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

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

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

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

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

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

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

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

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

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

TY  - CONF
AU  - Markelić, Milica
AU  - Otašević, Vesna
AU  - Gudelj, Anđelija
AU  - Saksida, Tamara
AU  - Stančić, Ana
AU  - Veličković, Ksenija
AU  - Krstić, Jelena
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6404
AB  - Recently, it has been suggested that nutrient deprivation (ND) may be effective as an adjuvant 
therapy to hepatocellular carcinoma (HCC) cell treatment with sorafenib (Sfb)1. These results 
suggest that ND-mediated priming of HCC cells to Sfb is positively correlated with the p53 status, 
suggesting the essential role of p53 in priming of HCC cells for regulated cell death (RCD). 
Preliminary data indicated morphological signs of ferroptotic RCD, so we aimed to determine whether 
ferroptosis plays a role in the removal of HCC cells in vitro with respect to their p53 status. To 
this end, p53 wild-type (p53WT) and p53 knockout (p53KO) HepG2 cells were grown in growth medium or 
in starvation medium and treated with Sfb or with ferroptosis inducer, Rsl- 3, for 6 h. 
Morphological signs of RCD and nuclear translocation (i.e. activation) of Nrf2, (master regulator 
of ferroptosis-related signalling pathways), as well as protein levels of antioxidative defence 
(AD) enzymes (CAT, CuZnSOD, MnSOD) and ferroptosis-related proteins (GPX4, xCT) were analysed. The 
AD response to Rsl-3 treatment in p53WT cells was similar regardless of nutritional status, as the 
level of all analysed enzymes increased. The response to Sfb was enhanced by ND as CAT and CuZnSOD 
were elevated. p53KO cells responded quite differently, even when treated with Rsl-3, increasing 
only MnSOD. Starved Sfb-treated p53KO cells even decreased expression of AD enzymes. All signs of a 
proferroptotic response examined were present in starved p53WT cells (regardless of treatment): 
decreased nuclear translocation of Nrf2, GPX4, and xCT expression. Nrf2 activation and GPX4 
expression were also decreased in starved p53KO cells (especially upon treatment with Sfb or 
Rsl-3), but accompanied by compensatory overexpressed xCT. These results may be indicative of 
enhanced AD in p53KO cells and may therefore explain, at least in part, their resistance to 
treatment with Sfb+ND which, as presented here, induces ferroptosis in p53WT HepG2 cells.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Proferroptotic response to nutrient deprivation in hepatocellular carcinoma cells is related to p53 status
SP  - 86
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6404
ER  - 

@conference{
author = "Markelić, Milica and Otašević, Vesna and Gudelj, Anđelija and Saksida, Tamara and Stančić, Ana and Veličković, Ksenija and Krstić, Jelena",
year = "2023",
abstract = "Recently, it has been suggested that nutrient deprivation (ND) may be effective as an adjuvant 
therapy to hepatocellular carcinoma (HCC) cell treatment with sorafenib (Sfb)1. These results 
suggest that ND-mediated priming of HCC cells to Sfb is positively correlated with the p53 status, 
suggesting the essential role of p53 in priming of HCC cells for regulated cell death (RCD). 
Preliminary data indicated morphological signs of ferroptotic RCD, so we aimed to determine whether 
ferroptosis plays a role in the removal of HCC cells in vitro with respect to their p53 status. To 
this end, p53 wild-type (p53WT) and p53 knockout (p53KO) HepG2 cells were grown in growth medium or 
in starvation medium and treated with Sfb or with ferroptosis inducer, Rsl- 3, for 6 h. 
Morphological signs of RCD and nuclear translocation (i.e. activation) of Nrf2, (master regulator 
of ferroptosis-related signalling pathways), as well as protein levels of antioxidative defence 
(AD) enzymes (CAT, CuZnSOD, MnSOD) and ferroptosis-related proteins (GPX4, xCT) were analysed. The 
AD response to Rsl-3 treatment in p53WT cells was similar regardless of nutritional status, as the 
level of all analysed enzymes increased. The response to Sfb was enhanced by ND as CAT and CuZnSOD 
were elevated. p53KO cells responded quite differently, even when treated with Rsl-3, increasing 
only MnSOD. Starved Sfb-treated p53KO cells even decreased expression of AD enzymes. All signs of a 
proferroptotic response examined were present in starved p53WT cells (regardless of treatment): 
decreased nuclear translocation of Nrf2, GPX4, and xCT expression. Nrf2 activation and GPX4 
expression were also decreased in starved p53KO cells (especially upon treatment with Sfb or 
Rsl-3), but accompanied by compensatory overexpressed xCT. These results may be indicative of 
enhanced AD in p53KO cells and may therefore explain, at least in part, their resistance to 
treatment with Sfb+ND which, as presented here, induces ferroptosis in p53WT HepG2 cells.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Proferroptotic response to nutrient deprivation in hepatocellular carcinoma cells is related to p53 status",
pages = "86",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6404"
}

Markelić, M., Otašević, V., Gudelj, A., Saksida, T., Stančić, A., Veličković, K.,& Krstić, J.. (2023). Proferroptotic response to nutrient deprivation in hepatocellular carcinoma cells is related to p53 status. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 86.
https://hdl.handle.net/21.15107/rcub_ibiss_6404

Markelić M, Otašević V, Gudelj A, Saksida T, Stančić A, Veličković K, Krstić J. Proferroptotic response to nutrient deprivation in hepatocellular carcinoma cells is related to p53 status. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:86.
https://hdl.handle.net/21.15107/rcub_ibiss_6404 .

