TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Lazarević, Milica
AU  - Ignjatović, Đurđica
AU  - Tomić, Mirko
AU  - Nikolovski, Neda
AU  - Bjelobaba, Ivana
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6643
AB  - We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
PB  - Elsevier
T2  - Immunology Letters
T1  - Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate
VL  - 267
DO  - 10.1016/j.imlet.2024.106852
SP  - 106852
ER  - 

@article{
author = "Stegnjaić, Goran and Jevtić, Bojan and Lazarević, Milica and Ignjatović, Đurđica and Tomić, Mirko and Nikolovski, Neda and Bjelobaba, Ivana and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe and Stanisavljević, Suzana",
year = "2024",
abstract = "We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.",
publisher = "Elsevier",
journal = "Immunology Letters",
title = "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate",
volume = "267",
doi = "10.1016/j.imlet.2024.106852",
pages = "106852"
}

Stegnjaić, G., Jevtić, B., Lazarević, M., Ignjatović, Đ., Tomić, M., Nikolovski, N., Bjelobaba, I., Momčilović, M., Dimitrijević, M., Miljković, Đ.,& Stanisavljević, S.. (2024). Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters
Elsevier., 267, 106852.
https://doi.org/10.1016/j.imlet.2024.106852

Stegnjaić G, Jevtić B, Lazarević M, Ignjatović Đ, Tomić M, Nikolovski N, Bjelobaba I, Momčilović M, Dimitrijević M, Miljković Đ, Stanisavljević S. Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters. 2024;267:106852.
doi:10.1016/j.imlet.2024.106852 .

Stegnjaić, Goran, Jevtić, Bojan, Lazarević, Milica, Ignjatović, Đurđica, Tomić, Mirko, Nikolovski, Neda, Bjelobaba, Ivana, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, Stanisavljević, Suzana, "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate" in Immunology Letters, 267 (2024):106852,
https://doi.org/10.1016/j.imlet.2024.106852 . .

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  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Lazarević, Milica
AU  - Ignjatović, Đurđica
AU  - Tomić, Mirko
AU  - Nikolovski, Neda
AU  - Bjelobaba, Ivana
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6644
AB  - We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
PB  - Elsevier
T2  - Immunology Letters
T1  - Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate
VL  - 267
DO  - 10.1016/j.imlet.2024.106852
SP  - 106852
ER  - 

@article{
author = "Stegnjaić, Goran and Jevtić, Bojan and Lazarević, Milica and Ignjatović, Đurđica and Tomić, Mirko and Nikolovski, Neda and Bjelobaba, Ivana and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe and Stanisavljević, Suzana",
year = "2024",
abstract = "We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.",
publisher = "Elsevier",
journal = "Immunology Letters",
title = "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate",
volume = "267",
doi = "10.1016/j.imlet.2024.106852",
pages = "106852"
}

Stegnjaić, G., Jevtić, B., Lazarević, M., Ignjatović, Đ., Tomić, M., Nikolovski, N., Bjelobaba, I., Momčilović, M., Dimitrijević, M., Miljković, Đ.,& Stanisavljević, S.. (2024). Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters
Elsevier., 267, 106852.
https://doi.org/10.1016/j.imlet.2024.106852

Stegnjaić G, Jevtić B, Lazarević M, Ignjatović Đ, Tomić M, Nikolovski N, Bjelobaba I, Momčilović M, Dimitrijević M, Miljković Đ, Stanisavljević S. Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters. 2024;267:106852.
doi:10.1016/j.imlet.2024.106852 .

Stegnjaić, Goran, Jevtić, Bojan, Lazarević, Milica, Ignjatović, Đurđica, Tomić, Mirko, Nikolovski, Neda, Bjelobaba, Ivana, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, Stanisavljević, Suzana, "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate" in Immunology Letters, 267 (2024):106852,
https://doi.org/10.1016/j.imlet.2024.106852 . .

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  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Dimitrijević, Mirjana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6363
AB  - Experimental autoimmune encephalomyelitis (EAE) in inbred rodents commonly shows different clinical courses, so that the diseased animals can be clustered into four groups: mild. moderate, severe and lethal. Our aim was to determine biomolecular markers in the preclinical phase of EAE that allow the prediction of clinical course. 
Methods: Female Dark Agouti rats were immunized with spinal cord homogenate without adjuvant and examined for four weeks for clinical signs of EAE. Cells and sera from blood collected on days 0, 3, and 7 after immunization were processed for detection of proinflammatory cytokines (IL-1, IL-6, TNF, and IFN) by "real-time" RT-PCR and ELISA, respectively. 
Results: Induction of EAE resulted in the downregulation of IFN and TNF in the preclinical phase of disease, whereas IL-1 and IL-6 expression levels were unaffected. However, there was no correlation between the relative expression of IFN or TNF and the cumulative clinical score (sum of daily clinical scores), suggesting that they are not predictive markers of EAE severity. Our preliminary results that suggest a negative correlation between IL-1 expression level before EAE induction and cumulative score require further justification. 
Conclusion: The proinflammatory cytokines investigated so far in our study cannot be considered as good biomarkers of EAE severity. However, the downregulation of IFN and TNF in the blood cells during the asymptomatic phase of EAE suggests that they enter the central nervous system early from the bloodstream, which argues for the study of chemokine and/or chemokine receptors expression as potential biomarkers for the clinical courses of EAE.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate
SP  - 89
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6363
ER  - 

@conference{
author = "Stegnjaić, Goran and Lazarević, Milica and Jevtić, Bojan and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Mostarica Stojković, Marija and Miljković, Đorđe and Dimitrijević, Mirjana",
year = "2023",
abstract = "Experimental autoimmune encephalomyelitis (EAE) in inbred rodents commonly shows different clinical courses, so that the diseased animals can be clustered into four groups: mild. moderate, severe and lethal. Our aim was to determine biomolecular markers in the preclinical phase of EAE that allow the prediction of clinical course. 
Methods: Female Dark Agouti rats were immunized with spinal cord homogenate without adjuvant and examined for four weeks for clinical signs of EAE. Cells and sera from blood collected on days 0, 3, and 7 after immunization were processed for detection of proinflammatory cytokines (IL-1, IL-6, TNF, and IFN) by "real-time" RT-PCR and ELISA, respectively. 
Results: Induction of EAE resulted in the downregulation of IFN and TNF in the preclinical phase of disease, whereas IL-1 and IL-6 expression levels were unaffected. However, there was no correlation between the relative expression of IFN or TNF and the cumulative clinical score (sum of daily clinical scores), suggesting that they are not predictive markers of EAE severity. Our preliminary results that suggest a negative correlation between IL-1 expression level before EAE induction and cumulative score require further justification. 
Conclusion: The proinflammatory cytokines investigated so far in our study cannot be considered as good biomarkers of EAE severity. However, the downregulation of IFN and TNF in the blood cells during the asymptomatic phase of EAE suggests that they enter the central nervous system early from the bloodstream, which argues for the study of chemokine and/or chemokine receptors expression as potential biomarkers for the clinical courses of EAE.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate",
pages = "89",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6363"
}

Stegnjaić, G., Lazarević, M., Jevtić, B., Stanisavljević, S., Nikolovski, N., Momčilović, M., Mostarica Stojković, M., Miljković, Đ.,& Dimitrijević, M.. (2023). Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 89.
https://hdl.handle.net/21.15107/rcub_ibiss_6363

Stegnjaić G, Lazarević M, Jevtić B, Stanisavljević S, Nikolovski N, Momčilović M, Mostarica Stojković M, Miljković Đ, Dimitrijević M. Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:89.
https://hdl.handle.net/21.15107/rcub_ibiss_6363 .

Stegnjaić, Goran, Lazarević, Milica, Jevtić, Bojan, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Mostarica Stojković, Marija, Miljković, Đorđe, Dimitrijević, Mirjana, "Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):89,
https://hdl.handle.net/21.15107/rcub_ibiss_6363 .

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Stanisavljević, Suzana
AU  - Mićanović, Dragica
AU  - Jevtić, Bojan
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6294
AB  - Innate lymphoid cells type 3 (ILC3s) are the first line sentinels at the mucous
tissues, where they contribute to the homeostatic immune response in a major
way. Also, they have been increasingly appreciated as important modulators of
chronic inflammatory and autoimmune responses, both locally and systemically.
The proper identification of ILC3 is of utmost importance for meaningful studies
on their role in immunity. Flow cytometry is the method of choice for the
detection and characterization of ILC3. However, the analysis of ILC3-related
papers shows inconsistency in ILC3 phenotypic definition, as different inclusion
and exclusion markers are used for their identification. Here, we present these
discrepancies in the phenotypic characterization of human and mouse ILC3s. We
discuss the pros and cons of using various markers for ILC3 identification.
Furthermore, we consider the possibilities for the efficient isolation and
propagation of ILC3 from different organs and tissues for in-vitro and in-vivo
studies. This paper calls upon uniformity in ILC3 definition, isolation, and
propagation for the increased possibility of confluent interpretation of ILC3’s
role in immunity.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Immunology
T1  - ILC3: a case of conflicted identity
VL  - 14
DO  - 10.3389/fimmu.2023.1271699
SP  - 1271699
ER  - 

