Immunomodulatory and antioxidant properties of 10-hydroxy-2-decanoic acid

10-hidroksi-2-dekanoična kiselina (10-HDA) je jedinstvena i najzastupljenija nezasićena masna kiselina matičnog mleča. Iako prvi naučni radovi o ovoj masnoj kiselini datiraju još od pedesetih godina prošlog veka, dosadašnja istraživanja, uglavnom na in vitro animalnim modelima, su pokazala njeno anti-inflamatorno svojstvo. Međutim, veoma malo se zna o njenoj imunomodulatornoj i antioksidativnoj ulozi. Stoga smo mi u ovoj studiji ispitivali efekat 10-HDA na funkcije humanih ćelija imunskog sistema in vitro, kao i njeno potencijalno antioksidativno svojstvo. Dobijeni rezultati su pokazali da je 10-HDA u milimolarnim koncentracijama (1mM i 2mM) inhibirala oksidativni prasak humanih neutrofila periferne krvi stimulisanih forbol-12-miristat-13-acetatom (PMA), N-formil-L-metionil-L-leucil-L-fenilalaninom (fMLP) ili opsonizovanim zimozanom (opZy) u kulturi. Osim toga, ova masna kiselina je u istim koncentracijama inhibirala kako spontanu, tako i PMA, fMLP i opZy indukovanu apoptozu, ali i intenzitet PMA uzrokovane NEToze (engl. Neutrophil Extracellular Traps) humanih neutrofila. U kulturama humanih mononuklearnih ćelija periferne krvi (PBMNC) stimulisanim fitohemaglutininom (PHA) 10-HDA je u koncentraciji od 500μM ispoljila pretežno supresivni efekat na proliferaciju PBMNC. Ovaj proces je bio praćen smanjenom produkcijom interleukina (IL)-2. U istoj koncentraciji, 10- HDA je inhibirala sekreciju IL-1β i faktora nekroze tumora (TNF)-α. Analizirajući citokinski T „helper“ (Th) profil u ovim kulturama pokazano je da je 10-HDA, u koncentraciji od 500μM, inhibirala Th1 i Th2 polarizaciju imunskog odgovora, a nije značajnije modulisala Th17 imunski odgovor. Takođe, u ovoj studiji je ispitivan uticaj 10-HDA na maturaciju i funkciju humanih dendritskih ćelija monocitnog porekla (MoDC). 10-HDA je, u koncentraciji od 500μM, inhibirala maturaciju MoDC stimulisanih lipopolisaharidom (LPS). Ovako stimulisane MoDC su produkovale manje količine IL-12, IL-18 i TNF-α, i inhibirale Th1 i Th2 polarizaciju imunskog odgovora, što je zaključeno na osnovu smanjenja koncentracije interferona (IFN)-γ i IL-4 u supernatantima ko-kultura 10-HDA-tretiranih MoDC i alogenih CD4+ T limfocita periferne krvi. Nasuprot ovim rezultatima, 10-HDA je, u niskoj koncentraciji (50μM), stimulisala Th1, a inhibirala Th2 imunski odgovor. Ispitujući antioksidativno svojstvo 10-HDA, na eksperimentalnim modelima bez ćelija, u kojima se reaktivne kiseonične vrste produkuju čisto hemijskim putem, pokazano je da ova masna kiselina, u milimolarnim koncentracijama (1mM- 4mM), ima sposobnost da „sakuplja“, odnosno reaguje sa superoksid anjon radikalom i hipohlornom kiselinom i tako smanjuje njihovo reaktivno delovanje. Na osnovu dobijenih rezultata može se zaključiti da 10-HDA ispoljava dozno- zavisan efekat na odgovor humanih imunskih ćelija in vitro, pri čemu u visokim koncentracijama (0,5mM-2mM) deluje inhibitorno, a u niskim koncentracijama (50μM) blago stimulatorno. Takođe, pokazano je da 10-HDA u milimolarnim koncentracijama (1mM-4mM) ispoljava direktno antioksidativno svojstvo.10-hydroxy-2-decanoic acid (10-HDA) is unique and the most common fatty acid of royal jelly. Although the first scientific papers about this fatty acid originate from fifties of the last century, very little is known about its immunomodulatory and antioxidative activity. Therefore, we examined the effects of 10-HDA on the function of human immune cells in vitro, as well as its potential antioxidative properties. The obtained results showed that 10-HDA at millimolar concentrations (1mM and 2mM) inhibited oxidative burst of human peripheral blood neutrophils stimulated with phorbol-12-myristate-13-acetate (PMA), N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or opsonized zymosan (opZy) and neutrophil extracellular traps formation induced by PMA. In addition, 10-HDA at the same concentrations inhibited spontaneous apoptosis, as well as PMA-, fMLP- and opZy-induced apoptosis of neutrophils. 10-HDA, at concentration of 500μM, inhibited the proliferation of phytohaemagglutinin-activated human peripheral blood mononuclear cells (PBMNCs), and the process was followed by a decrease in the production of interleukin 2 (IL-2). At the same concentration, 10-HDA inhibited the production of IL-1β and tumor necrosis factor-α (TNF-α) by stimulated PBMNCs. Regarding T helper (Th) cytokine profile, higher concentration of 10-HDA (500μM), in contrast to the lower one (50μM), inhibited both Th1 and Th2 responses, whereas the Th17 response was not significantly modulated, as judged by the levels of interferon-γ (IFN-γ), IL-5 and IL-17A in culture supernatants, respectively. The effect of 10-HDA on maturation and functions of human monocyte-derived dendritic cells (MoDCs) was also investigated. A lower dose (50 μM) stimulated T helper (Th)1 and down-regulated Th2 immune responses, as judged by the levels of IFN-γ and IL-4, respectively, in supernatants of 10-HDA-treated MoDCs cultivated with allogeneic CD4+ T cells. In contrast, a higher dose of 10-HDA (500 μM) inhibited maturation of lipopolysaccharide (LPS)-stimulated MoDCs. Such treated MoDCs produced lower levels of IL-12, IL-18 and TNF-α and down-regulated both Th1 and Th2 immune responses. Examining the antioxidant properties by using cell-free systems, we demonstrated that 10- HDA at millimolar concentrations is a scavenger of superoxide anion radical and HOCl. In conclusion, our results suggest that 10-HDA exerts different activity on human immune cells, depending on applied concentrations, which is important when considering its therapeutic immunomodulatory property. In addition, it was shown that 10-HDA, at millimolar concentrations, exerts direct antioxidant properties

