1、1 SCI写作高大上句型写作高大上句型1000例例701800701、In addition to its role in.accumulating evidence suggests that hypoxiaparticipatesinthedevelopmentofXXX702、Despitetheinvivoevidencesuggestingthat.therolemoderatehypoxicmilieuplaysinvascularinflammationandatherogenesisremainsobscure.703、Thepresentstudyusedprimarymou
2、seperitonealmacrophagestotestthehypothesis that a physiologically relevant level of tanshinone IIA nfluencesmacrophageexpressionofatherosclerosisassociatedgenesviaactivationoftheAktand_cateninpathways.704、XXXplayscentralrolesininflammatoryailments.705、Interestingly,recentevidencesuggeststhat.Accumul
3、atingevidencehasfurtherdemonstratedthat.;.alsofunctionsinvariousotherfundamentalbiologicalandpathologicalprocessessuchasinnateimmunityandinflammation706、Additionally,wedemonstrateinhumanmacrophagesthat;.etalrecentlyreportedthat.707、Thepresentstudydemonstratesthat.mayfurtheramplifytheinflammatorymili
4、eu.Our observations expand the mechanistic understanding of macrophageactivationandprovidenewinsightintothepathogenesisofchronicinflammatorydiseases.708、ThepresentstudydemonstratesthatAktactivationinhumanmonocytederivedmacrophagesbychronicmoderatehypoxiacausesinactivationofGSK3andnuclearaccumulation
5、ofcatenin.Collectively,thesestudiesindicatethatAktplaysapivotalroleintheproinflammatoryphenotypeofmacrophages,providinganewmechanisminmacrophagebiology,709、DespiteevidencefortheroleofAktincateninaccumulation.couldalsomediatetheseresponses,asubjectforfuturestudy.710、Biologicalmechanismsunderlying.dif
6、fer.2 711、Largescaleclinicalstudieshavedemonstratedthatsimvastatin,anHMGCoAreductaseinhibitor,andlosartan,anAT1receptorblocker,preventandretardtheprogressionofcoronaryheartdisease.712、Themechanismsofthisbenefitmayrelatetotheabilityofthesetherapiestoreduce713、Thepresentstudyisthefirstreportdemonstrat
7、ingthat.714、Thisworklendssupportfordevelopingimmunizationstrategiestoboostnaturalantibodyprotectionandpotentiallylimitatherosclerosis.715、Overall,ourdataprovidethefirstdirectevidencethat716、Interestingly,itisnoteworthythat,alimitationofourstudyisthat717、Takentogether,theseobservationsindicatethat.ex
8、tendourobservationsto.andsuggestthatalternationsproducedinwithcombinedtherapymayhavefunctionalsignificance.718、However,several recent examples have dramatically underlined thatextrapolationofsurrogatemarkersofAStoactualcardiovasculareventsisrisky.719、The presentstudyextendsourpriorobservationsThepre
9、sentresultsareconsistentwith.importantly,thebenefitwasderivedprimarilyfrom.720、Thepresentstudyextendsandcomplementstheseobservationsbyfocusingontherelative.with721、Boosting HDLC is a current strategy for preventing clinical events.Wbinedstatin/tanshinoneiiAtherapypartiallyreverses.Ourobservations ra
10、ised the possibility that.could provide insight into therapeuticefficacyofantiASinterventions.722、We hypothesized that combination therapy with a statin/Tanshinone,amonomerisolatedfromtraditionalChinesemedicineTanshen,wouldmodifylipidprofileandplaquestabilityandthesemodificationsmightprovideinsighti
11、ntoitsanti3 ASandantiinflammatoryproperties.723、Totestthisproposal,weusetoinvestigatetheimpactofintensivelipidlowering withTSourobservationsalsoindicatethatcombinedtherapy.724、ItisnowwidelyappreciatedthatplaqueruptureisanimportantcomponentofACS,inadysfunctionalstate.725、Thearticlebyetalelucidateimpo
