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

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

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

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

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

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

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

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

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

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

TY  - CONF
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos
AU  - Tsiailanis, Antonis
AU  - Tzakos, Andreas G
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - https://benbedphar.org/wp-content/uploads/2023/10/abstract_book_Graz_final.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6474
AB  - Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) are
transcription factors involved in the regulation of drug-metabolizing enzymes. Moreover,
both of them can modulate the immune response. AhR activation can lead to the activation
or inhibition of specific immune cells, especially at barrier tissues such as skin, lungs, gutassociated lymphoid tissue, etc. Nrf2 was also shown to play a role in the anti-inflammatory
process by inhibiting the recruitment of inflammatory cells and regulating anti-inflammatory
gene expression. Nrf2 gene transcription can be directly modulated by AhR activation, as
the Nrf2 promoter possesses three xenobiotic response element-like elements that were
shown to be able to bind AhR in response to a known Ahr agonist TCDD.
In this study, we explored the effect of newly synthetized AhR agonists (indole-based
derivatives) termed C46 and B19 on mouse macrophage differentiation. Peritoneal cells
were incubated with 1.5 µM of AhR ligands for 24 h, after which the proinflammatory M1
(F4/80+CD40+) and anti-inflammatory M2 (F4/80+CD206+) macrophage phenotype was
determined by flow cytometry. The results indicate that both compounds push
macrophages towards a more inflammatory state, as C46 tripled the M1/M2 ratio in culture,
while B19 doubled it, compared to the DMSO (0.005% v/v) control. Additionally, both
mRNA and protein expression of cytochrome P450 1A1 (CYP1A1), commonly used as an
indicator of AhR activation, were also increased by C46 and B19. Finally, western blot
analysis showed that both of the tested AhR ligands downregulated the protein expression
of Nrf2 within the treated cells.
These results suggest that AhR activation and subsequent Nrf2 down-regulation by the
newly synthesized AhR agonists C46 and B19 boosted the proinflammatory phenotype of
mouse peritoneal macrophages.
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  - Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6474
ER  - 

@conference{
author = "Koprivica, Ivan and Jonić, Natalija and Chatzigiannis, Christos and Tsiailanis, Antonis and Tzakos, Andreas G and Stojanović, Ivana D.",
year = "2023",
abstract = "Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) are
transcription factors involved in the regulation of drug-metabolizing enzymes. Moreover,
both of them can modulate the immune response. AhR activation can lead to the activation
or inhibition of specific immune cells, especially at barrier tissues such as skin, lungs, gutassociated lymphoid tissue, etc. Nrf2 was also shown to play a role in the anti-inflammatory
process by inhibiting the recruitment of inflammatory cells and regulating anti-inflammatory
gene expression. Nrf2 gene transcription can be directly modulated by AhR activation, as
the Nrf2 promoter possesses three xenobiotic response element-like elements that were
shown to be able to bind AhR in response to a known Ahr agonist TCDD.
In this study, we explored the effect of newly synthetized AhR agonists (indole-based
derivatives) termed C46 and B19 on mouse macrophage differentiation. Peritoneal cells
were incubated with 1.5 µM of AhR ligands for 24 h, after which the proinflammatory M1
(F4/80+CD40+) and anti-inflammatory M2 (F4/80+CD206+) macrophage phenotype was
determined by flow cytometry. The results indicate that both compounds push
macrophages towards a more inflammatory state, as C46 tripled the M1/M2 ratio in culture,
while B19 doubled it, compared to the DMSO (0.005% v/v) control. Additionally, both
mRNA and protein expression of cytochrome P450 1A1 (CYP1A1), commonly used as an
indicator of AhR activation, were also increased by C46 and B19. Finally, western blot
analysis showed that both of the tested AhR ligands downregulated the protein expression
of Nrf2 within the treated cells.
These results suggest that AhR activation and subsequent Nrf2 down-regulation by the
newly synthesized AhR agonists C46 and B19 boosted the proinflammatory phenotype of
mouse peritoneal macrophages.",
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 = "Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6474"
}

Koprivica, I., Jonić, N., Chatzigiannis, C., Tsiailanis, A., Tzakos, A. G.,& Stojanović, I. D.. (2023). Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands. 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., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6474

Koprivica I, Jonić N, Chatzigiannis C, Tsiailanis A, Tzakos AG, Stojanović ID. Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands. 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;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6474 .

Koprivica, Ivan, Jonić, Natalija, Chatzigiannis, Christos, Tsiailanis, Antonis, Tzakos, Andreas G, Stojanović, Ivana D., "Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands" 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):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6474 .

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sergio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6295
AB  - Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T regulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for modulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry.
Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice. 
Conclusion: C43 can modulate the immune response through the intestine by promoting the immunosuppressive Treg population.
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  - Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6295
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sergio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T regulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for modulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry.
Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice. 
Conclusion: C43 can modulate the immune response through the intestine by promoting the immunosuppressive Treg population.",
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 = "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6295"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. 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., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6295

Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6295 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sergio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6295 .