Landspout across Novi Beograd, 24 may 2012: Synoptic analysis

In this study we have analysed a case of the landspout across Novi Beograd on 24 May 2012. We have used a synoptic analysis method in the research and the description of the landspout event is based on visual evidence and photographs. According to the available data, it can be concluded that there were favourable conditions for a landspout development since there was a process and an increased amount of instability. The landspout occured within the northeast stream which moved over Belgrade and further toward the southeast and west. Based upon synoptic data analysis, it can’t be said that there was a cold air advection. Surface air was warm enough, but not the air in the upper layers of the atmosphere. The conditions for a landspout development were favourable - high relative air humidity and increased vertical and horizontal air currents

Pojava trombe na Novom Beogradu 24. maja 2012. godine - sinoptička analiza

In this study we have analysed a case of the landspout across Novi Beograd on 24 May 2012. We have used a synoptic analysis method in the research and the description of the landspout event is based on visual evidence and photographs. According to the available data, it can be concluded that there were favourable conditions for a landspout development since there was a process and an increased amount of instability. The landspout occured within the northeast stream which moved over Belgrade and further toward the southeast and west. Based upon synoptic data analysis, it can't be said that there was a cold air advection. Surface air was warm enough, but not the air in the upper layers of the atmosphere. The conditions for a landspout development were favourable - high relative air humidity and increased vertical and horizontal air currents.U radu je prikazan slučaj pojave trombe 24.05.2012. na Novom Beogradu. U istraživanju je korišćen metod sinoptičke analize, a opis pojave trombe temelji se na vizuelnom opažanju i fotografijama. Prema raspoloživim podacima može se zaključiti da su uslovi za razvoj trombe bili povoljni, jer je postojao i proces i povećana energija nestabilnosti. Tromba se javila u sklopu severoistočne struje koja se premeštala preko Beograda dalje na jugozapad i zapad. Na osnovu analize sinoptičkog materijala, ne može se reći da se radilo o advekciji jako hladnog vazduha. Bilo je dovoljno toplote u prizemlju, ali ne i po visini. Postojali su povoljni uslovi za nastanak trombe - visoka vlažnost vazduha, izražena vertikalna i horizontalna strujanja