12、rtantpotentialmechanismswherebyOXLDLcontributestocellulardysfunctionviaERstressthatisultimatelymanifestinplaquerupture.726、Insupportofthisconcept,ourinvestigationoftheeffectsofonrevealedthat.An important role of.has also been demonstrated in several diseases,includingand727、Studiesofalsosupportthere
13、levanceofAtoBandCinadvancedatheroscleroticplaques,however,itisstillunclearwhetherhasaroleinplaquerupture.728、Unfortunately,theabsenceofasuitableanimalmodelthatresemblinghumanatherosclerosishasgreatlyhinderedtheinvestigationofthemolecularmechanismsofplaqueruptureandevaluationoftheeffectsofplaquestabi
14、lizingagentsinvivo729、Thefindingsinthepresentstudyunderlinetheimportanceofin.730、Thereareseverallimitationstothepresentstudy.canbeusedinfuturestudiestofurtherourunderstandingof.731、Multiplemechanismshavebeenpostulatedforthedevelopmentofdiabeticnephropathy,including.oxidativestress,inflammation,andhe
15、modynamicchanges.732、Therefore,multitargetedtherapeuticinterventionsshouldberequiredforDN.733、Recently,ithasbeenreportedthatseveralherbssuchas.havemultitargetedatheroprotectiveeffectinAS.Inthepresentstudy,wedemonstratedthemultitargetedrenoprotectiveeffectsofTanshinoneIIAonAS734、Tothebestofourknowled
16、ge,thisisthefirstreportshowingthat.735、Moreevidenceforthisconceptcomesfrommanybasicandclinicalobservations.4 736、playafundamentalroleinplaqueformationandstability.737、Asreportedinpreviousstudies,738、Theexcellenttechnicalsupportofisgreatlyappreciated.Partofthisworkwillbeincludedinthedoctoralthesisof.
17、739、ItmaybemechanisticallyinvolvedintheplaquedisruptionthatproducesACS.740、Although clinical appreciation of.has since increased significantly,themechanismbywhichremainsunclear.741、Therefore,it is conceivable that.Insight that drawn from animal modelsthat.supportthishypothesis.742、Aconsensusemergest
18、hattheseprocessesareindelicatebalanceandhavepotentiallyopposingrolesinplaqueprogressionanddestabilization.743、contributeaprovocativearticleproposingahithertounappreciatedroleofHO1COpathwayinatherogenesis.744、Themechanismofniacinloweringofaisuncertainbutappears,unlikelytobemediatedbysuppressionof.745
19、、This work,as well as related findings from other groups,provides a firmpathophysiological foundation for potential involvement of Chlamydia inatherosclerosisandlocallipoproteinmetabolismwithinatheroma.746、WecurrentlyviewtheevidenceforaroleofChlamydiainatherosclerosisasfollows:747、A concordant data
20、set suggests that.in agreement with Dr ShorsobservationsPlausiblebiologicalmechanismsforapotentiationofatherogenesisby748、We thank Dr Shor for his intriguing comments regarding the role of inatherosclerosis.WeagreethatStrongevidencelinksandInconclusion,weshareDrShorsfascinationwiththepossibleroleofC
21、hlamydiapneumoniaeinatherogenesis.Webelievethat.5 749、Overlastdecade,appreciationoftheroleof inflammationinatherosclerosishasburgeoned.750、Although.,substantial advances in basic and experimental science haveilluminated the role of inflammation and the underlying cellular and molecularmechanismsthat
22、contributetoatherogenesis751、Compellingevidencefortheimportanceofinflammationandatherosclerosisatboththebasicandclinicallevelhasevolvedinparallel.752、Accumulating data indicate that insights gained from the link betweeninflammationandatherosclerosiscanyieldpredictiveandprognosticinformationofconside
23、rableclinicalutility.753、Thecurrentnotionthatinflammationandimmuneresponsecontributetoatherogenesishasgarneredincreasedinterest.754、Ourcurrentconceptsrecognizethebiologicalattributesoftheatheromaaskeydeterminantsofitsclinicalsignificance.Thisreviewwillweavetogetherlaboratoryandclinicaladvancestoprov