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

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

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

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

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

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sergio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6296
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has an important role in regulating the immune system, with high expression in Th17 CD4+ T cells and T regulatory cells (Treg). The expression of AhR is especially important at mucosal surfaces where it is involved in balancing the immune response towards external factors. The aim of our research was to evaluate the effect on the gut immune system of a novel fluorescent indole-containing compound that was designed as a putative AhR ligand (encoded C43). By using the EROD assay, we determined that C43 has mild AhR agonistic activity. Sort-purified mesenteric lymph node (MLN) CD4+ cells were treated with C43 for 24 h and flow cytometry analysis (FCM) showed that the Treg/Th17 ratio shifted in favour of Tregs. Zebrafish embryos were used for the evaluation of potential C43 toxicity. No nephrotoxicity, hepatotoxicity or cardiotoxicity was detected, even at the highest concentrations. Next, C43 was orally administered to healthy male C57BL/6 mice for 5 consecutive days, and later its effects on the gut immune system were recorded by analyzing the MLNs. FCM unveiled a higher proportion of Treg cells that expressed CYP1A1 (downstream effector of AhR) and the ratio of Treg/Th1 shifted towards Tregs. The presence of C43 was also visualized by confocal microscopy in the small intestine lamina propria of treated animals. With such results obtained from healthy animals, C43 presents a promising compound for the treatment of inflammatory diseases that generally involve activation of the gut immune system.
PB  - European Federation of Immunological Societies (EFIS)
C3  - Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia
T1  - Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity
SP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6296
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sergio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has an important role in regulating the immune system, with high expression in Th17 CD4+ T cells and T regulatory cells (Treg). The expression of AhR is especially important at mucosal surfaces where it is involved in balancing the immune response towards external factors. The aim of our research was to evaluate the effect on the gut immune system of a novel fluorescent indole-containing compound that was designed as a putative AhR ligand (encoded C43). By using the EROD assay, we determined that C43 has mild AhR agonistic activity. Sort-purified mesenteric lymph node (MLN) CD4+ cells were treated with C43 for 24 h and flow cytometry analysis (FCM) showed that the Treg/Th17 ratio shifted in favour of Tregs. Zebrafish embryos were used for the evaluation of potential C43 toxicity. No nephrotoxicity, hepatotoxicity or cardiotoxicity was detected, even at the highest concentrations. Next, C43 was orally administered to healthy male C57BL/6 mice for 5 consecutive days, and later its effects on the gut immune system were recorded by analyzing the MLNs. FCM unveiled a higher proportion of Treg cells that expressed CYP1A1 (downstream effector of AhR) and the ratio of Treg/Th1 shifted towards Tregs. The presence of C43 was also visualized by confocal microscopy in the small intestine lamina propria of treated animals. With such results obtained from healthy animals, C43 presents a promising compound for the treatment of inflammatory diseases that generally involve activation of the gut immune system.",
publisher = "European Federation of Immunological Societies (EFIS)",
journal = "Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia",
title = "Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity",
pages = "17",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6296"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity. in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia
European Federation of Immunological Societies (EFIS)., 17.
https://hdl.handle.net/21.15107/rcub_ibiss_6296

Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity. in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia. 2023;:17.
https://hdl.handle.net/21.15107/rcub_ibiss_6296 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sergio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity" in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia (2023):17,
https://hdl.handle.net/21.15107/rcub_ibiss_6296 .

