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简介：Thispaperaimstotheresearchoftheimpactoffluidshearstressontheadhesionbetweenvascularendothelialcellsandleukocyteinducedbytumornecrosisfactor-α(TNF-α)bymicrofliudicchiptechnology.Microfluidicchipwasfabricatedbysoftlithograph;Endothelialmicrofluidicchipwasconstructedbyoptimizingtypesoftheextracellularmatrixproteinsmodifiedinthemicrochannelandcellincubationtime;humanumbilicalveinendothelialcellsEA.Hy926linedinthemicrochannelwereexposedtofluidshearstressof1.68dynes/cm~2and8.4dynes/cm~2respectively.Meanwhile,adhesionbetweenEA.Hy926cellsandleukocytewasinducedbyTNF-αunderaflowcondition.EA.Hy926cellculturedinthestaticconditionwasusedascontrolgroup.Thenumbersoffluorescently-labeledleukocyteinmicrochannelwerecountedtoquantizetheadhesionlevelbetweenEA.Hy926cellsandleukocyte;cellimmunofluorescencetechniquewasusedtodetecttheintercellularadhesionmolecule(ICAM-1)expression.TheconstructedendothelialmicrofluidicchipcanaffordtothefluidshearstressandrespondtoexogenousstimulusofTNF-α;comparedwiththeadhesionnumbersofleukocyteincontrolgroup,adhesionbetweenEA.Hy926cellsexposedtolowfluidshearstressandleukocytewasreducedunderthestimulusofTNF-αataconcentrationof10ng/ml(P<0.05);leukocyteadhesionwithEA.Hy926cellsexposedtohighfluidshearstresswasreducedsignificantlythanEA.Hy926cellsincontrolgroupandEA.1Hy926cellsexposedtolowfluidshearstress(P<0.01);theregulationmechanismoffluidshearstresstotheadhesionbetweenEA.Hy926cellsandleukocyteinducedbyTNF-αwasthroughthewayofICAM-1.Theendothelialmicrofluidicchipfabricatedinthispapercouldbeusedtostudythefunctionsofendothelialcellinvitroandprovideanewtechnicalplatformforexploringthepathophysiologyoftherelatedcardiovascularsystemdiseasesunderaflowenvironment.

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简介：BACKGROUND:Culturesfrommultipleportionsofumbilicalcordbloodmesenchymalstemcellshavebeenshowntoundergomorerapidproliferationandattachmentthansingleportions.OBJECTIVE:Toobservegrowthofbasicfibroblastgrowthfactor(bFGF)-inducedculturesofhumanamnion-derivedmesenchymalstemcells(AMSCs)anddifferentiationintoneuronal-likecells.DESIGN,TIMEANDSETTING:Comparativeobservation.ThestudywasperformedattheLaboratoryofMicrobiologyandImmunology,BasicMedicalSchoolofZhengzhouUniversityfromJanuarytoMay2008.METHODS:Amniafromfull-term,uterine-incisiondeliveryweredonatedby12healthywomen.AMSCswereobtainedbycellseparationandculturetechniques,andwerepassagedandinducedbybFGF.Fromthethirdpassage,atotalof1mLAMSCs,atadensityof1.0×10~4/mL,wasseparatelyharvestedfromsixsamples,whichservedasgroupA.Atotalof1mLAMSCs,atadensityof1.0×10~4/mL,washarvestedseparatelyfromtheremainingsixsamples,whichservedasgroupB.Atotalof0.5mLfromthesixsamplesofgroupAand0.5mLfromthesixsamplesofgroupBwerecombinedtoformgroupC.MAINOUTCOMEMEASURES:Differencesincellquantityamongthethreegroupswerecomparedbycellquantificationand3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide(MTT)analysis.Expressionofaglialcellmarker,neuron-specificenolase,andnestinwasdetectedinthethreegroupsbyimmunocytochemistry.RESULTS:CellquantificationandMTTanalysisoflivecells,aswellasAMSCabsorbance,weresignificantlygreateringroupCcomparedwithgroupsAandBat18daysofculture(P<0.05),andnosignificantdifferencewasobservedbetweengroupsAandB.Glialfibrillaryacidicprotein,neuron-specificenolase,andnestinwereexpressedinallgroupsfollowingbFGFinduction.CONCLUSION:MixedAMSCculturespromotedproliferation,andbFGF-inducedAMSCsdifferentiatedintoneuronal-likecells.

