Halogenated boroxine K2[B3O3F4OH] (HB), an inorganic derivative of cyclic anhydride of boronic acid, is patented as a boron-containing compound with potential for the treatment of both benign and malignant skin changes. HB has effectively inhibited the growth of several carcinoma cell lines. Because of the growing interest in autophagy induction as a therapeutic approach in bladder carcinoma (BC), we aimed to assess the effects of HB on metabolic phenotype and autophagy levels in 5637 human bladder carcinoma cells (BC). Cytotoxicity was evaluated using the alamar blue assay, and the degree of autophagy was determined microscopically. Mitochondrial respiration and glycolysis were measured simultaneously. The relative expression of autophagy-related genes BECN1, P62, BCL-2, and DRAM1 was determined by real-time PCR. HB affected cell growth, while starvation significantly increased the level of autophagy in the positive control compared to the basal level of autophagy in the untreated negative control. In HB-treated cultures, the degree of autophagy was higher compared to the basal level, and metabolic phenotypes were altered; both glycolysis and oxidative phosphorylation (OXPHOS) were decreased by HB at 0.2 and 0.4 mg/mL. Gene expression was deregulated towards autophagy induction and expansion. In conclusion, HB disrupted the bioenergetic metabolism and reduced the intracellular survival potential of BC cells. Further molecular studies are needed to confirm these findings and investigate their applicative potential.

Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = −0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient’s level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.

Background: Frequent episodes of nasal symptoms are the usual clinical manifestations (CM) of allergic rhinitis (AR) and have a significant negative impact on health-related quality of life (HRQoL) in adolescents. The purpose of this cross-sectional study was to test the hypothesis that cytokines in nasal mucus may be associated with HRQoL in adolescents with AR. Methods: European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), “The Adolescent Rhinoconjunctivitis Quality of Life Questionnaire” (AdolRQLQ) and the Total 4 Symptom Score (T4SS) scoring system were administered to 113 adolescents with AR, nonallergic rhinitis (NAR) and to healthy control subjects. Nasal secretions were sampled and tested for 13 cytokines using a multiplex flow cytometric bead assay. Results: The AR group had significantly lower EQ-5D-3L (0.661 ± 0.267 vs. 0.943 ± 0.088; p < 0.001) and higher AdolRQLQ total scores (2.76 ± 1.01 vs. 1.02 ± 0.10; p < 0.001) compared to the control group. The AR group had higher concentrations of IL-1β (p = 0.002), IL-6 (p = 0.031), IL-8 (p < 0.001), IL17-A (p = 0.013) and IL-18 (p = 0.014) compared to the control group, and IL-1β, IL-6, IL17-A and IL-18 were significantly (p < 0.050) increased with disease progression. Cytokines IL-1β, IL-6, as well as severe CM, were identified as significant predictors of lower HRQoL in adolescents with AR. Conclusions: This study identified IL-1β, IL-6, as well as severe CM, as predictors of lower HRQoL in adolescents with AR. However, these results should only serve as a starting point for additional confirmation research.

<p>Diabetic retinopathy (DR) is a chronic microvascular complication of diabetes. Due to the dramatic increase in the number of diabetes cases, the prevalence of DR has also risen, making it the leading cause of blindness among the working-age population worldwide, despite the availability of screenings and modern therapeutic options. Risk factors for the development and progression of DR (duration of diabetes, hypertension, hyperglycemia, dyslipidemia, and genetic factors) have been investigated in numerous epidemiological studies and clinical researches, but the research results were not consistent. In recent years, there has been considerable interest in the study of dyslipidemia in diabetes as one of the factors that could influence the onset and progression of DR, as well as apolipoproteins as potentially better biomarkers for DR. The results of our research also point in that direction. Identifying the risk factors for DR is crucial for enabling adequate prevention and raising awareness among individuals with diabetes about the importance of taking appropriate measures to prevent this microvascular complication.</p>

<p>Bacterial resistance to antibiotics is a problem that arose simultaneously with the beginning of their use and on a global level represents one of the biggest threats to public health. At the beginning of the twenty-first century, the emphasis of the medical and pharmaceutical public is on Gram-negative bacteria, especially enterobacteria, which show resistance to most, and some to all, available antibiotics. Treatment of infections caused by multiresistant bacteria is a big challenge for clinicians. Although bacterial resistance to antibiotics is a global problem, resistance rates vary significantly from country to country, and when it comes to hospital pathogens, from institution to institution. Monitoring antibiotic resistance in one&rsquo;s own environment is one of the first steps in the prevention and control of infections caused by multiresistant bacteria.</p>

