Contribution of hyperglycemia-induced changes in microglia to Alzheimer's disease pathology.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive and functional impairments. The investigation of AD has focused on the formation of senile plaques, composed mainly by amyloid ß (Aß) peptide, and neurofibrillary tangles (NFTs) in the brain. Senile plaques and NFTs cause the excessive recruitment and activation of microglia, thus generating neuroinflammation and neuronal damage. Among the risk factors for the development of AD, diabetes has increasingly attracted attention. Hyperglycemia, the fundamental characteristic of diabetes, is involved in several mechanisms that give rise to microglial overactivation, resulting in neuronal damage and cognitive impairment. Indeed, various studies have identified the correlation between diabetes and AD. The aim of this review is to describe various mechanisms of the hyperglycemia-induced overactivation of microglia, which leads to neuroinflammation and neuronal damage and consequently contributes to the pathology of AD. The disruption of the regulation of microglial activity by hyperglycemia occurs through many mechanisms, including a greater production of reactive oxygen species (ROS) and glycation end products (AGEs), and a decrease in the elimination of Aß. The future direction of research on the relation between hyperglycemia and AD is addressed, such as the importance of determining whether the hyperglycemia-induced harmful effects on microglial activity can be reversed or attenuated if blood glucose returns to a normal level.

The Ability of Chlorophyll to Trap Carcinogen Aflatoxin B1: A Theoretical Approach.

The coordination of one and two aflatoxin B1 (AFB1, a potent carcinogen) molecules with chlorophyll a (chl a) was studied at a theoretical level. Calculations were performed using the M06-2X method in conjunction with the 6-311G(d,p) basis set, in both gas and water phases. The molecular electrostatic potential map shows the chemical activity of various sites of the AFB1 and chl a molecules. The energy difference between molecular orbitals of AFB1 and chl a allowed for the establishment of an intermolecular interaction. A charge transfer from AFB1 to the central cation of chl a was shown. The energies of the optimized structures for chl a show two configurations, unfolded and folded, with a difference of 15.41 kcal/mol. Chl a appeared axially coordinated to the plane (α-down or ß-up) of the porphyrin moiety, either with the oxygen atom of the ketonic group, or with the oxygen atom of the lactone moiety of AFB1. The complexes of maximum stability were chl a 1-α-E-AFB1 and chl a 2-ß-E-AFB1, at -36.4 and -39.2 kcal/mol, respectively. Additionally, with two AFB1 molecules were chl a 1-D-2AFB1 and chl a 2-E-2AFB1, at -60.0 and -64.8 kcal/mol, respectively. Finally, biosorbents containing chlorophyll could improve AFB1 adsorption.

In vitro and computational studies of natural products related to perezone as anti-neoplastic agents.

Many natural phyto-products as perezone (Per) exhibit anti-cancer activities. Using experimental and computational studies, it was described that Poly ADP-ribose polymerase 1(PARP-1) inhibition and the induction of oxidative stress state explain the pro-apoptotic activity of Per. The aim of this study was to evaluate two phyto-products related to Per as anti-cancer agents: hydroxyperezone (OHPer) and its monoangelate (OHPer-MAng). These molecules were structurally characterized employing thermal analysis, IR spectrophotometry and X-ray diffraction techniques. The phyto-compounds evaluated in vitro in six cancer cell lines (K562, MCF-7, MDA-MB-231, HeLa, U373, A549) and non-malignant cells determinate their cytotoxicity, type of induced cell death, ability to avoid cell migration and changes at the redox status of the cell. Using, in vitro and computational studies provided the inhibition of PARP-1 and its potential binding mode. Cell proliferation assays demonstrated that OHPer-MAng treatment significantly induces apoptosis in triple negative breast cancer (TNBC) cell line (MDA-MB-231 IC50 = 3.53 µM), being particularly less cytotoxic to Vero cells (IC50 = 313.92 µM), human lymphocytes (IC50 = 221.46 µM) and rat endothelial cells (IC50=> 400 µM). The treatment of MDA-MB-231 cells with OHPer-MAng showed inhibition of migration by cancer cells. The induction of an oxidative stress state, similar to other quinones and PARP-1 inhibition explains the pro-apoptotic activity of OHPer-MAng. Docking studies showed that OHPer-MAng establishes great non-bonding interactions with the lateral chains of Tyr235, Hys201, Tyr246, Ser203, Asn207, and Gly233 located at the catalytic site of PARP-1, also demonstrating the anti-cancer activity of OHPer-MAng in TNBC cell line.

Comparative study using different infrared zones of the solventless activation of organic reactions.

In this work, the results of a study comparing the use of irradiation from different regions of the infrared spectrum for the promotion of several organic reactions, are presented and discussed. This use of eco-conditions provides a green approach to chemical synthesis. A set of ten different organic reactions were evaluated, including the Knoevenagel, Hantzsch, Biginelli and Meldrum reactions. It is important to highlight the use of a commercial device that produces infrared irradiation in the near infrared region and its distribution by convection providing heating uniformity, significantly reducing reaction times, achieving good yields and proceeding in the absence of solvent. It is also worth noting that a variety of different reactions may be performed at the same time. Finally, the products obtained were identified using TLC, together with corresponding MS-data, complementarily in comparison of NMR (1)H and (13)C data with literature information.