Pomegranate peel extract (PoPEx) has been shown to have antioxidant and anti-inflammatory properties, but its effect on the adaptive immune system has not been sufficiently investigated. In this study, the treatment of human peripheral blood mononuclear cells (PBMC) with PoPEx (range 6.25–400 µg/mL) resulted in cytotoxicity at concentrations of 100 µg/mL and higher, due to the induction of apoptosis and oxidative stress, whereas autophagy was reduced. At non-cytotoxic concentrations, the opposite effect on these processes was observed simultaneously with the inhibition of PHA-induced PBMC proliferation and a significant decrease in the expression of CD4. PoPEx differently modulated the expression of activation markers (CD69, CD25, ICOS) and PD1 (inhibitory marker), depending on the dose and T-cell subsets. PoPEx (starting from 12.5 µg/mL) suppressed the production of Th1 (IFN-γ), Th17 (IL-17A, IL-17F, and IL-22), Th9 (IL-9), and proinflammatory cytokines (TNF-α and IL-6) in culture supernatants. Lower concentrations upregulated Th2 (IL-5 and IL-13) and Treg (IL-10) responses as well as CD4+CD25hiFoxp3+ cell frequency. Higher concentrations of PoPEx increased the frequency of IL-10- and TGF-β-producing T-cells (much higher in the CD4+ subset). In conclusion, our study suggested for the first time complex immunoregulatory effects of PoPEx on T cells, which could assist in the suppression of chronic inflammatory and autoimmune diseases.

Carvacrol is the main compound of essential oils extracted primarily from Thymus and Origanum species. Its various biological activities were confirmed: antioxidant, anti-inflammatory, antibacterial, antifungal, anti-tumour, antinematodal and vasorelaxant action. Although vasodilation mediated by carvacrol was previously described, the exact mechanism of its action has not yet been established. Hence, the aim of this study was to investigate carvacrol vasoactivity on human umbilical arteries (HUA) and different pathways involved in its mechanism of action using tissue bath methodology. Carvacrol caused a significant decrease in vascular tension of 5-HT-pre-contracted umbilical arteries, with EC50 of 442.13 ± 33.8 µM (mean ± standard error of the mean - SEM). At 300 µM, carvacrol shifted downward the 5-HT concentration-response curve with statistical significance of p < 0.001 obtained for the four highest concentrations. At concentration of 1 mM, carvacrol completely abolished BaCl2-induced contraction in Ca2+-free Krebs-Ringer bicarbonate solution (p < 0.001). Isopentenyl pyrophosphate, the antagonist of TRPV3 channel, was able to decrease the efficacy of carvacrol (p < 0.001). The vasorelaxant effect of carvacrol seems to involve the blocking of L-type of Ca2+ channels on smooth muscle cells. However, the role of TRPV3 channels in carvacrol-induced vasodilation of HUA cannot be excluded either.

Introduction: The early approaches to prevent the spread of COVID-19 included lockdown and social distancing measures, leading to university closures. These measures forced unparalleled changes to the delivery of healthcare education. Concerns included the preparedness of faculty and students to e-learning as well as the routine availability and funding of equipment and internet bundles. This needed addressing with fully trained healthcare professionals required given rising inappropriate use of antibiotics in India, growing prevalence of non-communicable diseases as well as an increasing number of patients with joint comorbidities. Consequently, there is a need to ascertain the current impact of the pandemic on healthcare student education across India. Materials and Methods: This was a pilot study among 10 purposely selected healthcare educators in both private and public universities. The questionnaire built on published studies. Results: Identified challenges included a lack of familiarity with online education, no bedside teaching, lack of equipment and affordability of internet bundles, poor internet connectivity and postponed examinations. Ways forward included training faculty on e-learning, providing students with loans and other financial support to purchase equipment and internet bundles, establishing COVID-19 prevention protocols and protective equipment, recording lectures and tutorials to make up for lost time and simulated methods to teach clinical aspects. Conclusion: Despite challenges, there was a rapid move to online learning among surveyed universities. Alongside this, courses to address lack of familiarity with e-learning approaches with hybrid teaching approaches here to stay. The next step will be to undertake a wider study and to use the combined findings to provide future guidance.

Cardiovascular diseases are the leading cause of death and the main cause of disability. In the last decade, homocysteine has been found to be a risk factor or a marker for cardiovascular diseases, including myocardial infarction (MI) and heart failure (HF). There are indications that vitamin B6 plays a significant role in the process of transsulfuration in homocysteine metabolism, specifically, in a part of the reaction in which homocysteine transfers a sulfhydryl group to serine to form α-ketobutyrate and cysteine. Therefore, an elevated homocysteine concentration (hyperhomocysteinemia) could be a consequence of vitamin B6 and/or folate deficiency. Hyperhomocysteinemia in turn could damage the endothelium and the blood vessel wall and induce worsening of atherosclerotic process, having a negative impact on the mechanisms underlying MI and HF, such as oxidative stress, inflammation, and altered function of gasotransmitters. Given the importance of the vitamin B6 in homocysteine metabolism, in this paper, we review its role in reducing oxidative stress and inflammation, influencing the functions of gasotransmitters, and improving vasodilatation and coronary flow in animal models of MI and HF.

