TY  - JOUR
AU  - Šaponjić, Jasna
AU  - Mejías, Rebeca
AU  - Nikolovski, Neda
AU  - Dragic, Milorad
AU  - Canak, Asuman
AU  - Papoutsopoulou, Stamatia
AU  - Gürsoy-Özdemir, Yasemin
AU  - Fladmark, Kari
AU  - Ntavaroukas, Panagiotis
AU  - Bayar Muluk, Nuray
AU  - Zeljkovic Jovanovic, Milica
AU  - Fontán-Lozano, Ángela
AU  - Comi, Cristoforo
AU  - Marino, Franca
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6685
AB  - Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological
approaches used to study the changes in central and peripheral immunity in PD, the advantages and
limitations of the techniques, and their applicability to humans. Although a single animal model
cannot replicate all pathological features of the human disease, neuroinflammation is present in
most animal models of PD and plays a critical role in understanding the involvement of the immune
system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the
central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture
models do not fully reflect the complexity of disease progression, they are limited in their ability to
mimic long-term effects and need validation through in vivo studies. They are an indispensable tool
for understanding the interplay between the IS and the pathogenesis of this disease. Understanding
the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD.
We believe that the development of methodological guidelines for experiments with animal models
and PD patients is crucial to ensure the validity and consistency of the results.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease
IS  - 8
VL  - 25
DO  - 10.3390/ijms25084330
SP  - 4330
ER  - 

@article{
author = "Šaponjić, Jasna and Mejías, Rebeca and Nikolovski, Neda and Dragic, Milorad and Canak, Asuman and Papoutsopoulou, Stamatia and Gürsoy-Özdemir, Yasemin and Fladmark, Kari and Ntavaroukas, Panagiotis and Bayar Muluk, Nuray and Zeljkovic Jovanovic, Milica and Fontán-Lozano, Ángela and Comi, Cristoforo and Marino, Franca",
year = "2024",
abstract = "Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological
approaches used to study the changes in central and peripheral immunity in PD, the advantages and
limitations of the techniques, and their applicability to humans. Although a single animal model
cannot replicate all pathological features of the human disease, neuroinflammation is present in
most animal models of PD and plays a critical role in understanding the involvement of the immune
system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the
central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture
models do not fully reflect the complexity of disease progression, they are limited in their ability to
mimic long-term effects and need validation through in vivo studies. They are an indispensable tool
for understanding the interplay between the IS and the pathogenesis of this disease. Understanding
the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD.
We believe that the development of methodological guidelines for experiments with animal models
and PD patients is crucial to ensure the validity and consistency of the results.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease",
number = "8",
volume = "25",
doi = "10.3390/ijms25084330",
pages = "4330"
}

Šaponjić, J., Mejías, R., Nikolovski, N., Dragic, M., Canak, A., Papoutsopoulou, S., Gürsoy-Özdemir, Y., Fladmark, K., Ntavaroukas, P., Bayar Muluk, N., Zeljkovic Jovanovic, M., Fontán-Lozano, Á., Comi, C.,& Marino, F.. (2024). Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease. in International Journal of Molecular Sciences
Basel: MDPI., 25(8), 4330.
https://doi.org/10.3390/ijms25084330

Šaponjić J, Mejías R, Nikolovski N, Dragic M, Canak A, Papoutsopoulou S, Gürsoy-Özdemir Y, Fladmark K, Ntavaroukas P, Bayar Muluk N, Zeljkovic Jovanovic M, Fontán-Lozano Á, Comi C, Marino F. Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease. in International Journal of Molecular Sciences. 2024;25(8):4330.
doi:10.3390/ijms25084330 .

Šaponjić, Jasna, Mejías, Rebeca, Nikolovski, Neda, Dragic, Milorad, Canak, Asuman, Papoutsopoulou, Stamatia, Gürsoy-Özdemir, Yasemin, Fladmark, Kari, Ntavaroukas, Panagiotis, Bayar Muluk, Nuray, Zeljkovic Jovanovic, Milica, Fontán-Lozano, Ángela, Comi, Cristoforo, Marino, Franca, "Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease" in International Journal of Molecular Sciences, 25, no. 8 (2024):4330,
https://doi.org/10.3390/ijms25084330 . .

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  - Mićanović, Dragica
AU  - Stegnjaić, Goran
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Foresti, Roberta
AU  - Motterlini, Roberto
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2023
UR  - https://benbedphar.org/wp-content/uploads/2023/10/abstract_book_Graz_final.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6473
AB  - Type 1 diabetes (T1D) is an autoimmune disease that leads to the death of insulin-producing
pancreatic β-cells. The autoimmune response in T1D becomes chronic as a consequence of
regulatory mechanisms unable to counteract this disease. In this study, we evaluated the
anti-diabetic potential of a new hybrid compound (HYCO-3) consisting of a CO-releasing
molecule conjugated to a fumaric ester derivative that is known to activate the Nrf2 and
increase the expression of the CO-producing enzyme heme oxygenase-1. T1D was induced
in C57BL/6 mice treated intraperitoneally for 5 consecutive days with multiple low doses of
streptozotocin (40 mg/kg BW). HYCO-3 (25 mg/kg BW daily) was administered by oral
gavage while the control group received the vehicle (DMSO/sesame oil) for 14 days, starting
on the first day of streptozotocin treatment. To evaluate the development of T1D, glycaemia
and body mass were measured weekly. At the end of the experiment the pancreas was
collected and histochemical analyses for insulin expression were performed. Insulitis, the
infiltration of immune cells in the pancreas, was also assessed. We found that treatment
with HYCO-3 lowered blood glucose levels compared to the control group in association
with a lower insulitis grade and a higher expression of insulin in pancreatic islets.
Furthermore, to assess the effect of HYCO-3 on antigen specific response, cells from the
draining pancreatic lymph nodes of diabetic animals were stimulated with insulin and
HYCO-3 to assess the production of pro-inflammatory markers in cell supernatants. HYCO-
3 was able to down-regulate the production of IL-17 in the cultures where antigen specific
response was induced with insulin.
Overall, our results show that HYCO-3 ameliorated T1D in C57BL/6 mice by inhibiting the
recruitment of immune cells into the pancreas. These results warrant future investigation of
cellular and molecular mechanisms by which HYCO-3 acts on immune cells that are of
importance in the pathogenesis of T1D.
PB  - BenBedPhar Consortium
C3  - 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
T1  - HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model
SP  - 46
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6473
ER  - 