简介：Objective:Squamousesophagealcarcinomaishighlyprevalentindevelopingcountries,especiallyinChina.TuBeiMu(TBM),atraditionalfolkmedicine,hasbeenusedtotreatesophagealsquamouscellcarcinoma(ESCC)foralongterm.tubeimosideI(TBMS1)isthemaincomponentofTBM,exhibitinggreatanticancerpotential.Inthisstudy,weinvestigatedthemechanismofTBMS1cytotoxiceffectonEC109cells.Methods:Comparativenuclearproteomicapproachwasappliedinthecurrentstudyandweidentifiedseveralalteredproteinspots.Furtherbiochemicalstudieswerecarriedouttodetectthemitochondrialmembranepotential,cellcycleandcorrespondingproteins’expressionandlocation.Results:SubcellularproteomicstudyinthenucleusfromEC109cellsrevealedthatalteredproteinswereassociatedwithmitochondrialfunctionandcellproliferation.FurtherbiochemicalstudiesshowedthatTBMS1-inducedmoleculareventswererelatedtomitochondria-inducedintrinsicapoptosisandP21-cyclinB1/cdc2complex-relatedG2/Mcellcyclearrest.Conclusions:ConsideringtheconventionalapplicationofTBMinesophagealcancer,TBMS1thereforemayhaveagreatpotentialasachemotherapeuticdrugcandidateforESCC.

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简介：介绍Cystone是为各种各样的尿混乱在印度使用的同意的Ayurvedicpolyherbal专卖药品，包括urolithiasis。试图在urolithiasis把Cystone的保护的效果与导致hyperoxaluria的氧化应力和钙盐水晶免职作比较。方法乙烯乙二醇(例如)(0.75%，V/V)在喝，水被给老鼠28天与Cystone(500和750mg/kg身体重量)的同时的处理导致urolithiasis，并且urolithiasis的各种各样的尿风险因素和抗氧化剂标记被估计。例如结果处理导致增加的尿体积和降低的尿pH与盐的增加的尿排泄一起，在未经治疗的动物的钙和磷酸盐。这些变化在未经治疗的老鼠的肾引起了广泛的钙盐水晶免职，增加的类脂化合物peroxidation和抗氧化剂酶(草皮，过氧化氢酶和GPx)的减少的活动。Cystone阻止了这些hyperoxaluric表明并且在两剂量在对待的老鼠禁止了钙盐水晶免职。结论Cystone治疗由改进肾的织物抗氧化剂地位和多尿对导致hyperoxaluria的氧化应力和钙盐水晶免职提供保护。

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简介：AbstractBackground:The transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/β-catenin pathway plays an important role, notably with regard to TGF-β1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-β1-induced EMT, although the underlying mechanism have not yet been fully elucidated.Methods:Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-β1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and β-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results:Both 1α, 25(OH)2D3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001.Conclusion:1α, 25(OH)2D3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.

简介：导致骨胶原的关节炎(中央情报局)是一个动物模型，它非常在致病和病理类似于人的风湿性关节炎(RA)。证据建议T淋巴细胞或他们的功能的抑制能减轻关节炎的前进。那么arthritogenicT房间受体(TCR)的管理编码病原的TCRV可变区域的可变区域肽或DNA疫苗可以为对自体免疫的疾病设计特定的免疫疗法提供有用信息。热吃惊蛋白质(HSP)有提起antigenicimmunogenicity和HSP70的功能对关节炎有保护的效果。我们以前在中央情报局老鼠的关节表明了病原的占优势的T房间受体V5.2和V8.2clonotypes的存在。在这研究，我们构造了recombinant真核细胞的表示向量pTARGET-TCRV5.2/8.2-HSP70，并且在中央情报局老鼠上评估了他们的保护的效果。保护的效果被注射这些recombinantDNA在中央情报局老鼠观察疫苗，能减轻关节炎索引，减少在浆液的IFN-C和古怪抗体的层次，和增加IL-4的层次。病理学的变化不象在控制中央情报局老鼠观察的那些一样严肃。与二支联合疫苗注射的老鼠比与单个疫苗管理的中央情报局老鼠显示出更好保护的效果。这些结果证明recombinantDNA疫苗pTARGET-TCRV5.2-HSP70和pTARGET-TCRV8.2-HSP70能显著地减轻中央情报局老鼠的关节炎的症状，并且如果这二支疫苗在联合被使用，更好保护的效果能被完成。

简介：AbstractBackground:We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice.Methods:Intestinal epithelial CCL7 overexpression (CCL7tgIEC) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing.Results:We found that the CCL7tgIEC mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7tgIEC mice compared to WT. Furthermore, HFD-fed CCL7tgIEC mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis.Conclusions:Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.

