Search results for "Mechanism"
showing 10 items of 1835 documents
The Efflux Pump MexXY/OprM Contributes to the Tolerance and Acquired Resistance of Pseudomonas aeruginosa to Colistin
2020
The intrinsic resistance of Pseudomonas aeruginosa to polymyxins in part relies on the addition of 4-amino-4-deoxy-l-arabinose (Ara4N) molecules to the lipid A of lipopolysaccharide (LPS), through induction of operon arnBCADTEF-ugd (arn) expression. As demonstrated previously, at least three two-component regulatory systems (PmrAB, ParRS, and CprRS) are able to upregulate this operon when bacteria are exposed to colistin. In the present study, gene deletion experiments with the bioluminescent strain PAO1::lux showed that ParRS is a key element in the tolerance of P. aeruginosa to this last-resort antibiotic (i.e., resistance to early drug killing). Other loci of the ParR regulon, such as th…
In Vivo Studies on the Anti-Inflammatory Activity of Pachymic and Dehydrotumulosic Acids
2000
Pachymic and dehydrotumulosic acids were studied in different models of acute and chronic inflammation. They proved to be active in most of the methods applied. None of them were active against arachidonic acid-induced ear edema. Dehydrotumulosic acid significantly diminished the mouse ear edema induced by ethyl phenylpropiolate, while pachymic acid was ineffective. When the putative corticoid-like mechanism of both compounds was explored, pachymic acid activity was partially abolished by the glucocorticoid receptor antagonist progesterone, but dehydrotumulosic acid activity was not affected. In vivo experiments demonstrated the inhibition by both principles of the phospholipase A2 (PLA2)-i…
Design, synthesis, DNA-binding and cytotoxicity evaluation of new potential combilexines
2002
Combilexines, compounds in which a DNA intercalator is linked to a minor groove binding component, interact with the DNA in a sequence specific manner to yield in most cases compounds with anticancer activity. A series of new compounds closely related to netropsin in which the two components were linked by an amide group was synthesised as potential combilexines. As some of these compounds showed cytotoxic activity in vitro, an attempt was made to rationalise their mechanism of action. The DNA binding characteristics of the carboxamides were evaluated by thermal denaturation experiments and by ethidium bromide displacement assay. Their ability to inhibit the topoisomerase I was also determi…
Prediction of quinolone activity against Mycobacterium avium by molecular topology and virtual computational screening.
2000
ABSTRACT We conducted a quantitative structure-activity relationship study using a database of 158 quinolones previously tested against Mycobacterium avium-M. intracellulare complex in order to develop a model capable of predicting the activity of new quinolones against the M. avium-M. intracellulare complex in vitro. Topological indices were used as structural descriptors and were related to anti- M. avium-M. intracellulare complex activity by using the linear discriminant analysis (LDA) statistical technique. The discriminant equation thus obtained correctly classified 137 of the 158 quinolones, including 37 of a test group of 44 randomly chosen compounds. This model was then applied to 2…
Anti- Toxoplasma Activities of 24 Quinolones and Fluoroquinolones In Vitro: Prediction of Activity by Molecular Topology and Virtual Computational Te…
2000
ABSTRACT The apicoplast, a plastid-like organelle of Toxoplasma gondii , is thought to be a unique drug target for quinolones. In this study, we assessed the in vitro activity of quinolones against T. gondii and developed new quantitative structure-activity relationship models able to predict this activity. The anti- Toxoplasma activities of 24 quinolones were examined by means of linear discriminant analysis (LDA) using topological indices as structural descriptors. In parallel, in vitro 50% inhibitory concentrations (IC 50 s) were determined in tissue culture. A multilinear regression (MLR) analysis was then performed to establish a model capable of classifying quinolones by in vitro acti…
Screening for inhibitors of HIV gp120-CD4 binding using an enzyme-linked immunoabsorbent assay.
1993
Binding of the HIV-1 major viral surface glycoprotein, gp120, to the major cell receptor, CD4, is essential for HIV infection of the target cell and syncytium formation. An enzyme-linked immunoassay using solid phase CD4 was used to quantitate the binding of HIV-1 gp120 to CD4, and to assess the activity and mechanism of action of putative inhibitors of that reaction. Monoclonal antibodies to the gp120 binding site on CD4 (e.g., Leu3a) blocked gp120 binding, while monoclonal antibodies to other portions of CD4 (e.g. OKT4) did not. Both aurintricarboxylic acid and sulfonated polysaccharides (e.g., dextran sulfate) blocked CD4-gp120 interactions by binding to the CD4 component. Human polyclon…
Empagliflozin in heart failure with preserved ejection fraction: decoding its molecular mechanism of action using artificial intelligence
2021
Abstract Rationale The use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) to treat heart failure with preserved ejection fraction (HFpEF) is under investigation in ongoing clinical trials, but the exact mechanism of action is unclear. Here we aimed to use artificial intelligence (AI) to characterize the mechanism of action of empagliflozin in HFpEF at the molecular level. Methods We retrieved information regarding HFpEF pathophysiological motifs and differentially expressed genes/proteins, together with empagliflozin target information and bioflags, from specialized publicly available databases. Artificial neural networks and deep learning AI were used to model the molecular effec…
Regenerative Medicine: Does Erythropoietin have a Role?
2009
Regenerative Medicine, a recent new medical domain, aims to develop new therapies through the stimulation of natural regenerative processes also in human beings. In this field, Erythropoietin (EPO) represents a significant subject of research. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on the central nervous system, cardiovascular system and renal tissue. This action is carried out through one of few regenerative activities of human beings: angiogenesis. This mechanism, which involves endothelial stem cells and VEGF (Vascular Endothelial Growth Factor), has been experimentally demonstrated with Recombinant human erythropoietin (r…
Moderate consumption of beer reduces liver triglycerides and aortic cholesterol deposit in LDLr-/- apoB100/100 mice.
2006
This study was designed to address the effects of a moderate consumption of beer on serum and liver lipid parameters and on the development of aortic lesions in a mouse model associated with a human atherogenic lipoprotein profile. LDLr(-/-) apoB(100/100) mice received each day during 12 weeks either water, mild beer (0.570g of ethanol/kg of body weight) or ethanol-free beer in a single pure dose. Serum and liver lipid parameters were analyzed and atherosclerotic lesions were estimated in heart and aorta through their total cholesterol content. mRNA levels of enzymes and receptors involved in lipoprotein uptake, in fatty acid esterification and oxidation, and in reverse cholesterol transpor…
An Insight into the Role of Postmortem Immunohistochemistry in the Comprehension of the Inflammatory Pathophysiology of COVID-19 Disease and Vaccine-…
2021
On 11 March 2020, the World Health Organization (WHO) declared a pandemic due to the spread of COVID-19 from Wuhan, China, causing high mortality rates all over the world. The related disease, which mainly affects the lungs, is responsible for the onset of Diffuse Alveolar Damage (DAD) and a hypercoagulability state, frequently leading to Severe Acute Respiratory Syndrome (SARS) and multiorgan failure, particularly in old and severe-critically ill patients. In order to find effective therapeutic strategies, many efforts have been made aiming to shed light on the pathophysiology of COVID-19 disease. Moreover, following the late advent of vaccination campaigns, the need for the comprehension …