Markelić, Milica, Otašević, Vesna, Gudelj, Anđelija, Saksida, Tamara, Stančić, Ana, Veličković, Ksenija, Krstić, Jelena, "Proferroptotic response to nutrient deprivation in hepatocellular carcinoma cells is related to p53 status" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):86,
https://hdl.handle.net/21.15107/rcub_ibiss_6404 .

TY  - JOUR
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Grigorov, Ilijana
AU  - Mićanović, Dragica
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Savić, Nevena
AU  - Gudelj, Anđelija
AU  - Otašević, Vesna
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6071
AB  - Introduction: Recently, the involvement of ferroptotic cell death in the reduction of β-cell mass in diabetes has been demonstrated. To elucidate the mechanisms of β-cell ferroptosis and potential antidiabetic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in vivo, a mouse model of type 1 diabetes (T1D) was used.

Methods: Animals were divided into three groups: control (vehicle-treated), diabetic (streptozotocin-treated, 40 mg/kg, from days 1-5), and diabetic treated with Fer-1 (1 mg/kg, from days 1-21). On day 22, glycemia and insulinemia were measured and pancreases were isolated for microscopic analyses.

Results: Diabetes disturbed general parameters of β-cell mass (islet size, β-cell abundance and distribution) and health (insulin and PDX-1 expression), increased lipid peroxidation in islet cells, and phagocytic removal of iron-containing material. It also downregulated the main players of the antiferroptotic pathway - Nrf2, GPX4, and xCT. In contrast, Fer-1 ameliorated the signs of deterioration of β-cell/islets, decreased lipid peroxidation, and reduced phagocytic activity, while upregulated expression of Nrf2 (and its nuclear translocation), GPX4, and xCT in β-cell/islets.

Discussion: Overall, our study confirms ferroptosis as an important mode of β-cell death in T1D and suggests antiferroptotic agents as a promising strategy for the prevention and treatment of diabetes
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Endocrinology
T1  - Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy
VL  - 14
DO  - 10.3389/fendo.2023.1227498
SP  - 1227498
ER  - 

@article{
author = "Markelić, Milica and Stančić, Ana and Saksida, Tamara and Grigorov, Ilijana and Mićanović, Dragica and Veličković, Ksenija and Martinović, Vesna and Savić, Nevena and Gudelj, Anđelija and Otašević, Vesna",
year = "2023",
abstract = "Introduction: Recently, the involvement of ferroptotic cell death in the reduction of β-cell mass in diabetes has been demonstrated. To elucidate the mechanisms of β-cell ferroptosis and potential antidiabetic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in vivo, a mouse model of type 1 diabetes (T1D) was used.

Methods: Animals were divided into three groups: control (vehicle-treated), diabetic (streptozotocin-treated, 40 mg/kg, from days 1-5), and diabetic treated with Fer-1 (1 mg/kg, from days 1-21). On day 22, glycemia and insulinemia were measured and pancreases were isolated for microscopic analyses.

Results: Diabetes disturbed general parameters of β-cell mass (islet size, β-cell abundance and distribution) and health (insulin and PDX-1 expression), increased lipid peroxidation in islet cells, and phagocytic removal of iron-containing material. It also downregulated the main players of the antiferroptotic pathway - Nrf2, GPX4, and xCT. In contrast, Fer-1 ameliorated the signs of deterioration of β-cell/islets, decreased lipid peroxidation, and reduced phagocytic activity, while upregulated expression of Nrf2 (and its nuclear translocation), GPX4, and xCT in β-cell/islets.

Discussion: Overall, our study confirms ferroptosis as an important mode of β-cell death in T1D and suggests antiferroptotic agents as a promising strategy for the prevention and treatment of diabetes",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Endocrinology",
title = "Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy",
volume = "14",
doi = "10.3389/fendo.2023.1227498",
pages = "1227498"
}

Markelić, M., Stančić, A., Saksida, T., Grigorov, I., Mićanović, D., Veličković, K., Martinović, V., Savić, N., Gudelj, A.,& Otašević, V.. (2023). Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy. in Frontiers in Endocrinology
Lausanne: Frontiers Media SA., 14, 1227498.
https://doi.org/10.3389/fendo.2023.1227498

Markelić M, Stančić A, Saksida T, Grigorov I, Mićanović D, Veličković K, Martinović V, Savić N, Gudelj A, Otašević V. Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy. in Frontiers in Endocrinology. 2023;14:1227498.
doi:10.3389/fendo.2023.1227498 .

