The effects of EGCG supplementation on pancreatic islet α and ß cells distribution in adult male mice.

Tea and tea products are widely used as the most popular beverage in the world. EGCG is the most abundant bioactive tea polyphenol in green tea, which has positive effects on the prevention and treatment of diabetes. However, the impact of EGCG exposure on glucose homeostasis and islets in adult mice have not been reported. In this study, we studied glucose homeostasis and the morphological and molecular changes of pancreatic islet α and ß cells in adult male mice after 60 d of exposure to 1 and 10 mg/kg/day EGCG by drinking water. Glucose homeostasis was not affected in both EGCG groups. The expression of pancreatic duodenal homebox1 (Pdx1) in ß cells was upregulated, which might be related to increased insulin level, ß cell mass and ß cell proliferation in 10 mg/kg/day EGCG group. The expression of aristaless-related homeobox (Arx) in α cells did not change significantly, which corresponded with the unchanged α-cell mass. The significant reduction of musculoaponeurotic fibrosarcoma oncogene homolog B (MafB) positive α-cells might be associated with decreased glucagon level in both EGCG groups. These results suggest that EGCG supplementation dose-dependent increases ß cell mass of adult mice and affects the levels of serum insulin and glucagon. Our results show that regular tea drinking in healthy people may have the possibility of preventing diabetes.

Prenatal EGCG consumption causes obesity and perturbs glucose homeostasis in adult mice.

Epigallocatechin gallate (EGCG) has a wide consumption for its health advantages. The current study investigates the effects of prenatal EGCG administration on glucose metabolism and obesity in adulthood. Pregnant C57BL/6J mice were supplemented with EGCG in drinking water (3 µg/mL) for 16 d. Abdominal obesity was observed in both male and female adult mice, which was associated with the upregulation of adipose-specific genes, including C/ebpα and Srebf1 (Srebf1 only in males), and the downregulation of genes related to lipolysis, such as Acox1, Atgl and Pdk4 (only in males) in visceral adipose tissue. Elevated fasting glucose levels and hyperinsulinemia were observed in adult males, while females exhibit lower glucose level in glucose tolerance test, which might be due to reduced glucagon levels. Though hepatic expression of the insulin receptor signaling pathway was upregulated in males and was not altered in females, prenatal treatment with EGCG downregulated the expression of this signaling pathway in the skeletal muscle of adult mice, which was further demonstrated in primary human skeletal muscle cells treated with EGCG. The methylation levels in promotor of genes related to the insulin receptor signaling were matched with their transcription in mice, while the expression of acetylated histones was downregulated in human skeletal muscle cells. These results suggest that EGCG consumption during pregnancy should be a risk factor for the disruption of glucose homeostasis in adulthood.

EGCG exposure during pregnancy affects uterine histomorphology in F1 female mice and the underlying mechanisms.

Although epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to have many benefits, the effect of EGCG exposure in utero on adult uterine development is unclear. In this study, pregnant C57BL/6 mice were exposed to 1 mg/kg body weight (bw) EGCG dissolved in drinking water from gestational days 0.5-16.5. A significant decrease in uterine weight was observed in the adult female mice, accompanied by uterine atrophy, inflammation, and fibrosis in the endometrium. Uterine atrophy was attributed to the thinning of the endometrial stromal layer and a significant reduction in endometrial cell proliferation. The expression levels of related proteins in the NF-κB and RAF/MEK/ERK signaling pathways were significantly increased, which might be responsible for the occurrence of inflammation. Activation of the transforming growth factor beta (TGF-ß1)/Smad signaling pathway might be involved in the development of endometrial fibrosis. The changes in the expression of estrogen receptor α, ß (ERα, ERß), progesterone receptor (PGR), and androgen receptor (AR) might lead to changes in the aforementioned signaling pathways. The promoter region methylation level of Esr2 was increased, and the expression of DNMT3A was evaluated. Our study indicates a risk of EGCG intake during pregnancy affecting uterine development in offspring.

Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer.

Apolipoprotein B mRNA editing enzyme catalytic polypeptide 3B (APOBEC3B) plays an important role in tumor mutagenesis. However, its clinical significance in gastric cancer (GC) remains largely unknown. We enrolled a total of 482 GC patients from Zhongshan Hospital, Fudan University for immunohistochemistry (IHC) staining to evaluate the prognostic and predictive values of APOBEC3B. Genomic and phenotypic datasets from the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) cohort were downloaded for external validation and complementary bioinformatic analysis. Fresh specimens of additional 60 patients from Zhongshan Hospital, Fudan University were collected to detect CD8+ T cell phenotype with flow cytometry (FCM). The high expression of APOBEC3B indicated inferior overall survival (OS, P < .001 and P = .003) and disease-free survival (DFS, P < .001 and P < .001), yet superior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) in TNM stage II patients. The tumor microenvironment (TME) of APOBEC3B-enriched tumors was characterized by reduced infiltration of tumor reactive CD8+ T cells expressing both effector molecules and immune checkpoints. APOBEC3B high CD8+ T cell high GC patients were most likely to benefit from ACT and PD-1 blockade. Our study demonstrates that APOBEC3B was an independent prognostic and predictive factor in GC. The potential interplay between APOBEC3B and CD8+ T cells merited further investigations.

CSCD: a database for cancer-specific circular RNAs.

Circular RNA (circRNA) is a large group of RNA family extensively existed in cells and tissues. High-throughput sequencing provides a way to view circRNAs across different samples, especially in various diseases. However, there is still no comprehensive database for exploring the cancer-specific circRNAs. We collected 228 total RNA or polyA(-) RNA-seq samples from both cancer and normal cell lines, and identified 272 152 cancer-specific circRNAs. A total of 950 962 circRNAs were identified in normal samples only, and 170 909 circRNAs were identified in both tumor and normal samples, which could be further used as non-tumor background. We constructed a cancer-specific circRNA database (CSCD, http://gb.whu.edu.cn/CSCD). To understand the functional effects of circRNAs, we predicted the microRNA response element sites and RNA binding protein sites for each circRNA. We further predicted potential open reading frames to highlight translatable circRNAs. To understand the association between the linear splicing and the back-splicing, we also predicted the splicing events in linear transcripts of each circRNA. As the first comprehensive cancer-specific circRNA database, we believe CSCD could significantly contribute to the research for the function and regulation of cancer-associated circRNAs.