Aluminum-induced alterations of purinergic signalling in embryonic neural progenitor cells.

The ubiquitous presence of aluminum in the environment leads to a high likelihood of human exposure. Neurotoxicity of the trivalent cationic form of this metal (Al3+) occurs in the central nervous system via accumulation of Al in cells of neural origin, including neural progenitor cells (NPCs). NPCs play a key role in the development and regeneration of the brain throughout life; therefore, this metal may contribute to neuropathological conditions. Here, we evaluated the effects of different Al3+ concentrations (0-50 µM) on the purinergic system of NPCs isolated from embryonic telencephalons, cultured as neurospheres. Al3+ adhered to the cell surface of neurospheres reducing extracellular ATP release, as well as ATP, ADP, and AMP hydrolysis by NTPDase and 5'-nucleotidase, respectively. In addition, impaired nucleotide release by Al3+ reduced P2Y1 and adenosine A2A receptors expression in differentiated neurospheres. These receptors are crucial for NPC proliferation during brain development and self-repair against external stimuli, such as metal exposure. Thus, Al3+ represents an environmental agent linked to neurodegeneration through alterations in the ATP-signalling pathway, proving to be a potential mechanism associated with NPC proliferation and brain degeneration.

Aluminum affects neural phenotype determination of embryonic neural progenitor cells.

Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer's disease (AD). The Al-free ion (Al3+) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al3+ (in the chloride form-AlCl3) at different concentrations (0.1-100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Al3+ at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al3+ had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker ß3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Al3+ caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.

Regioselective synthesis, biological evaluation, and molecular docking of dihydropyrimidin-4-ols as acetylcholinesterase inhibitors.

A new series of 3,6-disubstituted 2-(methylthio)-4-(trifluoromethyl)-3,4-dihydropyrimidin-4-ols displaying methyl, phenyl, aryl, and heteroaryl groups at the 6-position; and methyl, ethyl, allyl, and phenyl groups at the 3-position of the dihydropyrimidine ring, were synthesized and evaluated in vitro for acetylcholinesterase inhibitory activity. Seven compounds showed activity with IC50 values in the lower micromolar range. The compound 4-trifluoromethyl-6-(4-fluorophenyl)-3-methyl-2-methylthio-3,4-dihydropyrimidin-4-ol (6e) had the best inhibitory activity (IC50 2.2 ± 0.9 µm) and this inhibition was characterized as competitive. The molecular docking study showed that the acetylcholinesterase enzyme accommodates compound 6e in its catalytic site. The enantiomers of compound 6e, present similar interactions: π-π stacking interactions between the aromatic ring of the ligand's 4-fluorophenyl moiety and the aromatic rings of the electron-rich Trp84; and H-bonds between the hydroxyl group of Tyr121 and the hydroxyl moiety from 6e. The antioxidant effect of the dihydropyrimidin-4-ols was also investigated.

Alteraciones en mucosa bucal y percepción de salud oral en adultos mayores portadores de prótesis / Oral mucosal alterations and oral health perception in older adults bearing dental prostheses

Actualmente, los problemas asociados al progresivo envejecimiento de la población son objeto de mayor atención, debido al aumento de las personas mayores, especialmente en las sociedades industrializadas. En el corto y el mediano plazo, estaremos frente a una población importante de adultos mayores; así, se tendrá que asumir la atención de este grupo poblacional. Estas personas pueden haber perdido piezas dentarias y la instalación de un aparato protésico constituye una solución para rehabilitar la función del sistema estomatognático. La terapia prostodóntica debe conservar la salud de los tejidos bucales y disminuir la resorción ósea. El descubrimiento y la prevención de las lesiones significará prolongar la esperanza y la calidad de vida de las personas de la tercera edad. La forma en que las personas perciben su salud bucal está relacionada con el bienestar; una boca saludable contribuye a que se sienta bien y ayuda a su satisfacción. Por ello, la percepción de salud bucal puede ser considerada como un factor predictor de la calidad de vida y se asocia a una variedad de indicadores de salud general y conductas saludables. Existen estudios que informan sobre la asociación entre la autopercepción de la salud bucal global con la autopercepción específica de limitaciones funcionales bucales. Los instrumentos para evaluar la calidad de vida relacionada con la salud bucal, son sensibles para detectar la influencia de los tratamientos odontológicos en la percepción del paciente sobre su salud bucal, lo que podría ser útil para relacionar satisfacción y percepción del paciente en relación a su rehabilitación

Alteraciones en mucosa bucal y percepción de salud oral en adultos mayores portadores de prótesis / Oral mucosal alterations and oral health perception in older adults bearing dental prostheses

Actualmente, los problemas asociados al progresivo envejecimiento de la población son objeto de mayor atención, debido al aumento de las personas mayores, especialmente en las sociedades industrializadas. En el corto y el mediano plazo, estaremos frente a una población importante de adultos mayores; así, se tendrá que asumir la atención de este grupo poblacional. Estas personas pueden haber perdido piezas dentarias y la instalación de un aparato protésico constituye una solución para rehabilitar la función del sistema estomatognático. La terapia prostodóntica debe conservar la salud de los tejidos bucales y disminuir la resorción ósea. El descubrimiento y la prevención de las lesiones significará prolongar la esperanza y la calidad de vida de las personas de la tercera edad. La forma en que las personas perciben su salud bucal está relacionada con el bienestar; una boca saludable contribuye a que se sienta bien y ayuda a su satisfacción. Por ello, la percepción de salud bucal puede ser considerada como un factor predictor de la calidad de vida y se asocia a una variedad de indicadores de salud general y conductas saludables. Existen estudios que informan sobre la asociación entre la autopercepción de la salud bucal global con la autopercepción específica de limitaciones funcionales bucales. Los instrumentos para evaluar la calidad de vida relacionada con la salud bucal, son sensibles para detectar la influencia de los tratamientos odontológicos en la percepción del paciente sobre su salud bucal, lo que podría ser útil para relacionar satisfacción y percepción del paciente en relación a su rehabilitación(AU)

Binding of NorR to three DNA sites is essential for promoter activation of the flavorubredoxin gene, the nitric oxide reductase of Escherichia coli.

NorR is a nitric oxide sensor that in Escherichia coli regulates the gene encoding for flavorubredoxin, an enzyme involved in nitrosative detoxification. The present work shows that although purified NorR can bind independently to each of three binding sites in the flavorubredoxin gene promoter, the presence of all sites is required for in vivo nitric oxide-dependent induction of the flavorubredoxin gene. Furthermore, trimerization of NorR upon binding to the three sites was observed by protein cross-linking experiments. These results reveal the importance of the multiple DNA binding sites present on NorR-dependent promoters and suggest that the functional form of NorR is a trimer.