C/EBPα Regulates FOXC1 to Modulate Tumor Growth by Interacting with PPARγ in Hepatocellular Carcinoma.

BACKGROUND: Forkhead box C1 (FOXC1) is an important cancer-associated gene in tumor. PPAR-γ and C/EBPα are both transcriptional regulators involved in tumor development. OBJECTIVE: We aimed to clarify the function of PPAR-γ, C/EBPα in hepatocellular carcinoma (HCC) and the relationship of PPAR-γ, C/EBPα and FOXC1 in HCC. METHODS: Western blotting, immunofluorescent staining, and immunohistochemistry were used to evaluate protein expression. qRT-PCR was used to assess mRNA expression. Co-IP was performed to detect the protein interaction. And ChIP and fluorescent reporter detection were used to determine the binding between protein and FOXC1 promoter. RESULTS: C/EBPα could bind to FOXC1 promoter and PPAR-γ could strengthen C/EBPα's function. Expressions of C/EBPα and PPAR-γ were both negatively related to FOXC1 in human HCC tissue. Confocal displayed that C/EBPα was co-located with FOXC1 in HepG2 cells. C/EBPα could bind to FOXC1 promoter by ChIP. Luciferase activity detection exhibited that C/EBPα could inhibit FOXC1 promoter activity, especially FOXC1 promoter from -600 to -300 was the critical binding site. Only PPAR-γ could not influence luciferase activity but strengthen inhibited effect of C/EBPα. Further, the Co-IP displayed that PPAR-γ could bind to C/EBPα. When C/EBPα and PPAR-γ were both high expressed, cell proliferation, migration, invasion, and colony information were inhibited enormously. C/EBPα plasmid combined with or without PPAR-γ agonist MDG548 treatment exhibited a strong tumor inhibition and FOXC1 suppression in mice. CONCLUSION: Our data establish C/EBPα targeting FOXC1 as a potential determinant in the HCC, which supplies a new pathway to treat HCC. However, PPAR-γ has no effect on FOXC1 expression.

Effects of dual modified resistant indica rice starch on azoxymethane-induced incipient colon cancer in mice.

In this study, the effects of different doses of dual modification-treated (DMT) indica rice resistant starch (IR-RS) on azoxymethane (AOM)-induced early colon cancer in mice were investigated. The investigated factors included body weight, gastrointestinal emptying rate, the number and morphology of aberrant crypt foci (ACFs) and the specific expressions of adenomatous polyposis coli (APC), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cytochrome c genes. The results demonstrated that DMT IR-RS controlled the increase in the body weights of the mice, increased the gastrointestinal emptying rates and reduced the numbers of ACFs and aberrant crypts. Reverse transcription-polymerase chain reaction revealed that DMT IR-RS promoted the expression of APC, Bax and cytochrome c and inhibited the expression of Bcl-2. These results demonstrate that a DMT IR-RS diet may induce apoptosis and has beneficial health effects in AOM-induced early colon cancer in mice.

The roles of methanogens and acetogens in dechlorination of trichloroethene using different electron donors.

We evaluated the effects of methanogens and acetogens on the function and structure of microbial communities doing reductive dechlorination of trichloroethene (TCE) by adding four distinct electron donors: lactate, a fermentable organic; acetate, a non-fermentable organic; methanol, a fermentable 1-C (carbon) organic; and hydrogen gas (H2), the direct electron donor for reductive dechlorination by Dehalococcoides. The fermentable electron donors had faster dechlorination rates, more complete dechlorination, and higher bacterial abundances than the non-fermentable electron donors during short-term tests. Phylotypes of Dehalococcoides were relatively abundant (≥9%) for the cultures fed with fermentable electron donors but accounted for only ~1-2% of the reads for the cultures fed by the non-fermentable electron donors. Routing electrons to methanogenesis and a low ratio of Dehalococcoides/methanogenesis (Dhc/mcrA) were associated with slow and incomplete reductive dechlorination with methanol and H2. When fermentable substrates were applied as electron donors, a Dhc/mcrA ratio ≥6.4 was essential to achieve fast and complete dechlorination of TCE to ethene. When methanogenesis was suppressed using 2-bromoethanesulfonate (BES), achieving complete dechlorination of TCE to ethane required a minimum abundance of the mcrA gene. Methanobacterium appeared to be important for maintaining a high dechlorination rate, probably by providing Dehalococcoides with cofactors other than vitamin B12. Furthermore, the presence of homoacetogens also was important to maintain a high dechlorination rate, because they provided acetate as Dehalococcoides's obligatory carbon source and possibly cofactors.