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M
AU  - Koprivica, Ivan
AU  - Marinho, Sérgio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Dimitrijević, Mirjana
AU  - Jovanović, Anđelina
AU  - Jovanović, Milan B
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5731
AB  - Aril ugljovodonični receptor (AhR) je transkripcioni faktor aktiviran ligandom i prevashodno je eksprimiran u imunskom tkivu creva. Kako istraživanja ukazuju na povezanost mukoznog imuniteta i različitih inflamatornih i autoimunskih oboljenja, ispitivali smo modulaciju imunskih ćelija creva pomoću novosintetisanog liganda AhR (šifra C43). Primenjen u kulturi mišjih CD4+ ćelija izolovanih iz mezenteričnih limfnih čvorova (MLČ), kao i na humanim ćelijama izolovanih iz tonzila, C43 je značajno uvećao udeo Treg nakon 24h. Nakon što je pokazano da C43 ne ostvaruje toksičnost (ni pri najvećim koncentracijama) pri razviću embriona zebrica (lat. Danio rerio), gavažom je 5 dana davan zdravim C57BL/6 mužjacima. U odnosu zastupljenosti Th1/Treg u MLČ, uočeno je pomeranje balansa ka Treg, kao i povećanje udela Treg koje eksprimiraju Cyp1a1 (nishodni signalni molekul od AhR) kod tretiranih miševa. Kada je C43 gavažom davan C57BL/6 mužjacima kojima je dijabetes tipa 1 (DT1) indukovan streptozotocinom, glikemijski indeksi su bili niži, a histološka analiza pankreasa je pokazala bolje očuvanje β ćelija i pankreasnih ostrvaca. Analiza lamine proprije tankog creva je pokazala povećanje udela tolerogenih dendritskih ćelija (tolDC), dok je udeo CD11b+MHCII+ ćelija bio snižen. Udeo Treg je takođe bio veći, kao i Cyp1a1+ Treg i IL-10+ Treg. Analizom pankreasnog limfnog čvora uočeno je sniženje udela Th1 i CD8+ ćelija, uz povećanje udela tolDC koje eksprimiraju indolamin 2,3-dioksigenazu, što je zabeleženo i u inflitratima pankreasa. Na osnovu dobijenih rezultata može se zaključiti da C43 ostvaruje antiinflamatorni efekat u DT1 i da pristup stimulacije AhR u mukozi creva može imati povoljan efekat u modulaciji autoimunosti i/ili inflamatornih oboljenja.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia
T1  - Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5731
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M and Koprivica, Ivan and Marinho, Sérgio and Moura-Alves, Pedro and Pavić, Aleksandar and Dimitrijević, Mirjana and Jovanović, Anđelina and Jovanović, Milan B and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "Aril ugljovodonični receptor (AhR) je transkripcioni faktor aktiviran ligandom i prevashodno je eksprimiran u imunskom tkivu creva. Kako istraživanja ukazuju na povezanost mukoznog imuniteta i različitih inflamatornih i autoimunskih oboljenja, ispitivali smo modulaciju imunskih ćelija creva pomoću novosintetisanog liganda AhR (šifra C43). Primenjen u kulturi mišjih CD4+ ćelija izolovanih iz mezenteričnih limfnih čvorova (MLČ), kao i na humanim ćelijama izolovanih iz tonzila, C43 je značajno uvećao udeo Treg nakon 24h. Nakon što je pokazano da C43 ne ostvaruje toksičnost (ni pri najvećim koncentracijama) pri razviću embriona zebrica (lat. Danio rerio), gavažom je 5 dana davan zdravim C57BL/6 mužjacima. U odnosu zastupljenosti Th1/Treg u MLČ, uočeno je pomeranje balansa ka Treg, kao i povećanje udela Treg koje eksprimiraju Cyp1a1 (nishodni signalni molekul od AhR) kod tretiranih miševa. Kada je C43 gavažom davan C57BL/6 mužjacima kojima je dijabetes tipa 1 (DT1) indukovan streptozotocinom, glikemijski indeksi su bili niži, a histološka analiza pankreasa je pokazala bolje očuvanje β ćelija i pankreasnih ostrvaca. Analiza lamine proprije tankog creva je pokazala povećanje udela tolerogenih dendritskih ćelija (tolDC), dok je udeo CD11b+MHCII+ ćelija bio snižen. Udeo Treg je takođe bio veći, kao i Cyp1a1+ Treg i IL-10+ Treg. Analizom pankreasnog limfnog čvora uočeno je sniženje udela Th1 i CD8+ ćelija, uz povećanje udela tolDC koje eksprimiraju indolamin 2,3-dioksigenazu, što je zabeleženo i u inflitratima pankreasa. Na osnovu dobijenih rezultata može se zaključiti da C43 ostvaruje antiinflamatorni efekat u DT1 i da pristup stimulacije AhR u mukozi creva može imati povoljan efekat u modulaciji autoimunosti i/ili inflamatornih oboljenja.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia",
title = "Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5731"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Dimitrijević, M., Jovanović, A., Jovanović, M. B., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa. in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5731

Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Dimitrijević M, Jovanović A, Jovanović MB, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa. in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia. 2023;.
https://hdl.handle.net/21.15107/rcub_ibiss_5731 .

Jonić, Natalija, Chatzigiannis, Christos M, Koprivica, Ivan, Marinho, Sérgio, Moura-Alves, Pedro, Pavić, Aleksandar, Dimitrijević, Mirjana, Jovanović, Anđelina, Jovanović, Milan B, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa" in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia (2023),
https://hdl.handle.net/21.15107/rcub_ibiss_5731 .

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

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

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

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

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

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Stojanović, Ivana D.
AU  - Koprivica, Ivan
AU  - Pejnović, Nada
AU  - Šavikin, Katarina
AU  - Ćujić-Nikolić, Nada
AU  - Saksida, Tamara
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5021
AB  - Chokeberry has exhibited cardioprotective, anti-bacterial, immunomodulating and anti-cancer properties. Chokeberry extract (CE) was tested in the model of melanoma induced by B16 cells inoculation in C57BL/6 mice.

CE treatment that began 7 days before inoculation and continued through the observation period, delayed melanoma appearance and increased infiltration of immune cells in the tumor microenvironment (TME). Levels of TNF, perforin, granzyme B and IL-1β did not differ between the CE-treated and control animals, but the TME of CE-treated mice contained more IFN-γ-producing cells and a lesser frequency of CCR5-expressing MDSC. In vitro, CE displayed no direct cytotoxicity to B16 cells. However, splenocytes isolated from CE-treated animals exerted strong cytotoxic effect on B16 cells in vitro. Neutralization of IFN-γ diminished the observed B16 death, suggesting that this effect was mediated mainly by splenocyte-derived IFN-γ.

In conclusion, pre-treatment with CE stimulated the anti-tumor immune response by enhancing IFN-γ-producing cells to act against melanoma.
PB  - Amsterdam : Elsevier
T2  - Journal of Functional Foods
T1  - Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells
VL  - 95
DO  - 10.1016/j.jff.2022.105185
SP  - 105185
ER  - 

@article{
author = "Mićanović, Dragica and Stojanović, Ivana D. and Koprivica, Ivan and Pejnović, Nada and Šavikin, Katarina and Ćujić-Nikolić, Nada and Saksida, Tamara",
year = "2022",
abstract = "Chokeberry has exhibited cardioprotective, anti-bacterial, immunomodulating and anti-cancer properties. Chokeberry extract (CE) was tested in the model of melanoma induced by B16 cells inoculation in C57BL/6 mice.

CE treatment that began 7 days before inoculation and continued through the observation period, delayed melanoma appearance and increased infiltration of immune cells in the tumor microenvironment (TME). Levels of TNF, perforin, granzyme B and IL-1β did not differ between the CE-treated and control animals, but the TME of CE-treated mice contained more IFN-γ-producing cells and a lesser frequency of CCR5-expressing MDSC. In vitro, CE displayed no direct cytotoxicity to B16 cells. However, splenocytes isolated from CE-treated animals exerted strong cytotoxic effect on B16 cells in vitro. Neutralization of IFN-γ diminished the observed B16 death, suggesting that this effect was mediated mainly by splenocyte-derived IFN-γ.