@article{
author = "Koprivica, Ivan and Stanisavljević, Suzana and Mićanović, Dragica and Jevtić, Bojan and Stojanović, Ivana D. and Miljković, Đorđe",
year = "2023",
abstract = "Innate lymphoid cells type 3 (ILC3s) are the first line sentinels at the mucous
tissues, where they contribute to the homeostatic immune response in a major
way. Also, they have been increasingly appreciated as important modulators of
chronic inflammatory and autoimmune responses, both locally and systemically.
The proper identification of ILC3 is of utmost importance for meaningful studies
on their role in immunity. Flow cytometry is the method of choice for the
detection and characterization of ILC3. However, the analysis of ILC3-related
papers shows inconsistency in ILC3 phenotypic definition, as different inclusion
and exclusion markers are used for their identification. Here, we present these
discrepancies in the phenotypic characterization of human and mouse ILC3s. We
discuss the pros and cons of using various markers for ILC3 identification.
Furthermore, we consider the possibilities for the efficient isolation and
propagation of ILC3 from different organs and tissues for in-vitro and in-vivo
studies. This paper calls upon uniformity in ILC3 definition, isolation, and
propagation for the increased possibility of confluent interpretation of ILC3’s
role in immunity.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Immunology",
title = "ILC3: a case of conflicted identity",
volume = "14",
doi = "10.3389/fimmu.2023.1271699",
pages = "1271699"
}

Koprivica, I., Stanisavljević, S., Mićanović, D., Jevtić, B., Stojanović, I. D.,& Miljković, Đ.. (2023). ILC3: a case of conflicted identity. in Frontiers in Immunology
Lausanne: Frontiers Media SA., 14, 1271699.
https://doi.org/10.3389/fimmu.2023.1271699

Koprivica I, Stanisavljević S, Mićanović D, Jevtić B, Stojanović ID, Miljković Đ. ILC3: a case of conflicted identity. in Frontiers in Immunology. 2023;14:1271699.
doi:10.3389/fimmu.2023.1271699 .

Koprivica, Ivan, Stanisavljević, Suzana, Mićanović, Dragica, Jevtić, Bojan, Stojanović, Ivana D., Miljković, Đorđe, "ILC3: a case of conflicted identity" in Frontiers in Immunology, 14 (2023):1271699,
https://doi.org/10.3389/fimmu.2023.1271699 . .

TY  - CONF
AU  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6300
AB  - Experimental autoimmune encephalomyelitis (EAE) is commonly induced with
central nervous system antigens mixed with complete Freund’s adjuvant (CFA). This
adjuvant has a confounding influence on the translational capacity of EAE as multiple
sclerosis (MS) model. Thus, we developed a novel subtype of EAE induced in Dark
Agouti (DA) rats with spinal cord homogenate (SCH) without CFA and characterized
it as a reliable MS model. Despite genetic homogeneity of experimental animals and
controlled environmental conditions, we observed variations in EAE clinical course in
SCH-immunized DA rats and four clinical groups were identified: lethal, severe,
moderate, and mild. Immune cells of spinal cord, small intestine lamina propria and
lymph nodes draining the site of immunization were compared between moderate and
severe group. Higher numbers of CD4+ T cells, regulatory T cells (Treg), helper T
cells type 1 (Th1) and 17 (Th17), and B cells were detected in the spinal cords of
severe group. Also, higher levels of interferon (IFN)-γ and interleukin (IL)-6 and an
increased proportion of Th1 and Th17 cells were detected in the lamina propria of the
severe group. Aminoguanidine – an inducible nitric oxide synthase inhibitor that was
applied to the rats during the effector phase of the disease ameliorated EAE and
imposed a shift of clinical outcomes towards milder variants. Our results suggest that
different clinical outcomes in DA rats come as a consequence of variability in the
strength of the effector mechanisms exerted within the CNS. The study of the
underlying mechanisms for the observed variability is necessary.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6300
ER  - 

@conference{
author = "Lazarević, Milica and Stegnjaić, Goran and Jevtić, Bojan and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe",
year = "2023",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is commonly induced with
central nervous system antigens mixed with complete Freund’s adjuvant (CFA). This
adjuvant has a confounding influence on the translational capacity of EAE as multiple
sclerosis (MS) model. Thus, we developed a novel subtype of EAE induced in Dark
Agouti (DA) rats with spinal cord homogenate (SCH) without CFA and characterized
it as a reliable MS model. Despite genetic homogeneity of experimental animals and
controlled environmental conditions, we observed variations in EAE clinical course in
SCH-immunized DA rats and four clinical groups were identified: lethal, severe,
moderate, and mild. Immune cells of spinal cord, small intestine lamina propria and
lymph nodes draining the site of immunization were compared between moderate and
severe group. Higher numbers of CD4+ T cells, regulatory T cells (Treg), helper T
cells type 1 (Th1) and 17 (Th17), and B cells were detected in the spinal cords of
severe group. Also, higher levels of interferon (IFN)-γ and interleukin (IL)-6 and an
increased proportion of Th1 and Th17 cells were detected in the lamina propria of the
severe group. Aminoguanidine – an inducible nitric oxide synthase inhibitor that was
applied to the rats during the effector phase of the disease ameliorated EAE and
imposed a shift of clinical outcomes towards milder variants. Our results suggest that
different clinical outcomes in DA rats come as a consequence of variability in the
strength of the effector mechanisms exerted within the CNS. The study of the
underlying mechanisms for the observed variability is necessary.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats",
pages = "42",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6300"
}

Lazarević, M., Stegnjaić, G., Jevtić, B., Stanisavljević, S., Nikolovski, N., Momčilović, M., Dimitrijević, M.,& Miljković, Đ.. (2023). Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 42.
https://hdl.handle.net/21.15107/rcub_ibiss_6300

Lazarević M, Stegnjaić G, Jevtić B, Stanisavljević S, Nikolovski N, Momčilović M, Dimitrijević M, Miljković Đ. Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:42.
https://hdl.handle.net/21.15107/rcub_ibiss_6300 .

Lazarević, Milica, Stegnjaić, Goran, Jevtić, Bojan, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, "Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):42,
https://hdl.handle.net/21.15107/rcub_ibiss_6300 .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Paunović, Verica
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Jevtić, Bojan
AU  - Jonić, Natalija
AU  - Stojanović, Ivana D.
AU  - Pejnović, Nada
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5557
AB  - Recent data indicate the link between the number and function of T regulatory cells (Treg)
in the gut immune tissue and initiation and development of autoimmunity associated with type
1 diabetes (T1D). Since type 3 innate lymphoid cells (ILC3) in the small intestine are essential for
maintaining FoxP3+ Treg and there are no data about the possible role of ILC3 in T1D pathogenesis,
the aim of this study was to explore ILC3-Treg link during the development of T1D. Mature diabetic
NOD mice had lower frequencies of IL-2-producing ILC3 and Treg in small intestine lamina propria
(SILP) compared to prediabetic NOD mice. Similarly, in multiple low doses of streptozotocin (MLDS)-
induced T1D in C57BL/6 mice, hyperglycemic mice exhibited lower numbers of ILC3, IL-2+ ILC3
and Treg in SILP compared to healthy controls. To boost T1D severity, mice were treated with
broad-spectrum antibiotics (ABX) for 14 days prior to T1D induction by MLDS. The higher incidence
of T1D in ABX-treated mice was associated with significantly lower frequencies of IL-2+ ILC3 and
FoxP3+ Treg in SILP compared with mice without ABX treatment. The obtained findings show that
the lower proportions of IL-2-expressing ILC3 and FoxP3+ Treg in SILP coincided with diabetes
progression and severity.
PB  - MDPI
PB  - Basel: MDPI
T2  - Molecules
T1  - Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine
IS  - 8
VL  - 28
DO  - 10.3390/molecules28083366
SP  - 3366
ER  - 

@article{
author = "Saksida, Tamara and Paunović, Verica and Koprivica, Ivan and Mićanović, Dragica and Jevtić, Bojan and Jonić, Natalija and Stojanović, Ivana D. and Pejnović, Nada",
year = "2023",
abstract = "Recent data indicate the link between the number and function of T regulatory cells (Treg)
in the gut immune tissue and initiation and development of autoimmunity associated with type
1 diabetes (T1D). Since type 3 innate lymphoid cells (ILC3) in the small intestine are essential for
maintaining FoxP3+ Treg and there are no data about the possible role of ILC3 in T1D pathogenesis,
the aim of this study was to explore ILC3-Treg link during the development of T1D. Mature diabetic
NOD mice had lower frequencies of IL-2-producing ILC3 and Treg in small intestine lamina propria
(SILP) compared to prediabetic NOD mice. Similarly, in multiple low doses of streptozotocin (MLDS)-
induced T1D in C57BL/6 mice, hyperglycemic mice exhibited lower numbers of ILC3, IL-2+ ILC3
and Treg in SILP compared to healthy controls. To boost T1D severity, mice were treated with
broad-spectrum antibiotics (ABX) for 14 days prior to T1D induction by MLDS. The higher incidence
of T1D in ABX-treated mice was associated with significantly lower frequencies of IL-2+ ILC3 and
FoxP3+ Treg in SILP compared with mice without ABX treatment. The obtained findings show that
the lower proportions of IL-2-expressing ILC3 and FoxP3+ Treg in SILP coincided with diabetes
progression and severity.",
publisher = "MDPI, Basel: MDPI",
journal = "Molecules",
title = "Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine",
number = "8",
volume = "28",
doi = "10.3390/molecules28083366",
pages = "3366"
}

Saksida, T., Paunović, V., Koprivica, I., Mićanović, D., Jevtić, B., Jonić, N., Stojanović, I. D.,& Pejnović, N.. (2023). Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine. in Molecules
MDPI., 28(8), 3366.
https://doi.org/10.3390/molecules28083366

Saksida T, Paunović V, Koprivica I, Mićanović D, Jevtić B, Jonić N, Stojanović ID, Pejnović N. Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine. in Molecules. 2023;28(8):3366.
doi:10.3390/molecules28083366 .

