Evaluation of antioxidant activation by potential nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Keap1 complex inhibitors

Purpose: To investigate the binding affinities of forty-one (41) National Cancer Institute (NCI)-generated compounds, to the Nrf2 ligand, and possible activation of Nrf2 in the MCF-7 cell line.Methods: To investigate the inhibition of the Nrf2/Keap1 complex, the MCF-7 cell line was treated with each of the 41 compounds, at a working concentration of 30 μM. The extent of Nrf2 activation and corresponding Nrf2/Keap1 complex inhibition was evaluated in terms of Nrf2 expression and its antioxidant-associated enzyme gamma-glutamylcysteine synthetase (GCS), using western blotanalysis.Results: Twenty-nine compounds out of the 41 targeted compounds activated GCS, and some showed comparable or greater activation capacity than the standard Nrf2 activator tBHQ. To confirm that the activation of GCS was mediated via Nrf2 activation, cell lysates were tested for their Nrf2 protein expression, and it was found that Nrf2 was activated by the examined compounds for more than 24 h, indicating that the effect of the chosen compounds were not transient.Conclusion: These results might be useful for identifying better targets for cytoprotection, and for oxidative stress alleviation through Nrf2 pathway activation. Further studies are required on the effects of these targets on the prevention and treatment of various oxidative stress disorders, including cancer.

Transcription activation is enhanced by multivalent interactions independent of liquid-liquid phase separation

Transcription factors (TFs) consist of a DNA binding and an activation domain (AD) that are considered to be independent and exchangeable modules. However, recent studies conclude that also the physico-chemical properties of the AD can control TF assembly at chromatin via driving a phase separation into “transcriptional condensates”. Here, we dissected the mechanism of transcription activation at a reporter gene array with real-time single-cell fluorescence microscopy readouts. Our comparison of different synthetic TFs reveals that the phase separation propensity of the AD correlates with high transcription activation capacity by increasing binding site occupancy, residence time and the recruitment of co-activators. However, we find that the actual formation of phase separated TF liquid-like droplets has a neutral or inhibitory effect on transcription induction. Thus, our study suggests that the ability of a TF to phase separate reflects the functionally important property of the AD to establish multivalent interactions but does not by itself enhance transcription.

IMMUNOLOGICAL FEATURES IN CHILDREN WITH HEMORRHAGIC VASCULITIS

Currently the incidence of hemorrhagic vasculitis in children is characterized by an increase in all age groups what may be associated with environmental problems, chronic infection as well as food and drugs allergy. To date there are no biomarkers predicting the further development of hemorrhagic exanthema at the onset of the disease and followed its outcome. The quantitative and functional features of cellular and humoral immunity in children with hemorrhagic vasculitis of various origins accompanied by hemorrhagic exanthema at the onset of the disease are presented in this article. The reduction of γδТ-cells number in the peripheral blood correlated with levels of specific antineutrophil cytoplasmic antibodies and IgG EBNA-1 antibodies against a high ability of γδТ-cells to activation were established in children with systemic (immunocomplex) vasculitis. At the contrast, the background of a normal γδT-lymphocytes’ content was associated with the decrease in γδТ-cells activation capacity in children with hemorrhagic vasculitis of infectious-allergic genesis. Thus, quantitative and functional changes in γδТ-lymphocytes can be a potential labor biomarker for early diagnosis of systemic or infectious-allergic hemorrhagic vasculitis in children what may be used for the further disease course prediction.

Thermally Aerated Geopolymers as Lightweight Construction Material

In this research work, thermal foaming of bottom ash and sodium silicate geopolymer is proposed as a production process for light weight bricks. The composition and temperatures were studied and optimized to get the most suitable intumescence properties for the lightweight construction applications. For this purpose, four different compositions (i.e., 10%, 20%, 30%, and 40% bottom ash (BA)) were cured at four different curing temperatures (CT) (i.e., 200, 400, 500, and 600 °C). Sodium silicate (SS) to sodium hydroxide (SH) ratio was kept constant in order to keep the activation capacity of the solution constant in all the samples so that the effect of composition and CT could be studied effectively. All samples were characterized by bulk density, foamability, compression test, XRD, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), water absorption index (WAI), and weight loss index (WLI). These characterizations finally led to the optimized parameters to get the most appropriate intumescence properties. It was found that bottom ash and sodium silicate geopolymer foams have good potential to produce lightweight aerated blocks.

Grape Cane Extracts as Multifunctional Rejuvenating Cosmetic Ingredient: Evaluation of Sirtuin Activity, Tyrosinase Inhibition and Bioavailability Potential

Grape canes are waste biomass of viticulture containing bioactive polyphenols valuable in cosmetics. Whereas several studies reported the cosmetic activities of E-resveratrol, only few described the potential of E-ε-viniferin, the second major constituent of grape cane extracts (GCE), and none of them investigated GCE as a natural blend of polyphenols for cosmetic applications. In this study, we considered the potential of GCE from polyphenol-rich grape varieties as multifunctional cosmetic ingredients. HPLC analysis was performed to quantify major polyphenols in GCE i.e., catechin, epicatechin, E-resveratrol, E-piceatannol, ampelopsin A, E-ε-viniferin, hopeaphenol, isohopeaphenol, E-miyabenol C and E-vitisin B from selected cultivars. Skin whitening potential through tyrosinase inhibition assay and the activation capacity of cell longevity protein (SIRT1) of GCE were compared to pure E-resveratrol and E-ε-viniferin. Drug-likeness of GCE polyphenols were calculated, allowing the prediction of skin permeability and bioavailability. Finally, the present data enabled the consideration of GCE from polyphenol-rich varieties as multifunctional cosmetic ingredients in accordance with green chemistry practices.