Upregulation of Cathepsin X in Glioblastoma: Interplay with γ-Enolase and the Effects of Selective Cathepsin X Inhibitors

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Understanding GBM pathobiology and discovering novel therapeutic targets are critical to finding efficient treatments. Upregulation of the lysosomal cysteine carboxypeptidase cathepsin X has been linked to immune dysfunction and neurodegenerative diseases, but its role in cancer and particularly in GBM progression in patients is unknown. In this study, cathepsin X expression and activity were found to be upregulated in human GBM tissues compared to low-grade gliomas and nontumor brain tissues. Cathepsin X was localized in GBM cells as well as in tumor-associated macrophages and microglia. Subsequently, potent irreversible (AMS36) and reversible (Z7) selective cathepsin X inhibitors were tested in vitro. Selective cathepsin X inhibitors decreased the viability of patient-derived GBM cells as well as macrophages and microglia that were cultured in conditioned media of GBM cells. We next examined the expression pattern of neuron-specific enzyme γ-enolase, which is the target of cathepsin X. We found that there was a correlation between high proteolytic activity of cathepsin X and C-terminal cleavage of γ-enolase and that cathepsin X and γ-enolase were colocalized in GBM tissues, preferentially in GBM-associated macrophages and microglia. Taken together, our results on patient-derived material suggest that cathepsin X is involved in GBM progression and is a potential target for therapeutic approaches against GBM.     

Lipid oxidative changes in chitosan-oregano coated traditional dry fermented sausage Petrovská klobása

The effect of a chitosan coating with added essential oil of oregano (Origanum vulgare) on lipid oxidation of dry fermented sausage (Petrovská klobása) was investigated. Fatty acid profile, aldehyde contents and sensory analysis of odor and flavor were determined after drying and during seven months of storage.     

Implementation of Artificial Neural Networks in Modeling the Water-Air Temperature Relationship of the River Drava

Water temperature directly affects the physical, biological and chemical characteristics of the river and determines the fitness and life of all aquatic organisms. It has direct and indirect effects on nearly all aspects of stream ecology. Accurately estimating water temperature is a complex problem. The purpose of this article is to analyze the relationship between the air and water temperature of the River Drava by constructing an artificial neural network (ANN) model and choosing appropriate network architectures for the River Drava’s daily river water temperature as well as demonstrating its application in improving the interpretation of the results. A linear regression model, as well as a stochastic model are also constructed and compared to ANN models consisting of a multilayer perceptron neural network and a radial basis function network. The results indicate that the ANN models are much better models and that ANNs are powerful tools that can be used for the estimation of daily mean river temperature.     

Non-iterative parameter estimation of the 2R-1C model suitable for low-cost embedded hardware

Frontiers of Information Technology & Electronic Engineering - Parameter estimation of the 2R-1C model is usually performed using iterative methods that require high-performance processing...     

Dual Escherichia coli DNA Gyrase A and B Inhibitors with Antibacterial Activity

The emergence of multidrug-resistant bacteria is a global health threat necessitating the discovery of new antibacterials and novel strategies for fighting bacterial infections. We report first-in-class DNA gyrase B (GyrB) inhibitor/ciprofloxacin hybrids that display antibacterial activity against Escherichia coli. Whereas DNA gyrase ATPase inhibition experiments, DNA gyrase supercoiling assays, and in vitro antibacterial assays suggest binding of the hybrids to the E. coli GyrA and GyrB subunits, an interaction with the GyrA fluoroquinolone-binding site seems to be solely responsible for their antibacterial activity. Our results provide a foundation for a new concept of facilitating entry of nonpermeating GyrB inhibitors into bacteria by conjugation with ciprofloxacin, a highly permeable GyrA inhibitor. A hybrid molecule containing GyrA and GyrB inhibitor parts entering the bacterial cell would then elicit a strong antibacterial effect by inhibition of both the GyrA and GyrB subunits of DNA gyrase and potentially slow bacterial resistance development.     

