Clinical significance of HDAC9 in hepatocellular carcinoma.

In recent years, most related studies have found that chronic hepatitis B virus infection is the main cause of hepatocellular carcinoma (HCC), but the specific pathogenesis is still unclear. To investigate the function of HDAC in hepatocellular carcinoma (HCC), this study used qRT-PCR to determine the expression levels of miR-376a and HDAC9 mNRA in HCC and para-cancerous tissues. The clinical significance of HDAC9 in HCC was assessed in a study cohort containing 37 patients with HCC using immunohistochemistry. The expression level of miR-376a in liver cancer tissues was significantly lower than that in para-cancerous tissues, while the expression level of HDAC9 mRNA in liver cancer tissue was significantly higher than that in para-cancerous tissues. The expression of HDAC9 occurred mainly in the nucleus. There was a significant correlation between tumor differentiation and HDAC9. Survival analysis showed that HCC patients with higher HDAC9 expression had poorer prognosis, and subsequent multivariate analysis showed that HDAC9 expression level was an independent predictor. There was a definite correlation between HDAC9 and the expressions of AFP and Ki67. These results suggest that the expression level of HDAC9 in HCC is abnormally high while the expression level of miR-376a is significantly decreased, indicating that HDAC9 may be a potential prognostic indicator of HCC.

Mast cell degranulation promotes ischemia-reperfusion injury in rat liver.

BACKGROUND: Mast cells (MCs) play a role in ischemia-reperfusion (I/R) injury in many organs. However, a recent study found that MCs are not involved in I/R injury in isolated rat livers that were perfused only for 1 h. The purpose of this study is to reevaluate the role of MCs in hepatic I/R injury in rat. MATERIALS AND METHODS: A warm hepatic I/R injury model of 1 h ischemia followed by 24 h of reperfusion was used. MC modulation was induced via cromolyn injection or a method called MC depletion using compound 48/80. The effects of MC modulation were evaluated by toluidine blue staining and assessment of mast cell tryptase in sera. The role of MCs in I/R injury was evaluated by hematoxylin and eosin staining graded by Suzuki criteria, alanine aminotransferase and aspartate aminotransferase levels in sera, and malondialdehyde levels in liver homogenates. RESULTS: First, MC degranulation peaked after 2 h of reperfusion and liver damage peaked after approximately 6 h of reperfusion. Second, a method called MC depletion previously used in the skin with repeated injections of compound 48/80 worked similarly in the hepatic setting. Third, stabilization of MCs with cromolyn or depletion of MCs with compound 48/80 each decreased hepatic I/R injury. The most noticeable effects of cromolyn and compound 48/80 treatment were observed after approximately 6 h of reperfusion. CONCLUSIONS: MC degranulation promotes hepatic I/R injury in rats.

Preconditioning donor liver with Nodosin perfusion lessens rat ischemia reperfusion injury via heme oxygenase-1 upregulation.

BACKGROUND AND AIM: Ischemia reperfusion injury (IRI) remains a major cause of graft injury, dysfunction and even failure post-transplantation. Heme oxygenase 1 (HO-1) has been found to be an attractive target for anti-inflammatory therapies and a potential candidate responsible for cell injury. The objective of this study was to investigate whether preconditioning the donor liver with Nodosin perfusion upregulates HO-1 and then lessens IRI in rat models. METHODS: Wistar rats were divided into four groups: experimental group, control group, positive control group and negative control group in which the donor liver was preconditioned with Nodosin, lactated ringer's solution, cobalt protoporphyrin and zinc protoporphyrin perfusion, respectively. We measured HO-1 expression and enzyme activity in rat livers of each group ex vivo at 0, 1 and 2 h after perfusion. At 1 h after perfusion, donor livers of Wistar rats were transplanted into Sprague-Dawley rats orthotopically. Serum transaminase levels, degree of cell apoptosis and Suzuki's score were used to assess ischemia/reperfusion injury in recipients at 24 h after transplantation. RESULTS: Ex vivo, donor liver preconditioning with Nodosin perfusion induced HO-1 expression and enzyme activity significantly, compared with the control group (P < 0.05). In vivo, serum transaminase levels, cell apoptosis degree and Suzuki's score of representative recipients in the Nodosin group were lower than that in the control group (P < 0.05). Preconditioning with Nodosin perfusion induced HO-1 protein mainly in Kupffer cells. CONCLUSIONS: This study suggests that preconditioning with Nodosin perfusion provides a potential protective effect through inducing HO-1 expression to attenuate ischemia/reperfusion injury in liver transplantation.

The hepatic protective mechanism of Ginkgo biloba extract in rats with obstructive jaundice.

The objective of our study was to examine the hepatic protective mechanism of Ginkgo biloba extract (GBE) in rats with obstructive jaundice (OJ). Twenty rats underwent bile duct ligation and received daily intraperitoneal injections of either control saline or Ginkgo biloba extract for 14 days. Ten sham-operated rats had their bile duct exposed but not ligated or sectioned. Serum alanine transaminase (ALT) was analyzed for liver function tests and liver damage was further assessed by histologic examination. The levels of endothelin 1 (ET-1) and nitric oxide (NO) in blood and liver homogenate were measured. The serum alanine transaminase was elevated in the bile duct ligation rats (BDL rats); GBE could significantly lower serum transaminase level and ameliorate liver histological damage. ET-1 and NO levels in both plasma and liver tissue were also elevated in common bile duct (CBD)-ligated rats, but this increase was significantly decreased by GBE treatment. Moreover, the degree of liver damage severity positively correlates with high levels of ET-1 and NO. GBE mediated the liver protective effect at least in part by suppressing overproduction of ET-1 and NO and restoring a proper balance between ET-1 and NO to some extent.