Saksida, Tamara, Paunović, Verica, Koprivica, Ivan, Mićanović, Dragica, Jevtić, Bojan, Jonić, Natalija, Stojanović, Ivana D., Pejnović, Nada, "Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine" in Molecules, 28, no. 8 (2023):3366,
https://doi.org/10.3390/molecules28083366 . .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Tsiailanis, Antonios D.
AU  - Lazarević, Milica
AU  - Gkalpinos, Vasileios K.
AU  - Nikolovski, Neda
AU  - Antoniou, Thomas
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas G.
AU  - Jevtić, Bojan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5305
AB  - Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for
its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was
synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological
potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was
found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically,
PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO,
and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune
encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system
(CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective
to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.
PB  - Basel: MDPI
T2  - Molecules
T1  - Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis
IS  - 24
VL  - 27
DO  - 10.3390/molecules27248770
SP  - 8770
ER  - 

@article{
author = "Stegnjaić, Goran and Tsiailanis, Antonios D. and Lazarević, Milica and Gkalpinos, Vasileios K. and Nikolovski, Neda and Antoniou, Thomas and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Miljković, Đorđe and Tzakos, Andreas G. and Jevtić, Bojan",
year = "2022",
abstract = "Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for
its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was
synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological
potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was
found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically,
PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO,
and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune
encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system
(CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective
to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis",
number = "24",
volume = "27",
doi = "10.3390/molecules27248770",
pages = "8770"
}

Stegnjaić, G., Tsiailanis, A. D., Lazarević, M., Gkalpinos, V. K., Nikolovski, N., Antoniou, T., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Miljković, Đ., Tzakos, A. G.,& Jevtić, B.. (2022). Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis. in Molecules
Basel: MDPI., 27(24), 8770.
https://doi.org/10.3390/molecules27248770

Stegnjaić G, Tsiailanis AD, Lazarević M, Gkalpinos VK, Nikolovski N, Antoniou T, Stanisavljević S, Dimitrijević M, Momčilović M, Miljković Đ, Tzakos AG, Jevtić B. Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis. in Molecules. 2022;27(24):8770.
doi:10.3390/molecules27248770 .

Stegnjaić, Goran, Tsiailanis, Antonios D., Lazarević, Milica, Gkalpinos, Vasileios K., Nikolovski, Neda, Antoniou, Thomas, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Miljković, Đorđe, Tzakos, Andreas G., Jevtić, Bojan, "Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis" in Molecules, 27, no. 24 (2022):8770,
https://doi.org/10.3390/molecules27248770 . .

TY  - CONF
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Tsiailanis, Antonios D
AU  - Antoniou, Thomas
AU  - Gkalpinos, Vasileios K
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas G
AU  - Jevtić, Bojan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6299
AB  - This study aimed to evaluate the effects of a synthetic gallic acid (GA) derivative in the
central nervous system (CNS) autoimmunity, i.e. in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in DA
rats by injection of autologous spinal cord homogenate, with a gallic acid derivative being
applied subcutaneously (20 mg/kg, day 7-22 post-immunization). GA derivative
ameliorated EAE. Cells from lymph nodes draining the site of immunization (DLNC),
isolated in the inductive phase of the disease, and spinal cord immune cells (SCIC),
isolated at the peak of disease, were exposed to GA derivative in vitro. Encephalitogenic
cytokines, interferon (IFN)-γ and interleukin (IL)-17, were decreased in SCIC and DLNC
under the influence of GA derivative. The proportion of IL-17-producing CD4+ T cells was
reduced in SCIC (flow cytometry). Treatment of microglial BV2 cells with GA derivative
led to inhibition of NO, IL-6, and tumor necrosis factor release. These results imply that
the synthesized GA derivative is a potent immunomodulator, able to ameliorate EAE. Its
effects on the CNS autoimmunity are related to the inhibition of encephalitogenic T cells
and macrophage/microglia activity in our study.
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  - The effect of a gallic acid derivative on encephalitogenic cells
SP  - 140
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6299
ER  - 

@conference{
author = "Stegnjaić, Goran and Lazarević, Milica and Tsiailanis, Antonios D and Antoniou, Thomas and Gkalpinos, Vasileios K and Nikolovski, Neda and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Miljković, Đorđe and Tzakos, Andreas G and Jevtić, Bojan",
year = "2022",
abstract = "This study aimed to evaluate the effects of a synthetic gallic acid (GA) derivative in the
central nervous system (CNS) autoimmunity, i.e. in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in DA
rats by injection of autologous spinal cord homogenate, with a gallic acid derivative being
applied subcutaneously (20 mg/kg, day 7-22 post-immunization). GA derivative
ameliorated EAE. Cells from lymph nodes draining the site of immunization (DLNC),
isolated in the inductive phase of the disease, and spinal cord immune cells (SCIC),
isolated at the peak of disease, were exposed to GA derivative in vitro. Encephalitogenic
cytokines, interferon (IFN)-γ and interleukin (IL)-17, were decreased in SCIC and DLNC
under the influence of GA derivative. The proportion of IL-17-producing CD4+ T cells was
reduced in SCIC (flow cytometry). Treatment of microglial BV2 cells with GA derivative
led to inhibition of NO, IL-6, and tumor necrosis factor release. These results imply that
the synthesized GA derivative is a potent immunomodulator, able to ameliorate EAE. Its
effects on the CNS autoimmunity are related to the inhibition of encephalitogenic T cells
and macrophage/microglia activity in our study.",
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 = "The effect of a gallic acid derivative on encephalitogenic cells",
pages = "140",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6299"
}

Stegnjaić, G., Lazarević, M., Tsiailanis, A. D., Antoniou, T., Gkalpinos, V. K., Nikolovski, N., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Miljković, Đ., Tzakos, A. G.,& Jevtić, B.. (2022). The effect of a gallic acid derivative on encephalitogenic cells. 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., 140.
https://hdl.handle.net/21.15107/rcub_ibiss_6299

Stegnjaić G, Lazarević M, Tsiailanis AD, Antoniou T, Gkalpinos VK, Nikolovski N, Stanisavljević S, Dimitrijević M, Momčilović M, Miljković Đ, Tzakos AG, Jevtić B. The effect of a gallic acid derivative on encephalitogenic cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:140.
https://hdl.handle.net/21.15107/rcub_ibiss_6299 .

Stegnjaić, Goran, Lazarević, Milica, Tsiailanis, Antonios D, Antoniou, Thomas, Gkalpinos, Vasileios K, Nikolovski, Neda, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Miljković, Đorđe, Tzakos, Andreas G, Jevtić, Bojan, "The effect of a gallic acid derivative on encephalitogenic cells" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):140,
https://hdl.handle.net/21.15107/rcub_ibiss_6299 .

TY  - CONF
AU  - Jevtić, Bojan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6298
AB  - Multiple sclerosis is a chronic inflammatory, demyelinating, and neurodegenerative
disorder of the central nervous system. More than 2.5 million people suffer from this
disease worldwide. It is assumed that the autoimmune response to myelin antigens in the
CNS is the main cause of the disease. Experimental autoimmune encephalomyelitis (EAE)
is a widely used animal model for studying MS. However, EAEmodels resemble only
particular aspects of the MS pathogenesis. EAE is classically induced with the CNS
antigens emulsified in complete Freund’s adjuvant (CFA). CFA consist of paraffin oil
supplemented with Mycobacterium, and its application potentiates innate immune
response, prolongs the presence and effective transport of antigen in the lymphatic system.
However, CFA has a confounding influence on the results and the translational capacity as
a multiple sclerosis model. Our group has successfully excluded CFA from immunization
regime. In a recent study, we compared clinical, histological, cellular and molecular
properties between spinal cord homogenate (SCH) and SCH+CFA immunized Dark
Agouti rats. We have observed higher clinical score in rats without CFA and greater
number of immune cell infiltrates at the peak of EAE in the same animals. Further,
stronger myelin basic protein-specific T cell immune response is evokedin the draining
lymph nodes of CFA-free compared to CFA immunized rats. In the CNS, high abundance
of CD8+T cells is detected at the onset of disease. Also, enrichment in CD8+ and CD4+
macrophageswas observed in the CNS during EAE. Therefore, CFA-free EAE is a reliable
model for studying CNS autoimmunity.
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  - Adjuvant-free animal model for studying CNS autoimmunity
SP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6298
ER  - 

@conference{
author = "Jevtić, Bojan",
year = "2022",
abstract = "Multiple sclerosis is a chronic inflammatory, demyelinating, and neurodegenerative
disorder of the central nervous system. More than 2.5 million people suffer from this
disease worldwide. It is assumed that the autoimmune response to myelin antigens in the
CNS is the main cause of the disease. Experimental autoimmune encephalomyelitis (EAE)
is a widely used animal model for studying MS. However, EAEmodels resemble only
particular aspects of the MS pathogenesis. EAE is classically induced with the CNS
antigens emulsified in complete Freund’s adjuvant (CFA). CFA consist of paraffin oil
supplemented with Mycobacterium, and its application potentiates innate immune
response, prolongs the presence and effective transport of antigen in the lymphatic system.
However, CFA has a confounding influence on the results and the translational capacity as
a multiple sclerosis model. Our group has successfully excluded CFA from immunization
regime. In a recent study, we compared clinical, histological, cellular and molecular
properties between spinal cord homogenate (SCH) and SCH+CFA immunized Dark
Agouti rats. We have observed higher clinical score in rats without CFA and greater
number of immune cell infiltrates at the peak of EAE in the same animals. Further,
stronger myelin basic protein-specific T cell immune response is evokedin the draining
lymph nodes of CFA-free compared to CFA immunized rats. In the CNS, high abundance
of CD8+T cells is detected at the onset of disease. Also, enrichment in CD8+ and CD4+
macrophageswas observed in the CNS during EAE. Therefore, CFA-free EAE is a reliable
model for studying CNS autoimmunity.",
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 = "Adjuvant-free animal model for studying CNS autoimmunity",
pages = "33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6298"
}

Jevtić, B.. (2022). Adjuvant-free animal model for studying CNS autoimmunity. 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., 33.
https://hdl.handle.net/21.15107/rcub_ibiss_6298

Jevtić B. Adjuvant-free animal model for studying CNS autoimmunity. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:33.
https://hdl.handle.net/21.15107/rcub_ibiss_6298 .

