TY  - JOUR
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Sopta, Jelena
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Ivanović, Anđelija
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4090
AB  - Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium
is an anti‑ischemic agent that shifts energy production from fatty acid oxidation to less oxygen‑
consuming glycolysis. Thus, we investigated the effects of a 4‑week meldonium pre‑treatment
(300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that
meldonium ameliorates I/R‑induced liver inflammation and injury, as confirmed by liver histology,
and by attenuation of serum alanine‑ and aspartate aminotransferase activity, serum and liver
high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and
the phosphorylated nuclear factor kappa‑light‑chain‑enhancer of activated B cells. Through the
increased hepatic activation of the nuclear factor erythroid 2‑related factor 2, meldonium improves
the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum
and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione
and free thiol groups content, and hepatic copper‑zinc superoxide dismutase, manganese superoxide
dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results,
it can be concluded that meldonium represent a protective agent against I/R‑induced liver injury, with
a clinical significance in surgical procedures.
PB  - Nature Publishing Group
T2  - Scientific Reports
T1  - The effects of meldonium on the acute ischemia/reperfusion liver injury in rats
IS  - 1
VL  - 11
DO  - 10.1038/s41598-020-80011-y
SP  - 1305
ER  - 

@article{
author = "Đurašević, Siniša and Stojković, Maja and Sopta, Jelena and Pavlović, Slađan and Borković Mitić, Slavica and Ivanović, Anđelija and Jasnić, Nebojša and Tosti, Tomislav and Đurović, Saša and Đorđević, Jelena and Todorović, Zoran",
year = "2021",
abstract = "Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium
is an anti‑ischemic agent that shifts energy production from fatty acid oxidation to less oxygen‑
consuming glycolysis. Thus, we investigated the effects of a 4‑week meldonium pre‑treatment
(300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that
meldonium ameliorates I/R‑induced liver inflammation and injury, as confirmed by liver histology,
and by attenuation of serum alanine‑ and aspartate aminotransferase activity, serum and liver
high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and
the phosphorylated nuclear factor kappa‑light‑chain‑enhancer of activated B cells. Through the
increased hepatic activation of the nuclear factor erythroid 2‑related factor 2, meldonium improves
the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum
and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione
and free thiol groups content, and hepatic copper‑zinc superoxide dismutase, manganese superoxide
dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results,
it can be concluded that meldonium represent a protective agent against I/R‑induced liver injury, with
a clinical significance in surgical procedures.",
publisher = "Nature Publishing Group",
journal = "Scientific Reports",
title = "The effects of meldonium on the acute ischemia/reperfusion liver injury in rats",
number = "1",
volume = "11",
doi = "10.1038/s41598-020-80011-y",
pages = "1305"
}

Đurašević, S., Stojković, M., Sopta, J., Pavlović, S., Borković Mitić, S., Ivanović, A., Jasnić, N., Tosti, T., Đurović, S., Đorđević, J.,& Todorović, Z.. (2021). The effects of meldonium on the acute ischemia/reperfusion liver injury in rats. in Scientific Reports
Nature Publishing Group., 11(1), 1305.
https://doi.org/10.1038/s41598-020-80011-y

Đurašević S, Stojković M, Sopta J, Pavlović S, Borković Mitić S, Ivanović A, Jasnić N, Tosti T, Đurović S, Đorđević J, Todorović Z. The effects of meldonium on the acute ischemia/reperfusion liver injury in rats. in Scientific Reports. 2021;11(1):1305.
doi:10.1038/s41598-020-80011-y .

Đurašević, Siniša, Stojković, Maja, Sopta, Jelena, Pavlović, Slađan, Borković Mitić, Slavica, Ivanović, Anđelija, Jasnić, Nebojša, Tosti, Tomislav, Đurović, Saša, Đorđević, Jelena, Todorović, Zoran, "The effects of meldonium on the acute ischemia/reperfusion liver injury in rats" in Scientific Reports, 11, no. 1 (2021):1305,
https://doi.org/10.1038/s41598-020-80011-y . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Kotur-Stevuljević, Jelena
AU  - Simić, Ljubica
AU  - Sopta, Jelena
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://doi.org/10.1007/s10753-020-01302-0
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32857321
UR  - https://radar.ibiss.bg.ac.rs/123456789/3869
AB  - Monocytes' plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43lowCD11b+ and CCR2-CX3CR1+CD43hiCD11b+ cells (corresponding to "classical" and "non-classical" monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.
PB  - Springer
T2  - Inflammation
T1  - Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats.
VL  - 43
DO  - 10.1007/s10753-020-01302-0
SP  - 2312
EP  - 2331
ER  - 