MORPHOLOGICAL AND IMMUNOCYTOCHEMICAL CHARACTERISTICS OF STROMAL GASTROINTESTINAL TUMORS

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of gastrointestinal system and they are characterised by extreme variability in clinical, hystopathological and genetic features. It is considered that all GISToms have a malignant potential. Ethiological factors which cause GISToms have not been clarified yet, and genetic basis is not easy to be determined since GISToms are mostly sporadic. However, certain genetic and cytogenetic aberations which have been determined can be considered to have an impact on the onset of GISToms. Macroscopic picture is polymorphic, but they can most frequently be seen as large, mushroom-like, intraluminal, clearly limited pseudo-incapsulated submucosal masses. Hystomorphology of these tumors shows a high spectar of structural and cellular variations. They are most frequently built out of spindle cells (60-70% of cases), rarely of epitheloid (about 30% of cases) and very rarely of mixed and transitional type (intermedial). Stroma is predominantly loose or poorly colagenized with neoangiogenesis, which is markedly in GISToms with a higher malignant potential. Most of GISToms (95%) express transmembrane receptors KIT (CD 117), CD 34, vimentine, specific neurogenic and smooth muscle cells markers. The most successful therapies are: surgical ressection, imatinib and sunitinib (in case of imatinib resistence) therapy (tyrosine kinase receptor blockers). Research are being conducted all over the world with the aim of finding new and more efficient drug therapies that would not manifest resistency

Inventory of meat industry polluters in Vojvodina region

Inventory of Polluters is the register of information and data on environmental polluters and represents a major starting point for identifying and monitoring of pollution sources. One of the objectives of the National project of the Ministry of Education and Science no 46009: Improvement and development of hygienic and technological procedures in production of animal originating foodstuffs with the aim of producing high-quality and safe products competitive on the global market, is to establish the Inventory of Polluters from the meat industry acquiring all the data required by the Serbian legislation. The meat industry sector emerges as one of the top two or three most significant contributors to the most serious environmental problems, at every scale from local to global. Inventory of Polluters will include the information and data from polluters identified on the territory of AP Vojvodina from the meat industry sector. According to the obtained results, the total number of potential water pollutants within this sector totals up to 94 legal entities

Pseudo-persistent pollutant in the environment : emerging substances

In the recent time, considerable interest has grown concerning the presence of the emerging substances, EmS. These are contaminants that have been recently detected in the environment due to their long-term, pseudo-persistent and increased use. Most of EmS are wide spread and applied in different fields using as pharmaceuticals, for both human and animal uses, household chemicals, personal care products, nanomaterial, anticorrosive and agriculture chemicals and others. European legislation did not regulate the status and the maximum allowed concentration of most EmS. EmS might jeopardize surface water and ground water resources, particularly, drinking water production. The preliminary results of Danube surface water in vicinity of Novi Sad show presence of benzotriasole and caffeine. These newly recognized contaminants represent a shift in traditional thinking of protection scenario and eco status of environment and water bodies

Transformation of Abandoned Railways into Tourist Itineraries/Routes: Model of Revitalization of Marginal Rural Areas

Railways that were once utilized by conventional speed trains but now lay technologically outdated and neglected are scarcely in use today, with many lying abandoned. These rail networks sprawl across vast areas, posing a substantial impediment to sustainable land use and management. Our research advocates for the adoption of tourist itinerary/route as a viable model for the transformation of abandoned railways into sustainable and functional systems. This innovative concept involves repurposing abandoned railways into tourist itineraries with the aim of utilizing them for tourism and commercial ventures. Recognizing a knowledge gap, particularly the absence of scientifically grounded models, on a selected case study (abandoned regional railway number 223 in the Toplica District, Serbia), we develop and present a model for the identification and Tourist Evaluation of Abandoned Railways (TEAR model). The defined model comprises a total of 27 sub-indicators categorized into four groups of indicators: natural tourist values (NV), anthropogenic tourist values (AV), tourist attractiveness of the railway (TA), and functional values (FV). The findings from the TEAR model suggest that the abandoned railway holds significant tourism value, with a rating of ≥0.7. Specifically, three sets of indicators—NV, AV, and TA—indicate a high level of tourist values (≥0.7), while FV falls within a moderate range of tourist values (0.4 ≤ V < 0.7). This endeavor not only supports sustainable local and regional development but also contributes to the enhancement of rural landscapes and the revitalization of rural areas. Importantly, this initiative aligns directly and indirectly with several Sustainable Development Goals (SDGs), thus fostering progress towards broader economic, societal, and environmental objectives

