SQLE facilitates the pancreatic cancer progression via the lncRNA-TTN-AS1/miR-133b/SQLE axis.

Studies have shown that SQLE is highly expressed in a variety of tumours and promotes tumour progression. However, the role of SQLE in pancreatic cancer (PC) has not been reported. Here, we aim to study the role and molecular mechanism of SQLE in PC. Immunohistochemistry and functional experiments showed that SQLE was highly expressed in PC tissues and promoted the proliferation and invasion of PC cells. Terbinafine, an inhibitor of SQLE, inhibited this effect. In order to further study the upstream mechanism that regulates SQLE, we used bioinformatics technology to lock miR-133b and lncRNA-TTN-AS. In situ hybridization was used to detect the expression of miR-133b and lncRNA-TTN-AS1 in PC tissues. The luciferase reporter gene experiment was used to confirm the binding of miR-133b and lncRNA-TTN-AS1. The results showed that miR-133b was down-regulated in PC tissues and negatively correlated with the expression of SQLE. LncRNA-TTN-AS1 was upregulated in pancreatic cancer tissues and positively correlated with the expression of SQLE. Luciferase gene reporter gene analysis confirmed lncRNA-TTN-AS1 directly binded to miR-133b. Therefore, we propose that targeting the lncRNA-TTN-AS1/miR-133b/SQLE axis is expected to provide new ideas for the clinical treatment of PC patients.

Adult diffuse hepatic hemangiomatosis: A case report and review of the literature.

Diffuse hepatic hemangiomatosis (DHH) is an extremely rare disease, especially in adults. We present a case of DHH involving the entire liver in a 62-year-old male with a giant hemangioma next to the superior mesenteric vein. Based on what we could find in PubMed with pathological evidence, there are only seventeen cases of adult DHH reported in the literature. The female-to-male ratio is 2.4:1. Most patients consult for abdominal pain or distension. Radiographic examination shows multiple diffuse liver nodules. On MRI, these lesions show hypointense T1 and hyperintense T2. Some lesions may show peripheral rim enhancement in the arterial phase but no portovenous washout. In total, 47% of patients with DHH have one or more giant hemangioma(s). Pathology shows that the lesions are lined with flat endothelial cells without cellular atypia, which are stained positive for vascular endothelial markers. Liver failure is the main cause of death. Some patients can be improved by partial hepatectomy. However, there is no effective treatment for most patients. Liver transplantation should be considered in patients with liver failure or congestive heart failure caused by DHH. We attempt to classify DHH into two types based on the distribution of DHH and their treatment.

Rapid CO breath test screening of drugs for protective effects on ribavirin-induced hemolysis in a rabbit model: a pilot study.

Hemolytic anemia is a major side effect of ribavirin antiviral treatment for chronic hepatitis C. Ribavirin dose reduction may compromise the antiviral response and erythropoietin can take several weeks to alleviate anemia. The purpose of the present study was to screen potentially protective drugs against ribavirin-induced hemolytic anemia in a rabbit model, using our modified CO breath test for measuring erythrocyte (RBC) lifespan, the gold standard diagnostic index of hemolysis. Fifteen rabbits were divided randomly into five groups (N = 3/group): one vehicle control group, one ribavirin (only)-treated (RBV) group, and three groups initially treated with ribavirin only, followed by a combination of ribavirin with prednisone (RBV + Pred), polyene phosphatidyl choline (RBV + PPC), or reduced glutathione (RBV + GSH). RBC lifespan was calculated from accumulated CO measured in a closed rebreath apparatus, blood volume measured by the Evan's blue dye (EBD) dilution test, and hemoglobin concentration data. The RBC lifespan was normal in the vehicle control group (44-60 d), but reduced significantly in all of the ribavirin-treated groups before the addition of screened drugs (17-35 d). RBC lifespan rebounded significantly with the addition of glutathione, but not with the addition of prednisone or polyene phosphatidyl choline. A similar overall drug effect pattern was seen in the hemoglobin concentration and reticulocyte count data. In conclusion, the results of this pilot study indicate that reduced glutathione can attenuate ribavirin-induced hemolytic anemia, and that the RBC lifespan measured with our modified rapid CO breath test is feasible and reliable for use in animal studies.

Alteration of hepatic nuclear receptor-mediated signaling pathways in hepatitis C virus patients with and without a history of alcohol drinking.

UNLABELLED: The current study tests a hypothesis that nuclear receptor signaling is altered in chronic hepatitis C patients and that the altered pattern is specific to alcohol drinking history. The expression of a panel of more than 100 genes encoding nuclear receptors, coregulators, and their direct/indirect targets was studied in human livers. Gene expression pattern was compared between 15 normal donor livers and 23 hepatitis C virus (HCV) genotype 1-positive livers from patients without a drinking history (matched for age, sex, and body mass index). HCV infection increased the expression of nuclear receptors small heterodimer partner and constitutive androstane receptor (CAR) as well as genes involved in fatty acid trafficking, bile acid synthesis and uptake, and inflammatory response. However, the expression of retinoid X receptor (RXR) α, peroxisomal proliferator-activated receptor (PPAR) α and ß as well as steroid regulatory element-binding protein (SREBP)-1c was decreased in HCV-infected livers. Gene expression pattern was compared in chronic hepatitis C patients with and without a drinking history. Alcohol drinking increased the expression of genes involved in fatty acid uptake, trafficking, and oxidation, but decreased the expression of genes responsible for gluconeogenesis. These changes were consistent with reduced fasting plasma glucose levels and altered expression of upstream regulators that include RXRα, PPARα, and CAR. The messenger RNA levels of fibroblast growth factor 21, interleukin-10, and fatty acid synthase, which are all regulated by nuclear receptors, showed independent correlation with hepatic HCV RNA levels. CONCLUSION: Our findings suggest that those genes and pathways that showed altered expression could potentially be therapeutic targets for HCV infection and/or alcohol drinking-induced liver injury.