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简介：Heatshockprotein70(HSP70)maintainsCa~(2+)homeostasisinPC12cells,whichmayprotectagainstapoptosis;however,themechanismsofneuroprotectionareunclear.Therefore,inthisstudy,weexaminedCa~(2+)levelsinPC12cellstransfectedwithanexogenouslentiviralHSP70geneexpressionconstruct,andwesubsequentlysubjectedthecellstoischemia-hypoxia/reoxygenationinjury.HSP70overexpressionincreasedneuronalviabilityandATPaseactivity,anditdecreasedcellularreactiveoxygenspecieslevelsandintracellularCa~(2+)concentrationafterhypoxia/reoxygenation.HSP70overexpressionenhancedtheproteinandmRNAexpressionlevelsofsarcoplasmic/endoplasmicreticulumCa~(2+)-ATPase(SERCA),butitdecreasedtheproteinandmRNAlevelsofinositol1,4,5-trisphosphatereceptor(IP3R),therebyleadingtodecreasedintracellularCa~(2+)concentrationafterischemia-hypoxia/reoxygenation.TheseresultssuggestthatexogenousHSP70protectsagainstischemia-hypoxia/reoxygenationinjury,atleastinpart,bymaintainingcellularCa~(2+)homeostasis,byupregulatingSERCAexpressionandbydownregulatingIP_3Rexpression.

简介：AbstractBackground:Macrophages play an important role in renal ischemia reperfusion injury, but the functional changes of macrophages under hypoxia/reoxygenation and the related mechanism are unclear and need to be further clarified.Methods:The effects of hypoxia/reoxygenation on functional characteristics of RAW264.7 macrophages were analyzed through the protein expression detection of pro-inflammatory factors TNF-α and CD80, anti-inflammatory factors ARG-1 and CD206. The functional implications of C-X3-C motif chemokine receptor 1(CX3CR1) down-regulation in hypoxic macrophages were explored using small interfering RNA technology. Significance was assessed by the parametric t-test or nonparametric Mann-Whitney test for two group comparisons, and a one-way ANOVA or the Kruskal-Wallis test for multiple group comparisons.Results:Hypoxia/reoxygenation significantly increased the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and chemokine C-X3-C motif chemokine ligand 1 (CX3CL1)/CX3CR1 and inhibited the protein expression of M2-related anti-inflammatory factors ARG-1 and CD206 in a time-dependent manner in RAW264.7 cells. However, the silencing of CX3CR1 in RAW264.7 cells using specific CX3CR1-siRNA, significantly attenuated the increase in protein expression of TNF-α (P < 0.05) and CD80 (P < 0.01) and the inhibition of ARG-1 (P < 0.01) and CD206 (P < 0.01) induced by hypoxia/reoxygenation. In addition, we also found that hypoxia/reoxygenation could significantly enhance the migration (2.2-fold, P < 0.01) and adhesion capacity (1.5-fold, P < 0.01) of RAW264.7 macrophages compared with the control group, and CX3CR1-siRNA had an inhibitory role (40% and 20% reduction, respectively). For elucidating the mechanism, we showed that the phosphorylation levels of ERK (P < 0.01) and the p65 subunit of NF-κB (P < 0.01) of the RAW264.7 cells in the hypoxic/reoxygenation group were significantly increased, which could be attenuated by down-regulation of CX3CR1 expression (P < 0.01, both). ERK inhibitors also significantly blocked the effects of hypoxic/reoxygenation on the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and M2-related anti-inflammatory factors ARG-1 and CD206. Moreover, we found that conditioned medium from polarized M1 macrophages induced by hypoxia/reoxygenation, notably increased the degree of apoptosis of hypoxia/reoxygenation-induced TCMK-1 cells, and promoted the protein expression of pro-apoptotic proteins bax (P < 0.01) and cleaved-caspase 3 (P < 0.01) and inhibited the expression of anti-apoptotic protein bcl-2 (P < 0.01), but silencing CX3CR1 in macrophages had a protective role. Finally, we also found that the secretion of soluble CX3CL1 in RAW264.7 macrophages under hypoxia/reoxygenation was significantly increased.Conclusions:The findings suggest that hypoxia/reoxygenation could promote M1 polarization, cell migration, and adhesion of macrophages, and that polarized macrophages induce further apoptosis of hypoxic renal tubular epithelial cells by regulating of CX3CL1/CX3CR1 signaling pathway.

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：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：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

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。

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：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.

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：Sheng-Mai-San(SMS),awell-knownChinesemedicinalplantformula,iswidelyusedforthetreatmentofcardiacdiseasescharacterizedbydeficiencyofQiandYinsyndrome.Amousechronicintermittenthypoxia(CIH)modelwasestablishedtomimictheprimaryclinicalfeaturesofdeficiencyofQiandYinsyndrome.MiceexperiencedCIHfor28days(nadir7%topeak8%oxygen,20minperday),resultinginleftventricle(LV)dysfunctionandstructureabnormalities.AfteradministrationofSMS(0.55,1.1,and5.5g·kg-1·d-1)forfourweeks,improvedcardiacfunctionwasobserved,asindicatedbytheincreaseintheejectionfractionfromtheLVonechocardiography.SMSalsopreservedthestructuralintegrityoftheLVagainsteccentrichypotrophy,tissuevacuolization,andmitochondrialinjuryasmeasuredbyhistology,electronmicroscopy,andultrasoundassessments.Mechanistically,theantioxidanteffectsofSMSweredemonstrated;SMSwasabletosuppressmitochondrialapoptosisasindicatedbythereductionofseveralpro-apoptoticfactors(Bax,cytochromec,andcleavedcaspase-3)andup-regulationoftheanti-apoptosisfactorBcl-2.Inconclusion,theseresultsdemonstratethatSMStreatmentcanprotectthestructureandfunctionoftheLVandthattheprotectiveeffectsofthisformulaareassociatedwiththeregulationofthemitochondrialapoptosispathway.

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简介：调查在在hypoxic下面的gliomaangiogenesis的受体(u-PA/u-PAR)系统调节的尿激类型plasminogenactivator/urokinase-typeplasminogen的角色的目的，我们在导致的组织缺氧上学习了调节glioma的媒介的效果在人的象endothelial一样ECV304房间增长，apoptosis，在vitro的绳索形成和u-PA/u-PAR表示的变化。方法MTT试金被用来在房间增长检验变化。房间apoptosis被染色的Hoechst33258分析。Matrigel像绳索的形成试金被用来在vitro评估ECV304房间的angiogenesis能力。u-PA/u-PARmRNA的表情被量的即时RT-PCR检测。结果组织缺氧禁止了ECV304房间增长并且导致了房间apoptosis。当不normoxic调节了部分堵住的U251glioma房间的媒介(N厘米)时，Hypoxic调节了媒介(H厘米)ECV304房间增长和apoptosis上的组织缺氧的效果。U251glioma房间的H厘米也支持了在matrigel上播种的ECV304房间的绳索形成。当u-PA或u同等monoclonal抗体被增加进ECV304房间culturing媒介时，绳索形成能力部分被禁止。U251glioma房间的H厘米在ECV304房间导致了uPA和uPAR表示。这些建议那个u-PA/u-PAR系统的结论被hypoxicmicroenviroment涉及gliomaangiogenesistrigged。

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