ABSTRACT
OBJECTIVE To investigate the protective effect of Codonopsis Pilosula Polysaccharide (CPPS) on improving of the memory consolidation disorder induced by Cycloheximide and its possible mechanisms in mice. METHODS The mice was divided into five groups, as normal control group, cycloheximid model group, piracetam positive control group, CPPS 300 mg · kg- 1 group, and CPPS 150 mg·kg-1 group. The mice respectively were given saline, piracetam, and CPPS for 15 d. The memory consolidation disorder model in mice was established by ip. Cyclohexylamine, and orally administered CPPS(300 mg·kg-1 or 150 mg·kg-1) every day. Then experimental groups were subjected Morris Water Maze test. Western blotting analysis were used to analysis the expression of CaMKⅡ/CREB signaling pathways. RESULTS Morris water maze experiment showed that cyclohexylamine can cause memory consolidation disorder(P<0.01), and giving piracetam and CPPS (300 mg · kg- 1) can improve spatial memory impairment in mice(P<0.05, P<0.01). Western blotting experiment results show that compared with normal control group, CaMKⅡ and CREB contents of brain in model group mice had significant decreased(P<0.001); Compared with model group, CaMK Ⅱ and CREB contents of brain tissue in piracetam and CPPS groups increased significantly(P<0.05,P<0.01,P<0.001). CONCLUSION Cyclo?heximide can induce the memory consolidation disorder, and its effect in mice related to CaMK/CREB signaling pathways. CPPS can improved this memory disorder by influence CaMKⅡ/CREB signaling pathways.
ABSTRACT
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
Subject(s)
Carcinoma, Squamous Cell/genetics , Chromosomes, Human, Pair 2/genetics , Esophageal Neoplasms/genetics , Asian People/genetics , China , Chromosomes, Human, Pair 10/genetics , Genetic Predisposition to Disease , Genetic Variation , Genome-Wide Association Study , Haplotypes , Humans , Polymorphism, Single Nucleotide , Recombination, GeneticABSTRACT
We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.
