TY  - CONF
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Šavikin, Katarina
AU  - Šenerović, Lidija
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5769
AB  - Аронија (lat. Aronia melanocarpa), воће карактеристично по тамним
бобицама опорог укуса, садржи мноштво фенолних једињења заслужних за
антиоксидативна својства ове биљне врсте. Водени екстракт плода ароније
(ВЕПА) у овом истраживању показао је проинфламацијско дејство: in vitro
је повећао фагоцитну способност макрофага и стимулисао продукцију
азот моноксида, као и диференцијацију проинфламацијских Т лимфоцита,
а in vivo након оралне примене је повећао заступљеност ефекторских Т
лимфоцита у Пејеровим плочама, као и продукцију IFN-γ на системском
нивоу. Да би се додатно испитао проинфламацијски потенцијал ВЕПА,
коришћени су експериментални мишји модели инфекције бактеријом
Listeria monocytogenes и меланома. Показано је да претретман ВЕПА не
само умањује губитак телесне масе и помаже ерадикацију инфекције, већ
и у Пејеровим плочама и слезини доводи до повећане заступљености CD8+
Т лимфоцита и CD11b+ макрофага, који се одликују већом фагоцитном
способношћу. У моделу меланома на мишевима, након седмодневног
претретмана ВЕПА индукован је меланом поткожним давањем 2.5х105 Б16
ћелија и орални третман ВЕПА је настављен до краја експеримента. Осим
што је успорио развој тумора и његову запремину, претретман је повећао
инфилтрацију имунских ћелија у тумор, као и заступљеност IFN-γ+ ћелија
унутар NK+, CD4+ и CD8+ ћелија, док је заступљеност супресорских ћелија
смањена. Ови резултати указују на потенцијал примене ароније у превенцији
стања и болести у којима је неопходна стимулација проинфламацијског
имунског одговора.
AB  - Aronija (lat. Aronia melanocarpa), voće karakteristično po tamnim bobicama oporog ukusa, sadrži mnoštvo fenolnih jedinjenja zaslužnih za antioksidativna svojstva ove biljne vrste. Vodeni ekstrakt ploda aronije (VEPA) u ovom istraživanju pokazao je proinflamacijsko dejstvo: in vitro je povećao fagocitnu sposobnost makrofaga i stimulisao produkciju azot monoksida, kao i diferencijaciju proinflamacijskih T limfocita, a in vivo nakon oralne primene je povećao zastupljenost efektorskih T limfocita u Pejerovim pločama, kao i produkciju IFN-γ na sistemskom nivou. Da bi se dodatno ispitao proinflamacijski potencijal VEPA, korišćeni su eksperimentalni mišji modeli infekcije bakterijom Listeria monocytogenes i melanoma. Pokazano je da pretretman VEPA ne samo umanjuje gubitak telesne mase i pomaže eradikaciju infekcije, već i u Pejerovim pločama i slezini dovodi do povećane zastupljenosti CD8+ T limfocita i CD11b+ makrofaga, koji se odlikuju većom fagocitnom sposobnošću. U modelu melanoma na miševima, nakon sedmodnevnog pretretmana VEPA indukovan je melanom potkožnim davanjem 2.5h105 B16 ćelija i oralni tretman VEPA je nastavljen do kraja eksperimenta. Osim što je usporio razvoj tumora i njegovu zapreminu, pretretman je povećao infiltraciju imunskih ćelija u tumor, kao i zastupljenost IFN-γ+ ćelija unutar NK+, CD4+ i CD8+ ćelija, dok je zastupljenost supresorskih ćelija smanjena. Ovi rezultati ukazuju na potencijal primene aronije u prevenciji stanja i bolesti u kojima je neophodna stimulacija proinflamacijskog imunskog odgovora.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia
T1  - Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora
T1  - Утицај воденог екстракта плода ароније на имунски систем у мишјим моделима инфекције и тумора
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5769
ER  - 

@conference{
author = "Mićanović, Dragica and Saksida, Tamara and Koprivica, Ivan and Vujičić, Milica and Šavikin, Katarina and Šenerović, Lidija and Despotović, Sanja and Pejnović, Nada and Stojanović, Ivana D.",
year = "2021",
abstract = "Аронија (lat. Aronia melanocarpa), воће карактеристично по тамним
бобицама опорог укуса, садржи мноштво фенолних једињења заслужних за
антиоксидативна својства ове биљне врсте. Водени екстракт плода ароније
(ВЕПА) у овом истраживању показао је проинфламацијско дејство: in vitro
је повећао фагоцитну способност макрофага и стимулисао продукцију
азот моноксида, као и диференцијацију проинфламацијских Т лимфоцита,
а in vivo након оралне примене је повећао заступљеност ефекторских Т
лимфоцита у Пејеровим плочама, као и продукцију IFN-γ на системском
нивоу. Да би се додатно испитао проинфламацијски потенцијал ВЕПА,
коришћени су експериментални мишји модели инфекције бактеријом
Listeria monocytogenes и меланома. Показано је да претретман ВЕПА не
само умањује губитак телесне масе и помаже ерадикацију инфекције, већ
и у Пејеровим плочама и слезини доводи до повећане заступљености CD8+
Т лимфоцита и CD11b+ макрофага, који се одликују већом фагоцитном
способношћу. У моделу меланома на мишевима, након седмодневног
претретмана ВЕПА индукован је меланом поткожним давањем 2.5х105 Б16
ћелија и орални третман ВЕПА је настављен до краја експеримента. Осим
што је успорио развој тумора и његову запремину, претретман је повећао
инфилтрацију имунских ћелија у тумор, као и заступљеност IFN-γ+ ћелија
унутар NK+, CD4+ и CD8+ ћелија, док је заступљеност супресорских ћелија
смањена. Ови резултати указују на потенцијал примене ароније у превенцији
стања и болести у којима је неопходна стимулација проинфламацијског
имунског одговора., Aronija (lat. Aronia melanocarpa), voće karakteristično po tamnim bobicama oporog ukusa, sadrži mnoštvo fenolnih jedinjenja zaslužnih za antioksidativna svojstva ove biljne vrste. Vodeni ekstrakt ploda aronije (VEPA) u ovom istraživanju pokazao je proinflamacijsko dejstvo: in vitro je povećao fagocitnu sposobnost makrofaga i stimulisao produkciju azot monoksida, kao i diferencijaciju proinflamacijskih T limfocita, a in vivo nakon oralne primene je povećao zastupljenost efektorskih T limfocita u Pejerovim pločama, kao i produkciju IFN-γ na sistemskom nivou. Da bi se dodatno ispitao proinflamacijski potencijal VEPA, korišćeni su eksperimentalni mišji modeli infekcije bakterijom Listeria monocytogenes i melanoma. Pokazano je da pretretman VEPA ne samo umanjuje gubitak telesne mase i pomaže eradikaciju infekcije, već i u Pejerovim pločama i slezini dovodi do povećane zastupljenosti CD8+ T limfocita i CD11b+ makrofaga, koji se odlikuju većom fagocitnom sposobnošću. U modelu melanoma na miševima, nakon sedmodnevnog pretretmana VEPA indukovan je melanom potkožnim davanjem 2.5h105 B16 ćelija i oralni tretman VEPA je nastavljen do kraja eksperimenta. Osim što je usporio razvoj tumora i njegovu zapreminu, pretretman je povećao infiltraciju imunskih ćelija u tumor, kao i zastupljenost IFN-γ+ ćelija unutar NK+, CD4+ i CD8+ ćelija, dok je zastupljenost supresorskih ćelija smanjena. Ovi rezultati ukazuju na potencijal primene aronije u prevenciji stanja i bolesti u kojima je neophodna stimulacija proinflamacijskog imunskog odgovora.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia",
title = "Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora, Утицај воденог екстракта плода ароније на имунски систем у мишјим моделима инфекције и тумора",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5769"
}

Mićanović, D., Saksida, T., Koprivica, I., Vujičić, M., Šavikin, K., Šenerović, L., Despotović, S., Pejnović, N.,& Stojanović, I. D.. (2021). Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora. in Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5769

Mićanović D, Saksida T, Koprivica I, Vujičić M, Šavikin K, Šenerović L, Despotović S, Pejnović N, Stojanović ID. Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora. in Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia. 2021;.
https://hdl.handle.net/21.15107/rcub_ibiss_5769 .

Mićanović, Dragica, Saksida, Tamara, Koprivica, Ivan, Vujičić, Milica, Šavikin, Katarina, Šenerović, Lidija, Despotović, Sanja, Pejnović, Nada, Stojanović, Ivana D., "Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora" in Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia (2021),
https://hdl.handle.net/21.15107/rcub_ibiss_5769 .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Despotović, Sanja
AU  - Šavikin, Katarina
AU  - Janković, Teodora
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5783
AB  - Many plant extracts are well known for their anti-oxidant, anti-bacterial and antiinflammatory
activities including Aronia berry-derived juices and powders. In
comparison to other black berries, Aronia berries have a greater content of phenolic
constituents such as procyanidins, anthocyanins and phenolic acids with antioxidative
and anti-inflammatory properties. However, the effects of aronia berries extract on the
immune response parameters have been only sporadically assessed. When administered
orally to healthy C57BL/6 mice (50 mg/kg body weight), aronia extract exerted
immunomodulatory effects as evidenced by decreased proportion of F4/80+
macrophages, CD11c+ dendritic cells, CD4+ T helper cells, CD8+ T cytotoxic
lymphocytes and CD4+CD25- activated lymphocytes within the gut-associated
lymphoid tissue. Surprisingly, oral consumption of chokeberry extract in doses of either
200 mg/kg bw or 50 mg/kg bw in mice with multiple low dose streptozotocin-induced
type 1 diabetes resulted in the increase of blood glucose levels. Further, our study shows
that this detrimental effect on type 1 diabetes pathogenesis may be a consequence of
the pro-inflammatory nature of the extract. This is based on the evident stimulation of
macrophages and dendritic cells by the extract through up-regulation of proinflammatory
mediators such as nitric oxide, IL-12, IL-6 and TNF in vitro. Also, this
extract augmented differentiation of IFN-γ-producing T helper 1 cells in vitro.
Collectively, the obtained results imply that our particular aronia berries fruit extract
displays pro-inflammatory characteristics and that care should be taken when these
berries are to be included in the human diet.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - Aronia berries fruit water extract stimulates cells of the immune system in vitro and in vivo
SP  - 130
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5783
ER  - 

@conference{
author = "Mićanović, Dragica and Saksida, Tamara and Koprivica, Ivan and Vujičić, Milica and Despotović, Sanja and Šavikin, Katarina and Janković, Teodora and Stojanović, Ivana D.",
year = "2021",
abstract = "Many plant extracts are well known for their anti-oxidant, anti-bacterial and antiinflammatory
activities including Aronia berry-derived juices and powders. In
comparison to other black berries, Aronia berries have a greater content of phenolic
constituents such as procyanidins, anthocyanins and phenolic acids with antioxidative
and anti-inflammatory properties. However, the effects of aronia berries extract on the
immune response parameters have been only sporadically assessed. When administered
orally to healthy C57BL/6 mice (50 mg/kg body weight), aronia extract exerted
immunomodulatory effects as evidenced by decreased proportion of F4/80+
macrophages, CD11c+ dendritic cells, CD4+ T helper cells, CD8+ T cytotoxic
lymphocytes and CD4+CD25- activated lymphocytes within the gut-associated
lymphoid tissue. Surprisingly, oral consumption of chokeberry extract in doses of either
200 mg/kg bw or 50 mg/kg bw in mice with multiple low dose streptozotocin-induced
type 1 diabetes resulted in the increase of blood glucose levels. Further, our study shows
that this detrimental effect on type 1 diabetes pathogenesis may be a consequence of
the pro-inflammatory nature of the extract. This is based on the evident stimulation of
macrophages and dendritic cells by the extract through up-regulation of proinflammatory
mediators such as nitric oxide, IL-12, IL-6 and TNF in vitro. Also, this
extract augmented differentiation of IFN-γ-producing T helper 1 cells in vitro.
Collectively, the obtained results imply that our particular aronia berries fruit extract
displays pro-inflammatory characteristics and that care should be taken when these
berries are to be included in the human diet.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "Aronia berries fruit water extract stimulates cells of the immune system in vitro and in vivo",
pages = "130",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5783"
}

Mićanović, D., Saksida, T., Koprivica, I., Vujičić, M., Despotović, S., Šavikin, K., Janković, T.,& Stojanović, I. D.. (2021). Aronia berries fruit water extract stimulates cells of the immune system in vitro and in vivo. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 130.
https://hdl.handle.net/21.15107/rcub_ibiss_5783

Mićanović D, Saksida T, Koprivica I, Vujičić M, Despotović S, Šavikin K, Janković T, Stojanović ID. Aronia berries fruit water extract stimulates cells of the immune system in vitro and in vivo. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2021;:130.
https://hdl.handle.net/21.15107/rcub_ibiss_5783 .

Mićanović, Dragica, Saksida, Tamara, Koprivica, Ivan, Vujičić, Milica, Despotović, Sanja, Šavikin, Katarina, Janković, Teodora, Stojanović, Ivana D., "Aronia berries fruit water extract stimulates cells of the immune system in vitro and in vivo" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2021):130,
https://hdl.handle.net/21.15107/rcub_ibiss_5783 .

