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.

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.

Autophagy is a dynamic process, conserved in all eukaryotes. It is responsible for the degradation of cytoplasmic content. Autophagy is crucial in cell survival and cell death. It plays a significant role in the cell response to stress, nutrient deficiencies, embryonic development, tumor suppression, response to pathogens and aging. The process of autophagy is also involved in the pathology of human diseases, such as cancer, diabetes, cardiomyopathy, and neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Autophagy is a mechanism that involves degradation of cells, proteins, damaged organelles and pathogens through the lysosomal mechanisms, thus autophagy supports cell survival during starvation, hypoxia and metabolic stress. However, if extensive and/or excessive, autophagy can promote apoptosis (type I) or function as an alternative cell-death pathway, called autophagic cell death (type II). Autophagy can either promote cancer cell death, or serve as a survival mechanism against apoptosis or necrosis induced by various anticancer treatments. Given the contradictory role of autophagy during tumor initiation and progression, the use of autophagy in therapy depends on the context and must be approached individually

Abstract Although prostate cancer accounts for the highest number of newly diagnosed cases of cancer in men, it represents a specific diagnostic challenge in modern oncology. The standard diagnosis of prostatic carcinoma begins with the screening of serum concentrations of PSA (Prostate Specific Antigen). If the concentration of serum PSA levels is above 4 ng/mL, the patient is further referred to a digital rectal examination in order to determine an increase in prostate volume. In cases where enlargement of the prostate is observed, the next step is biopsy of prostate tissue. This physically painful and invasive approach to confirm the diagnosis is often unnecessary because, in many cases, the patohistologic analysis determines diagnosis of benign prostatic hyperplasia, and not a tumor. In this study, we investigated the possibilities of detection and measurement of the relative level of gene expression of the KLK3 (Kallikrein-related peptidase 3), PCA3 (Prostate Cancer Gene 3) and TEMPRSS: ERG (Transmembrane protease serine2 and in-ETS erythroblostosis virus E26 oncogene homolog) genes from the urine samples of patients with prostatic diseases and healthy controls. Urine was the sample of choice because it is taken in a non-invasive manner, and could potentially serve to make better selection to biopsy. One of the selected genes (KLK3) differed significantly in the samples of various pathological conditions of the prostate, and therefore we consider that its further investigation is reasonable.

Objectives: The global burden of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the corona virus disease-19 (COVID-19) is enormous No definitive treatment and prophylactic guidelines for COVID-19 currently exist except for physical distancing and aerial barriers between individuals This work explored the natural compound-binding efficiency of SARS-CoV-2 proteins essential for host cell interaction and infection Methods: The binding activity of artemisinin to SARS-CoV-2 spike glycoprotein (Protein Data Bank (PDB) ID: 6VYB), SARS-CoV-2 main protease (3C-like main protease (3CLpro);PDB ID: 6Y84) and SARS-CoV-2 papain-like protease (PLpro;PDB ID: 6W9C), were tested using in silico methods Moreover, chloroquine and hesperidin were used as the positive control of binding affinity and proven therapeutic effect, respectively Results: The highest affinities for binding to all tested SARS-CoV-2 proteins are observed for hesperidin (-5 8,-10 0, and -8 1 kcal/mol), then for artemisinin (-4 8,-8 3, and -6 0 kcal/mol), and the lowest for chloroquine (-4 1,-8 2, and -4 8 kcal/mol) Artemisinin, hesperidin, and chloroquine had similar positioning toward targeted proteins at specific sites when these interactions were visualized Conclusion: This study shows that artemisinin has the potential to bind and inhibit the SARS-CoV-2 spike protein, the 3CLpro main protease, and PLpro proteinase similar to hesperidin and chloroquine that have been proven as antivirals in previous preclinical and clinical studies