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Oleinska kiselina - uticaj na zdravlje i status u fosfolipidima plazme u srpskoj populaciji
Get PDFOleic acid has many beneficial effects on human health. One of the main dietary sources of oleic acid is olive oil. Non-Mediterranean European countries, including Serbia, have low habitual olive oil consumption, but other vegetable oils also contain different amounts of oleic acid. In infants and young children m ilk is the most important source of fatty acids, including oleic acid. Furthermore, fatty acid composition of plasma phospholipids reflects dietary intake and fatty acid metabolism. In patients with serious chronic diseases fatty acid status is altered independently on the intake. Here we reviewed status of oleic acid in healthy persons as well as in patients with different chronic diseases in Serbia.Oleinska kiselina ima ima višestrukepozitivne efekte na život i zdravlje ljudi. Jedan od glavnih izvora oleinske kiseline je maslinovo ulje. Evropske zemlje, koje nepripadaju mediteranskoj regiji, među kojima je i Srbija, retko koriste maslinovo ulje u ishrani, ali i druga biljna ulja sadrže oleinsku kiselinu u različitom procentu. Kod odojčadi i dece mlađeg uzrasta, mleko je najvažniji izvor masnih kiselina, uključujući i oleinsku. Dijetetski unos masnih kiselina i njihov metabolizam u telu, odražava masnokiselinski sastav ufosfolipidima plazme. Kod pacijenata sa teškim hroničnim oboljenjima, masnokiselinski sastav je promenjen nezavisno od unosa. U ovom radu je prikazan status oleinske kiseline kod zdravih osoba, kao i kod pacijenata sa različitim hroničnim oboljenjima u Srbiji
Epidemiology of Taenia saginata taeniosis/cysticercosis: a systematic review of the distribution in West and Central Africa
Get PDFBackground: The zoonotic tapeworm Taenia saginata, although causing only minor discomfort in humans, is responsible for considerable economic losses in the livestock sector due to condemnation or downgrading of infected beef carcasses. An overview of current knowledge on the distribution and prevalence of this parasite in West and Central Africa is lacking. Methods: We conducted a systematic review, collecting information on published and grey literature about T. saginata taeniosis and bovine cysticercosis from 27 countries/territories in West and Central Africa, published between January 1st, 1990 and December 31st, 2017. Results: The literature search retrieved 1672 records, of which 51 and 45 were retained for a qualitative and quantitative synthesis, respectively. Non-specified human taeniosis cases were described for Nigeria, Cameroon, Senegal, Burkina Faso, Democratic Republic Congo, Guinea, and Ivory Coast (seven out of 27 countries/territories), while T. saginata taeniosis specifically was only reported for Cameroon. Most prevalence estimates for taeniosis ranged between 0-11%, while three studies from Nigeria reported prevalence estimates ranging between 23-50%. None of the studies included molecular confirmation of the causative species. The presence of bovine cysticercosis was reported for Benin, Burkina Faso, Cameroon, Central African Republic, Chad, Democratic Republic Congo, Ghana, Guinea, Ivory Coast, Mali, Niger, Nigeria, Senegal, and Tristan da Cunha (14 out of 27 countries/territories). Prevalence estimates ranged between 0-29%. Conclusions: Our systematic review has revealed that human taeniosis and bovine cysticercosis are seriously understudied in West and Central Africa. The high prevalence estimates of both conditions suggest an active dissemination of this parasite in the region, calling for a concerted One Health action from public health, veterinary health and food surveillance sectors
Standardized Aronia melanocarpa Extract as Novel Supplement against Metabolic Syndrome: A Rat Model
