TY  - JOUR
AU  - Milanović, Marijana
AU  - Bekić, Marina
AU  - Đokić, Jelena
AU  - Vučević, Dragana
AU  - Čolić, Miodrag
AU  - Tomić, Sergej
PY  - 2024
UR  - https://www.ijbs.com/v20p1064.htm
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2313
AB  - Alpha-ketoglutarate (αKG) emerged as a key regulator of energetic and redox metabolism in cells, affecting the immune response in various conditions. However, it remained unclear how the exogenous αKG modulates the functions of dendritic cells (DCs), key cells regulating T-cell response. Here we found that non-toxic doses of αKG display anti-inflammatory properties in human APC-T cell interaction models. In a model of monocyte-derived (mo)DCs, αKG impaired the differentiation, and the maturation of moDCs induced with lipopolysaccharide (LPS)/interferon (IFN)-γ, and decreased their capacity to induce Th1 cells. However, αKG also promoted IL-1β secretion by mature moDCs, despite inflammasome downregulation, potentiating their Th17 polarizing capacity. αKG induced the expression of anti-oxidative enzymes and hypoxia-induced factor (HIF)-1α in moDCs, activated Akt/FoxO1 pathway and increased autophagy flux, oxidative phosphorylation (OXPHOS) and glycolysis. This correlated with a higher capacity of immature αKG-moDCs to induce Th2 cells, and conventional regulatory T cells in an indolamine-dioxygenase (IDO)-1-dependent manner. Additionally, αKG increased moDCs’ capacity to induce non-conventional T regulatory (Tr)-1 and IL-10-producing CD8+T cells via up-regulated immunoglobulin-like transcript (ILT3) expression in OXPHOS-dependent manner. These results suggested that exogenous αKG-altered redox metabolism in moDCs contributed to their tolerogenic properties, which could be relevant for designing more efficient therapeutic approaches in DCs-mediated immunotherapies.
PB  - Ivyspring International
T2  - International Journal of Biological Sciences
T2  - International Journal of Biological Sciences
T1  - Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response
EP  - 1087
IS  - 3
SP  - 1064
VL  - 20
DO  - 10.7150/ijbs.91109
ER  - 

@article{
author = "Milanović, Marijana and Bekić, Marina and Đokić, Jelena and Vučević, Dragana and Čolić, Miodrag and Tomić, Sergej",
year = "2024",
abstract = "Alpha-ketoglutarate (αKG) emerged as a key regulator of energetic and redox metabolism in cells, affecting the immune response in various conditions. However, it remained unclear how the exogenous αKG modulates the functions of dendritic cells (DCs), key cells regulating T-cell response. Here we found that non-toxic doses of αKG display anti-inflammatory properties in human APC-T cell interaction models. In a model of monocyte-derived (mo)DCs, αKG impaired the differentiation, and the maturation of moDCs induced with lipopolysaccharide (LPS)/interferon (IFN)-γ, and decreased their capacity to induce Th1 cells. However, αKG also promoted IL-1β secretion by mature moDCs, despite inflammasome downregulation, potentiating their Th17 polarizing capacity. αKG induced the expression of anti-oxidative enzymes and hypoxia-induced factor (HIF)-1α in moDCs, activated Akt/FoxO1 pathway and increased autophagy flux, oxidative phosphorylation (OXPHOS) and glycolysis. This correlated with a higher capacity of immature αKG-moDCs to induce Th2 cells, and conventional regulatory T cells in an indolamine-dioxygenase (IDO)-1-dependent manner. Additionally, αKG increased moDCs’ capacity to induce non-conventional T regulatory (Tr)-1 and IL-10-producing CD8+T cells via up-regulated immunoglobulin-like transcript (ILT3) expression in OXPHOS-dependent manner. These results suggested that exogenous αKG-altered redox metabolism in moDCs contributed to their tolerogenic properties, which could be relevant for designing more efficient therapeutic approaches in DCs-mediated immunotherapies.",
publisher = "Ivyspring International",
journal = "International Journal of Biological Sciences, International Journal of Biological Sciences",
title = "Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response",
pages = "1087-1064",
number = "3",
volume = "20",
doi = "10.7150/ijbs.91109"
}

Milanović, M., Bekić, M., Đokić, J., Vučević, D., Čolić, M.,& Tomić, S.. (2024). Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response. in International Journal of Biological Sciences
Ivyspring International., 20(3), 1064-1087.
https://doi.org/10.7150/ijbs.91109

Milanović M, Bekić M, Đokić J, Vučević D, Čolić M, Tomić S. Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response. in International Journal of Biological Sciences. 2024;20(3):1064-1087.
doi:10.7150/ijbs.91109 .