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Despotović, Sanja
AU  - Šavikin, Katarina
AU  - Janković, Teodora
AU  - Stojanović, Ivana D.
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3591
AB  - Chokeberry (Aronia melanocarpa) is known for its anti-oxidant, anti-inflammatory and anti-diabetic properties. Since the effects of chokeberry extract on the immune response have been only sporadically assessed, our aim was to investigate chokeberry fruit water extract on the immune response in vivo and in vitro. When administered orally to healthy mice, the extract exerted immunomodulatory effects in the gut evidenced by the altered proportion of macrophages, dendritic cells and T cells. Importantly, oral consumption of the chokeberry extract resulted in blood glucose level increase in C57BL/6 mice with chemically-induced diabetes. These in vivo results were corroborated by observed up-regulation of nitric oxide and interelukin-1β production in macrophages and dendritic cells, up-regulated phagocytic activity of macrophages, increased T and B lymphocytes proportions and differentiation of interferon-γ-producing T cells in vitro. The obtained results imply that our chokeberry extract stimulates pro-inflammatory properties in immune cells of innate and adaptive immunity.
PB  - Elsevier Ltd.
T2  - Journal of Functional Foods
T1  - Chokeberry (Aronia melanocarpa) fruit extract modulates immune response in vivo and in vitro
VL  - 66
DO  - 10.1016/j.jff.2020.103836
SP  - 103836
ER  - 

@article{
author = "Mićanović, Dragica and Saksida, Tamara and Koprivica, Ivan and Vujičić, Milica and Despotović, Sanja and Šavikin, Katarina and Janković, Teodora and Stojanović, Ivana D.",
year = "2020",
abstract = "Chokeberry (Aronia melanocarpa) is known for its anti-oxidant, anti-inflammatory and anti-diabetic properties. Since the effects of chokeberry extract on the immune response have been only sporadically assessed, our aim was to investigate chokeberry fruit water extract on the immune response in vivo and in vitro. When administered orally to healthy mice, the extract exerted immunomodulatory effects in the gut evidenced by the altered proportion of macrophages, dendritic cells and T cells. Importantly, oral consumption of the chokeberry extract resulted in blood glucose level increase in C57BL/6 mice with chemically-induced diabetes. These in vivo results were corroborated by observed up-regulation of nitric oxide and interelukin-1β production in macrophages and dendritic cells, up-regulated phagocytic activity of macrophages, increased T and B lymphocytes proportions and differentiation of interferon-γ-producing T cells in vitro. The obtained results imply that our chokeberry extract stimulates pro-inflammatory properties in immune cells of innate and adaptive immunity.",
publisher = "Elsevier Ltd.",
journal = "Journal of Functional Foods",
title = "Chokeberry (Aronia melanocarpa) fruit extract modulates immune response in vivo and in vitro",
volume = "66",
doi = "10.1016/j.jff.2020.103836",
pages = "103836"
}

Mićanović, D., Saksida, T., Koprivica, I., Vujičić, M., Despotović, S., Šavikin, K., Janković, T.,& Stojanović, I. D.. (2020). Chokeberry (Aronia melanocarpa) fruit extract modulates immune response in vivo and in vitro. in Journal of Functional Foods
Elsevier Ltd.., 66, 103836.
https://doi.org/10.1016/j.jff.2020.103836

Mićanović D, Saksida T, Koprivica I, Vujičić M, Despotović S, Šavikin K, Janković T, Stojanović ID. Chokeberry (Aronia melanocarpa) fruit extract modulates immune response in vivo and in vitro. in Journal of Functional Foods. 2020;66:103836.
doi:10.1016/j.jff.2020.103836 .

Mićanović, Dragica, Saksida, Tamara, Koprivica, Ivan, Vujičić, Milica, Despotović, Sanja, Šavikin, Katarina, Janković, Teodora, Stojanović, Ivana D., "Chokeberry (Aronia melanocarpa) fruit extract modulates immune response in vivo and in vitro" in Journal of Functional Foods, 66 (2020):103836,
https://doi.org/10.1016/j.jff.2020.103836 . .

TY  - CHAP
AU  - Vujičić, Milica
AU  - Despotović, Sanja
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
AU  - Harris, James
AU  - Morand, Eric F.
PY  - 2020
UR  - http://link.springer.com/10.1007/978-1-4939-9936-1_17
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3535
AB  - Macrophage migration inhibitory factor (MIF) is a molecule with multiple functions: from enforcing the immune system to fight bacterial infection to the regulation of insulin activity. Also, MIF is expressed by enterocytes that line the intestinal border toward the lumen, and in M cells, where it regulates phagocytosis of antigens from the lumen of the gut and their transport to Peyer's patches. Since there were no data on the role of MIF in the maintenance of the intestinal barrier, we used MIF-deficient mice bred on C57BL/6 background as a model for the investigation of intestinal permeability. The obtained results indicate that the absence of MIF increases intestinal permeability. Here we describe two methods for measuring intestinal permeability in mice: detection of orally delivered FITC-dextran in the serum and transmission electron microscopy used for visualization and measurement of cell-to-cell connections width.
PB  - Humana, New York, NY
T2  - Macrophage Migration Inhibitory Factor
T1  - The Effect of Macrophage Migration Inhibitory Factor on Intestinal Permeability: FITC-Dextran Serum Measurement and Transmission Electron Microscopy.
DO  - 10.1007/978-1-4939-9936-1_17
SP  - 193
EP  - 201
ER  - 

@inbook{
author = "Vujičić, Milica and Despotović, Sanja and Saksida, Tamara and Stojanović, Ivana D. and Harris, James and Morand, Eric F.",
year = "2020",
abstract = "Macrophage migration inhibitory factor (MIF) is a molecule with multiple functions: from enforcing the immune system to fight bacterial infection to the regulation of insulin activity. Also, MIF is expressed by enterocytes that line the intestinal border toward the lumen, and in M cells, where it regulates phagocytosis of antigens from the lumen of the gut and their transport to Peyer's patches. Since there were no data on the role of MIF in the maintenance of the intestinal barrier, we used MIF-deficient mice bred on C57BL/6 background as a model for the investigation of intestinal permeability. The obtained results indicate that the absence of MIF increases intestinal permeability. Here we describe two methods for measuring intestinal permeability in mice: detection of orally delivered FITC-dextran in the serum and transmission electron microscopy used for visualization and measurement of cell-to-cell connections width.",
publisher = "Humana, New York, NY",
journal = "Macrophage Migration Inhibitory Factor",
booktitle = "The Effect of Macrophage Migration Inhibitory Factor on Intestinal Permeability: FITC-Dextran Serum Measurement and Transmission Electron Microscopy.",
doi = "10.1007/978-1-4939-9936-1_17",
pages = "193-201"
}

Vujičić, M., Despotović, S., Saksida, T., Stojanović, I. D., Harris, J.,& Morand, E. F.. (2020). The Effect of Macrophage Migration Inhibitory Factor on Intestinal Permeability: FITC-Dextran Serum Measurement and Transmission Electron Microscopy.. in Macrophage Migration Inhibitory Factor
Humana, New York, NY., 193-201.
https://doi.org/10.1007/978-1-4939-9936-1_17

Vujičić M, Despotović S, Saksida T, Stojanović ID, Harris J, Morand EF. The Effect of Macrophage Migration Inhibitory Factor on Intestinal Permeability: FITC-Dextran Serum Measurement and Transmission Electron Microscopy.. in Macrophage Migration Inhibitory Factor. 2020;:193-201.
doi:10.1007/978-1-4939-9936-1_17 .

Vujičić, Milica, Despotović, Sanja, Saksida, Tamara, Stojanović, Ivana D., Harris, James, Morand, Eric F., "The Effect of Macrophage Migration Inhibitory Factor on Intestinal Permeability: FITC-Dextran Serum Measurement and Transmission Electron Microscopy." in Macrophage Migration Inhibitory Factor (2020):193-201,
https://doi.org/10.1007/978-1-4939-9936-1_17 . .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Despotović, Sanja
AU  - Šavikin, Katarina
AU  - Janković, Teodora
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5777
AB  - Chokeberry (Aronia melanocarpa) is known for its strong anti-oxidant properties. Antiinflammatory,
anti-hypertensive and anti-diabetogenic activities of orally consumed
chokeberry extracts have also been reported. The effects of chokeberry extract on the
immune response parameters have been only sporadically assessed. Therefore, the aim of
our study was to investigate the effects of orally consumed chokeberry extract on the
immune response in vivo and in vitro in healthy and in diabetic C57BL/6 mice, in which
diabetes was induced by multiple low doses of streptozotocin (MLDS). Chokeberry extract
administered to healthy mice (50 mg/kg body weight) exerted immunomodulatory effects
as evidenced by decreased proportion of F4/80+ macrophages, CD11c+ dendritic cells,
CD4+ T helper cells, CD8+ T cytotoxic lymphocytes and CD4+CD25- activated T
lymphocytes within the gut-associated lymphoid tissue. Surprisingly, oral consumption of
chokeberry extract in doses of either 200 mg/kg bw or 50 mg/kg bw in diabetic mice
resulted in the increase of blood glucose levels. In an attempt to decipher the underlying
mechanisms of chokeberry extract effects in the context of autoimmune/inflammatory
disease, we have evaluated its effects in vitro on purified immune cells. Seemingly, the
chokeberry extract exerted pro-inflammatory effects in vitro through the up-regulation of
nitric oxide and IL-1β production in macrophages and dendritic cells, increased
macrophage CD86-related activation and promotion of type 1 T helper cells (IFN-γ+)
differentiation. In addition, an increased proportion of CD4+, CD8+ and B lymphocytes
within the spleen was observed. Collectively, the obtained results imply that our particular
chokeberry extract displays pro-inflammatory characteristics and that care should be taken
when chokeberry is to be included in the human diet.
PB  - Belgrade: Faculty of Chemistry
C3  - The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.
T1  - Chokeberry (Aronia melanocarpa) fruit extract modulates mouse immune response in vivo and in vitro
SP  - 96
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5777
ER  - 

@conference{
author = "Mićanović, Dragica and Saksida, Tamara and Koprivica, Ivan and Vujičić, Milica and Despotović, Sanja and Šavikin, Katarina and Janković, Teodora and Stojanović, Ivana D.",
year = "2019",
abstract = "Chokeberry (Aronia melanocarpa) is known for its strong anti-oxidant properties. Antiinflammatory,
anti-hypertensive and anti-diabetogenic activities of orally consumed
chokeberry extracts have also been reported. The effects of chokeberry extract on the
immune response parameters have been only sporadically assessed. Therefore, the aim of
our study was to investigate the effects of orally consumed chokeberry extract on the
immune response in vivo and in vitro in healthy and in diabetic C57BL/6 mice, in which
diabetes was induced by multiple low doses of streptozotocin (MLDS). Chokeberry extract
administered to healthy mice (50 mg/kg body weight) exerted immunomodulatory effects
as evidenced by decreased proportion of F4/80+ macrophages, CD11c+ dendritic cells,
CD4+ T helper cells, CD8+ T cytotoxic lymphocytes and CD4+CD25- activated T
lymphocytes within the gut-associated lymphoid tissue. Surprisingly, oral consumption of
chokeberry extract in doses of either 200 mg/kg bw or 50 mg/kg bw in diabetic mice
resulted in the increase of blood glucose levels. In an attempt to decipher the underlying
mechanisms of chokeberry extract effects in the context of autoimmune/inflammatory
disease, we have evaluated its effects in vitro on purified immune cells. Seemingly, the
chokeberry extract exerted pro-inflammatory effects in vitro through the up-regulation of
nitric oxide and IL-1β production in macrophages and dendritic cells, increased
macrophage CD86-related activation and promotion of type 1 T helper cells (IFN-γ+)
differentiation. In addition, an increased proportion of CD4+, CD8+ and B lymphocytes
within the spleen was observed. Collectively, the obtained results imply that our particular
chokeberry extract displays pro-inflammatory characteristics and that care should be taken
when chokeberry is to be included in the human diet.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.",
title = "Chokeberry (Aronia melanocarpa) fruit extract modulates mouse immune response in vivo and in vitro",
pages = "96",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5777"
}

Mićanović, D., Saksida, T., Koprivica, I., Vujičić, M., Despotović, S., Šavikin, K., Janković, T.,& Stojanović, I. D.. (2019). Chokeberry (Aronia melanocarpa) fruit extract modulates mouse immune response in vivo and in vitro. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.
Belgrade: Faculty of Chemistry., 96.
https://hdl.handle.net/21.15107/rcub_ibiss_5777

Mićanović D, Saksida T, Koprivica I, Vujičić M, Despotović S, Šavikin K, Janković T, Stojanović ID. Chokeberry (Aronia melanocarpa) fruit extract modulates mouse immune response in vivo and in vitro. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.. 2019;:96.
https://hdl.handle.net/21.15107/rcub_ibiss_5777 .

Mićanović, Dragica, Saksida, Tamara, Koprivica, Ivan, Vujičić, Milica, Despotović, Sanja, Šavikin, Katarina, Janković, Teodora, Stojanović, Ivana D., "Chokeberry (Aronia melanocarpa) fruit extract modulates mouse immune response in vivo and in vitro" in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia. (2019):96,
https://hdl.handle.net/21.15107/rcub_ibiss_5777 .

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - https://www.frontiersin.org/article/10.3389/fimmu.2018.03130/full
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6335294
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3249
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response causes the death of insulin-producing pancreatic β-cells, while inefficient regulatory mechanisms allow that response to become chronic. Ethyl pyruvate (EP), a stable pyruvate derivate and certified inhibitor of an alarmin-high mobility group box 1 (HMGB1), exerts anti-oxidant and anti-inflammatory properties in animal models of rheumatoid arthritis and encephalomyelitis. To test its therapeutic potential in T1D, EP was administered intraperitoneally to C57BL/6 mice with multiple low-dose streptozotocin (MLDS)-induced T1D. EP treatment decreased T1D incidence, reduced the infiltration of cells into the pancreatic islets and preserved β-cell function. Apart from reducing HMGB1 expression, EP treatment successfully interfered with the inflammatory response within the local pancreatic lymph nodes and in the pancreas. Its effect was restricted to boosting the regulatory arm of the immune response through up-regulation of tolerogenic dendritic cells (CD11c+CD11b-CD103+) within the pancreatic infiltrates and through the enhancement of regulatory T cell (Treg) levels (CD4+CD25highFoxP3+). These EP-stimulated Treg displayed enhanced suppressive capacity reflected in increased levels of CTLA-4, secreted TGF-β, and IL-10 and in the more efficient inhibition of effector T cell proliferation compared to Treg from diabetic animals. Higher levels of Treg were a result of increased differentiation and proliferation (Ki67+ cells), but also of the heightened potency for migration due to increased expression of adhesion molecules (CD11a and CD62L) and CXCR3 chemokine receptor. Treg isolated from EP-treated mice had the activated phenotype and T-bet expression more frequently, suggesting that they readily suppressed IFN-γ-producing cells. The effect of EP on Treg was also reproduced in vitro. Overall, our results show that EP treatment reduced T1D incidence in C57BL/6 mice predominantly by enhancing Treg differentiation, proliferation, their suppressive capacity, and recruitment into the pancreas.
T2  - Frontiers in Immunology
T1  - Ethyl Pyruvate Stimulates Regulatory T Cells and Ameliorates Type 1 Diabetes Development in Mice.
VL  - 9
DO  - 10.3389/fimmu.2018.03130
SP  - 3130
ER  - 

@article{
author = "Koprivica, Ivan and Vujičić, Milica and Mićanović, Dragica and Saksida, Tamara and Stojanović, Ivana D.",
year = "2019",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response causes the death of insulin-producing pancreatic β-cells, while inefficient regulatory mechanisms allow that response to become chronic. Ethyl pyruvate (EP), a stable pyruvate derivate and certified inhibitor of an alarmin-high mobility group box 1 (HMGB1), exerts anti-oxidant and anti-inflammatory properties in animal models of rheumatoid arthritis and encephalomyelitis. To test its therapeutic potential in T1D, EP was administered intraperitoneally to C57BL/6 mice with multiple low-dose streptozotocin (MLDS)-induced T1D. EP treatment decreased T1D incidence, reduced the infiltration of cells into the pancreatic islets and preserved β-cell function. Apart from reducing HMGB1 expression, EP treatment successfully interfered with the inflammatory response within the local pancreatic lymph nodes and in the pancreas. Its effect was restricted to boosting the regulatory arm of the immune response through up-regulation of tolerogenic dendritic cells (CD11c+CD11b-CD103+) within the pancreatic infiltrates and through the enhancement of regulatory T cell (Treg) levels (CD4+CD25highFoxP3+). These EP-stimulated Treg displayed enhanced suppressive capacity reflected in increased levels of CTLA-4, secreted TGF-β, and IL-10 and in the more efficient inhibition of effector T cell proliferation compared to Treg from diabetic animals. Higher levels of Treg were a result of increased differentiation and proliferation (Ki67+ cells), but also of the heightened potency for migration due to increased expression of adhesion molecules (CD11a and CD62L) and CXCR3 chemokine receptor. Treg isolated from EP-treated mice had the activated phenotype and T-bet expression more frequently, suggesting that they readily suppressed IFN-γ-producing cells. The effect of EP on Treg was also reproduced in vitro. Overall, our results show that EP treatment reduced T1D incidence in C57BL/6 mice predominantly by enhancing Treg differentiation, proliferation, their suppressive capacity, and recruitment into the pancreas.",
journal = "Frontiers in Immunology",
title = "Ethyl Pyruvate Stimulates Regulatory T Cells and Ameliorates Type 1 Diabetes Development in Mice.",
volume = "9",
doi = "10.3389/fimmu.2018.03130",
pages = "3130"
}

Koprivica, I., Vujičić, M., Mićanović, D., Saksida, T.,& Stojanović, I. D.. (2019). Ethyl Pyruvate Stimulates Regulatory T Cells and Ameliorates Type 1 Diabetes Development in Mice.. in Frontiers in Immunology, 9, 3130.
https://doi.org/10.3389/fimmu.2018.03130

Koprivica I, Vujičić M, Mićanović D, Saksida T, Stojanović ID. Ethyl Pyruvate Stimulates Regulatory T Cells and Ameliorates Type 1 Diabetes Development in Mice.. in Frontiers in Immunology. 2019;9:3130.
doi:10.3389/fimmu.2018.03130 .

