Nucleo forte que contiene1/4/2024 ![]() ![]() Patients with contraindications to pegylated interferon were not eligible. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum α fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. All rights reserved.Įffect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.īourlière, Marc Rabiega, Pascaline Ganne-Carrie, Nathalie Serfaty, Lawrence Marcellin, Patrick Barthe, Yoann Thabut, Dominique Guyader, Dominique Hezode, Christophe Picon, Magali Causse, Xavier Leroy, Vincent Bronowicki, Jean Pierre Carrieri, Patrizia Riachi, Ghassan Rosa, Isabelle Attali, Pierre Molina, Jean Michel Bacq, Yannick Tran, Albert Grangé, Jean Didier Zoulim, Fabien Fontaine, Hélène Alric, Laurent Bertucci, Inga Bouvier-Alias, Magali Carrat, Fabriceįindings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. Copyright © 2012 Federation of European Biochemical Societies. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. Our results show that DOR acts in basal autophagy. However, the mechanisms regulating basal autophagy still remain unknown. ![]() While autophagy has been mostly described as a stress-response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. Mauvezin, Caroline Sancho, Ana Ivanova, Saska Palacin, Manuel Zorzano, AntonioĭOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. Nonetheless, we summarize the current knowledge of nucleos(t)ide synthesis inhibition-related innate immunity and propose it as a newly emerging antiviral mechanism of nucleoside analogs.ĭOR undergoes nucleo-cytoplasmic shuttling, which involves passage through the nucleolus. The precise crosstalk between these two independent processes remains to be determined. Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. Nucleoside analogs generally interfere with cellular nucleos(t)ide synthesis pathways, resulting in the depletion or imbalance of (d)NTP pools. In recent years, gemcitabine, a cytidine analog in clinical use for the treatment of many solid tumors, was also shown to have antiviral activity against a broad range of viruses. Nucleoside analogs have been frequently identified as antiviral agents. Shin, Hye Jin Kim, Chonsaeng Cho, Sungchan Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity.
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