Jevtić, Bojan, "Adjuvant-free animal model for studying CNS autoimmunity" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):33,
https://hdl.handle.net/21.15107/rcub_ibiss_6298 .

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  - JOUR
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Diamantis, Dimitrois A
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Tzakos, Andreas G
AU  - Miljković, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5085
AB  - Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of
the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative
of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model
of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis
(EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg)
from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening
the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced
production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from
the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified
from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in
macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and
tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses antiencephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of
multiple sclerosis are warranted.
PB  - Amsterdam : Elsevier
T2  - Immunology Letters
T1  - Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis
VL  - 251-252
DO  - 10.1016/j.imlet.2022.09.006
SP  - 9
EP  - 19
ER  - 

@article{
author = "Stegnjaić, Goran and Lazarević, Milica and Diamantis, Dimitrois A and Nikolovski, Neda and Jevtić, Bojan and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Tzakos, Andreas G and Miljković, Đorđe",
year = "2022",
abstract = "Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of
the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative
of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model
of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis
(EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg)
from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening
the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced
production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from
the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified
from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in
macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and
tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses antiencephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of
multiple sclerosis are warranted.",
publisher = "Amsterdam : Elsevier",
journal = "Immunology Letters",
title = "Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis",
volume = "251-252",
doi = "10.1016/j.imlet.2022.09.006",
pages = "9-19"
}

Stegnjaić, G., Lazarević, M., Diamantis, D. A., Nikolovski, N., Jevtić, B., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Tzakos, A. G.,& Miljković, Đ.. (2022). Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis. in Immunology Letters
Amsterdam : Elsevier., 251-252, 9-19.
https://doi.org/10.1016/j.imlet.2022.09.006

Stegnjaić G, Lazarević M, Diamantis DA, Nikolovski N, Jevtić B, Stanisavljević S, Dimitrijević M, Momčilović M, Tzakos AG, Miljković Đ. Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis. in Immunology Letters. 2022;251-252:9-19.
doi:10.1016/j.imlet.2022.09.006 .

Stegnjaić, Goran, Lazarević, Milica, Diamantis, Dimitrois A, Nikolovski, Neda, Jevtić, Bojan, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Tzakos, Andreas G, Miljković, Đorđe, "Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis" in Immunology Letters, 251-252 (2022):9-19,
https://doi.org/10.1016/j.imlet.2022.09.006 . .

TY  - JOUR
AU  - Vuković, Mladen
AU  - Lazarević, Miloš
AU  - Mitić, Dijana
AU  - Jakšić Karišik, Milica
AU  - Ilić, Branislav
AU  - Andrić, Miroslav
AU  - Jevtić, Bojan
AU  - Roganović, Jelena
AU  - Milašin, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5164
AB  - OBJECTIVE The study aimed to investigate acetylsalicylic acid (ASA) effects on osteo/odontogenic differentiation and proliferation of dental pulp stem cells (DPSCs) in vitro and the potential involvement of adenosine monophosphate-activated protein kinase (AMPK) pathway in these processes. DESIGN DPSCs were isolated from third molars pulp tissues of five patients and grown in osteogenic medium alone or supplemented with ASA. Expression of DPSCs markers was tested by flow-cytometry. Cytotoxicity of ASA at concentrations of 10, 50 and 100 µg/ml was tested by MTT and NR assays. Osteo/odontogenic differentiation was analyzed via alizarin red staining and ALP activity. Quantitative PCR (qPCR) was used for osteo/odontogenic markers' (DSPP, BMP2, BMP4, BSP, OCN and RUNX2) and c-Myc expression analysis. AMPK inhibition of ASA-induced osteo/odontogenesis was tested by qPCR of selected markers (DSPP, OCN and RUNX2). RESULTS Cytotoxicity assays showed that only the highest ASA dose decreased cell viability (89.1 %). The smallest concentration of ASA applied on DPSCs resulted in a remarkable enhancement of osteo/odontogenic differentiation, as judged by increased mineralized nodules' formation, ALP activity and gene expression of analyzed markers (increase between 2 and 30 folds), compared to untreated cells. ASA also increased DPSCs proliferation. Interestingly, AMPK inhibition per se upregulated DSPP, OCN and RUNX2; the gene upregulation was higher when ASA treatment was also included. c-Myc expression level decreased in cultures treated with ASA, indicating undergoing differentiation processes. CONCLUSIONS Low concentrations of ASA (corresponding to the standard use in cardiovascular patients), were shown to stimulate osteo/odontogenic differentiation of dental pulp stem cells.
PB  - Oxford: Pergamon-Elsevier Science Ltd
T2  - Archives of Oral Biology
T1  - Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.
VL  - 144
DO  - 10.1016/j.archoralbio.2022.105564
SP  - 105564
ER  - 

@article{
author = "Vuković, Mladen and Lazarević, Miloš and Mitić, Dijana and Jakšić Karišik, Milica and Ilić, Branislav and Andrić, Miroslav and Jevtić, Bojan and Roganović, Jelena and Milašin, Jelena",
year = "2022",
abstract = "OBJECTIVE The study aimed to investigate acetylsalicylic acid (ASA) effects on osteo/odontogenic differentiation and proliferation of dental pulp stem cells (DPSCs) in vitro and the potential involvement of adenosine monophosphate-activated protein kinase (AMPK) pathway in these processes. DESIGN DPSCs were isolated from third molars pulp tissues of five patients and grown in osteogenic medium alone or supplemented with ASA. Expression of DPSCs markers was tested by flow-cytometry. Cytotoxicity of ASA at concentrations of 10, 50 and 100 µg/ml was tested by MTT and NR assays. Osteo/odontogenic differentiation was analyzed via alizarin red staining and ALP activity. Quantitative PCR (qPCR) was used for osteo/odontogenic markers' (DSPP, BMP2, BMP4, BSP, OCN and RUNX2) and c-Myc expression analysis. AMPK inhibition of ASA-induced osteo/odontogenesis was tested by qPCR of selected markers (DSPP, OCN and RUNX2). RESULTS Cytotoxicity assays showed that only the highest ASA dose decreased cell viability (89.1 %). The smallest concentration of ASA applied on DPSCs resulted in a remarkable enhancement of osteo/odontogenic differentiation, as judged by increased mineralized nodules' formation, ALP activity and gene expression of analyzed markers (increase between 2 and 30 folds), compared to untreated cells. ASA also increased DPSCs proliferation. Interestingly, AMPK inhibition per se upregulated DSPP, OCN and RUNX2; the gene upregulation was higher when ASA treatment was also included. c-Myc expression level decreased in cultures treated with ASA, indicating undergoing differentiation processes. CONCLUSIONS Low concentrations of ASA (corresponding to the standard use in cardiovascular patients), were shown to stimulate osteo/odontogenic differentiation of dental pulp stem cells.",
publisher = "Oxford: Pergamon-Elsevier Science Ltd",
journal = "Archives of Oral Biology",
title = "Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.",
volume = "144",
doi = "10.1016/j.archoralbio.2022.105564",
pages = "105564"
}

Vuković, M., Lazarević, M., Mitić, D., Jakšić Karišik, M., Ilić, B., Andrić, M., Jevtić, B., Roganović, J.,& Milašin, J.. (2022). Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.. in Archives of Oral Biology
Oxford: Pergamon-Elsevier Science Ltd., 144, 105564.
https://doi.org/10.1016/j.archoralbio.2022.105564

Vuković M, Lazarević M, Mitić D, Jakšić Karišik M, Ilić B, Andrić M, Jevtić B, Roganović J, Milašin J. Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.. in Archives of Oral Biology. 2022;144:105564.
doi:10.1016/j.archoralbio.2022.105564 .

Vuković, Mladen, Lazarević, Miloš, Mitić, Dijana, Jakšić Karišik, Milica, Ilić, Branislav, Andrić, Miroslav, Jevtić, Bojan, Roganović, Jelena, Milašin, Jelena, "Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro." in Archives of Oral Biology, 144 (2022):105564,
https://doi.org/10.1016/j.archoralbio.2022.105564 . .