@conference{
author = "Mićanović, Dragica and Stegnjaić, Goran and Nikolovski, Neda and Momčilović, Miljana and Foresti, Roberta and Motterlini, Roberto and Miljković, Đorđe and Saksida, Tamara",
year = "2023",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease that leads to the death of insulin-producing
pancreatic β-cells. The autoimmune response in T1D becomes chronic as a consequence of
regulatory mechanisms unable to counteract this disease. In this study, we evaluated the
anti-diabetic potential of a new hybrid compound (HYCO-3) consisting of a CO-releasing
molecule conjugated to a fumaric ester derivative that is known to activate the Nrf2 and
increase the expression of the CO-producing enzyme heme oxygenase-1. T1D was induced
in C57BL/6 mice treated intraperitoneally for 5 consecutive days with multiple low doses of
streptozotocin (40 mg/kg BW). HYCO-3 (25 mg/kg BW daily) was administered by oral
gavage while the control group received the vehicle (DMSO/sesame oil) for 14 days, starting
on the first day of streptozotocin treatment. To evaluate the development of T1D, glycaemia
and body mass were measured weekly. At the end of the experiment the pancreas was
collected and histochemical analyses for insulin expression were performed. Insulitis, the
infiltration of immune cells in the pancreas, was also assessed. We found that treatment
with HYCO-3 lowered blood glucose levels compared to the control group in association
with a lower insulitis grade and a higher expression of insulin in pancreatic islets.
Furthermore, to assess the effect of HYCO-3 on antigen specific response, cells from the
draining pancreatic lymph nodes of diabetic animals were stimulated with insulin and
HYCO-3 to assess the production of pro-inflammatory markers in cell supernatants. HYCO-
3 was able to down-regulate the production of IL-17 in the cultures where antigen specific
response was induced with insulin.
Overall, our results show that HYCO-3 ameliorated T1D in C57BL/6 mice by inhibiting the
recruitment of immune cells into the pancreas. These results warrant future investigation of
cellular and molecular mechanisms by which HYCO-3 acts on immune cells that are of
importance in the pathogenesis of T1D.",
publisher = "BenBedPhar Consortium",
journal = "5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria",
title = "HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model",
pages = "46",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6473"
}

Mićanović, D., Stegnjaić, G., Nikolovski, N., Momčilović, M., Foresti, R., Motterlini, R., Miljković, Đ.,& Saksida, T.. (2023). HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
BenBedPhar Consortium., 46.
https://hdl.handle.net/21.15107/rcub_ibiss_6473

Mićanović D, Stegnjaić G, Nikolovski N, Momčilović M, Foresti R, Motterlini R, Miljković Đ, Saksida T. HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria. 2023;:46.
https://hdl.handle.net/21.15107/rcub_ibiss_6473 .

Mićanović, Dragica, Stegnjaić, Goran, Nikolovski, Neda, Momčilović, Miljana, Foresti, Roberta, Motterlini, Roberto, Miljković, Đorđe, Saksida, Tamara, "HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model" in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria (2023):46,
https://hdl.handle.net/21.15107/rcub_ibiss_6473 .

TY  - CONF
AU  - Stegnjaić, Goran
AU  - Mićanović, Dragica
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Saksida, Tamara
AU  - Foresti, Roberta
AU  - Motterlini, Roberto
AU  - Miljković, Đorđe
PY  - 2023
UR  - https://benbedphar.org/wp-content/uploads/2023/10/abstract_book_Graz_final.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6476
AB  - HYCOs are a novel class of hybrid compounds consisting of fumaric esters conjugated to
carbon monoxide-releasing molecules (CO-RMs). They were designed based on the
consideration that fumaric esters are known to activate the transcription factor Nrf2 and that
CO possesses potent anti-inflammatory properties. The dual action of these hybrids has
shown promising therapeutic effects. in animal models of psoriasis and multiple sclerosis.
We have recently started with the group of Drs Motterlini and Foresti in France a
collaborative research project relevant to the BenBedPhar COST Action, focusing on the
immunomodulatory effects of HYCOs. These effects were examined in vitro in cultures of
myeloid-derived cells (macrophages and dendritic cells), lymph node cells, immune cells
isolated from the inflamed central nervous system, and microglia. By assessing the
production of immunoactive molecules, including nitric oxide, reactive oxygen species and
cytokines, we provide evidence that HYCOs display immunomodulatory effects in all cell
populations examined in vitro. Moreover, we were able to demonstrate that HYCOs are
efficient in ameliorating type 1 diabetes in an animal model of this autoimmune disease. Our
results indicate that HYCOs are Nrf2 activators with promising immunomodulatory
therapeutic properties.
PB  - BenBedPhar Consortium
C3  - 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
T1  - Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues
SP  - 21
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6476
ER  - 

@conference{
author = "Stegnjaić, Goran and Mićanović, Dragica and Nikolovski, Neda and Momčilović, Miljana and Saksida, Tamara and Foresti, Roberta and Motterlini, Roberto and Miljković, Đorđe",
year = "2023",
abstract = "HYCOs are a novel class of hybrid compounds consisting of fumaric esters conjugated to
carbon monoxide-releasing molecules (CO-RMs). They were designed based on the
consideration that fumaric esters are known to activate the transcription factor Nrf2 and that
CO possesses potent anti-inflammatory properties. The dual action of these hybrids has
shown promising therapeutic effects. in animal models of psoriasis and multiple sclerosis.
We have recently started with the group of Drs Motterlini and Foresti in France a
collaborative research project relevant to the BenBedPhar COST Action, focusing on the
immunomodulatory effects of HYCOs. These effects were examined in vitro in cultures of
myeloid-derived cells (macrophages and dendritic cells), lymph node cells, immune cells
isolated from the inflamed central nervous system, and microglia. By assessing the
production of immunoactive molecules, including nitric oxide, reactive oxygen species and
cytokines, we provide evidence that HYCOs display immunomodulatory effects in all cell
populations examined in vitro. Moreover, we were able to demonstrate that HYCOs are
efficient in ameliorating type 1 diabetes in an animal model of this autoimmune disease. Our
results indicate that HYCOs are Nrf2 activators with promising immunomodulatory
therapeutic properties.",
publisher = "BenBedPhar Consortium",
journal = "5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria",
title = "Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues",
pages = "21",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6476"
}

Stegnjaić, G., Mićanović, D., Nikolovski, N., Momčilović, M., Saksida, T., Foresti, R., Motterlini, R.,& Miljković, Đ.. (2023). Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
BenBedPhar Consortium., 21.
https://hdl.handle.net/21.15107/rcub_ibiss_6476

Stegnjaić G, Mićanović D, Nikolovski N, Momčilović M, Saksida T, Foresti R, Motterlini R, Miljković Đ. Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria. 2023;:21.
https://hdl.handle.net/21.15107/rcub_ibiss_6476 .

Stegnjaić, Goran, Mićanović, Dragica, Nikolovski, Neda, Momčilović, Miljana, Saksida, Tamara, Foresti, Roberta, Motterlini, Roberto, Miljković, Đorđe, "Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues" in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria (2023):21,
https://hdl.handle.net/21.15107/rcub_ibiss_6476 .