@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Bufan, Biljana and Nacka-Aleksić, Mirjana and Kosec, Duško and Pilipović, Ivan and Kotur-Stevuljević, Jelena and Simić, Ljubica and Sopta, Jelena and Leposavić, Gordana",
year = "2020",
abstract = "Monocytes' plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43lowCD11b+ and CCR2-CX3CR1+CD43hiCD11b+ cells (corresponding to "classical" and "non-classical" monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.",
publisher = "Springer",
journal = "Inflammation",
title = "Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats.",
volume = "43",
doi = "10.1007/s10753-020-01302-0",
pages = "2312-2331"
}

Dimitrijević, M., Arsenović-Ranin, N., Bufan, B., Nacka-Aleksić, M., Kosec, D., Pilipović, I., Kotur-Stevuljević, J., Simić, L., Sopta, J.,& Leposavić, G.. (2020). Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats.. in Inflammation
Springer., 43, 2312-2331.
https://doi.org/10.1007/s10753-020-01302-0

Dimitrijević M, Arsenović-Ranin N, Bufan B, Nacka-Aleksić M, Kosec D, Pilipović I, Kotur-Stevuljević J, Simić L, Sopta J, Leposavić G. Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats.. in Inflammation. 2020;43:2312-2331.
doi:10.1007/s10753-020-01302-0 .

Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Bufan, Biljana, Nacka-Aleksić, Mirjana, Kosec, Duško, Pilipović, Ivan, Kotur-Stevuljević, Jelena, Simić, Ljubica, Sopta, Jelena, Leposavić, Gordana, "Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats." in Inflammation, 43 (2020):2312-2331,
https://doi.org/10.1007/s10753-020-01302-0 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Lazarević Macanović, Mirjana
AU  - Milovanović, Petar
AU  - Đurić, Marija
AU  - Sopta, Jelena
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S0014480017305646?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3076
AB  - Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-γ + and IL-17 + IFN-γ + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3+ T regulatory cells (Treg) did not differ between sexes. Thus, CD4+ Teff cells/Treg ratio, and IL-17+ T cells/Treg and IFN-γ + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4+ T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-γ-dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis.
T2  - Experimental and Molecular Pathology
T1  - Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease.
IS  - 1
VL  - 105
DO  - 10.1016/j.yexmp.2018.05.007
SP  - 10
EP  - 22
ER  - 

@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Bufan, Biljana and Nacka-Aleksić, Mirjana and Lazarević Macanović, Mirjana and Milovanović, Petar and Đurić, Marija and Sopta, Jelena and Leposavić, Gordana",
year = "2018",
abstract = "Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-γ + and IL-17 + IFN-γ + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3+ T regulatory cells (Treg) did not differ between sexes. Thus, CD4+ Teff cells/Treg ratio, and IL-17+ T cells/Treg and IFN-γ + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4+ T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-γ-dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis.",
journal = "Experimental and Molecular Pathology",
title = "Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease.",
number = "1",
volume = "105",
doi = "10.1016/j.yexmp.2018.05.007",
pages = "10-22"
}

Dimitrijević, M., Arsenović-Ranin, N., Bufan, B., Nacka-Aleksić, M., Lazarević Macanović, M., Milovanović, P., Đurić, M., Sopta, J.,& Leposavić, G.. (2018). Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease.. in Experimental and Molecular Pathology, 105(1), 10-22.
https://doi.org/10.1016/j.yexmp.2018.05.007

Dimitrijević M, Arsenović-Ranin N, Bufan B, Nacka-Aleksić M, Lazarević Macanović M, Milovanović P, Đurić M, Sopta J, Leposavić G. Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease.. in Experimental and Molecular Pathology. 2018;105(1):10-22.
doi:10.1016/j.yexmp.2018.05.007 .

Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Bufan, Biljana, Nacka-Aleksić, Mirjana, Lazarević Macanović, Mirjana, Milovanović, Petar, Đurić, Marija, Sopta, Jelena, Leposavić, Gordana, "Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease." in Experimental and Molecular Pathology, 105, no. 1 (2018):10-22,
https://doi.org/10.1016/j.yexmp.2018.05.007 . .