简介：OurpreliminarystudiesconfirmedthatanactiveprincipleregionofBuyangHuanwudecoction,comprisingalkaloid,polysaccharide,aglycon,glucosideandvolatileoil,caninducebonemarrowmesenchymalstemcelldifferentiationintoneurons.Mitogen-activatedproteinkinasesignalingwasidentifiedasoneofthekeypathwaysunderlyingthisdifferentiationprocess.Thepresentstudyshowsphosphorylatedextracellularsignal-regulatedproteinkinaseandphosphorylatedp38proteinexpressionwasincreasedafterdifferentiation.Cellularsignalingpathwayblockingagents,PD98059andSB203580,inhibitedextracellularsignal-regulatedproteinkinaseandp38inmitogen-activatedproteinkinasesignalingpathwaysrespectively.mRNAandproteinexpressionoftheneuronalmarker,neuronspecificenolase,andneuralstemcellmarker,nestin,weredecreasedinbonemarrowmesenchymalstemcellsaftertreatmentwiththeactiveprincipleregionofBuyangHuanwudecoction.Experimentalfindingsindicatethat,extracellularsignal-regulatedproteinkinaseandp38inmitogen-activatedproteinkinasesignalingpathwaysparticipateinbonemarrowmesenchymalstemcelldifferentiationintoneuron-likecells,inducedbytheactiveprincipleregionofBuyangHuanwudecoction.

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简介：AbstractBackground:To date, there is only scare evidence characterizing the temporal features and progression of metabolic dysfunction in high-fat diet (HFD)-fed obese mice. Hence, its specific pathogenesis remains unclear.Methods:Sixty 6-week-old male C57BL/6J mice were randomly divided into HFD and control diet (CD) groups and sacrificed at 1, 5, 9, 13, 17, and 21 weeks, respectively. At weekly intervals, intraperitoneal glucose tolerance testing (IPGTT) and intraperitoneal insulin tolerance testing (IPITT) were performed in both groups. A detailed time course in HFD-fed mice was investigated by evaluating the initiation of glucose homeostasis impairment, dyslipidemia, systemic insulin sensitivity, monocyte chemoattractant protein-1 (MCP-1) levels, epididymal white adipose tissue (eWAT) expansion, macrophage content changes, proinflammatory (M1)/anti-inflammatory (M2) macrophage imbalance, lipid accumulation in the liver, and β-cell morphometry in the pancreas.Results:In the HFD group, progressive weight gain and impairments in glucose metabolism (elevated fasting blood glucose and area under the curve (AUC) of IPGTT) were observed from the 3rd week, and a significantly elevated AUC of IPITT was first detected after week 7 of HFD feeding. As for dyslipidemia, after 9 weeks of feeding, the low-density lipoprotein cholesterol level and total cholesterol level in HFD group were significantly higher than those in the CD group (all P < 0.05), whereas no significant differences were shown in triglyceride level. Adipocyte size increased significantly in the HFD group in the 1st week, a phenotypic switch in eWAT from anti-inflammatory (M2) to pro-inflammatory (M1) macrophages was observed in the 5th week, and the metabolic inflammation was distinct in eWAT in the 9th week. Additionally, liver steatosis was considerably obvious at the 17th week and pancreatic β-cell morphometry did not change during 21 weeks of HFD feeding.Conclusion:The eWAT expansion was detected early in HFD-induced obese mice, which occurred prior to obvious insulin resistance.

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简介：BACKGROUND:Ithasbeendemonstratedthattransforminggrowthfactor-β(TGF-β)andbrain-derivedneurotrophicfactor(BDNF)caninducestemcelldifferentiationintoneuron-likecells.OBJECTIVE:ToinvestigatetheefficacyofTGF-βandBDNFatinducingthedifferentiationofadultratbonemarrowstromalcells(BMSCs)intoneuron-likecells,bothincombinationoralone.DESIGN,TIMEANDSETTING:AcomparativeobservationexperimentwasperformedattheDepartmentofOrthopedics,FirstAffiliatedHospitalofLiaoningMedicalUniversitybetweenOctober2007andJanuary2008.MATERIALS:TGF-βandBDNFwerepurchasedfromSigma,USA;mouseanti-ratneuronspecificenolase,neurofilamentandglialfibrillaryacidicproteinwerepurchasedfromBeijingHMHLBiochemLtd.,China.METHODS:BMSCswereisolatedfromratsaged4weeksandincubatedwithTGF-β(1μg/L)and/orBDNF(50μg/mL).MAINOUTCOMEMEASURES:Expressionofneuron-specificenolase,neurofilamentandglialfibrillaryacidicproteinweredeterminedbyimmunocytochemistry.RESULTS:BMSCsdifferentiatedintoneuron-likecellsfollowinginductionofTGF-βandBDNF,andexpressedbothneuron-specificenolaseandneurofilament.ThepercentofpositivecellswassignificantlygreaterinthecombinationgroupthanthoseinducedwithTGF-βorBDNFalone(P<0.01).CONCLUSION:TreatmentofBMSCswithacombinationofTGF-βandBDNFinduceddifferentiationintoneuron-likecells,withtheinductionbeingsignificantlygreaterthanwithTGF-βorBDNFalone.