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  - 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  - 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  - 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  - Koprivica, Ivan
AU  - Nikolovski, Neda
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
PY  - 2022
UR  - https://link.springer.com/10.1007/s00011-021-01529-z
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8742706
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4766
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4778
AB  - Ethyl pyruvate (EP) has potent influence on redox processes, cellular metabolism, and inflammation. It has been intensively studied in numerous animal models of systemic and organ-specific disorders whose pathogenesis involves a strong immune component. Here, basic chemical and biological properties of EP are discussed, with an emphasis on its redox and metabolic activity. Further, its influence on myeloid and T cells is considered, as well as on intracellular signaling beyond its effect on immune cells. Also, the effects of EP on animal models of chronic inflammatory and autoimmune disorders are presented. Finally, a possibility to apply EP as a treatment for such diseases in humans is discussed. Scientific papers cited in this review were identified using the PubMed search engine that relies on the MEDLINE database. The reference list covers the most important findings in the field in the past twenty years.
PB  - Basel: Springer Nature Switzerland AG
T2  - Inflammation Research
T1  - Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.
DO  - 10.1007/s00011-021-01529-z
ER  - 

@article{
author = "Koprivica, Ivan and Nikolovski, Neda and Stojanović, Ivana D. and Miljković, Đorđe",
year = "2022",
abstract = "Ethyl pyruvate (EP) has potent influence on redox processes, cellular metabolism, and inflammation. It has been intensively studied in numerous animal models of systemic and organ-specific disorders whose pathogenesis involves a strong immune component. Here, basic chemical and biological properties of EP are discussed, with an emphasis on its redox and metabolic activity. Further, its influence on myeloid and T cells is considered, as well as on intracellular signaling beyond its effect on immune cells. Also, the effects of EP on animal models of chronic inflammatory and autoimmune disorders are presented. Finally, a possibility to apply EP as a treatment for such diseases in humans is discussed. Scientific papers cited in this review were identified using the PubMed search engine that relies on the MEDLINE database. The reference list covers the most important findings in the field in the past twenty years.",
publisher = "Basel: Springer Nature Switzerland AG",
journal = "Inflammation Research",
title = "Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.",
doi = "10.1007/s00011-021-01529-z"
}

Koprivica, I., Nikolovski, N., Stojanović, I. D.,& Miljković, Đ.. (2022). Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.. in Inflammation Research
Basel: Springer Nature Switzerland AG..
https://doi.org/10.1007/s00011-021-01529-z

Koprivica I, Nikolovski N, Stojanović ID, Miljković Đ. Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.. in Inflammation Research. 2022;.
doi:10.1007/s00011-021-01529-z .

Koprivica, Ivan, Nikolovski, Neda, Stojanović, Ivana D., Miljković, Đorđe, "Ethyl pyruvate, a versatile protector in inflammation and autoimmunity." in Inflammation Research (2022),
https://doi.org/10.1007/s00011-021-01529-z . .

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  - Koprivica, Ivan
AU  - Nikolovski, Neda
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
PY  - 2022
UR  - https://link.springer.com/10.1007/s00011-021-01529-z
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8742706
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4766
AB  - Ethyl pyruvate (EP) has potent influence on redox processes, cellular metabolism, and inflammation. It has been intensively studied in numerous animal models of systemic and organ-specific disorders whose pathogenesis involves a strong immune component. Here, basic chemical and biological properties of EP are discussed, with an emphasis on its redox and metabolic activity. Further, its influence on myeloid and T cells is considered, as well as on intracellular signaling beyond its effect on immune cells. Also, the effects of EP on animal models of chronic inflammatory and autoimmune disorders are presented. Finally, a possibility to apply EP as a treatment for such diseases in humans is discussed. Scientific papers cited in this review were identified using the PubMed search engine that relies on the MEDLINE database. The reference list covers the most important findings in the field in the past twenty years.
PB  - Basel: Springer Nature Switzerland AG
T2  - Inflammation Research
T1  - Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.
DO  - 10.1007/s00011-021-01529-z
ER  - 

@article{
author = "Koprivica, Ivan and Nikolovski, Neda and Stojanović, Ivana D. and Miljković, Đorđe",
year = "2022",
abstract = "Ethyl pyruvate (EP) has potent influence on redox processes, cellular metabolism, and inflammation. It has been intensively studied in numerous animal models of systemic and organ-specific disorders whose pathogenesis involves a strong immune component. Here, basic chemical and biological properties of EP are discussed, with an emphasis on its redox and metabolic activity. Further, its influence on myeloid and T cells is considered, as well as on intracellular signaling beyond its effect on immune cells. Also, the effects of EP on animal models of chronic inflammatory and autoimmune disorders are presented. Finally, a possibility to apply EP as a treatment for such diseases in humans is discussed. Scientific papers cited in this review were identified using the PubMed search engine that relies on the MEDLINE database. The reference list covers the most important findings in the field in the past twenty years.",
publisher = "Basel: Springer Nature Switzerland AG",
journal = "Inflammation Research",
title = "Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.",
doi = "10.1007/s00011-021-01529-z"
}

Koprivica, I., Nikolovski, N., Stojanović, I. D.,& Miljković, Đ.. (2022). Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.. in Inflammation Research
Basel: Springer Nature Switzerland AG..
https://doi.org/10.1007/s00011-021-01529-z

Koprivica I, Nikolovski N, Stojanović ID, Miljković Đ. Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.. in Inflammation Research. 2022;.
doi:10.1007/s00011-021-01529-z .

Koprivica, Ivan, Nikolovski, Neda, Stojanović, Ivana D., Miljković, Đorđe, "Ethyl pyruvate, a versatile protector in inflammation and autoimmunity." in Inflammation Research (2022),
https://doi.org/10.1007/s00011-021-01529-z . .

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  - 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  - Nikolovski, Neda
AU  - Božić, Iva
AU  - Miljković, Đorđe
AU  - Lavrnja, Irena
PY  - 2021
UR  - https://www.eurekaselect.com/185602/article
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4477
AB  - BACKGROUND Benfotiamine is a synthetic liposoluble derivative of vitamin B1 that has been shown to have anti-inflammatory properties. OBJECTIVE To study the effects of benfotiamine on dendritic cells. METHODS Dendritic cells were obtained from murine bone marrow precursor cells in the presence of GM-CSF. Benfotiamine was applied to the cell culture during the process of bone marrow cell differentiation into dendritic cells. Dendritic cells were stimulated with lipopolysaccharide (LPS) and expression of MHC class II molecules and CD86 was determined by flow cytometry, while levels of tumor necrosis factor (TNF) and interleukin (IL)-1β in cell culture supernatants were measured by ELISA. F-Actin, NF-κB and Nrf2 were visualized by immunofluorescent staining and microscopy. RESULTS Benfotiamine potently reduced LPS-induced expression of MHC class II molecules and CD86, in addition to suppressing the release of pro-inflammatory cytokines TNF and IL-1β. It also prevented LPS-imposed morphological changes of dendritic cells, i.e. enlargement and intensified protrusions. The effects were paralleled with the reduction of NF-κB translocation to the nucleus, but not of Nrf2 activation inhibition. CONCLUSION Having in mind the importance of dendritic cells for the configuration of the immune response, our results imply that benfotiamine has the ability to regulate the immune response through inhibition of inflammatory properties of dendritic cells.
T2  - Endocrine, Metabolic & Immune Disorders - Drug Targets
T1  - Benfotiamine Reduces Dendritic Cell Inflammatory Potency.
IS  - 7
VL  - 21
DO  - 10.2174/1871530320999200905114135
SP  - 1344
EP  - 1351
ER  - 

