Reactions of 3-formylchromone with active methylene and methyl compounds and some subsequent reactions of the resulting condensation products

This review presents a survey of the condensations of 3-formylchromone with various active methylene and methyl compounds, e.g. malonic or barbituric acid derivatives, five-membered heterocycles, etc. The utilisation of the condensation products for the synthesis of different heterocyclic systems, which is based on the ability of the gamma-pyrone ring to be opened by the nucleophilic attack is also reviewed. Finally, the applications of microwave irradiation as an unconventional method of reaction activation in the synthesis of condensation products is described and the biological activity of some chromone derivatives is noted.     

Acrylamide-Derived Ionome,Metabolic, and Cell Cycle Alterations Are Alleviated by Ascorbic Acid in the Fission Yeast

Acrylamide (AA), is a chemical with multiple industrial applications, however, it can be found in foods that are rich in carbohydrates. Due to its genotoxic and cytotoxic effects, AA has been classified as a potential carcinogen. With the use of spectrophotometry, ICP-OES, fluorescence spectroscopy, and microscopy cell growth, metabolic activity, apoptosis, ROS production, MDA formation, CAT and SOD activity, ionome balance, and chromosome segregation were determined in Schizosaccharomyces pombe. AA caused growth and metabolic activity retardation, enhanced ROS and MDA production, and modulated antioxidant enzyme activity. This led to damage to the cell homeostasis due to ionome balance disruption. Moreover, AA-induced oxidative stress caused alterations in the cell cycle regulation resulting in chromosome segregation errors, as 4.07% of cells displayed sister chromatid non-disjunction during mitosis. Ascorbic acid (AsA, Vitamin C), a strong natural antioxidant, was used to alleviate the negative impact of AA. Cell pre-treatment with AsA significantly improved AA impaired growth, and antioxidant capacity, and supported ionome balance maintenance mainly due to the promotion of calcium uptake. Chromosome missegregation was reduced to 1.79% (44% improvement) by AsA pre-incubation. Results of our multiapproach analyses suggest that AA-induced oxidative stress is the major cause of alteration to cell homeostasis and cell cycle regulation.     

The DI-SPME Method for Determination of Selected Narcotics and Their Metabolites,and Application to Bone Marrow and Whole Blood Analysis

The present investigation utilised the quick and easy SPME/LC-MS method to determine selected narcotic substances and their metabolites in whole blood. The study included qualitative analysis and validation of the method. Analytes were determined in the linearity range of 25–300 ng/mL. The precision during and between days (in general CV < 13.41%), and the LOD which results in between 0.36 and 11.08 ng/mL, and the LOQ between 1.20 and 36.90 ng/mL were investigated. The validation results obtained, as well as the results of subsequent in-laboratory tests, confirmed the applicability of the method in the analysis of blood samples. An attempt to apply the method to the analysis of bone marrow samples has yielded promising results; however, more detailed studies are needed in this area.     

Synthesis and Systematic Study on the Effect of Different PEG Units on Stability of PEGylated,Integrin-αvβ6-Specific A20FMDV2 Analogues in Rat Serum and Human Plasma

A20FMDV2 is a 20-mer peptide that exhibits high selectivity and affinity for the tumour-related αvβ6 integrin that can compete with extracellular ligands for the crucial RGD binding site, playing a role as a promising αvβ6-specific inhibitor for anti-cancer therapies. Unfortunately, the clinical value of A20FMDV2 is limited by its poor half-life in blood caused by rapid renal excretion and its reported high susceptibility to serum proteases. The incorporation of poly (ethylene glycol) chains, coined PEGylation, is a well-established approach to improve the pharmacokinetic properties of drug molecules. Here, we report a systematic study on the incorporation of a varying number of ethylene glycol units (1–20) into the A20FMDV2 peptide to establish the effects of PEGylation size on the peptide stability in both rat serum and human plasma. In addition, the effect of acetyl and propionyl PEGylation handles on peptide stability is also described. Selected peptide analogues were assessed for integrin-αvβ6-targeted binding, showing good specificity and activity in vitro. Stability studies in rat serum established that all of the PEGylated peptides displayed good stability, and an A20FMDV2 peptide containing twenty ethylene glycol units (PEG₂₀) was the most stable. Surprisingly, the stability testing in human plasma identified shorter PEGs (PEG₂ and PEG₅) as more resistant to degradation than longer PEGs, a trend which was also observed with affinity binding to integrin αvβ6.     

Biochemical and Molecular Investigation of the Effect of Saponins and Terpenoids Derived from Leaves of Ilex aquifolium on Lipid Metabolism of Obese Zucker Rats

Ilex paraguariensis, the holly tree, is a plant with recognized biological properties, whose aqueous infusions are known as “Yerba mate”, that regulate lipid metabolism, reduce obesity, and improve brain stimulation. In the present study, the effect of standardized saponin and terpenoid fractions of a European taxon, Ilex aquifolium, on blood biochemical parameters in a rat model of metabolic disorder, (fa/fa) Zucker, are presented. The profiles of the volatile fractions of two species and six European varieties of Ilex were investigated. After selecting the best variety, the saponin and terpenoid fractions were isolated and standardized, and animals were fed 10 mg kg⁻¹ b.w. for 8 weeks. A statistically significant decrease in liver adiposity was observed, confirmed by histology and quantitative identification (gas chromatography–mass spectrometry analyses of hepatic lipids. RT-qPCR analysis of gene expression in the aorta revealed that the administration of the terpenoid fraction downregulated LOX-1, suggesting a reduction in atherosclerotic stimuli. In addition, a statistically significant reduction (p < 0.05) in PPARγ for the saponin fraction was observed in the liver. The expression of the ACAT-1 gene in the liver, responsible for the formation of cholesterol esters, increased significantly in the group receiving the terpenoid fraction compared to the control, which was also confirmed by the analysis of individual blood biochemical parameters. The opposite effect was observed for saponins. Taking the above into account, it is shown for the first time that Ilex aquifolium can be a source of compounds that positively influence lipid metabolism.     

Analytical performance of glucometers in a tertiary care hospital

Point-of-care (POC) testing of glucose (glucometers) represents a convenient alternative to monitor glycemia since the measurement procedure is performed without delay after sampling of the capillary blood, thereby avoiding the metabolism by the blood cells of glucose present in plasma. Likely because of sample instability, there is no proficiency test provider in Brazil for this type of POC sample. In this context, this study aimed to evaluate the analytical performance of glucometers used in a tertiary care hospital. The glucometers used were the Accu-Chek Performa^® model from Roche Diagnostics, which use the principle of amperometry. The reference method was the reaction with modified hexokinase/glucose-6-phosphate in a Dimension^® device. The stability evaluation of the control samples showed that it can be performed up to 90 min after the collection of whole blood samples. In the two rounds performed, only one result of the 17 glucometers evaluated was out of the threshold of two standard deviation. Thus, this method for control of glucometers met the expectations and enabled comparing the glucometers in a hospital. Given the current quality guidelines, daily internal quality control of glucometers is recommended, besides at least two annual comparisons between the results of the glucometers and the reference method and one EQA every 3 months.