Human serum albumin (HSA) is one of the most important transporters for drugs in the systemic circulation. In this study, we investigated the interaction of rosuvastatin (ROS) and atorvastatin (ATO) with HSA. Binding of a drug molecule to HSA significantly affects the pharmacokinetics of the drug as it increases drug solubility in plasma, decreases toxicity and protects molecules from oxidation. This study was made using fluorescence spectroscopy and molecular modeling approach. Fluorescence spectra were recorded for two different statins brands at seven different concentrations. The results revealed that both statins (ROS and ATO) cause the fluorescence quenching of the HSA solution. ROS and ATO binds strongly to HSA with the binding constant (Kb) of 1.0246×106 and 0,9018×106, respectively. In addition, it was observed that high concentrations of ATO cause a shift of the emission maximum towards longer wavelengths (red-shift), which may be due to the unfolding of protein chains or denaturation. Furthermore, it was calculated that HSA possesses one binding site for ROS and ATO. Results from molecular docking showed that ROS has a higher affinity for Sudlow site I compared to Sudlow site II and the main binding forces are hydrogen bonds. ATO has nearly equal affinity for both binding sites on HSA, and the main binding forces are hydrophobic interactions.

Introduction: Statins are lipid lowering medications, used for the prevention of cardiovascular diseases (CVD), but have shown to increase the risk of Type 2 diabetes mellitus. The aim of this study was to investigate the effects of high-potency statins, atorvastatin, and rosuvastatin on fasting glucose (FG) and hemoglobin A1c (HbA1c) in CVD patients. Methods: The case–control study included 123 patients from Tuzla Canton, Bosnia, and Herzegovina, with a diagnosis of CVD, treated in three health centers: Public Health Center Gračanica, Banovići, and Čelić. Of total patients, 84 were statin users (39 atorvastatin users and 45 rosuvastatin users) and 39 were not. Demographic data, diagnosis, and data of the therapy were taken from the medical records, as well as data of the FG and HbA1c, measured before or within 3 months of the statin therapy introduction. For the same patients, FG and HbA1c were also measured at least 3 months after the introduction of therapy. Results: Obtained results have shown a significant increase of FG in CVD patients on statin therapy in relation to control (p = 0.034). Comparing the diabetogenic effects of atrovastatin and rosuvastatin, it was found that the HbA1c in patients on atorvastatin therapy was significantly higher comparing to those on rosuvastatain therapy (p = 0.028). The FG was significantly increased (p = 0.027) after atrovastatin therapy. Similar results were obtained in diabetogenic CVD patients, where HbA1c on atorvastatin therapy was significantly higher comparing to HbA1c in those on rosuvastatain therapy (p = 0.039). A significant correlation was found between the increase in FG and HbA1c with the duration of atorvastatin therapy (p = 0.001 and p = 0.033), and between the increase in HbA1c and the duration of rosuvastatin therapy (p = 0.001). Conclusion: Long-term therapy with high-potency statins, atorvastatin, and rosuvastatin, may increase levels of FG and HbA1c in patients with CVD, where atorvastatin shows more significant effects.

Objective. The aim of this study was to investigate students’ knowledge, attitudes and hesitancy regarding COVID-19 vaccination. Methods. A cross-sectional questionnaire-based survey was conducted among a total of 1282 medical students and 509 non-medical students at four public universities in Bosnia and Herzegovina: Tuzla, Sarajevo, Banja Luka, and Mostar. Results. A significantly higher rate of vaccination was observed in the group of medical students as well as a higher level of knowledge about vaccination in general and vaccines against the COVID-19 disease. Students who received the COVID-19 vaccine had a higher level of knowledge about vaccination in general and COVID-19 vaccines in particular compared to the non-vaccinated students in the medical and non-medical groups, respectively. Furthermore, vaccinated students, regardless of the course they are taking, showed generally stronger positive attitudes compared to non-vaccinated students, regarding the safety and effectiveness of the COVID-19 vaccine. Both groups of students believe that the rapid development of the vaccine is contributing to refusal or hesitancy to receive a vaccine against COVID-19. Social media/networks were the main sources of information about the COVID-19 vaccine. We did not find any contribution of social media to the reduced level of COVID-19 vaccine coverage. Conclusion. Education of students about the benefits of the COVID-19 vaccine will lead to its better acceptance as well as the development of more positive attitudes towards vaccination in general, especially having in mind that students are the future population of parents, who will make decisions about vaccinating their children.