简介：Capsaicin(trans-8-methyl-N-vanillyl-6-nonenamide)isthemaincomponentinhotpeppers,includingredchilipeppers,alapenos,andhabanero,belongingtothegenusCapsicum.Capsaicinisapotentantioxidantthatinterfereswithfreeradicalactivities.Inthepresentstudy,thepossibleprotectiveeffectofcapsaicinwasstudiedagainstmethylmethanesulphonate(MMS)inducedtoxicityinthirdinstarlarvaeoftransgenicDrosophilamelanogaster(hsp70-lacZ)Bg~9.ThethirdinstarwasallowedtofeedonthediethavingdifferentdosesofcapsaicinandMMSseparatelyandincombination.TheresultssuggestedthattheexposureofthirdinstarlarvaetothediethavingMMSaloneshowedsignificanthsp70expressionaswellastissueDNAandoxidativedamage,whereasthelarvaefeedonthediethavingMMSandcapsaicinshowedadecreaseinthetoxiceffectsfor48-hofexposure.Inconclusion,capsaicinshowedadose-dependentdecreaseinthetoxiceffectsinducedbyMMSinthethirdinstarlarvaeoftransgenicDrosophilamelanogaster.

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简介：客观：为了调查抵抗和颠倒的机制，在导致cisplatin的multidrug抵抗ligustrazine和cyclosporinA完成卵巢的癌症房间线3Ao/cDDP。方法：用每周期在30mgcisplatin从临床的化疗计算的相应剂量，我们建立了3Ao/cDDP，3Ao每次在10渭g/ml在常规间隔并且反复暴露了到cisplatin的高级集中24个小时。LRP，MRP，P-gp，GST蟺和TopoII的表情是与FCM检测的份量上。为药抵抗颠倒，没有cytotoxicity，cyclosporinA和ligustrazine在最大的剂量单身地或在联合被管理。抑制率被MTT试金决定。结果：3Ao/cDDP在4.5个月以后被建立，与抵抗因素1.6它类似于临床的抵抗度。MRP和P-gp的低表示层次在3Ao和3Ao/cDDP被发现(P>0.05)，并且在3Ao/cDDP的LRP和GST蟺表示层次比在3Ao的那些显著地高(P<0.005andP<0.05，分别地)，并且在3Ao/cDDP的TopoII显著地更低对3Ao(P<0.05)。cDDP的抑制率是20.807卤0.015%，加ligustrazine的cDDP27.421卤0.07%(P>0.05对cDDP)，加cyclosporinA的cDDP49.635卤0.021%(P<0.01对cDDP)，并且加ligustrazine和cyclosporinA的cDDP58.861卤0.014%(P<0.01对cDDP)。结论：3Ao/cDDP，由cisplatin导致了并且由为上皮的卵巢的癌症模仿临床的化疗的特征建立了，是为cisplatinresistanceinvitro的调查的一个理想的模型。在3Ao/cDDP的Cisplatin抵抗能被说明为由更高的LRP，GST蟺和更低的TopoII表示并且没与MRP或P-gp被联系。Ligustrazine没在A能颠倒的cisplatin抵抗，而是cyclosporin上有重要颠倒效果抵抗有效地。

简介：ThepresentstudyestablishedachronicexperimentalautoimmuneencephalomyelitismodelinC57BL/6miceinducedbymyelinoligodendrocyteglycoproteinpeptidesandcompleteFreund'sadjuvant.Onsetlatencywas12days,withanincidencerateof100%.Neuropathologicalcharacteristicsincludedperivascularinflammatorycellinfiltration,demyelination,neuronaldegeneration,andaxonaldamagewithincerebralandmyelicwhitematter.Electronmicroscopyrevealedswollenmitochondria,completeorgandisappearance,andfusedorbrokenmyelinsheathstructure,whichwereaccompaniedbymyelinsheathreconstruction.Moreover,axonaldamagewasnotconsistentwithdemyelinationdistribution,andseverityofaxonaldamagedidnotcorrelatewithdemyelination.Resultssuggestedthataxonaldamageinanexperimentalautoimmuneencephalomyelitismodelisnotsecondarytoinflammatorydemyelination.