TY  - JOUR
AU  - Aničić, Neda
AU  - Gašić, Uroš
AU  - Lu, Feng
AU  - Ćirić, Ana
AU  - Ivanov, Marija
AU  - Jevtić, Bojan
AU  - Dimitrijević, Milena
AU  - Anđelković, Boban
AU  - Skorić, Marijana
AU  - Nestorović Živković, Jasmina
AU  - Mao, Yingle
AU  - Liu, Jia
AU  - Tang, Chunping
AU  - Soković, Marina
AU  - Ye, Yang
AU  - Mišić, Danijela
PY  - 2021
UR  - https://doi.org/10.3390/ph14050414
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4249
AB  - Two Balkan Peninsula endemics, Nepeta rtanjensis and N. argolica subsp. argolica, both characterized by specialized metabolite profiles predominated by iridoids and phenolics, are differentiated according to the stereochemistry of major iridoid aglycone nepetalactone (NL). For the first time, the present study provides a comparative analysis of antimicrobial and immunomodulating activities of the two Nepeta species and their major iridoids isolated from natural sources—cis,transNL, trans,cis-NL, and 1,5,9-epideoxyloganic acid (1,5,9-eDLA), as well as of phenolic acid rosmarinic acid (RA). Methanol extracts and pure iridoids displayed excellent antimicrobial activity against eight strains of bacteria and seven strains of fungi. They were especially potent against food-borne pathogens such as L. monocytogenes, E. coli, S. aureus, Penicillium sp., and Aspergillus sp. Targeted iridoids were efficient agents in preventing biofilm formation of resistant P. aeruginosa strain, and they displayed additive antimicrobial interaction. Iridoids are, to a great extent, responsible for the prominent antimicrobial activities of the two Nepeta species, although are probably minor contributors to the moderate immunomodulatory effects. The analyzed iridoids and RA, individually or in mixtures, have the potential to be used in the pharmaceutical industry as potent antimicrobials, and in the food industry to increase the shelf life and safety of food products.
PB  - MDPI AG
T2  - Pharmaceuticals
T1  - Antimicrobial and Immunomodulating Activities of Two Endemic Nepeta Species and Their Major Iridoids Isolated from Natural Sources
IS  - 5
VL  - 14
DO  - 10.3390/ph14050414
SP  - 414
ER  - 

@article{
author = "Aničić, Neda and Gašić, Uroš and Lu, Feng and Ćirić, Ana and Ivanov, Marija and Jevtić, Bojan and Dimitrijević, Milena and Anđelković, Boban and Skorić, Marijana and Nestorović Živković, Jasmina and Mao, Yingle and Liu, Jia and Tang, Chunping and Soković, Marina and Ye, Yang and Mišić, Danijela",
year = "2021",
abstract = "Two Balkan Peninsula endemics, Nepeta rtanjensis and N. argolica subsp. argolica, both characterized by specialized metabolite profiles predominated by iridoids and phenolics, are differentiated according to the stereochemistry of major iridoid aglycone nepetalactone (NL). For the first time, the present study provides a comparative analysis of antimicrobial and immunomodulating activities of the two Nepeta species and their major iridoids isolated from natural sources—cis,transNL, trans,cis-NL, and 1,5,9-epideoxyloganic acid (1,5,9-eDLA), as well as of phenolic acid rosmarinic acid (RA). Methanol extracts and pure iridoids displayed excellent antimicrobial activity against eight strains of bacteria and seven strains of fungi. They were especially potent against food-borne pathogens such as L. monocytogenes, E. coli, S. aureus, Penicillium sp., and Aspergillus sp. Targeted iridoids were efficient agents in preventing biofilm formation of resistant P. aeruginosa strain, and they displayed additive antimicrobial interaction. Iridoids are, to a great extent, responsible for the prominent antimicrobial activities of the two Nepeta species, although are probably minor contributors to the moderate immunomodulatory effects. The analyzed iridoids and RA, individually or in mixtures, have the potential to be used in the pharmaceutical industry as potent antimicrobials, and in the food industry to increase the shelf life and safety of food products.",
publisher = "MDPI AG",
journal = "Pharmaceuticals",
title = "Antimicrobial and Immunomodulating Activities of Two Endemic Nepeta Species and Their Major Iridoids Isolated from Natural Sources",
number = "5",
volume = "14",
doi = "10.3390/ph14050414",
pages = "414"
}

Aničić, N., Gašić, U., Lu, F., Ćirić, A., Ivanov, M., Jevtić, B., Dimitrijević, M., Anđelković, B., Skorić, M., Nestorović Živković, J., Mao, Y., Liu, J., Tang, C., Soković, M., Ye, Y.,& Mišić, D.. (2021). Antimicrobial and Immunomodulating Activities of Two Endemic Nepeta Species and Their Major Iridoids Isolated from Natural Sources. in Pharmaceuticals
MDPI AG., 14(5), 414.
https://doi.org/10.3390/ph14050414

Aničić N, Gašić U, Lu F, Ćirić A, Ivanov M, Jevtić B, Dimitrijević M, Anđelković B, Skorić M, Nestorović Živković J, Mao Y, Liu J, Tang C, Soković M, Ye Y, Mišić D. Antimicrobial and Immunomodulating Activities of Two Endemic Nepeta Species and Their Major Iridoids Isolated from Natural Sources. in Pharmaceuticals. 2021;14(5):414.
doi:10.3390/ph14050414 .

Aničić, Neda, Gašić, Uroš, Lu, Feng, Ćirić, Ana, Ivanov, Marija, Jevtić, Bojan, Dimitrijević, Milena, Anđelković, Boban, Skorić, Marijana, Nestorović Živković, Jasmina, Mao, Yingle, Liu, Jia, Tang, Chunping, Soković, Marina, Ye, Yang, Mišić, Danijela, "Antimicrobial and Immunomodulating Activities of Two Endemic Nepeta Species and Their Major Iridoids Isolated from Natural Sources" in Pharmaceuticals, 14, no. 5 (2021):414,
https://doi.org/10.3390/ph14050414 . .

TY  - CONF
AU  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Diamantis, Dimitris
AU  - Papaemmanouil, Christina
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Tzakos, Andreas G
AU  - Miljković, Đorđe
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6297
AB  - Rosmarinic acid is a polyphenolic compound, abundantly presentin herbs of the Lamiaceae
family. The aim of the study was to evaluate a recently developed rosmarinic acid
derivative (RAd), with an enhanced ability of diffusion through biological membranes 1, in
preclinical settingsof the central nervous system autoimmunity. To this extent,
experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis
was used. EAE was induced in DA rats by subcutaneous injection of autologous spinal
cord homogenate 2, while treatment with RAd (30 mg/kg) started at 7 day post
immunization and lasted for 15 days. Subcutaneous RAd administration successfully
ameliorated EAE, leading to abbreviation of the disease duration and reducement of
maximal, cumulative and meanclinical score. Also, RAd effects on draining lymph node
cells (DLNC) isolated in the inductive phase of EAE and spinal cord immune cells (SCIC)
obtained at the peak of the diseasewere evaluated. In vitro treatment with RAd (5 μM)
reduced production of major encephalitogenic cytokines, i.e.interferon (IFN)-γ and
interleukin (IL)-17, both in DLNC and SCIC. The reduction of IFN-γ and IL-17
production under the influence of RAd was also detected in the CD4+ T cells purified
fromDLNC, thus suggesting that RAd had a direct effect on CD4+ T cells. Additionally,
the effects of in vitro treatment with RAd were examinedon macrophages (Mf), immune
cells with important role in EAE pathogenesis. Treatment of peritoneal Mf,obtained from
non-immunized DA rats, with RAd (25 μM) led to reduction of NO and IL-6 production,
exterted no effect on IL-1beta production, and elevated tumor necrosis factor production in
Mf. Expression of MHC II and co-stimulatory molecule CD80, the phagocytic ability and
the production of reactive oxygen species in RAd-treated Mf were also downregulated.
Our results imply that RAd possesses anti-inflammatory and antiencephalitogenicproperties. Thus, further studies on the mechanisms behind the observed
effects and their relevance for the therapy of multiple sclerosis are warranted.
PB  - Belgrade: Faculty of Chemistry
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats
SP  - 79
EP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6297
ER  - 

@conference{
author = "Lazarević, Milica and Stegnjaić, Goran and Diamantis, Dimitris and Papaemmanouil, Christina and Nikolovski, Neda and Jevtić, Bojan and Tzakos, Andreas G and Miljković, Đorđe",
year = "2021",
abstract = "Rosmarinic acid is a polyphenolic compound, abundantly presentin herbs of the Lamiaceae
family. The aim of the study was to evaluate a recently developed rosmarinic acid
derivative (RAd), with an enhanced ability of diffusion through biological membranes 1, in
preclinical settingsof the central nervous system autoimmunity. To this extent,
experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis
was used. EAE was induced in DA rats by subcutaneous injection of autologous spinal
cord homogenate 2, while treatment with RAd (30 mg/kg) started at 7 day post
immunization and lasted for 15 days. Subcutaneous RAd administration successfully
ameliorated EAE, leading to abbreviation of the disease duration and reducement of
maximal, cumulative and meanclinical score. Also, RAd effects on draining lymph node
cells (DLNC) isolated in the inductive phase of EAE and spinal cord immune cells (SCIC)
obtained at the peak of the diseasewere evaluated. In vitro treatment with RAd (5 μM)
reduced production of major encephalitogenic cytokines, i.e.interferon (IFN)-γ and
interleukin (IL)-17, both in DLNC and SCIC. The reduction of IFN-γ and IL-17
production under the influence of RAd was also detected in the CD4+ T cells purified
fromDLNC, thus suggesting that RAd had a direct effect on CD4+ T cells. Additionally,
the effects of in vitro treatment with RAd were examinedon macrophages (Mf), immune
cells with important role in EAE pathogenesis. Treatment of peritoneal Mf,obtained from
non-immunized DA rats, with RAd (25 μM) led to reduction of NO and IL-6 production,
exterted no effect on IL-1beta production, and elevated tumor necrosis factor production in
Mf. Expression of MHC II and co-stimulatory molecule CD80, the phagocytic ability and
the production of reactive oxygen species in RAd-treated Mf were also downregulated.
Our results imply that RAd possesses anti-inflammatory and antiencephalitogenicproperties. Thus, further studies on the mechanisms behind the observed
effects and their relevance for the therapy of multiple sclerosis are warranted.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats",
pages = "79-80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6297"
}

Lazarević, M., Stegnjaić, G., Diamantis, D., Papaemmanouil, C., Nikolovski, N., Jevtić, B., Tzakos, A. G.,& Miljković, Đ.. (2021). The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry., 79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6297

Lazarević M, Stegnjaić G, Diamantis D, Papaemmanouil C, Nikolovski N, Jevtić B, Tzakos AG, Miljković Đ. The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6297 .

