1,721,127 research outputs found
Rottlerin: bases for a possible usage in psoriasis
No full textRottlerin is a natural polyphenolic compound, which was initially indicated and marketed as a PKC delta inhibitor and recently proposed and patented as an anti-hypertensive drug. In vitro results from our Laboratory and data from the literature suggest a potential use of Rottlerin in the treatment/control of psoriasis, a skin disease characterized by abnormal cellular proliferation, abnormal angiogenesis and inflammation. Rottlerin, indeed, is an antioxidant and a potent inhibitor of the transcription factor NFkappaB, a key mediator of immune responses and a crucial regulator of cell cycle and apoptosis in immune cells, endothelial cells and keratinocytes. Herein, we will review the multiple activities of Rottlerin (antioxidant, antiproliferative, antiangiogenic and anti-inflammatory) that give to the drug the potential to be used as a new therapeutic approach against psoriasis
Novel PKCs activate ERK through PKD1 in MCF-7 cells
No full textPKCs can have opposite effects on ERK phosphorylation. Novel (n)PKCs can inhibit ERK by phosphorylation of Raf-1, classical and atypical PKCs can activate ERK by removing an inhibitory protein from Raf-1. The aim of this work was to clarify how PMA-activated PKCs lead to ERK activation in MCF-7 cells expressing mainly nPKCs. Using chemical inhibitors and antibodies against PKCs, delivered into cells by the Chariot transfection system, we found that nPKCs activate ERK through transphosphorylation of PKD1, the blockage of which prevented PMA-stimulated ERK activation. We conclude that the nPKCs/PKD1 cascade is determinant for ERK activation by PMA in MCF-7 cells. © 2010 The Society for In Vitro Biology
Functional interactions of protein kinase A and C in signalling networks: a recapitulation
No full textOn the basis of evidence collected from the literature, we propose a general model by which protein kinase (PK) A and the different PKC isoforms can inversely affect cell growth. Molecular switches, which are able to direct the signal towards antiproliferative or mitogenic pathways, are the different isoforms of Raf and PKC. Conflicting data are also reported and discussed in an attempt to reconcile them
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Immunoreactive forms of atrial natriuretic peptide in rabbit atrial heart tissue
No full textA variety of biologically active atrial natriuretic peptides (ANPs) exist.
In the present paper a study of the molecular heterogeneity of rabbit ANP is reported. Fractions from Sephadex G-50 chromatography of atria acetic acid extracts were assayed for their immunological and natriuretic activities. Correlation between the two activities was found not to be linear, nevertheless a fraction was shown to contain the highest quantity of immunoreactive hormone and to be also responsible for the major natriuretic response. Gel electrophoresis analysis of this fraction followed by immunoblotting with anti-ANP serum, showed the presence of three immunoreactive bands of different molecular weight (3,400-6,500; 16,000; 30,000 daltons), probably corresponding to different forms of the hormone
Molecular assembly of endogenous and synthetic big atrial natriuretic peptide and its implications in amyloidogenesis
No full textThe aggregation process of alpha-hANP has been investigated in vitro at physiological concentrations by gel chromatographic procedures using a radiolabeled tracer incubated in PBS and in plasma. In PBS big forms of ANP are organized as a peak eluting from both Sephacryl S-100 and S-300 HR in the void volume of the columns; in plasma, besides this major peak, a second radioactive peak is evident, eluting from Sephacryl S-100 HR around the HSA region. After gel chromatography on Sephacryl S-300 HR the major peak appears to consist of three components of different molecular size. Some information about the nature of these peak materials comes from the result of parallel incubations of partially aggregated (seed or nucleus) and aggregate depleted tracer. The comparison between the two time courses of big ANP formation indicates that: (a) ANP aggregation is a nucleation-dependent process, with a lag time longer than 8 days, at picogram peptide levels and (b) the aggregated forms of peptide are those eluting in the void volume, the other plasma peaks being probably expression of a binding, neither saturable or reversible, to some plasma components. The principle of seeded polymerization, used to detect ANP aggregates present in the plasma, indicates that: (a) the endogenous big ANP cannot act as a nucleus for polymerization and it likely consists of non-fibrillar ANP aggregates and/or bound ANP, and (b) this experimental approach can be suitable to evidence ANP binding plasma factors for further characterization studies
Molecular analysis and susceptibility patterns of meticillin-resistant Staphylococcus aureus (MRSA) strains circulating in the community in the Ligurian area, a northern region of Italy: emergence of USA300 and EMRSA-15 clones
No full textFor many years meticillin-resistant Staphylococcus aureus (MRSA) has been considered a typical nosocomial pathogen. Recently, MRSA has emerged as a frequent cause of infections in the community. A multicentre surveillance study was carried out in the Ligurian area of Italy to evaluate the incidence, molecular nature and susceptibility patterns of MRSA strains circulating among outpatients. The genetic background of MRSA strains was analysed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Determination of antimicrobial susceptibility patterns, staphylococcal cassette chromosome mec (SCCmec) type, accessory gene regulator (agr) group and Panton-Valentine leukocidin (PVL) production was also performed. In total, 12 (6.4%) of 188 S. aureus isolates collected during 2006-2007 were found to be MRSA by phenotypic and genotypic methods. Analysis of isolates by PFGE showed that the majority of strains (11/12) belonged to two well-known international clones (EMRSA-15 and USA300) and their variations. High variability regarding SCCmec IV subtypes, susceptibility patterns and PVL toxin production were found among members of the USA300 clonal group, even when displaying the same PFGE profiles. The remaining MRSA strain belonged to sequence type (ST) 8, agr group I and carried SCCmec type I. Both community-associated MRSA and healthcare-associated MRSA epidemic international clones circulate among outpatients in our region. It is alarming that members of the most represented clonal group in our collection (USA300) can acquire multiresistance as well as PVL genes. Infection control measures in our area should be improved to avoid the selection of microorganisms displaying both traits simultaneously as well as the spread of these epidemic international clones
Cutaneous MMPs are differently modulated by environmental stressors in old and young mice.
No full textSkin is frequently exposed to pro-oxidative insults such as UV light, ozone (O(3)) and cigarette smoke (CS), which are able to deplete antioxidants and induce oxidation products affecting skin pathophysiology. Skin turnover and regeneration are largely dependent on extracellular matrix metabolism, which is under the control of matrix metalloproteinases, MMPs. The present study evaluated cutaneous MMPs activity upon environmental pollutants exposure and analyzed the response of old and young animals. For this purpose, SKH-1 hairless mice (8 weeks and 18 months old) were exposed for 6h/day to 0.25ppm of O(3) or to UV radiation (0.3 MED) or to CS for 4 days. Gelatin zymography revealed an increase of MMP-2 in both young and old animals, after exposure to pollutants, while MMP-9, undetectable in unexposed subjects, was strongly induced only in old mice. Casein zymography and Western blot analysis showed an increase of MMP-12 in the aged group after environmental stressors exposure. TIMP-1 and -2 expression levels did not change. The current study demonstrates the ability of certain environmental pollutants to affect the ECM turnover through modulation of specific MMPs, and confirms the higher susceptibility of old subjects to exogenous pro-oxidant insults
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