Background and Objectives: Cigarette smoking among the youth population has increased significantly in developing countries, including Bosnia and Herzegovina. However, no extant literature assesses the prevalence of tobacco use, nor identifies factors associated with smoking. This study determined the prevalence of cigarette smoking among a specific cohort of students and assessed factors related to tobacco use in this population. Materials and Methods: This cross-sectional study included 1200 students at all faculties of Banja Luka University. Data were collected from questionnaires adapted from the Global Youth Tobacco Survey (GYTS) and the Global Health Professional Student Survey (GHPSS) standardized questionnaires and were analyzed using descriptive statistics, Pearson’s χ2 test, and logistic regression. Results: When the prevalence of cigarette smoking within the last thirty days was recorded, we found that 34.1% of students smoked within this period. Nearly three-quarters (74.9%) of the student population had smoked or experimented with cigarette smoking. However, medical students were 27.2% less likely to smoke than their counterparts from other faculties. Overall, 87% of all students were aware of the harmful effects of cigarette smoking, 79% were aware of the harmful effects of secondhand smoke, and 65% reported that it was difficult to quit. Increased spending of personal money was associated with a higher probability of smoking, while exposure to secondhand smoke increased the odds of smoking by 62%. Conclusion: Policies, strategies, and action plans should be introduced in order to reduce the prevalence of smoking among university students and to create a smoke-free environment at the various universities involved.

Disruption of the alveolar–endothelial barrier caused by inflammation leads to the progression of septic acute lung injury (ALI). In the present study, we investigated the beneficial effects of simvastatin on the endotoxin lipopolysaccharide (LPS)-induced ALI and its related mechanisms. A model of ALI was induced within experimental sepsis developed by intraperitoneal injection of a single non-lethal LPS dose after short-term simvastatin pretreatment (10–40 mg/kg orally). The severity of the lung tissue inflammatory injury was expressed as pulmonary damage scores (PDS). Alveolar epithelial cell apoptosis was confirmed by TUNEL assay (DNA fragmentation) and expressed as an apoptotic index (AI), and immunohistochemically for cleaved caspase-3, cytochrome C, and anti-apoptotic Bcl-xL, an inhibitor of apoptosis, survivin, and transcriptional factor, NF-kB/p65. Severe inflammatory injury of pulmonary parenchyma (PDS 3.33 ± 0.48) was developed after the LPS challenge, whereas simvastatin significantly and dose-dependently protected lung histology after LPS (p < 0.01). Simvastatin in a dose of 40 mg/kg showed the most significant effects in amelioration alveolar epithelial cells apoptosis, demonstrating this as a marked decrease of AI (p < 0.01 vs. LPS), cytochrome C, and cleaved caspase-3 expression. Furthermore, simvastatin significantly enhanced the expression of Bcl-xL and survivin. Finally, the expression of survivin and its regulator NF-kB/p65 in the alveolar epithelium was in strong positive correlation across the groups. Simvastatin could play a protective role against LPS-induced ALI and apoptosis of the alveolar–endothelial barrier. Taken together, these effects were seemingly mediated by inhibition of caspase 3 and cytochrome C, a finding that might be associated with the up-regulation of cell-survival survivin/NF-kB/p65 pathway and Bcl-xL.

Abstract not available Bangladesh Journal of Medical Science Vol. 21 No. 02 April’22 Page : 221-232

Healthcare workers (HCW) in primary healthcare centres in the Republic of Srpska, Bosnia and Herzegovina, are on the first combat line with COVID-19. This study aimed to assess the seroprevalence of SARS-CoV-2 among HCW at the primary healthcare centres and to analyse the risk exposure to COVID-19, clinical signs and vaccination status. A cross-sectional study was conducted among HCW at the selected primary healthcare centres between 19 March and 30 April 2021. Antibodies against the SARS-CoV-2 virus were detected by enzyme-linked immunosorbent assay (ELISA). A total of 1,023 HCW (mean age 45 years; 71% female) were included in the study. The anti-SARS-CoV-2 antibodies were detected in 69.5% of all participants. There was a significant difference in seropositivity among primary healthcare centres from different geographical regions. As many as 432 (42%) of all participants had confirmed COVID-19 symptoms before the study and, 84.8% of them were seropositive. This study showed that 702 primary HCW were vaccinated with any of these vaccines: Sputnik V, Sinopharm, Pfizer/Biontech. High titre of SARS-CoV-2 antibodies was found amongst those who received one (92.6%) or both (97.2%) doses of vaccines. In this study, we report high prevalence of SARS-CoV-2 antibody among HCW in primary healthcare in the Republic of Srpska, Bosnia and Herzegovina during the third pandemic wave.

