentialforattenuatinghippocampalneuronalapoptosisinducedbyamyloid-betaprotein,andprovidesexperimentalsupportfortreatmentofneurodegenerativediseasesusinggenetherapy.

简介：AIMToinvestigatetherolesandinteractionsofmutThomolog（MTH）-1andhypoxia-induciblefactor（HIF）-1αinhumancolorectalcancer（CRC）.METHODS：TheexpressionanddistributionofHIF-1αandMTH-1proteinsweredetectedinhumanCRCtissuesbyimmunohistochemistryandquantitativerealtimepolymerasechainreaction（qRT-PCR）.SW480andHT-29cellswereexposedtonormoxiaorhypoxia.ProteinandmRNAlevelsofHIF-1αandMTH-1wereanalyzedbywesternblottingandqRT-PCR,respectively.InordertodeterminetheeffectofHIF-1αontheexpressionofMTH-1andtheamountof8-oxodeoxyguanosinetriphosphate（dGTP）inSW480andHT-29cells,HIF-1αwassilencedwithsmallinterferingRNA（siRNA）.GrowthstudieswereconductedoncellswithHIF-1αinhibitionusingaxenografttumormodel.Finally,MTH-1proteinwasdetectedbywesternblottinginvivo.RESULTS：HighMTH-1mRNAexpressionwasdetectedin64.2%ofcases（54/84）,andthiswassignificantlycorrelatedwithtumorstage（P=0.023）andsize（P=0.043）.HIF-1αproteinexpressionwascorrelatedsignificantlywithMTH-1expression（R=0.640;P〈0.01）inhumanCRCtissues.HypoxicstressinducedmRNAandproteinexpressionofMTH-1inSW480andHT-29cells.InhibitionofHIF-1αbysiRNAdecreasedtheexpressionofMTH-1andledtotheaccumulationof8-oxo-dGTPinSW480andHT-29cells.Intheinvivoxenografttumormodel,expressionofMTH-1wasdecreasedintheHIF-1αsiRNAgroup,andthetumorvolumewasmuchsmallerthanthatinthemocksiRNAgroup.CONCLUSION：MTH-1expressioninCRCcellswasupregulatedviaHIF-1αinresponsetohypoxicstress,emphasizingthecrucialroleofHIF-1α-inducedMTH-1intumorgrowth.

简介：Objective:TostudythesequentialchangesofHIF-1α(hypoxia-induciblefactor1alpha)inexperimentalspinalcordinjuryinratsandtoanalyzeitspotentialeffectsinSCI.Methods:AstaticcompressionmodelofSCIwasemployedinthisstudy.ExpressionsofHIF-1αweremeasuredwithimmunohistochemicalstaining,whileflowcytometrywasusedtodeterminetheapoptoticratioandbcl-2expressions.Results:HIF-1αbegantoincrease1dayafterinjury,andreachedthepeakat3-7days.Twoweekslater,itdeclinedsignificantly.ThesequentialchangesofHIF-1αcoincidedwellwiththealterationsofapoptoticratioandcontentsofbel-2.Conclusions:HIF-1αpossiblyparticipatesinthesecondaryischemicandhypoxicproceduresafterspinalcordinjury,andmaymediatethetraumaticapoptosis.FurtherunderstandingofHIF-1αmayprovidenewtherapeuticregimensforSCI.

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简介：AbstractBackground:Mesenchymal stem or stromal cells (MSCs) derived from the induced pluripotent stem cells (iPSCs) have uniform biological activity, which makes the clinical application of MSCs in bone repair possible. Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration. The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs.Methods:Sema3A and HIF1α were linked together with the three (GGGGS; G, glycine; S, serine) peptide fragment, and their co-expression in iPSC-MSCs was mediated by a lentiviral vector. The fusion protein retained the immune reactivity for both Sema3A and HIF1α as determined with Western blotting. iPSC-MSCs were infected with overexpression lentivirus (oeLenti) as negative control, oeLenti-Sema3A, oeLenti-HIF1α or oeLenti-Sema3A-HIF1α lentiviruses.Results:Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs (the activity and/or expression of osteoblast markers, such as alkaline phosphatase, osteopontin, and osteocalcin, were upregulated), and suppressed cell survival. The Sema3A-HIF1α fusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival. We further seeded iPSC-MSCs modified by SemaA-HIF1α overexpression onto hydroxyapatite (HA) scaffolds, and evaluated their growth and differentiation on this three-dimensional material. Additional data indicated that, as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes, cells cultured in HA scaffolds grew (blank vs. HA scaffolds: 0.83 vs. 1.39 for survival) and differentiated better (blank vs. HA scaffolds: 11.29 vs. 16.62 for alkaline phosphatase activity).Conclusion:Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.