Milanović, Marijana, Bekić, Marina, Đokić, Jelena, Vučević, Dragana, Čolić, Miodrag, Tomić, Sergej, "Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response" in International Journal of Biological Sciences, 20, no. 3 (2024):1064-1087,
https://doi.org/10.7150/ijbs.91109 . .

TY  - JOUR
AU  - Drakul, Marija
AU  - Tomić, Sergej
AU  - Bekić, Marina
AU  - Mihajlović, Dušan
AU  - Vasiljević, Miloš
AU  - Rakočević, Sara
AU  - Đokić, Jelena
AU  - Popović, Nikola
AU  - Bokonjić, Dejan
AU  - Čolić, Miodrag
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/23/16829
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2220
AB  - Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-β, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-β) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-β+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Sitagliptin Induces Tolerogenic Human Dendritic Cells
IS  - 23
SP  - 16829
VL  - 24
DO  - 10.3390/ijms242316829
ER  - 

@article{
author = "Drakul, Marija and Tomić, Sergej and Bekić, Marina and Mihajlović, Dušan and Vasiljević, Miloš and Rakočević, Sara and Đokić, Jelena and Popović, Nikola and Bokonjić, Dejan and Čolić, Miodrag",
year = "2023",
abstract = "Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-β, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-β) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-β+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Sitagliptin Induces Tolerogenic Human Dendritic Cells",
number = "23",
pages = "16829",
volume = "24",
doi = "10.3390/ijms242316829"
}

Drakul, M., Tomić, S., Bekić, M., Mihajlović, D., Vasiljević, M., Rakočević, S., Đokić, J., Popović, N., Bokonjić, D.,& Čolić, M.. (2023). Sitagliptin Induces Tolerogenic Human Dendritic Cells. in International Journal of Molecular Sciences
MDPI., 24(23), 16829.
https://doi.org/10.3390/ijms242316829

Drakul M, Tomić S, Bekić M, Mihajlović D, Vasiljević M, Rakočević S, Đokić J, Popović N, Bokonjić D, Čolić M. Sitagliptin Induces Tolerogenic Human Dendritic Cells. in International Journal of Molecular Sciences. 2023;24(23):16829.
doi:10.3390/ijms242316829 .

Drakul, Marija, Tomić, Sergej, Bekić, Marina, Mihajlović, Dušan, Vasiljević, Miloš, Rakočević, Sara, Đokić, Jelena, Popović, Nikola, Bokonjić, Dejan, Čolić, Miodrag, "Sitagliptin Induces Tolerogenic Human Dendritic Cells" in International Journal of Molecular Sciences, 24, no. 23 (2023):16829,
https://doi.org/10.3390/ijms242316829 . .

TY  - JOUR
AU  - Čolić, Miodrag
AU  - Miljuš, Nataša
AU  - Đokić, Jelena
AU  - Bekić, Marina
AU  - Krivokuća, Aleksandra
AU  - Tomić, Sergej
AU  - Radojević, Dušan
AU  - Radanović, Marina
AU  - Eraković, Mile
AU  - Ismaili, Bashkim
AU  - Škrbić, Ranko
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/20/15407
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2167
AB  - Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low—10; high—40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6, MCP-1, GRO-α, RANTES, IP-10, HIF-1α, SDF-1, and HGF but increased the expression of IL-8, TLR3, TGF-β, TGF-β/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES, MMP3, and BMP2 but inhibited TLR2 and GRO-α gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4, HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs. PoPEx also potentiated most genes’ expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions
IS  - 20
SP  - 15407
VL  - 24
DO  - 10.3390/ijms242015407
ER  - 

@article{
author = "Čolić, Miodrag and Miljuš, Nataša and Đokić, Jelena and Bekić, Marina and Krivokuća, Aleksandra and Tomić, Sergej and Radojević, Dušan and Radanović, Marina and Eraković, Mile and Ismaili, Bashkim and Škrbić, Ranko",
year = "2023",
abstract = "Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low—10; high—40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6, MCP-1, GRO-α, RANTES, IP-10, HIF-1α, SDF-1, and HGF but increased the expression of IL-8, TLR3, TGF-β, TGF-β/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES, MMP3, and BMP2 but inhibited TLR2 and GRO-α gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4, HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs. PoPEx also potentiated most genes’ expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions",
number = "20",
pages = "15407",
volume = "24",
doi = "10.3390/ijms242015407"
}

