Stimulation of Dopamine D4 Receptors in the Nucleus Accumbens Shell Increases Palatable Food Intake in Satiated Male Rats: Modulation by NMDA and AMPA Receptors.

Background/objectives: Palatability significantly influences food consumption, often leading to overeating and obesity by activating the brain's reward systems. The nucleus accumbens (NAc) plays a central role in this process, modulating reward mechanisms primarily via dopamine through D2-like receptors (D2R, D3R, D4R). While the involvement of D2 receptors in feeding is well-documented, the role of D4 receptors (D4Rs) is less clear.

Leishmania mexicana gp63 is the enzyme responsible for cyclooxygenase (COX) activity in this parasitic protozoa.

Cyclooxygenase-2 (COX-2) is an enzyme responsible of prostaglandins production, such as prostaglandin E (PGE), an immune response modulator that regulates the immune system to inhibit Th1 and to promote Th2 cytokines production. Many parasites modulate their host immune response through PGE effects; however, in parasites, only one protein with COX activity has been described, the α-actinin of Entamoeba histolytica. Prostanoids production has been reported in some species of Leishmania but not the enzymes responsible of their production.

Orally administered Taenia solium Calreticulin prevents experimental intestinal inflammation and is associated with a type 2 immune response.

Intestinal helminth antigens are inducers of type 2 responses and can elicit regulatory immune responses, resulting in dampened inflammation. Several platyhelminth proteins with anti-inflammatory activity have been reported. We have identified, cloned and expressed the Taenia solium calreticulin (rTsCRT) and shown that it predominantly induces a type 2 response characterized by IgG1, IL-4 and IL-5 production in mice.

Isoindoline Derivatives of α-Amino Acids as Cyclooxygenase 1 and 2 Inhibitors.

IC50 values were obtained for two series of isoindolines derived from α-amino acids over cyclooxygenase 1 and 2 (COX-1 and COX-2). In order to explain the biological activity observed, a structure-activity relationship (SAR) model was achieved for the tested compounds and 19 reference compounds with known selective inhibitory activity, through the correlation of the binding energies calculated from rigid docking of the best conformations into the catalytic sites of COX-1 and COX-2, as well as their molecular descriptors: Log P, molecular weight (MW), volume (V), and solvation energy (Esol) versus their experimental IC50 values by MLR and LS-SVM methods. The model probed whether the COX-1 and COX-2 inhibitory activities of the isoindolines correlate with steric, hydrophobic, and thermodynamic parameters.