简介：ApoptosisproducedinBcellsthroughFas(APO-1,CD95)triggeringisregulatedbysignalsderivedfromothersurfacereceptors:CD40engagementproducesupregulationofFasexpressionandmarkedsusceptibilitytoFas-inducedcelldeath,whereasantigenreceptorengagement,orIL-4Rengagement,inhibitsFaskillingandinsodoinginducesastateofFas-resistance,eveninotherwisesensitive,CD40-stimulatedtargets.SurfaceimmunoglobulinandIL-4RutilizeatleastpartiallydistinctpathwaystoproduceFas-resistancethatdifferentiallydependonPKCandSTAT6,respectively.Further,surfaceimmunoglobulinsignalingforinducibleFas-resistancebypassesBtk,requiresNF-κB,andentailsnewmacromolecularsynthesis.TerminaleffectorsofBcellFas-resistanceincludetheknownanti-apoptoticgeneproducts,Bcl-XLandFLIP,andanovelanti-apoptoticgenethatencodesFAIM(FasApoptosisInhibitoryMolecule).faimwasidentifiedbydifferentialdisplayandexistsintwoalternativelysplicedforms;faim-Sisbroadlyexpressed,butfaim-Lexpressionistissue-specific.TheFAIMsequenceishighlyevolutionarilyconserved,suggestinganimportantroleforthismoleculethroughoutphylogeny.InducibleresistancetoFaskillingishypothesizedtoprotectforeignantigen-specificBcellsduringpotentiallyhazardousinteractionswithFasL-bearingTcells,whereasautoreactiveBcellsfailtobecomeFas-resistantandaredeletedviaFas-dependentcytotoxicity.InadvertentoraberrantacquisitionofFas-resistancemaypermitautoreactiveBcellstoescapeFasdeletion,andmalignantlymphocytestoimpedeanti-tumorimmunity.

简介：<正>ThesusceptibilityofprimaryBcellstoFas(APO-1,CD95)-mediatedapoptosisisregulatedbysignalsderivedfromadditionalsurfacereceptors.CD40engagementproducesupregulationofFasexpressionandinducesmarkedsensitivitytoFas-inducedcelldeath,whereasBcellantigenreceptor(BCR)engagementinhibitsFaskillingandtherebyproducesFas-resistance,eveninotherwisesusceptible,CD40-stimulatedtargets.BCRsignalingforinducibleFas-resistancedevelopsoveraperiodof12hoursanddependson

简介：在对杆菌thuringiensis(Berliner)(Bt)的内毒素的害虫的抵抗是对这简历杀虫剂的实用性的主要威胁，两个都用作传统的明确的表达并且在转基因的庄稼。为成功的抵抗管理策略的发展的一个关键要求是性质的分子的理解和抗性机制的继承。这个信息能被用来设计将推迟或抵抗Bt抵抗的管理策略。最好已知的Bt抗性机制在刷子边阶膜受体的激活。这类抵抗有继承的一个大部分后退的模式，它启用了抵抗管理途径包含，高剂量和避难处策略的设计。最近的观察建议另外的抗性机制是可能的，包括扣押的机制在通过可诱导的有免疫力的反应的内脏腔的毒素。与忍耐联系到毒素的提高的有免疫力的地位能被母体影响传给随后的代，它在这块地里为抵抗管理有含意。高dose/refugestrategy不能为这些其他的抗性机制的管理是适当的，如果可诱导的主导的抵抗或忍耐机制在这块地里经常发生，另外的策略不得不被发展。