Čolić, M., Miljuš, N., Đokić, J., Bekić, M., Krivokuća, A., Tomić, S., Radojević, D., Radanović, M., Eraković, M., Ismaili, B.,& Škrbić, R.. (2023). Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions. in International Journal of Molecular Sciences, 24(20), 15407.
https://doi.org/10.3390/ijms242015407

Čolić M, Miljuš N, Đokić J, Bekić M, Krivokuća A, Tomić S, Radojević D, Radanović M, Eraković M, Ismaili B, Škrbić R. Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions. in International Journal of Molecular Sciences. 2023;24(20):15407.
doi:10.3390/ijms242015407 .

Čolić, Miodrag, Miljuš, Nataša, Đokić, Jelena, Bekić, Marina, Krivokuća, Aleksandra, Tomić, Sergej, Radojević, Dušan, Radanović, Marina, Eraković, Mile, Ismaili, Bashkim, Škrbić, Ranko, "Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions" in International Journal of Molecular Sciences, 24, no. 20 (2023):15407,
https://doi.org/10.3390/ijms242015407 . .

TY  - JOUR
AU  - Čolić, Miodrag
AU  - Bekić, Marina
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Savikin, Katarina
AU  - Miljus, Nataša
AU  - Marković, Milan
AU  - Skrbić, Ranko
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1605
AB  - Pomegranate peel extract (PoPEx) has been shown to have antioxidant and anti-inflammatory properties, but its effect on the adaptive immune system has not been sufficiently investigated. In this study, the treatment of human peripheral blood mononuclear cells (PBMC) with PoPEx (range 6.25-400 mu g/mL) resulted in cytotoxicity at concentrations of 100 mu g/mL and higher, due to the induction of apoptosis and oxidative stress, whereas autophagy was reduced. At non-cytotoxic concentrations, the opposite effect on these processes was observed simultaneously with the inhibition of PHA-induced PBMC proliferation and a significant decrease in the expression of CD4. PoPEx differently modulated the expression of activation markers (CD69, CD25, ICOS) and PD1 (inhibitory marker), depending on the dose and T-cell subsets. PoPEx (starting from 12.5 mu g/mL) suppressed the production of Th1 (IFN-gamma), Th17 (IL-17A, IL-17F, and IL-22), Th9 (IL-9), and proinflammatory cytokines (TNF-alpha and IL-6) in culture supernatants. Lower concentrations upregulated Th2 (IL-5 and IL-13) and Treg (IL-10) responses as well as CD4+CD25hiFoxp3+ cell frequency. Higher concentrations of PoPEx increased the frequency of IL-10- and TGF-beta-producing T-cells (much higher in the CD4+ subset). In conclusion, our study suggested for the first time complex immunoregulatory effects of PoPEx on T cells, which could assist in the suppression of chronic inflammatory and autoimmune diseases.
PB  - MDPI, Basel
T2  - Pharmaceutics
T1  - Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture
IS  - 6
VL  - 14
DO  - 10.3390/pharmaceutics14061140
ER  - 

@article{
author = "Čolić, Miodrag and Bekić, Marina and Tomić, Sergej and Đokić, Jelena and Radojević, Dušan and Savikin, Katarina and Miljus, Nataša and Marković, Milan and Skrbić, Ranko",
year = "2022",
abstract = "Pomegranate peel extract (PoPEx) has been shown to have antioxidant and anti-inflammatory properties, but its effect on the adaptive immune system has not been sufficiently investigated. In this study, the treatment of human peripheral blood mononuclear cells (PBMC) with PoPEx (range 6.25-400 mu g/mL) resulted in cytotoxicity at concentrations of 100 mu g/mL and higher, due to the induction of apoptosis and oxidative stress, whereas autophagy was reduced. At non-cytotoxic concentrations, the opposite effect on these processes was observed simultaneously with the inhibition of PHA-induced PBMC proliferation and a significant decrease in the expression of CD4. PoPEx differently modulated the expression of activation markers (CD69, CD25, ICOS) and PD1 (inhibitory marker), depending on the dose and T-cell subsets. PoPEx (starting from 12.5 mu g/mL) suppressed the production of Th1 (IFN-gamma), Th17 (IL-17A, IL-17F, and IL-22), Th9 (IL-9), and proinflammatory cytokines (TNF-alpha and IL-6) in culture supernatants. Lower concentrations upregulated Th2 (IL-5 and IL-13) and Treg (IL-10) responses as well as CD4+CD25hiFoxp3+ cell frequency. Higher concentrations of PoPEx increased the frequency of IL-10- and TGF-beta-producing T-cells (much higher in the CD4+ subset). In conclusion, our study suggested for the first time complex immunoregulatory effects of PoPEx on T cells, which could assist in the suppression of chronic inflammatory and autoimmune diseases.",
publisher = "MDPI, Basel",
journal = "Pharmaceutics",
title = "Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture",
number = "6",
volume = "14",
doi = "10.3390/pharmaceutics14061140"
}

