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.

ABSTRACT Population genetic studies have shown that the Bosnian-Herzegovinian (B&H) population is a part of the European gene pool, but there has been limited information on the genetic structure of ancient B&H populations. This study aimed to determine the frequency and distribution of mitochondrial DNA (mtDNA) haplogroups for a medieval Bosnian population. Thirty-four samples, excavated from medieval necropolises located within the borders of medieval Bosnia, were analyzed. Sequencing of the mtDNA hypervariable segment 1 (HVS1) region and RFLP analysis were performed for haplogroup determination. All 32 samples were identified as haplogroup H, with subhaplogroups H2a and H5 in 30 and 2 samples, respectively. The frequency of the H haplogroup was significantly different between the studied samples and previous studies of contemporary B&H populations, where the H haplogroup frequency was approximately half that of the ancient population studied here. A significant difference in H haplogroup frequency compared with other medieval populations outside of Bosnia was also observed: the ancient B&H population is most similar to ancient Italians. These results provide insight into the mitochondrial landscape of populations that inhabited the territory of present-day Bosnia and Herzegovina in the Middle Ages. Our study reveals that inhabitants of medieval Bosnia carried genetic lineages that exist today in B&H populations, suggesting continuity of mtDNA haplogroups over a long period of time, regardless of various historical demographic events that shaped the genetic structure of the modern B&H population.

abstract:Population genetic studies have shown that the Bosnian-Herzegovinian (B&H) population is a part of the European gene pool, but there has been limited information on the genetic structure of ancient B&H populations. This study aimed to determine the frequency and distribution of mitochondrial DNA (mtDNA) haplogroups for a medieval Bosnian population. Thirty-four samples, excavated from medieval necropolises located within the borders of medieval Bosnia, were analyzed. Sequencing of the mtDNA hypervariable segment 1 (HVS1) region and RFLP analysis were performed for haplogroup determination. All 32 samples were identified as haplogroup H, with subhaplogroups H2a and H5 in 30 and 2 samples, respectively. The frequency of the H haplogroup was significantly different between the studied samples and previous studies of contemporary B&H populations, where the H haplogroup frequency was approximately half that of the ancient population studied here. A significant difference in H haplogroup frequency compared with other medieval populations outside of Bosnia was also observed: the ancient B&H population is most similar to ancient Italians. These results provide insight into the mitochondrial landscape of populations that inhabited the territory of present-day Bosnia and Herzegovina in the Middle Ages. Our study reveals that inhabitants of medieval Bosnia carried genetic lineages that exist today in B&H populations, suggesting continuity of mtDNA haplogroups over a long period of time, regardless of various historical demographic events that shaped the genetic structure of the modern B&H population.

The aim of the paper is to present the results of the VNTR gene polymorphism genetic variants molecular typing for endothelial nitric oxide synthase (eNOS) in human population of Tuzla Canton. Based on the analysis of the distribution of eNOS gene genotypes in the total sample of respondents, the highest frequency was recorded for the (b/b) genotype, which was 73.0%. For the heterozygous (a/b) genotype of the eNOS gene, a frequency of 24.0% was determined, and a frequency of 3.0% was recorded for the (a/a) genotype. The research resulted in a database of local and global significance, namely, the incorporation of these data into the existing regional and European genetic database.

Apoptosis induction is a promising approach in targeting tumor cells. As halogenated boroxine (HB) shows antitumor activity, but its mechanism of action in hematological tumors remains unclear, in this study, we aimed to analyze apoptosis triggering in normal and UT‐7 leukemia cells by HB. Methods for assessing cell viability and cytotoxicity, apoptosis detection, relative expression of 84 apoptosis‐associated genes and BCL‐2, and functional analysis were applied. Pronounced HB activities in inhibition of cell viability, cytotoxicity, and apoptosis induction with measurable differences between tumor and normal cells were found. HB modulated the expression of 21 genes, predominantly downregulated the antiapoptotic genes in leukemia. The functional association revealed HB's impact on inhibition of NF‐κB signaling pathway. BCL‐2 expression decreasing was found only in UT‐7 leukemia. This study identified HB as an apoptosis inducer affecting leukemia but not normal cells considering mechanisms of selective activity that may be a great advantage of HB applications.

Background/Aim: Irritable bowel syndrome (IBS) belongs to the gastrointestinal disorders characterised by abdominal discomfort and pain, altered constipation, diarrhoea and stomach distension. The aim was to assess relationship between the selected genetic polymorphisms with IBS, their combined genotype effect as well as to assess a difference in the distribution of allele and genotype frequencies of selected loci between case and control group. Methods: This was a prospective study which included 29 participants, 20 individuals diagnosed with IBS based on Rome III criteria and 9 healthy individuals. The study analysed the selected genetic polymorphisms as possible risk factors for IBS according to the model of the case-control study. Genotyping was performed for FKBP5, DRD2 and DAT polymorphisms qualified as risk factors for IBS in previous researches. Results: The results revealed a significant association between DAT polymorphism with IBS, both, at the allelic level (p = 0.006) and genotype level (p = 0.031). Individuals with 434 allelic variant in the genotype have six time higher probability for developing IBS, in comparison to the individuals without this allelic variant. The statistical association between other analysed polymorphism and IBS was not reached. The analysis of combined effects of selected polymorphisms revealed no association with IBS, except FKBP5 and DAT which result was at the level of statistical significance (p = 0.05). Conclusion: Further analysis which would include DAT polymorphism with larger sample size, as well as other genes involved in dopamine neurotransmitter system would be of great interest to define closer conclusion of IBS aetiology.

CAT gene encodes catalase, a key antioxidant enzyme in the body against oxidative stress. This enzyme plays an important role in the molecular mechanisms of inflammation, apoptosis, mutagenesis and tumorigenesis. Anti-oxidant L-carnitine is used in food supplementation, medical co-treatment and bodyweight regulation. We aimed to investigate molecular basis of L-carnitine commercial preparations supplementation in reducing oxidative stress with customized CAT gene assay in vitro. Human lymphocytes cell culture was established using standard procedure and treated with range of concentrations of L-carnitine in two preparations. We tested two preparations: 500 mg tablets of L-carnitine and liquid L-carnitine with vitamin B6. L-carnitine significantly reduced the expression of CAT gene in cultured lymphocytes at concentrations of 50 μmol/l and 250 μmol/l compared to negative control, (p = 0,001; p = 0,001; respectively). The L-carnitine liquid supplement with vitamin B6 also reduced the transcription of CAT gene at concentrations of 50 μmol/l and 250 μmol/l as compared to the negative control (p = 0,018; p = 0,006; respectively). Selected L-carnitine preparations modulated the transcriptional activity of the antioxidant enzyme gene in human lymphocyte culture, indicating its possible effects in inhibition of pro-inflammatory processes that involve catalase activity.

Abstract 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.