宫颈癌患者血浆中E-钙黏着蛋白基因启动子区的甲基化状态

肿瘤细胞可以释放DNA进入患者的血浆/血清中,并可作为无创伤性诊断肿瘤的标记物。采用甲基化特异性聚合酶链式反应(MS-PCR)结合亚硫酸盐测序法对151例宫颈癌患者血浆和对应的30例组织中E-钙黏着蛋白基因启动子区甲基化状态进行检测,并与化学发光法检测患者血清的鳞状上皮癌抗原(SCC)相比较,发现此方法的灵敏度为40.39%,特异性为100%,正确性为49.72%,血浆和组织的符合率为76.67%。宫颈炎、子宫肌瘤和正常人的血浆中均未检测到甲基化状态的存在。随着临床分期和组织学分级的增加,E-钙黏着蛋白基因甲基化的检出率也在逐渐增加,与SCC结果相比,MS-PCR方法在早期和恶性度高的宫颈癌中的诊断效果良好。使用E-钙黏着蛋白基因作为分子标记可以对宫颈癌患者进行无创伤性早期诊断和预后的评估。     

Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine

The multiple transmembrane protein Niemann-Pick C1 like1 (NPC1L1) is essential for intestinal cholesterol absorption. Ezetimibe binds to NPC1L1 and is a clinically used cholesterol absorption inhibitor. Recent studies in cultured cells have shown that NPC1L1 mediates cholesterol uptake through vesicular endocytosis that can be blocked by ezetimibe. However, how NPC1L1 and ezetimibe work in the small intestine is unknown. In this study, we found that NPC1L1 distributed in enterocytes of villi and transit-amplifying cells of crypts. Acyl-CoA cholesterol acyltransferase 2 (ACAT2), another important protein for cholesterol absorption by providing cholesteryl esters to chylomicrons, was mainly presented in the apical cytoplasm of enterocytes. NPC1L1 and ACAT2 were highly expressed in jejunum and ileum. ACAT1 presented in the Paneth cells of crypts and mesenchymal cells of villi. In the absence of cholesterol, NPC1L1 was localized on the brush border of enterocytes. Dietary cholesterol induced the internalization of NPC1L1 to the subapical layer beneath the brush border and became partially colocalized with the endosome marker Rab11. Ezetimibe blocked the internalization of NPC1L1 and cholesterol and caused their retention in the plasma membrane. This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo.     

Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes

Background

Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).

Methodology and Principal Findings

Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).

Conclusion

Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.     

Governmental policies on HIV infection in China

EVOLUTION OF THE GOVERNMENT POLI- CIES Looking back 20 and more years, one could have hardly imagined that such great changes would have happened to the governmental policies on HIV/AIDS in China. In the earlier phase of the epidemic, laws and regulations were drafted based on the practices and experiences of preven- tion and control of other infectious diseases, such as isolation, quarantine and compulsory testing and examina- tions etc. When the HIV/AIDS epidemic was firstl…     

Improved Cardiac Contractility of Human Recombinant Growth Hormone on the Congestive Heart Failure of Pig

1Introduction Congestiveheartfailureisamultipleaetiology,high prevalence,cardiovasculardisorderwithpoorprognosis. Medicaltreatmentofdilatedcardiomyopathyisaimedat alleviatingthesymptomsofheartfailure.Diuretics,ACE inhibitorsandbeta blockershavefavourableeffectson symptoms,exercisecapacityandmortality[1-3].Growth hormone(GH)andinsulin likegrowthfactor(IGF) 1 areinvolvedinseveralphysiologicalprocessessuchas thecontrolofmusclemassandfunction,bodycomposi tionandtheregulationofnutrientmetaboli…     

A Computational Model of Soil Adhesion and Resistance for a Non-smooth Bulldozing Plate

1IntroductionAdhesive forces exist between soil and the surfacesof soil-engaging components[1,2].Soil adhesion increasesthe running resistance and energy consumption,andaffects the operating quality.Soil adhesion also reducesthe working productivity of terrain machines,even worseit makes terrain machines fail to run.Reducing theadhesive force of the soil-engaging machines will have aprofound influence for cultivation.Through theinvestigation of soil animals,we have found that soilanimals poss…     

A Stable Upstream Stem-loop Structure Enhances Selection of the First 5'-ORF-AUG as a Main Start Codon for Translation Initiation of Human ACAT1 mRNA

Acyl-coenzyme A:cholesterol acyltransferase (ACAT)is an integral membrane protein, which is mainly locatedin rough endoplasmic reticulum (ER), and is responsiblefor catalyzing the intracellular formation of cholesterylester from cholesterol and long-chain fatty acyl-coenzymeA [1,2]. Human ACAT1 cDNA K1 was firstly cloned andfunctionally expressed in 1993 [3]. Further studies withspecific anti-ACAT1 antibody (DM10) illustrated that onemajor 50 kD ACAT1 protein was expressed in various…     

Phylogenetic clusters of rhizobia revealed by genome structures

Rhizobiaareagriculturallyandenvironmentallyimportantbacteria.Theirsymbiosiswithleguminousplantsisresponsibleformostoftheatmosphericni-trogenfixedonland.Classificationofthesebacteriabasedontheirnaturalrelationshipswillpromotetheirapplication.Thisresearchemploysanewphylogeneticmethod,i.e.,revelationandcomparisonofgenomestructure,tocategorizerhizobia.Phylogenyisthestudyoftheevolutionaryrelationshipsamongorgan-isms[1].Currentlyphylogeneticrelationshipsamongrhizobiaaremostlyinferredfromcomparisons…     

Differentiation potential of bone marrow mesenchymal stem cells into retina in normal and laser-injured rat eye

Withinthebonemarrowstromathereexistsasubsetofnonhematopoieticcellsreferredtoasmes-enchymalstemormesenchymalprogenitorcells.Mesenchymalstemcells(MSCs)areapopulationofpluripotentcellswithinthehuman,birdorrodentbonemarrowmicroenvironmentdefinedbytheirability,eitherinvitroorinvivo,todifferentiateintocellsoftheosteogenic,chondrogenic,tendonogenic,adipo-genic,neuralcellsandmyogeniclineages[1].Themethodologiestoisolateandculture-expandMSCsfromhumanbonemarrowforestablishingthecellularortissuediffere…     

Three-dimensional structure determination of capsid of Aedes albopictus C6/36 cell densovirus

Apreviously-unknownviruswasfoundchroni-callyinfectingC6/36cellsthatwereusedtoculturedenguevirus.Afterisolationandpurification,RT,PCRandsequencingwereperformedwithrandomprimers.TheresultsshowthattheviralgenomeisssDNAandis4096ntinlength(GenBankAccessionNo.AY095351).Thenucleicacidsequenceofthispreviously-undescribedvirussharesabout90%iden-titywiththatofAedesaegyptidensonucleosisvirusandtheaminoacidsequencesofthreeproteinsen-codedbythenucleicacidshareabout89%—93%identitieswiththoseofAedesa…