Obesity phenotype induced by high-fat diet promotes diethylnitrosamine (DEN)-induced precancerous lesions by M1 macrophage polarization in mice liver.

Liver precancerous lesions are the key to improving the efficacy of cancer treatment because of the extremely poor prognosis of HCC patients in moderate and late stages. Obesity-related HCC progression is closely related to the inflammatory microenvironment, in which macrophages are one of the major constituents. In the present study, we ask whether obesity promotes diethylnitrosamine (DEN)-induced precancerous lesions by M1 macrophage polarization. First, an association between obesity and liver precancerous lesions was determined by histopathological observations, immunochemistry and immunoblotting. The characteristics of early precancerous lesions (trabecular thickening) appeared earlier eight weeks in obese mice than in normal diet mice after DEN induction. The glutathione S-transferase placental-1 (Gstp 1) and alpha-fetoprotein (AFP) expression in obese mice after DEN induction was higher than that in the same period after DEN injection in normal diet mice. Furthermore, there was a significant increase in the total macrophage number (F4/80+) of DEN and M1 macrophage number (CD86+F4/80+) in obese mice compared with that in normal diet mice. Besides, the expressions of four pro-inflammatory factors in DEN-induced obese mice were significantly higher compared with that in normal diet mice. Additionally, angiogenesis was revealed by immunostaining assay to be associated with the inflammatory response. All the results demonstrate that obesity promotes DEN-induced precancerous lesions by inducing M1 macrophage polarization and angiogenesis.

Oligosaccharides of Polygonatum Cyrtonema Hua ameliorates dextran sulfate sodium-induced colitis and regulates the gut microbiota.

Ulcerative colitis (UC) is one common chronic inflammatory bowel disease that causes severe side effects, and expensive treatment limits effective and sustained treatment of UC. Fructooligosaccharide was isolated from Polygonatum Cyrtonema Hua (PFOS) and exhibits anti-inflammatory effects. Therefore, we are curious whether PFOS could be used for the treatment of UC. PFOS was introduced via intragastric gavage to C57BL/6 J mice exposed to acute colitis induced by DSS. The results showed that doses of PFOS at 2 and 5 mg/kg/day alleviated the DSS-induced histopathological damage and improved intestinal barrier function. qPCR analysis revealed that PFOS exerted a significant downregulation of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and upregulation of antioxidant genes, including superoxide dismutase1 (SOD1), glutathion peroxidase2 (GPX2), and nuclear factor erythroid 2 related factor2 (Nrf2). Furthermore, PFOS suppressed the DSS-induced disruption of the mucosal barrier by downregulating MMP13. Moreover, using 16 S rRNA gene-based microbiota analysis, PFOS could selectively enhance the growth of probiotics, including Bifidobacterium, Alloprevofella, and Alistipes. Our findings indicated that PFOS attenuated DSS-induced colitis in mice, suggesting that PFOS might be used as an efficacious supplement for reducing inflammatory bowel disease.