Čolić, M., Bekić, M., Tomić, S., Đokić, J., Radojević, D., Savikin, K., Miljus, N., Marković, M.,& Skrbić, R.. (2022). Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture. in Pharmaceutics
MDPI, Basel., 14(6).
https://doi.org/10.3390/pharmaceutics14061140

Čolić M, Bekić M, Tomić S, Đokić J, Radojević D, Savikin K, Miljus N, Marković M, Skrbić R. Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture. in Pharmaceutics. 2022;14(6).
doi:10.3390/pharmaceutics14061140 .

Čolić, Miodrag, Bekić, Marina, Tomić, Sergej, Đokić, Jelena, Radojević, Dušan, Savikin, Katarina, Miljus, Nataša, Marković, Milan, Skrbić, Ranko, "Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture" in Pharmaceutics, 14, no. 6 (2022),
https://doi.org/10.3390/pharmaceutics14061140 . .

TY  - JOUR
AU  - Bekić, Marina
AU  - Radanović, Marina
AU  - Đokić, Jelena
AU  - Tomić, Sergej
AU  - Eraković, Mile
AU  - Radojević, Dušan
AU  - Duka, Milos
AU  - Marković, Dejan
AU  - Marković, Milan
AU  - Ismaili, Bashkim
AU  - Bokonjić, Dejan
AU  - Čolić, Miodrag
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1558
AB  - Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-alpha, RANTES, TLR-2, HIF-1 alpha, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-alpha were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-beta, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis
IS  - 7
VL  - 23
DO  - 10.3390/ijms23073510
ER  - 

@article{
author = "Bekić, Marina and Radanović, Marina and Đokić, Jelena and Tomić, Sergej and Eraković, Mile and Radojević, Dušan and Duka, Milos and Marković, Dejan and Marković, Milan and Ismaili, Bashkim and Bokonjić, Dejan and Čolić, Miodrag",
year = "2022",
abstract = "Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-alpha, RANTES, TLR-2, HIF-1 alpha, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-alpha were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-beta, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis",
number = "7",
volume = "23",
doi = "10.3390/ijms23073510"
}

Bekić, M., Radanović, M., Đokić, J., Tomić, S., Eraković, M., Radojević, D., Duka, M., Marković, D., Marković, M., Ismaili, B., Bokonjić, D.,& Čolić, M.. (2022). Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis. in International Journal of Molecular Sciences
MDPI, Basel., 23(7).
https://doi.org/10.3390/ijms23073510

Bekić M, Radanović M, Đokić J, Tomić S, Eraković M, Radojević D, Duka M, Marković D, Marković M, Ismaili B, Bokonjić D, Čolić M. Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis. in International Journal of Molecular Sciences. 2022;23(7).
doi:10.3390/ijms23073510 .

Bekić, Marina, Radanović, Marina, Đokić, Jelena, Tomić, Sergej, Eraković, Mile, Radojević, Dušan, Duka, Milos, Marković, Dejan, Marković, Milan, Ismaili, Bashkim, Bokonjić, Dejan, Čolić, Miodrag, "Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis" in International Journal of Molecular Sciences, 23, no. 7 (2022),
https://doi.org/10.3390/ijms23073510 . .

TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Vasilev, Saša
AU  - Dinić, Miroslav
AU  - Golić, Nataša
AU  - Vučević, Dragana
AU  - Čolić, Miodrag
AU  - Tomić, Sergej
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1875
AB  - The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.
PB  - Novi Sad : Faculty of Sciences, Department of Biology and Ecology
C3  - Biologia Serbica
T1  - Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition
IS  - 1 (Special Edition)
SP  - 98
VL  - 43
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1875
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Gruden-Movsesijan, Alisa and Ilić, Nataša and Vasilev, Saša and Dinić, Miroslav and Golić, Nataša and Vučević, Dragana and Čolić, Miodrag and Tomić, Sergej and Đokić, Jelena",
year = "2021",
abstract = "The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.",
publisher = "Novi Sad : Faculty of Sciences, Department of Biology and Ecology",
journal = "Biologia Serbica",
title = "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition",
number = "1 (Special Edition)",
pages = "98",
volume = "43",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1875"
}

Radojević, D., Bekić, M., Gruden-Movsesijan, A., Ilić, N., Vasilev, S., Dinić, M., Golić, N., Vučević, D., Čolić, M., Tomić, S.,& Đokić, J.. (2021). Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica
Novi Sad : Faculty of Sciences, Department of Biology and Ecology., 43(1 (Special Edition)), 98.
https://hdl.handle.net/21.15107/rcub_imagine_1875

Radojević D, Bekić M, Gruden-Movsesijan A, Ilić N, Vasilev S, Dinić M, Golić N, Vučević D, Čolić M, Tomić S, Đokić J. Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica. 2021;43(1 (Special Edition)):98.
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

Radojević, Dušan, Bekić, Marina, Gruden-Movsesijan, Alisa, Ilić, Nataša, Vasilev, Saša, Dinić, Miroslav, Golić, Nataša, Vučević, Dragana, Čolić, Miodrag, Tomić, Sergej, Đokić, Jelena, "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition" in Biologia Serbica, 43, no. 1 (Special Edition) (2021):98,
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

TY  - JOUR
AU  - Radojević, Dušan
AU  - Tomić, Sergej
AU  - Mihajlović, Dusan
AU  - Tolinački, Maja
AU  - Pavlović, Bojan
AU  - Vucević, Dragana
AU  - Bojić, Svetlana
AU  - Golić, Nataša
AU  - Čolić, Miodrag
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1475
AB  - Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher alpha-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-alpha, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-alpha, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Gut Microbes
T1  - Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro
IS  - 1
VL  - 13
DO  - 10.1080/19490976.2021.1921927
ER  - 

@article{
author = "Radojević, Dušan and Tomić, Sergej and Mihajlović, Dusan and Tolinački, Maja and Pavlović, Bojan and Vucević, Dragana and Bojić, Svetlana and Golić, Nataša and Čolić, Miodrag and Đokić, Jelena",
year = "2021",
abstract = "Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher alpha-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-alpha, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-alpha, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Gut Microbes",
title = "Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro",
number = "1",
volume = "13",
doi = "10.1080/19490976.2021.1921927"
}

Radojević, D., Tomić, S., Mihajlović, D., Tolinački, M., Pavlović, B., Vucević, D., Bojić, S., Golić, N., Čolić, M.,& Đokić, J.. (2021). Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro. in Gut Microbes
Taylor & Francis Inc, Philadelphia., 13(1).
https://doi.org/10.1080/19490976.2021.1921927

Radojević D, Tomić S, Mihajlović D, Tolinački M, Pavlović B, Vucević D, Bojić S, Golić N, Čolić M, Đokić J. Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro. in Gut Microbes. 2021;13(1).
doi:10.1080/19490976.2021.1921927 .

Radojević, Dušan, Tomić, Sergej, Mihajlović, Dusan, Tolinački, Maja, Pavlović, Bojan, Vucević, Dragana, Bojić, Svetlana, Golić, Nataša, Čolić, Miodrag, Đokić, Jelena, "Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro" in Gut Microbes, 13, no. 1 (2021),
https://doi.org/10.1080/19490976.2021.1921927 . .

TY  - JOUR
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Stevanović, Dejan
AU  - Ilić, Nataša
AU  - Gruden-Movsesijan, Alisa
AU  - Dinić, Miroslav
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Mitrović, Nebojša
AU  - Tomasević, Ratko
AU  - Mikić, Dragan
AU  - Stojanović, Dragos
AU  - Čolić, Miodrag
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1446
AB  - Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed similar to 140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with similar to 30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-gamma production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients
VL  - 12
DO  - 10.3389/fimmu.2021.614599
ER  - 