Koprivica, Ivan, Vujičić, Milica, Mićanović, Dragica, Saksida, Tamara, Stojanović, Ivana D., "Ethyl Pyruvate Stimulates Regulatory T Cells and Ameliorates Type 1 Diabetes Development in Mice." in Frontiers in Immunology, 9 (2019):3130,
https://doi.org/10.3389/fimmu.2018.03130 . .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5764
AB  - Obesity is a disorder characterized by a pro-inflammatory environment in visceral adipose tissue (VAT) due to increased infiltration of pro-inflammatory macrophages and a drop in regulatory T (Treg) cells. Macrophage migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine with versatile functions in innate and adaptive immunity. Although it has a predominantly pro-inflammatory role in the organism, its innate absence in MIF-KO mice leads to obesity. VAT in MIF-KO mice is larger in mass and the infiltration of immune cells per gram of VAT is not different than in WT controls. Also, MIF-KO VAT has the same distribution of immune cells (CD3+, CD4+, CD8+, CD19+ cells, M1 and M2 macrophages), but a higher expression and secretion of TNF-α and IL-1β. Surprisingly, Treg cells are more abundant in VAT of MIF-KO mice. Proliferation of Treg cells in VAT measured by BrdU incorporation is the same in both strains, suggesting that their increased number is not due to enhanced in situ division. Cytokines responsible for Treg suppressive action, IL-10 (denoted as CD4+IL-10+FoxP3+ cells) and TGF-β (secreted from VAT infiltrating cells), are underrepresented in VAT of MIF-KO mice. Based on these results, we can assume that Treg cells in VAT of MIF-KO mice are, albeit extensively present, less functional. This situation may be responsible for obesity development in the absence of MIF.
PB  - European Federation of Immunological Societies
C3  - Program and Abstracts: 10th EFIS-EJI South Eastern European Immunology School (SEEIS2018); 2018 Oct 19-22; Yerevan, Armenia
T1  - The role of regulatory T cells in the development of obesity in MIF-KO mice
SP  - 20
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5764
ER  - 

@conference{
author = "Mićanović, Dragica and Koprivica, Ivan and Vujičić, Milica and Stojanović, Ivana D. and Saksida, Tamara",
year = "2018",
abstract = "Obesity is a disorder characterized by a pro-inflammatory environment in visceral adipose tissue (VAT) due to increased infiltration of pro-inflammatory macrophages and a drop in regulatory T (Treg) cells. Macrophage migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine with versatile functions in innate and adaptive immunity. Although it has a predominantly pro-inflammatory role in the organism, its innate absence in MIF-KO mice leads to obesity. VAT in MIF-KO mice is larger in mass and the infiltration of immune cells per gram of VAT is not different than in WT controls. Also, MIF-KO VAT has the same distribution of immune cells (CD3+, CD4+, CD8+, CD19+ cells, M1 and M2 macrophages), but a higher expression and secretion of TNF-α and IL-1β. Surprisingly, Treg cells are more abundant in VAT of MIF-KO mice. Proliferation of Treg cells in VAT measured by BrdU incorporation is the same in both strains, suggesting that their increased number is not due to enhanced in situ division. Cytokines responsible for Treg suppressive action, IL-10 (denoted as CD4+IL-10+FoxP3+ cells) and TGF-β (secreted from VAT infiltrating cells), are underrepresented in VAT of MIF-KO mice. Based on these results, we can assume that Treg cells in VAT of MIF-KO mice are, albeit extensively present, less functional. This situation may be responsible for obesity development in the absence of MIF.",
publisher = "European Federation of Immunological Societies",
journal = "Program and Abstracts: 10th EFIS-EJI South Eastern European Immunology School (SEEIS2018); 2018 Oct 19-22; Yerevan, Armenia",
title = "The role of regulatory T cells in the development of obesity in MIF-KO mice",
pages = "20",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5764"
}

Mićanović, D., Koprivica, I., Vujičić, M., Stojanović, I. D.,& Saksida, T.. (2018). The role of regulatory T cells in the development of obesity in MIF-KO mice. in Program and Abstracts: 10th EFIS-EJI South Eastern European Immunology School (SEEIS2018); 2018 Oct 19-22; Yerevan, Armenia
European Federation of Immunological Societies., 20.
https://hdl.handle.net/21.15107/rcub_ibiss_5764

Mićanović D, Koprivica I, Vujičić M, Stojanović ID, Saksida T. The role of regulatory T cells in the development of obesity in MIF-KO mice. in Program and Abstracts: 10th EFIS-EJI South Eastern European Immunology School (SEEIS2018); 2018 Oct 19-22; Yerevan, Armenia. 2018;:20.
https://hdl.handle.net/21.15107/rcub_ibiss_5764 .

Mićanović, Dragica, Koprivica, Ivan, Vujičić, Milica, Stojanović, Ivana D., Saksida, Tamara, "The role of regulatory T cells in the development of obesity in MIF-KO mice" in Program and Abstracts: 10th EFIS-EJI South Eastern European Immunology School (SEEIS2018); 2018 Oct 19-22; Yerevan, Armenia (2018):20,
https://hdl.handle.net/21.15107/rcub_ibiss_5764 .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Despotović, Sanja
AU  - Soković Bajić, Svetlana
AU  - Lalić, Ivana
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Golić, Natasa
AU  - Tolinački, Maja
AU  - Stojanović, Ivana D.
PY  - 2018
UR  - http://www.nature.com/articles/s41598-018-24706-3
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5910418
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3049
AB  - Macrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-γ in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the "leakage" of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function.
T2  - Scientific Reports
T1  - The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier.
IS  - 1
VL  - 8
DO  - 10.1038/s41598-018-24706-3
SP  - 6337
ER  - 

@article{
author = "Vujičić, Milica and Saksida, Tamara and Despotović, Sanja and Soković Bajić, Svetlana and Lalić, Ivana and Koprivica, Ivan and Mićanović, Dragica and Golić, Natasa and Tolinački, Maja and Stojanović, Ivana D.",
year = "2018",
abstract = "Macrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-γ in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the "leakage" of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function.",
journal = "Scientific Reports",
title = "The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier.",
number = "1",
volume = "8",
doi = "10.1038/s41598-018-24706-3",
pages = "6337"
}

Vujičić, M., Saksida, T., Despotović, S., Soković Bajić, S., Lalić, I., Koprivica, I., Mićanović, D., Golić, N., Tolinački, M.,& Stojanović, I. D.. (2018). The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier.. in Scientific Reports, 8(1), 6337.
https://doi.org/10.1038/s41598-018-24706-3

Vujičić M, Saksida T, Despotović S, Soković Bajić S, Lalić I, Koprivica I, Mićanović D, Golić N, Tolinački M, Stojanović ID. The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier.. in Scientific Reports. 2018;8(1):6337.
doi:10.1038/s41598-018-24706-3 .

Vujičić, Milica, Saksida, Tamara, Despotović, Sanja, Soković Bajić, Svetlana, Lalić, Ivana, Koprivica, Ivan, Mićanović, Dragica, Golić, Natasa, Tolinački, Maja, Stojanović, Ivana D., "The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier." in Scientific Reports, 8, no. 1 (2018):6337,
https://doi.org/10.1038/s41598-018-24706-3 . .

TY  - CONF
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Mićanović, Dragica
AU  - Stojanović, Ivana D.
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5788
AB  - Dijabetes tip 1 (DT1) je autoimunska bolest koja se javlja kao posledica uništavanja insulin-produkujućih beta-ćelija pankreasa. Pokrenut imunski odgovor ima jake proinflamatorne karakteristike, a neefikasna regulatorna kontrola autoimuskog odgovora dopušta da odgovor postane hroničan. Etil piruvat (EP), stabilni derivat piruvata, pokazao je antioksidantna i antiinflamatorna svojstva u različitim modelima bolesti. Radi ispitivanja potencijala EP u terapiji DT1, bolest je kod C57BL/6 miševa uzorkovana višestrukim malim dozama streptozotocina (STZ) (40 mg/kg t.t, 5 dana) i EP primenjivan intraperitonealno (100 mg/kg t.t, 9 dana) na profilaktički način (istovremeno sa prvim STZ).

EP tretman značajno je smanjio incidencu DT1 i doveo do smanjene infiltracije ćelija u pankreasna ostrvca. Ex vivo analiza imunskih ćelija slezine, pankreasnih limfnih čvorova (PLČ) i mononuklearnih pankreasnih infiltrata (MNPI) metodom protočne citofluorimetrije pokazala je da EP tretman nije promenio broj imunskih ćelija u ovim tkivima, a ni relativnu zastupljenost Th1, Th17 i Th2 ćelija. Međutim, EP tretman je doveo do značajno povećane zastupljenosti regulatornih T ćelija (Treg, CD4+CD25high) u PLČ i MNPI. Nakon EP tretmana, u PLČ su sve Treg bile GITR+CD127-, a došlo je i do porasta zastupljenosti CD101+ Treg, što asocira na njihovu potentniju supresivnu aktivnost. To je dokazano i u in vitro testu supresije proliferacije efektorskih T ćelija (Tef), gde su Treg iz miševa tretiranih EP pokazale značajno veću moć inhibicije sve do odnosa 1:8 u korist Tef. Pored toga, povećani su i broj CXCR3+ Treg i prisustvo CD11a i CD62L po ćeliji, što može ukazati na povećanu migraciju Treg u pankreas. Međutim, porast zastupljenosti Ki67+ Treg ukazuje i na povećanje proliferacije Treg nakon EP tretmana. Ovi rezultati ukazuju na to da EP tretman smanjuje učestalost DT1 kod C57BL/6 miševa kroz povećanje proliferacije i supresivnih sposobnosti Treg, kao i njihovog regrutovanja u pankreas.

(Istraživanje finansirano iz projekta OI 173013 MPNTR Republike Srbije)
PB  - Belgrade: Serbian Academy of Sciences and Arts; 2018.
C3  - Naučni skup Svetski dan imunologije 2018; 2018 Apr 26; Belgrade, Serbia
T1  - Efekat primene etil piruvata na regulatorne T ćelije prilikom razvoja dijabetesa tip 1
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5788
ER  - 

@conference{
author = "Koprivica, Ivan and Vujičić, Milica and Saksida, Tamara and Mićanović, Dragica and Stojanović, Ivana D.",
year = "2018",
abstract = "Dijabetes tip 1 (DT1) je autoimunska bolest koja se javlja kao posledica uništavanja insulin-produkujućih beta-ćelija pankreasa. Pokrenut imunski odgovor ima jake proinflamatorne karakteristike, a neefikasna regulatorna kontrola autoimuskog odgovora dopušta da odgovor postane hroničan. Etil piruvat (EP), stabilni derivat piruvata, pokazao je antioksidantna i antiinflamatorna svojstva u različitim modelima bolesti. Radi ispitivanja potencijala EP u terapiji DT1, bolest je kod C57BL/6 miševa uzorkovana višestrukim malim dozama streptozotocina (STZ) (40 mg/kg t.t, 5 dana) i EP primenjivan intraperitonealno (100 mg/kg t.t, 9 dana) na profilaktički način (istovremeno sa prvim STZ).

EP tretman značajno je smanjio incidencu DT1 i doveo do smanjene infiltracije ćelija u pankreasna ostrvca. Ex vivo analiza imunskih ćelija slezine, pankreasnih limfnih čvorova (PLČ) i mononuklearnih pankreasnih infiltrata (MNPI) metodom protočne citofluorimetrije pokazala je da EP tretman nije promenio broj imunskih ćelija u ovim tkivima, a ni relativnu zastupljenost Th1, Th17 i Th2 ćelija. Međutim, EP tretman je doveo do značajno povećane zastupljenosti regulatornih T ćelija (Treg, CD4+CD25high) u PLČ i MNPI. Nakon EP tretmana, u PLČ su sve Treg bile GITR+CD127-, a došlo je i do porasta zastupljenosti CD101+ Treg, što asocira na njihovu potentniju supresivnu aktivnost. To je dokazano i u in vitro testu supresije proliferacije efektorskih T ćelija (Tef), gde su Treg iz miševa tretiranih EP pokazale značajno veću moć inhibicije sve do odnosa 1:8 u korist Tef. Pored toga, povećani su i broj CXCR3+ Treg i prisustvo CD11a i CD62L po ćeliji, što može ukazati na povećanu migraciju Treg u pankreas. Međutim, porast zastupljenosti Ki67+ Treg ukazuje i na povećanje proliferacije Treg nakon EP tretmana. Ovi rezultati ukazuju na to da EP tretman smanjuje učestalost DT1 kod C57BL/6 miševa kroz povećanje proliferacije i supresivnih sposobnosti Treg, kao i njihovog regrutovanja u pankreas.