In conclusion, pre-treatment with CE stimulated the anti-tumor immune response by enhancing IFN-γ-producing cells to act against melanoma.",
publisher = "Amsterdam : Elsevier",
journal = "Journal of Functional Foods",
title = "Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells",
volume = "95",
doi = "10.1016/j.jff.2022.105185",
pages = "105185"
}

Mićanović, D., Stojanović, I. D., Koprivica, I., Pejnović, N., Šavikin, K., Ćujić-Nikolić, N.,& Saksida, T.. (2022). Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells. in Journal of Functional Foods
Amsterdam : Elsevier., 95, 105185.
https://doi.org/10.1016/j.jff.2022.105185

Mićanović D, Stojanović ID, Koprivica I, Pejnović N, Šavikin K, Ćujić-Nikolić N, Saksida T. Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells. in Journal of Functional Foods. 2022;95:105185.
doi:10.1016/j.jff.2022.105185 .

Mićanović, Dragica, Stojanović, Ivana D., Koprivica, Ivan, Pejnović, Nada, Šavikin, Katarina, Ćujić-Nikolić, Nada, Saksida, Tamara, "Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells" in Journal of Functional Foods, 95 (2022):105185,
https://doi.org/10.1016/j.jff.2022.105185 . .

TY  - JOUR
AU  - Li, Hanluo
AU  - Ziemer, Mirjana
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Đmura, Goran
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Simon, Jan-Christoph
AU  - Lethaus, Bernd
AU  - Savković, Vuk
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4775
AB  - Wound  healing  of  acute  full-thickness  injuries  and  chronic  non-healing  ulcers  leads  to  delayed  wound  closure,  prolonged recovery period and hypertrophic scarring, generating a demand for an autologous cell therapy and a relevant pre-clinical research  models for  wound healing.  In this study, an  immunocompetent model  for  wound  healing  was  employed  using a syngeneic murine cell line of mesenchymal stem cells cultured from the mouse whisker hair follicle outer root sheath (named moMSCORS). moMSCORS were isolated using an air-liquid interface method, expanded  in vitro  and characterized according to the MSC definition criteria - cell viability,  in vitro  proliferation, MSC phenotype and multi-lineage differentiations. Moreover, upon applying moMSCORS in an  in vivo  full-thickness wound model in the syngeneic C57BL/6 mice, the treated wounds displayed different morphology to that of the untreated wound beds. Quantitative evaluation of angiogenesis, granulation and wound closure involving clinical scoring and software-based quantification indicated a lower degree of inflammation in the treated wounds. Histological staining of treated wounds by the means of H&E, Alcian Blue, PicroSirius Red and αSMA immune labelling showed lower cellularity, less collagen filaments as well as thinner dermal and epidermal layers compared with the untreated wounds, indicating a general reduction of hypertrophic scars. The decreased inflammation, accelerated wound closure and non-hypertrophic scarring, which were facilitated by moMSCORS, hereby address a common problem of hypertrophic scars and non-physiological tissue properties upon wound closure, and additionally offer an  in  vivo  model  for  the  autologous  cell-based  wound  healing.
PB  - Basel: Springer Nature Switzerland AG
T2  - Stem Cell Reviews and Reports
T1  - Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model
DO  - 10.1007/s12015-021-10288-7
ER  - 

@article{
author = "Li, Hanluo and Ziemer, Mirjana and Stojanović, Ivana D. and Saksida, Tamara and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Đmura, Goran and Mićanović, Dragica and Koprivica, Ivan and Krajnović, Tamara and Drača, Dijana and Simon, Jan-Christoph and Lethaus, Bernd and Savković, Vuk",
year = "2022",
abstract = "Wound  healing  of  acute  full-thickness  injuries  and  chronic  non-healing  ulcers  leads  to  delayed  wound  closure,  prolonged recovery period and hypertrophic scarring, generating a demand for an autologous cell therapy and a relevant pre-clinical research  models for  wound healing.  In this study, an  immunocompetent model  for  wound  healing  was  employed  using a syngeneic murine cell line of mesenchymal stem cells cultured from the mouse whisker hair follicle outer root sheath (named moMSCORS). moMSCORS were isolated using an air-liquid interface method, expanded  in vitro  and characterized according to the MSC definition criteria - cell viability,  in vitro  proliferation, MSC phenotype and multi-lineage differentiations. Moreover, upon applying moMSCORS in an  in vivo  full-thickness wound model in the syngeneic C57BL/6 mice, the treated wounds displayed different morphology to that of the untreated wound beds. Quantitative evaluation of angiogenesis, granulation and wound closure involving clinical scoring and software-based quantification indicated a lower degree of inflammation in the treated wounds. Histological staining of treated wounds by the means of H&E, Alcian Blue, PicroSirius Red and αSMA immune labelling showed lower cellularity, less collagen filaments as well as thinner dermal and epidermal layers compared with the untreated wounds, indicating a general reduction of hypertrophic scars. The decreased inflammation, accelerated wound closure and non-hypertrophic scarring, which were facilitated by moMSCORS, hereby address a common problem of hypertrophic scars and non-physiological tissue properties upon wound closure, and additionally offer an  in  vivo  model  for  the  autologous  cell-based  wound  healing.",
publisher = "Basel: Springer Nature Switzerland AG",
journal = "Stem Cell Reviews and Reports",
title = "Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model",
doi = "10.1007/s12015-021-10288-7"
}

