appropriate risk management. Three coordination compounds featuring different types of tetracopper(II) cores, namely [O ⊂ Cu4N(CH2CH2O)34(BOH)4][BF4]2 (1), [Cu4(μ4-H2edte)(μ5-H2edte)(sal)2]n·7nH2O, (H4edte = N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine, H2sal = salicylic acid) (2), and [Cu4(μ3-Hbes)4(μ-hba)K(H2O)3]n, H3bes = N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (3), were assayed for their potency to inhibit the acetyl (AChE) and butyrylcholinesterase (BuChE) enzymes aiming to test these compounds as potential dual inhibitors in the treatment of Alzheimer's disease. All the investigated compounds showed a strong inhibitory potency toward both enzymes with IC50 values in micromolar range of concentration; compound 1 displayed the most potent inhibitory behaviour toward both enzymes. The mechanism of the AChE and BuChE inhibition was examined by enzyme kinetic measurements. The obtained kinetic parameters, Vmax and Km indicated an uncompetitive type of inhibition of both enzymes by compound 1. For the other two compounds a non-competitive inhibition mode was observed. To get further insight into the mechanism of action and to elucidate binding modes in details we examined the interactions of 1-3 with acetylcholinesterase, using molecular docking approach. Grid based docking studies indicated that these compounds can bind to peripheral anionic site (PAS) of the AChE with Ki values in micromolar range. Moreover, blind docking revealed the capability of investigated compounds to bind to new allosteric site (i.e. binding site II) distinct from PAS. Showing that these Cu-based compounds can act as new allosteric inhibitors of AChE and identifying novel allosteric binding site on AChE represents a significant contribution toward the design of novel and more effective inhibitors of AChE. Hyperprolactinemia is a common but neglected adverse effect of antipsychotic agents. Current treatments for antipsychotic-induced hyperprolactinemia exert their action mainly through the mechanism of enhancing the inhibitory effect of dopamine on prolactin secretion; however, patients have to endure the risk of psychotic relapse or exacerbation. Topiramate, a new anticonvulsant, is widely used in the treatment of numerous psychiatric conditions. It can antagonize α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate (KA) glutamate receptors and enhance the inhibitory activity of γ-amino butyric acid (GABA). Inhibition of AMPA and KA receptors and increased GABA activity has been proved to have an inhibitory effect on prolactin release. Thus, topiramate may be an effective agent in the treatment of antipsychotic-induced hyperprolactinemia. Parkinson's disease (PD) is a progressive degenerative nervous system disorder and is the second most common neurodegenerative disorder in the elderly population. The disease originates from the loss of dopamine-producing neurons in the substantia nigra in the brain, resulting in unregulated activity of the basal ganglia. Αlpha-synuclein (α-syn) is a protein found to aggregate in the substantia nigra region of patients with PD, forming Lewy Body inclusions; its aggregation may contribute to neuronal cell death in PD. This work hypothesizes about the synergistic relationship between α-syn aggregation and neuroinflammation to up-regulate expression of the serine protease inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1). The protease, plasmin, has been shown to cleave extracellular α-syn (including its monomeric, oligomeric, and fibrillary forms), resulting in less aggregation and Lewy Body formation. The zymogen plasminogen is converted to its active serine protease form, plasmin, either by tissue plasminogen activator (tPA) or by urokinase plasminogen activator (uPA) bound to urokinase receptor (uPAR). Both tPA and uPA/uPAR are inhibited by PAI-1. Thus, when PAI-1 levels increase, less plasmin is generated, which would lead to reduced proteolysis of α-syn. Expression of PAI-1 is increased both in inflammatory environments and in the presence of extracellular α-syn aggregates. This scenario suggests a pathological amplification loop increased extracellular α-syn aggregation activates an inflammatory response from microglia and astrocytes, increasing PAI-1 levels, and decreasing the generation of plasmin. With reduced plasmin, less α-syn can be cleaved, and aggregation continues, sustaining the pathological process. Understanding this putative pathogenic loop could provide insight into the means by which neurodegeneration progresses in PD, and it may offer possible novel therapeutic strategies. Chirality seems to play a key role in mineralization. Indeed, in biominerals, the biomolecules that guide the formation and organization of inorganic crystals and help construct materials with exceptional mechanical properties, are homochiral. read more Here, we show that addition of homochiral l-(+)-tartaric acid improved the mechanical properties of brushite bioceramics by decreasing their crystal size, following the classic Hall-Petch strengthening effect; d-(-)-tartaric acid had the opposite effect. Adding l-(+)-Tar increased both the compressive strength (26 MPa) and the fracture toughness (0.3 MPa m1/2) of brushite bioceramics, by 33% and 62%, respectively, compared to brushite bioceramics without additives. In addition, l-(+)-tartaric acid enabled the fabrication of cements with high powder-to-liquid ratios, reaching a compressive strength and fracture toughness as high as 32.2 MPa and 0.6 MPa m1/2, respectively, approximately 62% and 268% higher than that of brushite bioceramics prepared without additives, respnot been studied yet. In this study, we showed that homochiral l-(+)-tartaric acid can regulate the crystal structure and improve the mechanical properties of a calcium-phosphate cement. Hence, these findings open the door for a new way of designing strong bone cement and highlight the importance of chirality in bioceramics. Damaged articular cartilage has limited self-healing capabilities, leading to degeneration that affects millions of people. Although cartilage tissue engineering is considered a promising approach for treatment, robust and long-term chondrogenesis within a 3-dimensional (3D) scaffold remains a major challenge for complete regeneration. Most current approaches involve incorporation of transforming growth factor-β (TGF-β) into the scaffold, but have limited utility owing to the short functional half-life and/or rapid clearance of TGF-β. In this study, we have tested the incorporation of graphene oxide nanosheets (GO) within a photopolymerizable poly-D, l-lactic acid/polyethylene glycol (PDLLA) hydrogel, for its applicability in sustained release of the chondroinductive growth factor TGF-β3. We found that with GO incorporation, the hydrogel scaffold (GO/PDLLA) exhibited enhanced initial mechanical strength, i.e., increased compressive modulus, and supported long-term, sustained release of TGF-β3 for up to 4 weeks.