Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations.

Glioblastoma is an aggressive primary tumor of the central nervous system (CNS). Is the most aggressive among infiltrative gliomas arising from the CNS. This tumor has low patient survival rate and several studies aiming at developing new drugs have increased. Patients with this cancer type face significant morbidity and mortality. This study evaluated the antineoplastic activity of synthetic chalcones (3a-3f) using in vitro glioblastoma models and molecular modeling. Cytotoxicity assay showed that Astrocitoma Hospital Ofir Loyola No 1 (AHOL1) and Uppsala 87 neoplastic glioblastoma lines (U87) cellular viability were significantly reduced compared to Healthy human fibroblasts cell lines (AN27) when exposed to chalcones. Interaction with the serine amino acid was present in the most promising and the reference binder docking, suggesting its importance inhibiting cell growth. Comparative analysis between the reference ligands and the molecules showed that the amino acid LYS352 present in all fittings, suggesting that this is the main amino acid for interaction with tubulin and are consistent with those in cytotoxicity assay, suggesting antineoplastic potential in glioblastoma. Long trajectory molecular dynamics studies were also carried out in order to investigate stability and conformations amongst the chalcones bound tubulin as well, in comparison to doxorubicin (here used as control), however future studies are needed to further assess the mechanism of inhibition of chalcones used in this investigation.Communicated by Ramaswamy H. Sarma.

Can Paraplegia by Disruption of the Spinal Cord Tissue Be Reversed? The Signs of a New Perspective.

Central nervous system (CNS) trauma is often related to tissue loss, leading to partial or complete disruption of spinal cord function due to neuronal death. Although generally irreversible, traditional therapeutic efforts, such as physical therapy exercises, are generally recommended, but with a poor or reduced improvement of the microenvironment, which in turn stimulates neuroplasticity and neuroregeneration. Mesenchymal stem cells (MSCs) have paracrine, immunomodulatory, and anti-inflammatory effects. Here we use stem cells to see if they can promote not only physical but also the functional regeneration of neuronal tissue in dogs with CNS traumas. Two dogs, one with chronic spinal cord injury and one with subacute spinal cord injury, underwent infusion of autologous MSCs in association with physiotherapy. The two treatments in combination were able to partially or completely recover the dog's walking movement again. The treatment of MSCs in association with physical therapy improved the microenvironment, which could be evidence of a paradigm shift that the CNS is not capable of functional regeneration after aggressive traumas. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1812-1820, 2020. © 2019 American Association for Anatomy.