简介：Thisstudywasconductedtoevaluatethecriticalthermalmaximum(CTMax),theroutinemetabolismrate(MO2)andthelimitingoxygensaturation(LOS)ofthreesalmonidswithfourdifferentbodyweightsrangingfrom16gto131g.TheCTMaxwasestimatedatthreedifferentheatingratesincluding0.5℃min^-1,1℃h^-1and2℃d^-1.ResultsshowedthattheCTMaxofmapletrout(Oncorhynchusmykiss)wasthehighest,whichwasfollowedbysteelheadtrout(O.mykiss)andAtlanticsalmon(Salmonsalar).TheCTMaxofthesalmonidfishdecreasedwiththeincrementofbodyweight,andwassignificantlyinfluencedbytheheatingrate.TheMO2ofthesalmonidfishincreasedwiththeincrementoftemperature,anddecreasedwiththeincrementofbodyweight.Suffocationpointsofthefishdecreasedwithincreasingbodyweightandtemperature.SteelheadtroutwasmoretoleranttohypoxiathanmapletroutandAtlanticsalmon,whiletheMO2ofAtlanticsalmonwasthehighestamongthesethreesalmonids.TheLOSofthefishgenerallyhadapositivetrendwithtemperatureandbodyweight,andtheLOSofsteelheadtroutwassignificantlylowerthanthatofmapletroutandAtlanticsalmon.Inconclusion,mapletroutwasthemosttolerantkindtohightemperature,whilesteelheadtroutwasthemosttoleranttohypoxiaamongthreekindsofsalmonids.Moreover,theabilitiestotoleratehighertemperatureofthreesalmonidswereaffectedbytheirbodyweightandtheheatingrate,whiletheabilitiestotoleratehypoxiawereinfluencedbytheirbodyweightandthewatertemperature.

简介：Objective:Toexploretherelationshipbetweenneuronalapoptosisandhypoxiaortraumaticinjury.Methods:Ratneuronsprimarilyculturedinvitroweretreatedwithhypoxia(thehypoxiagroup)ortraumaticinjury(thetraumagroup).Theneuronalapoptosiswasevaluatedwithmicroscope,TUNEL(terminaldeoxynucleotidyltransferasemediatedx-dUTPnickendlabeling)staining,flowcytometry,agarosegetelectrophoresisandimmunohistochemistry.Results:Morphologicalchangesofapoptosisappearedinthetreatedneurons,andtheDNAfragmentationshowed“ladder”break.Theapoptoticindexwas10.8%inthehypoxiagroupand4.8%inthetraumagroup,whileitwasonly1.6%inthecontrolgroup.Theexpressionofapoptosis-associatedgenes(c-myc,fasandfasL)increased.Conclusions:Hypoxiaortraumaticinjurycaninduceneuronalapoptosis,anditsmolecularmechanismisprobablyrelatedtotheexpressionsofapoptosis-associatedgenes.

简介：有免疫力的房间，特别地巨噬细胞，在导致组织缺氧的煽动性的反应起关键作用。小GTPaseRhoB被许多刺激很快通常导致并且被描述了为细胞骨架组织和泡和膜受体trafficking的一个重要管理者。然而，RhoB是否涉及导致组织缺氧的煽动性的反应，是未知的。这里，我们在巨噬细胞在RhoB表示的RhoB和机制和意义的表示上调查了组织缺氧的效果。我们显著地发现了那组织缺氧upregulated在老鼠的RAW264.7房间，鼠标腹巨噬细胞，和怒气的RhoB的表达式。RhoB的导致组织缺氧的表示被组织缺氧可诱导的factor-1(HIF-1)的一个特定的禁止者显著地堵住，c6月N终端kinase(JNK)，或细胞外信号的调整蛋白质kinase(英皇家空军之阶级最低之兵)，显示那激活组织缺氧的HIF-1，JNK，和英皇家空军之阶级最低之兵被组织缺氧涉及RhoB的upregulation。RhoB表示击倒不仅interleukin-1贝它(IL-1)的显著地压制的基础生产，interleukin6(IL-6)，并且在normoxia而且更多的肿瘤坏死因素alpha(TNF-)显著地减少了这些cytokines的刺激组织缺氧的生产。而且，我们证明RhoB增加了NF-Btranscriptional的原子factor-kappaB(NF-B)活动，和抑制活动显著地减少了IL-1，IL-6，和TNF-的增加RhoB的mRNA层次。最后，我们证明RhoB提高了房间粘附并且在normoxia和组织缺氧禁止了房间移植。一起拿，这些结果建议RhoB在巨噬细胞和煽动性的反应的导致组织缺氧的激活起一个重要作用。