@article{
author = "Nikolovski, Neda and Božić, Iva and Miljković, Đorđe and Lavrnja, Irena",
year = "2021",
abstract = "BACKGROUND Benfotiamine is a synthetic liposoluble derivative of vitamin B1 that has been shown to have anti-inflammatory properties. OBJECTIVE To study the effects of benfotiamine on dendritic cells. METHODS Dendritic cells were obtained from murine bone marrow precursor cells in the presence of GM-CSF. Benfotiamine was applied to the cell culture during the process of bone marrow cell differentiation into dendritic cells. Dendritic cells were stimulated with lipopolysaccharide (LPS) and expression of MHC class II molecules and CD86 was determined by flow cytometry, while levels of tumor necrosis factor (TNF) and interleukin (IL)-1β in cell culture supernatants were measured by ELISA. F-Actin, NF-κB and Nrf2 were visualized by immunofluorescent staining and microscopy. RESULTS Benfotiamine potently reduced LPS-induced expression of MHC class II molecules and CD86, in addition to suppressing the release of pro-inflammatory cytokines TNF and IL-1β. It also prevented LPS-imposed morphological changes of dendritic cells, i.e. enlargement and intensified protrusions. The effects were paralleled with the reduction of NF-κB translocation to the nucleus, but not of Nrf2 activation inhibition. CONCLUSION Having in mind the importance of dendritic cells for the configuration of the immune response, our results imply that benfotiamine has the ability to regulate the immune response through inhibition of inflammatory properties of dendritic cells.",
journal = "Endocrine, Metabolic & Immune Disorders - Drug Targets",
title = "Benfotiamine Reduces Dendritic Cell Inflammatory Potency.",
number = "7",
volume = "21",
doi = "10.2174/1871530320999200905114135",
pages = "1344-1351"
}

Nikolovski, N., Božić, I., Miljković, Đ.,& Lavrnja, I.. (2021). Benfotiamine Reduces Dendritic Cell Inflammatory Potency.. in Endocrine, Metabolic & Immune Disorders - Drug Targets, 21(7), 1344-1351.
https://doi.org/10.2174/1871530320999200905114135

Nikolovski N, Božić I, Miljković Đ, Lavrnja I. Benfotiamine Reduces Dendritic Cell Inflammatory Potency.. in Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021;21(7):1344-1351.
doi:10.2174/1871530320999200905114135 .

Nikolovski, Neda, Božić, Iva, Miljković, Đorđe, Lavrnja, Irena, "Benfotiamine Reduces Dendritic Cell Inflammatory Potency." in Endocrine, Metabolic & Immune Disorders - Drug Targets, 21, no. 7 (2021):1344-1351,
https://doi.org/10.2174/1871530320999200905114135 . .

TY  - JOUR
AU  - Mansilla, M. J.
AU  - Presas-Rodríguez, S.
AU  - Teniente-Serra, A.
AU  - González-Larreategui, I.
AU  - Quirant-Sánchez, B.
AU  - Fondelli, F.
AU  - Nikolovski, Neda
AU  - Iwaszkiewicz-Grześ, D.
AU  - Chwojnicki, K.
AU  - Miljković, Đorđe
AU  - Trzonkowski, P.
AU  - Ramo-Tello, C.
AU  - Martínez-Cáceres, E. M.
PY  - 2021
UR  - https://doi.org/10.1038/s41423-020-00618-z
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4235
AB  - Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients (tolerogenic dendritic cells, regulatory T cells, mesenchymal stem cells, and vaccination with T cells). Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis (EAE) model of MS in animals, in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.
PB  - Springer Nature
T2  - Cellular and Molecular Immunology
T1  - Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy
IS  - 6
VL  - 18
DO  - 10.1038/s41423-020-00618-z
SP  - 1353
EP  - 1374
ER  - 

@article{
author = "Mansilla, M. J. and Presas-Rodríguez, S. and Teniente-Serra, A. and González-Larreategui, I. and Quirant-Sánchez, B. and Fondelli, F. and Nikolovski, Neda and Iwaszkiewicz-Grześ, D. and Chwojnicki, K. and Miljković, Đorđe and Trzonkowski, P. and Ramo-Tello, C. and Martínez-Cáceres, E. M.",
year = "2021",
abstract = "Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients (tolerogenic dendritic cells, regulatory T cells, mesenchymal stem cells, and vaccination with T cells). Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis (EAE) model of MS in animals, in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.",
publisher = "Springer Nature",
journal = "Cellular and Molecular Immunology",
title = "Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy",
number = "6",
volume = "18",
doi = "10.1038/s41423-020-00618-z",
pages = "1353-1374"
}

Mansilla, M. J., Presas-Rodríguez, S., Teniente-Serra, A., González-Larreategui, I., Quirant-Sánchez, B., Fondelli, F., Nikolovski, N., Iwaszkiewicz-Grześ, D., Chwojnicki, K., Miljković, Đ., Trzonkowski, P., Ramo-Tello, C.,& Martínez-Cáceres, E. M.. (2021). Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy. in Cellular and Molecular Immunology
Springer Nature., 18(6), 1353-1374.
https://doi.org/10.1038/s41423-020-00618-z

Mansilla MJ, Presas-Rodríguez S, Teniente-Serra A, González-Larreategui I, Quirant-Sánchez B, Fondelli F, Nikolovski N, Iwaszkiewicz-Grześ D, Chwojnicki K, Miljković Đ, Trzonkowski P, Ramo-Tello C, Martínez-Cáceres EM. Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy. in Cellular and Molecular Immunology. 2021;18(6):1353-1374.
doi:10.1038/s41423-020-00618-z .

Mansilla, M. J., Presas-Rodríguez, S., Teniente-Serra, A., González-Larreategui, I., Quirant-Sánchez, B., Fondelli, F., Nikolovski, Neda, Iwaszkiewicz-Grześ, D., Chwojnicki, K., Miljković, Đorđe, Trzonkowski, P., Ramo-Tello, C., Martínez-Cáceres, E. M., "Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy" in Cellular and Molecular Immunology, 18, no. 6 (2021):1353-1374,
https://doi.org/10.1038/s41423-020-00618-z . .

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  - 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  - JOUR
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Mansilla, M. José
AU  - Petković, Filip
AU  - Blaževski, Jana
AU  - Timotijević, Gordana
AU  - Navarro-Barriuso, Juan
AU  - Martinez-Caceres, Eva
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0171298518302201?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3265
AB  - Dendritic cells (DC) are responsible for the initiation and shaping of the adaptive immune response and are in the focus of autoimmunity research. We were interested in comparison of DC obtained from autoimmunity-prone Dark Agouti (DA) rats and autoimmunity-resistant Albino Oxford (AO) rats. DC were generated from bone marrow precursors and matured (mDC) by lipopolysaccharide. Tolerogenic DC (tolDC) obtained by vitamin D3 treatment were studied in parallel. Profile of cytokine production was different in AO and DA mDC and tolDC. Expression of MHC class II molecules and CD86 were higher in DA DC, while vitamin D3 reduced their expression in dendritic cells of both strains. Allogeneic proliferation of CD4+ T cells was reduced by AO tolDC, but not with DA tolDC in comparison to respective mDC. Finally, expression of various genes identified as differentially expressed in human mDC and tolDC was also analyzed in AO and DA DC. Again, AO and DA DC differed in the expression of the analyzed genes. To conclude, AO and DA DC differ in production of cytokines, expression of antigen presentation-related molecules and in regulation of CD4+ T proliferation. The difference is valuable for understanding the divergence of the strains in their susceptibility to autoimmunity.
T2  - Immunobiology
T1  - Comparison of dendritic cells obtained from autoimmunty-prone and resistant rats.
DO  - 10.1016/j.imbio.2019.01.001
ER  - 