Li, H., Ziemer, M., Stojanović, I. D., Saksida, T., Maksimović-Ivanić, D., Mijatović, S., Đmura, G., Mićanović, D., Koprivica, I., Krajnović, T., Drača, D., Simon, J., Lethaus, B.,& Savković, V.. (2022). Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model. in Stem Cell Reviews and Reports
Basel: Springer Nature Switzerland AG..
https://doi.org/10.1007/s12015-021-10288-7

Li H, Ziemer M, Stojanović ID, Saksida T, Maksimović-Ivanić D, Mijatović S, Đmura G, Mićanović D, Koprivica I, Krajnović T, Drača D, Simon J, Lethaus B, Savković V. Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model. in Stem Cell Reviews and Reports. 2022;.
doi:10.1007/s12015-021-10288-7 .

Li, Hanluo, Ziemer, Mirjana, Stojanović, Ivana D., Saksida, Tamara, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Đmura, Goran, Mićanović, Dragica, Koprivica, Ivan, Krajnović, Tamara, Drača, Dijana, Simon, Jan-Christoph, Lethaus, Bernd, Savković, Vuk, "Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model" in Stem Cell Reviews and Reports (2022),
https://doi.org/10.1007/s12015-021-10288-7 . .

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

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

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

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

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

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Diamantis, Dimitris
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas G.
AU  - Stojanović, Ivana D.
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320521011711
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4700
AB  - Aims: Rosmarinic acid (RA) is a polyphenol that occurs in plants of the Lamiaceae family. Phenethyl ester of RA (PERA), a novel RA derivative, has been developed and evaluated in vivo in an animal model of type 1 diabetes (T1D). Methods: T1D was induced in male C57BL/6 mice using multiple low doses of streptozotocin (STZ) administered intraperitoneally for 5 consecutive days. Intraperitoneal administration of PERA (2.5 mg/kg bw) began from the first STZ injection and continued for 20 days. Key findings: PERA-treated mice exhibited lower incidence of T1D (monitored up to 38 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. PERA treatment significantly down-regulated the proportions of CD11b+ and CD11c+ myeloid cells in the immune cell infiltrates in the pancreatic islets early during T1D pathogenesis (on day 9 after T1D induction), while on day 15, PERA significantly reduced the proportions of CD11c+, CD8+, Th1 and Th17 cells. Simultaneously, it was found that the cells from the pancreatic infiltrates of PERA-treated mice produced significantly less reactive oxygen species than cells from the control group. Significance: These findings suggest that PERA efficiently prevented T1D development in mice. Interestingly, PERA attenuated the inflammatory process in the islets through temporally specific interference with the innate and adaptive immune response and therefore shows great promise for further clinical evaluation as a novel T1D therapeutic.
T2  - Life Sciences
T1  - Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice
VL  - 288
DO  - 10.1016/j.lfs.2021.120184
SP  - 120184
ER  - 

@article{
author = "Koprivica, Ivan and Jonić, Natalija and Diamantis, Dimitris and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas G. and Stojanović, Ivana D.",
year = "2022",
abstract = "Aims: Rosmarinic acid (RA) is a polyphenol that occurs in plants of the Lamiaceae family. Phenethyl ester of RA (PERA), a novel RA derivative, has been developed and evaluated in vivo in an animal model of type 1 diabetes (T1D). Methods: T1D was induced in male C57BL/6 mice using multiple low doses of streptozotocin (STZ) administered intraperitoneally for 5 consecutive days. Intraperitoneal administration of PERA (2.5 mg/kg bw) began from the first STZ injection and continued for 20 days. Key findings: PERA-treated mice exhibited lower incidence of T1D (monitored up to 38 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. PERA treatment significantly down-regulated the proportions of CD11b+ and CD11c+ myeloid cells in the immune cell infiltrates in the pancreatic islets early during T1D pathogenesis (on day 9 after T1D induction), while on day 15, PERA significantly reduced the proportions of CD11c+, CD8+, Th1 and Th17 cells. Simultaneously, it was found that the cells from the pancreatic infiltrates of PERA-treated mice produced significantly less reactive oxygen species than cells from the control group. Significance: These findings suggest that PERA efficiently prevented T1D development in mice. Interestingly, PERA attenuated the inflammatory process in the islets through temporally specific interference with the innate and adaptive immune response and therefore shows great promise for further clinical evaluation as a novel T1D therapeutic.",
journal = "Life Sciences",
title = "Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice",
volume = "288",
doi = "10.1016/j.lfs.2021.120184",
pages = "120184"
}

Koprivica, I., Jonić, N., Diamantis, D., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A. G.,& Stojanović, I. D.. (2022). Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice. in Life Sciences, 288, 120184.
https://doi.org/10.1016/j.lfs.2021.120184

Koprivica I, Jonić N, Diamantis D, Mićanović D, Saksida T, Pejnović N, Tzakos AG, Stojanović ID. Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice. in Life Sciences. 2022;288:120184.
doi:10.1016/j.lfs.2021.120184 .