Markelić, Milica, Stančić, Ana, Saksida, Tamara, Grigorov, Ilijana, Mićanović, Dragica, Veličković, Ksenija, Martinović, Vesna, Savić, Nevena, Gudelj, Anđelija, Otašević, Vesna, "Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy" in Frontiers in Endocrinology, 14 (2023):1227498,
https://doi.org/10.3389/fendo.2023.1227498 . .

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  - CONF
AU  - Savić, Nevena
AU  - Otašević, Vesna
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Stančić, Ana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5195
AB  - Један од узрока патолошких промена јетре током Diabetes mellitus-a (ДМ) јесте повећање ћелијске смрти. До данас је описана апоптоза, некроза и аутофагија хепатоцита.1 Циљ ове студије био је испитивање укључености фероптозе, ћелијске смрти која настаје услед интезивираног процеса липидне пероксидације зависне од гвожђа, на развој патолошких промена јетре у ДМ, коришћењем фероптотског инхибитора феростатина-1 (Фер-1). Мужјаци C57BL/6 мишева подељени су у три групе: 1. контрола (К); 2. дијабетeс (индукован стрептозотоцином, Д) и 3. дијабетес + Фер-1 (ДФ). У групи Д забележена је смањена експресија цитопротективног транскрипционог фактора Nrf2 (енгл. nuclear factor (erythroid-derived-2)-related factor2), што је случај и са његовим таргетним протеинима битним за регулисање процеса фероптозе, као што су кључни ензим за уклањање липидних пероксида, GPx4 (глутатион пероксидаза 4), цистеин-глутаматни трансмембрански антипортер (xCT) укључен у регулацију метаболизма глутатиона и хем оксигеназа 1 (HO-1) која регулише метаболизам гвожђа. У групи ДФ забележено је значајно повећање експресије Nrf2, GPx4, xCT и HO-1. Маркер липидне пероксидације 4-HNE повећан је у хепатоцитима Д групе, а смањен у ДФ групи. Наши резултати показују да хепатоцити у ДМ подлежу фероптози, с обзиром на чињеницу да Фер-1 делује цитопротективно, активирајући Nrf2-зависну сигналну каскаду. Ово нас упућује на фероптозу као нову терапеутску мету у лечењу патолошких промена јетре у ДМ и то стимулисаном активацијом Nrf2.
AB  - Jedan od uzroka patoloških promena jetre tokom Diabetes mellitus-a (DM) jeste povećanje ćelijske smrti. Do danas je opisana apoptoza, nekroza i autofagija hepatocita.1 Cilj ove studije bio je ispitivanje uključenosti feroptoze, ćelijske smrti koja nastaje usled inteziviranog procesa lipidne peroksidacije zavisne od gvožđa, na razvoj patoloških promena jetre u DM, korišćenjem feroptotskog inhibitora ferostatina-1 (Fer-1). Mužjaci C57BL/6 miševa podeljeni su u tri grupe: 1. kontrola (K); 2. dijabetes (indukovan streptozotocinom, D) i 3. dijabetes + Fer-1 (DF). U grupi D zabeležena je smanjena ekspresija citoprotektivnog transkripcionog faktora Nrf2 (engl. nuclear factor (erythroid-derived-2)-related factor2), što je slučaj i sa njegovim targetnim proteinima bitnim za regulisanje procesa feroptoze, kao što su ključni enzim za uklanjanje lipidnih peroksida, GPx4 (glutation peroksidaza 4), cistein-glutamatni transmembranski antiporter (xCT) uključen u regulaciju metabolizma glutationa i hem oksigenaza 1 (HO-1) koja reguliše metabolizam gvožđa. U grupi DF zabeleženo je značajno povećanje ekspresije Nrf2, GPx4, xCT i HO-1. Marker lipidne peroksidacije 4-HNE povećan je u hepatocitima D grupe, a smanjen u DF grupi. Naši rezultati pokazuju da hepatociti u DM podležu feroptozi, s obzirom na činjenicu da Fer-1 deluje citoprotektivno, aktivirajući Nrf2-zavisnu signalnu kaskadu. Ovo nas upućuje na feroptozu kao novu terapeutsku metu u lečenju patoloških promena jetre u DM i to stimulisanom aktivacijom Nrf2.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Допринос фероптозе патолошким променама јетре дијабетичних мишева
T1  - Doprinos feroptoze patološkim promenama jetre dijabetičnih miševa
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5195
ER  - 

