Search results for "Mace"
showing 10 items of 4713 documents
Use of deep learning methods to translate drug-induced gene expression changes from rat to human primary hepatocytes
2020
In clinical trials, animal and cell line models are often used to evaluate the potential toxic effects of a novel compound or candidate drug before progressing to human trials. However, relating the results of animal and in vitro model exposures to relevant clinical outcomes in the human in vivo system still proves challenging, relying on often putative orthologs. In recent years, multiple studies have demonstrated that the repeated dose rodent bioassay, the current gold standard in the field, lacks sufficient sensitivity and specificity in predicting toxic effects of pharmaceuticals in humans. In this study, we evaluate the potential of deep learning techniques to translate the pattern of …
Common Hits Approach: Combining Pharmacophore Modeling and Molecular Dynamics Simulations.
2017
We present a new approach that incorporates flexibility based on extensive MD simulations of protein-ligand complexes into structure-based pharmacophore modeling and virtual screening. The approach uses the multiple coordinate sets saved during the MD simulations and generates for each frame a pharmacophore model. Pharmacophore models with the same pharmacophore features are pooled. In this way the high number of pharmacophore models that results from the MD simulation is reduced to only a few hundred representative pharmacophore models. Virtual screening runs are performed with every representative pharmacophore model; the screening results are combined and rescored to generate a single hi…
Genetics and Gene Therapy of Anderson-Fabry Disease.
2018
Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In the presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry's disease is confirmed by the demonstration of absence or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay …
Nutrient sensing pathways as therapeutic targets for healthy ageing
2017
Introduction: In the present paper, the authors have discussed anti-aging strategies which aim to slow the aging process and to delay the onset of age-related diseases, focusing on nutrient sensing pathways (NSPs) as therapeutic targets. Indeed, several studies have already demonstrated that both in animal models and humans, dietary interventions might have a positive impact on the aging process through the modulation of these pathways. Areas covered: Achieving healthy aging is the main challenge of the twenty-first century because lifespan is increasing, but not in tandem with good health. The authors have illustrated different approaches that can act on NSPs, modulating the rate of the ag…
Effects of ibuprofen and carbamazepine on the ion transport system and fatty acid metabolism of temperature conditioned juveniles of Solea senegalens…
2018
The increasing presence of pharmaceuticals in aquatic environments in the last decades, derived from human and veterinary use, has become an important environmental problem. Previous studies have shown that ibuprofen (IB) and carbamazepine (CBZ) modify physiological and biochemical processes in Senegalese sole (Solea senegalensis) in a temperature-dependent manner. In other vertebrates, there is evidence that both of these pharmaceuticals interfere with the ‘arachidonic acid (AA) cascade’, which is responsible for the biosynthesis of numerous enzymes that are involved in the osmoregulatory process. The present work aims to study the temperature-dependent effects of these two pharmaceuticals…
MPLA-coated hepatitis B virus surface antigen (HBsAg) nanocapsules induce vigorous T cell responses in cord blood derived human T cells.
2016
Chronic hepatitis B virus (HBV) infection is the most prevalent serious liver infection in the world. A frequent route of infection represents mother-to-child transmission. Efficient control of HBV replication depends on antigen-specific cellular immune response mediated by dendritic cells (DCs). Aim of the present study was to evaluate optimized adjuvant combinations, efficiently maturing monocyte-derived neonatal and adult dendritic cells (moDCs). In addition, the potential of polymeric HBsAg-nanocapsules (HBsAg-NCs) was investigated regarding up-take by moDCs and the subsequent induction of specific T cell responses in a human co-culture model. Simultaneous stimulation of moDCs with MPLA…
Effects of 3,5-diiodo-L-thyronine on the liver of high fat diet fed rats
2016
Experimental studies have highlighted that the administration of 3,5-diiodo-L-thyronine (T2) to rats fed diets rich in lipids induces a decrease of cholesterol and triglycerides plasma levels and body weight (BW) without inducing liver steatosis. On the basis of these observations we carried out some experimental <em>in vivo</em> studies to assess the effects of multiple high doses of T2 on the pituitary thyroid axis of rats fed diet rich in lipids. Fifteen male Wistar rats were divided into three groups of five animals each. The first group (N group) received standard diet, the second group was fed with a high fat diet (HFD group), while the third group (HFDT2 group) was additi…
The Sea Urchin sns5 Chromatin Insulator Shapes the Chromatin Architecture of a Lentivirus Vector Integrated in the Mammalian Genome.
2016
Lentivirus vectors are presently the favorite vehicles for therapeutic gene transfer in hematopoietic cells. Nonetheless, these vectors integrate randomly throughout the genome, exhibiting variegation of transgene expression due to the spreading of heterochromatin into the vector sequences. Moreover, the cis-regulatory elements harbored by the vector could disturb the proper transcription of resident genes neighboring the integration site. The incorporation of chromatin insulators in flanking position to the transferred unit can alleviate both the above-mentioned dangerous effects, due to the insulator-specific barrier and enhancer-blocking activities. In this study, we report the valuable …
Pharmaceutical Approaches to Target Antibiotic Resistance Mechanisms
2017
There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activation of efflux pumps. Here we assess the current landscape and challenges in the treatment of antibiotic resistance mechanisms at both bacterial cell and community levels. We also discuss the potential clinical application of chemical inhibitors of antibiotic resistance mechanisms as add-on treatments for serious drug-resistant infections. Enzymatic inhibitors, such as the deriv…
Identification of biological targets through the correlation between cell line chemosensitivity and protein expression pattern.
2021
Matching biological data sequences is one of the most interesting ways to discover new bioactive compounds. In particular, matching cell chemosensitivity with a protein expression profile can be a useful approach to predict the activity of compounds against definite biological targets. In this review, we discuss this correlation. First, we analyze case studies in which some known drugs, acting on known targets, show a good correlation between their antiproliferative activities and protein expression when a large panel of tumor cells is considered. Then, we highlight how the application of in silico methods based on the correlation between cell line chemosensitivity and gene/protein expressi…