Get PDFThe aim of our study was to examine the effects of different dietary strategies, high-fat (HFd) or standard diet (Sd) alone or in combination with standardized oral supplementation (0.45 mL/kg/day) of Aronia melanocarpa extract (SAE) in rats with metabolic syndrome (MetS). SAE is an official product of pharmaceutical company Pharmanova (Belgrade, Serbia); however, the procedure for extraction was done by EU-Chem company (Belgrade, Serbia). Rats were divided randomly into six groups: control with Sd, control with Sd and SAE, MetS with HFd, MetS with HFd and SAE, MetS with Sd and MetS with Sd and SAE during 4 weeks. At the end of the 4-week protocol, cardiac function and liver morphology were assessed, while in the blood samples glucose, insulin, iron levels and systemic redox state were determined. Our results demonstrated that SAE had the ability to lower blood pressure and exert benefits on in vivo and ex vivo heart function. Moreover, SAE improved glucose tolerance, attenuated pathological liver alterations and oxidative stress present in MetS. Obtained beneficial effects of SAE were more prominent in combination with changing dietary habits. Promising potential of SAE supplementation alone or in combination with different dietary protocols in triggering cardioprotection should be further examined in future
Heterogeneity of Scaling of the Observed Global Temperature Data
Get PDFWe investigated the scaling properties of two datasets of the observed near-surface global temperature data anomalies: the Met Office and the University of East Anglia Climatic Research Unit HadCRUT4 dataset and the NASA GISS Land-Ocean Temperature Index (LOTI) dataset. We used detrended fluctuation analysis of second-order (DFA2) and wavelet-based spectral (WTS) analysis to investigate and quantify the global pattern of scaling in two datasets and to better understand cyclic behavior as a possible underlying cause of the observed forms of scaling. We found that, excluding polar and parts of subpolar regions because of their substantial data inhomogeneity, the global temperature pattern is long-range autocorrelated. Our results show a remarkable heterogeneity in the long-range dynamics of the global temperature anomalies in both datasets. This finding is in agreement with previous studies. We additionally studied the DFA2 and the WTS behavior of the local station temperature anomalies and satellite-based temperature estimates and found that the observed diversity of global scaling can be attributed both to the intrinsic variability of data and to the methodology-induced variations that arise from deriving the global temperature gridded data from the original local sources. Finally, we found differences in global temperature scaling patterns of the two datasets and showed instances where spurious scaling is introduced in the global datasets through a spatial infilling procedure or the optimization of integrated satellite records
Myeloid-Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets
Get PDFMyeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early-MDSCs, monocytic-MDSCs, and polymorphonuclear-MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T-cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune-mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune-mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research
Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib in vitro by altering cell bioenergetics
Get PDFObjective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPAR gamma, on melanoma cells as a potential agent for repurposing in melanoma treatment. Methods: Expression of AGTR1 and PPAR gamma mRNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method. Results: Both AGTR1 and PPAR gamma mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell apoptosis. Increased glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the treatment. Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression
Analiza ekspresije eNOS i angiogenih faktora HIF-1alfa i VEGF u mijeloproliferativnim neoplazmama: veza sa prisustvom mutacija u genima za JAK2 i CALR
Get PDFhematopoiesis characterized by a disorder of proliferation of one or more myeloid cell lines. MPNs include 3 entities: polycythemia (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The most common disorder in MPN is the JAK2V617F mutation present in 97% of patients diagnosed with PV and 50-60% of patients with ET and PMF diagnoses. The JAK2V617F mutation induces the constituent activation of the innate signal pathways (JAK2 / STAT3, PI3K / AKT, MAPK) involved in myeloproliferation. The second most common somatic mutation, which is present in most JAK2V617F negative ET and PMF patients, is associated with the calreteculin (CALR) encoding genome present in 31.9% ET and 31.7% of PMF patients. In the