简介：Detrendedfluctuationanalysis(DFA)isfitforstudiesonthelong-rangeexponentialcorrelationofnon-stationarytimeserial.Inthispaper,inordertofindahypoxiaadaptabilityevaluationcriterion,theheartrateandSaO2signalsareanalyzedbythismethod.Thedemarcateexponentaboutfit-good-groupandfit-bad-groupinhypoxiaandnormalairarecalculatedandcompared.Theresultshowsαisdifferentindifferentsituation,theαinhypoxiaismuchhigherthanαofbreathinnormalair.Andαoffit-good-groupishigherthanfit-bad-group.ItshowsthatDFAcouldbeagoodcriteriontoanalyzehypoxiaadaptability,whichisusefulintheanalysisofhypoxiaphysiologysignal.

简介：Objective:Stromalinteractionmolecule1(STIM1)overexpressionhasbeenreportedtoplayanimportantroleinprogressionofseveralcancers.However,themechanismofSTIM1overexpressionanditsrelationshipwithhypoxiainpancreaticductaladenocarcinoma(PDAC)remainsunclear.Methods:STIM1andHIF-1αexpressionwastestedusingimmunohistochemistryintissuemicroarray(TMA)includingpancreaticcancerandmatchednormalpancreatictissues,andtheirrelationshipswithclinicopathologicalparameterswerestatisticallyanalyzed.q-PCR,Westernblot,ChIP,andluciferaseassaywereemployedto030analyzetranscriptionalregulationbetweenHIF-1αandSTIM1inpancreaticcancerPANC-1cells.Results:BothSTIM1andHIF-1αshowedhigherpositiveratesandup-regulatedexpressionincancertissuescomparedtothatofnormaltissues(P<0.05).TheKaplan–MeiermethodrevealedthathigherHIF-1αandSTIM1expressionlevelsweresignificantlycorrelatedwithdecreaseddisease-freesurvival(P=0.025andP=0.029,respectively).TheexpressionofHIF-1αshowedasignificantpositivecorrelationwiththatofSTIM1incancertissues(rs=0.3343,P=0.0011)andpancreaticcancercelllines.Furthermore,ChIPandluciferaseassaysconfirmedthatHIF-1αboundtotheSTIM1promoterandregulateditsexpressioninPANC-1cells.Conclusions:Inhypoxiamicroenvironment,up-regulatedexpressionofSTIM1mediatedbyHIF-1αpromotesPDACprogression.HIF-1αandSTIM1arepotentialprognosticmarkersand/ortherapeutictargetsforPDACtreatment.

简介：从米饭胼胝的二ABA-specifically-inducible蛋白质被降水与65100%孤立并且净化浸透(NH_4)_2SO_4，由DEAE-sepharose，TSK胶化，和二尺寸的电气泳动列在后面。有一样的分子的团(24.5kD)的蛋白质的等电位的点(pl)分别地是6.1和6.9。西方的污点分析显示在不同纸巾表示的蛋白质显然是不同的。A1(pl6.1)蛋白质仅仅在与骆驼毛的织物和种子胚胎(SE)对待的电话i被检测。然而，A2(pl6.9)蛋白质不仅在与骆驼毛的织物和SE对待的电话i，而且在白干燥胼胝被发现。因此，它建议二蛋白质可能在种子胚胎的过程起一些重要作用(或体细胞胚)形成。