@conference{
author = "Savić, Nevena and Otašević, Vesna and Saksida, Tamara and Markelić, Milica and Grigorov, Ilijana and Veličković, Ksenija and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Stančić, Ana",
year = "2022",
abstract = "Један од узрока патолошких промена јетре током Diabetes mellitus-a (ДМ) јесте повећање ћелијске смрти. До данас је описана апоптоза, некроза и аутофагија хепатоцита.1 Циљ ове студије био је испитивање укључености фероптозе, ћелијске смрти која настаје услед интезивираног процеса липидне пероксидације зависне од гвожђа, на развој патолошких промена јетре у ДМ, коришћењем фероптотског инхибитора феростатина-1 (Фер-1). Мужјаци C57BL/6 мишева подељени су у три групе: 1. контрола (К); 2. дијабетeс (индукован стрептозотоцином, Д) и 3. дијабетес + Фер-1 (ДФ). У групи Д забележена је смањена експресија цитопротективног транскрипционог фактора Nrf2 (енгл. nuclear factor (erythroid-derived-2)-related factor2), што је случај и са његовим таргетним протеинима битним за регулисање процеса фероптозе, као што су кључни ензим за уклањање липидних пероксида, GPx4 (глутатион пероксидаза 4), цистеин-глутаматни трансмембрански антипортер (xCT) укључен у регулацију метаболизма глутатиона и хем оксигеназа 1 (HO-1) која регулише метаболизам гвожђа. У групи ДФ забележено је значајно повећање експресије Nrf2, GPx4, xCT и HO-1. Маркер липидне пероксидације 4-HNE повећан је у хепатоцитима Д групе, а смањен у ДФ групи. Наши резултати показују да хепатоцити у ДМ подлежу фероптози, с обзиром на чињеницу да Фер-1 делује цитопротективно, активирајући Nrf2-зависну сигналну каскаду. Ово нас упућује на фероптозу као нову терапеутску мету у лечењу патолошких промена јетре у ДМ и то стимулисаном активацијом Nrf2., Jedan od uzroka patoloških promena jetre tokom Diabetes mellitus-a (DM) jeste povećanje ćelijske smrti. Do danas je opisana apoptoza, nekroza i autofagija hepatocita.1 Cilj ove studije bio je ispitivanje uključenosti feroptoze, ćelijske smrti koja nastaje usled inteziviranog procesa lipidne peroksidacije zavisne od gvožđa, na razvoj patoloških promena jetre u DM, korišćenjem feroptotskog inhibitora ferostatina-1 (Fer-1). Mužjaci C57BL/6 miševa podeljeni su u tri grupe: 1. kontrola (K); 2. dijabetes (indukovan streptozotocinom, D) i 3. dijabetes + Fer-1 (DF). U grupi D zabeležena je smanjena ekspresija citoprotektivnog transkripcionog faktora Nrf2 (engl. nuclear factor (erythroid-derived-2)-related factor2), što je slučaj i sa njegovim targetnim proteinima bitnim za regulisanje procesa feroptoze, kao što su ključni enzim za uklanjanje lipidnih peroksida, GPx4 (glutation peroksidaza 4), cistein-glutamatni transmembranski antiporter (xCT) uključen u regulaciju metabolizma glutationa i hem oksigenaza 1 (HO-1) koja reguliše metabolizam gvožđa. U grupi DF zabeleženo je značajno povećanje ekspresije Nrf2, GPx4, xCT i HO-1. Marker lipidne peroksidacije 4-HNE povećan je u hepatocitima D grupe, a smanjen u DF grupi. Naši rezultati pokazuju da hepatociti u DM podležu feroptozi, s obzirom na činjenicu da Fer-1 deluje citoprotektivno, aktivirajući Nrf2-zavisnu signalnu kaskadu. Ovo nas upućuje na feroptozu kao novu terapeutsku metu u lečenju patoloških promena jetre u DM i to stimulisanom aktivacijom Nrf2.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Допринос фероптозе патолошким променама јетре дијабетичних мишева, Doprinos feroptoze patološkim promenama jetre dijabetičnih miševa",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5195"
}

Savić, N., Otašević, V., Saksida, T., Markelić, M., Grigorov, I., Veličković, K., Martinović, V., Mićanović, D., Ivanović, A.,& Stančić, A.. (2022). Допринос фероптозе патолошким променама јетре дијабетичних мишева. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society..
https://hdl.handle.net/21.15107/rcub_ibiss_5195

Savić N, Otašević V, Saksida T, Markelić M, Grigorov I, Veličković K, Martinović V, Mićanović D, Ivanović A, Stančić A. Допринос фероптозе патолошким променама јетре дијабетичних мишева. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5195 .

Savić, Nevena, Otašević, Vesna, Saksida, Tamara, Markelić, Milica, Grigorov, Ilijana, Veličković, Ksenija, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Stančić, Ana, "Допринос фероптозе патолошким променама јетре дијабетичних мишева" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5195 .