This study conducted an initial investigation into the association between ACE gene insertion/deletion (I/D) polymorphisms (rs1799752) and hypertension in the Republic of Srpska, Bosnia and Herzegovina. The study featured two distinct groups, each with 100 subjects, systematically categorized based on hypertension status and gender. DNA was extracted, PCR-amplified, and analyzed by gel electrophoresis. Results revealed a higher prevalence of the DD genotype and the D allele in the hypertensive group, although statistical significance was not observed. The II genotype occurred in 18% of the hypertension group and 21% in the control group. A significant difference was found in allele I frequencies between the two groups (p=0.004), with no gender-related variations in ACE alleles. The limited sample size may have constrained the ability to detect statistically significant differences. The odds ratio for the (DD + ID) genotype compared to II was 1.2110 (95% CI: 0.6006 to 2.4418; p=0.5927), indicating no statistical significance. Furthermore, no significant associations were identified between ACE genotypes and alleles and gender. In summary, this preliminary study suggests a potential trend towards a higher prevalence of the ACE gene D allele and DD genotype in hypertensive individuals. However, due to the small sample size, these associations did not achieve statistical significance in this population. Larger-scale investigations are needed for more definitive insights into the relationship between ACE gene polymorphisms and hypertension.

<p><strong>Introduction. </strong>The improvement of new genetic testing strategies are getting to be progressively integrated into different parts of medicine. Progress has not been accompanied by the satisfactory level of genetic education but it has been accompanied with many ethical issues concering testing among medical students, doctors and the common population. Subsequently, the requirements for an adequate education in genetics for each group are expanding. The main goal of this paper is to examine attitudes regarding different aspects of genetic testing, and to determine differences in attitudes with respect to socio-demographic characteristics among the employees at the Faculty of Medicine in Foča, University of East Sarajevo.</p> <p><strong>Methods.</strong> Sixty-one employees of four study programs of the Faculty of Medicine in Foča participated in the research. An anonymous survey was conducted based on the voluntary consent of the respondents. It included two parts. The first part of the survey included socio-demographic questions (age, gender, educational level). The second part consisted of eight questions about genetic testing, which were related to the ethical justification of genetic testing.</p> <p><strong>Results.</strong> Out of the total number of respondents, 90.2% of respondents would undergo genetic testing for health reasons. A significantly higher number of respondents who had a master&rsquo;s degree (96.2%) would undergo genetic testing, compared to (88.9%) respondents who had an undergraduate degree (p=0.001). A significantly larger number of older respondents (29.6% over the age of 36) considered abortion justified in case of prenatal diagnosis of cancer at a later age, compared to 8.8% of the respondents belonging to the younger age group (from 26 to 35) (p=0.036).</p> <p><strong>Conclusion.</strong> We have shown that there is a different understanding among the population of different educational status and different age. Further on in the near future, it is our opinion that seminars should be organized regarding this science, in order to promote its importance.</p>

<p>&nbsp;</p> <p>Regardless of the fascinating progress of humanity, biotechnology and medicine, the outbreak of the global pandemic of the SARS-CoV-2 virus has shown us that we are just as vulnerable as in previous eras when communicable diseases decimated the world&rsquo;s population. But the discoveries made so far at the molecular level allow us to connect knowledge interdisciplinary and find solutions and therapeutic strategies where there seems to be no link. It was the previous coronavirus infections that served as a homologous model for finding the connection between the SARS-CoV-2 virus and autophagy. Autophagy, a conserved universal process of all eukaryotic cells responsible for cell survival under stressful circumstances, has been shown to play a significant role in viral invasions. It contributes to both direct and indirect antiviral responses such the elimination of viruses, the presentation of their antigens, and the reduction of inflammatory responses. The autophagy machinery of host cells can, however, be suppressed, evaded, or used by viruses to their benefit. Therefore, autophagy has an ambiguous role in coronavirus-related infections, especially in COVID-19.</p> <p>&nbsp;</p>

Abstract Anti-proliferative effects of halogenated boroxine – K2(B3O3F4OH) (HB) – have been confirmed in multiple cancer cell lines, including melanoma, but the exact mechanism of action is still unknown. This study aimed to determine its cytotoxic effects on human Caucasian melanoma (GR-M) cell growth in vitro as well as on the expression of cell death-related genes BCL-2, BECN1, DRAM1, and SQSTM1. GR-M and peripheral blood mononuclear (PBM) cells were treated with different HB concentrations and their growth inhibition and relative gene expression profiles were determined using the Alamar blue assay and real-time PCR. HB significantly inhibited cell growth of both GR-M and PBM cells but was even more effective in GR-M melanoma cells, as significant inhibition occurred at a lower HB concentration of 0.2 mg/mL. GR-M BCL-2 expression was significantly downregulated (P=0.001) at HB concentration of 0.4 mg/mL, which suggests that HB is a potent tumour growth inhibitor. At the same time, it upregulated BCL-2 expression in normal (PBM) cells, probably by activating protective mechanisms against induced cytotoxicity. In addition, all but the lowest HB concentrations significantly upregulated SQSTM1 (P=0.001) in GR-M cells. Upregulated BECN1 expression suggests early activation of autophagy at the lowest HB concentration in SQSTM1 cells and at all HB concentrations in PBM cells. Our findings clearly show HB-associated cell death and, along with previous cytotoxicity studies, reveal its promising anti-tumour potential.