case of various hematological malignancies, including MPN, as a reflection of increased angiogenesis, the presence of elevated expression of vascular endothelial growth factor (VEGF) has been described. Recent studies have shown the relationship between the expression of the VEGF gene and the levels of hypoxia-inducible factor-1 (HIF-1) and nitrogen monoxide (NO). Several studies have so far shown that NO can induce the production of VEGF via PI3K / Akt / PKB / HIF-1α times, but also acts as an inhibitor of HIF-1α expression. The aim of the study was to investigate the degree of expression and correlation of key angiogenic factors - HIF-1α, VEGF and endothelial NO synthase (eNOS) in the bone marrow, CD34+ cells and granulocytes of MPN patients according to JAK2 and CALR status and therapy. In addition, we used proinflammatory IL-6 to induce the expression of HIF-1α, VEGF and eNOS in the human HEL 92.1.7 cell line with a JAK2 mutation, as well as in differentiated macrophages. Also studied was the participation of various signaling pathways (JAK2 / STAT3, PI3K / Akt, MAPK) through which IL-6 achieved its effects on the HEL cell line model as well as in granulocyte of MPN patients. The results of this study have shown that angiogenic factors have a more pronounced expression in granulocytes than in CD34+ and bone marrow cells, which indicates the importance of inflammatory granulocytes in the development of angiogenesis. A significant negative correlation between HIF-1α and VEGF protein expression, as well as HIF-1α and eNOS, was shown, while there was a significant positive correlation between VEGF and eNOS in granulocytes of MPN patients. Standard treatment with hydroxyurea in MPN patients has antiangiogenic potential in terms of reducing all three angiogenic factors - HIF-1α, VEGF and eNOS in granulocytes...Mijeloproliferativne neoplazme (MPN) predstavljaju klonalne bolesti matičnih ćelija hematopoeze koje karakteriše poremećaj proliferacije jedne ili više mijeloidnih ćelijskih linija. MPN obuhvataju 3 entiteta: policitemiju veru (PV), esencijalnu trombocitemiju (ET) i primarnu mijelofibrozu (PMF). Najzastupljeniji poremećaj kod MPN je JAK2V617F mutacija koja je prisutna kod 97% pacijenata sa dijagnozom PV i 50-60% pacijenata sa dijagnozama ET i PMF. JAK2V617F mutacija indukuje konstitutivnu aktivaciju nishodnih signalnih puteva (JAK2/STAT3, PI3K/AKT, MAPK) koji su uključeni u mijeloproliferaciju. Druga najzastupljenija somatska mutacija, koja je prisutna kod većine JAK2V617F negativnih ET i PMF pacijenata, povezana je sa genom koji kodira kalretikulin (CALR) prisutna kod 31,9% ET i 31,7% PMF pacijenata. Kod različitih hematoloških maligniteta, uključujući i MPN, kao odraz pojačane angiogeneze, opisano je prisustvo povišene ekspresije faktora rasta vaskularnog endotela (VEGF). U novijim istraživanjima pokazana je veza između ekspresije VEGF gena i nivoa hipoksija-inducibilnog faktora-1 (HIF-1) azot monoksida (NO). Nekoliko studija do sada je pokazalo da NO može indukovati produkciju VEGF putem PI3K/Akt/PKB/HIF-1α puta, ali i da deluje kao inhibitor HIF-1α ekspresije. Cilj istraživanja ove disertacije bilo je ispitivanje stepena ekspresije i korelacija ključnih angiogenih faktora - HIF-1α, VEGF i endotelne NO sintaze (eNOS) u kostnoj srži, CD34+ ćelijama i granulocitima MPN pacijenata prema JAK2 i CALR statusu i terapiji. Pored toga, koristili smo proinflamatorni IL-6 da indukujemo ekspresiju HIF-1α, VEGF i eNOS u humanoj HEL 92.1.7 ćelijskoj liniji sa JAK2 mutacijom, kao i u diferentovanim makrofagama. Takođe ispitivano je učešće različitih signalnih puteva (JAK2/STAT3, PI3K/Akt, MAPK) putem kojih IL-6 ostvaruje svoje efekte, na modelu HEL ćelijske linije kao i kod granulocita MPN pacijenata. Rezultati ove studije su pokazali da angiogeni faktori imaju izraženiju ekspresiju u granulocitima nego u CD34+ i ćelijama kostne srži, što ukazuje na značaj inflamatornih granulocita u razvoju angiogeneze. Pokazana je i značajna negativna korelacija između proteinske ekspresije HIF-1α i VEGF, kao i HIF-1α i eNOS, dok između VEGF i eNOS postoji značajna pozitivna korelacija kod granulocita MPN pacijenata. Standardno lečenje primenom hidroksiureje kod MPN pacijenata ima antiangiogeni potencijal u smislu smanjenja sva tri angiogena faktora – HIF-1α, VEGF i eNOS u granulocitima..