Aims: The aims of the study were to analyse the polyphenols of Pulicaria dysenterica (L.) Bernh. methanolic extracts from aerial and underground parts, assessment of antioxidant activity and to evaluate their cytotoxicity on HeLa cells of cervical cancer. Methodology: The total phenolic content (TPC) of extracts was determined by the Folin-Ciocalteu spectrophotometric method. The qualitative and quantitative analysis of individual polyphenolic compounds were performed by the reverse phase HPLC method. The antioxidant capacity was evaluated by both, 2,2-diphenyl1-picrylhydrazyl radical and FRAP assay, while cytotoxicity of the extracts was assessed by MTT assay. Results: TPC of the samples were 127.62±2.22 and 244.12±8.84 mg gallic acid equivalent/g extract. In the extracts chlorogenic acid in amount of 10.06±0.96 and 11.32±0.28 mg/g, flavonoid rutin in amount of 5.68±0.13 mg/g and three caffeic acid derivatives were recorded. Extract from underground parts achieved better antioxidant activity with IC50 value 55.36±0.75 µg/mL and FRAP value 2411.12±37.22 µmol Fe2+g-1 compared to the one from aerial parts. Extract from aerial parts achieved better cytotoxic activity with 50% inhibition of viability (IC50) at concentration of 0.389±0.07 mg/mL, against HeLa cells, compared to the extract from underground parts. Conclusion: Analyzed Pulicaria dysenterica extracts contained phenolic acids and flavonoids. The extracts showed good antioxidant activity and cytotoxic properties against HeLa cells in vitro.

Aims: Industrial processed food, pharmaceutical and cosmetical products contain numerous substances the safety of which has been widely concerned. Potassium sorbate (PS) is a common preservative used in a wide-range of products. Sunset yellow (SY) is one of the most commonly used dye in food and pharmaceutical industry. Several studies suggested cytotoxic and genotoxic potential of SY and PS in different cell lines. These effects can lead to organ damage and cancer development. The aim of this study is to investigate cytotoxic and genotoxic potential of two widely used food additives, SY and PS, in Jurkat cell line. Methodology: PrestoBlue assay was used to assess the cytotoxic potential of SY and PS. For observation of DNA damage, cytostatic and cytotoxic effects, the cytokinesis-block micronucleus cytome (CBMN) assay was performed. Results: Decrease of cell viability in Jurkat cell line was observed after 24-hour exposure to both SY and PS. CBMN assay has revealed significant increase of necrotic cells (P<0.05). Genotoxic biomarkers were in physiological range after 24-hour exposure to both analyzed additives. Conclusion: Our findings suggest that SY, as well as PS have cytotoxic potential in Jurkat cell line, as a result of increased number of necrotic cells. Higher cytotoxic effect was caused by SY compared to PS. However, genotoxic potential was not recorded for any of the food additives analyzed.

Aim To investigate interleukin 6 (IL-6) values depending on duration of diabetes mellitus (DM) and evaluate possible correlation with diabetic polyneuropathy. Methods The research study included 90 patients with DM divided into three groups (30 patients each) according to the duration of DM: group A - patients who had DM for less than 10 years, group B - duration of DM was 10 to 20 years, and group C - patients with DM over 20 years. Control group (K) included 30 healthy participants. Results IL-6 was significantly higher in the healthy control group, 180.318 pg/mL±94.18, than in group A, 47.23pg/ml±34.8, group B, 43.31pg/ml±33.17, and group C, 70.39 pg/ml±59.26 (p=0.0001). All groups had significantly different values of IL-6 between each other (p=0.0001). Level of IL-6 was in correlation with diabetic polyneuropathy in the group A (the youngest participants) (p=0.0001). In other groups there was no significant correlation between IL-6 and diabetic polyneuropathy. Conclusion The level of IL-6 was in correlation with neuropathy among younger patients. A higher level of IL-6 in the control group than in diabetic groups is a sign of stronger inflammatory response among younger and healthy people than in patients with DM.