Koprivica, Ivan, Jonić, Natalija, Diamantis, Dimitris, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas G., Stojanović, Ivana D., "Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice" in Life Sciences, 288 (2022):120184,
https://doi.org/10.1016/j.lfs.2021.120184 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5781
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
regulatory immune mechanisms that would attenuate disease progression
have shown little or no beneficial effects. We introduced microparticles (MPs) loaded
with Transforming Growth Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA),
both known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower and was accompanied by down-regulation
in the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice
SP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5781
ER  - 

@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2021",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
regulatory immune mechanisms that would attenuate disease progression
have shown little or no beneficial effects. We introduced microparticles (MPs) loaded
with Transforming Growth Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA),
both known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower and was accompanied by down-regulation
in the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5781"
}

Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2021). ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 100.
https://hdl.handle.net/21.15107/rcub_ibiss_5781

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

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

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Pejnović, Nada
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5780
AB  - Ethyl pyruvate (EP) is a stable form of pyruvate that has shown potent anti-oxidant and
anti-inflammatory properties both in vitro and in vivo and was able to ameliorate
systemic inflammation and multiple organ dysfunctions in multiple animal models. Our
recent study suggests that the application of EP in the mouse model of type 1 diabetes
successfully prevents the clinical manifestation of the disease by augmenting the
number of tolerogenic dendritic cells and regulatory T cells (Treg). Our present study
indicates that during in vitro differentiation of CD4+ naïve cells into Treg, the addition
of EP stimulated Treg generation. This was in line with the observed increased
proliferation of newly differentiated Treg (Ki67+FoxP3+). Surprisingly, EP did not
scavenge reactive oxygen species (ROS), but rather stimulated ROS production by
Treg. In Treg, ROS is mainly generated during oxidative phosphorylation (OXPHOS)
during which the majority of energy for the cell is produced. EP probably acted as a
substrate in Krebs cycle because the cells produced more pyruvate dehydrogenase,
which converts pyruvate to acetyl CoA. EP treatment also resulted in less kinase of
pyruvate dehydrogenase, which acts as an inhibitor of Krebs cycle. As a result, there
was an evident stimulation of OXPHOS, confirmed by increased ATP production in
differentiated Treg. Additionally, EP exerted its stimulatory function on Treg in healthy
C57BL/6 mice. When given either intraperitoneally or per os, EP increased Treg
numbers within the peritoneal cavity or gut-associated lymphoid tissue, respectively.
Seemingly, EP promoted differentiation of Treg in vivo and did not affect their
suppressive properties (proportion of CTLA-4+, CD39+, PD-1+, IL-10+ Treg) or their
affinity towards specific effector T helper cells (RORγT+, Tbet+ or GATA-3+ Treg). In
conclusion, EP acts as specific metabolic fuel for Treg generation, likely because these
cells mainly rely on OXPHOS-derived energy
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo
SP  - 8
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5780
ER  - 

@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Pejnović, Nada and Saksida, Tamara and Stojanović, Ivana D.",
year = "2021",
abstract = "Ethyl pyruvate (EP) is a stable form of pyruvate that has shown potent anti-oxidant and
anti-inflammatory properties both in vitro and in vivo and was able to ameliorate
systemic inflammation and multiple organ dysfunctions in multiple animal models. Our
recent study suggests that the application of EP in the mouse model of type 1 diabetes
successfully prevents the clinical manifestation of the disease by augmenting the
number of tolerogenic dendritic cells and regulatory T cells (Treg). Our present study
indicates that during in vitro differentiation of CD4+ naïve cells into Treg, the addition
of EP stimulated Treg generation. This was in line with the observed increased
proliferation of newly differentiated Treg (Ki67+FoxP3+). Surprisingly, EP did not
scavenge reactive oxygen species (ROS), but rather stimulated ROS production by
Treg. In Treg, ROS is mainly generated during oxidative phosphorylation (OXPHOS)
during which the majority of energy for the cell is produced. EP probably acted as a
substrate in Krebs cycle because the cells produced more pyruvate dehydrogenase,
which converts pyruvate to acetyl CoA. EP treatment also resulted in less kinase of
pyruvate dehydrogenase, which acts as an inhibitor of Krebs cycle. As a result, there
was an evident stimulation of OXPHOS, confirmed by increased ATP production in
differentiated Treg. Additionally, EP exerted its stimulatory function on Treg in healthy
C57BL/6 mice. When given either intraperitoneally or per os, EP increased Treg
numbers within the peritoneal cavity or gut-associated lymphoid tissue, respectively.
Seemingly, EP promoted differentiation of Treg in vivo and did not affect their
suppressive properties (proportion of CTLA-4+, CD39+, PD-1+, IL-10+ Treg) or their
affinity towards specific effector T helper cells (RORγT+, Tbet+ or GATA-3+ Treg). In
conclusion, EP acts as specific metabolic fuel for Treg generation, likely because these
cells mainly rely on OXPHOS-derived energy",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo",
pages = "8",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5780"
}

Koprivica, I., Mićanović, D., Pejnović, N., Saksida, T.,& Stojanović, I. D.. (2021). Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 8.
https://hdl.handle.net/21.15107/rcub_ibiss_5780

Koprivica I, Mićanović D, Pejnović N, Saksida T, Stojanović ID. Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2021;:8.
https://hdl.handle.net/21.15107/rcub_ibiss_5780 .

Koprivica, Ivan, Mićanović, Dragica, Pejnović, Nada, Saksida, Tamara, Stojanović, Ivana D., "Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2021):8,
https://hdl.handle.net/21.15107/rcub_ibiss_5780 .