Detection and genotyping of Toxoplasma gondii in wild canids in Serbia
No full textTo gain insight into the population structure of the protozoan parasite Toxoplasma gondii in wildlife in Serbia, multiplex nested PCR- RFLP was performed on T. gondii DNA positive samples of heart tissue of three wild canid species, including red foxes (Vulpes vulpes), golden jackals (Canis aureus) and grey wolves (Canis lupus). Out of 110 samples (28 red foxes, 72 golden jackals, 10 wolves), 30 (27.3%) were positive for T. gondii DNA, of which 24 were genotyped (nine red foxes, 13 golden jackals and two wolves). The results showed a large dominance of lineage II (n = 20, 83.4%) over lineage III (n = 4, 16.7%) strains. Lineage II comprised four archetypes, 14 variants and one which remained undetermined, while within lineage III there were three archetypes and one variant strain. However, a notable difference in diversity was observed among the examined canids, with eight (88.9%) of the nine strains detected in red foxes distinct, vs. six (46.1%) distinct strains of the 13 detected in golden jackals. Since anthropogenic food sources are a major reservoir of archetypal lineage II and III T. gondii strains, the results suggest that the golden jackal may be outcompeting the red fox, forcing it to hunt wild mammals and birds for sustenance, thereby increasing its chances of infection with variant strains. In addition to presenting the first data on the T. gondii population structure in wild canids in Serbia, this is the first report ever on T. gondii genotypes in golden jackals, a species with an increasing presence in Europe and another important reservoir of domestically circulating T. gondii strains
Antigenotoxic and antioxidant potential of medicinal mushrooms (Immune Assist) against DNA damage induced by free radicals-an in vitro study
Get PDFImmune Assist (IA) is produced from extract of six species of medical mushrooms: Agaricus blazei - Cordyceps sinensis - Grifola frondosa - Ganoderma lucidum - Coriolus versicolor - Lentinula edodes. The genoprotective potential of IA was evaluated for the first time. Significant antigenotoxic effects were detected in human peripheral blood cells against H2O2 induced DNA damage, in the pretreatment and in the posttreatment. The most efficient concentration of IA in pretreatment was 500 mu g/mL, while in posttreatment it was the concentration of 250 mu g/mL. Kinetics of attenuation of H2O2 induced DNA damage in posttreatment with the optimal concentration of IA showed significant decrease in the number of damaged cells at all time periods (15-60 min), reaching the greatest reduction after 15 and 45 min. Remarkable center dot OH scavenging properties and moderate reducing power, together with the modest DPPH scavenging activity, could be responsible for the great attenuation of DNA damage after 15 min of exposure to IA, while reduction of DNA damage after 45 min could be the result in additional stimulation of the cell's repair machinery. Our results suggest that IA displayed antigenotoxic and antioxidant properties. A broader investigation of its profile in biological systems is needed
Synthesis, characterization and biological study of new dinuclear zinc(ii) and nickel(ii) octaaza macrocyclic complexes
Get PDFTwo new nitrato complexes of zinc and nickel with 1,4,8,11-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane (tpmc), have been synthesized and characterized. The IR spectral peaks showed that the coordinated and ionic nitrate ions are in agreement with the formula proposed by elemental analysis. Conductometric titrations predicted methanol to be a convenient solvent for synthesis and revealed the stoichiometry of the complexes, while molar electrical conductivities indicated a 1 : 3 complex electrolyte type for the zinc complex, and a 1 : 2 complex electrolyte type for the nickel complex. The optimized complex structure was obtained by molecular modeling and density functional theory calculations. The biological activity of the novel complexes was examined by screening eight different bacterial strains and two cancer cell lines. The zinc complex showed better antimicrobial activity against the bacterial strains, while the complexes did not show significance antiproliferative activity toward cancer cells MCF-7 and MDA-MB-231