简介：Genomicresearchhasmadealargenumberofsequencesofnovelgenesorexpressedsequencetagsavailable.Toinvestigatefunctionsofthesegenes,asystemforconditionalcontrolofgeneexpressionwouldbeausefultool.Inducibletransgeneexpressionthatusesgreenfluorescentproteingene(gfp)asareportergenehasbeeninvestigatedintransgeniccelllinesofcotton(COT;GossypiumhirsutumL.),Fraserfir[FRA;Abiesfraseri(Pursh)Poir],Nordmannfir(NOR;AbiesnordmannianaLk.),andrice(RIC;OryzasativaL.Cv.Radon).Transgeniccelllineswereusedtotestthefunctionofthechemicalinducerdexamethasone.Inducibletransgeneexpressionwasobservedwithfluorescenceandconfocalmicroscopy,andwasconfirmedbynorthernblotanalyses.Dexamethasoneat5mg/Linducedgfpexpressiontothenearlyhighestlevel48haftertreatmentinCOT,FRA,NOR,andRIC.Dexamethasoneat10mg/LinhibitedthegrowthoftransgeniccellsinFRAandNOR,butnotCOTandRIC.Theseresultsdemonstratedthatconcentrationsofinducerforoptimuminduciblegeneexpressionsystemvariedamongtransgeniccelllines.Theinduciblegeneexpressionsystemdescribedherewasveryeffectiveandcouldbevaluableinevaluatingthefunctionofnovelgene.

简介：ＴＢｕｒｎＲｅｓｅａｒｃｈＩｎｓｔｉｔｕｔｅ，ＳｏｕｔｈｗｅｓｔｅｒｎＨｏｓｐｉｔａｌ，ＴｈｉｒｄＭｉｌｉｔａｒｙＭｅｄｉｃａｌＣｏｌｅｇｅ，Ｃｈｏｎｇｑｉｎｇ４０００３８，Ｃｈｉｎａ（ＣｈｉＬＸ，ＹａｎｇＺＣ，ＷａｎｇＸａｎｄＬｉＡ）Ｔｈｉｓｓｔ...

简介：ThepresentstudywasdesignedtodeterminetheeffectsofatraditionalChinesemedicine,calledQishenYiqiDroppingPillonchronichypoxia-inducedmyocardialinjury.ToestablisharatchronichypoxiamodeltobeusedintheevaluationofthetherapeuticeffectsoftheQishenYiqiDroppingPill,Sprague-Dawley(SD)ratswererandomlydividedintothreegroups:thecontrol,model,andtreatmentgroups(n=10pergroup).Theanimalswerehousedinaplexiglasscontainer.Thecontrolanimalswereundernormaloxygenconcentrationandthemodelandtreatmentgroupswereexposedtoairandnitrogenfor5weeks.TheratsinthetreatmentgroupwereorallyadministeredtheQishenYiqiDroppingpill(35mg·kg-1·d-1)for5weeks.Afterthetreatment,thecardiacfunctionandmorphologywereanalyzed,andtheexpressionlevelsofhypoxia-induciblefactor1α(HIF-1α)weredeterminedusingWesternblotting.Ourresultsindicatedthatthecardiacfunctionwasimpaired,cellapoptosiswasenhanced,andHIF-1αexpressionwasup-regulatedinthemodelgroup,comparedtothecontrolgroup.ThesechangeswereamelioratedbythetreatmentwiththeQishenYiqiDroppingPill.Inconclusion,QishenYiqiDroppingpillcanamelioratemyocardialinjuryinducedbychronichypoxia,improvecardiacfunction,anddecreasemyocardialcellapoptosis,whichmayprovideabasisforitsclinicaluseforthetreatmentofchroniccardiovasculardiseases

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简介：客观：为了探索完整的自动动物的可行性，建立动物的试验性的舱在normobaric/hypobarichypoxic和高二氧化碳环境当模特儿。方法：60只SPF班男SD老鼠被划分成二个组，20为normobaric，hypoxic条件和其它40为比重低於脑脊髓液，hypoxic条件。为每个组，我们检验了肺的动脉的压力和颈动脉由使用生理的多察觉者测量的老鼠的动脉的压力指示物，并且在结构观察了肺的脉管的变化。结果:有高二氧化碳环境的normobaric/hypobarichypoxic能支持肺的高血压的形成并且在肺的脉管的改变加速变化，并且支持恰好室的肥大。结论：临床的应用证明试验性的舱精确地观察了并且控制的动物。结果安全、可靠、可再现。舱能成功地与高二氧化碳环境在normobaric/hypobarichypoxic建立肺的高血压模型，并且由氧的缺乏引起以便学习许多循环和呼吸疾病的生理的机制，它为临床的研究提供了一个试验性的技术平台。