1,721,090 research outputs found
Nanoparticle-based systems for liver therapy: Overcoming fibrosis and enhancing drug efficacy
CORE TIP: Liver diseases, including fibrosis and hepatocellular carcinoma, represent major global health challenges with limited treatment options, partly due to drug delivery barriers. Therapeutic efficacy is hindered by factors such as portal hypertension, vascular alterations, and particularly the fibrotic microenvironment. This review summarizes the latest advances in nanoparticle-based delivery strategies targeting liver fibrosis, focusing on lipid-based, polymeric, and inorganic nanoparticles (NPs). It also explores emerging combinatorial technologies including gene delivery platforms and ultrasound-assisted microbubble systems. Finally, it briefly integrates toxicity issues, translational considerations and artificial intelligence-guided NPs to provide a comprehensive yet focused overview of promising therapeutic avenues
The lobular expression of the rat asialoglycoprotein receptor is regulated at post-transcriptional level
The purpose of this study was to define the distribution of the
asialoglycoprotein receptor (ASGP-R) main peptide, rat hepatic lectin
(RHL)-1, within the rat liver lobule and to investigate its possible modulation
in physiological states characterised by marked changes of receptorial
expression. In particular, we chose livers from rats partially hepatectomised
or at the end of pregnancy, as models, respectively, of decreased or increased
expression of the ASGP-R, and used the in situ hybridisation and
immunocytochemistry techniques to analyse in parallel the lobular
distributions of RHL-1 mRNA and protein. In normal rat liver, although the
RHL-1 mRNA was homogeneously distributed, the RHL-1 peptide was
predominantly localised on the surface of pericentral hepatocytes with a
gradient of expression towards the periportal zone. This gradient of
expression of RHL-1 peptide was reduced in regenerating livers, in which the
positive stain was restricted to a few layers of cells around the central vein. In
contrast, livers at the end of pregnancy showed an overall increase of the
peptide with a concomitant flattening of the gradient across the liver plate. In
all the conditions, we never observed important changes in the pattern of
expression of the specific mRNA. These findings indicate that the distribution
of ASGP-R is heterogeneous across the liver lobule, with a pattern of
expression prevalently modulated at the posttranscriptional level
Independent modulation of galactose-specific receptor expression in rat liver cells
The expression of galactose-specific receptors on liver cells from rats at the end of pregnancy and from estrogen-treated animals was studied. The number and distribution of binding sites were estimated on hepatocytes and Kupffer and endothelial cells in vitro as well as in situ by means of protein-gold complexes. Hepatocytes and endothelial cells from pregnant rats showed an increased binding activity of at least three times for hepatocytes and one and a half times for endothelial cells with respect to normal rat livers. The increase in the hepatocyte receptor expression was paralleled by an increase in the level of its specific messenger RNA (mRNA). On Kupffer cells, a decreased number of binding sites, at least three times less than control values, was measured. The correlation between the altered hormonal level during pregnancy and the expression of galactose binding sites was examined in hepatocytes and Kupffer cells isolated from virgin rats treated with the synthetic estrogen diethylstilbesterol. In estrogen-treated rats both the binding sites and the specific mRNA of hepatocytes increased as compared with vehicle-treated or untreated animals. In contrast, in Kupffer cells both the estrogen treatment as well as vehicle-only injection led to a significant reduction in the expression of binding sites as compared with virgin untreated animals. To establish whether the decrease of galactose binding sites in Kupffer cells was related to the activation of macrophages or to the removal of plasma membrane caused by enhanced nonspecific phagocytosis, in situ binding experiments were performed after lipopolysaccharide (LPS)-stimulation or latex-bead phagocytosis. Nonspecific phagocytosis does not affect the binding activity, which instead appears strongly reduced after LPS injection. These findings suggest an independent response of galactose-specific receptor expression systems in the different types of liver cells to modulating agents
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
HCV core protein affects expression and localization of adhesion molecules in MMHD3 cells
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