@article{
author = "Nikolovski, Neda and Jevtić, Bojan and Mansilla, M. José and Petković, Filip and Blaževski, Jana and Timotijević, Gordana and Navarro-Barriuso, Juan and Martinez-Caceres, Eva and Mostarica Stojković, Marija and Miljković, Đorđe",
year = "2019",
abstract = "Dendritic cells (DC) are responsible for the initiation and shaping of the adaptive immune response and are in the focus of autoimmunity research. We were interested in comparison of DC obtained from autoimmunity-prone Dark Agouti (DA) rats and autoimmunity-resistant Albino Oxford (AO) rats. DC were generated from bone marrow precursors and matured (mDC) by lipopolysaccharide. Tolerogenic DC (tolDC) obtained by vitamin D3 treatment were studied in parallel. Profile of cytokine production was different in AO and DA mDC and tolDC. Expression of MHC class II molecules and CD86 were higher in DA DC, while vitamin D3 reduced their expression in dendritic cells of both strains. Allogeneic proliferation of CD4+ T cells was reduced by AO tolDC, but not with DA tolDC in comparison to respective mDC. Finally, expression of various genes identified as differentially expressed in human mDC and tolDC was also analyzed in AO and DA DC. Again, AO and DA DC differed in the expression of the analyzed genes. To conclude, AO and DA DC differ in production of cytokines, expression of antigen presentation-related molecules and in regulation of CD4+ T proliferation. The difference is valuable for understanding the divergence of the strains in their susceptibility to autoimmunity.",
journal = "Immunobiology",
title = "Comparison of dendritic cells obtained from autoimmunty-prone and resistant rats.",
doi = "10.1016/j.imbio.2019.01.001"
}

Nikolovski, N., Jevtić, B., Mansilla, M. J., Petković, F., Blaževski, J., Timotijević, G., Navarro-Barriuso, J., Martinez-Caceres, E., Mostarica Stojković, M.,& Miljković, Đ.. (2019). Comparison of dendritic cells obtained from autoimmunty-prone and resistant rats.. in Immunobiology.
https://doi.org/10.1016/j.imbio.2019.01.001

Nikolovski N, Jevtić B, Mansilla MJ, Petković F, Blaževski J, Timotijević G, Navarro-Barriuso J, Martinez-Caceres E, Mostarica Stojković M, Miljković Đ. Comparison of dendritic cells obtained from autoimmunty-prone and resistant rats.. in Immunobiology. 2019;.
doi:10.1016/j.imbio.2019.01.001 .

Nikolovski, Neda, Jevtić, Bojan, Mansilla, M. José, Petković, Filip, Blaževski, Jana, Timotijević, Gordana, Navarro-Barriuso, Juan, Martinez-Caceres, Eva, Mostarica Stojković, Marija, Miljković, Đorđe, "Comparison of dendritic cells obtained from autoimmunty-prone and resistant rats." in Immunobiology (2019),
https://doi.org/10.1016/j.imbio.2019.01.001 . .