Lazarević, Milica, Stegnjaić, Goran, Diamantis, Dimitris, Papaemmanouil, Christina, Nikolovski, Neda, Jevtić, Bojan, Tzakos, Andreas G, Miljković, Đorđe, "The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):79-80,
https://hdl.handle.net/21.15107/rcub_ibiss_6297 .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Stegnjaić, Goran
AU  - Krishnamoorthy, Gurumoorthy
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Jevtić, Bojan
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4200
AB  - Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.
PB  - Elsevier BV
T2  - Journal of Neuroimmunology
T1  - Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.
VL  - 354
DO  - 10.1016/j.jneuroim.2021.577547
SP  - 577547
ER  - 

@article{
author = "Lazarević, Milica and Nikolovski, Neda and Stanisavljević, Suzana and Dimitrijević, Mirjana and Stegnjaić, Goran and Krishnamoorthy, Gurumoorthy and Mostarica Stojković, Marija and Miljković, Đorđe and Jevtić, Bojan",
year = "2021",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.",
publisher = "Elsevier BV",
journal = "Journal of Neuroimmunology",
title = "Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.",
volume = "354",
doi = "10.1016/j.jneuroim.2021.577547",
pages = "577547"
}

Lazarević, M., Nikolovski, N., Stanisavljević, S., Dimitrijević, M., Stegnjaić, G., Krishnamoorthy, G., Mostarica Stojković, M., Miljković, Đ.,& Jevtić, B.. (2021). Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.. in Journal of Neuroimmunology
Elsevier BV., 354, 577547.
https://doi.org/10.1016/j.jneuroim.2021.577547

Lazarević M, Nikolovski N, Stanisavljević S, Dimitrijević M, Stegnjaić G, Krishnamoorthy G, Mostarica Stojković M, Miljković Đ, Jevtić B. Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.. in Journal of Neuroimmunology. 2021;354:577547.
doi:10.1016/j.jneuroim.2021.577547 .

Lazarević, Milica, Nikolovski, Neda, Stanisavljević, Suzana, Dimitrijević, Mirjana, Stegnjaić, Goran, Krishnamoorthy, Gurumoorthy, Mostarica Stojković, Marija, Miljković, Đorđe, Jevtić, Bojan, "Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies." in Journal of Neuroimmunology, 354 (2021):577547,
https://doi.org/10.1016/j.jneuroim.2021.577547 . .

TY  - CONF
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Diamantis, Dimitris
AU  - Papaemmanouil, Christina
AU  - Mićanović, Dragica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Saksida, Tamara
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4877
AB  - Rosmarinic acid (RA) is a polyphenol compound that naturally occurs in plants of the Lamiaceae family. A novel rosmarinic acid derivative (RAd) has been developed and tested in the animal model of type 1 diabetes (T1D) and the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). T1D was induced in male C57BL/6 mice using streptozotocin that was applied intraperitoneally for five consecutive days. EAE was induced in Dark Agouti (DA) rats by subcutaneous injection of autologous spinal cord homogenate. For T1D, intraperitoneal administration of RAd (10 mg/kg bw) began from the first streptozotocin injection and continued for 20 days, while for EAE, subcutaneous administration of RAd (28 mg/kg bw) started with the first clinical signs of the disease and continued for 15 days. RAd‐treated mice exhibited lower incidence of T1D (monitored up to 45 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. Additionally, RAd ameliorated EAE in DA rats. In T1D, RAd treatment significantly down‐regulated the proportions of CD11b⁺ and CD11c⁺ myeloid cells in the immune cell infiltrates in the pancreas, detected on day 10 after T1D induction. However, the proportions of cells of adaptive immunity (CD4⁺, CD8⁺, Th1, Th17) were comparable between the groups. These results suggest that chemically modified RA shows great promise for anti‐inflammatory approaches in autoimmune and inflammatory diseases, while our previous research illustrated that unmodified RA exerted no effect on T1D pathogenesis.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model
DO  - 10.1002/eji.202170200
SP  - 399
ER  - 

@conference{
author = "Koprivica, Ivan and Jonić, Natalija and Diamantis, Dimitris and Papaemmanouil, Christina and Mićanović, Dragica and Stegnjaić, Goran and Jevtić, Bojan and Saksida, Tamara and Miljković, Đorđe and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "Rosmarinic acid (RA) is a polyphenol compound that naturally occurs in plants of the Lamiaceae family. A novel rosmarinic acid derivative (RAd) has been developed and tested in the animal model of type 1 diabetes (T1D) and the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). T1D was induced in male C57BL/6 mice using streptozotocin that was applied intraperitoneally for five consecutive days. EAE was induced in Dark Agouti (DA) rats by subcutaneous injection of autologous spinal cord homogenate. For T1D, intraperitoneal administration of RAd (10 mg/kg bw) began from the first streptozotocin injection and continued for 20 days, while for EAE, subcutaneous administration of RAd (28 mg/kg bw) started with the first clinical signs of the disease and continued for 15 days. RAd‐treated mice exhibited lower incidence of T1D (monitored up to 45 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. Additionally, RAd ameliorated EAE in DA rats. In T1D, RAd treatment significantly down‐regulated the proportions of CD11b⁺ and CD11c⁺ myeloid cells in the immune cell infiltrates in the pancreas, detected on day 10 after T1D induction. However, the proportions of cells of adaptive immunity (CD4⁺, CD8⁺, Th1, Th17) were comparable between the groups. These results suggest that chemically modified RA shows great promise for anti‐inflammatory approaches in autoimmune and inflammatory diseases, while our previous research illustrated that unmodified RA exerted no effect on T1D pathogenesis.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model",
doi = "10.1002/eji.202170200",
pages = "399"
}

Koprivica, I., Jonić, N., Diamantis, D., Papaemmanouil, C., Mićanović, D., Stegnjaić, G., Jevtić, B., Saksida, T., Miljković, Đ., Tzakos, A.,& Stojanović, I. D.. (2021). Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 399.
https://doi.org/10.1002/eji.202170200

Koprivica I, Jonić N, Diamantis D, Papaemmanouil C, Mićanović D, Stegnjaić G, Jevtić B, Saksida T, Miljković Đ, Tzakos A, Stojanović ID. Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;:399.
doi:10.1002/eji.202170200 .

Koprivica, Ivan, Jonić, Natalija, Diamantis, Dimitris, Papaemmanouil, Christina, Mićanović, Dragica, Stegnjaić, Goran, Jevtić, Bojan, Saksida, Tamara, Miljković, Đorđe, Tzakos, Andreas, Stojanović, Ivana D., "Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting (2021):399,
https://doi.org/10.1002/eji.202170200 . .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4234
AB  - Significance: Autoimmune diseases are progressively affecting westernized societies, asthe proportion of individuals suffering from autoimmunity is steadily increasing over thepast decades. Understanding the role of reactive oxygen species (ROS) in modulation ofthe immune response in the pathogenesis of autoimmune disorders is of utmostimportance. The focus of this review is the regulation of ROS production within tolerogenicdendritic cells (tolDC) and regulatory T (Treg) cells that have the essential role in theprevention of autoimmune diseases and significant potency in their therapy.Recent Advances: It is now clear that ROS are extremely important for the proper functionof both DC and T cells. Antigen processing/presentation and the ability of DC to activate Tcells depend upon the ROS availability. Treg differentiation, suppressive function andstability are profoundly influenced by ROS presence.Critical Issues: Although a plethora of results on the relation between ROS and immunecells exists, it remains unclear whether ROS modulation is a productive way for skewing Tcells and DC towards a tolerogenic phenotype. Also, the possibility of ROS modulation forenhancement of regulatory properties of DC and Treg during their preparation for use incellular therapy has to be clarified.Future Directions: Studies of DC and T cell redox regulation should allow for theimprovement of the therapy of autoimmune diseases. This could be achieved through thedirect therapeutic application of ROS modulators in autoimmunity or indirectly, throughROS-dependent enhancement of tolDC and Treg preparation for cell-basedimmunotherapy.
PB  - Mary Ann Liebert, Inc.
T2  - Antioxidants & Redox Signaling
T1  - Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity
IS  - 5
VL  - 34
DO  - 10.1089/ars.2019.7999
SP  - 364
EP  - 382
ER  - 

