ABSTRACT
A new lignan, sonneralignan A (1), along with two known lignan compounds, (+)-lariciresinol-9-O-ß-D-glucopyranoside (2) and (-)isolariciresinol-9-O-ß-D-glucopyranoside (3) were isolated from the n-butanol extract of the mangrove Sonneratia apetala fruit. The structures of the compounds were elucidated on the basis of extensive spectral analysis. The evaluation of activity showed that compound 1 exhibited significant anti-aging activity, which extended the mean lifespan of Caenorhabditis elegans by up to 19.13% (p < 0.05) and 55.29% (p < 0.01) under normal and heat stress cultivation conditions, respectively. Molecular docking studies showed that compound 1 was bound to the DNA binding domain of DAF-16 and promoted the conformation of DAF-16, thus strengthening the interaction between the DAF-16 and related DNA. TRP-252, SER-250 and SER-249 of the binding region might be the key amino residues during the interaction.
ABSTRACT
BACKGROUND: Studies investigating the association of 2R/3R polymorphism in the thymidylate synthase 5'-untranslated enhanced region (TSER) and colorectal cancer (CRC) risk have reported conflicting results. Thus, a meta-analysis was performed to summarize the data on the potential association. METHODS: Pubmed, Embase and CBM databases were searched for all available studies. Links between the TSER 2R/3R polymorphism and CRC risk were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Seven case-control studies with a total of 2723 cases and 4030 controls were included in this meta-analysis. The results showed that the 3R variant of TSER 2R/3R polymorphism contributes to CRC risk in two comparison models (OR 3R vs. 2R =1.10, 95%CI 1.02-1.18, P = 0.015; OR Homozygote comparison model = 1.22 1.04-1.43, 95%CI 1.04- 1.43, P = 0.012). Subgroup analyses by ethnicity further demonstrated a contribution in Caucasians with three comparison models (OR 3R vs. 2R = 1.10, 95%CI 1.02-1.19, P = 0.015; OR Homozygote comparison model = 1.21, 95%CI 1.03-1.41, P = 0.019; OR Recessive comparison model = 1.18, 95%CI 1.05-1.33, P = 0.008). However, the association in the Asian population was still uncertain due to the limited data (all P values were more than 0.05). CONCLUSIONS: Our meta-analysis suggests that the 3R variant of Thymidylate synthase 5'-untranslated enhanced region 2R/3R polymorphism contributes to gastric cancer risk in the Caucasian population, while any association in Asian populations needs further study.
