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Introduction/Objective. The main aim of this study was to assess COVID-19 vaccination effectiveness (VE) of BBIBP-CorV, Gam-COVID-Vac, BNT162b2, and ChAdOx1-nCoV-19 in Serbia during the first three months of rollout. Methods. The data from the Serbian National Immunization Registry, the Primary Health Centre Report, and the University Clinical Centre Report for Kragujevac, Serbia, for the period from January 1 to March 31, 2021 were used to compare COVID-19 vaccinated population to unvaccinated individuals in terms of laboratory confirmed SARS-CoV-2 infection, COVID-19-related hospitalization and intensive care unit (ICU) admission due to COVID-19. VE was estimated based on the incidence rate ratio, adjusted for age and sex. Results. Overall VE after the first dose reached 20.6%, 28.2%, and 56.1%, and 55.7%, 63.9%, and 79.8%, after the second dose for SARS-CoV-2 infection, COVID-19-related hospitalization, and ICU admission, respectively. BNT162b2 exhibited 96.7% VE against infection and no hospitalization after the second dose. Complete vaccination with BBIBP-CorV and Gam-COVID-Vac demonstrated VE of 43.2% and 78.6% against infection, 56.9% and 85.3% against hospitalization, and 82.3% and 52.7% against ICU admission, respectively. ChAdOx1-nCoV-19 after the first received dose showed VE of 10.3% and 74.7% against infection and hospitalization, with no ICU admission. Conclusion. COVID-19 vaccination in general, as well as each of the four studied vaccines, reduces the risk of SARS-CoV-2 infection, hospitalization due to COVID-19, and COVID-19-related ICU admission. Vaccine effectiveness significantly increases with the second received dose for all study outcomes.

Introduction/Objective. The duration of vaccine-induced protection against SARS-CoV-2 is shown to be limited. The aim of this study was to assess vaccine effectiveness (VE) of a third dose of four different COVID-19 vaccines during Delta variant predominance in Serbia. Methods. The data for the period from August 18, to October 1, 2021 were used to estimate the incidence rates (IR) of the SARS-CoV-2 infection, COVID-19-related hospitalization, and intensive care unit (ICU) admission. The study included 41,186 fully vaccinated subjects, of which 13,589 had received the third dose. VE was estimated based on the IR ratio following vaccination with three vs. two doses. Results. We found that a third dose of all investigated vaccines reduces the incidence of both SARS-CoV-2 infection and severe illness that requires hospitalization or ICU admission. The highest VE against infection demonstrated BNT162b2, followed by Gam-COVID-Vac and BBIBP-CorV. Third dose vaccination reduced the risk of hospitalization (IR = 0 for Gam-COVID-Vac and BBIBP-CorV), and ICU admission (IR = 0 for all vaccines). The hazard distributions for SARS-CoV-2 infection and hospitalization following vaccination with three versus two doses were significantly different. Conclusion. These findings indicate that an additional, third dose of studied vaccine boosters protection against all investigated outcomes.

As cancer remains a significant global health challenge, there is an increasing need for novel therapeutic approaches. We investigated the antitumor potential of Juniperus communis berry essential oil on cervical cancer HeLa and colorectal HCT 116 cells. Cytotoxicity was evaluated through the MTT assay, revealing concentration-dependent reductions in cell viability. A clonogenic assay demonstrated long-term cytotoxic effects. Apoptosis markers were assessed via flow cytometric analysis and showed an induction of the intrinsic pathway in both cell lines, demonstrated by the elevated levels of cleaved caspase-3, Bax/Bcl-2 ratio, JC-10 monomer formation, and cytochrome C migration to the cytosol. The treatment inhibited cell-survival pathways in HCT 116 cells and arrested HeLa cells in the S phase. An extensive molecular docking screening provided insight into the binding affinity and interaction patterns of the essential oil components with NADH ubiquinone oxidoreductase and superoxide dismutase enzymes, further confirming the induction of the intrinsic pathway of apoptosis. The obtained in silico and in vitro results indicated the anticancer potential of J. communis berry essential oil as it interferes with cancer cell molecular mechanisms. Our findings highlight J. communis berry essential oil as a promising natural agent with anticancer potential. [ABSTRACT FROM AUTHOR]