@article{
author = "Tomić, Sergej and Đokić, Jelena and Stevanović, Dejan and Ilić, Nataša and Gruden-Movsesijan, Alisa and Dinić, Miroslav and Radojević, Dušan and Bekić, Marina and Mitrović, Nebojša and Tomasević, Ratko and Mikić, Dragan and Stojanović, Dragos and Čolić, Miodrag",
year = "2021",
abstract = "Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed similar to 140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with similar to 30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-gamma production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients",
volume = "12",
doi = "10.3389/fimmu.2021.614599"
}

Tomić, S., Đokić, J., Stevanović, D., Ilić, N., Gruden-Movsesijan, A., Dinić, M., Radojević, D., Bekić, M., Mitrović, N., Tomasević, R., Mikić, D., Stojanović, D.,& Čolić, M.. (2021). Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients. in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 12.
https://doi.org/10.3389/fimmu.2021.614599

Tomić S, Đokić J, Stevanović D, Ilić N, Gruden-Movsesijan A, Dinić M, Radojević D, Bekić M, Mitrović N, Tomasević R, Mikić D, Stojanović D, Čolić M. Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients. in Frontiers in Immunology. 2021;12.
doi:10.3389/fimmu.2021.614599 .

Tomić, Sergej, Đokić, Jelena, Stevanović, Dejan, Ilić, Nataša, Gruden-Movsesijan, Alisa, Dinić, Miroslav, Radojević, Dušan, Bekić, Marina, Mitrović, Nebojša, Tomasević, Ratko, Mikić, Dragan, Stojanović, Dragos, Čolić, Miodrag, "Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients" in Frontiers in Immunology, 12 (2021),
https://doi.org/10.3389/fimmu.2021.614599 . .

TY  - CONF
AU  - Radojević, Dušan
AU  - Tomić, Sergej
AU  - Mihajlović, Dusan
AU  - Tolinački, Maja
AU  - Pavlović, Bojan
AU  - Vucević, Dragana
AU  - Bojić, Svetlana
AU  - Golić, Nataša
AU  - Čolić, Miodrag
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1437
PB  - Wiley, Hoboken
C3  - European Journal of Immunology
T1  - Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition
EP  - 32
SP  - 32
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1437
ER  - 

@conference{
author = "Radojević, Dušan and Tomić, Sergej and Mihajlović, Dusan and Tolinački, Maja and Pavlović, Bojan and Vucević, Dragana and Bojić, Svetlana and Golić, Nataša and Čolić, Miodrag and Đokić, Jelena",
year = "2021",
publisher = "Wiley, Hoboken",
journal = "European Journal of Immunology",
title = "Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition",
pages = "32-32",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1437"
}

Radojević, D., Tomić, S., Mihajlović, D., Tolinački, M., Pavlović, B., Vucević, D., Bojić, S., Golić, N., Čolić, M.,& Đokić, J.. (2021). Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition. in European Journal of Immunology
Wiley, Hoboken., 51, 32-32.
https://hdl.handle.net/21.15107/rcub_imagine_1437

Radojević D, Tomić S, Mihajlović D, Tolinački M, Pavlović B, Vucević D, Bojić S, Golić N, Čolić M, Đokić J. Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition. in European Journal of Immunology. 2021;51:32-32.
https://hdl.handle.net/21.15107/rcub_imagine_1437 .

Radojević, Dušan, Tomić, Sergej, Mihajlović, Dusan, Tolinački, Maja, Pavlović, Bojan, Vucević, Dragana, Bojić, Svetlana, Golić, Nataša, Čolić, Miodrag, Đokić, Jelena, "Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition" in European Journal of Immunology, 51 (2021):32-32,
https://hdl.handle.net/21.15107/rcub_imagine_1437 .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1613
AB  - Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles
EP  - 789
SP  - 776
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
ER  - 

@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "789-776",
volume = "96",
doi = "10.1016/j.msec.2018.11.073"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C
Elsevier., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science and Engineering C, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 . .

