ABSTRACT
Dimethyl fumarate (DMF) is generally used to treat psoriasis and multiple sclerosis. In the present study, we aimed to investigate the effects of DMF on hepatocellular carcinoma progression and its mechanism of action. In vitro, cell viability was examined using CCK-8 assay; cell cycle was analyzed by flow cytometry; angiogenesis was detected using tube formation assay; and autophagic flux assay results were examined using fluorescence microscopy. We also used western blotting to explore the potential mechanisms. In vivo, tumor xenograft experiment was performed with nude mice, and liver function, renal function, and routine blood counts were assessed using biochemical tests. Dimethyl fumarate inhibited tumor growth and angiogenesis in hepatocellular carcinoma, both in vitro and in vivo. Dimethyl fumarate decreased autophagy in hepatocellular carcinoma cells. Treatment with DMF activated SOCS3, which led to repression of JAK1 and STAT3 phosphorylation. DMF inhibited cell proliferation, angiogenesis, and autophagy via activation of the SOCS3/JAK1/STAT3 signaling pathway. This finding may provide a novel approach for the treatment of hepatocellular carcinoma.
ABSTRACT
AIM: To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS: Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (ΔΨm) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, and peroxynitrite was semi-quantified by western blotting of 3-nitrotyrosine. RESULTS: Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of ΔΨm induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION: Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up-regulation of the PI3K/Akt/eNOS/NO pathway.
Subject(s)
Liver Transplantation/methods , Reperfusion Injury/prevention & control , Animals , Ischemic Preconditioning/methods , Liver Transplantation/adverse effects , Male , Membrane Potential, Mitochondrial , Nitric Oxide Synthase Type III/metabolism , Rats , Rats, Sprague-Dawley , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolismABSTRACT
OBJECTIVE: To establish a prediction model for spontaneous rupture of primary liver cancer. METHODS: The clinical data of 77 patients with spontaneous rupture of primary liver cancer and 95 primary liver cancer patients without spontaneous rupture were collected and compared. The risk factors of spontaneous rupture of primary liver cancer were analyzed with multivariate logistic regression. RESULTS: Multivariate logistic regression analysis revealed that moderate or severe ascites, liver cirrhosis, protrusion of tumor from the liver surface, tumor size ≥ 5 cm were independent risk factors of spontaneous rupture of primary liver cancer. The area under the receiver operating characteristic curve of the established model for spontaneous rupture was 0.862 (P<0.05). CONCLUSION: The established model base on the severity of ascites, liver cirrhosis, protrusion of tumor and large tumor size can effectively estimate the risk of spontaneous rupture of primary liver cancer.
