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MiR-519d belongs to the chromosome 19 miRNA cluster (C19MC), the largest human miRNA cluster. One of its members, miR-519d, is over-expressed in hepatocellular carcinoma (HCC) and we characterized its contribution to hepatocarcinogenesis. In HCC cells, the over-expression of miR-519d promotes cell proliferation, invasion and impairs apoptosis following anticancer treatments. These functions are, at least in part, exerted through the direct targeting of CDKN1A/p21, PTEN, AKT3 and TIMP2. The mechanisms underlying miR-519d aberrant expression in HCC were assayed by genomic DNA amplification, methylation analysis and ChIP assay. The aberrant hypomethylation of C19MC and TP53 were respectively identified as an epigenetic change allowing the aberrant expression of miR-519d and one of the factors able to activate its transcription. In conclusion, we assessed the oncogenic role of miR-519d in HCC by characterizing its biological functions, including the modulation of response to anticancer treatments and by identifying CDKN1A/p21, PTEN, AKT3 and TIMP2 among its targets.

Human cytomegalovirus (CMV) is an ubiquitous pathogen that can cause severe and often fatal infections in immunocompromised patients. Patients with cirrhosis often show various degrees of impaired cellular immunity that could lead to acute CMV reactivation. The aim of the present study was to determine whether laboratory findings of active CMV infections are common in patients with cirrhosis. Fifty-five patients with cirrhosis were studied for acute CMV infection by virological (antigenemia and quantitative polymerase chain reaction in polymorphonuclear leukocytes) and serological (detection of anti-CMV IgM by immunoblot) methods. The same tests were carried out on 50 blood donors and on 20 chronic hepatitis patients, considered as control populations. Acute or recent CMV infection had occurred in 31 (56%) of 55 patients with cirrhosis, whereas only 1 out of 20 (5%) patients with chronic non-cirrhotic liver disease and none of the 50 blood donors had laboratory signs of active CMV infection. The difference between patients with cirrhosis and the control groups was significant (P < 0.001, chi(2) test). CMV in patients with cirrhosis was not related to age, gender, hepatitis C virus infection or hepatocellular carcinoma. There was no significant correlation between impairment of liver function and the presence of active CMV infection. Patients with cirrhosis should be considered at risk for CMV infection, that seems to be mild and asymptomatic.

Background: A decrease in portal flow is an important pharmacological effect of drugs used for the prophylaxis of variceal bleeding. Aim: To assess the acute and chronic effects of propranolol, and the effect of the acute addition of isosorbide-5-mononitrate, on splanchnic circulation. Methods: Measurements of portal blood flow volume (PBFV) and of Doppler ultrasound pulsatility index of the superior mesenteric, femoral and interlobar renal arteries were performed in 10 cirrhotic patients with varices at baseline, 90 min after propranolol or placebo, after 30 days of chronic propranolol treatment and 45 min after the addition of isosorbide-5-mononitrate. Results: The mean PBFV was significantly lower at all times than at baseline, with the greatest mean percentage decrease achieved after the addition of isosorbide-5-mononitrate (≥ 20% in all patients). Acute changes, however, did not predict the chronic effects in many patients. Isosorbide-5-mononitrate significantly increased the mesenteric and femoral pulsatility indices, whereas no significant change was observed in the kidney. Conclusions: Propranolol significantly decreases PBFV, but chronic effects cannot be reliably predicted by the acute change. All patients achieved a decrease in PBFV of ≥ 20% after the acute addition of isosorbide-5-mononitrate to chronic propranolol treatment.