(Istraživanje finansirano iz projekta OI 173013 MPNTR Republike Srbije)",
publisher = "Belgrade: Serbian Academy of Sciences and Arts; 2018.",
journal = "Naučni skup Svetski dan imunologije 2018; 2018 Apr 26; Belgrade, Serbia",
title = "Efekat primene etil piruvata na regulatorne T ćelije prilikom razvoja dijabetesa tip 1",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5788"
}

Koprivica, I., Vujičić, M., Saksida, T., Mićanović, D.,& Stojanović, I. D.. (2018). Efekat primene etil piruvata na regulatorne T ćelije prilikom razvoja dijabetesa tip 1. in Naučni skup Svetski dan imunologije 2018; 2018 Apr 26; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts; 2018...
https://hdl.handle.net/21.15107/rcub_ibiss_5788

Koprivica I, Vujičić M, Saksida T, Mićanović D, Stojanović ID. Efekat primene etil piruvata na regulatorne T ćelije prilikom razvoja dijabetesa tip 1. in Naučni skup Svetski dan imunologije 2018; 2018 Apr 26; Belgrade, Serbia. 2018;.
https://hdl.handle.net/21.15107/rcub_ibiss_5788 .

Koprivica, Ivan, Vujičić, Milica, Saksida, Tamara, Mićanović, Dragica, Stojanović, Ivana D., "Efekat primene etil piruvata na regulatorne T ćelije prilikom razvoja dijabetesa tip 1" in Naučni skup Svetski dan imunologije 2018; 2018 Apr 26; Belgrade, Serbia (2018),
https://hdl.handle.net/21.15107/rcub_ibiss_5788 .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Mostarica Stojković, Marija
AU  - Nikolovski, Neda
AU  - Stojanović, Ivana D.
AU  - Stošić-Grujičić, Stanislava
PY  - 2018
UR  - http://doi.wiley.com/10.1002/jcp.26338
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29215791
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2959
AB  - Particulate adjuvants have shown increasing promise as effective, safe, and durable agents for the stimulation of immunity, or alternatively, the suppression of autoimmunity. Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ-specific autoimmune disease-type 1 diabetes (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that initiates beta cell death and triggers immune cell infiltration into the pancreatic islets. The results of this study indicate that the single in vivo application of CI to MLDS-treated DA rats, CBA/H mice, or C57BL/6 mice successfully counteracted the development of insulitis and hyperglycemia. The protective action was obtained either when CI was applied 7 days before, simultaneously with the first dose of streptozotocin, or 1 day after MLDS treatment. Ex vivo cell analysis of C57BL/6 mice showed that CI treatment reduced the proportion of proinflammatory F4/80+ CD40+ M1 macrophages and activated T lymphocytes in the spleen. Moreover, the treatment down-regulated the number of inflammatory CD4+ IFN-γ+ cells in pancreatic lymph nodes, Peyer's patches, and pancreas-infiltrating mononuclear cells, while simultaneously potentiating proportion of CD4+ IL17+ cells. The regulatory arm of the immune system represented by CD3+ NK1.1+ (NKT) and CD4+ CD25+ FoxP3+ regulatory T cells was potentiated after CI treatment. In vitro analysis showed that CI down-regulated CD40 and CD80 expression on dendritic cells thus probably interfering with their antigen-presenting ability. In conclusion, particulate adjuvant CI seems to suppress the activation of the innate immune response, which further affects the adaptive immune response directed toward pancreatic beta cells.
T2  - Journal of Cellular Physiology
T1  - Protective effects of carbonyl iron against multiple low-dose streptozotocin-induced diabetes in rodents.
IS  - 6
VL  - 233
DO  - 10.1002/jcp.26338
SP  - 4990
EP  - 5001
ER  - 

@article{
author = "Vujičić, Milica and Saksida, Tamara and Mostarica Stojković, Marija and Nikolovski, Neda and Stojanović, Ivana D. and Stošić-Grujičić, Stanislava",
year = "2018",
abstract = "Particulate adjuvants have shown increasing promise as effective, safe, and durable agents for the stimulation of immunity, or alternatively, the suppression of autoimmunity. Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ-specific autoimmune disease-type 1 diabetes (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that initiates beta cell death and triggers immune cell infiltration into the pancreatic islets. The results of this study indicate that the single in vivo application of CI to MLDS-treated DA rats, CBA/H mice, or C57BL/6 mice successfully counteracted the development of insulitis and hyperglycemia. The protective action was obtained either when CI was applied 7 days before, simultaneously with the first dose of streptozotocin, or 1 day after MLDS treatment. Ex vivo cell analysis of C57BL/6 mice showed that CI treatment reduced the proportion of proinflammatory F4/80+ CD40+ M1 macrophages and activated T lymphocytes in the spleen. Moreover, the treatment down-regulated the number of inflammatory CD4+ IFN-γ+ cells in pancreatic lymph nodes, Peyer's patches, and pancreas-infiltrating mononuclear cells, while simultaneously potentiating proportion of CD4+ IL17+ cells. The regulatory arm of the immune system represented by CD3+ NK1.1+ (NKT) and CD4+ CD25+ FoxP3+ regulatory T cells was potentiated after CI treatment. In vitro analysis showed that CI down-regulated CD40 and CD80 expression on dendritic cells thus probably interfering with their antigen-presenting ability. In conclusion, particulate adjuvant CI seems to suppress the activation of the innate immune response, which further affects the adaptive immune response directed toward pancreatic beta cells.",
journal = "Journal of Cellular Physiology",
title = "Protective effects of carbonyl iron against multiple low-dose streptozotocin-induced diabetes in rodents.",
number = "6",
volume = "233",
doi = "10.1002/jcp.26338",
pages = "4990-5001"
}

Vujičić, M., Saksida, T., Mostarica Stojković, M., Nikolovski, N., Stojanović, I. D.,& Stošić-Grujičić, S.. (2018). Protective effects of carbonyl iron against multiple low-dose streptozotocin-induced diabetes in rodents.. in Journal of Cellular Physiology, 233(6), 4990-5001.
https://doi.org/10.1002/jcp.26338

Vujičić M, Saksida T, Mostarica Stojković M, Nikolovski N, Stojanović ID, Stošić-Grujičić S. Protective effects of carbonyl iron against multiple low-dose streptozotocin-induced diabetes in rodents.. in Journal of Cellular Physiology. 2018;233(6):4990-5001.
doi:10.1002/jcp.26338 .

Vujičić, Milica, Saksida, Tamara, Mostarica Stojković, Marija, Nikolovski, Neda, Stojanović, Ivana D., Stošić-Grujičić, Stanislava, "Protective effects of carbonyl iron against multiple low-dose streptozotocin-induced diabetes in rodents." in Journal of Cellular Physiology, 233, no. 6 (2018):4990-5001,
https://doi.org/10.1002/jcp.26338 . .

TY  - CONF
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5774
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response causes insulin-producing pancreatic β-cell death. Ethyl pyruvate (EP), a stable pyruvate derivate, has exerted antioxidant and anti-inflammatory properties in several disease models. To test its therapeutic potential in T1D, EP was administered intraperitoneally to C57BL/6 mice with multiple low-dose streptozotocin (STZ)-induced T1D.

EP treatment decreased T1D incidence and reduced the infiltration of cells into the pancreatic islets. Еx vivo analysis by flow cytometry showed that the EP treatment didn’t change the number of immune cells in the spleen, pancreatic lymph nodes (PLN) or pancreatic mononuclear infiltrates (PMNI), nor the relative percentages of Th1, Th17 and Th2 cells. However, EP treatment increased the levels of regulatory T cells (Treg) in PLN and PMNI. After the EP treatment, all PLN Treg were GITR+CD127-, and an increase was noted in the percentage of CD101+Treg, indicating a stronger suppressive activity. That was confirmed by an in vitro suppression assay, in which Treg from EP treated mice showed a higher capacity to supress effector T cell proliferation. The number of CXCR3+Treg and the presence of CD11а and CD62L per cell increased, which might imply an increase in Treg migration into the pancreas. However, a rise in the presence of Кi67+Treg suggested that EP treatment also promotes Treg proliferation. These results show that EP treatment reduces T1D incidence in C57BL/6 mice by enhancing Treg proliferation, suppressive capacity, and recruitment into the pancreas
PB  - European Federation of Immunological Societies
C3  - Abstract book: 5th European Congress of Immunology; 2018 Sep 2-5; Amsterdam, The Netherlands
T1  - Ethyl pyruvate treatment enhances regulatory T cell proliferation and function in type 1 diabetes
SP  - 345
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5774
ER  - 

@conference{
author = "Koprivica, Ivan and Vujičić, Milica and Saksida, Tamara and Stojanović, Ivana D.",
year = "2018",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response causes insulin-producing pancreatic β-cell death. Ethyl pyruvate (EP), a stable pyruvate derivate, has exerted antioxidant and anti-inflammatory properties in several disease models. To test its therapeutic potential in T1D, EP was administered intraperitoneally to C57BL/6 mice with multiple low-dose streptozotocin (STZ)-induced T1D.

EP treatment decreased T1D incidence and reduced the infiltration of cells into the pancreatic islets. Еx vivo analysis by flow cytometry showed that the EP treatment didn’t change the number of immune cells in the spleen, pancreatic lymph nodes (PLN) or pancreatic mononuclear infiltrates (PMNI), nor the relative percentages of Th1, Th17 and Th2 cells. However, EP treatment increased the levels of regulatory T cells (Treg) in PLN and PMNI. After the EP treatment, all PLN Treg were GITR+CD127-, and an increase was noted in the percentage of CD101+Treg, indicating a stronger suppressive activity. That was confirmed by an in vitro suppression assay, in which Treg from EP treated mice showed a higher capacity to supress effector T cell proliferation. The number of CXCR3+Treg and the presence of CD11а and CD62L per cell increased, which might imply an increase in Treg migration into the pancreas. However, a rise in the presence of Кi67+Treg suggested that EP treatment also promotes Treg proliferation. These results show that EP treatment reduces T1D incidence in C57BL/6 mice by enhancing Treg proliferation, suppressive capacity, and recruitment into the pancreas",
publisher = "European Federation of Immunological Societies",
journal = "Abstract book: 5th European Congress of Immunology; 2018 Sep 2-5; Amsterdam, The Netherlands",
title = "Ethyl pyruvate treatment enhances regulatory T cell proliferation and function in type 1 diabetes",
pages = "345",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5774"
}

Koprivica, I., Vujičić, M., Saksida, T.,& Stojanović, I. D.. (2018). Ethyl pyruvate treatment enhances regulatory T cell proliferation and function in type 1 diabetes. in Abstract book: 5th European Congress of Immunology; 2018 Sep 2-5; Amsterdam, The Netherlands
European Federation of Immunological Societies., 345.
https://hdl.handle.net/21.15107/rcub_ibiss_5774

Koprivica I, Vujičić M, Saksida T, Stojanović ID. Ethyl pyruvate treatment enhances regulatory T cell proliferation and function in type 1 diabetes. in Abstract book: 5th European Congress of Immunology; 2018 Sep 2-5; Amsterdam, The Netherlands. 2018;:345.
https://hdl.handle.net/21.15107/rcub_ibiss_5774 .

Koprivica, Ivan, Vujičić, Milica, Saksida, Tamara, Stojanović, Ivana D., "Ethyl pyruvate treatment enhances regulatory T cell proliferation and function in type 1 diabetes" in Abstract book: 5th European Congress of Immunology; 2018 Sep 2-5; Amsterdam, The Netherlands (2018):345,
https://hdl.handle.net/21.15107/rcub_ibiss_5774 .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Stošić-Grujičić, Stanislava
AU  - Perović, Milka
AU  - Kanazir, Selma
AU  - Stojanović, Ivana D.
PY  - 2018
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29254086
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2948
AB  - Alzheimer's disease (AD) is characterized by accumulation of amyloid-β plaques that further promotes microglia-mediated neuroinflammatory responses and inflammation in the brain. Emerging data are revealing the relation between gut-associated lymphoid tissue (GALT) cells and CNS, as effector cells primed in the gut might home to the brain. This study aimed to determine cell composition of GALT in 5xFAD mice, an established model for AD. Immune cells isolated from Peyer's patches (PP) and mesenteric lymph nodes (MLN) were stained with surface and intracellular markers for T helper (Th) subpopulations, B lymphocytes and macrophages and analyzed cytofluorimetrically, while cytokine expression and production were determined by qPCR and ELISA, respectively. Inflammation was detected in GALT of 5xFAD mice with established AD pathology. Although the production of IFN-γ, IL-4, and IL-10 was comparable between the strains, lower IL-17 production was observed in PP and MLN cells. This phenomenon could not be attributed to a lower abundance of Th17 cells, or cytokines that initiate their formation or propagation (TGF-β, IL-6, and IL-23). Also, reduced IL-17 production was not a consequence of altered Il-17 mRNA transcription or deficiency of Rorγt, a key transcription factor for IL-17. However, the expression of miR-155 (a non-coding micro RNA that promotes the development of Th17 cells), was significantly lower in MLN cells of 5xFAD mice. In contrast, mice without AD neuropathology did not have inflammation in GALT or altered Th17 numbers, nor decreased IL-17 production. In conclusion, the observed changes in GALT of 5xFAD mice mirror the disease progression and might reflect inadequate immune surveillance in the gut and lead to enhanced AD pathology.
T2  - Journal of Alzheimer's disease : JAD
T2  - Journal of Alzheimer's disease : JAD
T1  - Impaired IL-17 Production in Gut-Residing Immune Cells of 5xFAD Mice with Alzheimer’s Disease Pathology
IS  - 2
VL  - 61
DO  - 10.3233/JAD-170538
SP  - 619
EP  - 630
ER  - 

@article{
author = "Saksida, Tamara and Koprivica, Ivan and Vujičić, Milica and Stošić-Grujičić, Stanislava and Perović, Milka and Kanazir, Selma and Stojanović, Ivana D.",
year = "2018",
abstract = "Alzheimer's disease (AD) is characterized by accumulation of amyloid-β plaques that further promotes microglia-mediated neuroinflammatory responses and inflammation in the brain. Emerging data are revealing the relation between gut-associated lymphoid tissue (GALT) cells and CNS, as effector cells primed in the gut might home to the brain. This study aimed to determine cell composition of GALT in 5xFAD mice, an established model for AD. Immune cells isolated from Peyer's patches (PP) and mesenteric lymph nodes (MLN) were stained with surface and intracellular markers for T helper (Th) subpopulations, B lymphocytes and macrophages and analyzed cytofluorimetrically, while cytokine expression and production were determined by qPCR and ELISA, respectively. Inflammation was detected in GALT of 5xFAD mice with established AD pathology. Although the production of IFN-γ, IL-4, and IL-10 was comparable between the strains, lower IL-17 production was observed in PP and MLN cells. This phenomenon could not be attributed to a lower abundance of Th17 cells, or cytokines that initiate their formation or propagation (TGF-β, IL-6, and IL-23). Also, reduced IL-17 production was not a consequence of altered Il-17 mRNA transcription or deficiency of Rorγt, a key transcription factor for IL-17. However, the expression of miR-155 (a non-coding micro RNA that promotes the development of Th17 cells), was significantly lower in MLN cells of 5xFAD mice. In contrast, mice without AD neuropathology did not have inflammation in GALT or altered Th17 numbers, nor decreased IL-17 production. In conclusion, the observed changes in GALT of 5xFAD mice mirror the disease progression and might reflect inadequate immune surveillance in the gut and lead to enhanced AD pathology.",
journal = "Journal of Alzheimer's disease : JAD, Journal of Alzheimer's disease : JAD",
title = "Impaired IL-17 Production in Gut-Residing Immune Cells of 5xFAD Mice with Alzheimer’s Disease Pathology",
number = "2",
volume = "61",
doi = "10.3233/JAD-170538",
pages = "619-630"
}

Saksida, T., Koprivica, I., Vujičić, M., Stošić-Grujičić, S., Perović, M., Kanazir, S.,& Stojanović, I. D.. (2018). Impaired IL-17 Production in Gut-Residing Immune Cells of 5xFAD Mice with Alzheimer’s Disease Pathology. in Journal of Alzheimer's disease : JAD, 61(2), 619-630.
https://doi.org/10.3233/JAD-170538

Saksida T, Koprivica I, Vujičić M, Stošić-Grujičić S, Perović M, Kanazir S, Stojanović ID. Impaired IL-17 Production in Gut-Residing Immune Cells of 5xFAD Mice with Alzheimer’s Disease Pathology. in Journal of Alzheimer's disease : JAD. 2018;61(2):619-630.
doi:10.3233/JAD-170538 .