24、ideanupdateoninflammationinatherosclerosis.755、Duringrecentyears,experimentsingeneticallyalteredmicehavelentfurthersupporttothehypothesisthat756、Inclinicalstudies,itwasobservedthatclinicalinterventionstudiesshowedthat.757、However,themechanismbywhichthisoccursisnotclearlydefined.758、Thisisthefirstrep
25、orttodemonstratethat,inamodelofatherosclerosis,.759、Thisperceptionisfosteredbyastudyevaluatingdenovoatherogenesisinexperimentalmurineatherosclerosis,whichshowed.760、However,several large studies evaluating the role offailed to show anassociation betweenand prevalence of AS,suggesting that.Thus,the r
26、oleofremainsundefined.Fromthesedata,wehypothesizedthat.761、Theseresultsidentifyanewfunctionofthecoagulationsystem,resultingin6 enhancedplaquestabilityduringdenovoatherogenesis.762、Plateletaggregationplaysacriticalroleinmyocardialinfarctionandstroke;however,theroleofplateletsecretioninatherosclerotic
27、vasculardiseaseispoorlyunderstood.Therefore,weexaminedthehypothesisthat763、Previousstudieshaveestablishedthat.Inconfirmationofthesefindings,wefoundthatXXX764、Toexaminetheeffectof.on.Micewereplacedonahighfatdietbeginningat6weeksofagetoacceleratethedevelopmentofatheroscleroticlesions.765、Microscopicex
28、aminationconfirmedthat.Consistentwiththisnotion,wefoundthat.and atherosclerotic remodeling were markedly attenuated in the injuredvesselsfrommicewith766、Inneointimalsizeandcontentofactinpositivesmoothmusclecells,CD45positiveleukocytes,andMac3positivemacrophages.767、Itwillbeimportanttofurtherelucidat
29、ethesemechanismsandtoexplorethepotentialutilityof.asatherapeutictargetinatherothromboticdisease.768、Basedonthesedata,wehaverecentlyinvestigatedwhetherOurpreviousfindingshaverevealedahithertounknowneffectof,suggestinganewdirectroleofadiposetissueinthepathogenesisof769、Basedonthisinitialwork,wehavefur
30、thercharacterized.Together,theseclinical and experimental data support a key role forIn the present study,weinvestigatedtheroleof770、RecentstudiesfromanimalmodelssupportanovelroleforMorerecently,Theprecise molecular mechanism of the cardiodepressive effect of.is not yetunderstood.771、Toaddressthepot
31、entialroleofinatherogenesis,wefirstinvestigatedtheexpressionthenstudiedtheeffectof772、.showedamorepronouncedinflammatoryprofileinthevascularwallas7 detectedbyqPCR773、ExperimentalevidenceontheroleofCRPinatherogenesisandvasculardiseaseismixed/controversial.774、ToevaluatetheexpressionofPTX3duringathero
32、genesis,weperformedatimecourseexperimentinApoEKOmicefedachowdietandinvestigatedPTX3mRNAandproteinexpressionintheaortas.Inagreement,775、The most important finding of this study was the observed interactionbetweenand776、THEmechanismsunderlyingtheattenuationofAngIIinducedactionsbySTSremainsanareaofcons
33、iderableinterest.777、XXXplayapotentiatingroleinthegrowthprocessbyactivatingseveralsignalingpathways.778、Anotherquestionarisingfromthepresentstudyis:Whydosetreatmentfailtosuppress angIIinduced.in myocytes?One possibility is that/one possibleexplanationforthisactionisthat.779、Theexpressionof.predomina
34、teoverexpressionlevel.780、BecauseCaisthoughttobeanimportant,themodulationofangIImediatedchangesinprovidesarationaleforthereversalofsomeangIIeffectsbySTS.781、Anincreasingnumberofpublishedstudiesareinvestigatingthepleiotropiceffectsofstatins,withdivergingresults.Theseresultsstresstheneedforalargermult