Transformation of Abandoned Railways into Tourist Itineraries/Routes: Model of Revitalization of Marginal Rural Areas

Railways that were once utilized by conventional speed trains but now lay technologically outdated and neglected are scarcely in use today, with many lying abandoned. These rail networks sprawl across vast areas, posing a substantial impediment to sustainable land use and management. Our research advocates for the adoption of tourist itinerary/route as a viable model for the transformation of abandoned railways into sustainable and functional systems. This innovative concept involves repurposing abandoned railways into tourist itineraries with the aim of utilizing them for tourism and commercial ventures. Recognizing a knowledge gap, particularly the absence of scientifically grounded models, on a selected case study (abandoned regional railway number 223 in the Toplica District, Serbia), we develop and present a model for the identification and Tourist Evaluation of Abandoned Railways (TEAR model). The defined model comprises a total of 27 sub-indicators categorized into four groups of indicators: natural tourist values (NV), anthropogenic tourist values (AV), tourist attractiveness of the railway (TA), and functional values (FV). The findings from the TEAR model suggest that the abandoned railway holds significant tourism value, with a rating of ≥0.7. Specifically, three sets of indicators—NV, AV, and TA—indicate a high level of tourist values (≥0.7), while FV falls within a moderate range of tourist values (0.4 ≤ V < 0.7). This endeavor not only supports sustainable local and regional development but also contributes to the enhancement of rural landscapes and the revitalization of rural areas. Importantly, this initiative aligns directly and indirectly with several Sustainable Development Goals (SDGs), thus fostering progress towards broader economic, societal, and environmental objectives

Assessment of the Attractiveness of Natural Resources and Landscapes of the Kopaonik National Park (Serbia): Framework and Importance for Tourism Development

This research presents a methodological framework for assessing the attractiveness of natural resources and landscapes and their importance for tourism development. The research is conducted in the area of Kopaonik Mountain in Serbia, which is partly, due to its natural values, declared a natural heritage of exceptional importance Protection Category I, i.e. the National Park. The goal of this paper is to identify and assess the tourist attractiveness of the natural resources (relief, hydrological and climatological characteristics, and vegetation) and landscapes in the National Park (NP) Kopaonik area. There are two independent methods used to assess the tourist attractiveness of natural resources and landscapes in this study. The first method is based on numerical and statistical analysis and quantitatively expresses the attractiveness of natural resources/elements (relief, climate, hydrology and vegetation) separately and all together, indicating the overall attractiveness of natural resources for tourism development. The second method envisages 8 criteria according to which natural landscapes are scored on a scale from 0 to 3. Based on a clearly defined model for assessing the attractiveness of natural resources and landscapes, we conclude that the area of Kopaonik National Park has a high level of tourist attractiveness

Assessment of the Attractiveness of Natural Resources and Landscapes of the Kopaonik National Park (Serbia): Framework and Importance for Tourism Development

This research presents a methodological framework for assessing the attractiveness of natural resources and landscapes and their importance for tourism development. The research is conducted in the area of Kopaonik Mountain in Serbia, which is partly, due to its natural values, declared a natural heritage of exceptional importance Protection Category I, i.e. the National Park. The goal of this paper is to identify and assess the tourist attractiveness of the natural resources (relief, hydrological and climatological characteristics, and vegetation) and landscapes in the National Park (NP) Kopaonik area. There are two independent methods used to assess the tourist attractiveness of natural resources and landscapes in this study. The first method is based on numerical and statistical analysis and quantitatively expresses the attractiveness of natural resources/elements (relief, climate, hydrology and vegetation) separately and all together, indicating the overall attractiveness of natural resources for tourism development. The second method envisages 8 criteria according to which natural landscapes are scored on a scale from 0 to 3. Based on a clearly defined model for assessing the attractiveness of natural resources and landscapes, we conclude that the area of Kopaonik National Park has a high level of tourist attractiveness