Saksida, Tamara, Koprivica, Ivan, Vujičić, Milica, Stošić-Grujičić, Stanislava, Perović, Milka, Kanazir, Selma, Stojanović, Ivana D., "Impaired IL-17 Production in Gut-Residing Immune Cells of 5xFAD Mice with Alzheimer’s Disease Pathology" in Journal of Alzheimer's disease : JAD, 61, no. 2 (2018):619-630,
https://doi.org/10.3233/JAD-170538 . .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Šavikin, Katarina
AU  - Nikolovski, Neda
AU  - Živković, Jelena
AU  - Saksida, Tamara
AU  - Momčilović, Miljana
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Stanisavljević, Suzana
AU  - Miljković, Đorđe
AU  - Menković, Nebojša
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1756464617303353
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2793
AB  - Pomegranate peel extract (PPE) was obtained by aqueous-ethanol extraction and was abundant in punicalin, punicalagin and ellagic acid. As these compounds are known to act against inflammation and oxidative stress in synergistic fashion, effects of PPE were tested in vitro on immune cells and in animal models of multiple sclerosis and type 1 diabetes (T1D). In vitro, PPE inhibited interleukin-17 (IL-17) production from gut-associated lymphoid tissue (GALT) cells. PPE also reduced production of IL-17 in activated T cells isolated from animals with experimental autoimmune encephalomyelitis (EAE). It efficiently down-regulated clinical symptoms of EAE in DA rats and of streptozotocin-induced T1D in C57BL/6 mice. The effect of PPE in T1D was mediated by inhibition of immune cell infiltration into pancreatic islets and through interference with IL-17 and IFN-γ production in GALT. Our results suggest that PPE has the potential to be used as phytopharmaceutical for certain autoimmune and chronic inflammatory disorders.
T2  - Journal of Functional Foods
T1  - Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes
VL  - 35
DO  - 10.1016/j.jff.2017.06.021
SP  - 522
EP  - 530
ER  - 

@article{
author = "Stojanović, Ivana D. and Šavikin, Katarina and Nikolovski, Neda and Živković, Jelena and Saksida, Tamara and Momčilović, Miljana and Koprivica, Ivan and Vujičić, Milica and Stanisavljević, Suzana and Miljković, Đorđe and Menković, Nebojša",
year = "2017",
abstract = "Pomegranate peel extract (PPE) was obtained by aqueous-ethanol extraction and was abundant in punicalin, punicalagin and ellagic acid. As these compounds are known to act against inflammation and oxidative stress in synergistic fashion, effects of PPE were tested in vitro on immune cells and in animal models of multiple sclerosis and type 1 diabetes (T1D). In vitro, PPE inhibited interleukin-17 (IL-17) production from gut-associated lymphoid tissue (GALT) cells. PPE also reduced production of IL-17 in activated T cells isolated from animals with experimental autoimmune encephalomyelitis (EAE). It efficiently down-regulated clinical symptoms of EAE in DA rats and of streptozotocin-induced T1D in C57BL/6 mice. The effect of PPE in T1D was mediated by inhibition of immune cell infiltration into pancreatic islets and through interference with IL-17 and IFN-γ production in GALT. Our results suggest that PPE has the potential to be used as phytopharmaceutical for certain autoimmune and chronic inflammatory disorders.",
journal = "Journal of Functional Foods",
title = "Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes",
volume = "35",
doi = "10.1016/j.jff.2017.06.021",
pages = "522-530"
}

Stojanović, I. D., Šavikin, K., Nikolovski, N., Živković, J., Saksida, T., Momčilović, M., Koprivica, I., Vujičić, M., Stanisavljević, S., Miljković, Đ.,& Menković, N.. (2017). Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes. in Journal of Functional Foods, 35, 522-530.
https://doi.org/10.1016/j.jff.2017.06.021

Stojanović ID, Šavikin K, Nikolovski N, Živković J, Saksida T, Momčilović M, Koprivica I, Vujičić M, Stanisavljević S, Miljković Đ, Menković N. Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes. in Journal of Functional Foods. 2017;35:522-530.
doi:10.1016/j.jff.2017.06.021 .

Stojanović, Ivana D., Šavikin, Katarina, Nikolovski, Neda, Živković, Jelena, Saksida, Tamara, Momčilović, Miljana, Koprivica, Ivan, Vujičić, Milica, Stanisavljević, Suzana, Miljković, Đorđe, Menković, Nebojša, "Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes" in Journal of Functional Foods, 35 (2017):522-530,
https://doi.org/10.1016/j.jff.2017.06.021 . .

TY  - CONF
AU  - Saksida, Tamara
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Nikolić, Ivana
AU  - Vujičić, Milica
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5766
AB  - Macrophage migration inhibitory factor (MIF) is a molecule expressed both by the immune
cells, like T, B lymphocytes and macrophages, and non-immune cells, like adipocytes,
hepatocytes and beta cells of pancreatic islets. It has actions in the innate and adaptive
immunity, such as a part in regulating the interleukin-17 expression and production, but also
in the development of chemically induced type 1 diabetes in mice. This paper summarizes our
results on the role of MIF in the development of obesity and type 2 diabetes, done in vitro on
beta cell models and murine pancreatic islets, as well as in vivo, when mice with MIF deletion
(MIF-KO) and their wild type (wt) counterparts were on a high fat diet. It is considered that
obesity can develop as a consequence of altered intestinal permeability, so potential leakage of
the intestinal barrier is investigated in the MIF-KO and wt mice. Also, the interplay between
MIF and regulatory T cells, as an important regulator of inflammation in the adipose tissue, is
explored at the level of visceral adipose tissue.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry of Control in Life and Technology: Serbian Biochemical Society Seventh Conference with International Participation. 2017 Nov 10; Belgrade, Serbia
T1  - The role of macrophage migration inhibitory factor in the development of obesity and altered intestinal permeability
SP  - 101
EP  - 107
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5766
ER  - 

@conference{
author = "Saksida, Tamara and Mićanović, Dragica and Koprivica, Ivan and Nikolić, Ivana and Vujičić, Milica and Stošić-Grujičić, Stanislava and Stojanović, Ivana D.",
year = "2017",
abstract = "Macrophage migration inhibitory factor (MIF) is a molecule expressed both by the immune
cells, like T, B lymphocytes and macrophages, and non-immune cells, like adipocytes,
hepatocytes and beta cells of pancreatic islets. It has actions in the innate and adaptive
immunity, such as a part in regulating the interleukin-17 expression and production, but also
in the development of chemically induced type 1 diabetes in mice. This paper summarizes our
results on the role of MIF in the development of obesity and type 2 diabetes, done in vitro on
beta cell models and murine pancreatic islets, as well as in vivo, when mice with MIF deletion
(MIF-KO) and their wild type (wt) counterparts were on a high fat diet. It is considered that
obesity can develop as a consequence of altered intestinal permeability, so potential leakage of
the intestinal barrier is investigated in the MIF-KO and wt mice. Also, the interplay between
MIF and regulatory T cells, as an important regulator of inflammation in the adipose tissue, is
explored at the level of visceral adipose tissue.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry of Control in Life and Technology: Serbian Biochemical Society Seventh Conference with International Participation. 2017 Nov 10; Belgrade, Serbia",
title = "The role of macrophage migration inhibitory factor in the development of obesity and altered intestinal permeability",
pages = "101-107",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5766"
}

Saksida, T., Mićanović, D., Koprivica, I., Nikolić, I., Vujičić, M., Stošić-Grujičić, S.,& Stojanović, I. D.. (2017). The role of macrophage migration inhibitory factor in the development of obesity and altered intestinal permeability. in Biochemistry of Control in Life and Technology: Serbian Biochemical Society Seventh Conference with International Participation. 2017 Nov 10; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 101-107.
https://hdl.handle.net/21.15107/rcub_ibiss_5766

Saksida T, Mićanović D, Koprivica I, Nikolić I, Vujičić M, Stošić-Grujičić S, Stojanović ID. The role of macrophage migration inhibitory factor in the development of obesity and altered intestinal permeability. in Biochemistry of Control in Life and Technology: Serbian Biochemical Society Seventh Conference with International Participation. 2017 Nov 10; Belgrade, Serbia. 2017;:101-107.
https://hdl.handle.net/21.15107/rcub_ibiss_5766 .

Saksida, Tamara, Mićanović, Dragica, Koprivica, Ivan, Nikolić, Ivana, Vujičić, Milica, Stošić-Grujičić, Stanislava, Stojanović, Ivana D., "The role of macrophage migration inhibitory factor in the development of obesity and altered intestinal permeability" in Biochemistry of Control in Life and Technology: Serbian Biochemical Society Seventh Conference with International Participation. 2017 Nov 10; Belgrade, Serbia (2017):101-107,
https://hdl.handle.net/21.15107/rcub_ibiss_5766 .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Jevtić, Bojan
AU  - Milovanović, Boško
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0165247817301979
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2854
AB  - C57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice. Also, C57BL/6 mice are generally considered T helper (Th)1-biased and BALB/c Th2-biased mice. Having in mind increasingly appreciated role of gut associated lymphoid tissue (GALT) cells in autoimmunity, especially in relation to gut Th17 and regulatory T (Treg) cells, our aim was to determine if there are differences in proportion of CD4 + T cell populations in mesenteric lymph nodes and Peyer's p atches of these mouse strains. Lower proportion of Treg was observed in NOD PP, Th2 cells dominated in BALB/c mice in mesenteric lymph nodes (MLN) and Peyer's patches (PP), while Th1 cells prevailed in C57BL/6 MLN. Intradermal immunization of mice with complete Freund's adjuvant resulted in significant difference in Th cell distribution in GALT of NOD mice. Differences were less pronounced in C57BL/6 mice, while GALT of BALB/c mice was almost unresponsive to the immunization. The observed strain- and tissue-dependent changes in Treg proportion after the immunization was probably a consequence of different CCR2 or CCR6-related migration patterns and/or in situ Treg proliferation. In conclusion, NOD, a highly autoimmunity-prone mouse strain, exhibits more profound GALT-related immune response upon immunization compared to the strains that are less prone to autoimmunity.
T2  - Immunology Letters
T1  - Strain-specific helper T cell profile in the gut-associated lymphoid tissue
VL  - 190
DO  - 10.1016/j.imlet.2017.08.017
SP  - 282
EP  - 288
ER  - 

@article{
author = "Stanisavljević, Suzana and Nikolovski, Neda and Vujičić, Milica and Saksida, Tamara and Jevtić, Bojan and Milovanović, Boško and Momčilović, Miljana and Miljković, Đorđe and Stojanović, Ivana D.",
year = "2017",
abstract = "C57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice. Also, C57BL/6 mice are generally considered T helper (Th)1-biased and BALB/c Th2-biased mice. Having in mind increasingly appreciated role of gut associated lymphoid tissue (GALT) cells in autoimmunity, especially in relation to gut Th17 and regulatory T (Treg) cells, our aim was to determine if there are differences in proportion of CD4 + T cell populations in mesenteric lymph nodes and Peyer's p atches of these mouse strains. Lower proportion of Treg was observed in NOD PP, Th2 cells dominated in BALB/c mice in mesenteric lymph nodes (MLN) and Peyer's patches (PP), while Th1 cells prevailed in C57BL/6 MLN. Intradermal immunization of mice with complete Freund's adjuvant resulted in significant difference in Th cell distribution in GALT of NOD mice. Differences were less pronounced in C57BL/6 mice, while GALT of BALB/c mice was almost unresponsive to the immunization. The observed strain- and tissue-dependent changes in Treg proportion after the immunization was probably a consequence of different CCR2 or CCR6-related migration patterns and/or in situ Treg proliferation. In conclusion, NOD, a highly autoimmunity-prone mouse strain, exhibits more profound GALT-related immune response upon immunization compared to the strains that are less prone to autoimmunity.",
journal = "Immunology Letters",
title = "Strain-specific helper T cell profile in the gut-associated lymphoid tissue",
volume = "190",
doi = "10.1016/j.imlet.2017.08.017",
pages = "282-288"
}

Stanisavljević, S., Nikolovski, N., Vujičić, M., Saksida, T., Jevtić, B., Milovanović, B., Momčilović, M., Miljković, Đ.,& Stojanović, I. D.. (2017). Strain-specific helper T cell profile in the gut-associated lymphoid tissue. in Immunology Letters, 190, 282-288.
https://doi.org/10.1016/j.imlet.2017.08.017

Stanisavljević S, Nikolovski N, Vujičić M, Saksida T, Jevtić B, Milovanović B, Momčilović M, Miljković Đ, Stojanović ID. Strain-specific helper T cell profile in the gut-associated lymphoid tissue. in Immunology Letters. 2017;190:282-288.
doi:10.1016/j.imlet.2017.08.017 .