Hypoglycemic effect of triterpenoid-rich extracts from Euryale ferox shell on normal and streptozotocin-diabetic mice.

The antioxidant effects of the triterpenoid-rich extracts from Euryale ferox shell (ES) have been confirmed in vitro. This study examined whether the triterpenoid-rich extract from ES eases human hyperglycemia and diabetes caused by metabolic disorders. Normal and streptozocin (STZ)-induced diabetic mice were used as controls for the four groups that received the triterpenoid-rich extracts of ES suspended in distilled water orally at doses of 200, 300, 400, 500±2 mg/L. Body weight, blood glucose and pancreatic tissue morphology were observed after 4 weeks. The expression of protein tyrosine phosphatase-1B (PTP1B) and insulin receptor substrate (IRS-1) proteins, which are related to the regulation of glucose metabolism in vivo, were also investigated. Compared with the model group (LD50 900±2 mg/L), it was found that the triterpenoid-rich extracts of ES could regulate glucose metabolism (P<0.01) and cause body weight to return to normal levels (P<0.05). Islet morphology recovered well, the expression of the negative regulation protein PTP1B gene was reduced and insulin receptor IRS-1 protein expression was increased. These data prove that the triterpenoid-rich extracts from ES have a therapeutic effect on diabetes by insulin resistance.

Structure characterization and hypoglycemic effects of dual modified resistant starch from indica rice starch.

Hypoglycemic effects of indica rice resistant starch (IR-RS) were investigated. We prepared IR-RS using a method that combined physical modification and enzyme modification, and the RS content was 47.0%. Differential scanning calorimetry--thermal gravimetric analysis showed that IR-RS have higher enthalpy and less loss of mass than single modified RS, heat-moisture RS and native starch. Scanning electron microscopy revealed that IR-RS displayed more compact spatial structure. IR-RS products displayed a mixture of B-and V-type x-ray diffraction patterns and the cyrstallinity was 51.0%. IR-RS significantly affected body weight, blood glucose, organ indices and serum lipid levels. These results demonstrated that dual modification changed the structure of indica rice starch and affected its digestibility as well as the blood glucose levels of the diabetic mice who consumed it.

Hypoglycemic and hypolipidemic effects of a triterpenoid-rich extract from Euryale shell on streptozotocin-induced diabetic mice.

The hypoglycemic and hypolipidemic effects of a triterpenoid-rich extract from the Euryale shell (ES) was analyzed in streptozotocin-induced diabetic mice. Normal and diabetic mice treated with glimepiride were used as negative and positive controls, respectively. Body weight, organ weight index and cholesterol-related lipid profile parameters were observed after 4 weeks. The hypoglycemic activity was assessed by fasting blood glucose (FBG) and fasting insulin (FINS) to calculate the insulin sensitivity index (ISI). In addition, the potentially regulative mechanisms on insulin resistance were discussed. The results indicated that a triterpenoid-rich extract of ES could inhibit reduction in the body weight of diabetic mice and regulate glucose metabolism. The hypolipidemic action after this extract supplementation was confirmed by significant (p<0.05) decreases in the levels of cholesterol, LDL and triglycerides and increase in HDL compared with the untreated diabetic mice, especially when using a high dose, which suggested that the ES extract could effectively reverse the abnormal enlargement of the liver and spleen (p<0.01). The present data suggest that the triterpenoid-rich extract from the ES has both hypoglycemic and hypolipidemic effects that can not only help cure and manage diabetes but also improve insulin resistance (IR).