BACKGROUND Type 2 diabetes mellitus (T2DM) is commonly associated with hyperglycemia, dyslipidemia, oxidative stress and inflammation which are well known cardiovascular risk factors. Pomegranate peel polyphenols have a proven hypolipemic, antioxidant and anti-inflammatory activity. However, there is a lack of clinical studies that would confirm its antioxidant and anti-inflammatory effects in diabetic patients. The potential of pomegranate peel extract (PoPEx) to counteract inflammation and oxidative stress in T2DM patients was investigated. For this purpose, a randomized, double-blind placebo-controlled study involving adult T2DM patients treated with PoPEx or placebo for eight-weeks was conducted. METHODS Patients were randomly divided into two groups: the first group (n = 30) received capsules containing PoPEx 250 mg twice daily, while the placebo group (n = 30) received placebo capsules twice daily. Plasma concentration of inflammatory factors (interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and high sensitivity C reactive protein (hsCRP)), oxidative stress biomarkers (thiobarbituric acid reactive substances (TBARS), nitrites (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), total antioxidant capacity (TAC)), homocysteine and lipid profile were analyzed. RESULTS The PoPEx treatment showed a significant reduction of inflammatory factors (IL-6, TNF-α, hsCRP), oxidative stress biomarkers (TBARS, NO2-, O2-) and homocysteine, while the TAC was increased. Moreover, a significant improvement in lipid profile was observed in the PoPEx group. Additional analysis showed a significant inverse correlation between the decrements of all measured inflammatory markers and TAC in the PoPEx group. CONCLUSIONS The study demonstrated that eight-week-long PoPEx administration had favorable effects on inflammatory status and oxidative stress biomarkers in diabetic patients.

The aim of the study was to assess the seroprevalence of SARS-CoV-2 in the Republic of Srpska, Bosnia and Herzegovina, and to analyse the knowledge, attitudes and practices of the population toward COVID-19. This population-based study was conducted in a group of 1,855 randomly selected individuals from all municipalities from 1 December 2020 to 15 January 2021. All individuals were asked to sign a consent form and to fill in a questionnaire, following which a blood samples were collected. Total anti-SARS-CoV-2 antibodies were determined in serum specimens using the total Ab ELISA assay. The overall seroprevalence rate was 40.3%. Subjects aged <65 years were 2.06 times more likely to be seropositive than those aged ≥65, and 30% of seropositive individuals presented no COVID-19 symptoms. The household members of seropositive individuals were 2.24 times more likely to develop COVID-19 symptoms than the household members of seronegative individuals. More than 95% of respondents believe that preventive measures are very important to control the infection transmission. Majority of respondents wear the masks properly, maintain the required physical distance whenever possible and wash hands with soap. Nearly 50% of individuals were of the opinion that the vaccine could prevent the infection. This study showed that an overall SARS-CoV-2 seropositivity rate by the middle of January 2021 was very high. Attitudes and practices regarding the COVID-19 indicate that additional efforts should be taken in order to improve the health education with a focus on preventive measures and vaccination.

Background/Aim: Sulphur mineral water is widely used in the treatment of musculoskeletal diseases. Hydrogen sulphide is an important regulator of bone metabolism and its application in the treatment of osteoporosis is intensively researched. The aim of this study was to analyse biochemical and histological effects of H2S containing mineral water of "Mlječanica" spring on ovariectomy-induced experimental osteoporosis in rats. Methods: In this experiment a 14-week-old Wistar female rats were used. The animals undergone bilateral ovariectomy (OVX groups) as an experimental model for oestrogen-deficient osteoporosis. After six weeks, animals were divided into control and the experimental group. Rats from the experimental group treated with H2S (SW group) containing mineral water ad libitum during five weeks. Biochemical parameters for monitoring sulphur water effects were concentration in serum of osteocalcin, alkaline phosphatase, calcium and phosphorus. Histological analyses of the left tibia coloured with haematoxylin-eosin were carried out. Results: Regarding the biochemical parameters, a statistically significant increase was observed in the OVX group for osteocalcin, alkaline phosphatase calcium and phosphorus compared to the sham-operated (CNT) group (p < 0.01). In SW + OVX, alkaline phosphatase was statistically significantly decreased (p < 0.01) and serum osteocalcin and phosphorus increased (p < 0.01). Calcium values were increased without significance. In the OVX + SW group, histological analyses showed numerous osteoblasts along the trabecular endosteum and the growth of young chondrocytes in the central bone zone and their migration to the peripheral parts. Conclusion: Drinking the H2S containing "Mlječanica" mineral water has led to decreased alkaline phosphatase, increased osteocalcin and phosphorus concentration in serum and stimulated the bone reparation in osteoporotic rats.