TY  - CONF
AU  - Otašević, Vesna
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Vučetić, Milica
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Savić, Nevena
AU  - Stančić, Ana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5197
AB  - Кључни патолошки догађај у настанку дијабетеса је губитак функционалних β-ћелија. Улога фероптозе, новоописаног типа регулисане ћелијске смрти зависне од гвожђа, у смањењу популације β-ћелија код дијабетеса није довољно испитана. Стога је у овом раду испитиван допринос фероптозе умирању β-ћелија у дијабетичним условима in vivo и in vitro. Код мишева са дијабетесом индукованим стрептозотоцином, СТЗ забележено је значајно повећање инфилтрације макрофага и акумулације липидних пероксида у острвцима панкреаса, праћено смањењем популације инсулин позитивних ћелија, експресије глутатион пероксидазе 4, GPX4, цистеин/глутамат транспортера xCT и хем оксигеназе 1. Резултати добијени in vitro на Rin-5f β-ћелијама су показали да дијабетични услови (висока концентрација глукозе, СТЗ, цитокини и водоник пероксид снижавају експресију транскрипционог фактора Nrf2, GPX4 и митохондријални мембрански потенцијал, а повећавају продукцију реактивних врста кисеоника, акумулацију слободног гвожђа, липидних пероксида и смртност β-ћелија. Примена инхибитора фероптозе, феростатина-1 у потпуности је поништила наведене промене, тј. остварила позитивне ефекте на β-ћелије/панкреас дијабетичних животиња, осим у случају in vitro третмана цитокинима, указујући на разлике између дијабетогених стимулуса у одређивању судбине β-ћелија. Наведени резултати показују да модулирање тј. инхибиција фероптозе у дијабетесу може бити нови обећавајући приступ за очување популације β-ћелија и третман дијабетеса.
AB  - Ključni patološki događaj u nastanku dijabetesa je gubitak funkcionalnih β-ćelija. Uloga feroptoze, novoopisanog tipa regulisane ćelijske smrti zavisne od gvožđa, u smanjenju populacije β-ćelija kod dijabetesa nije dovoljno ispitana. Stoga je u ovom radu ispitivan doprinos feroptoze umiranju β-ćelija u dijabetičnim uslovima in vivo i in vitro. Kod miševa sa dijabetesom indukovanim streptozotocinom, STZ zabeleženo je značajno povećanje infiltracije makrofaga i akumulacije lipidnih peroksida u ostrvcima pankreasa, praćeno smanjenjem populacije insulin pozitivnih ćelija, ekspresije glutation peroksidaze 4, GPX4, cistein/glutamat transportera xCT i hem oksigenaze 1. Rezultati dobijeni in vitro na Rin-5f β-ćelijama su pokazali da dijabetični uslovi (visoka koncentracija glukoze, STZ, citokini i vodonik peroksid snižavaju ekspresiju transkripcionog faktora Nrf2, GPX4 i mitohondrijalni membranski potencijal, a povećavaju produkciju reaktivnih vrsta kiseonika, akumulaciju slobodnog gvožđa, lipidnih peroksida i smrtnost β-ćelija. Primena inhibitora feroptoze, ferostatina-1 u potpunosti je poništila navedene promene, tj. ostvarila pozitivne efekte na β-ćelije/pankreas dijabetičnih životinja, osim u slučaju in vitro tretmana citokinima, ukazujući na razlike između dijabetogenih stimulusa u određivanju sudbine β-ćelija. Navedeni rezultati pokazuju da moduliranje tj. inhibicija feroptoze u dijabetesu može biti novi obećavajući pristup za očuvanje populacije β-ćelija i tretman dijabetesa.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Фероптоза у дијабетесу и дијабетичним компликацијама
T1  - Feroptoza u dijabetesu i dijabetičnim komplikacijama
SP  - 279
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5197
ER  - 

