Search results for "CELLULAR"

Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluat…

2017

Background: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. Aim: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. Methods: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. Results: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin lev…

Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study

2016

Background & Aims: All oral direct acting antivirals (DAA) have been shown to improve the liver function of patients with decompensated cirrhosis but it is presently unknown whether this clinical improvement may lead to the delisting of some patients. The aim of this study was to assess if and which patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting. Methods: 103 consecutive listed patients without hepatocellular carcinoma were treated with different DAA combinations in 11 European centres between February 2014 and February 2015. Results: The cumulative incidence of inactivated and delisted patients by competing risk analysis…

Matrix metalloproteinases 2 and 9, and extracellular matrix in Kaposi's sarcoma

2010

Matrix metalloproteinases (MMPs) are associated with Kaposi's sarcoma (KS) tumorigenesis and may contribute to the mechanism of KS invasive growth. To date, only a few MMPs have been studied in KS lesions, and exactly which MMPs are involved in KS development and progression remains unanswered. However, MMPs 2 and 9 have been associated with different phases of angiogenesis, but their role in the proteolytic modification of the extracellular matrix has not been investigated. The results of this study confirm that MMPs, specifically MMP-2 and MMP-9, can contribute to angiogenesis by disrupting the vessel basement membrane and other extracellular matrix barriers, and enabling endothelial cell…

RNA marker modifications reveal the necessity for rigorous preparation protocols to avoid artifacts in epitranscriptomic analysis

2021

Abstract The accurate definition of an epitranscriptome is endangered by artefacts resulting from RNA degradation after cell death, a ubiquitous yet little investigated process. By tracing RNA marker modifications through tissue preparation protocols, we identified a major blind spot from daily lab routine, that has massive impact on modification analysis in small RNAs. In particular, m6,6A and Am as co-varying rRNA marker modifications, appeared in small RNA fractions following rRNA degradation in vitro and in cellulo. Analysing mouse tissue at different time points post mortem, we tracked the progress of intracellular RNA degradation after cell death, and found it reflected in RNA modific…

2015

Oligodendrocytes myelinate neuronal axons in the central nervous system (CNS) facilitating rapid transmission of action potentials by saltatory conduction. Myelin basic protein (MBP) is an essential component of myelin and its absence results in severe hypomyelination in the CNS of rodents. Mbp mRNA is not translated immediately after exit from the nucleus in the cytoplasm, but is transported to the plasma membrane in RNA transport granules in a translationally silenced state. We have previously identified the small non-coding RNA 715 (sncRNA715) as an inhibitor of Mbp translation associated with RNA granules. Argonaute (Ago) proteins and small RNAs form the minimal core of the RNA induced …

Targeted delivery of siRNAs against hepatocellular carcinoma-related genes by a galactosylated polyaspartamide copolymer

2021

Given the lack of effective treatments for Hepatocellular carcinoma (HCC), the development of novel therapeutic approaches is very urgent. Here, siRNAs were delivered to HCC cells by a synthetic polymer containing α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide-(PHEA) derivatized with diethylene triamine (DETA) and bearing in the side chain galactose (GAL) linked via a polyethylene glycol (PEG) to obtain (PHEA-DETA-PEG-GAL, PDPG). The GAL residue allows the targeting to the asialo-glycoprotein receptor (ASGPR), overexpressed in HCC cells compared to normal hepatocytes. Uptake studies performed using a model siRNA or a siRNA targeted against the enhanced green fluorescence protein, demonstrated …

AP-1 Transcription Factor Serves as a Molecular Switch between Chlamydia pneumoniae Replication and Persistence

2015

ABSTRACT Chlamydia pneumoniae is a Gram-negative bacterium that causes acute or chronic respiratory infections. As obligate intracellular pathogens, chlamydiae efficiently manipulate host cell processes to ensure their intracellular development. Here we focused on the interaction of chlamydiae with the host cell transcription factor activator protein 1 (AP-1) and its consequence on chlamydial development. During Chlamydia pneumoniae infection, the expression and activity of AP-1 family proteins c-Jun, c-Fos, and ATF-2 were regulated in a time- and dose-dependent manner. We observed that the c-Jun protein and its phosphorylation level significantly increased during C. pneumoniae development.…

Enhancing Gene Knockdown Efficiencies by Comparing siRNA-Loaded Cationic Nanogel Particles of Different Sizes

2015

lt;pgt;In order to silence the expression levels of pathogenic genes, small interfering RNA (siRNA) requires a nano-sized carrier for its safe and stable delivery into cells. In this research highlight, we focus on well-defined cationic nanohydrogel particles developed in our group for such purposes. To investigate the nanogels’ mechanism for enhanced knockdown efficiencies, we recently synthesized two sets of particles with similar material composition and siRNA-loading characteristics, but – according to the manufacturing process – of different sizes. Within this study, 100-nm-sized nanogel particles loaded with siRNA accumulated inside the lysosomes already after 4 h and could not induce…

SNAT2 silencing prevents the osmotic induction of transport system A and hinders cell recovery from hypertonic stress.

2005

AbstractUnder hypertonic conditions the induction of SLC38A2/SNAT2 leads to the stimulation of transport system A and to the increase in the cell content of amino acids. In hypertonically stressed human fibroblasts transfection with two siRNAs for SNAT2 suppressed the increase in SNAT2 mRNA and the stimulation of system A transport activity. Under the same condition, the expansion of the intracellular amino acid pool was significantly lowered and cell volume recovery markedly delayed. It is concluded that the up-regulation of SNAT2 is essential for the rapid restoration of cell volume after hypertonic stress.

Algorithms for Graph and Network Analysis: Graph Alignment

2019

In this article we discuss the problem of graph alignment, which has been longly referred to for the purpose of analyzing and comparing biological networks. In particular, we describe different facets of graph alignment, according to the number of input networks, the fixed output objective, the possible heterogeneity of input data. Accordingly, we will discuss pairwise and multiple alignment, global and local alignment, etc. Moreover, we provide a comprehensive overview of the algorithms and techniques proposed in the literature to solve each of the specific considered types of graph alignment. In order to make the material presented here complete and useful to guide the reader in the use o…