FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10) human hepatocellular carcinoma, 66.7% (6/9) liver cancer cell lines and 100% (6/6) colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2′-deoxycytidine (Aza), indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS) generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis.

Effects of oxymatrine on experimental hepatic fibrosis and its mechanism in vivo

Nickel-based alloy coatings were widely used for the remanufacturing of dies and moulds by laser cladding, but the crack sensitivity would be increase due to the higher strength and hardness, which reduced the wear resistance of Ni-based alloys. In this paper, Ni-based coatings with the addition of a plastic phase (an austenitic stainless net) were prepared using laser cladding technology, and the CeO ₂ was added in cladding layers. The cracking mechanism, microhardness, microstructure, phase composition, and wear properties were investigated. The relationship between thermal stress and the elastic and plastic fracture had been developed from the standpoint of fracture mechanics and thermal elastic fracture mechanics. The fracture criterion of the nickel-based coating was obtained, and the study has shown that the crack sensitivity could be reduced by decreasing the thermal expansion coefficient Δ α . Thus, a new method was proposed, which the stainless steel nets were prefabricated on the substrate. It was found that the number of cracks reduced significantly with the addition of stainless steel net. When the stainless steel net with 14 mesh was added in Ni-based coatings, the average microhardness of nickel composite coating was 565 HV _0.2 , which was 2.6 times higher than that of the 45 steel substrate. Although the rare earth oxide 4 wt.% CeO ₂ and stainless steel net were added in the Ni-based coating reducing the microhardness (the average microhardness is 425 HV _0.2 ), the wear resistance of it improved substantially. The wear volume of Ni-based composite coating was 0.56×10 ⁻⁵ mm ³ ·N ⁻¹ ·m ⁻¹ , which was 85.1% lower than that of 45 steel. The experiment results have shown that the Nickel-based composite coating is equipped with low crack sensitivity and high abrasive resistance with austenitic stainless net and the rare earth oxide 4 wt.% CeO ₂ . This research offers an efficient solution to produce components with low crack susceptibility and high wear-resistance coatings fabricated by laser cladding.