Intensification of Mass Transfer in the Extraction Process with a Nanofluid Prepared in a Natural Deep Eutectic Solvent

The phytotoxic residues after olive oil production and residue leaves after pruning contain valuable bioactive compounds. A natural deep eutectic solvent (NADES) and an ethanol-water mixture were used for polyphenol extraction from olive pomace and leaves. Type of solvent, extraction temperature, and particle size of the leaves were optimized. NADES demonstrated better efficiency in the extraction process than conventional solvents; with higher temperature and smaller fraction of olive leaves, a higher yield of polyphenols was obtained from leaves. Extraction with a nanofluid as solvent was carried out. A stable nanofluid was prepared from NADES by adding Al₂O₃ nanoparticles. A higher yield was obtained with nanofluid from leaves, while an improvement of polyphenol extraction was achieved after the removal of oil from olive pomace.     

Antioxidant activity of medicinal plant extracts in cookies

The antioxidant activity of ethanolic extracts of parsley, buckthorn, mint, caraway, and their mixture "Vitalplant" was evaluated, and the potential of "Vitalplant" mixture extract to retard the process of lipid oxidation in cookies was tested. The antioxidant activity was estimated by 2 direct (ESR) and 4 indirect (spectrophotometric) tests and correlated with the total phenolic and flavonoid content. The potential of "Vitalplant" mixture extract to retard the process of lipid oxidation in cookies was measured by thiobarbituric acid (TBA)-reactive-substances assay (TBARS) and DPPH˙ (1,1-diphenyl-2-picryl-hydrazyl) test. Significantly different (P < 0.05) amounts of total phenolics were found among extracts in the following order: mint > buckthorn > "Vitalplant" > parsley > caraway. Total flavonoid content varied from 0.510% (parsley) to 2.05% ("Vitalplant"). A statistically significant correlation was found between IC(50) values on DPPH˙ and total flavonoid content of the samples (r=- 0.94, P < 0.05) and between IC(50) values on DPPH˙ and IC(50) values on O(2) (·-) scavenging activity (r= 0.89, P < 0.05). A correlation between reducing activity and total phenolic content was found to be positive and statistically significant (r= 0.94, P < 0.05). "Vitalplant" mixture exhibited a relatively high antioxidant activity in most of the tests, which can be explained by synergistic effects of the ingredients of which it is composed. Finally, "Vitalplant" extract addition (2%, 4%, and 6%) improved antioxidant activity and oxidative stability of the cookies in dose-dependent manner. PRACTICAL APPLICATION: Supplementation of cookies with a mixture of Petroselini fructus, Frangulae cortex, Mentha piperitae folium, Carvi fructus can retard the process of lipid oxidation and elevate antioxidant activity of the final product.     

Synthesis and biological evaluation of N-acylhydrazones as inhibitors of MurC and MurD ligases

The Mur ligases have an essential role in the intracellular biosynthesis of bacterial peptidoglycan, and they represent attractive targets for the design of novel antibacterials. A series of compounds with an N-acylhydrazone scaffold were synthesized and screened for inhibition of the MurC and MurD enzymes from Escherichia coli. Compounds with micromolar inhibitory activities against both MurC and MurD were identified, and some of them also showed antibacterial activity.     

Separation of Hydrocarbons by Means of Liquid-Liquid Extraction with Deep Eutectic Solvents

Liquid-liquid equilibria for six ternary systems with choline chloride urea or choline chloride glycerol (molar ratio, 1:2) as selective solvent were experimentally determined at atmospheric pressure and 25°C. Equilibrium data were presented with tie lines. Extraction experiments with three-component systems were performed. The suitability of deep eutectic solvents for the separation of pyridine and toluene from n-hexane, and n-butanol from toluene was evaluated in terms of properties of solvents, solute distribution ratio, and extraction efficiency. Choline chloride glycerol has a better potential for separation of pyridine from its mixture with n-hexane. The equilibrium data were well described with the NRTL model.