9 research outputs found
Rapid Generation of Privileged Substructure-Based Compound Libraries with Structural Diversity and Drug-Likeness
A library of privileged-substructure-based,
heterocyclic compounds
was constructed by a sequence of Ugi four-component reactions incorporating
the indole motif and microwave-assisted cyclizations in branched pathways.
Cheminformatic analysis confirmed that the library exhibited a high
degree of structural diversity and good drug-likeness
Mechanism of Pyrazine Formation Intervened by Oxidized Methionines during Thermal Degradation of the Methionine–Glucose Amadori Compound
Methionine
(Met) oxidation was observed during thermal degradation
of methionine/glucose-derived Amadori rearrangement product (MG-ARP).
The effects of oxidized methionine products, methionine sulfoxide
(MetSO) and methionine sulfone (MetSO2), on pyrazine yields
of the MG-ARP model were investigated. The pyrazine contents in the
MG-ARP/Met and MG-ARP/MetSO models were found lower compared to those
in the MG-ARP/MetSO2 model, and the inefficiency of pyrazine
formation in the MG-ARP/Met model was proposed due to the fact that
Met oxidation competitively inhibited the oxidation of dihydropyrazines
for pyrazine formation in spite of relatively high methylglyoxal (MGO)
content. The models of MGO mixed with Met, MetSO, or MetSO2 were established for further investigation of the mechanism for
the involvement of Met oxidation in pyrazine formation. It was observed
that the aldolization or carbonyl-amine reaction of MetSO with MGO
was another important reason for the inhibition of pyrazine formation,
except for the competitive inhibition of oxidative formation of MetSO
on dihydropyrazine oxidation, and the adduct of MGO–MetSO was
identified by MS/MS. These results also accounted for the phenomenon
of low pyrazine yields but high yields of long-chain substituted pyrazines,
which were converted from dihydropyrazines with the aldehyde involvement
Association of polymorphisms in the heparanase gene (HPSE) with hepatocellular carcinoma in Chinese populations
<div><p>Abstract Heparanase activity is involved in cancer growth and development in humans and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be associated with tumors. In this study, we investigated whether SNPs in HPSE were a risk factor for hepatocellular carcinoma (HCC) by undertaking a comprehensive haplotype-tagging, case-control study. For this, six haplotype-tagging SNPs (htSNPs) in HPSE were genotyped in 400 HCC patients and 480 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A log-additive model revealed significant correlations between the HPSE polymorphisms rs12331678 and rs12503843 and the risk of HCC in the overall samples (p = 0.0046 and p = 0.0055). When the analysis was stratified based on hepatitis B virus (HBV) carrier status, significant interactions between rs12331678 and rs12503843 and HBV were observed. Conditional logistic regression analysis for the independent effect of one significant SNP suggested that rs12331678 or rs12503843 contributed an independent effect to the significant association with the risk of HCC, respectively. Our findings suggest that the SNPs rs12331678 and rs12503843 are HCC risk factors, although the potential functional roles of these two SNPs remain to be fully elucidated.</p></div
Combined effects of the genetic variants in the <i>PTEN</i>, <i>AKT1</i>, <i>MDM2</i> and <i>p53</i> genes on the risk of nasopharyngeal carcinoma.
<p>Abbreviations: OR, odds ratio; CI, confidence interval.</p>a<p><i>χ<sup>2</sup></i> test for the distribution of genotypes between patients and control subjects.</p>b<p><i>P</i> values were calculated by multivariate logistic regression, adjusted for age, sex, smoking and drinking status, smoking level, and nationality.</p>c<p><i>χ</i><sup>2</sup> test for the <i>P</i><sub>trend</sub> value of genotypes between patients and control subjects.</p>d<p>Low-risk group, individuals carrying 0–2 risk genotypes; high-risk group, individuals carrying 3-4 risk genotypes.</p><p>*<i>P</i> value remained significant after c°rrection for multiple comparisons (<i>P</i> = 0.048).</p
Haplotypes of <i>AKT1</i> polymorphisms and the risk of nasopharyngeal carcinoma.
<p>(<i>a</i>) Genomic structure of the <i>AKT1</i> locus and the polymorphic sites used. Exons (boxes) and introns are not drawn to scale; open boxes represent noncoding sequences, and filled boxes represent coding sequences. The physical distance between SNPs is shown in nucleotides. (<i>b</i>) Linkage disequilibrium (LD) map of SNPs based on <i>D</i> ´. (<i>c</i>) LD map of SNPs based on <i>r</i><sup>2</sup>. (<i>d</i>) Global <i>P</i> values from single-locus and multi-locus (two to five) based association analysis. (<i>e</i>) Haplotypes showing significant genetic associations with the risk of nasopharyngeal carcinoma. The two-SNP core haplotype is highlighted in gray.</p
Stratification analysis of the combined genotypes of the <i>PTEN</i>, <i>AKT1</i>, <i>MDM2</i> and <i>p53</i> polymorphisms and risk of nasopharyngeal carcinoma.
<p>Abbreviations: OR, odds ratio; CI, confidence interval.</p>a<p>ORs and <i>P</i> values were calculated by multivariate logistic regression, adjusted for age, sex, smoking and drinking status, smoking level and nationality when appropriate within the strata.</p>b<p>For differences in ORs within each stratum.</p>c<p>Low-risk group, individuals carrying 0–2 risk genotypes; high-risk group, individuals carrying 3–4 risk genotypes.</p
Primers and restriction enzymes used to investigate polymorphisms in the <i>PTEN</i>, <i>AKT1</i> and <i>p53</i> genes.
a<p>Italicized lowercase letters indicate base mismatches.</p>b<p>Designated rs2498799 in previous literature.</p
L'Écho : grand quotidien d'information du Centre Ouest
31 août 19181918/08/31 (A47).Appartient à l’ensemble documentaire : PoitouCh
Semiquantitative PCR for <i>HJURP</i>.
<p>Expression of <i>HJURP</i> for the three different genotypes of rs3771333 was measured in RNA from Epstein-Barr virus (EBV)-transformed blood lymphocyte cell lines derived from 53 unrelated Chinese individuals. Forty-three individuals carry A/A, 9 carry A/C and 1 carrys C/C genotype. Normalization for mRNA quantity was performed with human <i>GAPDH</i> control primers for each sample. The horizontal bars indicate the mean values for each genotype, with the mean value of A/A carriers designated as 1. We found that the expression of <i>HJURP</i> mRNA in C allele carriers had a lower level compared with the A/A carriers (<i>P</i> = 0.0078; <i>t</i> test).</p