@conference{
author = "Otašević, Vesna and Saksida, Tamara and Markelić, Milica and Grigorov, Ilijana and Vučetić, Milica and Veličković, Ksenija and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Savić, Nevena and Stančić, Ana",
year = "2022",
abstract = "Кључни патолошки догађај у настанку дијабетеса је губитак функционалних β-ћелија. Улога фероптозе, новоописаног типа регулисане ћелијске смрти зависне од гвожђа, у смањењу популације β-ћелија код дијабетеса није довољно испитана. Стога је у овом раду испитиван допринос фероптозе умирању β-ћелија у дијабетичним условима in vivo и in vitro. Код мишева са дијабетесом индукованим стрептозотоцином, СТЗ забележено је значајно повећање инфилтрације макрофага и акумулације липидних пероксида у острвцима панкреаса, праћено смањењем популације инсулин позитивних ћелија, експресије глутатион пероксидазе 4, GPX4, цистеин/глутамат транспортера xCT и хем оксигеназе 1. Резултати добијени in vitro на Rin-5f β-ћелијама су показали да дијабетични услови (висока концентрација глукозе, СТЗ, цитокини и водоник пероксид снижавају експресију транскрипционог фактора Nrf2, GPX4 и митохондријални мембрански потенцијал, а повећавају продукцију реактивних врста кисеоника, акумулацију слободног гвожђа, липидних пероксида и смртност β-ћелија. Примена инхибитора фероптозе, феростатина-1 у потпуности је поништила наведене промене, тј. остварила позитивне ефекте на β-ћелије/панкреас дијабетичних животиња, осим у случају in vitro третмана цитокинима, указујући на разлике између дијабетогених стимулуса у одређивању судбине β-ћелија. Наведени резултати показују да модулирање тј. инхибиција фероптозе у дијабетесу може бити нови обећавајући приступ за очување популације β-ћелија и третман дијабетеса., Ključni patološki događaj u nastanku dijabetesa je gubitak funkcionalnih β-ćelija. Uloga feroptoze, novoopisanog tipa regulisane ćelijske smrti zavisne od gvožđa, u smanjenju populacije β-ćelija kod dijabetesa nije dovoljno ispitana. Stoga je u ovom radu ispitivan doprinos feroptoze umiranju β-ćelija u dijabetičnim uslovima in vivo i in vitro. Kod miševa sa dijabetesom indukovanim streptozotocinom, STZ zabeleženo je značajno povećanje infiltracije makrofaga i akumulacije lipidnih peroksida u ostrvcima pankreasa, praćeno smanjenjem populacije insulin pozitivnih ćelija, ekspresije glutation peroksidaze 4, GPX4, cistein/glutamat transportera xCT i hem oksigenaze 1. Rezultati dobijeni in vitro na Rin-5f β-ćelijama su pokazali da dijabetični uslovi (visoka koncentracija glukoze, STZ, citokini i vodonik peroksid snižavaju ekspresiju transkripcionog faktora Nrf2, GPX4 i mitohondrijalni membranski potencijal, a povećavaju produkciju reaktivnih vrsta kiseonika, akumulaciju slobodnog gvožđa, lipidnih peroksida i smrtnost β-ćelija. Primena inhibitora feroptoze, ferostatina-1 u potpunosti je poništila navedene promene, tj. ostvarila pozitivne efekte na β-ćelije/pankreas dijabetičnih životinja, osim u slučaju in vitro tretmana citokinima, ukazujući na razlike između dijabetogenih stimulusa u određivanju sudbine β-ćelija. Navedeni rezultati pokazuju da moduliranje tj. inhibicija feroptoze u dijabetesu može biti novi obećavajući pristup za očuvanje populacije β-ćelija i tretman dijabetesa.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Фероптоза у дијабетесу и дијабетичним компликацијама, Feroptoza u dijabetesu i dijabetičnim komplikacijama",
pages = "279",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5197"
}

Otašević, V., Saksida, T., Markelić, M., Grigorov, I., Vučetić, M., Veličković, K., Martinović, V., Mićanović, D., Ivanović, A., Savić, N.,& Stančić, A.. (2022). Фероптоза у дијабетесу и дијабетичним компликацијама. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 279.
https://hdl.handle.net/21.15107/rcub_ibiss_5197

Otašević V, Saksida T, Markelić M, Grigorov I, Vučetić M, Veličković K, Martinović V, Mićanović D, Ivanović A, Savić N, Stančić A. Фероптоза у дијабетесу и дијабетичним компликацијама. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:279.
https://hdl.handle.net/21.15107/rcub_ibiss_5197 .

Otašević, Vesna, Saksida, Tamara, Markelić, Milica, Grigorov, Ilijana, Vučetić, Milica, Veličković, Ksenija, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Savić, Nevena, Stančić, Ana, "Фероптоза у дијабетесу и дијабетичним компликацијама" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):279,
https://hdl.handle.net/21.15107/rcub_ibiss_5197 .

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  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Veličković, Ksenija
AU  - Savić, Nevena
AU  - Otašević, Vesna
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4910
AB  - The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.
PB  - London:Hindawi
T2  - Oxidative Medicine and Cellular Longevity
T1  - Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions
VL  - 2022
DO  - 10.1155/2022/3873420
SP  - 3873420
ER  - 

@article{
author = "Stančić, Ana and Saksida, Tamara and Markelić, Milica and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Veličković, Ksenija and Savić, Nevena and Otašević, Vesna",
year = "2022",
abstract = "The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.",
publisher = "London:Hindawi",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions",
volume = "2022",
doi = "10.1155/2022/3873420",
pages = "3873420"
}

Stančić, A., Saksida, T., Markelić, M., Vučetić, M., Grigorov, I., Martinović, V., Mićanović, D., Ivanović, A., Veličković, K., Savić, N.,& Otašević, V.. (2022). Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions. in Oxidative Medicine and Cellular Longevity
London:Hindawi., 2022, 3873420.
https://doi.org/10.1155/2022/3873420

Stančić A, Saksida T, Markelić M, Vučetić M, Grigorov I, Martinović V, Mićanović D, Ivanović A, Veličković K, Savić N, Otašević V. Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions. in Oxidative Medicine and Cellular Longevity. 2022;2022:3873420.
doi:10.1155/2022/3873420 .