Stanisavljević, Suzana, Nikolovski, Neda, Vujičić, Milica, Saksida, Tamara, Jevtić, Bojan, Milovanović, Boško, Momčilović, Miljana, Miljković, Đorđe, Stojanović, Ivana D., "Strain-specific helper T cell profile in the gut-associated lymphoid tissue" in Immunology Letters, 190 (2017):282-288,
https://doi.org/10.1016/j.imlet.2017.08.017 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
PY  - 2017
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641700011V
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2898
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/1477
AB  - Type 1 diabetes (T1D) is an autoimmune disorder with a strong inflammatory component. Autoreactive cells specifically target insulin-producing β-cells, which leads to loss of glucose homeostasis. T1D remains incurable and versatile; potentially beneficial therapeutics are being tested worldwide. Possible candidates for the treatment of autoimmune diabetes are plants and their extracts since they are rich in biophenols, substances that act as secondary metabolites, and have verified antioxidant and antiinflammatory effects. Salvianolic acid B (SalB) is a biophenol and one of the major constituents of Origanum vulgare ssp. hirtum (Greek oregano) extracts which in our previous studies was shown to exhibit an antidiabetic effect in mice. The aim of the present study was to determine whether SalB is responsible for the observed effects of Greek oregano extracts. SalB was applied in vitro to macrophages and lymphocytes isolated from C57BL/6 mice, as well as in vivo in the model of T1D induced by multiple low doses (MLD) of streptozotocin (STZ). SalB did not affect the viability of cells, but it significantly decreased secretion of nitric oxide (NO) and TNF in lipopolysaccharide (LPS)-stimulated macrophages, as well as the secretion of IFN-γ in concanavalin A (ConA)-stimulated lymphocytes. However, when applied in vivo, SalB at a dose of 2.5 mg/kg b.w., applied for 10 consecutive days, failed to protect mice from diabetes development. In conclusion, SalB exerts immunomodulatory effects in vitro, but is not effective in prevention of T1D in vivo. It probably requires cooperation with some other substances for the maximum efficacy exhibited by oregano extracts.
T2  - Archives of Biological Sciences
T1  - Salvianolic acid B: In vitro and in vivo effects on the immune system
IS  - 4
VL  - 69
DO  - 10.2298/ABS170216011V
SP  - 658
EP  - 663
ER  - 

@article{
author = "Vujičić, Milica and Saksida, Tamara and Stojanović, Ivana D.",
year = "2017",
abstract = "Type 1 diabetes (T1D) is an autoimmune disorder with a strong inflammatory component. Autoreactive cells specifically target insulin-producing β-cells, which leads to loss of glucose homeostasis. T1D remains incurable and versatile; potentially beneficial therapeutics are being tested worldwide. Possible candidates for the treatment of autoimmune diabetes are plants and their extracts since they are rich in biophenols, substances that act as secondary metabolites, and have verified antioxidant and antiinflammatory effects. Salvianolic acid B (SalB) is a biophenol and one of the major constituents of Origanum vulgare ssp. hirtum (Greek oregano) extracts which in our previous studies was shown to exhibit an antidiabetic effect in mice. The aim of the present study was to determine whether SalB is responsible for the observed effects of Greek oregano extracts. SalB was applied in vitro to macrophages and lymphocytes isolated from C57BL/6 mice, as well as in vivo in the model of T1D induced by multiple low doses (MLD) of streptozotocin (STZ). SalB did not affect the viability of cells, but it significantly decreased secretion of nitric oxide (NO) and TNF in lipopolysaccharide (LPS)-stimulated macrophages, as well as the secretion of IFN-γ in concanavalin A (ConA)-stimulated lymphocytes. However, when applied in vivo, SalB at a dose of 2.5 mg/kg b.w., applied for 10 consecutive days, failed to protect mice from diabetes development. In conclusion, SalB exerts immunomodulatory effects in vitro, but is not effective in prevention of T1D in vivo. It probably requires cooperation with some other substances for the maximum efficacy exhibited by oregano extracts.",
journal = "Archives of Biological Sciences",
title = "Salvianolic acid B: In vitro and in vivo effects on the immune system",
number = "4",
volume = "69",
doi = "10.2298/ABS170216011V",
pages = "658-663"
}

Vujičić, M., Saksida, T.,& Stojanović, I. D.. (2017). Salvianolic acid B: In vitro and in vivo effects on the immune system. in Archives of Biological Sciences, 69(4), 658-663.
https://doi.org/10.2298/ABS170216011V

Vujičić M, Saksida T, Stojanović ID. Salvianolic acid B: In vitro and in vivo effects on the immune system. in Archives of Biological Sciences. 2017;69(4):658-663.
doi:10.2298/ABS170216011V .

Vujičić, Milica, Saksida, Tamara, Stojanović, Ivana D., "Salvianolic acid B: In vitro and in vivo effects on the immune system" in Archives of Biological Sciences, 69, no. 4 (2017):658-663,
https://doi.org/10.2298/ABS170216011V . .

TY  - JOUR
AU  - Nikolić, Ivana
AU  - Stojanović, Ivana D.
AU  - Vujičić, Milica
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Saksida, Tamara
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0171298516303746
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2484
AB  - Bovine colostrum is a rich source of nutrients and immunologically active components that play a role in conveying passive immunity to the offspring, protection and maturation of new-born's gastrointestinal tract. Colostrum has exerted positive effects in diseases affecting gastrointestinal tract, as well as type 2 diabetes (T2D). However, health-promoting effects in type 1 diabetes have not been reported. The aim of this study was to investigate therapeutic value of oral administration of standardized bovine colostrum derivative (SBCD) in three models of type 1 diabetes (T1D): spontaneously developed T1D in NOD mice and BB-DP rats, and in chemically induced T1D in C57BL/6 mice with multiple low doses of streptozotocin (MLDS). SBCD was administered per os and the disease development was evaluated by weekly measurement of blood glucose and by histological analyses of the pancreas. SBCD administration prevented diabetes development in all three models, as indicated by euglicaemia. Ex vivo analysis of cytokine expression and production in the spleen and mesenteric lymph nodes (MLN) in MLDS challenged mice revealed a strong modulation of the immune response. In the MLN cells SBCD disrupted harmful Th17 response induced by MLDS. Expression of Th1 signature cytokine IFN-γ was down-regulated in MLN cells of SBCD-treated mice, while IL-4 secretion (Th2 cytokine) was up-regulated in comparison to diabetic group. Modulation of the immune response seen in the MLN protruded to the spleen, giving overall less infiltration of immune cells to the pancreas. SBCD acted on immune cells and halted (auto) aggression towards pancreatic beta cells. Moreover, SBCD induced beta cell proliferation. Hence, this derivative could be tested in diabetes and other similar diseases with aberrant immune response.
T2  - Immunobiology
T1  - Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents
IS  - 2
VL  - 222
DO  - 10.1016/j.imbio.2016.09.013
SP  - 272
EP  - 279
ER  - 

@article{
author = "Nikolić, Ivana and Stojanović, Ivana D. and Vujičić, Milica and Fagone, Paolo and Mangano, Katia and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Saksida, Tamara",
year = "2017",
abstract = "Bovine colostrum is a rich source of nutrients and immunologically active components that play a role in conveying passive immunity to the offspring, protection and maturation of new-born's gastrointestinal tract. Colostrum has exerted positive effects in diseases affecting gastrointestinal tract, as well as type 2 diabetes (T2D). However, health-promoting effects in type 1 diabetes have not been reported. The aim of this study was to investigate therapeutic value of oral administration of standardized bovine colostrum derivative (SBCD) in three models of type 1 diabetes (T1D): spontaneously developed T1D in NOD mice and BB-DP rats, and in chemically induced T1D in C57BL/6 mice with multiple low doses of streptozotocin (MLDS). SBCD was administered per os and the disease development was evaluated by weekly measurement of blood glucose and by histological analyses of the pancreas. SBCD administration prevented diabetes development in all three models, as indicated by euglicaemia. Ex vivo analysis of cytokine expression and production in the spleen and mesenteric lymph nodes (MLN) in MLDS challenged mice revealed a strong modulation of the immune response. In the MLN cells SBCD disrupted harmful Th17 response induced by MLDS. Expression of Th1 signature cytokine IFN-γ was down-regulated in MLN cells of SBCD-treated mice, while IL-4 secretion (Th2 cytokine) was up-regulated in comparison to diabetic group. Modulation of the immune response seen in the MLN protruded to the spleen, giving overall less infiltration of immune cells to the pancreas. SBCD acted on immune cells and halted (auto) aggression towards pancreatic beta cells. Moreover, SBCD induced beta cell proliferation. Hence, this derivative could be tested in diabetes and other similar diseases with aberrant immune response.",
journal = "Immunobiology",
title = "Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents",
number = "2",
volume = "222",
doi = "10.1016/j.imbio.2016.09.013",
pages = "272-279"
}

Nikolić, I., Stojanović, I. D., Vujičić, M., Fagone, P., Mangano, K., Stošić-Grujičić, S., Nicoletti, F.,& Saksida, T.. (2017). Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents. in Immunobiology, 222(2), 272-279.
https://doi.org/10.1016/j.imbio.2016.09.013

Nikolić I, Stojanović ID, Vujičić M, Fagone P, Mangano K, Stošić-Grujičić S, Nicoletti F, Saksida T. Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents. in Immunobiology. 2017;222(2):272-279.
doi:10.1016/j.imbio.2016.09.013 .

Nikolić, Ivana, Stojanović, Ivana D., Vujičić, Milica, Fagone, Paolo, Mangano, Katia, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Saksida, Tamara, "Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents" in Immunobiology, 222, no. 2 (2017):272-279,
https://doi.org/10.1016/j.imbio.2016.09.013 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Vasić, Bobana
AU  - Nikolić, Ivana
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
PY  - 2017
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641600096V
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2978
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/812
AB  - Nuclear protein 1 (NUPR1) is a transcription cofactor that senses stressful conditions and modulates cellular response by promoting or inhibiting apoptosis. NUPR1 is usually highly expressed in tumor cells where it enables them to adapt and resist environmental stress or chemotherapeutic compounds. NUPR1 can be involved in cell proliferation. Data about the involvement of NUPR1 in the proliferation and apoptosis of lymphocytes are scarce. Therefore, in this study we focused on the role of NUPR1 in lymphocyte physiology and found that NUPR1 might be involved in the initiation of their proliferation. Lymphocytes were isolated from the cervical lymph nodes of C57BL/6 mice. NUPR1 expression subsided 24 h after the induction of proliferation by a mitogen. Also, stressful conditions after cell isolation led to increased NUPR1 mRNA and protein expression in vitro that coincided with cell apoptosis. Similarly, apoptosis induction by staurosporine, a broad-range protein kinase inhibitor, led to increased NUPR1 expression. In addition, NUPR1 inhibition by smallinterfering RNA prevented the staurosporine-induced apoptosis (judging from decreased caspase activity) in the whole cell population of cervical lymph nodes. However, NUPR1 absence was irrelevant to the induction of apoptosis in CD3+ T lymphocytes, suggesting that NUPR1 is probably a mediator of apoptosis in other immune cell populations within the lymph node, such as B lymphocytes. In conclusion, our results suggest that NUPR1 is important for the initiation of lymphocyte cell division and for the apoptotic process of non-T cells during stressful conditions.
T2  - Archives of Biological Sciences
T1  - The role of NUPR1 in lymphocyte proliferation and apoptosis
IS  - 2
VL  - 69
DO  - 10.2298/ABS160707096V
SP  - 261
EP  - 267
ER  - 

@article{
author = "Vujičić, Milica and Vasić, Bobana and Nikolić, Ivana and Saksida, Tamara and Stojanović, Ivana D.",
year = "2017",
abstract = "Nuclear protein 1 (NUPR1) is a transcription cofactor that senses stressful conditions and modulates cellular response by promoting or inhibiting apoptosis. NUPR1 is usually highly expressed in tumor cells where it enables them to adapt and resist environmental stress or chemotherapeutic compounds. NUPR1 can be involved in cell proliferation. Data about the involvement of NUPR1 in the proliferation and apoptosis of lymphocytes are scarce. Therefore, in this study we focused on the role of NUPR1 in lymphocyte physiology and found that NUPR1 might be involved in the initiation of their proliferation. Lymphocytes were isolated from the cervical lymph nodes of C57BL/6 mice. NUPR1 expression subsided 24 h after the induction of proliferation by a mitogen. Also, stressful conditions after cell isolation led to increased NUPR1 mRNA and protein expression in vitro that coincided with cell apoptosis. Similarly, apoptosis induction by staurosporine, a broad-range protein kinase inhibitor, led to increased NUPR1 expression. In addition, NUPR1 inhibition by smallinterfering RNA prevented the staurosporine-induced apoptosis (judging from decreased caspase activity) in the whole cell population of cervical lymph nodes. However, NUPR1 absence was irrelevant to the induction of apoptosis in CD3+ T lymphocytes, suggesting that NUPR1 is probably a mediator of apoptosis in other immune cell populations within the lymph node, such as B lymphocytes. In conclusion, our results suggest that NUPR1 is important for the initiation of lymphocyte cell division and for the apoptotic process of non-T cells during stressful conditions.",
journal = "Archives of Biological Sciences",
title = "The role of NUPR1 in lymphocyte proliferation and apoptosis",
number = "2",
volume = "69",
doi = "10.2298/ABS160707096V",
pages = "261-267"
}

Vujičić, M., Vasić, B., Nikolić, I., Saksida, T.,& Stojanović, I. D.. (2017). The role of NUPR1 in lymphocyte proliferation and apoptosis. in Archives of Biological Sciences, 69(2), 261-267.
https://doi.org/10.2298/ABS160707096V

Vujičić M, Vasić B, Nikolić I, Saksida T, Stojanović ID. The role of NUPR1 in lymphocyte proliferation and apoptosis. in Archives of Biological Sciences. 2017;69(2):261-267.
doi:10.2298/ABS160707096V .

Vujičić, Milica, Vasić, Bobana, Nikolić, Ivana, Saksida, Tamara, Stojanović, Ivana D., "The role of NUPR1 in lymphocyte proliferation and apoptosis" in Archives of Biological Sciences, 69, no. 2 (2017):261-267,
https://doi.org/10.2298/ABS160707096V . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Vasić, Bobana
AU  - Nikolić, Ivana
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
PY  - 2016
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641600096V
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2690
AB  - Nuclear protein 1 (NUPR1) is a transcription cofactor that senses stressful conditions and modulates cellular response by promoting or inhibiting apoptosis. NUPR1 is usually highly expressed in tumor cells where it enables them to adapt and resist environmental stress or chemotherapeutic compounds. NUPR1 can be involved in cell proliferation. Data about the involvement of NUPR1 in the proliferation and apoptosis of lymphocytes are scarce. Therefore, in this study we focused on the role of NUPR1 in lymphocyte physiology and found that NUPR1 might be involved in the initiation of their proliferation. Lymphocytes were isolated from the cervical lymph nodes of C57BL/6 mice. NUPR1 expression subsided 24 h after the induction of proliferation by a mitogen. Also, stressful conditions after cell isolation led to increased NUPR1 mRNA and protein expression in vitro that coincided with cell apoptosis. Similarly, apoptosis induction by staurosporine, a broad-range protein kinase inhibitor, led to increased NUPR1 expression. In addition, NUPR1 inhibition by smallinterfering RNA prevented the staurosporine-induced apoptosis (judging from decreased caspase activity) in the whole cell population of cervical lymph nodes. However, NUPR1 absence was irrelevant to the induction of apoptosis in CD3+ T lymphocytes, suggesting that NUPR1 is probably a mediator of apoptosis in other immune cell populations within the lymph node, such as B lymphocytes. In conclusion, our results suggest that NUPR1 is important for the initiation of lymphocyte cell division and for the apoptotic process of non-T cells during stressful conditions.
T2  - Archives of Biological Sciences
T1  - The role of NUPR1 in lymphocyte proliferation and apoptosis
DO  - 10.2298/ABS160707096V
ER  - 

@article{
author = "Vujičić, Milica and Vasić, Bobana and Nikolić, Ivana and Saksida, Tamara and Stojanović, Ivana D.",
year = "2016",
abstract = "Nuclear protein 1 (NUPR1) is a transcription cofactor that senses stressful conditions and modulates cellular response by promoting or inhibiting apoptosis. NUPR1 is usually highly expressed in tumor cells where it enables them to adapt and resist environmental stress or chemotherapeutic compounds. NUPR1 can be involved in cell proliferation. Data about the involvement of NUPR1 in the proliferation and apoptosis of lymphocytes are scarce. Therefore, in this study we focused on the role of NUPR1 in lymphocyte physiology and found that NUPR1 might be involved in the initiation of their proliferation. Lymphocytes were isolated from the cervical lymph nodes of C57BL/6 mice. NUPR1 expression subsided 24 h after the induction of proliferation by a mitogen. Also, stressful conditions after cell isolation led to increased NUPR1 mRNA and protein expression in vitro that coincided with cell apoptosis. Similarly, apoptosis induction by staurosporine, a broad-range protein kinase inhibitor, led to increased NUPR1 expression. In addition, NUPR1 inhibition by smallinterfering RNA prevented the staurosporine-induced apoptosis (judging from decreased caspase activity) in the whole cell population of cervical lymph nodes. However, NUPR1 absence was irrelevant to the induction of apoptosis in CD3+ T lymphocytes, suggesting that NUPR1 is probably a mediator of apoptosis in other immune cell populations within the lymph node, such as B lymphocytes. In conclusion, our results suggest that NUPR1 is important for the initiation of lymphocyte cell division and for the apoptotic process of non-T cells during stressful conditions.",
journal = "Archives of Biological Sciences",
title = "The role of NUPR1 in lymphocyte proliferation and apoptosis",
doi = "10.2298/ABS160707096V"
}

Vujičić, M., Vasić, B., Nikolić, I., Saksida, T.,& Stojanović, I. D.. (2016). The role of NUPR1 in lymphocyte proliferation and apoptosis. in Archives of Biological Sciences.
https://doi.org/10.2298/ABS160707096V

Vujičić M, Vasić B, Nikolić I, Saksida T, Stojanović ID. The role of NUPR1 in lymphocyte proliferation and apoptosis. in Archives of Biological Sciences. 2016;.
doi:10.2298/ABS160707096V .

Vujičić, Milica, Vasić, Bobana, Nikolić, Ivana, Saksida, Tamara, Stojanović, Ivana D., "The role of NUPR1 in lymphocyte proliferation and apoptosis" in Archives of Biological Sciences (2016),
https://doi.org/10.2298/ABS160707096V . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Nikolić, Ivana
AU  - Kontogianni, Vassiliki G.
AU  - Saksida, Tamara
AU  - Charisiadis, Pantelis
AU  - Vasić, Bobana
AU  - Stošić-Grujičić, Stanislava
AU  - Gerothanassis, Ioannis P.
AU  - Tzakos, Andreas G.
AU  - Stojanović, Ivana D.
PY  - 2016
UR  - http://doi.wiley.com/10.1111/1750-3841.13333
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2979
AB  - Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MSn). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4+ and activated CD4+CD25+ T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy.
PB  - Blackwell Publishing Inc.
T2  - Journal of Food Science
T1  - Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice
IS  - 7
VL  - 81
DO  - 10.1111/1750-3841.13333
SP  - H1846
EP  - H1853
ER  - 

@article{
author = "Vujičić, Milica and Nikolić, Ivana and Kontogianni, Vassiliki G. and Saksida, Tamara and Charisiadis, Pantelis and Vasić, Bobana and Stošić-Grujičić, Stanislava and Gerothanassis, Ioannis P. and Tzakos, Andreas G. and Stojanović, Ivana D.",
year = "2016",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MSn). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4+ and activated CD4+CD25+ T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy.",
publisher = "Blackwell Publishing Inc.",
journal = "Journal of Food Science",
title = "Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice",
number = "7",
volume = "81",
doi = "10.1111/1750-3841.13333",
pages = "H1846-H1853"
}

Vujičić, M., Nikolić, I., Kontogianni, V. G., Saksida, T., Charisiadis, P., Vasić, B., Stošić-Grujičić, S., Gerothanassis, I. P., Tzakos, A. G.,& Stojanović, I. D.. (2016). Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice. in Journal of Food Science
Blackwell Publishing Inc.., 81(7), H1846-H1853.
https://doi.org/10.1111/1750-3841.13333

Vujičić M, Nikolić I, Kontogianni VG, Saksida T, Charisiadis P, Vasić B, Stošić-Grujičić S, Gerothanassis IP, Tzakos AG, Stojanović ID. Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice. in Journal of Food Science. 2016;81(7):H1846-H1853.
doi:10.1111/1750-3841.13333 .

Vujičić, Milica, Nikolić, Ivana, Kontogianni, Vassiliki G., Saksida, Tamara, Charisiadis, Pantelis, Vasić, Bobana, Stošić-Grujičić, Stanislava, Gerothanassis, Ioannis P., Tzakos, Andreas G., Stojanović, Ivana D., "Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice" in Journal of Food Science, 81, no. 7 (2016):H1846-H1853,
https://doi.org/10.1111/1750-3841.13333 . .

TY  - JOUR
AU  - Nikolić, Ivana
AU  - Saksida, Tamara
AU  - Vujičić, Milica
AU  - Stojanović, Ivana D.
AU  - Stošić-Grujičić, Stanislava
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1962
AB  - We have recently shown that carbon monoxide releasing molecule (CORM)-A1
   prevents type 1 diabetes induced in C57BL/6 mice with multiple low doses
   of streptozotocin (MLDS) by shifting the Th1/Th17/M1 balance towards a
   Th2/M2 response. In the present work we tested the hypothesis that
   CORM-A1 might influence regulatory arm of the immune response, as well
   as beta cell regeneration. CORM-A1 (2 mg/kg/day) was administered for 10
   days to mice induced with MLDS and/or depleted of low dose
   cyclophosphamide (CY)-sensitive FoxP3(+) T regulatory (Treg) cells.
   Besides monitoring hyperglycaemia, ex vivo analysis of spleen,
   pancreatic lymph nodes (PLN) and pancreas was performed at the end of
   treatment. In CORM-A1-treated MLDS-induced mice the improvement of
   hyperglycaemia was observed only without depletion of CY-sensitive
   FoxP3(+) Treg cells. This was accompanied by decreased levels of
   interleukin (IL)-12, IL-2 and early activation marker CD25 in the spleen
   and PLN and increased transforming growth factor (TGF)-beta, resulting
   in reduced lymphocyte proliferation in both organs. In parallel,
   decreased transcript levels of IL-2, but increased mRNA expression of
   TGF-beta, accompanied with up-regulation of Ki-67 protein expression was
   observed within pancreas. Together, the data suggested that besides the
   immunomodulatory potential, CORM-A1 probably induces beta cell
   regeneration. (C) 2015 European Federation of Immunological Societies.
   Published by Elsevier B.V. All rights reserved.
T2  - Immunology Letters
T1  - Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1:
 Immunomodulation and regeneration of islet beta cells
IS  - 1
VL  - 165
DO  - 10.1016/j.imlet.2015.03.009
SP  - 39
EP  - 46
ER  - 

@article{
author = "Nikolić, Ivana and Saksida, Tamara and Vujičić, Milica and Stojanović, Ivana D. and Stošić-Grujičić, Stanislava",
year = "2015",
abstract = "We have recently shown that carbon monoxide releasing molecule (CORM)-A1
   prevents type 1 diabetes induced in C57BL/6 mice with multiple low doses
   of streptozotocin (MLDS) by shifting the Th1/Th17/M1 balance towards a
   Th2/M2 response. In the present work we tested the hypothesis that
   CORM-A1 might influence regulatory arm of the immune response, as well
   as beta cell regeneration. CORM-A1 (2 mg/kg/day) was administered for 10
   days to mice induced with MLDS and/or depleted of low dose
   cyclophosphamide (CY)-sensitive FoxP3(+) T regulatory (Treg) cells.
   Besides monitoring hyperglycaemia, ex vivo analysis of spleen,
   pancreatic lymph nodes (PLN) and pancreas was performed at the end of
   treatment. In CORM-A1-treated MLDS-induced mice the improvement of
   hyperglycaemia was observed only without depletion of CY-sensitive
   FoxP3(+) Treg cells. This was accompanied by decreased levels of
   interleukin (IL)-12, IL-2 and early activation marker CD25 in the spleen
   and PLN and increased transforming growth factor (TGF)-beta, resulting
   in reduced lymphocyte proliferation in both organs. In parallel,
   decreased transcript levels of IL-2, but increased mRNA expression of
   TGF-beta, accompanied with up-regulation of Ki-67 protein expression was
   observed within pancreas. Together, the data suggested that besides the
   immunomodulatory potential, CORM-A1 probably induces beta cell
   regeneration. (C) 2015 European Federation of Immunological Societies.
   Published by Elsevier B.V. All rights reserved.",
journal = "Immunology Letters",
title = "Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1:
 Immunomodulation and regeneration of islet beta cells",
number = "1",
volume = "165",
doi = "10.1016/j.imlet.2015.03.009",
pages = "39-46"
}

Nikolić, I., Saksida, T., Vujičić, M., Stojanović, I. D.,& Stošić-Grujičić, S.. (2015). Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1:
 Immunomodulation and regeneration of islet beta cells. in Immunology Letters, 165(1), 39-46.
https://doi.org/10.1016/j.imlet.2015.03.009

Nikolić I, Saksida T, Vujičić M, Stojanović ID, Stošić-Grujičić S. Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1:
 Immunomodulation and regeneration of islet beta cells. in Immunology Letters. 2015;165(1):39-46.
doi:10.1016/j.imlet.2015.03.009 .

Nikolić, Ivana, Saksida, Tamara, Vujičić, Milica, Stojanović, Ivana D., Stošić-Grujičić, Stanislava, "Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1:
 Immunomodulation and regeneration of islet beta cells" in Immunology Letters, 165, no. 1 (2015):39-46,
https://doi.org/10.1016/j.imlet.2015.03.009 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Nikolić, Ivana
AU  - Stojanović, Ivana D.
AU  - Stošić-Grujičić, Stanislava
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2030
AB  - Compound A (CpdA), or
   2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethyl-ammonium chloride, is a
   stable analog of the hydroxyl phenyl aziridine precursor found in the
   Namibian shrub Salsola tuberculatiformis Botschantzev. It belongs to the
   group of so-called ``dissociated{''} GC receptor ligands that
   downmodulate pro-inflammatory gene expression via the transrepression
   mechanism, but without physically binding to DNA. We have recently
   reported that the in vivo administration of CpdA exerts a strong
   protective effect in a pharmacological model of type 1 diabetes in mice.
   The goal of this study was to investigate in more detail the effects of
   CpdA on multiple immune system components, as well as on target
   pancreatic beta cells in direct in vitro exposure. The utility of CpdA
   in diabetes prevention was evaluated through its addition to
   mitogen-activated spleen, lymph node and peritoneal cells of C57BL/6
   mice, and to murine pancreatic islets and INS-1 and RINm5F beta cell
   lines. CpdA modulated immune cell-derived cytokine production in vitro
   by restraining the pro-inflammatory M1/Th1/Th17 response and switching
   it towards an anti-inflammatory Th2 profile. However, it did not
   preserve beta cells from the cytotoxic action of inflammatory cytokines.
   Thus, the anti-diabetic properties of CpdA are mediated through the
   modulation of immune cell differentiation pathways rather than through
   rescue of target cells from autoimmune attack.
T2  - Archives of Biological Sciences
T1  - In vitro dissection of anti-diabetic effects of compound a, a dissociating glucocorticoid receptor ligand
IS  - 3
VL  - 67
DO  - 10.2298/ABS141107056V
SP  - 941
EP  - 947
ER  - 

@article{
author = "Vujičić, Milica and Saksida, Tamara and Nikolić, Ivana and Stojanović, Ivana D. and Stošić-Grujičić, Stanislava",
year = "2015",
abstract = "Compound A (CpdA), or
   2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethyl-ammonium chloride, is a
   stable analog of the hydroxyl phenyl aziridine precursor found in the
   Namibian shrub Salsola tuberculatiformis Botschantzev. It belongs to the
   group of so-called ``dissociated{''} GC receptor ligands that
   downmodulate pro-inflammatory gene expression via the transrepression
   mechanism, but without physically binding to DNA. We have recently
   reported that the in vivo administration of CpdA exerts a strong
   protective effect in a pharmacological model of type 1 diabetes in mice.
   The goal of this study was to investigate in more detail the effects of
   CpdA on multiple immune system components, as well as on target
   pancreatic beta cells in direct in vitro exposure. The utility of CpdA
   in diabetes prevention was evaluated through its addition to
   mitogen-activated spleen, lymph node and peritoneal cells of C57BL/6
   mice, and to murine pancreatic islets and INS-1 and RINm5F beta cell
   lines. CpdA modulated immune cell-derived cytokine production in vitro
   by restraining the pro-inflammatory M1/Th1/Th17 response and switching
   it towards an anti-inflammatory Th2 profile. However, it did not
   preserve beta cells from the cytotoxic action of inflammatory cytokines.
   Thus, the anti-diabetic properties of CpdA are mediated through the
   modulation of immune cell differentiation pathways rather than through
   rescue of target cells from autoimmune attack.",
journal = "Archives of Biological Sciences",
title = "In vitro dissection of anti-diabetic effects of compound a, a dissociating glucocorticoid receptor ligand",
number = "3",
volume = "67",
doi = "10.2298/ABS141107056V",
pages = "941-947"
}

Vujičić, M., Saksida, T., Nikolić, I., Stojanović, I. D.,& Stošić-Grujičić, S.. (2015). In vitro dissection of anti-diabetic effects of compound a, a dissociating glucocorticoid receptor ligand. in Archives of Biological Sciences, 67(3), 941-947.
https://doi.org/10.2298/ABS141107056V

Vujičić M, Saksida T, Nikolić I, Stojanović ID, Stošić-Grujičić S. In vitro dissection of anti-diabetic effects of compound a, a dissociating glucocorticoid receptor ligand. in Archives of Biological Sciences. 2015;67(3):941-947.
doi:10.2298/ABS141107056V .