@article{
author = "Saksida, Tamara and Jevtić, Bojan and Nikolovski, Neda and Miljković, Đorđe and Stojanović, Ivana D.",
year = "2021",
abstract = "Significance: Autoimmune diseases are progressively affecting westernized societies, asthe proportion of individuals suffering from autoimmunity is steadily increasing over thepast decades. Understanding the role of reactive oxygen species (ROS) in modulation ofthe immune response in the pathogenesis of autoimmune disorders is of utmostimportance. The focus of this review is the regulation of ROS production within tolerogenicdendritic cells (tolDC) and regulatory T (Treg) cells that have the essential role in theprevention of autoimmune diseases and significant potency in their therapy.Recent Advances: It is now clear that ROS are extremely important for the proper functionof both DC and T cells. Antigen processing/presentation and the ability of DC to activate Tcells depend upon the ROS availability. Treg differentiation, suppressive function andstability are profoundly influenced by ROS presence.Critical Issues: Although a plethora of results on the relation between ROS and immunecells exists, it remains unclear whether ROS modulation is a productive way for skewing Tcells and DC towards a tolerogenic phenotype. Also, the possibility of ROS modulation forenhancement of regulatory properties of DC and Treg during their preparation for use incellular therapy has to be clarified.Future Directions: Studies of DC and T cell redox regulation should allow for theimprovement of the therapy of autoimmune diseases. This could be achieved through thedirect therapeutic application of ROS modulators in autoimmunity or indirectly, throughROS-dependent enhancement of tolDC and Treg preparation for cell-basedimmunotherapy.",
publisher = "Mary Ann Liebert, Inc.",
journal = "Antioxidants & Redox Signaling",
title = "Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity",
number = "5",
volume = "34",
doi = "10.1089/ars.2019.7999",
pages = "364-382"
}

Saksida, T., Jevtić, B., Nikolovski, N., Miljković, Đ.,& Stojanović, I. D.. (2021). Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity. in Antioxidants & Redox Signaling
Mary Ann Liebert, Inc.., 34(5), 364-382.
https://doi.org/10.1089/ars.2019.7999

Saksida T, Jevtić B, Nikolovski N, Miljković Đ, Stojanović ID. Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity. in Antioxidants & Redox Signaling. 2021;34(5):364-382.
doi:10.1089/ars.2019.7999 .

Saksida, Tamara, Jevtić, Bojan, Nikolovski, Neda, Miljković, Đorđe, Stojanović, Ivana D., "Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity" in Antioxidants & Redox Signaling, 34, no. 5 (2021):364-382,
https://doi.org/10.1089/ars.2019.7999 . .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3766
AB  - Significance: Autoimmune diseases are progressively affecting westernized societies, as
the proportion of individuals suffering from autoimmunity is steadily increasing over the
past decades. Understanding the role of reactive oxygen species (ROS) in modulation of
the immune response in the pathogenesis of autoimmune disorders is of utmost
importance. The focus of this review is the regulation of ROS production within tolerogenic
dendritic cells (tolDC) and regulatory T (Treg) cells that have the essential role in the
prevention of autoimmune diseases and significant potency in their therapy.
Recent Advances: It is now clear that ROS are extremely important for the proper function
of both DC and T cells. Antigen processing/presentation and the ability of DC to activate T
cells depend upon the ROS availability. Treg differentiation, suppressive function and
stability are profoundly influenced by ROS presence.
Critical Issues: Although a plethora of results on the relation between ROS and immune
cells exists, it remains unclear whether ROS modulation is a productive way for skewing T
cells and DC towards a tolerogenic phenotype. Also, the possibility of ROS modulation for
enhancement of regulatory properties of DC and Treg during their preparation for use in
cellular therapy has to be clarified.
Future Directions: Studies of DC and T cell redox regulation should allow for the
improvement of the therapy of autoimmune diseases. This could be achieved through the
direct therapeutic application of ROS modulators in autoimmunity or indirectly, through
ROS-dependent enhancement of tolDC and Treg preparation for cell-based
immunotherapy.
PB  - Mary Ann Liebert, Inc.
T2  - Antioxidants & Redox Signaling
T1  - Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity
IS  - 5
VL  - 34
DO  - 10.1089/ars.2019.7999
SP  - 364
EP  - 382
ER  - 

@article{
author = "Saksida, Tamara and Jevtić, Bojan and Nikolovski, Neda and Miljković, Đorđe and Stojanović, Ivana D.",
year = "2021",
abstract = "Significance: Autoimmune diseases are progressively affecting westernized societies, as
the proportion of individuals suffering from autoimmunity is steadily increasing over the
past decades. Understanding the role of reactive oxygen species (ROS) in modulation of
the immune response in the pathogenesis of autoimmune disorders is of utmost
importance. The focus of this review is the regulation of ROS production within tolerogenic
dendritic cells (tolDC) and regulatory T (Treg) cells that have the essential role in the
prevention of autoimmune diseases and significant potency in their therapy.
Recent Advances: It is now clear that ROS are extremely important for the proper function
of both DC and T cells. Antigen processing/presentation and the ability of DC to activate T
cells depend upon the ROS availability. Treg differentiation, suppressive function and
stability are profoundly influenced by ROS presence.
Critical Issues: Although a plethora of results on the relation between ROS and immune
cells exists, it remains unclear whether ROS modulation is a productive way for skewing T
cells and DC towards a tolerogenic phenotype. Also, the possibility of ROS modulation for
enhancement of regulatory properties of DC and Treg during their preparation for use in
cellular therapy has to be clarified.
Future Directions: Studies of DC and T cell redox regulation should allow for the
improvement of the therapy of autoimmune diseases. This could be achieved through the
direct therapeutic application of ROS modulators in autoimmunity or indirectly, through
ROS-dependent enhancement of tolDC and Treg preparation for cell-based
immunotherapy.",
publisher = "Mary Ann Liebert, Inc.",
journal = "Antioxidants & Redox Signaling",
title = "Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity",
number = "5",
volume = "34",
doi = "10.1089/ars.2019.7999",
pages = "364-382"
}

Saksida, T., Jevtić, B., Nikolovski, N., Miljković, Đ.,& Stojanović, I. D.. (2021). Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity. in Antioxidants & Redox Signaling
Mary Ann Liebert, Inc.., 34(5), 364-382.
https://doi.org/10.1089/ars.2019.7999

Saksida T, Jevtić B, Nikolovski N, Miljković Đ, Stojanović ID. Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity. in Antioxidants & Redox Signaling. 2021;34(5):364-382.
doi:10.1089/ars.2019.7999 .

Saksida, Tamara, Jevtić, Bojan, Nikolovski, Neda, Miljković, Đorđe, Stojanović, Ivana D., "Redox Regulation of Tolerogenic Dendritic Cells and Regulatory T Cells in the Pathogenesis and Therapy of Autoimmunity" in Antioxidants & Redox Signaling, 34, no. 5 (2021):364-382,
https://doi.org/10.1089/ars.2019.7999 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Stegnjaić, Goran
AU  - Krishnamoorthy, Gurumoorthy
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Jevtić, Bojan
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4193
AB  - Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.
PB  - Elsevier BV
T2  - Journal of Neuroimmunology
T1  - Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.
VL  - 354
DO  - 10.1016/j.jneuroim.2021.577547
SP  - 577547
ER  - 

@article{
author = "Lazarević, Milica and Nikolovski, Neda and Stanisavljević, Suzana and Dimitrijević, Mirjana and Stegnjaić, Goran and Krishnamoorthy, Gurumoorthy and Mostarica Stojković, Marija and Miljković, Đorđe and Jevtić, Bojan",
year = "2021",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.",
publisher = "Elsevier BV",
journal = "Journal of Neuroimmunology",
title = "Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.",
volume = "354",
doi = "10.1016/j.jneuroim.2021.577547",
pages = "577547"
}

Lazarević, M., Nikolovski, N., Stanisavljević, S., Dimitrijević, M., Stegnjaić, G., Krishnamoorthy, G., Mostarica Stojković, M., Miljković, Đ.,& Jevtić, B.. (2021). Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.. in Journal of Neuroimmunology
Elsevier BV., 354, 577547.
https://doi.org/10.1016/j.jneuroim.2021.577547

Lazarević M, Nikolovski N, Stanisavljević S, Dimitrijević M, Stegnjaić G, Krishnamoorthy G, Mostarica Stojković M, Miljković Đ, Jevtić B. Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.. in Journal of Neuroimmunology. 2021;354:577547.
doi:10.1016/j.jneuroim.2021.577547 .

Lazarević, Milica, Nikolovski, Neda, Stanisavljević, Suzana, Dimitrijević, Mirjana, Stegnjaić, Goran, Krishnamoorthy, Gurumoorthy, Mostarica Stojković, Marija, Miljković, Đorđe, Jevtić, Bojan, "Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies." in Journal of Neuroimmunology, 354 (2021):577547,
https://doi.org/10.1016/j.jneuroim.2021.577547 . .