Four neutral Rh1–Rh4 complexes of the general formula [Rh2(CH3COO)4L2], where L is an N-alkylimidazole ligand, were synthesized and characterized using various spectroscopic techniques, and in the case of Rh4 the crystal structure was confirmed. Investigation of the interactions of these complexes with HSA by fluorescence spectroscopy revealed that the binding constants Kb are moderately strong (∼104 M−1), and site-marker competition experiments showed that the complexes bind to Heme site III (subdomain IB). Competitive binding studies for CT DNA using EB and HOE showed that the complexes bind to the minor groove, which was also confirmed by viscosity experiments. Molecular docking confirmed the experimental data for HSA and CT DNA. Antimicrobial tests showed that the Rh2–Rh4 complexes exerted a strong inhibitory effect on G+ bacteria B. cereus and G− bacteria V. parahaemolyticus as well as on the yeast C. tropicalis, which showed a higher sensitivity compared to fluconazole. The cytotoxic activity of Rh1–Rh4 complexes tested on three cancer cell lines (HeLa, HCT116 and MDA-MB-231) and on healthy MRC-5 cells showed that all investigated complexes elicited more efficient cytotoxicity on all tested tumor cells than on control cells. Investigation of the mechanism of action revealed that the Rh1–Rh4 complexes inhibit cell proliferation via different mechanisms of action, namely apoptosis (increase in expression of the pro-apoptotic Bax protein and caspase-3 protein in HeLa and HCT116 cells; changes in mitochondrial potential and mitochondrial damage; release of cytochrome c from the mitochondria; cell cycle arrest in G2/M phase in both HeLa and HCT116 cells together with a decrease in the expression of cyclin A and cyclin B) and autophagy (reduction in the expression of the protein p62 in HeLa and HCT116 cells). [ABSTRACT FROM AUTHOR]

Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic hepatitis C virus (HCV) infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver. [Projekat Ministarstva nauke Republike Srbije, br. III41010]

This paper presents the synthesis and structural characterization of a series of new ruthenium(II) complexes 1–7, with the general formula mer-[RuL3(N–N)Cl]Cl, where L is 2,2′:6′,2′′-terpyridine (tpy) or 4′-(4-chlorophenyl)-2,2′:6′,2′′-terpyridine (Cl-Ph-tpy) and N–N is o-benzoquinonediimine (o-bqdi), 2,3-naphthoquinonediimine (nqdi), 4,4′-dimethyl-2,2′-bipyridine (dmbpy) or 2,2′-bipyridine-4,4′-dicarboxylic acid (dcbpy). The kinetic results showed that the ligand substitution reactions of new Ru(II)-polypyridyl complexes with biomolecules were affected by different substituents and the aromaticity of meridional tridentate and bidentate spectator ligands as well as by the nature of the entering nucleophile. The reactivity of the complexes increases in the order: dmbpy < dcbipy < nqdi < o-bqdi. In addition, quantum chemical calculations were performed to support the interpretation and discussion of the experimental data. Furthermore, combining ethidium bromide (EB) and Hoechst 33258 (2-(4-hydroxyphenyl)-5-[5-(4-methylpiperazine-1-yl)benzimidazo-2-yl]-benzimidazole) fluorescence assay results implied that 1–7 might interact with calf thymus DNA through partial intercalation and/or minor groove binding. The human serum albumin (HAS)-fluorescence binding studies involving the site markers, eosin Y, as a marker for site I of subdomain IIA, and ibuprofen, as a marker for site II of subdomain IIIA, showed that Ru(II) compounds bind to both sites with moderately strong affinity (Kb = 104–106 M−1). Moreover, these DNA/HSA experimental results were confirmed by molecular docking. Complexes 2, 5 and 6 exerted good to strong and highly selective cytotoxic activity against breast adenocarcinoma (MDA-MB 231), colorectal carcinoma (HCT116) and cervix adenocarcinoma (HeLa). Depending on their structure and cell line, the complexes acted differently in terms of their influence on autophagy, the cell cycle and the engaged apoptotic pathway. [ABSTRACT FROM AUTHOR]

