Extracellular vesicles as innovative tool for diagnosis, regeneration and protection against neurological damage

Extracellular vesicles (EVs) have recently attracted a great deal of interest as they may represent a new biosignaling paradigm. According to the mode of biogenesis, size and composition, two broad categories of EVs have been described, exosomes and microvesicles. EVs have been shown to carry cargoes of signaling proteins, RNA species, DNA and lipids. Once released, their content is selectively taken up by near or distant target cells, influencing their behavior. Exosomes are involved in cell–cell communication in a wide range of embryonic developmental processes and in fetal–maternal communication. In the present review, an outline of the role of EVs in neural development, regeneration and diseases is presented. EVs can act as regulators of normal homeostasis, but they can also promote either neuroinflammation/degeneration or tissue repair in pathological conditions, depending on their content. Since EV molecular cargo constitutes a representation of the origin cell status, EVs can be exploited in the diagnosis of several diseases. Due to their capability to cross the blood–brain barrier (BBB), EVs not only have been suggested for the diagnosis of central nervous system disorders by means of minimally invasive procedures, i.e., “liquid biopsies”, but they are also considered attractive tools for targeted drug delivery across the BBB. From the therapeutic perspective, mesenchymal stem cells (MSCs) represent one of the most promising sources of EVs. In particular, the neuroprotective properties of MSCs derived from the dental pulp are here discussed

Innovative solutions for prehistoric paintings - atmospheric pressure plasma and phosphate consolidant for the preservation of the Magura Cave (Bulgaria)

The present study tackles the problem of a sustainable and efficient conservation of cave art, by using innovative materials and techniques for the different steps of the restoration process - Biodeactivation, Biocolonization prevention and Consolidation. The Magura cave in northwest Bulgaria is the case study. It contains an impressive display of prehistoric paintings made of guano as far back as 5\u2019500 years ago. In the last forty years the cave suffered progressive microbial colonization. The detrimental effects are biofilm formation, physical penetration into the stone and chemical reaction with the stone/paintings by pigments. Therefore, as a first step, we investigated biodeactivation by non-thermal plasma sterilization. The oxidative atmosphere obtained introducing Ar/O2 (0.2 and 0.1) in the plasma device, was carried out on lab samples inoculated with the targeted for Magura Cave microorganisms. The main advantage of the non-contact treatment with atmospheric pressure plasma (APP) is the lack of any mechanical and chemical modification of the underlying stone/guano layers. As for sterilization of wounds on human skin the plasma treatment on wet surfaces produces mainly hydrogen peroxide and nitrates which lead to a localized reduction of the pH. The obtained biodeactivation is assured without heat (< 40 \ub0C), toxic and environmentally harmful liquid. In a second step, we tested two possible alternatives for consolidation of the cave. A commercial ethyl silicate (ES) product was compared with an innovative phosphate treatment, based on application of a hydro-alcoholic solution of a phosphate salt (diammonium hydrogen phosphate, DAP). The consolidation efficiency and compatibility of the ES and DAP consolidants were investigated on samples representative for the Magura Cave substrate, i.e. stone alone and stone covered with guano to resemble the prehistoric drawings. In addition, a combination of plasma activation of the stone surface and consolidation was tested, to investigate whether the two treatments may have a synergistic effect, thus making the combined treatment more efficient than consolidation alone

Physico-chemical and pharmaceutical characterization of sulindac–proglumide binary system

Sulindac is a nonsteroidal anti-inflammatory drug with poor water solubility. This study presents a way to increase its dissolution rate while reducing the risk of gastrointestinal side effects. This approach considers the paired administration of sulindac with the gastroprotector proglumide, in the form of eutectic mixture. Theoretical and experimental methods proved that sulindac and proglumide form a simple eutectic system containing a molar fraction of proglumide of 0.7 at the eutectic point. The product with the eutectic composition, obtained by solvent evaporation, shows a significant improvement in the sulindac dissolution rate compared to the corresponding physical mixture

Shape fidelity and sterility assessment of 3D printed polycaprolactone and hydroxyapatite scaffolds

Polycaprolactone (PCL) and hydroxyapatite (HA) composite are widely used in tissue engineering (TE). They are fit to being processed with three-dimensional (3D) printing technique to create scaffolds with verifiable porosity. The current challenge is to guarantee the reliability and reproducibility of 3D printed scaffolds and to create sterile scaffolds which can be used for in vitro cell cultures. In this context it is important for successful cell culture, to have a protocol in order to evaluate the sterility of the printed scaffolds. We proposed a systematic approach to sterilise 90%PCL-10%HA pellets using a 3D bioprinter before starting the printing process. We evaluated the printability of PCL-HA composite and the shape fidelity of scaffolds printed with and without sterilised pellets varying infill pattern, and the sterility of 3D printed scaffolds following the method established by the United States Pharmacopoeia. Finally, the thermal analyses supported by the Fourier Transform Infrared Spectroscopy were useful to verify the stability of the sterilisation process in the PCL solid state with and without HA. The results show that the use of the 3D printer, according to the proposed protocol, allows to obtain sterile 3D PCL-HA scaffolds suitable for TE applications such as bone or cartilage repair

Enhancing the Pharmaceutical Behavior of Nateglinide by Cocrystallization: Physicochemical Assessment of Cocrystal Formation and Informed Use of Differential Scanning Calorimetry for Its Quantitative Characterization

The aim of this study was to synthetize cocrystals of nateglinide, an antidiabetic agent of bio- pharmaceutics classification system Class IIa, as a strategy to improve both the solubility and the dissolution rate of the drug. Benzamide was selected by a screening procedure as a suitable coformer, and binary mixtures with different compositions were prepared and analyzed by differential scanning calorimetry (DSC). An in-depth analysis of DSC data allowed obtaining both the eutectic mixture and cocrystal compositions. The rationale of such an analysis was highlighted and explained. Cocrystals were prepared by kneading and solvent evaporation. Their formation was proved by DSC and confirmed by X-ray powder diffraction, solid-state nuclear magnetic resonance, and Fourier-transform infrared spec- troscopy. The functional groups involved in the interaction leading to cocrystals formation were inves- tigated by spectroscopic techniques. The in vitro dissolution profiles show that cocrystals have definite better pharmaceutical performances than the pure drug

Extracellular vesicles as innovative tool for diagnosis, regeneration and protection against neurological damage

Abstract Extracellular vesicles (EVs) have recently attracted a great deal of interest as they may represent a new biosignaling paradigm. According to the mode of biogenesis, size and composition, two broad categories of EVs have been described, exosomes and microvesicles. EVs have been shown to carry cargoes of signaling proteins, RNA species, DNA and lipids. Once released, their content is selectively taken up by near or distant target cells, influencing their behavior. Exosomes are involved in cell–cell communication in a wide range of embryonic developmental processes and in fetal–maternal communication. In the present review, an outline of the role of EVs in neural development, regeneration and diseases is presented. EVs can act as regulators of normal homeostasis, but they can also promote either neuroinflammation/degeneration or tissue repair in pathological conditions, depending on their content. Since EV molecular cargo constitutes a representation of the origin cell status, EVs can be exploited in the diagnosis of several diseases. Due to their capability to cross the blood–brain barrier (BBB), EVs not only have been suggested for the diagnosis of central nervous system disorders by means of minimally invasive procedures, i.e., “liquid biopsies”, but they are also considered attractive tools for targeted drug delivery across the BBB. From the therapeutic perspective, mesenchymal stem cells (MSCs) represent one of the most promising sources of EVs. In particular, the neuroprotective properties of MSCs derived from the dental pulp are here discussed