Search results for "Response"
showing 10 items of 4136 documents
In vitro and in silico studies of polycondensed diazine systems as anti-parasitic agents
2012
Abstract Parasitic diseases caused by protozoarian agents are still relevant today more than ever. Recently, we synthesized several polycondensed diazine derivatives by means 1,3-dipolar cycloaddition reactions. A broad selection of these compounds were submitted to in vitro biological screening against Plasmodium falciparum , Leishmania infantum , Trypanosoma brucei , and Trypanosoma cruzi , resulting active at micromolar level. Induced Fit Docking/MM-GBSA studies were performed giving interesting indications about the probable mechanism of action of the most active compounds
Palladium(II)-Stabilized Pyridine-2-Diazotates: Synthesis, Structural Characterization, and Cytotoxicity Studies
2018
Well-defined diazotates are scarce. Here we report the synthesis of unprecedented homoleptic palladium(II) diazotate complexes. The palladium(II)-mediated nitrosylation of 2-aminopyridines with NaNO2 results in the formation of metal-stabilized diazotates, which were found to be cytotoxic to human ovarian cancer cells.
A Primary Evaluation of Potential Small-Molecule Inhibitors of the Astacin Metalloproteinase Ovastacin, a Novel Drug Target in Female Infertility Tre…
2020
Abstract Despite huge progress in hormonal therapy and improved in vitro fertilization methods, the success rates in infertility treatment are still limited. A recently discovered mechanism revealed the interplay between the plasma protein fetuin‐B and the cortical granule‐based proteinase ovastacin to be a novel key mechanism in the regulation of fertilization. Upon sperm–egg fusion, cleavage of a distinct zona pellucida component by ovastacin destroys the sperm receptor, enhances zona robustness, and eventually provides a definitive block against polyspermy. An untimely onset of this zona hardening prior to fertilization would consequently result in infertility. Physiologically, this proc…
Stress distribution of complete-arch implant-supported prostheses reinforced with silica-nylon mesh
2019
Made available in DSpace on 2020-12-12T01:20:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Background: This study evaluated the presence of a silica-nylon mesh and two cantilever lengths on the biomechanical behavior of complete-arch implant-supported prostheses. Material and Methods: Twenty-four (24) complete mandibular arch implant-supported prostheses were divided into 4 groups according to the presence of reinforcing mesh (with or without) and the cantilever length (molar-15 mm or premolar-5 mm). The specimens were submitted to strain gauge analysis (30-kgf, 10 s) at different points (molar and premolar). Three-dimensional models were created based on the in vitro spec…
The cold shock response of the psychrotrophic bacterium Pseudomonas fragi involves four low-molecular-mass nucleic acid-binding proteins
1997
The psychrotrophic bacterium Pseudomonas fragi was subjected to cold shocks from 30 or 20 to 5 degrees C. The downshifts were followed by a lag phase before growth resumed at a characteristic 5 degrees C growth rate. The analysis of protein patterns by two-dimentional gel electrophoresis revealed overexpression of 25 or 17 proteins and underexpression of 12 proteins following the 30- or 20-to-5 degrees C shift, respectively. The two downshifts shared similar variations of synthesis of 20 proteins. The kinetic analysis distinguished the induced proteins into cold shock proteins (Csps), which were rapidly but transiently overexpressed, and cold acclimation proteins (Caps), which were more or …
Conserved Structure and Promoter Sequence Similarity in the Mouse and Human Genes Encoding the Zinc Finger Factor BERF-1/BFCOL1/ZBP-89
2001
Abstract We have characterized the genomic structure of the mouse Zfp148 gene encoding Beta-Enolase Repressor Factor-1 (BERF-1), a Kruppel-like zinc finger protein involved in the transcriptional regulation of several genes, which is also termed ZBP-89, BFCOL1. The cloned Zfp148 gene spans 110 kb of genomic DNA encompassing the 5′-end region, 9 exons, 8 introns, and the 3′-untranslated region. The promoter region displays the typical features of a housekeeping gene: a high G+C content and the absence of canonical TATA and CAAT boxes consistent with the multiple transcription initiation sites determined by primary extension analysis. Computer-assisted search in the human genome database allo…
Rational design of allosteric modulators of the aromatase enzyme: An unprecedented therapeutic strategy to fight breast cancer.
2019
Estrogens play a key role in cellular proliferation of estrogen-receptor-positive (ER+) breast cancers (BCs). Suppression of estrogen production by competitive inhibitors of the enzyme aromatase (AIs) is currently one of the most effective therapies against ER + BC. Yet, the development of acquired resistance, after prolonged treatments with AIs, represents a clinical major concern. Serendipitous findings indicate that aromatase may be non-competitively inhibited by clinically employed drugs and/or industrial chemicals. Here, by performing in silico screening on two putative allosteric sites, molecular dynamics and free energy simulations, supported by enzymatic and cell-based assays, we id…
Design, synthesis and biological evaluation of novel stilbene-based antitumor agents
2008
A series of novel stilbene derivatives has been synthesized and studied with the main goal to investigate SAR of the amino compound 1a, as well as to improve its water solubility, a potentially negative aspect of the molecule that could be a serious obstacle for a pre-clinical development. We have obtained derivatives with good cytotoxic activity, in particular, the derivatives 5c and 6b could represent two novel leads for further investigation. Compound 8b, a morpholino-carbamate derivative, prodrug of 1a, has a very good solubility in water, and is active in suppressing growth of tumor cells at a concentration of 5000 nM, which is a concentration 100 times higher than the parent stilbene …
Impact of exogenous lactate on survival and radioresponse of carcinoma cells in vitro
2009
Tumour lactate levels have been shown to correlate with high radioresistance in tumour models in vivo. The study aimed to evaluate the impact of pathophysiological extracellular lactate concentrations and acidosis on the in vitro survival and radioresponse of various cancer cell lines.HCT-116, HT29 (colorectal) and FaDu (HNSCC) carcinoma cells were studied. Lactate release rates were determined, and expression of the monocarboxylate transporter MCT1 and its cofactor CD147 were monitored by immunofluorescence and flow cytometry. Colony formation was compared for cells exposed to 20 mM exogenous lactate, acidosis (pH 6.4) and lactate plus acidosis relative to control and dose response curves …
Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patien…
2015
OBJECTIVE: To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053).METHODS: Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoi…