TY  - JOUR
AU  - Mićanović, Dragica
AU  - Lazarević, Milica
AU  - Kulaš, Jelena
AU  - Despotović, Sanja
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Koprivica, Ivan
AU  - Mirkov, Ivana
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6633
AB  - Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.
PB  - Elsevier B.V.
T2  - European Journal of Pharmacology
T1  - Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice
VL  - 971
DO  - 10.1016/j.ejphar.2024.176509
SP  - 176509
ER  - 

@article{
author = "Mićanović, Dragica and Lazarević, Milica and Kulaš, Jelena and Despotović, Sanja and Stegnjaić, Goran and Jevtić, Bojan and Koprivica, Ivan and Mirkov, Ivana and Stanisavljević, Suzana and Nikolovski, Neda and Miljković, Đorđe and Saksida, Tamara",
year = "2024",
abstract = "Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmacology",
title = "Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice",
volume = "971",
doi = "10.1016/j.ejphar.2024.176509",
pages = "176509"
}

Mićanović, D., Lazarević, M., Kulaš, J., Despotović, S., Stegnjaić, G., Jevtić, B., Koprivica, I., Mirkov, I., Stanisavljević, S., Nikolovski, N., Miljković, Đ.,& Saksida, T.. (2024). Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice. in European Journal of Pharmacology
Elsevier B.V.., 971, 176509.
https://doi.org/10.1016/j.ejphar.2024.176509

Mićanović D, Lazarević M, Kulaš J, Despotović S, Stegnjaić G, Jevtić B, Koprivica I, Mirkov I, Stanisavljević S, Nikolovski N, Miljković Đ, Saksida T. Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice. in European Journal of Pharmacology. 2024;971:176509.
doi:10.1016/j.ejphar.2024.176509 .

Mićanović, Dragica, Lazarević, Milica, Kulaš, Jelena, Despotović, Sanja, Stegnjaić, Goran, Jevtić, Bojan, Koprivica, Ivan, Mirkov, Ivana, Stanisavljević, Suzana, Nikolovski, Neda, Miljković, Đorđe, Saksida, Tamara, "Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice" in European Journal of Pharmacology, 971 (2024):176509,
https://doi.org/10.1016/j.ejphar.2024.176509 . .

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Lazarević, Milica
AU  - Kulaš, Jelena
AU  - Despotović, Sanja
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Koprivica, Ivan
AU  - Mirkov, Ivana
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6633
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6634
AB  - Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.
PB  - Elsevier B.V.
T2  - European Journal of Pharmacology
T1  - Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice
VL  - 971
DO  - 10.1016/j.ejphar.2024.176509
SP  - 176509
ER  - 

@article{
author = "Mićanović, Dragica and Lazarević, Milica and Kulaš, Jelena and Despotović, Sanja and Stegnjaić, Goran and Jevtić, Bojan and Koprivica, Ivan and Mirkov, Ivana and Stanisavljević, Suzana and Nikolovski, Neda and Miljković, Đorđe and Saksida, Tamara",
year = "2024",
abstract = "Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmacology",
title = "Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice",
volume = "971",
doi = "10.1016/j.ejphar.2024.176509",
pages = "176509"
}

Mićanović, D., Lazarević, M., Kulaš, J., Despotović, S., Stegnjaić, G., Jevtić, B., Koprivica, I., Mirkov, I., Stanisavljević, S., Nikolovski, N., Miljković, Đ.,& Saksida, T.. (2024). Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice. in European Journal of Pharmacology
Elsevier B.V.., 971, 176509.
https://doi.org/10.1016/j.ejphar.2024.176509

Mićanović D, Lazarević M, Kulaš J, Despotović S, Stegnjaić G, Jevtić B, Koprivica I, Mirkov I, Stanisavljević S, Nikolovski N, Miljković Đ, Saksida T. Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice. in European Journal of Pharmacology. 2024;971:176509.
doi:10.1016/j.ejphar.2024.176509 .

Mićanović, Dragica, Lazarević, Milica, Kulaš, Jelena, Despotović, Sanja, Stegnjaić, Goran, Jevtić, Bojan, Koprivica, Ivan, Mirkov, Ivana, Stanisavljević, Suzana, Nikolovski, Neda, Miljković, Đorđe, Saksida, Tamara, "Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice" in European Journal of Pharmacology, 971 (2024):176509,
https://doi.org/10.1016/j.ejphar.2024.176509 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Despotović, Sanja
AU  - Ignjatović, Đurđica
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Fraser, Graeme L
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6501
AB  - Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.
PB  - Springer Nature
T2  - Journal of Neuroinflammation
T1  - Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity
VL  - 21
DO  - 10.1186/s12974-024-03017-7
SP  - 26
ER  - 

@article{
author = "Lazarević, Milica and Stegnjaić, Goran and Jevtić, Bojan and Despotović, Sanja and Ignjatović, Đurđica and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Fraser, Graeme L and Dimitrijević, Mirjana and Miljković, Đorđe",
year = "2024",
abstract = "Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.",
publisher = "Springer Nature",
journal = "Journal of Neuroinflammation",
title = "Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity",
volume = "21",
doi = "10.1186/s12974-024-03017-7",
pages = "26"
}

Lazarević, M., Stegnjaić, G., Jevtić, B., Despotović, S., Ignjatović, Đ., Stanisavljević, S., Nikolovski, N., Momčilović, M., Fraser, G. L., Dimitrijević, M.,& Miljković, Đ.. (2024). Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity. in Journal of Neuroinflammation
Springer Nature., 21, 26.
https://doi.org/10.1186/s12974-024-03017-7

Lazarević M, Stegnjaić G, Jevtić B, Despotović S, Ignjatović Đ, Stanisavljević S, Nikolovski N, Momčilović M, Fraser GL, Dimitrijević M, Miljković Đ. Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity. in Journal of Neuroinflammation. 2024;21:26.
doi:10.1186/s12974-024-03017-7 .

Lazarević, Milica, Stegnjaić, Goran, Jevtić, Bojan, Despotović, Sanja, Ignjatović, Đurđica, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Fraser, Graeme L, Dimitrijević, Mirjana, Miljković, Đorđe, "Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity" in Journal of Neuroinflammation, 21 (2024):26,
https://doi.org/10.1186/s12974-024-03017-7 . .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Nikolovski, Neda
AU  - Koprivica, Ivan
AU  - Despotović, Sanja
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Momčilović, Miljana
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5770
AB  - Примена етил-пирувата у третману аутоимунских болести је испитивана
у анималним моделима дијабетеса типа 1, мултипле склерозе и
миокардитиса. Показало се да етил-пируват ефикасно делује против
аутоимунских процеса и следствено доводи до побољшања клиничке
слике у овим моделима. Као главне мете деловања овог једињења
идентификоване су дендритске ћелије и Т лимфоцити. Утврђено је да
етил пируват потенцира толерогена својства денритских ћелија, као и
регулаторне Т лимфоците, a да инхибира ефекторске функције макрофага
и ограничава активацију и функцију ефекторских Т лимфоцита.
Инхибиторно дејство етил-пирувата на аутоимунске процесе је остварено
захваљујући његовим редокс и метаболичким ефектима, а пре свега
посредством његове интеракције са молекулом ХМГБ1. Имајући у виду да
су претходна истраживања показала да је примена етил-пирувата у људи
безбедна, будућа истраживања би морала бити усмерена ка транслацији
сазнања стечених у анималним моделима на терапијску примену овог
једињења у аутоимунским болестима.
AB  - Primena etil-piruvata u tretmanu autoimunskih bolesti je ispitivana u animalnim modelima dijabetesa tipa 1, multiple skleroze i miokarditisa. Pokazalo se da etil-piruvat efikasno deluje protiv autoimunskih procesa i sledstveno dovodi do poboljšanja kliničke slike u ovim modelima. Kao glavne mete delovanja ovog jedinjenja identifikovane su dendritske ćelije i T limfociti. Utvrđeno je da etil piruvat potencira tolerogena svojstva denritskih ćelija, kao i regulatorne T limfocite, a da inhibira efektorske funkcije makrofaga i ograničava aktivaciju i funkciju efektorskih T limfocita. Inhibitorno dejstvo etil-piruvata na autoimunske procese je ostvareno zahvaljujući njegovim redoks i metaboličkim efektima, a pre svega posredstvom njegove interakcije sa molekulom HMGB1. Imajući u vidu da su prethodna istraživanja pokazala da je primena etil-piruvata u ljudi bezbedna, buduća istraživanja bi morala biti usmerena ka translaciji saznanja stečenih u animalnim modelima na terapijsku primenu ovog jedinjenja u autoimunskim bolestima.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia
T1  - Etil-piruvat i autoimunske bolesti
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5770
ER  - 

@conference{
author = "Mićanović, Dragica and Nikolovski, Neda and Koprivica, Ivan and Despotović, Sanja and Jevtić, Bojan and Stanisavljević, Suzana and Momčilović, Miljana and Pejnović, Nada and Stojanović, Ivana D. and Miljković, Đorđe and Saksida, Tamara",
year = "2022",
abstract = "Примена етил-пирувата у третману аутоимунских болести је испитивана
у анималним моделима дијабетеса типа 1, мултипле склерозе и
миокардитиса. Показало се да етил-пируват ефикасно делује против
аутоимунских процеса и следствено доводи до побољшања клиничке
слике у овим моделима. Као главне мете деловања овог једињења
идентификоване су дендритске ћелије и Т лимфоцити. Утврђено је да
етил пируват потенцира толерогена својства денритских ћелија, као и
регулаторне Т лимфоците, a да инхибира ефекторске функције макрофага
и ограничава активацију и функцију ефекторских Т лимфоцита.
Инхибиторно дејство етил-пирувата на аутоимунске процесе је остварено
захваљујући његовим редокс и метаболичким ефектима, а пре свега
посредством његове интеракције са молекулом ХМГБ1. Имајући у виду да
су претходна истраживања показала да је примена етил-пирувата у људи
безбедна, будућа истраживања би морала бити усмерена ка транслацији
сазнања стечених у анималним моделима на терапијску примену овог
једињења у аутоимунским болестима., Primena etil-piruvata u tretmanu autoimunskih bolesti je ispitivana u animalnim modelima dijabetesa tipa 1, multiple skleroze i miokarditisa. Pokazalo se da etil-piruvat efikasno deluje protiv autoimunskih procesa i sledstveno dovodi do poboljšanja kliničke slike u ovim modelima. Kao glavne mete delovanja ovog jedinjenja identifikovane su dendritske ćelije i T limfociti. Utvrđeno je da etil piruvat potencira tolerogena svojstva denritskih ćelija, kao i regulatorne T limfocite, a da inhibira efektorske funkcije makrofaga i ograničava aktivaciju i funkciju efektorskih T limfocita. Inhibitorno dejstvo etil-piruvata na autoimunske procese je ostvareno zahvaljujući njegovim redoks i metaboličkim efektima, a pre svega posredstvom njegove interakcije sa molekulom HMGB1. Imajući u vidu da su prethodna istraživanja pokazala da je primena etil-piruvata u ljudi bezbedna, buduća istraživanja bi morala biti usmerena ka translaciji saznanja stečenih u animalnim modelima na terapijsku primenu ovog jedinjenja u autoimunskim bolestima.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia",
title = "Etil-piruvat i autoimunske bolesti",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5770"
}

Mićanović, D., Nikolovski, N., Koprivica, I., Despotović, S., Jevtić, B., Stanisavljević, S., Momčilović, M., Pejnović, N., Stojanović, I. D., Miljković, Đ.,& Saksida, T.. (2022). Etil-piruvat i autoimunske bolesti. in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5770

Mićanović D, Nikolovski N, Koprivica I, Despotović S, Jevtić B, Stanisavljević S, Momčilović M, Pejnović N, Stojanović ID, Miljković Đ, Saksida T. Etil-piruvat i autoimunske bolesti. in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5770 .

Mićanović, Dragica, Nikolovski, Neda, Koprivica, Ivan, Despotović, Sanja, Jevtić, Bojan, Stanisavljević, Suzana, Momčilović, Miljana, Pejnović, Nada, Stojanović, Ivana D., Miljković, Đorđe, Saksida, Tamara, "Etil-piruvat i autoimunske bolesti" in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5770 .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Šavikin, Katarina
AU  - Šenerović, Lidija
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5779
AB  - Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually
exhibit cardioprotective, anti-viral and anti-bacterial properties1. Our aim was to
investigate the effects of CE on the immune response in vivo and in vitro, which have been
only sporadically assessed. CE, administered orally to healthy mice, exerted
immunomodulatory effects in the gut, evidenced by the altered proportion of macrophages
(Mφ), dendritic cells (DC) and T cells. CE-pretreated BALB/c mice readily eradicated
orally ingested Listeria monocytogenes due to higher proportions of Mφ and CD8 T cells
both in the gut and spleen. Additionally, phagocytosis, ROS production and the
proportions of activated Mφ and DC, as well as perforin+ cells were enhanced in CEpretreated
infected mice. Also, CE pretreatment of C57BL/6 mice inoculated with B16
cells delayed melanoma appearance and increased infiltration of immune cells in the tumor
microenvironment (TME). The TME of CE-treated mice contained more IFN-γ+ cells and
a less of tumor-promoting CCR5+ MDSC. In vitro, CE displayed no direct cytotoxicity to
B16 cells. Splenocytes isolated from CE-treated animals exerted strong cytotoxic effect on
B16 cells and this effect was diminished by neutralization of IFN-γ. In conclusion, the CE
exhibits strong immunomodulatory properties and should be consumed with care.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma
SP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5779
ER  - 

@conference{
author = "Mićanović, Dragica and Koprivica, Ivan and Šavikin, Katarina and Šenerović, Lidija and Despotović, Sanja and Pejnović, Nada and Stojanović, Ivana D. and Saksida, Tamara",
year = "2022",
abstract = "Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually
exhibit cardioprotective, anti-viral and anti-bacterial properties1. Our aim was to
investigate the effects of CE on the immune response in vivo and in vitro, which have been
only sporadically assessed. CE, administered orally to healthy mice, exerted
immunomodulatory effects in the gut, evidenced by the altered proportion of macrophages
(Mφ), dendritic cells (DC) and T cells. CE-pretreated BALB/c mice readily eradicated
orally ingested Listeria monocytogenes due to higher proportions of Mφ and CD8 T cells
both in the gut and spleen. Additionally, phagocytosis, ROS production and the
proportions of activated Mφ and DC, as well as perforin+ cells were enhanced in CEpretreated
infected mice. Also, CE pretreatment of C57BL/6 mice inoculated with B16
cells delayed melanoma appearance and increased infiltration of immune cells in the tumor
microenvironment (TME). The TME of CE-treated mice contained more IFN-γ+ cells and
a less of tumor-promoting CCR5+ MDSC. In vitro, CE displayed no direct cytotoxicity to
B16 cells. Splenocytes isolated from CE-treated animals exerted strong cytotoxic effect on
B16 cells and this effect was diminished by neutralization of IFN-γ. In conclusion, the CE
exhibits strong immunomodulatory properties and should be consumed with care.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma",
pages = "98",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5779"
}

Mićanović, D., Koprivica, I., Šavikin, K., Šenerović, L., Despotović, S., Pejnović, N., Stojanović, I. D.,& Saksida, T.. (2022). Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 98.
https://hdl.handle.net/21.15107/rcub_ibiss_5779

Mićanović D, Koprivica I, Šavikin K, Šenerović L, Despotović S, Pejnović N, Stojanović ID, Saksida T. Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:98.
https://hdl.handle.net/21.15107/rcub_ibiss_5779 .

Mićanović, Dragica, Koprivica, Ivan, Šavikin, Katarina, Šenerović, Lidija, Despotović, Sanja, Pejnović, Nada, Stojanović, Ivana D., Saksida, Tamara, "Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):98,
https://hdl.handle.net/21.15107/rcub_ibiss_5779 .

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  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5781
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
regulatory immune mechanisms that would attenuate disease progression
have shown little or no beneficial effects. We introduced microparticles (MPs) loaded
with Transforming Growth Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA),
both known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower and was accompanied by down-regulation
in the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.
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  - ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice
SP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5781
ER  - 

@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2021",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
regulatory immune mechanisms that would attenuate disease progression
have shown little or no beneficial effects. We introduced microparticles (MPs) loaded
with Transforming Growth Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA),
both known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower and was accompanied by down-regulation
in the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.",
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 = "ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5781"
}

Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2021). ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice. 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., 100.
https://hdl.handle.net/21.15107/rcub_ibiss_5781

Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2021;:100.
https://hdl.handle.net/21.15107/rcub_ibiss_5781 .

Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2021):100,
https://hdl.handle.net/21.15107/rcub_ibiss_5781 .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Despotović, Sanja
AU  - Jonić, Natalija
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5776
AB  - Ethyl pyruvate (EP) has profound anti-inflammatory and immunomodulatory properties. Here, its effects on experimental autoimmune myocarditis (EAM) induced in mice by heart-specific myosin-alpha heavy chain peptide immunization were determined. EP was applied intraperitoneally, daily, starting with the immunization. Severity of EAM was determined by histological assessment of immune cell infiltrates into the heart at day 21 post immunization. Cells were phenotypically characterized by flow cytometry. Concentration of cytokines in cell culture supernatants and sera was determined by ELISA. EP reduced infiltration of immune cells into the heart and lessened heart inflammation. Smaller number of total immune cells, as well as of CD4+ T cells, CD11b+ and CD11c+ cells was isolated from the hearts of EP-treated mice. Reduced number of antigen-presenting cells, detected by CD11c, MHC class II, and CD86 antibodies, as well as of T helper (Th)1 and Th17 cells, detected by CD4, IFN- and IL-17 antibodies, was determined in mediastinal lymph nodes draining the heart, in parallel. The number of CD11c+, CD11c+MHC class II+, and CD11c+CD86+ cells was reduced in the spleen, as well. Lower production of IFN- and IL-17 by cells of the lymph nodes draining the site of immunization in response to the immunizing antigen was observed in EP-treated mice. Our results clearly imply that EP restrains autoimmunity in EAM. EP-based therapy for the treatment of myocarditis in humans should be investigated in the forthcoming studies.
PB  - John Wiley and Sons Inc
C3  - 6th European Congress of Immunology
T1  - Ethyl pyruvate ameliorates experimental autoimmune myocarditis
DO  - 10.1002/eji.202170200
SP  - 386
ER  - 

@conference{
author = "Mićanović, Dragica and Koprivica, Ivan and Despotović, Sanja and Jonić, Natalija and Pejnović, Nada and Stojanović, Ivana D. and Miljković, Đorđe and Saksida, Tamara",
year = "2021",
abstract = "Ethyl pyruvate (EP) has profound anti-inflammatory and immunomodulatory properties. Here, its effects on experimental autoimmune myocarditis (EAM) induced in mice by heart-specific myosin-alpha heavy chain peptide immunization were determined. EP was applied intraperitoneally, daily, starting with the immunization. Severity of EAM was determined by histological assessment of immune cell infiltrates into the heart at day 21 post immunization. Cells were phenotypically characterized by flow cytometry. Concentration of cytokines in cell culture supernatants and sera was determined by ELISA. EP reduced infiltration of immune cells into the heart and lessened heart inflammation. Smaller number of total immune cells, as well as of CD4+ T cells, CD11b+ and CD11c+ cells was isolated from the hearts of EP-treated mice. Reduced number of antigen-presenting cells, detected by CD11c, MHC class II, and CD86 antibodies, as well as of T helper (Th)1 and Th17 cells, detected by CD4, IFN- and IL-17 antibodies, was determined in mediastinal lymph nodes draining the heart, in parallel. The number of CD11c+, CD11c+MHC class II+, and CD11c+CD86+ cells was reduced in the spleen, as well. Lower production of IFN- and IL-17 by cells of the lymph nodes draining the site of immunization in response to the immunizing antigen was observed in EP-treated mice. Our results clearly imply that EP restrains autoimmunity in EAM. EP-based therapy for the treatment of myocarditis in humans should be investigated in the forthcoming studies.",
publisher = "John Wiley and Sons Inc",
journal = "6th European Congress of Immunology",
title = "Ethyl pyruvate ameliorates experimental autoimmune myocarditis",
doi = "10.1002/eji.202170200",
pages = "386"
}

Mićanović, D., Koprivica, I., Despotović, S., Jonić, N., Pejnović, N., Stojanović, I. D., Miljković, Đ.,& Saksida, T.. (2021). Ethyl pyruvate ameliorates experimental autoimmune myocarditis. in 6th European Congress of Immunology
John Wiley and Sons Inc., 386.
https://doi.org/10.1002/eji.202170200

Mićanović D, Koprivica I, Despotović S, Jonić N, Pejnović N, Stojanović ID, Miljković Đ, Saksida T. Ethyl pyruvate ameliorates experimental autoimmune myocarditis. in 6th European Congress of Immunology. 2021;:386.
doi:10.1002/eji.202170200 .

Mićanović, Dragica, Koprivica, Ivan, Despotović, Sanja, Jonić, Natalija, Pejnović, Nada, Stojanović, Ivana D., Miljković, Đorđe, Saksida, Tamara, "Ethyl pyruvate ameliorates experimental autoimmune myocarditis" in 6th European Congress of Immunology (2021):386,
https://doi.org/10.1002/eji.202170200 . .

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Despotović, Sanja
AU  - Koprivica, Ivan
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4672
AB  - Ethyl pyruvate (EP) has profound anti-inflammatory and immunomodulatory properties.
Here, its effects were determined on experimental autoimmune myocarditis (EAM) induced in mice
by heart-specific myosin-alpha heavy chain peptide immunization. EP was applied intraperitoneally,
daily, starting with the immunization. Severity of EAM was determined by histological assessment
of immune cell infiltrates into the heart. Cells were phenotypically characterized by flow cytometry.
Concentration of cytokines in cell culture supernatants and sera was determined by ELISA.
EP reduced the infiltration of immune cells into the heart and lessened heart inflammation. Smaller
number of total immune cells, as well as of CD11b+ and CD11c+ cells were isolated from the hearts of
EP-treated mice. A reduced number of antigen-presenting cells, detected by anti-CD11c, MHC class
II and CD86 antibodies, as well as of T helper (Th)1 and Th17 cells, detected by anti-CD4, IFN-
 and
IL-17 antibodies, was determined in mediastinal lymph nodes draining the heart, in parallel. In the
spleen, only the number of CD11c+ cells were reduced, but not of the other examined populations,
thus implying limited systemic effect of EP. Reduced production of IFN-
 and IL-17 by myosin-alpha
heavy chain peptide-restimulated cells of the lymph nodes draining the site of immunization was
observed in EP-treated mice. Our results clearly imply that EP restrains autoimmunity in EAM.
Therapeutic application of EP in the treatment of myocarditis in humans should be addressed in the
forthcoming studies.
PB  - Basel: MDPI
T2  - Biomolecules
T1  - Ethyl Pyruvate Ameliorates Experimental Autoimmune Myocarditis
IS  - 12
VL  - 11
DO  - 10.3390/biom11121768
SP  - 1768
ER  - 

@article{
author = "Mićanović, Dragica and Despotović, Sanja and Koprivica, Ivan and Miljković, Đorđe and Saksida, Tamara",
year = "2021",
abstract = "Ethyl pyruvate (EP) has profound anti-inflammatory and immunomodulatory properties.
Here, its effects were determined on experimental autoimmune myocarditis (EAM) induced in mice
by heart-specific myosin-alpha heavy chain peptide immunization. EP was applied intraperitoneally,
daily, starting with the immunization. Severity of EAM was determined by histological assessment
of immune cell infiltrates into the heart. Cells were phenotypically characterized by flow cytometry.
Concentration of cytokines in cell culture supernatants and sera was determined by ELISA.
EP reduced the infiltration of immune cells into the heart and lessened heart inflammation. Smaller
number of total immune cells, as well as of CD11b+ and CD11c+ cells were isolated from the hearts of
EP-treated mice. A reduced number of antigen-presenting cells, detected by anti-CD11c, MHC class
II and CD86 antibodies, as well as of T helper (Th)1 and Th17 cells, detected by anti-CD4, IFN-
 and
IL-17 antibodies, was determined in mediastinal lymph nodes draining the heart, in parallel. In the
spleen, only the number of CD11c+ cells were reduced, but not of the other examined populations,
thus implying limited systemic effect of EP. Reduced production of IFN-
 and IL-17 by myosin-alpha
heavy chain peptide-restimulated cells of the lymph nodes draining the site of immunization was
observed in EP-treated mice. Our results clearly imply that EP restrains autoimmunity in EAM.
Therapeutic application of EP in the treatment of myocarditis in humans should be addressed in the
forthcoming studies.",
publisher = "Basel: MDPI",
journal = "Biomolecules",
title = "Ethyl Pyruvate Ameliorates Experimental Autoimmune Myocarditis",
number = "12",
volume = "11",
doi = "10.3390/biom11121768",
pages = "1768"
}

Mićanović, D., Despotović, S., Koprivica, I., Miljković, Đ.,& Saksida, T.. (2021). Ethyl Pyruvate Ameliorates Experimental Autoimmune Myocarditis. in Biomolecules
Basel: MDPI., 11(12), 1768.
https://doi.org/10.3390/biom11121768

Mićanović D, Despotović S, Koprivica I, Miljković Đ, Saksida T. Ethyl Pyruvate Ameliorates Experimental Autoimmune Myocarditis. in Biomolecules. 2021;11(12):1768.
doi:10.3390/biom11121768 .

Mićanović, Dragica, Despotović, Sanja, Koprivica, Ivan, Miljković, Đorđe, Saksida, Tamara, "Ethyl Pyruvate Ameliorates Experimental Autoimmune Myocarditis" in Biomolecules, 11, no. 12 (2021):1768,
https://doi.org/10.3390/biom11121768 . .

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  - Martinović, Tamara
AU  - Ćirić, Darko
AU  - Pantić, Igor
AU  - Lalić, Katarina
AU  - Rasulić, Iva
AU  - Despotović, Sanja
AU  - Lalić, Ivana
AU  - Đuričić, Danica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Trajković, Vladimir
AU  - Bumbaširević, Vladimir
AU  - Kravić-Stevović, Tamara
PY  - 2019
UR  - https://klinbiolabmed.rs/wp-content/uploads/2022/05/Knjiga-sazetka-Kongresa.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6662
AB  - Uvod: Osobine tip 2 dijabetes melitusa (T2DM) su insulinska rezistencija, poremećena sekrecija insulina i hiperglikemija. Kao početna terapija T2DM koristi se metformin. Novija istraživanja su pokazala da u T2DM dolazi do morfoloških promena u izgledu nukleusa u vidu nepravilnosti oblika i binukelacije nukleusa.
Cilj: Cilj istraživanja je da se analiziraju ultrastrukturne karakteristike nukleusa limfocita periferne krvi kod pacijenata sa T2DM pomoću kompjuterizovane analize slike, fraktalne i teksturalne analize, kao i utvrđivanje efekta metformina na karakteristike nukleusa.
Metodologija: Mononuklearne ćelije izolovane iz periferne krvi novootkrivenih T2DM bolesnika, bolesnika lečenih metforminom i zdravih ispitanika analizirane su na transmisionom elektronskom mikroskopu (TEM). Primenom ImageJ programa analizirani su oblik i procenat heterohromatina, kao i fraktalna i teksturalna analiza nukleusa limfocita.
Rezultati: Limfociti zdravih osoba su imali okrugle, predominantno heterohromatične nukleuse i malu količinu citoplazme sa retko prisutnim organelama, dok su limfociti T2DM bolesnika imali euhromatične nukleu uz povećanje strukturnih praznina kod T2DM bolesnika. Nivo glukoze našte i HbA1c koreliraju sa fraktalnom dimenzijom i sa parametrima oblika nukleusa. Postoji korelacija između nivoa triglicerida u krvi i fraktalne dimenzije nukleusa.
Zaključak: Nukleusi limfocita bolesnika sa T2DM su nepravilnog oblika i sa većom količinom euhromatina, a promena njihovog izgleda je u vezi sa nivoom glikemije.
PB  - Beograd: Srpsko lekarsko društvo, Sekcija kliničke biohemije
C3  - Knjiga sažetaka: 1. kongres kliničkih biohemičara i specijalista laboratorijske medicine Srbije sa međunarodnim učešćem;  2019 Nov 27-29; Belgrade, Serbia
T1  - Uticaj glikemije i lipidnog statusa na morfološke karakteristike nukleusa kod pacijenata sa tip 2 dijabetes melitusom
SP  - 58
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6662
ER  - 

@conference{
author = "Martinović, Tamara and Ćirić, Darko and Pantić, Igor and Lalić, Katarina and Rasulić, Iva and Despotović, Sanja and Lalić, Ivana and Đuričić, Danica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Trajković, Vladimir and Bumbaširević, Vladimir and Kravić-Stevović, Tamara",
year = "2019",
abstract = "Uvod: Osobine tip 2 dijabetes melitusa (T2DM) su insulinska rezistencija, poremećena sekrecija insulina i hiperglikemija. Kao početna terapija T2DM koristi se metformin. Novija istraživanja su pokazala da u T2DM dolazi do morfoloških promena u izgledu nukleusa u vidu nepravilnosti oblika i binukelacije nukleusa.
Cilj: Cilj istraživanja je da se analiziraju ultrastrukturne karakteristike nukleusa limfocita periferne krvi kod pacijenata sa T2DM pomoću kompjuterizovane analize slike, fraktalne i teksturalne analize, kao i utvrđivanje efekta metformina na karakteristike nukleusa.
Metodologija: Mononuklearne ćelije izolovane iz periferne krvi novootkrivenih T2DM bolesnika, bolesnika lečenih metforminom i zdravih ispitanika analizirane su na transmisionom elektronskom mikroskopu (TEM). Primenom ImageJ programa analizirani su oblik i procenat heterohromatina, kao i fraktalna i teksturalna analiza nukleusa limfocita.
Rezultati: Limfociti zdravih osoba su imali okrugle, predominantno heterohromatične nukleuse i malu količinu citoplazme sa retko prisutnim organelama, dok su limfociti T2DM bolesnika imali euhromatične nukleu uz povećanje strukturnih praznina kod T2DM bolesnika. Nivo glukoze našte i HbA1c koreliraju sa fraktalnom dimenzijom i sa parametrima oblika nukleusa. Postoji korelacija između nivoa triglicerida u krvi i fraktalne dimenzije nukleusa.
Zaključak: Nukleusi limfocita bolesnika sa T2DM su nepravilnog oblika i sa većom količinom euhromatina, a promena njihovog izgleda je u vezi sa nivoom glikemije.",
publisher = "Beograd: Srpsko lekarsko društvo, Sekcija kliničke biohemije",
journal = "Knjiga sažetaka: 1. kongres kliničkih biohemičara i specijalista laboratorijske medicine Srbije sa međunarodnim učešćem;  2019 Nov 27-29; Belgrade, Serbia",
title = "Uticaj glikemije i lipidnog statusa na morfološke karakteristike nukleusa kod pacijenata sa tip 2 dijabetes melitusom",
pages = "58",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6662"
}

Martinović, T., Ćirić, D., Pantić, I., Lalić, K., Rasulić, I., Despotović, S., Lalić, I., Đuričić, D., Vučićević, L., Misirkić Marjanović, M., Trajković, V., Bumbaširević, V.,& Kravić-Stevović, T.. (2019). Uticaj glikemije i lipidnog statusa na morfološke karakteristike nukleusa kod pacijenata sa tip 2 dijabetes melitusom. in Knjiga sažetaka: 1. kongres kliničkih biohemičara i specijalista laboratorijske medicine Srbije sa međunarodnim učešćem;  2019 Nov 27-29; Belgrade, Serbia
Beograd: Srpsko lekarsko društvo, Sekcija kliničke biohemije., 58.
https://hdl.handle.net/21.15107/rcub_ibiss_6662

Martinović T, Ćirić D, Pantić I, Lalić K, Rasulić I, Despotović S, Lalić I, Đuričić D, Vučićević L, Misirkić Marjanović M, Trajković V, Bumbaširević V, Kravić-Stevović T. Uticaj glikemije i lipidnog statusa na morfološke karakteristike nukleusa kod pacijenata sa tip 2 dijabetes melitusom. in Knjiga sažetaka: 1. kongres kliničkih biohemičara i specijalista laboratorijske medicine Srbije sa međunarodnim učešćem;  2019 Nov 27-29; Belgrade, Serbia. 2019;:58.
https://hdl.handle.net/21.15107/rcub_ibiss_6662 .

Martinović, Tamara, Ćirić, Darko, Pantić, Igor, Lalić, Katarina, Rasulić, Iva, Despotović, Sanja, Lalić, Ivana, Đuričić, Danica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Trajković, Vladimir, Bumbaširević, Vladimir, Kravić-Stevović, Tamara, "Uticaj glikemije i lipidnog statusa na morfološke karakteristike nukleusa kod pacijenata sa tip 2 dijabetes melitusom" in Knjiga sažetaka: 1. kongres kliničkih biohemičara i specijalista laboratorijske medicine Srbije sa međunarodnim učešćem;  2019 Nov 27-29; Belgrade, Serbia (2019):58,
https://hdl.handle.net/21.15107/rcub_ibiss_6662 .

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5778
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response
causes the death of pancreatic β-cells. Attempts to induce anti-inflammatory/regulatory
immune mechanisms that would attenuate disease progression have shown little or no
beneficial effects. We introduced microparticles (MPs) loaded with Transforming Growth
Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA), both well-known stimulators of T
regulatory cell (Treg) differentiation and stabilization. Male C57BL/6 mice were treated
with multiple low doses of streptozotocin for T1D induction, and with vehicle, empty MPs,
or ATRA- and TGF-β-loaded MPs for 10 days (every other day). Both T1D incidence and
immune cell infiltration into the pancreatic islets was lower in ATRA/TGF-β-treated mice.
In Peyer’s patches (PP), ATRA/TGF-β up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β e xpression was r educed i n P P, a s w as t he r atio o f i NOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by a
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower, and was accompanied by down-regulation in
RORγt expression (key transcription factor of IL-17). The situation in the pancreatic
lymph nodes (PLN) was similar to PP regarding the down-regulation of Th1 cells.
Additionally, in response to ATRA/TGF-β treatment, the proliferation of T effector cells
was reduced in PLN, while Treg proliferated more, and several crucial markers of Treg
suppressive activity were increased. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg responses and inhibition of
Th1 cell differentiation in the draining lymph nodes, thus blocking the entrance of immune
cells into the pancreatic islets and protecting β-cells from further destruction.
PB  - Belgrade: Faculty of Chemistry
C3  - The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.
T1  - Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles
SP  - 113
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5778
ER  - 

@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando 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 pancreatic β-cells. Attempts to induce anti-inflammatory/regulatory
immune mechanisms that would attenuate disease progression have shown little or no
beneficial effects. We introduced microparticles (MPs) loaded with Transforming Growth
Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA), both well-known stimulators of T
regulatory cell (Treg) differentiation and stabilization. Male C57BL/6 mice were treated
with multiple low doses of streptozotocin for T1D induction, and with vehicle, empty MPs,
or ATRA- and TGF-β-loaded MPs for 10 days (every other day). Both T1D incidence and
immune cell infiltration into the pancreatic islets was lower in ATRA/TGF-β-treated mice.
In Peyer’s patches (PP), ATRA/TGF-β up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β e xpression was r educed i n P P, a s w as t he r atio o f i NOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by a
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower, and was accompanied by down-regulation in
RORγt expression (key transcription factor of IL-17). The situation in the pancreatic
lymph nodes (PLN) was similar to PP regarding the down-regulation of Th1 cells.
Additionally, in response to ATRA/TGF-β treatment, the proliferation of T effector cells
was reduced in PLN, while Treg proliferated more, and several crucial markers of Treg
suppressive activity were increased. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg responses and inhibition of
Th1 cell differentiation in the draining lymph nodes, thus blocking the entrance of immune
cells into the pancreatic islets and protecting β-cells from further destruction.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.",
title = "Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles",
pages = "113",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5778"
}

Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2019). Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.
Belgrade: Faculty of Chemistry., 113.
https://hdl.handle.net/21.15107/rcub_ibiss_5778

Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.. 2019;:113.
https://hdl.handle.net/21.15107/rcub_ibiss_5778 .

Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles" in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia. (2019):113,
https://hdl.handle.net/21.15107/rcub_ibiss_5778 .

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0014299919306739?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3486
AB  - Type 1 diabetes (T1D) is a multifactorial autoimmune disease that develops as a consequence of macrophage- and T cell-dependent pancreatic β-cell death. Multiple approaches for induction of anti-inflammatory/regulatory mechanisms that would attenuate T1D have been utilized, with little or no beneficial effects. To achieve prolonged stimulation of regulatory immune cells, we orally introduced microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and transforming growth factor-β (TGF-β) to C57BL/6 mice treated with multiple low doses of streptozotocin (MLDS) for T1D induction. Disease incidence was significantly lower in ATRA/TGF-β MPs-treated mice, as was the degree of immune cell infiltration into the pancreatic islets. In Peyer's patches (PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDCs) (CD11c+CD11b-CD103+), while the proportion of mature dendritic cells was not altered. This was accompanied by reduced Th1 and Th17 proportions and up-regulation of regulatory T cells (Tregs - CD4+CD25highFoxP3+). The immune cell composition in the pancreatic lymph nodes was similar to PP. Further, the proportion of effector Tbet+CD25med cells was decreased, while the proportion of Tbet+ Treg cells that specifically inhibit Th1 response was increased. Moreover, ATRA/TGF-β MPs treatment resulted in increased Treg proliferation and frequency of CTLA-4+PD1+ and CD39+IL-10+ Tregs, suggestive of their higher suppressive capacity. Reduced pancreatic infiltration may have been a consequence of lower cell capacity for matrix degradation. In conclusion, oral application of ATRA/TGF-β MPs ameliorated T1D through potentiation of tolDCs and Tregs, inhibition of Th1 response and prevention of the immune cell entrance into the islets.
T2  - European Journal of Pharmacology
T1  - Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice
VL  - 864
DO  - 10.1016/j.ejphar.2019.172721
SP  - 172721
ER  - 

@article{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2019",
abstract = "Type 1 diabetes (T1D) is a multifactorial autoimmune disease that develops as a consequence of macrophage- and T cell-dependent pancreatic β-cell death. Multiple approaches for induction of anti-inflammatory/regulatory mechanisms that would attenuate T1D have been utilized, with little or no beneficial effects. To achieve prolonged stimulation of regulatory immune cells, we orally introduced microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and transforming growth factor-β (TGF-β) to C57BL/6 mice treated with multiple low doses of streptozotocin (MLDS) for T1D induction. Disease incidence was significantly lower in ATRA/TGF-β MPs-treated mice, as was the degree of immune cell infiltration into the pancreatic islets. In Peyer's patches (PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDCs) (CD11c+CD11b-CD103+), while the proportion of mature dendritic cells was not altered. This was accompanied by reduced Th1 and Th17 proportions and up-regulation of regulatory T cells (Tregs - CD4+CD25highFoxP3+). The immune cell composition in the pancreatic lymph nodes was similar to PP. Further, the proportion of effector Tbet+CD25med cells was decreased, while the proportion of Tbet+ Treg cells that specifically inhibit Th1 response was increased. Moreover, ATRA/TGF-β MPs treatment resulted in increased Treg proliferation and frequency of CTLA-4+PD1+ and CD39+IL-10+ Tregs, suggestive of their higher suppressive capacity. Reduced pancreatic infiltration may have been a consequence of lower cell capacity for matrix degradation. In conclusion, oral application of ATRA/TGF-β MPs ameliorated T1D through potentiation of tolDCs and Tregs, inhibition of Th1 response and prevention of the immune cell entrance into the islets.",
journal = "European Journal of Pharmacology",
title = "Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice",
volume = "864",
doi = "10.1016/j.ejphar.2019.172721",
pages = "172721"
}

Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2019). Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice. in European Journal of Pharmacology, 864, 172721.
https://doi.org/10.1016/j.ejphar.2019.172721

Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice. in European Journal of Pharmacology. 2019;864:172721.
doi:10.1016/j.ejphar.2019.172721 .

Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice" in European Journal of Pharmacology, 864 (2019):172721,
https://doi.org/10.1016/j.ejphar.2019.172721 . .

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  - 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  - JOUR
AU  - Lalić, Ivana M.
AU  - Bichele, Rudolf
AU  - Repar, Anja
AU  - Despotović, Sanja Z.
AU  - Petričević, Saša
AU  - Laan, Martti
AU  - Peterson, Pärt
AU  - Westermann, Jürgen
AU  - Milićević, Živana
AU  - Mirkov, Ivana
AU  - Milićević, Novica M.
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S0940960217301553?via%3Dihub
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29289711
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3020
AB  - It is well known that bacterial lipopolysaccharide (LPS) induces migration of several cellular populations within the spleen. However, there are no data about the impact of LPS on B and T lymphocytes present in the red pulp. Therefore, we used an experimental model in which we tested the effects of intravenously injected LPS on the molecular, cellular and structural changes of the spleen, with special reference to the red pulp lymphocytes. We discovered that LPS induced a massive relocation of B and T lymphocytes from the splenic red pulp, which was independent of the tumor necrosis factor receptor-1 signaling axis. Early after LPS treatment, quantitative real-time PCR analysis revealed the elevated levels of mRNA encoding numerous chemokines and proinflammatory cytokines (XCL1, CXCL9, CXCL10, CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, TNFα and LTα) which affect the navigation and activities of B and T lymphocytes in the lymphoid tissues. An extreme increase in mRNA levels for CCL20 was detected in the white pulp of the LPS-treated mice. The CCL20-expressing cells were localized in the PALS. Some smaller CCL20-expressing cells were evenly dispersed in the B cell zone. Thus, our study provides new knowledge of how microbial products could be involved in shaping the structure of lymphatic organs.
T2  - Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft
T1  - Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen
VL  - 216
DO  - 10.1016/j.aanat.2017.12.002
SP  - 125
EP  - 134
ER  - 

@article{
author = "Lalić, Ivana M. and Bichele, Rudolf and Repar, Anja and Despotović, Sanja Z. and Petričević, Saša and Laan, Martti and Peterson, Pärt and Westermann, Jürgen and Milićević, Živana and Mirkov, Ivana and Milićević, Novica M.",
year = "2018",
abstract = "It is well known that bacterial lipopolysaccharide (LPS) induces migration of several cellular populations within the spleen. However, there are no data about the impact of LPS on B and T lymphocytes present in the red pulp. Therefore, we used an experimental model in which we tested the effects of intravenously injected LPS on the molecular, cellular and structural changes of the spleen, with special reference to the red pulp lymphocytes. We discovered that LPS induced a massive relocation of B and T lymphocytes from the splenic red pulp, which was independent of the tumor necrosis factor receptor-1 signaling axis. Early after LPS treatment, quantitative real-time PCR analysis revealed the elevated levels of mRNA encoding numerous chemokines and proinflammatory cytokines (XCL1, CXCL9, CXCL10, CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, TNFα and LTα) which affect the navigation and activities of B and T lymphocytes in the lymphoid tissues. An extreme increase in mRNA levels for CCL20 was detected in the white pulp of the LPS-treated mice. The CCL20-expressing cells were localized in the PALS. Some smaller CCL20-expressing cells were evenly dispersed in the B cell zone. Thus, our study provides new knowledge of how microbial products could be involved in shaping the structure of lymphatic organs.",
journal = "Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft",
title = "Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen",
volume = "216",
doi = "10.1016/j.aanat.2017.12.002",
pages = "125-134"
}

Lalić, I. M., Bichele, R., Repar, A., Despotović, S. Z., Petričević, S., Laan, M., Peterson, P., Westermann, J., Milićević, Ž., Mirkov, I.,& Milićević, N. M.. (2018). Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen. in Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft, 216, 125-134.
https://doi.org/10.1016/j.aanat.2017.12.002

Lalić IM, Bichele R, Repar A, Despotović SZ, Petričević S, Laan M, Peterson P, Westermann J, Milićević Ž, Mirkov I, Milićević NM. Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen. in Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft. 2018;216:125-134.
doi:10.1016/j.aanat.2017.12.002 .

Lalić, Ivana M., Bichele, Rudolf, Repar, Anja, Despotović, Sanja Z., Petričević, Saša, Laan, Martti, Peterson, Pärt, Westermann, Jürgen, Milićević, Živana, Mirkov, Ivana, Milićević, Novica M., "Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen" in Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft, 216 (2018):125-134,
https://doi.org/10.1016/j.aanat.2017.12.002 . .