New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin

Background: Doxorubicin (DOX) has been very effective against glioblastoma invitro. Its application in vivo is hampered because it cannot pass the blood–brainbarrier (BBB). Significant research efforts are invested to overcome this limitation.Sclareol (SC) is an aromatic compound naturally found in clary sage. Thecombination of SC and DOX showed promising effects in different tumor types invitro and in vivo. Therefore, we tested their combination and innovative hybridmolecules (SC:DOX) on glioblastoma cells with the expression of P-glycoprotein, amajor component of BBB and cancer multidrug resistance marker. Methods:Cytotoxicity and selectivity towards glioblastoma cells of SC, DOX, theircombination, and SC:DOX were examined by MTT assay. The effect of SC on DOXaccumulation was determined by flow cytometry. We also studied SC:DOXaccumulation, cellular uptake, localization imaging, and DNA damage induction.Results: The effects of simultaneous SC and DOX treatments demonstrated theconsiderable potential of SC to reverse DOX resistance in glioblastoma cells andincrease DOX accumulation. SC:DOX hybrids, named CON1 and CON2 were lesscytotoxic than DOX, but with reduced resistance and increased selectivity towardsglioblastoma cells. Cellular uptake of CON1 and CON2 was increased in glioblastomacells compared to DOX. Perinuclear localization of CON1 and CON2 vs. nuclearlocalization of DOX as well as no DNA damaging effects suggest a differentmechanism of action for SC:DOX. Conclusion: The combination of SC and DOX, andtheir innovative hybrids, could be considered a promising strategy that can overcomethe limitations of DOX application in glioblastoma.Kanazir S, Savić D, editors. Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. Belgrade : Serbian Neuroscience Society; 2023. p. 71

Fabrication of silver-decorated zinc oxide microrods by hydrothermal method

We report on hydrothermal synthesis of zinc oxide (ZnO) hexagonal microrods and microtubes. Zinc oxide seeds were deposited onto glass slides by dip coating and used as templates for hydrothermal growth of ZnO microcrystals. The process was carried out in an alkaline reaction medium with acetate and nitrate zinc precursors, using hexamethylene tetramine (HMT) as surfactant. The obtained ZnO microrods were successfully decorated with silver particles via dipping ZnO-containing glass slides in silver nitrate solution and subsequent UV irradiation (5 min). Zinc oxide and Ag/ZnO microparticles were characterized by SEM, EDS and XRD. The presented results are part of the larger concept of developing of anisotropic Ag/ZnO microrods for conversion of chemical to mechanical energy.X Serbian Ceramic Society Conference - Advanced Ceramics and Application : new frontiers in multifunctional material science and processing : program and the book of abstracts; September 26-27, 2022; Belgrad

The role of gut microbiota in depressive behavior and the effects of antidepressants

There is accumulating evidence demonstrating effects of gastrointestinal microbiota on brain function and behavior, including depressive behavior. We have demonstrated that antidepressants, the main drugs used for alleviating depression, affect gut microbiota composition as well, and in this way partly contribute to improvement of depressive symptoms. Specifically, our results showed that several types of antidepressants reduced abundance of bacterial genera Ruminococcus, while supplementation with R. flavefaciens diminished antidepressant-induced decrease of depressive behavior. Treatment with R. flavefaciens affected cortical gene networks, up-regulating genes involved in mitochondrial oxidative phosphorylation, while down-regulating genes involved in neuronal plasticity, suggesting a mechanism for microbial regulation of antidepressant treatment efficiency. In further studies, we are aiming to delineate the role of gut microbiota in conveying the long-term effects of adolescent stress on development of anxiety and depressive behavior

Deep UV fluorescence imaging study of Candida albicans cells treated with gold-riboflavin hydrocolloids

Fluorescent nanostructures were prepared by functionalization of gold nanoparticles with riboflavin molecules and used as probes for synchrotron radiation deep ultraviolet (SR-DUV) fluorescence imaging of gluteraldehyde-fixed Candida albicans cells. The nanoparticles were characterized by transmission electron microscopy (TEM) and optical spectroscopy techniques. The TEM analysis showed that the nanostructures were 6 nm in diameter, while the results of the fluorescence spectroscopies confirmed the photoluminescence of the nanoparticles. The SR-DUV imaging showed that it was possible to distinguish the fluorescence of the nanoparticles from the autofluorescence of the cells, as well as that the local maxima of the signal pertaining to the fluorescence of goldriboflavin nanostructures were mostly positioned on the surfaces of the C. albicans cells of spherical morphology

Impact of Clonal Variability on Phenolics and Radical Scavenging Activity of Grapes and Wines: A Study on the Recently Developed Merlot and Cabernet Franc Clones (<i>Vitis vinifera</i> L.)

<div><p>In this study, grapes and corresponding wines of Merlot /No 022, 025 and 029/ and Cabernet Franc /No 02, 010 and 012/ clones (recently developed) were evaluated regarding the total phenolic content, total anthocyanin content, and radical scavenging activity, aiming to better understand their quality and market potential. The nineteen individual polyphenols were quantified in studied grape samples using UHPLC coupled to a triple-quadrupole mass spectrometer. The mother grapes and wines were used as the relevant standards. In the grape, studied characteristics were monitored at three stages of berry development: green berry, véraison and mature berry. The mature grape of clones presented high values of total phenolics (3.81–10.89 g gallic acid equivalent kg^-1 frozen weight), anthocyanin content (359.00–1668.18 mg malvidin-3-<i>O</i>-glucoside kg^-1 frozen weight) and the radical scavenging activity (41.37–80.48 mmol trolox equivalent kg^-1 frozen weight) depending on the clone. Grapes and wines of Merlot No 025 and Cabernet Franc No 010 stood out with the highest values of all three parameters. Generally, the high correlation was observed between TPC and RSA values for green berries and mature grapes, as well as for wine samples. The most abundant phenolics in both Merlot and Cabernet Franc grapes were gallic acid, <i>p</i>-hydroxybenzoic acid, ferulic acid, catechin, epicatechin, gallocatechin gallate, catechin gallate, and rutin. Catechin, epicatechin, epigallocatechin, and catechin gallate, typical for the ripe grape of Merlot and Cabernet Franc clones, showed significant correlation with RSA values. Concentrations of individual polyphenols varied depending on the sample being studied and berry development stages. Merlot No 025 and Cabernet Franc No 010 grapes showed particularly interesting attributes for the production of high quality wines.</p></div