Vujičić, Milica, Saksida, Tamara, Nikolić, Ivana, Stojanović, Ivana D., Stošić-Grujičić, Stanislava, "In vitro dissection of anti-diabetic effects of compound a, a dissociating glucocorticoid receptor ligand" in Archives of Biological Sciences, 67, no. 3 (2015):941-947,
https://doi.org/10.2298/ABS141107056V . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Nikolić, Ivana
AU  - Kontogianni, Vassiliki G.
AU  - Saksida, Tamara
AU  - Charisiadis, Pantelis
AU  - Oreščanin Dušić, Zorana
AU  - Blagojević, Duško
AU  - Stošić-Grujičić, Stanislava
AU  - Tzakos, Andreas G.
AU  - Stojanović, Ivana D.
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1988
AB  - Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as
   a consequence of pancreatic beta-cell destruction and results in
   hyperglycaemia. Since current T1D therapy mainly involves insulin
   replacement, the aim of the present study was to evaluate the
   therapeutic potential of Origanum vulgare L. ssp. hirtum (Greek oregano)
   leaf extract rich in biophenols for the treatment of T1D. The
   phytochemical profile of methanolic oregano extract (MOE) and aqueous
   oregano extract (AOE) was determined by liquid
   chromatography/electrospray ion-trap tandem MS (LC/DAD/ESI-MSn), while
   their main compounds were quantified by HPLC with diode array detection.
   After establishing their potent in vitro antioxidant activity, the
   extracts were administered to C57BL/6 mice treated with multiple low
   doses of streptozotocin for diabetes induction. While prophylactic AOE
   therapy had no impact on diabetes induction, MOE reduced diabetes
   incidence and preserved normal insulin secretion. In addition, MOE
   scavenged reactive oxygen and nitrogen species and, therefore,
   alleviated the need for the up-regulation of antioxidant enzymes. MOE
   treatment specifically attenuated the pro-inflammatory response mediated
   by T helper 17 cells and enhanced anti-inflammatory T helper 2 and T
   regulatory cells through the impact on specific signalling pathways and
   transcription factors. Importantly, MOE preserved beta-cells from in
   vitro apoptosis via blockade of caspase 3. Finally, rosmarinic acid, a
   predominant compound in MOE, exhibited only partial protection from
   diabetes induction. In conclusion, acting as an antioxidant,
   immunomodulator and in an anti-apoptotic manner, MOE protected mice from
   diabetes development. Seemingly, there is more than one compound
   responsible for the beneficial effect of MOE.
T2  - British Journal of Nutrition
T1  - Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity
IS  - 5
VL  - 113
DO  - 10.1017/S0007114514004048
SP  - 770
EP  - 782
ER  - 

@article{
author = "Vujičić, Milica and Nikolić, Ivana and Kontogianni, Vassiliki G. and Saksida, Tamara and Charisiadis, Pantelis and Oreščanin Dušić, Zorana and Blagojević, Duško and Stošić-Grujičić, Stanislava and Tzakos, Andreas G. and Stojanović, Ivana D.",
year = "2015",
abstract = "Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as
   a consequence of pancreatic beta-cell destruction and results in
   hyperglycaemia. Since current T1D therapy mainly involves insulin
   replacement, the aim of the present study was to evaluate the
   therapeutic potential of Origanum vulgare L. ssp. hirtum (Greek oregano)
   leaf extract rich in biophenols for the treatment of T1D. The
   phytochemical profile of methanolic oregano extract (MOE) and aqueous
   oregano extract (AOE) was determined by liquid
   chromatography/electrospray ion-trap tandem MS (LC/DAD/ESI-MSn), while
   their main compounds were quantified by HPLC with diode array detection.
   After establishing their potent in vitro antioxidant activity, the
   extracts were administered to C57BL/6 mice treated with multiple low
   doses of streptozotocin for diabetes induction. While prophylactic AOE
   therapy had no impact on diabetes induction, MOE reduced diabetes
   incidence and preserved normal insulin secretion. In addition, MOE
   scavenged reactive oxygen and nitrogen species and, therefore,
   alleviated the need for the up-regulation of antioxidant enzymes. MOE
   treatment specifically attenuated the pro-inflammatory response mediated
   by T helper 17 cells and enhanced anti-inflammatory T helper 2 and T
   regulatory cells through the impact on specific signalling pathways and
   transcription factors. Importantly, MOE preserved beta-cells from in
   vitro apoptosis via blockade of caspase 3. Finally, rosmarinic acid, a
   predominant compound in MOE, exhibited only partial protection from
   diabetes induction. In conclusion, acting as an antioxidant,
   immunomodulator and in an anti-apoptotic manner, MOE protected mice from
   diabetes development. Seemingly, there is more than one compound
   responsible for the beneficial effect of MOE.",
journal = "British Journal of Nutrition",
title = "Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity",
number = "5",
volume = "113",
doi = "10.1017/S0007114514004048",
pages = "770-782"
}

Vujičić, M., Nikolić, I., Kontogianni, V. G., Saksida, T., Charisiadis, P., Oreščanin Dušić, Z., Blagojević, D., Stošić-Grujičić, S., Tzakos, A. G.,& Stojanović, I. D.. (2015). Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity. in British Journal of Nutrition, 113(5), 770-782.
https://doi.org/10.1017/S0007114514004048

Vujičić M, Nikolić I, Kontogianni VG, Saksida T, Charisiadis P, Oreščanin Dušić Z, Blagojević D, Stošić-Grujičić S, Tzakos AG, Stojanović ID. Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity. in British Journal of Nutrition. 2015;113(5):770-782.
doi:10.1017/S0007114514004048 .

Vujičić, Milica, Nikolić, Ivana, Kontogianni, Vassiliki G., Saksida, Tamara, Charisiadis, Pantelis, Oreščanin Dušić, Zorana, Blagojević, Duško, Stošić-Grujičić, Stanislava, Tzakos, Andreas G., Stojanović, Ivana D., "Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity" in British Journal of Nutrition, 113, no. 5 (2015):770-782,
https://doi.org/10.1017/S0007114514004048 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Nikolić, Ivana
AU  - Krajnović, Tamara
AU  - Cheng, Kai-Fan
AU  - VanPatten, Sonya
AU  - He, Mingzhu
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
AU  - Al-Abed, Yousef
AU  - Saksida, Tamara
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2141
AB  - Macrophage migration inhibitory factor is a multifunctional cytokine
   involved in the regulation of immune processes and also in apoptosis
   induction. Elevated MIF expression is detrimental for insulin-producing
   beta cells and MIF inhibition protected beta cells from several
   cytotoxic insults such as inflammatory cytokines, high fatty acids or
   high glucose concentrations. Therefore, the aim of this study was to
   investigate two newly synthesized small molecule MIF inhibitors (K664-1
   and K647-1) and to compare them with previously established effects of
   the prototypical MIF inhibitor, ISO-1. Our results indicate that K664-1
   and K647-1 are 160- and 40-fold more effective in inhibition of MIF's
   tautomerase activity than ISO-1. Also, new inhibitors confer beta cell
   protection from cytokine-triggered apoptosis at significantly lower
   concentrations than LSO-1. Although all three MIF inhibitors inhibit
   caspase 3 activity, K664-1 and K647-1 suppress pro-apoptotic BAX protein
   expression and up-regulate anti-apoptotic Bcl-2 mRNA. Finally, all three
   MIF inhibitors operate through blockade of nitric oxide production
   stimulated by cytokines. In conclusion, two novel MIF inhibitors are
   more potent than ISO-1 and operate through inhibition of the
   mitochondria-related apoptotic pathway. We propose that these compounds
   represent a unique class of anti-MIF antagonists that should be further
   tested for therapeutic use. (C) 2014 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death
VL  - 740
DO  - 10.1016/j.ejphar.2014.06.009
SP  - 683
EP  - 689
ER  - 

@article{
author = "Vujičić, Milica and Nikolić, Ivana and Krajnović, Tamara and Cheng, Kai-Fan and VanPatten, Sonya and He, Mingzhu and Stošić-Grujičić, Stanislava and Stojanović, Ivana D. and Al-Abed, Yousef and Saksida, Tamara",
year = "2014",
abstract = "Macrophage migration inhibitory factor is a multifunctional cytokine
   involved in the regulation of immune processes and also in apoptosis
   induction. Elevated MIF expression is detrimental for insulin-producing
   beta cells and MIF inhibition protected beta cells from several
   cytotoxic insults such as inflammatory cytokines, high fatty acids or
   high glucose concentrations. Therefore, the aim of this study was to
   investigate two newly synthesized small molecule MIF inhibitors (K664-1
   and K647-1) and to compare them with previously established effects of
   the prototypical MIF inhibitor, ISO-1. Our results indicate that K664-1
   and K647-1 are 160- and 40-fold more effective in inhibition of MIF's
   tautomerase activity than ISO-1. Also, new inhibitors confer beta cell
   protection from cytokine-triggered apoptosis at significantly lower
   concentrations than LSO-1. Although all three MIF inhibitors inhibit
   caspase 3 activity, K664-1 and K647-1 suppress pro-apoptotic BAX protein
   expression and up-regulate anti-apoptotic Bcl-2 mRNA. Finally, all three
   MIF inhibitors operate through blockade of nitric oxide production
   stimulated by cytokines. In conclusion, two novel MIF inhibitors are
   more potent than ISO-1 and operate through inhibition of the
   mitochondria-related apoptotic pathway. We propose that these compounds
   represent a unique class of anti-MIF antagonists that should be further
   tested for therapeutic use. (C) 2014 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death",
volume = "740",
doi = "10.1016/j.ejphar.2014.06.009",
pages = "683-689"
}

Vujičić, M., Nikolić, I., Krajnović, T., Cheng, K., VanPatten, S., He, M., Stošić-Grujičić, S., Stojanović, I. D., Al-Abed, Y.,& Saksida, T.. (2014). Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death. in European Journal of Pharmacology, 740, 683-689.
https://doi.org/10.1016/j.ejphar.2014.06.009

Vujičić M, Nikolić I, Krajnović T, Cheng K, VanPatten S, He M, Stošić-Grujičić S, Stojanović ID, Al-Abed Y, Saksida T. Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death. in European Journal of Pharmacology. 2014;740:683-689.
doi:10.1016/j.ejphar.2014.06.009 .

Vujičić, Milica, Nikolić, Ivana, Krajnović, Tamara, Cheng, Kai-Fan, VanPatten, Sonya, He, Mingzhu, Stošić-Grujičić, Stanislava, Stojanović, Ivana D., Al-Abed, Yousef, Saksida, Tamara, "Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death" in European Journal of Pharmacology, 740 (2014):683-689,
https://doi.org/10.1016/j.ejphar.2014.06.009 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Senerovic, Lidija
AU  - Nikolić, Ivana
AU  - Saksida, Tamara
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2171
AB  - Macrophage migration inhibitory factor (MIF) is a molecule with plethora
   of functions such as regulation of immune response, hormone-like,
   enzymatic and chaperone-like activity. Further, MIF is a major
   participant in glucose homeostasis since it is an autocrine stimulator
   of insulin secretion. MIF absence in male knockout mice (MW-MO) results
   in development of glucose intolerance, while sensitivity to insulin is
   fully preserved. Since our results confirm that beta cells from MIF-KO
   mice express, produce and secrete insulin similarly to beta cells of
   their wild type (WT) counterparts C57BL/6 mice, we hypothesize that
   MIF-KO-derived insulin is less active. Indeed, insulin from MIF-KO
   islets is unable to significantly induce glucose uptake into hepatocytes
   and to efficiently promote insulin-triggered Akt phosphorylation
   determined by immunoblot. However, MIF's tautomerase function is not
   crucial for insulin biosynthesis since MIF inhibitors had no impact on
   WT insulin activity. Importantly, MIF recognition by anti-MIF anti-body
   (ELISA) after in vitro co-incubation with purified insulin was
   significantly lower suggesting that insulin covers MIF immunodominant
   epitope. In addition, MIF binds insulin within beta cell as confirmed by
   co-immunoprecipitation. WT and MIF-KO-derived insulin exhibited
   different cleavage patterns suggesting different protein conformations.
   Finally, pre-incubation of recombinant MIF with insulin promotes
   formation of insulin hexamers. These results imply that MIF probably
   enables proper insulin folding what results in insulin full activity.
   This newly discovered feature of the cytokine MIF could be potentially
   important for commercially produced insulin, for increasing its
   stability and/or bioavailability. (C) 2014 Elsevier Ltd. All rights
   reserved.
T2  - Cytokine
T1  - The critical role of macrophage migration inhibitory factor in insulin
 activity
IS  - 1
VL  - 69
DO  - 10.1016/j.cyto.2014.05.013
SP  - 39
EP  - 46
ER  - 

@article{
author = "Vujičić, Milica and Senerovic, Lidija and Nikolić, Ivana and Saksida, Tamara and Stošić-Grujičić, Stanislava and Stojanović, Ivana D.",
year = "2014",
abstract = "Macrophage migration inhibitory factor (MIF) is a molecule with plethora
   of functions such as regulation of immune response, hormone-like,
   enzymatic and chaperone-like activity. Further, MIF is a major
   participant in glucose homeostasis since it is an autocrine stimulator
   of insulin secretion. MIF absence in male knockout mice (MW-MO) results
   in development of glucose intolerance, while sensitivity to insulin is
   fully preserved. Since our results confirm that beta cells from MIF-KO
   mice express, produce and secrete insulin similarly to beta cells of
   their wild type (WT) counterparts C57BL/6 mice, we hypothesize that
   MIF-KO-derived insulin is less active. Indeed, insulin from MIF-KO
   islets is unable to significantly induce glucose uptake into hepatocytes
   and to efficiently promote insulin-triggered Akt phosphorylation
   determined by immunoblot. However, MIF's tautomerase function is not
   crucial for insulin biosynthesis since MIF inhibitors had no impact on
   WT insulin activity. Importantly, MIF recognition by anti-MIF anti-body
   (ELISA) after in vitro co-incubation with purified insulin was
   significantly lower suggesting that insulin covers MIF immunodominant
   epitope. In addition, MIF binds insulin within beta cell as confirmed by
   co-immunoprecipitation. WT and MIF-KO-derived insulin exhibited
   different cleavage patterns suggesting different protein conformations.
   Finally, pre-incubation of recombinant MIF with insulin promotes
   formation of insulin hexamers. These results imply that MIF probably
   enables proper insulin folding what results in insulin full activity.
   This newly discovered feature of the cytokine MIF could be potentially
   important for commercially produced insulin, for increasing its
   stability and/or bioavailability. (C) 2014 Elsevier Ltd. All rights
   reserved.",
journal = "Cytokine",
title = "The critical role of macrophage migration inhibitory factor in insulin
 activity",
number = "1",
volume = "69",
doi = "10.1016/j.cyto.2014.05.013",
pages = "39-46"
}

Vujičić, M., Senerovic, L., Nikolić, I., Saksida, T., Stošić-Grujičić, S.,& Stojanović, I. D.. (2014). The critical role of macrophage migration inhibitory factor in insulin
 activity. in Cytokine, 69(1), 39-46.
https://doi.org/10.1016/j.cyto.2014.05.013

Vujičić M, Senerovic L, Nikolić I, Saksida T, Stošić-Grujičić S, Stojanović ID. The critical role of macrophage migration inhibitory factor in insulin
 activity. in Cytokine. 2014;69(1):39-46.
doi:10.1016/j.cyto.2014.05.013 .

Vujičić, Milica, Senerovic, Lidija, Nikolić, Ivana, Saksida, Tamara, Stošić-Grujičić, Stanislava, Stojanović, Ivana D., "The critical role of macrophage migration inhibitory factor in insulin
 activity" in Cytokine, 69, no. 1 (2014):39-46,
https://doi.org/10.1016/j.cyto.2014.05.013 . .