Plant extracts are widely used as biofungicides and medical bioproducts because of their eco-friendly nature and cost effectiveness. The present investigation focuses on the activity of a solvent based on industrial hemp extracts against two phytopathogenic fungi and five human pathogenic bacteria. The present study suggests the potential of the industrial hemp extracts for the development of novel broad spectrum herbal formulations used in plant protection and medicine.

Background/Aim: Hypomagnesaemia is one of the most detected electrolyte abnormalities in diabetics. Modulation of numerous cardiovascular pathophysiological processes is a potential goal for anti-diabetic therapy. Magnesium supplementation prevents subclinical tissue magnesium deficiency, thus delaying the onset of metabolic imbalance in diabetes, but long-term effects of magnesium supplementation in chronic diabetes and numerous pathophysiological processes remain unknown. Aim of this study was to determine the effects of subchronic intake of magnesium hydrocarbonate-rich mineral water on cardiometabolic markers and electrolytes in rats with streptozotocin-induced diabetes. Methods: A total of 28 Wistar, male rats, body weight 160 g at start, were divided into four groups of 7 each: two controls, group that drank tap water and received a single ip injection of saline (0.9 % NaCl) (TW-C), group that drank mineral water rich in magnesium hydrocarbonate and received a single ip injection of saline (0.9 % NaCl) (MW-C); and two experimental groups with streptozotocin-induced diabetes, group that drank tap water and received a single ip injection of streptozotocin (100 mg/kg) in saline (0.9 % NaCl, 1 mL) (TW-DM), group that drank mineral water rich in magnesium hydrocarbonate and received a single ip injection of streptozotocin (100 mg/kg) in saline (0.9 % NaCl, 1 mL) (MW-DM). Results: Regarding the biochemical parameters, a decrease was observed in the MW-C group for vitamin B12 and proteins, while triglycerides were higher compared to the TW-C group. By comparing the haemostatic biomarkers between TW-C and MW-C groups, a statistically significant decrease was found for fibrinogen, while the electrolyte analysis showed an increase in phosphates for the MW-C group. Biochemical value comparison between TW-DM and MWDM groups showed that magnesium hydrocarbonate usage in diabetic rats did not significantly reduce glycaemia although the average glycaemic values were lower in the group treated with magnesium hydrocarbonate. Regarding the electrolyte values, a statistically significant decrease was observed for sodium, potassium and phosphate in the MW-DM group. The MW-DM group also showed a significant increase in iron value compared to TW-DM group. Conclusion: Subchronic intake of magnesium hydrocarbonate-rich mineral water, as a form of magnesium supplementation, did not cause a significant improvement in glycaemia or normalisation of diabetes-induced dyslipidaemia. This study showed the reduction of fibrinogen value, thus indicating the possibility of usage of this form of magnesium supplementation in different pro-thrombogenic conditions.

Introduction. Combustible tobacco smoking accounts for nearly 30% of all cancer deaths in the United States of America and about 7 million deaths worldwide each year. Nowadays, e-cigarettes are increasingly used, especially among young people, but nicotine addiction that develops by such smoking easily converts to smoking combustible tobacco. Therefore, public health efforts must be directed to the prevention of initiation of smoking all nicotine-containing products. Role of Physicians. Medical doctors are very influential in smoking-related changes in local society, especially those who work in primary care, and they have an important role in both prevention and cessation of tobacco smoking. Tobacco smoking should be eliminated among medical doctors, yet many of them still smoke. The lowest percentage of smoking among physicians is in Oceania and North America (less than 11%) and the highest in Eurasia (25%). Smoking prevalence among medical students is higher than 35% in Georgia, Greece, Spain, and Italy, but less than 5% in the United States of America and Australia. In Serbia, 23% of physicians smoke. The age of physicians does not affect the number of smokers, but gender has a significant effect; women smoke less than men. Smoking Prevention and Cessation. Education about the effects of combustible tobacco smoking is a critical issue for successful smoking prevention and cessation; the best way is to provide educational programs on smoking at medical schools by introducing a mandatory course on combustible tobacco smoking at the beginning of the first year of study, especially in societies with a large percentage of smokers. Conclusion. In this paper, we showed how smoking can be eliminated among physicians and how they can affect the patients, public health policies, and antismoking campaigns.