ABSTRACT
The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.
ABSTRACT
OBJECTIVE: To evaluate the risk factors of colorectal cancer in China. METHODS: The results of 14 case-control studies from 1988 to 2000 were analyzed by means of Meta-analysis. The total numbers of cases and controls were 5034 and 5205 respectively. Dersimonian and Laird random effective models were applied in processing data. RESULTS: Light physical activities and dietary fibers were protective factors (pooled OR<0.8); while histories of fecal mucohemorrhage, chronic diarrhea and bowel polyps were highly associated with colorecatal cancer (pooled OR >4) The stratified results indicated that there were probably some differences between OR values of some factors if using different sources of cases and controls or using different data from the north and south of China. CONCLUSION: Risks of colorectal cancer are significantly associated with the histories of intestinal diseases or relative symptoms, fatty food, psychic attack and family history of cancers. The light physical activities and dietary fibers are probably protective factors.