TY  - DATA
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1615
AB  - 1. Experimental details for ICP-OES measurements; 1.1. Instrumental and operating conditions; 1.2.Solutions and Reagents; 1.3. Microwave assisted acid digestion; 1.4. Calibration curve 2. Experimental details for biocompatibility investigations of PCL/SeNPs; 2.1. Cell culture; 2.2.Determining citotoxicity of samples - MTT assay; 2.3. Determination of intracellular reactive oxygen species formation – DCFH-DA assay; 2.4. DNA damage (comet assay) Figure 1. SEM image of blank PCL microspheres Figure 2. XRD pattern of commercial PGA used in experiments Figure 3. Interaction with PCL/SeNPs in vivo by infiltrating cells. PCL/SeNPs (4mg/animal) were injected into sterile polyvinyl sponges implanted subcutaneously. The infiltrating cells were collected from the sponges after 3h and stained to anti-CD45/IgG Alexa 488 (Green) and Syto59 nuclear stain. PCL/SeNPs were detected as brightly scattering particles sized about 1-4 μm after 546nm laser excitation either intracellularly within granulocytes (A) or extracellularly (B). Note that some cells expressed strongly CD45 on the membrane and the cytoplasm, whereas others displayed a weak membrane expression and a strong expression in the granular ER at the nucleus level. Table 1. Melting temperatures Tm and corresponding enthalpies (heat) of fusion ΔHf of PCL/SeNPs samples taken after different time from different degradation mediums Table 2. Melting temperatures and corresponding enthalpies of PCL/SeNPs samples taken after different degradation periods from P. aeruginosa CFE medium
T2  - Materials Science and Engineering C
T1  - Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1615
ER  - 

@misc{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "1. Experimental details for ICP-OES measurements; 1.1. Instrumental and operating conditions; 1.2.Solutions and Reagents; 1.3. Microwave assisted acid digestion; 1.4. Calibration curve 2. Experimental details for biocompatibility investigations of PCL/SeNPs; 2.1. Cell culture; 2.2.Determining citotoxicity of samples - MTT assay; 2.3. Determination of intracellular reactive oxygen species formation – DCFH-DA assay; 2.4. DNA damage (comet assay) Figure 1. SEM image of blank PCL microspheres Figure 2. XRD pattern of commercial PGA used in experiments Figure 3. Interaction with PCL/SeNPs in vivo by infiltrating cells. PCL/SeNPs (4mg/animal) were injected into sterile polyvinyl sponges implanted subcutaneously. The infiltrating cells were collected from the sponges after 3h and stained to anti-CD45/IgG Alexa 488 (Green) and Syto59 nuclear stain. PCL/SeNPs were detected as brightly scattering particles sized about 1-4 μm after 546nm laser excitation either intracellularly within granulocytes (A) or extracellularly (B). Note that some cells expressed strongly CD45 on the membrane and the cytoplasm, whereas others displayed a weak membrane expression and a strong expression in the granular ER at the nucleus level. Table 1. Melting temperatures Tm and corresponding enthalpies (heat) of fusion ΔHf of PCL/SeNPs samples taken after different time from different degradation mediums Table 2. Melting temperatures and corresponding enthalpies of PCL/SeNPs samples taken after different degradation periods from P. aeruginosa CFE medium",
journal = "Materials Science and Engineering C",
title = "Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1615"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073. in Materials Science and Engineering C.
https://hdl.handle.net/21.15107/rcub_imagine_1615

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073. in Materials Science and Engineering C. 2019;.
https://hdl.handle.net/21.15107/rcub_imagine_1615 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073" in Materials Science and Engineering C (2019),
https://hdl.handle.net/21.15107/rcub_imagine_1615 .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1614
AB  - Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles
EP  - 789
SP  - 776
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
ER  - 

@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "789-776",
volume = "96",
doi = "10.1016/j.msec.2018.11.073"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C
Elsevier., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science and Engineering C, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 . .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Razić, Slavica
AU  - Jeremić, Sanja
AU  - Filipić, Metka
AU  - Zegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1292
AB  - Poly (e-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1-4 mu m with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants.
PB  - Elsevier, Amsterdam
T2  - Materials Science & Engineering C-Materials For Biological Applications
T1  - Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles
EP  - 789
SP  - 776
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
ER  - 

@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Razić, Slavica and Jeremić, Sanja and Filipić, Metka and Zegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (e-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1-4 mu m with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants.",
publisher = "Elsevier, Amsterdam",
journal = "Materials Science & Engineering C-Materials For Biological Applications",
title = "Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "789-776",
volume = "96",
doi = "10.1016/j.msec.2018.11.073"
}

Filipović, N., Veselinović, L., Razić, S., Jeremić, S., Filipić, M., Zegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science & Engineering C-Materials For Biological Applications
Elsevier, Amsterdam., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073

Filipović N, Veselinović L, Razić S, Jeremić S, Filipić M, Zegura B, Tomić S, Čolić M, Stevanović M. Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science & Engineering C-Materials For Biological Applications. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073 .