TY  - THES
AU  - Nikolovski, Neda
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3425
AB  - Multipla skleroza (MS) je hronična, inflamacijska, demijelinizirajuća bolest centralnog nervnog sistema (CNS-a). Autoimunski odgovor usmeren protiv CNS-a je bitan element patogeneze MS-e. Eksperimentalni autoimunski encefalomijelitis (EAE) predstavlja životinjski model MS-e pomoću kog se istražuju patogenetski mehanizmi ove bolesti. Glavne ćelije koje učestvuju u pokretanju autoimunskog odgovora usmerenog protiv CNS-a su antigen prezentujuće ćelije (APĆ) koje aktiviraju naivne CD4+ T-ćelije specifične za antigene CNS-a. Ove CD4+ T-ćelije se potom diferenciraju u efektorske Th1 (engl. T helper cells – Th ćelije) koje imaju sposobnost produkcije interferona γ (IFN-γ) i Th17 koje produkuju interleukin 17 (IL-17). Prolaskom kroz-krvno-moždanu barijeru, Th1 i Th17 ćelije dolaze u CNS gde ih reaktiviraju rezidentne APĆ, te one sva.ojim produktima privlače druge imunske ćelije u CNS, što sve dovodi do inflamacije koja vodi oštećenju tkiva CNS-a. Patogenezi bolesti doprinose i rezidentne ćelije CNS-a kao što su astrociti i mikroglija. Etil-piruvat (EP) je lipofilni estar pirogrožđane kiseline koji poseduje antioksidativna i antiinflamacijska svojstva. U ovoj studiji je ispitivan antiencefalitogeni efekat EP-a na tok EAE-a i ćelije ukjučene u patogenezu EAE-a. Takođe, ispitivan je i njegov in vitro i in vivo tolerogeni uticaj na dendritske ćelije (DĆ). Rezultati su pokazali da EP ostvaruje terapijsko dejstvo na EAE kada se daje pacovima svakodnevno, počev od pojave prvih kliničkih simptoma bolesti sve do njihovog inicijalnog oporavka. Svoj antiencefalitogeni efekat EP je ispoljio sprečavanjem infiltracije imunskih ćelija u CNS, inhibicijom produkcije IL-17 od strane CD4+ T-limfocita u kičmenoj moždini, čime je sprečio zapaljensku reakciju u CNS-u. EP je doveo i do redukcije broja reaktivnih makrofaga i ćelija mikroglije, kao i do inhibicije reaktivnosti astrocita. Takođe, sprečio je i oštećenje neurona. Jedan od mehanizama kojim je EP ostvario svoje dejstvo je inhibicija HMGB1 (grupa proteina visoke mobilnosti 1 (engl. High-mobility group box 1) u reaktivnim makrofagima/mikrogliji. Da EP ima i druge efekte na APĆ pokazali su rezultati na makrofagima, in vitro. EP je redukovao produkciju proinflamacijskih citokina od strane makrofaga i ekspresiju molekula bitnih za prezentaciju antigena na ovim ćelijama. Zatim, istraživanje je prošireno na DĆ kao profesionalne APĆ. Rezultati su pokazali da EP vrši tolerogeni uticaj na DĆ poreklom iz kostne srži miševa. Naime, tretman DĆ-a in vitro EP-om inhibira njihovu sposobnost efikasne prezentacije antigena, aktivacije T ćelija u alogenoj reakciji i produkcije proinflamacijskih citokina. Molekulski mehanizmi kojim EP ostvaruje svoje dejstvo na mišje DĆ, uključuju stimulaciju signalnog molekula nuklearnog faktora povezanog sa eritrocitima 2 (engl. Nuclear Factor Erythroid 2–related Factor 2-Nrf2) i enzima hem oksigenaze 1 (HO-1) i NQO1 (engl. NADPH-quinone oxidoreductase 1), kao i inhibiciju regulatornog proteina transkripcije nuklearnog faktora κB (NF-κB). EP-om tretirane DĆ ispoljavaju efekte in vivo inhibiranjem imunskog odgovora indukovanog kompletnim Frojndovim adjuvansom u miševa. Konačno, tolerogeno dejstvo EP-a pokazano je i na DĆ-ma diferenciranim iz monocita ljudi (engl. Monocyte derived Dendritic Cells - MoDĆ) dobrovoljnih davalaca krvi i pacijenata obolelih od MS-e. Iz rezultata ove doktorske disertacije proizilazi da je EP efikasno imunomodulacijsko jedinjenje koje inhibira EAE, kao i da je efikasno tolerogeno jedinjenje koje usmerava DĆ ka imunosupresivnom fenotipu. Samim tim, zaključuje se da EP ima potencijal da bude primenjen u terapiji MS-e. Primena EP bi mogla biti direktna ili u pripremi tolerogenih DĆ za ćelijsku imunoterapiju. Buduće predkliničke i kliničke studije bi trebalo da budu usmerene na istraživanje mogućnosti primene EP u terapiji MS-e, ali i drugih autoimunskih i hroničnih inflamacijskih bolesti. Ključne reči: eksperimentalni autoimunski encefalomijelitis, multipla skleroza, etil-piruvat, tolerogene dendritske ćelije Naučna oblast: Biologija Uža naučna oblast: Imunologija UDK broj: Anti-encephalitogenic mechanisms of ethyl pyruvate in experimental autoimmune encephalomyelitis Abstract Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) with proposed autoimmune pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate pathogenetic mechanisms of the disease. Antigen presenting cells (APC) are major cells that are involved in the initiation of the autoimmune response against the CNS by activating CNS-specific naive CD4+ T cells. Consequently, these CD4+ T cells differentiate into effector T helper cells 1 (Th1) that produce interferon γ (IFN-γ) and Th17 cells that produce interleukin 17 (IL-17). Passing through the blood brain barrier, Th1 and Th17 cells arrive in the CNS where they become reactivated by the resident APC. Afterwards, other immune cells infiltrate the CNS, thus causing inflammation and tissue damage. The resident cells of the CNS, such as astrocytes and microglia, also contribute to the disease pathogenesis. Ethyl pyruvate (EP) is a lipophilic ester of pyruvic acid that possesses anti-oxidative and anti-inflammatory properties. The anti-encephalitogenic effect of EP in EAE and on cells of the CNS involved in the disease pathogenesis, were investigated in this study. Also, its in vitro and in vivo tolerogenic effect on dendritic cells (DC) was studied. Results showed that EP had a therapeutic effect on EAE when applied to the rats once a day, starting from the first clinical symptoms until their initial recovery. EP prevented immune cells infiltration into the CNS and inhibited T cell production of IL-17 in the spinal cord. Thus, EP restrained the inflammatory reaction in the CNS and therefore exerted its anti-encephalitogenic effect. Furthermore, treatment with EP led to the reduction of macrophages and microglia cell number, inhibition of astrocyte activity, as well as neuron destruction. Inhibition of HMGB1 (High-Mobility Group Box 1) molecule in activated macrophages/microglia was one of the mechanisms of the EP effects in the CNS. Moreover, in vitro treatment of stimulated macrophages with EP showed that EP had also an impact on APC. Treatment with EP led to reduced production of pro-inflammatory cytokines by macrophages as well as to downregulation of the expression of molecules relevant for antigen presentation. Furthermore, EP had a tolerogenic effect on the major APC, i.e. DC. Mice bone marrow derived DC were investigated. In vitro treatment of DC with EP inhibited their ability to efficiently present antigens, to activate T cells in allogeneic reaction, and to produce pro-inflammatory cytokines. Molecular mechanisms involved in the tolerogenic effects of EP on mice DC included stimulation of nuclear factor erythroid 2–related factor 2 (Nrf2) signaling, increase of heme oxygenase-1 (HO1) and NADPH-quinone oxidoreductase 1 (NQO1) expression, and inhibition of nuclear factor κB (NF-κB) transcription factor activation. Also, EP-treated DC inhibited immune response in vivo induced with complete Freund’s adjuvant in mice. Finally, the tolerogenic effects of EP were demonstrated in human monocyte derived DC (MoDC) obtained from healthy individuals and MS patients. Results of this doctoral thesis show that EP ameliorates EAE and that is also an effective tolerogenic agent that shifts DC towards immune-suppressing phenotype. Thereby, EP has the potential to be applied in MS therapy. Its application could be direct or through generation of tolerogenic DC as a mean of cell-based immunotherapy. Future preclinical and clinical studies should be focused towards investigating the possible application of EP in MS therapy, as well as in other autoimmune and chronic inflammatory diseases.
AB  - Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) with proposed autoimmune pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate pathogenetic mechanisms of the disease. Antigen presenting cells (APC) are major cells that are involved in the initiation of the autoimmune response against the CNS by activating CNS-specific naive CD4+ T cells. Consequently, these CD4+ T cells differentiate into effector T helper cells 1 (Th1) that produce interferon γ (IFN-γ) and Th17 cells that produce interleukin 17 (IL-17). Passing through the blood brain barrier, Th1 and Th17 cells arrive in the CNS where they become reactivated by the resident APC. Afterwards, other immune cells infiltrate the CNS, thus causing inflammation and tissue damage. The resident cells of the CNS, such as astrocytes and microglia, also contribute to the disease pathogenesis. Ethyl pyruvate (EP) is a lipophilic ester of pyruvic acid that possesses anti-oxidative and anti-inflammatory properties. The anti-encephalitogenic effect of EP in EAE and on cells of the CNS involved in the disease pathogenesis, were investigated in this study. Also, its in vitro and in vivo tolerogenic effect on dendritic cells (DC) was studied. Results showed that EP had a therapeutic effect on EAE when applied to the rats once a day, starting from the first clinical symptoms until their initial recovery. EP prevented immune cells infiltration into the CNS and inhibited T cell production of IL-17 in the spinal cord. Thus, EP restrained the inflammatory reaction in the CNS and therefore exerted its anti-encephalitogenic effect. Furthermore, treatment with EP led to the reduction of macrophages and microglia cell number, inhibition of astrocyte activity, as well as neuron destruction. Inhibition of HMGB1 (High-Mobility Group Box 1) molecule in activated macrophages/microglia was one of the mechanisms of the EP effects in the CNS. Moreover, in vitro treatment of stimulated macrophages with EP showed that EP had also an impact on APC. Treatment with EP led to reduced production of pro-inflammatory cytokines by macrophages as well as to downregulation of the expression of molecules relevant for antigen presentation. Furthermore, EP had a tolerogenic effect on the major APC, i.e. DC. Mice bone marrow derived DC were investigated. In vitro treatment of DC with EP inhibited their ability to efficiently present antigens, to activate T cells in allogeneic reaction, and to produce pro-inflammatory cytokines. Molecular mechanisms involved in the tolerogenic effects of EP on mice DC included stimulation of nuclear factor erythroid 2–related factor 2 (Nrf2) signaling, increase of heme oxygenase-1 (HO1) and NADPH-quinone oxidoreductase 1 (NQO1) expression, and inhibition of nuclear factor κB (NF-κB) transcription factor activation. Also, EP-treated DC inhibited immune response in vivo induced with complete Freund’s adjuvant in mice. Finally, the tolerogenic effects of EP were demonstrated in human monocyte derived DC (MoDC) obtained from healthy individuals and MS patients. Results of this doctoral thesis show that EP ameliorates EAE and that is also an effective tolerogenic agent that shifts DC towards immune-suppressing phenotype. Thereby, EP has the potential to be applied in MS therapy. Its application could be direct or through generation of tolerogenic DC as a mean of cell-based immunotherapy. Future preclinical and clinical studies should be focused towards investigating the possible application of EP in MS therapy, as well as in other autoimmune and chronic inflammatory diseases.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Mehanizmi antiencefalitogenog dejstva etil-piruvata u eksperimentalnom autoimunskom encefalomijelitisu
T1  - Anti-encephalitogenic mechanisms of ethyl pyruvate in experimental autoimmune encephalomyelitis
SP  - 1
EP  - 122
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3425
ER  - 