TY  - JOUR
AU  - Miljković, Đorđe
AU  - Jevtić, Bojan
AU  - Stojanović, Ivana D.
AU  - Dimitrijević, Mirjana
PY  - 2021
UR  - www.frontiersin.org
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4227
AB  - Gut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS, i.e. T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases. Besides, they are also well known for their ability to stabilize the intestinal barrier and to shape the immune response to the gut microbiota. Thus, proper maintenance of the intestinal barrier and the establishment of the regulatory milieu in the gut performed by ILC3 may prevent activation of CNS antigen-specific Th17 cells by the molecular mimicry. Recent findings on the role of ILC3 in the gut-CNS axis and their relevance for MS pathogenesis will be discussed in this paper. Possibilities of ILC3 functional modulation for the benefit of MS patients will be addressed, as well.
PB  - Frontiers Media S.A.
T2  - Frontiers in Immunology
T1  - ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis
VL  - 12
DO  - 10.3389/fimmu.2021.657622
SP  - 1025
ER  - 

@article{
author = "Miljković, Đorđe and Jevtić, Bojan and Stojanović, Ivana D. and Dimitrijević, Mirjana",
year = "2021",
abstract = "Gut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS, i.e. T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases. Besides, they are also well known for their ability to stabilize the intestinal barrier and to shape the immune response to the gut microbiota. Thus, proper maintenance of the intestinal barrier and the establishment of the regulatory milieu in the gut performed by ILC3 may prevent activation of CNS antigen-specific Th17 cells by the molecular mimicry. Recent findings on the role of ILC3 in the gut-CNS axis and their relevance for MS pathogenesis will be discussed in this paper. Possibilities of ILC3 functional modulation for the benefit of MS patients will be addressed, as well.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Immunology",
title = "ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis",
volume = "12",
doi = "10.3389/fimmu.2021.657622",
pages = "1025"
}

Miljković, Đ., Jevtić, B., Stojanović, I. D.,& Dimitrijević, M.. (2021). ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis. in Frontiers in Immunology
Frontiers Media S.A.., 12, 1025.
https://doi.org/10.3389/fimmu.2021.657622

Miljković Đ, Jevtić B, Stojanović ID, Dimitrijević M. ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis. in Frontiers in Immunology. 2021;12:1025.
doi:10.3389/fimmu.2021.657622 .

Miljković, Đorđe, Jevtić, Bojan, Stojanović, Ivana D., Dimitrijević, Mirjana, "ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis" in Frontiers in Immunology, 12 (2021):1025,
https://doi.org/10.3389/fimmu.2021.657622 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Battaglia, Giuseppe
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Bruno, Valeria
AU  - Cavalli, Eugenio
AU  - Miljković, Đorđe
AU  - Nicoletti, Ferdinando
AU  - Momčilović, Miljana
AU  - Fagone, Paolo
PY  - 2020
UR  - https://www.mdpi.com/2076-3921/9/7/608
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32664399
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3819
AB  - The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.
PB  - MDPI AG
T2  - Antioxidants (Basel, Switzerland)
T2  - Antioxidants (Basel, Switzerland)
T1  - Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.
IS  - 7
VL  - 9
DO  - 10.3390/antiox9070608
SP  - 608
ER  - 

@article{
author = "Lazarević, Milica and Battaglia, Giuseppe and Jevtić, Bojan and Nikolovski, Neda and Bruno, Valeria and Cavalli, Eugenio and Miljković, Đorđe and Nicoletti, Ferdinando and Momčilović, Miljana and Fagone, Paolo",
year = "2020",
abstract = "The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.",
publisher = "MDPI AG",
journal = "Antioxidants (Basel, Switzerland), Antioxidants (Basel, Switzerland)",
title = "Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.",
number = "7",
volume = "9",
doi = "10.3390/antiox9070608",
pages = "608"
}

Lazarević, M., Battaglia, G., Jevtić, B., Nikolovski, N., Bruno, V., Cavalli, E., Miljković, Đ., Nicoletti, F., Momčilović, M.,& Fagone, P.. (2020). Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.. in Antioxidants (Basel, Switzerland)
MDPI AG., 9(7), 608.
https://doi.org/10.3390/antiox9070608

Lazarević M, Battaglia G, Jevtić B, Nikolovski N, Bruno V, Cavalli E, Miljković Đ, Nicoletti F, Momčilović M, Fagone P. Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.. in Antioxidants (Basel, Switzerland). 2020;9(7):608.
doi:10.3390/antiox9070608 .

Lazarević, Milica, Battaglia, Giuseppe, Jevtić, Bojan, Nikolovski, Neda, Bruno, Valeria, Cavalli, Eugenio, Miljković, Đorđe, Nicoletti, Ferdinando, Momčilović, Miljana, Fagone, Paolo, "Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis." in Antioxidants (Basel, Switzerland), 9, no. 7 (2020):608,
https://doi.org/10.3390/antiox9070608 . .

TY  - CONF
AU  - Jevtić, Bojan
AU  - Saksida, Tamara
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Paunović, Verica
AU  - Stojanović, Ivana D.
AU  - Pejnović, Nada
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5782
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the imbalance
between the CD4 or CD8 T effector (Teff) cells and the FoxP3+CD4 T regulatory cells
(Tregs) that leads to pancreatic beta-cells destruction causing insulin deficiency.
Environmental factors, diet and microbiome are associated with the recent rise in T1D
incidence. Intestinal immune cells must maintain a tolerogenic response in the gut that
involves the development of Tregs. Recent data show that IL-2-producing type 3 innate
lymphoid cells ILC3s (IL-2+ILC3) in the small intestine are essential for maintaining
FoxP3+ Tregs and oral tolerance to dietary antigens and reveal the previously unknown
direct communication between ILC3s and Treg cells in the gut. We investigated the
frequencies of small intestine lamina propria IL-2+ILC3s and FoxP3+ Tregs during
transition from prediabetes to diabetes in young and old female NOD mice. 20 weeks
old, diabetic NOD mice had higher frequencies of LinnegCD45+RORγt+CD127+ ILC3s
in small intestine lamina propria compared to 4 weeks of age-young NOD mice.
However, the frequencies of IL-2-producing ILC3s and CD4+CD25hiFoxP3+ Tregs
were significantly lower in diabetic NOD mice compared to young, prediabetic mice.
We next investigated how microbiota change before diabetes induction is reflected on
Treg and ILC3 populations. Male C57BL/6 mice were treated with broad spectrum
antibiotics (ABX) for 14 days and then T1D was induced by multiple low doses of
streptozotocin (STZ). Ex vivo cell analyses was done on day 10 after the first STZ
injection. The significantly higher incidence of T1D observed in ABX-treated mice
correlated with significantly lower frequencies of IL-2-producing ILC3s and
FoxP3+Tregs in small intestine lamina propria compared to mice treated with STZ only.
The obtained findings show that the decrease of tolerogenic ILC3s and FoxP3+Tregs in
small intestine is associated with the progression and higher incidence of T1D.
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  - The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice
SP  - 102
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5782
ER  - 

@conference{
author = "Jevtić, Bojan and Saksida, Tamara and Mićanović, Dragica and Koprivica, Ivan and Paunović, Verica and Stojanović, Ivana D. and Pejnović, Nada",
year = "2019",
abstract = "Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the imbalance
between the CD4 or CD8 T effector (Teff) cells and the FoxP3+CD4 T regulatory cells
(Tregs) that leads to pancreatic beta-cells destruction causing insulin deficiency.
Environmental factors, diet and microbiome are associated with the recent rise in T1D
incidence. Intestinal immune cells must maintain a tolerogenic response in the gut that
involves the development of Tregs. Recent data show that IL-2-producing type 3 innate
lymphoid cells ILC3s (IL-2+ILC3) in the small intestine are essential for maintaining
FoxP3+ Tregs and oral tolerance to dietary antigens and reveal the previously unknown
direct communication between ILC3s and Treg cells in the gut. We investigated the
frequencies of small intestine lamina propria IL-2+ILC3s and FoxP3+ Tregs during
transition from prediabetes to diabetes in young and old female NOD mice. 20 weeks
old, diabetic NOD mice had higher frequencies of LinnegCD45+RORγt+CD127+ ILC3s
in small intestine lamina propria compared to 4 weeks of age-young NOD mice.
However, the frequencies of IL-2-producing ILC3s and CD4+CD25hiFoxP3+ Tregs
were significantly lower in diabetic NOD mice compared to young, prediabetic mice.
We next investigated how microbiota change before diabetes induction is reflected on
Treg and ILC3 populations. Male C57BL/6 mice were treated with broad spectrum
antibiotics (ABX) for 14 days and then T1D was induced by multiple low doses of
streptozotocin (STZ). Ex vivo cell analyses was done on day 10 after the first STZ
injection. The significantly higher incidence of T1D observed in ABX-treated mice
correlated with significantly lower frequencies of IL-2-producing ILC3s and
FoxP3+Tregs in small intestine lamina propria compared to mice treated with STZ only.
The obtained findings show that the decrease of tolerogenic ILC3s and FoxP3+Tregs in
small intestine is associated with the progression and higher incidence of T1D.",
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 = "The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice",
pages = "102",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5782"
}

Jevtić, B., Saksida, T., Mićanović, D., Koprivica, I., Paunović, V., Stojanović, I. D.,& Pejnović, N.. (2019). The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of 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., 102.
https://hdl.handle.net/21.15107/rcub_ibiss_5782

Jevtić B, Saksida T, Mićanović D, Koprivica I, Paunović V, Stojanović ID, Pejnović N. The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2019;:102.
https://hdl.handle.net/21.15107/rcub_ibiss_5782 .

Jevtić, Bojan, Saksida, Tamara, Mićanović, Dragica, Koprivica, Ivan, Paunović, Verica, Stojanović, Ivana D., Pejnović, Nada, "The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2019):102,
https://hdl.handle.net/21.15107/rcub_ibiss_5782 .