Filipović, Nenad, Veselinović, Ljiljana, Razić, Slavica, Jeremić, Sanja, Filipić, Metka, Zegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science & Engineering C-Materials For Biological Applications, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 . .

TY  - JOUR
AU  - Marković, M.
AU  - Tomić, S.
AU  - Đokić, Jelena
AU  - Čolić, Miodrag
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/860
AB  - The pathophysiology of periapical lesions (PLs) is under control of pro-inflammatory and anti-inflammatory (mainly immunoregulatory) cytokines. We have recently established mesenchymal stem cells (MSCs) from PLs and showed their suppressive effects on the production of proinflammatory cytokines from PLs inflammatory cells (ICs). In this work we studied the production of interleukin (IL)-10, IL-27 and transforming growth factor (TGF)-β, by PL-ICs in direct or indirect contacts with PL-MSCs. PL-ICs, which were isolated from four different asymptomatic PLs, predominantly composed of lymphocytes, followed by neutrophil granulocytes, macrophages and plasma cells. PLMSCs, expressing typical MSC markers, were co-cultivated with PL-ICs at 1:10 ratio, either in direct contact or in a transwell-system, for 24 hours. The levels of cytokines in cell-culture supernatants were tested by ELISA. The results showed that PL-MSCs up-regulated the production of all three immunoregulatory cytokines by PL-ICs. PL-MSCs stimulated the production of IL-10 and IL-27 via soluble factors, whereas the up-regulation of TGF-β required direct cell-to-cell contacts. In conclusion, our results showed for the first time the involvement of PL-MSCs in restriction of inflammation in PLs by up-regulation of immunoregulatory cytokines.
PB  - Univerzitet u Nišu - Medicinski fakultet, Niš
T2  - Acta Facultatis Medicae Naissensis
T1  - Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture
EP  - 179
IS  - 3
SP  - 171
VL  - 32
DO  - 10.1515/afmnai-2015-0017
ER  - 

@article{
author = "Marković, M. and Tomić, S. and Đokić, Jelena and Čolić, Miodrag",
year = "2015",
abstract = "The pathophysiology of periapical lesions (PLs) is under control of pro-inflammatory and anti-inflammatory (mainly immunoregulatory) cytokines. We have recently established mesenchymal stem cells (MSCs) from PLs and showed their suppressive effects on the production of proinflammatory cytokines from PLs inflammatory cells (ICs). In this work we studied the production of interleukin (IL)-10, IL-27 and transforming growth factor (TGF)-β, by PL-ICs in direct or indirect contacts with PL-MSCs. PL-ICs, which were isolated from four different asymptomatic PLs, predominantly composed of lymphocytes, followed by neutrophil granulocytes, macrophages and plasma cells. PLMSCs, expressing typical MSC markers, were co-cultivated with PL-ICs at 1:10 ratio, either in direct contact or in a transwell-system, for 24 hours. The levels of cytokines in cell-culture supernatants were tested by ELISA. The results showed that PL-MSCs up-regulated the production of all three immunoregulatory cytokines by PL-ICs. PL-MSCs stimulated the production of IL-10 and IL-27 via soluble factors, whereas the up-regulation of TGF-β required direct cell-to-cell contacts. In conclusion, our results showed for the first time the involvement of PL-MSCs in restriction of inflammation in PLs by up-regulation of immunoregulatory cytokines.",
publisher = "Univerzitet u Nišu - Medicinski fakultet, Niš",
journal = "Acta Facultatis Medicae Naissensis",
title = "Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture",
pages = "179-171",
number = "3",
volume = "32",
doi = "10.1515/afmnai-2015-0017"
}

Marković, M., Tomić, S., Đokić, J.,& Čolić, M.. (2015). Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture. in Acta Facultatis Medicae Naissensis
Univerzitet u Nišu - Medicinski fakultet, Niš., 32(3), 171-179.
https://doi.org/10.1515/afmnai-2015-0017

Marković M, Tomić S, Đokić J, Čolić M. Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture. in Acta Facultatis Medicae Naissensis. 2015;32(3):171-179.
doi:10.1515/afmnai-2015-0017 .

Marković, M., Tomić, S., Đokić, Jelena, Čolić, Miodrag, "Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture" in Acta Facultatis Medicae Naissensis, 32, no. 3 (2015):171-179,
https://doi.org/10.1515/afmnai-2015-0017 . .