RESUMO
Obesity is a pandemic and a serious health problem in developed and undeveloped countries. Activation of estrogen receptor beta (ERß) has been shown to promote weight loss without modifying caloric intake, making it an attractive target for developing new drugs against obesity. This work aimed to predict new small molecules as potential ERß activators. A ligand-based virtual screening of the ZINC15, PubChem, and Molport databases by substructure and similarity was carried out using the three-dimensional organization of known ligands as a reference. A molecular docking screening of FDA-approved drugs was also conducted as a repositioning strategy. Finally, selected compounds were evaluated by molecular dynamic simulations. Compounds 1 (-24.27 ± 0.34 kcal/mol), 2 (-23.33 ± 0.3 kcal/mol), and 6 (-29.55 ± 0.51 kcal/mol) showed the best stability on the active site in complex with ERß with an RMSD < 3.3 Å. RMSF analysis showed that these compounds do not affect the fluctuation of the Cα of ERß nor the compactness according to the radius of gyration. Finally, an in silico evaluation of ADMET showed they are safe molecules. These results suggest that new ERß ligands could be promising molecules for obesity control.
Assuntos
Simulação de Dinâmica Molecular , Receptores de Estrogênio , Simulação de Acoplamento Molecular , Ligantes , Receptor beta de EstrogênioRESUMO
Neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3), NT-4, and NT-5, are proteins involved in several important functions of the central nervous system. The activation of the signaling pathways of these neurotrophins, or even by their immature form, pro-neurotrophins, starts with their recognition by cellular receptors, such as tropomyosin receptor kinase (Trk) and 75 kD NT receptors (p75NTR). The Trk receptor is considered to have a high affinity for attachment to specific neurotrophins, while the p75NTR receptor has less affinity for attachment with neurotrophins. The correct functioning of these signaling pathways contributes to proper brain development, neuronal survival, and synaptic plasticity. Unbalanced levels of neurotrophins and pro-neurotrophins have been associated with neurological disorders, illustrating the importance of these molecules in the central nervous system. Furthermore, reports have indicated that viruses can alter the normal levels of neurotrophins by interfering with their signaling pathways. This work discusses the importance of neurotrophins in the central nervous system, their signaling pathways, and how viruses can affect them.
Assuntos
Transdução de Sinais , Viroses , Sistema Nervoso Central , Humanos , Plasticidade Neuronal , Receptores de Superfície Celular , Transdução de Sinais/fisiologiaRESUMO
Exopolysaccharides (EPS) production is a characteristic that has been widely described for many lactic acid bacteria (LAB) of different genera and species, but little is known about the relationship between the functional properties of the producing bacteria and EPS synthesis. Although many studies were addressed towards the application of EPS-producing LAB in the manufacture of several dairy products (fermented milk, cheese) due to their interesting technological properties (increased hardness, water holding capacity, viscosity, etc.), there are not many reports about the functional properties of the EPS extract itself, especially for the genus Lactobacillus. The aim of the present revision is to focus on the species Lactobacillus fermentum with reported functional properties, with particular emphasis on those strains capable of producing EPS, and try to establish if there is any linkage between this property and their functional/probiotic roles, considering the most recent bibliography.
Assuntos
Produtos Fermentados do Leite/microbiologia , Microbiologia de Alimentos , Limosilactobacillus fermentum/fisiologia , Polissacarídeos Bacterianos/biossíntese , Animais , Antibiose , Bactérias/patogenicidade , Fenômenos Fisiológicos Bacterianos , Fermentação , Fatores Imunológicos , Limosilactobacillus fermentum/química , Probióticos/metabolismoRESUMO
Avian infectious laryngotracheitis (ILT) is a worldwide infectious disease that causes important economic losses in the poultry industry. Although it is known that ILT virus (ILTV) is present in Argentina, there is no information about the circulating strains. With the aim to characterize them, seven different genomic regions (thymidine kinase, glycoproteins D, G, B, C, and J, and infected cell polypeptide 4) were partially sequenced and compared between field samples. The gJ sequence resulted to be the most informative segment, it allowed the differentiation among field sample strains, and also, between wild and vaccine viruses. Specific changes in selected nucleotidic positions led to the definition of five distinct haplotypes. Tests for detection of clustering were run to test the null hypothesis that ILTV haplotypes were randomly distributed in time in Argentina and in space in the most densely populated poultry region of this country, Entre Rios. From this study, it was possible to identify a 46 km radius cluster in which higher proportions of haplotypes 4 and 5 were observed, next to a provincial route in Entre Rios and a significant decline of haplotype 5 between 2009 and 2011. Results here provide an update on the molecular epidemiology of ILT in Argentina, including data on specific genome segments that may be used for rapid characterization of the virus in the field. Ultimately, results will contribute to the surveillance of ILT in the country.