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Site-specific Methylation of Epigallocatechin Gallate (EGCG) by Bacterial O-methyltransferas
Gyeong-Guk PARK,Heewon NHO,Uk-Jae LEE,Joo-Hyun SEO,Byung-Gee KIM 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Green tea is well known for its various biological activities. It has been widely consumed as beverages and medicine in East Asia. The global green tea market is growing rapidly as consumer`s awareness of the efficacy of the Epigallocatechin-3-gallate (EGCG). EGCG, the main active ingredient catechin in green tea, shows health effects including potent antioxidant, anti-inflammatory, and anti-cancer. The bioavailability of EGCG by oral administration is relatively low related to its poor membrane permeability and stability in the gastrointestinal tract and blood. So structural modification was needed to improve the effect of oral EGCG. The methylated EGCG is the solution to overcome physiological disadvantages. It was reported that the oral absorption rate of EGCG’’3Me was significantly increased. Furthermore, its therapeutic effect against high blood pressure was also improved. And focused on the active site of the enzyme, we selected key residues by multiple sequence alignment and alanine scanning. The following work is to complete the site saturation mutagenesis and confirm the activity enhancement.
최수인,김나영,Ryoung Hee Nam,Ji Hyun Park,Heewon Nho,Jeong Eun Yu,Chin-Hee Song,Sun Min Lee,Dong Ho Lee 대한암예방학회 2021 Journal of cancer prevention Vol.26 No.4
The gut microbiota interacts with the host gut environment, which is influenced by such factors as sex, age, and host diet. These factors induce changes in the microbial composition. The aim of this study was to identify differences in the gut microbiome of Fisher-344 (F344) rats fed a high-fat diet (HFD), depending on their age and sex. Fecal microbiomes from 6-, 31-, and 74-week-old, and 2-year-old both male and female rats (corresponding to 5-, 30-, 60-, and 80-year-old humans) were analyzed using 16S rRNA gene sequencing, phylogenetic investigation of communities by reconstruction of unobserved states, and enterotype (E) assessment. Moreover, the effect of an HFD on colonic epithelial cells was measured using real-time quantitative PCR. Alpha diversity decreased in the HFD group regardless of age and sex. Based on the enterotype clustering of the whole fecal microbiome, clusters from male rats were divided into E1 and E2 enterotypes, while clusters from female rats were divided into E1, E2, and E3 enterotypes. The female E3 group showed a significantly high abundance in the Ruminococcus genus and expression of Tlr2 mRNA, which may reflect compensation to the HFD. Moreover, the female E3 group showed a lower ratio of opportunistic pathogenic strains to commensal strains compared to the female E2 group. Administration of an HFD influenced the rat fecal microbiota in all assessed age groups, which could be further differentiated by sex. In particular, female rats showed a compensatory enterotype response to an HFD compared to male rats. Key Words Rats, Diet, high-fat, Microbiota, Aging, Sex
Chin-Hee Song,Na Young Kim,Ryoung Hee Nam,Soo In Choi,Changhee Kang,Jaeyoung Jang,Heewon Nho,신은,이하나 대한암예방학회 2021 Journal of cancer prevention Vol.26 No.1
Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO female mice were sacrificed at week 2 and 16 after AOM injection. Severity of colitis, tumor incidence, and levels of inflammatory mediators were evaluated in AOM/DSS-treated WT and Nrf2 KO mice. Furthermore, qRT-PCR, Western blot abnalysis, and ELISA were performed in colon tissues. At week 2, AOM/DSS-induced colon tissue damages were significantly greater in Nrf2 KO than in WT mice. At week 16, tumor numbers (> 2 mm size) were significantly lower in both the proximal and distal colon in Nrf2 KO compared to WT. The overall incidences of adenoma/cancer of the proximal colon and submucosal invasive cancer of the distal colon were reduced by Nrf2 KO. The mRNA and protein expression levels of NF-κB-related mediators (i.e., iNOS and COX-2) and Nrf2-related antioxidants (i.e., heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit) were significantly lower in the Nrf2 KO than in WT mice. Interestingly, the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was higher in AOM/DSS-treated Nrf2 KO than in WT mice. Our results support the oncogenic effect of Nrf2 in the later stage of carcinogenesis and upregulation of tumor suppressor 15-PGDH might contribute to the repression of colitis-associated tumorigenesis in Nrf2 KO female mice. Key Words Col