ABSTRACT
S-NeuAc-α(2-6)-di-LacNAc (5) was efficiently synthesized by a [2+2] followed by a [1+4] glycosylation, and later conjugated with 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE) to form both single-layer and multi-layer homogeneous liposomes in the presence of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol. These liposomes were found to be weak inhibitors in both the influenza virus entry assay and the hemagglutination inhibition assay. The single layer liposome was found to more efficiently interfere with the entry of the H1N1 influenza virus into MDCK cells than the multilayer liposome containing 5.
Subject(s)
Antiviral Agents/pharmacology , Liposomes/chemistry , Oligosaccharides/chemistry , Zanamivir/pharmacology , Animals , Cholesterol/chemistry , Dogs , Glycosylation , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Influenza A Virus, H1N1 Subtype/drug effects , Madin Darby Canine Kidney Cells , Oligosaccharides/chemical synthesis , Phosphatidylethanolamines/chemistry , Virus Internalization/drug effectsABSTRACT
Recent genome-wide association studies have established the association between EXOC3L2 rs597668 variant and Alzheimer's disease (AD) in European population. However, recent studies reported inconsistent results in Asian population. Here, we performed a systematic review and meta-analysis to evaluate the impact of rs597668 on AD risk in Asian population using a total of 8686 samples including 2855 cases and 5831 controls. Meanwhile, we selected 17,008 AD cases and 37,154 controls in European population to evaluate the potential heterogeneity between East Asian and European populations. In East Asian population, we identified no potential heterogeneity with P=0.31 and I2 = 15.8%. By meta-analysis, we identified positive association between rs597668 and AD risk with P=0.023, OR=0.93, 95% CI 0.87-0.99. We further found significant heterogeneity in pooled Asian and European populations with P<0.0001 and I2 = 87.7%. The meta-analysis indicated negative association with P=0.66, OR=0.97, 95% CI 0.85-1.11. In summary, all these findings indicate that rs597668 C allele is a risk factor for AD in European population with OR=1.18 and P=2.49E-13. However the rs597668 C allele played a protective role in AD with OR=0.93 and P=0.023 in East Asian population.
Subject(s)
Alzheimer Disease/epidemiology , Alzheimer Disease/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic/genetics , Vesicular Transport Proteins/genetics , Asia/epidemiology , Case-Control Studies , Humans , PrognosisABSTRACT
An efficient, homogeneous synthesis of phospholipid conjugation of S-Neu5Acα2-6Galß1-4GluNAcß1-3 (3) and its 6-sulphate analogue 4 has been developed. The self-assembled micelles and liposomes of these trisaccharides formed in solution were found to be inhibitors interfering with the entry of the H1N1 influenza virus into MDCK cells. Compound 3 bearing a liposome and a micelle displayed superior inhibitory activity than its 6-sulfate congener 4 in both the virus neutralization assay and the hemagglutination inhibition assay.
