No abstract

A hallmark of the development of solid and hematological malignancies is the dysregulation of apoptosis, which leads to an imbalance between cell proliferation, cell survival and death. Halogenated boroxine [K2(B3O3F4OH)] (HB) is a derivative of cyclic anhydride of boronic acid, with reproducible anti‐tumor and anti‐proliferative effects in different cell models. Notably, these changes are observed to be more profound in tumor cells than in normal cells. Here, we investigated the underlying mechanisms through an extensive evaluation of (a) deregulated target genes and (b) their interactions and links with main apoptotic pathway genes upon treatment with an optimized concentration of HB. To provide deeper insights into the mechanism of action of HB, we performed identification, visualization, and pathway association of differentially expressed genes (DEGs) involved in regulation of apoptosis among tumor and non‐tumor cells upon HB treatment. We report that HB at a concentration of 0.2 mg·mL−1 drives tumor cells to apoptosis, whereas non‐tumor cells are not affected. Comparison of DEG profiles, gene interactions and pathway associations suggests that the HB effect and tumor‐‘selectivity’ can be explained by Bax/Bak‐independent mitochondrial depolarization by ROS generation and TRAIL‐like activation, followed by permanent inhibition of NFκB signaling pathway specifically in tumor cells.

At the end of December 2019, first identified cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started emerging. Ever since the emergence of the first case of infection with SARS-CoV-2 or COVID-19, it became the hottest research topic of numerous studies, in which scientists are trying to understand the path of infection, transmission, replication and viral action, all in order of finding a potential cure or vaccine applying various fundamental principles and methodologies. Using in silico method via AutoDock Vina 1.1.2., we analysed the binding affinity of six selected compounds from grapefruit seed extract (GSE) (narirutin, naringin, naringenin, limonin, ascorbic acid and citric acid) to SARS-CoV-2 main protease Mpro (PDB ID: 6Y84), using acetoside, remdesivir and gallic acid as a positive controls of binding affinity. Results showed highest affinity (rmsd l.b. 0.000; rmsd u.b. 0.000) for narirutin (-10.5), then for naringin (-10.1), acetoside (-10.0), limonin (-9.9), remdesivir (-9.6), naringenin (-8.2), ascorbic acid (-6.7), citric acid (-6.4) and gallic acid (-6.4), all expressed in kcal/mol. Our findings suggest that selected compounds from grapefruit seed extract represent potential inhibitors of SARS-CoV-2 Mpro, but further research is needed as well as preclinical and clinical trials for final confirmation of inhibitory functionality of these compounds.

Luteolin and delphinidin are the flavonoids with known protective roles. They inhibit genotoxic effects induced by halogenated boroxine (HB) in vitro. Statistically significant decrease in the number of micronuclei and nuclear buds and decrease in proportion of abnormal cells were observed before, but mechanism of their anti-genotoxic activity is still not clear. In our experiment we aimed to quantify HB effects on the relative expression of CAT (catalase) gene and explore antioxidative effects of luteolin and delphinidin via restoration of CAT gene activity. Cell cultures from peripheral blood lymphocytes of five healthy donors were established and treated with single and combined treatments of HB with luteolin or delphinidin. Total RNA was isolated from harvested cells and reverse-transcribed. SYBR based Real-Time PCR amplification method was used. Relative gene expression measurements were done using normalization of ratio of target (CAT) and housekeeping (GAPDH) genes. Intergroup variance analysis was done with REST® software. Luteolin itself lead to downregulation of relative CAT gene expression as well as HB. But simultaneous treatment of HB and bioflavonoids lead to upregulation. Delphinidin as indenpendent treatment and as simultaneous treatment caused upregulation of relative CAT gene expression. Obtained results may suggest protective role of delphinidin and luteolin to oxidative-stress damage caused by HB, and also that new approaches to the treatment applications of HB should include bioflavonoids and monitoring corresponding antioxidant system. Our findings indicate that there is a quantifiable effect of luteolin and delphinidine on antioxidant genes which could be used in exact monitoring of oxidative stress related events.

POSSIBLE FACTORS AND INTENSITY OF SOMATIZATION SYMPTOMS AS A RESPONSE TO STRESS IN THE STUDENT POPULATION