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SARS-CoV-2 is the causative agent of the COVID-19 pandemic, the acute respiratory disease which, so far, has led to over 7 million deaths. There are several symptoms associated with SARS-CoV-2 infections which include neurological and psychiatric disorders, at least in the case of pre-Omicron variants. SARS-CoV-2 infection can also promote the onset of glioblastoma in patients without prior malignancies. In this study, we focused on the Envelope protein codified by the virus genome, which acts as viroporin and that is reported to be central for virus propagation. In particular, we characterized the electrophysiological profile of E-protein transfected U251 and HEK293 cells through the patch-clamp technique and FURA-2 measurements. Specifically, we observed an increase in the voltage-dependent (Kv) and calcium-dependent (KCa) potassium currents in HEK293 and U251 cell lines, respectively. Interestingly, in both cellular models, we observed a depolarization of the mitochondrial membrane potential in accordance with an alteration of U251 cell growth. We, therefore, investigated the transcriptional effect of E protein on the signaling pathways and found several gene alterations associated with apoptosis, cytokines and WNT pathways. The electrophysiological and transcriptional changes observed after E protein expression could explain the impact of SARS-CoV-2 infection on gliomagenesis. [ABSTRACT FROM AUTHOR]

Thermo-oxidative stability testing plays a critical role in accurately predicting shelf life. These tests are performed in real time and under stress conditions, where degradation processes are accelerated by increasing storage conditions. In this study, high-performance liquid chromatography (HPLC) analyses were performed to evaluate the degradation of resveratrol in nutraceutical tablets as a function of time under different storage conditions in terms of temperature and relative humidity (RH), namely 25 °C/60% RH, 30 °C/65% RH, and 40 °C/75% RH. The latter is an accelerated test and is used to estimate shelf life for long-term storage. Resveratrol is present in both pure form and as a solid dispersion on magnesium dihydroxide microparticles (Resv@MDH). Degradation kinetic constants were determined at 25 °C, 30 °C, and 40 °C, and the Arrhenius behavior of the kinetic constants as a function of temperature was verified. The main results of this work are as follows: (i) the stability of resveratrol in nutraceutical tablets is affected by temperature; (ii) the dependence of the kinetic constants on temperature does not follow the Arrhenius equation, determining an overestimation of the degradation rate at 25 °C; in this regard a modified version of the Arrhenius equation that takes into account the deviation from linearity has been used to estimate the dependence of the kinetic constant on the temperature. These results suggest that accelerated testing does not provide a general model for predicting the shelf life of foods and dietary supplements. The reason may be due to possible matrix effects that result in different degradation mechanisms depending on the temperature. In this regard, symmetry relationships in the kinetics of chemical reactions resulting from microscopic reversibility and their relationship to the deviation from the Arrhenius equation are discussed. However, further research is needed to characterize the degradation mechanisms at different temperatures. The results of these studies would allow accurate prediction of food degradation to improve food safety and risk management and reduce food waste. In addition, knowledge of stability processes is necessary to ensure the maintenance of physiological processes by dietary supplements. [ABSTRACT FROM AUTHOR]

γ-Hydroxybutyric acid (GHB) is a psychotropic compound endogenous to the brain. Despite its potential physiological significance, the complete molecular mechanisms of action remain unexplained. To facilitate the isolation and identification of the high-affinity GHB binding site, we herein report the design and synthesis of the first 125I-labeled radioligands in the field, one of which contains a photoaffinity label which enables it to bind irreversibly to the high-affinity GHB binding sites. [ABSTRACT FROM AUTHOR]

Based on low solubility in water and high membrane permeability, resveratrol is collocated in the second class of the Biopharmaceutical Classification System, with limited absorption derived from a low dissolution rate. Solid microdispersion of resveratrol supported by magnesium dihydroxide (Resv@MDH, trademark Revifast®) represents a physical mixture of resveratrol (30% w/w) and magnesium dihydroxide (70% w/w) obtained by traditional techniques, such as mixing and micronization under appropriate conditions. Establishing the wide use of Revifast® in food supplements, in the present work we deepen its physicochemical characterization by using diffractometric and infrared analysis. No novel species are found in the Resv@MDH mixture except magnesium dihydroxide and resveratrol extracted from Polygonum cuspidatum. The results herein reported strengthened the safety of Revifast® ingredients for resveratrol-based food supplements. [ABSTRACT FROM AUTHOR]

Bile acids regulate nongenomic actions through the activation of TGR5, a membrane receptor that is G protein-coupled to the induction of adenylate cyclase. In this work, a training set of 43 bile acid derivatives is used to develop a molecular interaction field analysis (MFA) and a 3D-quantitative structure-activity relationship study (3D-QSAR) of TGR5 agonists. The predictive ability of the resulting model is evaluated using an external set of compounds with known TGR5 activity, and six bile acid derivatives whose unknown TGR5 activity is herein assessed with in vitro luciferase assay of cAMP formation. The results show a good predictive model and indicate a statistically relevant degree of correlation between the TGR5 activity and the molecular interaction fields produced by discrete positions of the bile acid scaffold. This information is instrumental to extend on a quantitative basis the current structure-activity relationships of bile acids as TGR5 modulators and will be fruitful to design new potent and selective agonists of the receptor.