Search results for "DISCOVERY"

Cannabidiol Treatment Might Promote Resilience to Cocaine and Methamphetamine Use Disorders: A Review of Possible Mechanisms

2019

Currently, there are no approved pharmacotherapies for addiction to cocaine and other psychostimulant drugs. Several studies have proposed that cannabidiol (CBD) could be a promising treatment for substance use disorders. In the present work, the authors describe the scarce preclinical and human research about the actions of CBD on the effects of stimulant drugs, mainly cocaine and methamphetamine (METH). Additionally, the possible mechanisms underlying the therapeutic potential of CBD on stimulant use disorders are reviewed. CBD has reversed toxicity and seizures induced by cocaine, behavioural sensitization induced by amphetamines, motivation to self-administer cocaine and METH, context- …

Salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole, a structural and analog of acetazolamide, show interesting carbonic anhydrase inhibitory properties…

2015

Three salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole (Hats) were prepared and characterized by physico-chemical methods. The p-toluensulfonate, the methylsulfonate, and the chlorhydrate monohydrate salts of Hats were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) and as anticonvulsants and diuretics, since many CAIs are clinically used as pharmacological agents. The three Hats salts exhibited diuretic and anticonvulsant activities with little neurotoxicity. The human (h) isoforms hCA I, II, IV, VII, IX, and XII were inhibited in their micromolar range by these salts, whereas pathogenic beta and gamma CAs showed similar, weak inhibitory profiles.

Cytotoxicity of natural products and derivatives toward MCF-7 cell monolayers and cancer stem-like mammospheres

2015

Abstract Although cancer stem-like cells (CSCs) are rare, they can enter a non-proliferative or dormant state and resist therapy. Furthermore, quiescent CSCs are responsible for metastases that can appear after curative surgical treatment of a primary tumor. Because of drug resistance of CSCs, the development of novel therapies is urgently required that specifically target CSCs. Purpose The aim of the present study was to investigate the potential of a panel of natural products and derivatives to inhibit CSC-enriched mammospheres of MCF-7 breast cancer cells. Methods CD44high/CD24low cells were identified by flow cytometry and maintained as mammospheres. As a control, we used two clinically…

Dendritic cells lentivirally engineered to overexpress interleukin-10 inhibit contact hypersensitivity responses, despite their partial activation in…

2010

Background Dendritic cells (DCs) constitute an attractive target for immunotherapeutic approaches. Because DCs are largely refractory to transfection with plasmid DNA, several viral transduction protocols were established. The potential side-effects of lentiviral transduction on the phenotype and activation state of DCs left unstimulated after transduction have not been assessed. There is a need to analyse these parameters as a result of the requirement of using DCs with a low activation state for therapeutic strategies intended to induce tolerance. Methods Lentivirally-transduced bone marrow (BM)-derived DCs (LV-DCs) in comparison with mock-transduced (Mock-DCs) and untreated DCs were anal…

Inorganic Mercury Sequestration by a Poly(ethylene imine) Dendrimer in Aqueous Solution

2015

The interaction of the G-2 poly(ethylene imine) dendrimer L, derived from ammonia as initiating core, with Hg(II) and HgCl4 2− was studied in aqueous solution by means of potentiometric (pH-metric) measurements. Speciation of these complex systems showed that L is able to form a wide variety of complexes including 1:1, 2:1, 3:1 and 3:2 metal-to-ligand species, of different protonation states, as well as the anion complexes ((H7L)HgCl4) 5+ and ((H8L)HgCl4) 6+ . The stability of the metal complexes is very high, making L an excellent sequestering agent for Hg(II), over a large pH range, and a promising ligand for the preparation of functionalized activated carbons to be employed in the remedi…

CH vs. HC—Promiscuous Metal Sponges in Antimicrobial Peptides and Metallophores

2023

Histidine and cysteine residues, with their imidazole and thiol moieties that deprotonate at approximately physiological pH values, are primary binding sites for Zn(II), Ni(II) and Fe(II) ions and are thus ubiquitous both in peptidic metallophores and in antimicrobial peptides that may use nutritional immunity as a way to limit pathogenicity during infection. We focus on metal complex solution equilibria of model sequences encompassing Cys–His and His–Cys motifs, showing that the position of histidine and cysteine residues in the sequence has a crucial impact on its coordination properties. CH and HC motifs occur as many as 411 times in the antimicrobial peptide database, while …

Always pay attention to which model of motor learning you are using

2022

This critical review considers the epistemological and historical background of the theoretical construct of motor learning for a more differentiated understanding. More than simply reflecting critically on the models that are used to solve problems—whether they are applied in therapy, physical education, or training practice—this review seeks to respond constructively to the recent discussion caused by the replication crisis in life sciences. To this end, an in-depth review of contemporary motor learning approaches is provided, with a pragmatism-oriented clarification of the researcher’s intentions on fundamentals (what?), subjects (for whom?), time intervals (when?), and purpose (for what…

Framework for pedagogical learning analytics

2018

Learning analytics is an emergent technological practice and a multidisciplinary scientific discipline, which goal is to facilitate effective learning and knowledge of learning. In this design science research, I combine knowledge discovery process, a concept of pedagogical knowledge, ethics of learning analytics and microservice architecture. The result is a framework for pedagogical learning analytics. The framework is applied and evaluated in the context of agency analytics. The framework contributes to the practical use of learning analytics.

Molecular Modelling Studies on Molecular Pathways Related to Tumorigenesis in the Discovery of New Lead Compounds.

2012

Case-specific performance of MM-PBSA, MM-GBSA, and SIE in virtual screening.

2015

In drug discovery the reliable prediction of binding free energies is of crucial importance. Methods that combine molecular mechanics force fields with continuum solvent models have become popular because of their high accuracy and relatively good computational efficiency. In this research we studied the performance of molecular mechanics generalized Born surface area (MM-GBSA), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), and solvated interaction energy (SIE) both in their virtual screening efficiency and their ability to predict experimentally determined binding affinities for five different protein targets. The protein-ligand complexes were derived with two different app…