@phdthesis{
author = "Nikolovski, Neda",
year = "2019",
abstract = "Multipla skleroza (MS) je hronična, inflamacijska, demijelinizirajuća bolest centralnog nervnog sistema (CNS-a). Autoimunski odgovor usmeren protiv CNS-a je bitan element patogeneze MS-e. Eksperimentalni autoimunski encefalomijelitis (EAE) predstavlja životinjski model MS-e pomoću kog se istražuju patogenetski mehanizmi ove bolesti. Glavne ćelije koje učestvuju u pokretanju autoimunskog odgovora usmerenog protiv CNS-a su antigen prezentujuće ćelije (APĆ) koje aktiviraju naivne CD4+ T-ćelije specifične za antigene CNS-a. Ove CD4+ T-ćelije se potom diferenciraju u efektorske Th1 (engl. T helper cells – Th ćelije) koje imaju sposobnost produkcije interferona γ (IFN-γ) i Th17 koje produkuju interleukin 17 (IL-17). Prolaskom kroz-krvno-moždanu barijeru, Th1 i Th17 ćelije dolaze u CNS gde ih reaktiviraju rezidentne APĆ, te one sva.ojim produktima privlače druge imunske ćelije u CNS, što sve dovodi do inflamacije koja vodi oštećenju tkiva CNS-a. Patogenezi bolesti doprinose i rezidentne ćelije CNS-a kao što su astrociti i mikroglija. Etil-piruvat (EP) je lipofilni estar pirogrožđane kiseline koji poseduje antioksidativna i antiinflamacijska svojstva. U ovoj studiji je ispitivan antiencefalitogeni efekat EP-a na tok EAE-a i ćelije ukjučene u patogenezu EAE-a. Takođe, ispitivan je i njegov in vitro i in vivo tolerogeni uticaj na dendritske ćelije (DĆ). Rezultati su pokazali da EP ostvaruje terapijsko dejstvo na EAE kada se daje pacovima svakodnevno, počev od pojave prvih kliničkih simptoma bolesti sve do njihovog inicijalnog oporavka. Svoj antiencefalitogeni efekat EP je ispoljio sprečavanjem infiltracije imunskih ćelija u CNS, inhibicijom produkcije IL-17 od strane CD4+ T-limfocita u kičmenoj moždini, čime je sprečio zapaljensku reakciju u CNS-u. EP je doveo i do redukcije broja reaktivnih makrofaga i ćelija mikroglije, kao i do inhibicije reaktivnosti astrocita. Takođe, sprečio je i oštećenje neurona. Jedan od mehanizama kojim je EP ostvario svoje dejstvo je inhibicija HMGB1 (grupa proteina visoke mobilnosti 1 (engl. High-mobility group box 1) u reaktivnim makrofagima/mikrogliji. Da EP ima i druge efekte na APĆ pokazali su rezultati na makrofagima, in vitro. EP je redukovao produkciju proinflamacijskih citokina od strane makrofaga i ekspresiju molekula bitnih za prezentaciju antigena na ovim ćelijama. Zatim, istraživanje je prošireno na DĆ kao profesionalne APĆ. Rezultati su pokazali da EP vrši tolerogeni uticaj na DĆ poreklom iz kostne srži miševa. Naime, tretman DĆ-a in vitro EP-om inhibira njihovu sposobnost efikasne prezentacije antigena, aktivacije T ćelija u alogenoj reakciji i produkcije proinflamacijskih citokina. Molekulski mehanizmi kojim EP ostvaruje svoje dejstvo na mišje DĆ, uključuju stimulaciju signalnog molekula nuklearnog faktora povezanog sa eritrocitima 2 (engl. Nuclear Factor Erythroid 2–related Factor 2-Nrf2) i enzima hem oksigenaze 1 (HO-1) i NQO1 (engl. NADPH-quinone oxidoreductase 1), kao i inhibiciju regulatornog proteina transkripcije nuklearnog faktora κB (NF-κB). EP-om tretirane DĆ ispoljavaju efekte in vivo inhibiranjem imunskog odgovora indukovanog kompletnim Frojndovim adjuvansom u miševa. Konačno, tolerogeno dejstvo EP-a pokazano je i na DĆ-ma diferenciranim iz monocita ljudi (engl. Monocyte derived Dendritic Cells - MoDĆ) dobrovoljnih davalaca krvi i pacijenata obolelih od MS-e. Iz rezultata ove doktorske disertacije proizilazi da je EP efikasno imunomodulacijsko jedinjenje koje inhibira EAE, kao i da je efikasno tolerogeno jedinjenje koje usmerava DĆ ka imunosupresivnom fenotipu. Samim tim, zaključuje se da EP ima potencijal da bude primenjen u terapiji MS-e. Primena EP bi mogla biti direktna ili u pripremi tolerogenih DĆ za ćelijsku imunoterapiju. Buduće predkliničke i kliničke studije bi trebalo da budu usmerene na istraživanje mogućnosti primene EP u terapiji MS-e, ali i drugih autoimunskih i hroničnih inflamacijskih bolesti. Ključne reči: eksperimentalni autoimunski encefalomijelitis, multipla skleroza, etil-piruvat, tolerogene dendritske ćelije Naučna oblast: Biologija Uža naučna oblast: Imunologija UDK broj: Anti-encephalitogenic mechanisms of ethyl pyruvate in experimental autoimmune encephalomyelitis Abstract Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) with proposed autoimmune pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate pathogenetic mechanisms of the disease. Antigen presenting cells (APC) are major cells that are involved in the initiation of the autoimmune response against the CNS by activating CNS-specific naive CD4+ T cells. Consequently, these CD4+ T cells differentiate into effector T helper cells 1 (Th1) that produce interferon γ (IFN-γ) and Th17 cells that produce interleukin 17 (IL-17). Passing through the blood brain barrier, Th1 and Th17 cells arrive in the CNS where they become reactivated by the resident APC. Afterwards, other immune cells infiltrate the CNS, thus causing inflammation and tissue damage. The resident cells of the CNS, such as astrocytes and microglia, also contribute to the disease pathogenesis. Ethyl pyruvate (EP) is a lipophilic ester of pyruvic acid that possesses anti-oxidative and anti-inflammatory properties. The anti-encephalitogenic effect of EP in EAE and on cells of the CNS involved in the disease pathogenesis, were investigated in this study. Also, its in vitro and in vivo tolerogenic effect on dendritic cells (DC) was studied. Results showed that EP had a therapeutic effect on EAE when applied to the rats once a day, starting from the first clinical symptoms until their initial recovery. EP prevented immune cells infiltration into the CNS and inhibited T cell production of IL-17 in the spinal cord. Thus, EP restrained the inflammatory reaction in the CNS and therefore exerted its anti-encephalitogenic effect. Furthermore, treatment with EP led to the reduction of macrophages and microglia cell number, inhibition of astrocyte activity, as well as neuron destruction. Inhibition of HMGB1 (High-Mobility Group Box 1) molecule in activated macrophages/microglia was one of the mechanisms of the EP effects in the CNS. Moreover, in vitro treatment of stimulated