Stančić, Ana, Saksida, Tamara, Markelić, Milica, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Veličković, Ksenija, Savić, Nevena, Otašević, Vesna, "Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions" in Oxidative Medicine and Cellular Longevity, 2022 (2022):3873420,
https://doi.org/10.1155/2022/3873420 . .

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  - Stančić, Ana
AU  - Veličković, Ksenija
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Saksida, Tamara
AU  - Savić, Nevena
AU  - Vučetić, Milica
AU  - Martinović, Vesna
AU  - Ivanović, Anđelija
AU  - Otašević, Vesna
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5160
AB  - Cell death plays an important role in diabetes-induced liver dysfunction. Ferroptosis is a
newly defined regulated cell death caused by iron-dependent lipid peroxidation. Our previous studies
have shown that high glucose and streptozotocin (STZ) cause  -cell death through ferroptosis and
that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, improves  -cell viability, islet morphology, and
function. This study was aimed to examine in vivo the involvement of ferroptosis in diabetes-related
pathological changes in the liver. For this purpose, male C57BL/6 mice, in which diabetes was induced
with STZ (40 mg/kg/5 consecutive days), were treated with Fer-1 (1 mg/kg, from day 1–21 day). It
was found that in diabetic mice Fer-1 improved serum levels of ALT and triglycerides and decreased
liver fibrosis, hepatocytes size, and binucleation. This improvement was due to the Fer-1-induced
attenuation of ferroptotic events in the liver of diabetic mice, such as accumulation of pro-oxidative
parameters (iron, lipofuscin, 4-HNE), decrease in expression level/activity of antioxidative defenserelated
molecules (GPX4, Nrf2, xCT, GSH, GCL, HO-1, SOD), and HMGB1 translocation from nucleus
into cytosol. We concluded that ferroptosis contributes to diabetes-related pathological changes in
the liver and that the targeting of ferroptosis represents a promising approach in the management of
diabetes-induced liver injury.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Involvement of Ferroptosis in Diabetes-Induced Liver Pathology
IS  - 16
VL  - 23
DO  - 10.3390/ijms23169309
SP  - 9309
ER  - 

@article{
author = "Stančić, Ana and Veličković, Ksenija and Markelić, Milica and Grigorov, Ilijana and Saksida, Tamara and Savić, Nevena and Vučetić, Milica and Martinović, Vesna and Ivanović, Anđelija and Otašević, Vesna",
year = "2022",
abstract = "Cell death plays an important role in diabetes-induced liver dysfunction. Ferroptosis is a
newly defined regulated cell death caused by iron-dependent lipid peroxidation. Our previous studies
have shown that high glucose and streptozotocin (STZ) cause  -cell death through ferroptosis and
that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, improves  -cell viability, islet morphology, and
function. This study was aimed to examine in vivo the involvement of ferroptosis in diabetes-related
pathological changes in the liver. For this purpose, male C57BL/6 mice, in which diabetes was induced
with STZ (40 mg/kg/5 consecutive days), were treated with Fer-1 (1 mg/kg, from day 1–21 day). It
was found that in diabetic mice Fer-1 improved serum levels of ALT and triglycerides and decreased
liver fibrosis, hepatocytes size, and binucleation. This improvement was due to the Fer-1-induced
attenuation of ferroptotic events in the liver of diabetic mice, such as accumulation of pro-oxidative
parameters (iron, lipofuscin, 4-HNE), decrease in expression level/activity of antioxidative defenserelated
molecules (GPX4, Nrf2, xCT, GSH, GCL, HO-1, SOD), and HMGB1 translocation from nucleus
into cytosol. We concluded that ferroptosis contributes to diabetes-related pathological changes in
the liver and that the targeting of ferroptosis represents a promising approach in the management of
diabetes-induced liver injury.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Involvement of Ferroptosis in Diabetes-Induced Liver Pathology",
number = "16",
volume = "23",
doi = "10.3390/ijms23169309",
pages = "9309"
}

Stančić, A., Veličković, K., Markelić, M., Grigorov, I., Saksida, T., Savić, N., Vučetić, M., Martinović, V., Ivanović, A.,& Otašević, V.. (2022). Involvement of Ferroptosis in Diabetes-Induced Liver Pathology. in International Journal of Molecular Sciences
Basel: MDPI., 23(16), 9309.
https://doi.org/10.3390/ijms23169309

Stančić A, Veličković K, Markelić M, Grigorov I, Saksida T, Savić N, Vučetić M, Martinović V, Ivanović A, Otašević V. Involvement of Ferroptosis in Diabetes-Induced Liver Pathology. in International Journal of Molecular Sciences. 2022;23(16):9309.
doi:10.3390/ijms23169309 .

