Therapeutic potential of LINS01 histamine H receptor antagonists as antineoplastic agents for triple negative breast cancer.

The aims of this work were to evaluate the expression of histamine H receptor (HR) in triple negative breast cancer (TNBC) samples and to investigate the antitumoral efficacy and safety of the LINS01 series of HR antagonists, through in silico, in vitro, and in vivo approaches. Antitumor activity of LINS01009, LINS01010, LINS01022, LINS01023 was assayed in vitro in 4T1 and MDA-MB-231 TNBC cells (0.01-100 μM), and in vivo in 4T1 tumors orthotopically established in BALB/c mice (1 or 20 mg/kg).

Nanomicellar Formulations Loaded with Histamine and Paclitaxel as a New Strategy to Improve Chemotherapy for Breast Cancer.

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Currently, paclitaxel (PTX) represents the first-line therapy for TNBC; however it presents a hydrophobic behavior and produces severe adverse effects. The aim of this work is to improve the therapeutic index of PTX through the design and characterization of novel nanomicellar polymeric formulations composed of a biocompatible copolymer Soluplus (S), surface-decorated with glucose (GS), and co-loaded either with histamine (HA, 5 mg/mL) and/or PTX (4 mg/mL).

Meditation Increases the Entropy of Brain Oscillatory Activity.

We address the hypothesis that the entropy of neural dynamics indexes the intensity and quality of conscious content. Previous work established that serotonergic psychedelics can have a dysregulating effect on brain activity, leading to subjective effects that present a considerable overlap with the phenomenology of certain meditative states. Here we propose that the prolonged practice of meditation results in endogenous increased entropy of brain oscillatory activity.

Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports.

The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings of peace, bliss and timelessness, life review, the sensation of traveling through a tunnel and an irreversible threshold. Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism. Anecdotal accounts of the similarity between NDEs and certain drug-induced altered states of consciousness prompted us to perform a large-scale comparative analysis of these experiences.

Metal bashing: iron deficiency and manganese overexposure impact on peripheral nerves.

Iron (Fe) deficiency (FeD) and manganese (Mn) overexposure (MnOE) may result in several neurological alterations in the nervous system. Iron deficiency produces unique neurological deficits due to its elemental role in central nervous system (CNS) development and myelination, which might persist after normalization of Fe in the diet. Conversely, MnOE is associated with diverse neurocognitive deficits.

The Varieties of the Psychedelic Experience: A Preliminary Study of the Association Between the Reported Subjective Effects and the Binding Affinity Profiles of Substituted Phenethylamines and Tryptamines.

Classic psychedelics are substances of paramount cultural and neuroscientific importance. A distinctive feature of psychedelic drugs is the wide range of potential subjective effects they can elicit, known to be deeply influenced by the internal state of the user ("set") and the surroundings ("setting"). The observation of cross-tolerance and a series of empirical studies in humans and animal models support agonism at the serotonin (5-HT) receptor as a common mechanism for the action of psychedelics.

DMT1 iron uptake in the PNS: bridging the gap between injury and regeneration.

Previous studies by our group demonstrated the key role of iron in Schwann cell maturation through an increase in cAMP, PKA activation and CREB phosphorylation. These studies opened the door to further research on non-transferrin-bound iron uptake, which revealed the presence of DMT1 mRNA all along SC progeny, hinting at a constitutive role of DMT1 in ensuring the provision of iron in the PNS. In light of these previous results, the present work evaluates the participation of DMT1 in the remyelination process following a demyelinating lesion promoted by sciatic nerve crush--a reversible model of Wallerian degeneration.

DMT1 as a candidate for non-transferrin-bound iron uptake in the peripheral nervous system.

Iron, either in its chelated form or as holotransferrin (hTf), prevents the dedifferentiation of Schwann cells (SC), cells responsible for the myelination of the peripheral nervous system (PNS). This dedifferentiation is promoted by serum deprivation through cAMP release, PKA activation, and CREB phosphorylation. Since iron elicits its effect in a transferrin (Tf)-free environment, in this work we postulate that non-transferrin-bound iron (NTBI) uptake must be involved.

Bone marrow mononuclear cells migrate to the demyelinated sciatic nerve and transdifferentiate into Schwann cells after nerve injury: attempt at a peripheral nervous system intrinsic repair mechanism.

In the present work, we analyzed whether endogenous and/or transplanted bone marrow mononuclear cells (BMMC) migrate spontaneously to the crushed sciatic nerve and whether they transdifferentiate into Schwann cells (SC) in order to help repair the damaged tissue. We also studied both the immunohistochemical evolution of myelin proteins MBP and P(0) and the myelin composition of both the proximal and distal stumps of the crushed sciatic nerve to determine the demyelination-remyelination period. Immunohistochemical analysis of crushed animals showed that the degeneration process consists of loss of nerve fiber integrity accompanied by degradation of myelin basic proteins MBP and P(0) , which is anticipated by protein cluster formation.