macrophages with EP showed that EP had also an impact on APC. Treatment with EP led to reduced production of pro-inflammatory cytokines by macrophages as well as to downregulation of the expression of molecules relevant for antigen presentation. Furthermore, EP had a tolerogenic effect on the major APC, i.e. DC. Mice bone marrow derived DC were investigated. In vitro treatment of DC with EP inhibited their ability to efficiently present antigens, to activate T cells in allogeneic reaction, and to produce pro-inflammatory cytokines. Molecular mechanisms involved in the tolerogenic effects of EP on mice DC included stimulation of nuclear factor erythroid 2–related factor 2 (Nrf2) signaling, increase of heme oxygenase-1 (HO1) and NADPH-quinone oxidoreductase 1 (NQO1) expression, and inhibition of nuclear factor κB (NF-κB) transcription factor activation. Also, EP-treated DC inhibited immune response in vivo induced with complete Freund’s adjuvant in mice. Finally, the tolerogenic effects of EP were demonstrated in human monocyte derived DC (MoDC) obtained from healthy individuals and MS patients. Results of this doctoral thesis show that EP ameliorates EAE and that is also an effective tolerogenic agent that shifts DC towards immune-suppressing phenotype. Thereby, EP has the potential to be applied in MS therapy. Its application could be direct or through generation of tolerogenic DC as a mean of cell-based immunotherapy. Future preclinical and clinical studies should be focused towards investigating the possible application of EP in MS therapy, as well as in other autoimmune and chronic inflammatory diseases., Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) with proposed autoimmune pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate pathogenetic mechanisms of the disease. Antigen presenting cells (APC) are major cells that are involved in the initiation of the autoimmune response against the CNS by activating CNS-specific naive CD4+ T cells. Consequently, these CD4+ T cells differentiate into effector T helper cells 1 (Th1) that produce interferon γ (IFN-γ) and Th17 cells that produce interleukin 17 (IL-17). Passing through the blood brain barrier, Th1 and Th17 cells arrive in the CNS where they become reactivated by the resident APC. Afterwards, other immune cells infiltrate the CNS, thus causing inflammation and tissue damage. The resident cells of the CNS, such as astrocytes and microglia, also contribute to the disease pathogenesis. Ethyl pyruvate (EP) is a lipophilic ester of pyruvic acid that possesses anti-oxidative and anti-inflammatory properties. The anti-encephalitogenic effect of EP in EAE and on cells of the CNS involved in the disease pathogenesis, were investigated in this study. Also, its in vitro and in vivo tolerogenic effect on dendritic cells (DC) was studied. Results showed that EP had a therapeutic effect on EAE when applied to the rats once a day, starting from the first clinical symptoms until their initial recovery. EP prevented immune cells infiltration into the CNS and inhibited T cell production of IL-17 in the spinal cord. Thus, EP restrained the inflammatory reaction in the CNS and therefore exerted its anti-encephalitogenic effect. Furthermore, treatment with EP led to the reduction of macrophages and microglia cell number, inhibition of astrocyte activity, as well as neuron destruction. Inhibition of HMGB1 (High-Mobility Group Box 1) molecule in activated macrophages/microglia was one of the mechanisms of the EP effects in the CNS. Moreover, in vitro treatment of stimulated macrophages with EP showed that EP had also an impact on APC. Treatment with EP led to reduced production of pro-inflammatory cytokines by macrophages as well as to downregulation of the expression of molecules relevant for antigen presentation. Furthermore, EP had a tolerogenic effect on the major APC, i.e. DC. Mice bone marrow derived DC were investigated. In vitro treatment of DC with EP inhibited their ability to efficiently present antigens, to activate T cells in allogeneic reaction, and to produce pro-inflammatory cytokines. Molecular mechanisms involved in the tolerogenic effects of EP on mice DC included stimulation of nuclear factor erythroid 2–related factor 2 (Nrf2) signaling, increase of heme oxygenase-1 (HO1) and NADPH-quinone oxidoreductase 1 (NQO1) expression, and inhibition of nuclear factor κB (NF-κB) transcription factor activation. Also, EP-treated DC inhibited immune response in vivo induced with complete Freund’s adjuvant in mice. Finally, the tolerogenic effects of EP were demonstrated in human monocyte derived DC (MoDC) obtained from healthy individuals and MS patients. Results of this doctoral thesis show that EP ameliorates EAE and that is also an effective tolerogenic agent that shifts DC towards immune-suppressing phenotype. Thereby, EP has the potential to be applied in MS therapy. Its application could be direct or through generation of tolerogenic DC as a mean of cell-based immunotherapy. Future preclinical and clinical studies should be focused towards investigating the possible application of EP in MS therapy, as well as in other autoimmune and chronic inflammatory diseases.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Mehanizmi antiencefalitogenog dejstva etil-piruvata u eksperimentalnom autoimunskom encefalomijelitisu, Anti-encephalitogenic mechanisms of ethyl pyruvate in experimental autoimmune encephalomyelitis",
pages = "1-122",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3425"
}

Nikolovski, N.. (2019). Mehanizmi antiencefalitogenog dejstva etil-piruvata u eksperimentalnom autoimunskom encefalomijelitisu. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-122.
https://hdl.handle.net/21.15107/rcub_ibiss_3425

Nikolovski N. Mehanizmi antiencefalitogenog dejstva etil-piruvata u eksperimentalnom autoimunskom encefalomijelitisu. in University of Belgrade, Faculty of Biology. 2019;:1-122.
https://hdl.handle.net/21.15107/rcub_ibiss_3425 .

Nikolovski, Neda, "Mehanizmi antiencefalitogenog dejstva etil-piruvata u eksperimentalnom autoimunskom encefalomijelitisu" in University of Belgrade, Faculty of Biology (2019):1-122,
https://hdl.handle.net/21.15107/rcub_ibiss_3425 .