Abstract: Apoptosis is a highly regulated and programmed cell breakdown process characterized by numerous changes. Since it is implicated in many pathological as well as physiological processes, it is vital to have reliable methods for detecting cell death. In this study, we compared several methods for detecting apoptosis and necrosis in human leukocytes. Apoptosis was induced either by incubating the cells with various doses of cycloheximide (CHX) or by 312nm UVB irradiation. The methods used for detecting apoptosis were light microscopy (May Grunwald–Giemsa and trypan blue staining), fluorescence microscopy (acridin orange/ethidium bromide and annexin V/propidium iodide staining) and agarose gel electrophoresis of fragmented genomic DNA. Our study showed that CHX-induced apoptosis in cultured peripheral blood mononuclear cells but had no effect on apoptosis in polymorphonuclear cells, so its effect depends on cell type. Evaluation and comparison of the methods for detecting apoptosis showed the following. A Giemsa-stained cytospin allows the main morphological characteristics of necrotic and apoptotic death to be recognized. Trypan blue staining, widely used for estimating cell viability, is valueless for detecting apoptosis. Both fluorescence methods provided reliable and reproducible results and distinguished clearly between subpopulations of apoptotic cells, and were closely intercorrelated. Although applicable to a wide spectrum of cell types, agar electrophoresis of extracted DNA cannot be applied to all cell types and apoptotic conditions. Generally, microscopic examination of acridin orange/ethidium bromide stained cells can be recommended as the most reliable of the methods tested. [Copyright &y& Elsevier]

Four neutral Rh1-Rh4 complexes of the general formula [Rh 2 (CH 3 COO) 4 L 2 ], where L is an N -alkylimidazole ligand, were synthesized and characterized using various spectroscopic techniques, and in the case of Rh4 the crystal structure was confirmed. Investigation of the interactions of these complexes with HSA by fluorescence spectroscopy revealed that the binding constants K b are moderately strong (∼10 4 M -1 ), and site-marker competition experiments showed that the complexes bind to Heme site III (subdomain IB). Competitive binding studies for CT DNA using EB and HOE showed that the complexes bind to the minor groove, which was also confirmed by viscosity experiments. Molecular docking confirmed the experimental data for HSA and CT DNA. Antimicrobial tests showed that the Rh2-Rh4 complexes exerted a strong inhibitory effect on G + bacteria B. cereus and G - bacteria V. parahaemolyticus as well as on the yeast C. tropicalis , which showed a higher sensitivity compared to fluconazole. The cytotoxic activity of Rh1-Rh4 complexes tested on three cancer cell lines (HeLa, HCT116 and MDA-MB-231) and on healthy MRC-5 cells showed that all investigated complexes elicited more efficient cytotoxicity on all tested tumor cells than on control cells. Investigation of the mechanism of action revealed that the Rh1-Rh4 complexes inhibit cell proliferation via different mechanisms of action, namely apoptosis (increase in expression of the pro-apoptotic Bax protein and caspase-3 protein in HeLa and HCT116 cells; changes in mitochondrial potential and mitochondrial damage; release of cytochrome c from the mitochondria; cell cycle arrest in G2/M phase in both HeLa and HCT116 cells together with a decrease in the expression of cyclin A and cyclin B) and autophagy (reduction in the expression of the protein p62 in HeLa and HCT116 cells).

Introduction: Coronary occlusion may cause acute myocardial infarction associated with many cellular and humoral disturbances of the immune system. The aim of this investigation was to examine phagocytic activity of peripherial blood monocytes and neutrophils as potential cellular markers of systemic immunological events in acute myocardial infarction., Material and Methods: This study included thirty patients following first acute myocardial infarction and thirty healthy volunteers. Immunological analyses were performed on admission and repeated on the second and seventh days after the acute event. Monocytes and neutrophils were obtained from heparinized whole blood after centrifugation and separation on density gradient and incubated with fixed number of heat inactivated and painted particles of yeast. We investigated the following parameters of phagocytic activity: percentage of phagocytosis, phagocytic index, absolute phagocytic index, phagocyte count in a fixed volume of peripherial blood and phagocytic capacity., Results: Except phagocytic index, all phagocytic parameters of monocytes and neutrophils were increased in acute myocardial infarction patients on admission and on the second day of hospitalization. On the seventh day after acute event only the mononuclear phagocyte count in fixed volume of peripheral blood showed significant increase in acute myocardial infarction patients, while percentage of phagocytosis, phagocyte count in fixed volume of peripheral blood and phagocyte capacity of neutrophils were increased during the whole investigated period., Conclusion: These data suggest that acute myocardial infarction was followed with strong systemic inflammatory response to myocardial damage. Furthermore, activated monocytes and neutrophils could be a significant source of free radicals, which might be involved in lipid peroxidation and cause tissue damage in early postinfarction period.