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

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

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

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

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

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Savić, Anisia
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5605
AB  - A novel way of regulating the function of immune cells has been discovered and is done by targeting the activation of the aryl hydrocarbon receptor (AhR)1. It is found that AhR is a ligand-activated transcription factor that responds to various aromatic compounds - exogenous such as plant flavonoids, polyphenolics and indoles and endogenous such as kynurenine2. By inhibiting its activation a pro-inflammatory immune response is promoted, whereas its activation gives an opposite effect1. Therefore, a selection of plant-derived indol derivatives was tested as an AhR ligand to establish their effects on the receptor’s activity. The one that was found to be a potent AhR antagonist was an indol derivative under the code C46 and was further tested on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed to the compound C46 in vitro in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. By using flow cytometry we established that C46 significantly and dose-dependently up-regulated the proportion of M1 macrophages (F4/80+CD40+) and not only that, but it affected only M1 macrophages, while the proportion of M2 (F4/80+CD206+) remained stable throughout the exposure to different concentrations of C46. In further analysis with DAF-FM staining, it was found that C46 increased the cytocidal function of macrophages, since their content of nitric oxide was increased. With intraperitoneal administration of C46 the results were similar - the proportion of M1 macrophages in the peritoneum was up-regulated, 72 h after the treatment. In conclusion, by blocking the AhR signal pathway with C46, a pro-inflammatory immune response could be achieved by promoting the M1 macrophage phenotype and it may as well be a a promising approach for future testing in animal models of cancer.
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor
SP  - 69
EP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5605
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Savić, Anisia and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "A novel way of regulating the function of immune cells has been discovered and is done by targeting the activation of the aryl hydrocarbon receptor (AhR)1. It is found that AhR is a ligand-activated transcription factor that responds to various aromatic compounds - exogenous such as plant flavonoids, polyphenolics and indoles and endogenous such as kynurenine2. By inhibiting its activation a pro-inflammatory immune response is promoted, whereas its activation gives an opposite effect1. Therefore, a selection of plant-derived indol derivatives was tested as an AhR ligand to establish their effects on the receptor’s activity. The one that was found to be a potent AhR antagonist was an indol derivative under the code C46 and was further tested on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed to the compound C46 in vitro in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. By using flow cytometry we established that C46 significantly and dose-dependently up-regulated the proportion of M1 macrophages (F4/80+CD40+) and not only that, but it affected only M1 macrophages, while the proportion of M2 (F4/80+CD206+) remained stable throughout the exposure to different concentrations of C46. In further analysis with DAF-FM staining, it was found that C46 increased the cytocidal function of macrophages, since their content of nitric oxide was increased. With intraperitoneal administration of C46 the results were similar - the proportion of M1 macrophages in the peritoneum was up-regulated, 72 h after the treatment. In conclusion, by blocking the AhR signal pathway with C46, a pro-inflammatory immune response could be achieved by promoting the M1 macrophage phenotype and it may as well be a a promising approach for future testing in animal models of cancer.",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor",
pages = "69-70",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5605"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Savić, A., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2021). Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society., 69-70.
https://hdl.handle.net/21.15107/rcub_ibiss_5605

Jonić N, Chatzigiannis CM, Koprivica I, Savić A, Mićanović D, Saksida T, Pejnović N, Tzakos A, Stojanović ID. Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:69-70.
https://hdl.handle.net/21.15107/rcub_ibiss_5605 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Savić, Anisia, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):69-70,
https://hdl.handle.net/21.15107/rcub_ibiss_5605 .

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4052
AB  - Obesity, a global health problem nowadays, is a state of low-grade chronic inflammation of adipose tissue (AT)
associated with increased adipocyte growth and proliferation and immune cell polarization towards an inflammatory
phenotype within the stromal vascular fraction (SVF). Pro-inflammatory cells in the AT produce
mediators of inflammation (IL-1β, TNF, macrophage migration inhibitory factor – MIF), thereby surpassing the
anti-inflammatory response mediated by IL-10 and TGF-β, cytokines produced by regulatory T (Treg) cells. In this
study we demonstrate that the absence of the pro-inflammatory cytokine MIF led to obesity and inflammation in
the visceral AT (VAT) in 6 months old MIF- /- mice. Besides the increment of pro-inflammatory AT macrophages
and the enhanced production of TNF and IL-1β, VAT of MIF- /- mice contained increased numbers of Treg cells.
In situ proliferation of Treg cells did not differ between MIF- /- and wild type mice, but Treg cells isolated from
the VAT of MIF-deficient mice, and not from the cervical lymph nodes, exhibited lower expression and production
of IL-10 and TGF-β. Additionally, SVF cells had significantly lower levels of STAT3 and IL-33, altogether
indicating that VAT Treg cells in MIF- /- mice, albeit abundantly present, are not fully functional. These results
indicate that MIF is a new regulator of VAT Treg cell function, necessary for their immunosuppressive activities.
PB  - Netherlands: Elsevier
T2  - Cytokine
T1  - Defective immunosuppressive function of Treg cells in visceral adipose tissue in MIF deficient mice
VL  - 138
DO  - 10.1016/j.cyto.2020.155372
SP  - 155372
ER  - 