Lead; Children; Soil pollution; Health risk assessment ABSTRACT: Soil contamination with heavy metals has pervaded many parts of the world which can influence on human health. Environmental and health risk assessment processes are key steps in obtaining information on potential adverse effects on human health which may arise as a result of exposure to heavy metals from the environment. Thirty samples of soil were collected in summer 2018, from 10 municipal playgrounds in Tuzla (Bosnia and Herzegovina) to perform health risk assessment for children exposed to lead (Pb) from soil during their outdoor play activities. The Pb concentrations were determined by ICP-AES. Soil contamination was assessed using contamination factor and geoaccumulation index. Non-cancer risk due to exposure to Pb from soil thorough ingestion, dermal contact and inhalation pathway was estimated using a deterministic methodology. The results of the risk assessment indicated that the highest risk is associated with the ingestion of soil particles compared to two other exposure pathways. The mean total Hazard Index value calculated was 5.34E-02, below the threshold value of 1, indicating there was no increased health risk due to children’s exposure to Pb. Although, the study showed there was no increased risk for children’s health due to exposure to Pb from soil, there is still a rising concern regarding possible adverse effects of Pb on children’s health. It is of great importance to monitor environmental pollution and continuously assess the risk to human health, not only thorough soil, but also through other important pathways of exposure such as food, water, air, toys, etc.

Arylmethylenebis(3-hydroxy-5,5-dimethyl-2-cyclohexen-1-one) derivatives (aryl=2-hydroxynaphthyl ( 1 ) and 3,4-dihydroxyphenyl ( 2 ) have been synthesized and their structures have been elucidated. Both compounds were examined for their antioxidant, antimicrobial and cytotoxic activity. Antioxidative activities of synthesized compounds were evaluated by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. The microbial screening was performed by diffusion method on bacterial strains Staphylococcus aureus , Enterococcus faecalis , Bacillus subtilis and Candida albicans . Cytotoxic activity was tested on liver hepatocellular carcinoma cell line (Hep G2) by Neutral red assay. Compared to compound 2 , compound 1 showed better antimicrobial and antifungal activity, while compound 2 showed better antioxidant activity with IC 50 of 0.0156 mM and FRAP value 50469.44 µmol/l Fe 2+ . Both compounds showed cytotoxic activity. Obtained results implicate the importance of arylmethylenebis(3-hydroxy-5,5-dimethyl-2-cyclohexen-1-on) derivatives as a potential antioxidant, antimicrobial and cytotoxic agents.

Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are detrimental, there is a lack of information on the toxicity of mixtures. In this study, two common heavy metals, lead and cadmium, were introduced individually and as mixtures to HL-60 and JURKAT cell lines for 24 hours. The study established that exposures to these two heavy metals induced cytotoxic and genotoxic effects on both cell lines. Also, cadmium exhibited a higher cytotoxic and genotoxic potential than lead. The cytotoxicity data of single metals were used to determine the mixtures interaction profile by using the effect additivity method. Metal mixtures showed synergistic effect in HL-60 cells and antagonistic effect in JURKAT cells, compared to individual metals. The combined effects should be considered in the risk assessment of heavy metal co-exposure and potency.

Introduction: The aim of this study was to determine the serum levels of malondialdehyde (MDA) in patients with invasive breast cancer in relation to its serum levels in patients with benign breast disease, and to investigate correlation between MDA serum levels with pathohistological prognostic factors (tumor size, lymph node involvement, and histologic grade [HG]), estrogen receptor (ER) status, and with breast cancer patient’s age and menopausal status. Methods: A total of 43 with well-documented invasive breast cancer were included in this study: 27 with positive axillary’s lymph nodes, and 16 with negative axillary’s lymph nodes, and 39 patients with findings of benign breast diseases. MDA determination in serum of breast cancer and benign breast disease patients was performed by the fluorimetric method, immunohistochemical staining was performed for ER, and routine pathohistological examination was conducted for pathohistological factors. Results: MDA serum levels in breast cancer patients were significantly higher than MDA serum levels in benign breast disease patients (p = 0.042). No statistically significant difference between MDA serum levels in breast cancer patients with and without lymph node metastases was found (p = 0.238). No statistically significant correlations between MDA serum levels and tumor size (p = 0.256), HG (p = 0.124), or number of positive lymph nodes (0.113) were found. A statistically significant correlation between serum MDA levels and ages of breast cancer patients with lymph node metastases was found (p = 0.006). Conclusion: Obtained results support the importance of MDA in the carcinogenesis of breast cancer. According to our findings, serum level of MDA could not be a useful prognostic factor in breast cancer.