35、icenterstudytoshedmorelightonthisimportantmechanisticissue782、Wereadwithgreatinteresttherecentarticleby。783、This investigation has resulted in several novel observations.First,to ourknowledge,ourfindingssuggestforthefirsttimeinvivothatFurthermore,ourdatasuggestthat.784、Acriticalassessmentofthedataga
36、theredinthisresearchwouldsuggestthattheprotectiveeffectsof.wereprimarilyattributedtothedownregulationof.8 785、TACEsiRNAhadnolongtermprotectiveeffectonhypertensionineitherSHRsorAngIIinfusedmice.However,wecannotexcludethatTACEsiRNAtreatmentcouldhaveashorttermortransientprotectiveeffectthatwasnonethele
37、ssinsufficienttopreventthedevelopmentofhypertensioninbothSHRsandAngIIinfusedmice.786、BecauseofthecomplexityoftheeffectsofTACEinhibitiononthetranscriptionofmultiplegenes,dedicatedstudiesarewarrantedtofurtherdissectthemechanismoftheshorttermrolesofTACEintheregulationofbloodpressureofhypertension787、Ho
38、wever,ourlongtermdataareconsistentwithpreviousresearchshowingthatthepharmacologicalinhibitionofdoesnotdecreasesystolicbloodpressureinAngIIinfusedmice.Ourlongtermdataarealsoinagreementwithpreviousresearchshowingthatpharmacologicalblockadedoesnotprotectmicefromagonistinducedhypertension.788、Previousst
39、udieshavefoundthat.Recently,anovelroleforADAM12wasreportedinfacilitatingactivationoftransforminggrowthfactorsignalingthroughSmads,whichisthemainpathwaymediatingthedevelopmentofagonistinducedfibrosis.789、Similarly,MMP2hasbeenshowntopromotethusfacilitatingSmadsignaling.790、Previousworkalsoshowedthat.A
40、lthoughthepotentialinvolvementofTACEin cardiac hypertrophy and fibrosis is suggested by previous research.TACEinvolvementintheseprocesseshasnotbeendemonstratedinvivo.791、ThisstudyhasidentifiednovelandsignificanteffectsofTACEsiRNAonbothcardiachypertrophyandfibrosisinvivo.Ourobservationsprovidethefirs
41、tinvivoevidencethatTACEexpressionregulatesthedevelopmentofcardiachypertrophyandfibrosisand,assuch,substantiallyexpandspreviousresearch.Takingourfindingstogether with previous investigations,we suggest that an overabundance ofvasoconstrictiveagonists(asoccursinhypertensivedisorders)couldposttranscrip
42、tionallyenhancetheactivityof9 792、Despiteextensiveresearch,aninteractionamongthepathwaysofTACE,ADAM12,andMMP2hasneverbeenidentified.Therefore,anovelfindingofthisresearchhasbeentheobservationthatbaselinegeneexpressionlevelsofTACEandADAM12aretranscriptionallyconnected,althoughfurtherresearchisnecessar
43、ytodissectthetranscriptionalpathwayslinkingthesemetalloproteinases.Togetherwithpreviouslyreported.793、ThisnotionissupportedbyourstudiesbothinmicewithagonistinducedcardiachypertrophyandinSHRs,amodelwherecardiachypertrophyislikelysignaledbymultipleagonists794、Thesecurrentfindingshavetherapeuticpotenti
44、alinhypertensiveheartdisease.Ourdatasuggestthat795、Thisisconsistentwiththeobservationby.etalthat.Inaddition,recentdatafrometal.,coupledwith.islargelyresponsibleforenhanced.796、TheseobservationsareinlinewithourpreviousstudiesdemonstratingthatItremainstobeelucidatedinwhich797、Multiplemechanismshavebee
45、npostulatedforSoitisalsoplausiblethatthebeneficialeffectoftanshinoneIIAinthetreatmentofcardiacfibrosiscouldrelatetothesuppressionofangIImediatedcellularresponse.798、Apossibleexplanationfortheresultsisthat.littleinformationexistswhetherthesameappliestothelatter,ie,whether799、Thereisextensiveevidencethatconsistentlyaccompanies.800、This has deleterious consequences on the severity of hypertension itself,because.