@article{
author = "Mićanović, Dragica and Koprivica, Ivan and Stojanović, Ivana D. and Saksida, Tamara",
year = "2021",
abstract = "Obesity, a global health problem nowadays, is a state of low-grade chronic inflammation of adipose tissue (AT)
associated with increased adipocyte growth and proliferation and immune cell polarization towards an inflammatory
phenotype within the stromal vascular fraction (SVF). Pro-inflammatory cells in the AT produce
mediators of inflammation (IL-1β, TNF, macrophage migration inhibitory factor – MIF), thereby surpassing the
anti-inflammatory response mediated by IL-10 and TGF-β, cytokines produced by regulatory T (Treg) cells. In this
study we demonstrate that the absence of the pro-inflammatory cytokine MIF led to obesity and inflammation in
the visceral AT (VAT) in 6 months old MIF- /- mice. Besides the increment of pro-inflammatory AT macrophages
and the enhanced production of TNF and IL-1β, VAT of MIF- /- mice contained increased numbers of Treg cells.
In situ proliferation of Treg cells did not differ between MIF- /- and wild type mice, but Treg cells isolated from
the VAT of MIF-deficient mice, and not from the cervical lymph nodes, exhibited lower expression and production
of IL-10 and TGF-β. Additionally, SVF cells had significantly lower levels of STAT3 and IL-33, altogether
indicating that VAT Treg cells in MIF- /- mice, albeit abundantly present, are not fully functional. These results
indicate that MIF is a new regulator of VAT Treg cell function, necessary for their immunosuppressive activities.",
publisher = "Netherlands: Elsevier",
journal = "Cytokine",
title = "Defective immunosuppressive function of Treg cells in visceral adipose tissue in MIF deficient mice",
volume = "138",
doi = "10.1016/j.cyto.2020.155372",
pages = "155372"
}

Mićanović, D., Koprivica, I., Stojanović, I. D.,& Saksida, T.. (2021). Defective immunosuppressive function of Treg cells in visceral adipose tissue in MIF deficient mice. in Cytokine
Netherlands: Elsevier., 138, 155372.
https://doi.org/10.1016/j.cyto.2020.155372

Mićanović D, Koprivica I, Stojanović ID, Saksida T. Defective immunosuppressive function of Treg cells in visceral adipose tissue in MIF deficient mice. in Cytokine. 2021;138:155372.
doi:10.1016/j.cyto.2020.155372 .

Mićanović, Dragica, Koprivica, Ivan, Stojanović, Ivana D., Saksida, Tamara, "Defective immunosuppressive function of Treg cells in visceral adipose tissue in MIF deficient mice" in Cytokine, 138 (2021):155372,
https://doi.org/10.1016/j.cyto.2020.155372 . .

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Savic, Anisia
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4883
AB  - Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that responds to various aromatic compounds, both endogenous such as kynurenine and exogenous such as natural plant flavonoids, polyphenolics and indoles. AhR has been recently identified as the regulator of immune cells function. The activation of AhR generally leads to the attenuation of the immune response, while its inhibition promotes the opposite effects. In this study we have selected several plant‐derived indol derivatives and tested them for their AhR ligand activity. A potent AhR antagonist was identified (code C46) and further evaluated on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed in vitro to compound C46 in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. Flow cytometry analysis showed that C46 significantly and dose‐dependently up‐regulated the proportion of M1 macrophages (F4/80+CD40+). Interestingly, C46 influenced only M1 macrophages, as the proportion of M2 (F4/80+CD206+) remained stable upon the exposure to C46. In addition, C46 increased the cytocidal function of macrophages by increasing the content of nitric oxide as determined by DAF‐FM staining. Similarly to in vitro effects, intraperitoneal C46 administration up‐regulated the proportion of M1 macrophages in the peritoneum, 72 h after the treatment. In conclusion, blocking of AhR pathway by C46 potentiates pro‐inflammatory function of macrophages and it may represent a promising approach for future testing in animal models of cancer.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype
DO  - 10.1002/eji.202170200
SP  - 207
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Savic, Anisia and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that responds to various aromatic compounds, both endogenous such as kynurenine and exogenous such as natural plant flavonoids, polyphenolics and indoles. AhR has been recently identified as the regulator of immune cells function. The activation of AhR generally leads to the attenuation of the immune response, while its inhibition promotes the opposite effects. In this study we have selected several plant‐derived indol derivatives and tested them for their AhR ligand activity. A potent AhR antagonist was identified (code C46) and further evaluated on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed in vitro to compound C46 in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. Flow cytometry analysis showed that C46 significantly and dose‐dependently up‐regulated the proportion of M1 macrophages (F4/80+CD40+). Interestingly, C46 influenced only M1 macrophages, as the proportion of M2 (F4/80+CD206+) remained stable upon the exposure to C46. In addition, C46 increased the cytocidal function of macrophages by increasing the content of nitric oxide as determined by DAF‐FM staining. Similarly to in vitro effects, intraperitoneal C46 administration up‐regulated the proportion of M1 macrophages in the peritoneum, 72 h after the treatment. In conclusion, blocking of AhR pathway by C46 potentiates pro‐inflammatory function of macrophages and it may represent a promising approach for future testing in animal models of cancer.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype",
doi = "10.1002/eji.202170200",
pages = "207"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Savic, A., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2021). Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 207.
https://doi.org/10.1002/eji.202170200

Jonić N, Chatzigiannis CM, Koprivica I, Savic A, Mićanović D, Saksida T, Pejnović N, Tzakos A, Stojanović ID. Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;:207.
doi:10.1002/eji.202170200 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Savic, Anisia, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting (2021):207,
https://doi.org/10.1002/eji.202170200 . .

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

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

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

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

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

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

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

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

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

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