Stančić, Ana, Veličković, Ksenija, Markelić, Milica, Grigorov, Ilijana, Saksida, Tamara, Savić, Nevena, Vučetić, Milica, Martinović, Vesna, Ivanović, Anđelija, Otašević, Vesna, "Involvement of Ferroptosis in Diabetes-Induced Liver Pathology" in International Journal of Molecular Sciences, 23, no. 16 (2022):9309,
https://doi.org/10.3390/ijms23169309 . .

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  - Otašević, Vesna
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Veličković, Ksenija
AU  - Grigorov, Ilijana
AU  - Stančić, Ana
PY  - 2022
UR  - uri:https://meetings.embo.org/event/22-thiol-oxidation
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5265
AB  - The key pathological event in the development of diabetes is the loss of functional β-cells. We examined here so far unknown the contribution of ferroptosis to β-cell death in diabetic conditions in vivo and in vitro. Thus, male C57BL/6 mice were divided into three groups: diabetic, (strepozotocin-treated 40 mg/kg/5 days), diabetic+ferrostatin-1-treated (Fer-1, 1 mg/kg from day 1-21) and control, while Rin-5F were treated with diabetes-mimicking factors: high glucose (25mM), hydrogen peroxide (75 μM), or streptozotocin (10mM) for 12h. In diabetic mice a significant increase in macrophage infiltration and lipid peroxide accumulation in pancreatic islets, followed by a decrease in an insulin-positive cell population, expression of GPX4, cysteine/glutamate transporter xCT and heme oxygenase 1 were observed. Applied diabetes-mimicking conditions increased death of Rin-5f β-cells, accumulation of reactive oxygen species, lipid peroxides and iron along with a decrease in the activation of transcription factor Nrf2, expression of GPX4 and mitochondrial membrane potential. The use of ferroptosis inhibitor, Fer-1, completely reversed examined ferroptosis-related changes, i.e. had positive effects on both pancreatic islets of diabetic animals and in vitro β-cells. These results show that modulation, i.e. inhibition of ferroptosis in diabetes may be a promising new approach to conserving β-cell populations and treating diabetes.
PB  - Heidelberg: European Molecular Biology Organization (EMBO)
C3  - EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13
T1  - Inhibition of ferroptosis increases the survival of β-cells
SP  - 52
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5265
ER  - 

@conference{
author = "Otašević, Vesna and Saksida, Tamara and Markelić, Milica and Veličković, Ksenija and Grigorov, Ilijana and Stančić, Ana",
year = "2022",
abstract = "The key pathological event in the development of diabetes is the loss of functional β-cells. We examined here so far unknown the contribution of ferroptosis to β-cell death in diabetic conditions in vivo and in vitro. Thus, male C57BL/6 mice were divided into three groups: diabetic, (strepozotocin-treated 40 mg/kg/5 days), diabetic+ferrostatin-1-treated (Fer-1, 1 mg/kg from day 1-21) and control, while Rin-5F were treated with diabetes-mimicking factors: high glucose (25mM), hydrogen peroxide (75 μM), or streptozotocin (10mM) for 12h. In diabetic mice a significant increase in macrophage infiltration and lipid peroxide accumulation in pancreatic islets, followed by a decrease in an insulin-positive cell population, expression of GPX4, cysteine/glutamate transporter xCT and heme oxygenase 1 were observed. Applied diabetes-mimicking conditions increased death of Rin-5f β-cells, accumulation of reactive oxygen species, lipid peroxides and iron along with a decrease in the activation of transcription factor Nrf2, expression of GPX4 and mitochondrial membrane potential. The use of ferroptosis inhibitor, Fer-1, completely reversed examined ferroptosis-related changes, i.e. had positive effects on both pancreatic islets of diabetic animals and in vitro β-cells. These results show that modulation, i.e. inhibition of ferroptosis in diabetes may be a promising new approach to conserving β-cell populations and treating diabetes.",
publisher = "Heidelberg: European Molecular Biology Organization (EMBO)",
journal = "EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13",
title = "Inhibition of ferroptosis increases the survival of β-cells",
pages = "52",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5265"
}

Otašević, V., Saksida, T., Markelić, M., Veličković, K., Grigorov, I.,& Stančić, A.. (2022). Inhibition of ferroptosis increases the survival of β-cells. in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13
Heidelberg: European Molecular Biology Organization (EMBO)., 52.
https://hdl.handle.net/21.15107/rcub_ibiss_5265

Otašević V, Saksida T, Markelić M, Veličković K, Grigorov I, Stančić A. Inhibition of ferroptosis increases the survival of β-cells. in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13. 2022;:52.
https://hdl.handle.net/21.15107/rcub_ibiss_5265 .

Otašević, Vesna, Saksida, Tamara, Markelić, Milica, Veličković, Ksenija, Grigorov, Ilijana, Stančić, Ana, "Inhibition of ferroptosis increases the survival of β-cells" in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13 (2022):52,
https://hdl.handle.net/21.15107/rcub_ibiss_5265 .

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 . .