TY  - JOUR
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Dinić, Miroslav
AU  - Bisenić, Aleksandar
AU  - Golić, Nataša
AU  - Vucević, Dragana
AU  - Đokić, Jelena
AU  - Tomić, Sergej
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1540
AB  - Over-activated myeloid cells and disturbance in gut microbiota composition are critical factors contributing to the pathogenesis of Multiple Sclerosis (MS). Myeloid-derived suppressor cells (MDSCs) emerged as promising regulators of chronic inflammatory diseases, including autoimmune diseases. However, it remained unclear whether MDSCs display any therapeutic potential in MS, and how this therapy modulates gut microbiota composition. Here, we assessed the potential of in vitro generated bone marrow-derived MDSCs to ameliorate experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats and investigated how their application associates with the changes in gut microbiota composition. MDSCs differentiated with prostaglandin (PG)E2 (MDSC-PGE2) and control MDSCs (differentiated without PGE2) displayed strong immunosuppressive properties in vitro, but only MDSC-PGE2 significantly ameliorated EAE symptoms. This effect correlated with a reduced infiltration of Th17 and IFN-gamma-producing NK cells, and an increased proportion of regulatory T cells in the CNS and spleen. Importantly, both MDSCs and MDSC-PGE2 prevented EAE-induced reduction of gut microbiota diversity, but only MDSC-PGE2 prevented the extensive alterations in gut microbiota composition following their early migration into Payer's patches and mesenteric lymph nodes. This phenomenon was related to the significant enrichment of gut microbial taxa with potential immunoregulatory properties, as well as higher levels of butyrate, propionate, and putrescine in feces. This study provides new insights into the host-microbiota interactions in EAE, suggesting that activated MDSCs could be potentially used as an efficient therapy for acute phases of MS. Considering a significant association between the efficacy of MDSC-PGE2 and gut microbiota composition, our findings also provide a rationale for further exploring the specific microbial metabolites in MS therapy.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Gut Microbes
T1  - Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis
IS  - 1
VL  - 14
DO  - 10.1080/19490976.2022.2127455
ER  - 

@article{
author = "Radojević, Dušan and Bekić, Marina and Gruden-Movsesijan, Alisa and Ilić, Nataša and Dinić, Miroslav and Bisenić, Aleksandar and Golić, Nataša and Vucević, Dragana and Đokić, Jelena and Tomić, Sergej",
year = "2022",
abstract = "Over-activated myeloid cells and disturbance in gut microbiota composition are critical factors contributing to the pathogenesis of Multiple Sclerosis (MS). Myeloid-derived suppressor cells (MDSCs) emerged as promising regulators of chronic inflammatory diseases, including autoimmune diseases. However, it remained unclear whether MDSCs display any therapeutic potential in MS, and how this therapy modulates gut microbiota composition. Here, we assessed the potential of in vitro generated bone marrow-derived MDSCs to ameliorate experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats and investigated how their application associates with the changes in gut microbiota composition. MDSCs differentiated with prostaglandin (PG)E2 (MDSC-PGE2) and control MDSCs (differentiated without PGE2) displayed strong immunosuppressive properties in vitro, but only MDSC-PGE2 significantly ameliorated EAE symptoms. This effect correlated with a reduced infiltration of Th17 and IFN-gamma-producing NK cells, and an increased proportion of regulatory T cells in the CNS and spleen. Importantly, both MDSCs and MDSC-PGE2 prevented EAE-induced reduction of gut microbiota diversity, but only MDSC-PGE2 prevented the extensive alterations in gut microbiota composition following their early migration into Payer's patches and mesenteric lymph nodes. This phenomenon was related to the significant enrichment of gut microbial taxa with potential immunoregulatory properties, as well as higher levels of butyrate, propionate, and putrescine in feces. This study provides new insights into the host-microbiota interactions in EAE, suggesting that activated MDSCs could be potentially used as an efficient therapy for acute phases of MS. Considering a significant association between the efficacy of MDSC-PGE2 and gut microbiota composition, our findings also provide a rationale for further exploring the specific microbial metabolites in MS therapy.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Gut Microbes",
title = "Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis",
number = "1",
volume = "14",
doi = "10.1080/19490976.2022.2127455"
}

Radojević, D., Bekić, M., Gruden-Movsesijan, A., Ilić, N., Dinić, M., Bisenić, A., Golić, N., Vucević, D., Đokić, J.,& Tomić, S.. (2022). Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis. in Gut Microbes
Taylor & Francis Inc, Philadelphia., 14(1).
https://doi.org/10.1080/19490976.2022.2127455

Radojević D, Bekić M, Gruden-Movsesijan A, Ilić N, Dinić M, Bisenić A, Golić N, Vucević D, Đokić J, Tomić S. Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis. in Gut Microbes. 2022;14(1).
doi:10.1080/19490976.2022.2127455 .

Radojević, Dušan, Bekić, Marina, Gruden-Movsesijan, Alisa, Ilić, Nataša, Dinić, Miroslav, Bisenić, Aleksandar, Golić, Nataša, Vucević, Dragana, Đokić, Jelena, Tomić, Sergej, "Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis" in Gut Microbes, 14, no. 1 (2022),
https://doi.org/10.1080/19490976.2022.2127455 . .

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  - Tertel, Tobias
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Stevanović, Dejan
AU  - Ilić, Nataša
AU  - Giebel, Bernd
AU  - Kosanović, Maja
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1517
AB  - COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13(+) and CD82(+) EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC(+) EVs than sera of the healthy donors and more CD24(+) EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.
PB  - Hoboken : Wiley
T2  - Journal of Extracellular Vesicles
T1  - Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients
IS  - 8
VL  - 11
DO  - 10.1002/jev2.12257
ER  - 

@article{
author = "Tertel, Tobias and Tomić, Sergej and Đokić, Jelena and Radojević, Dušan and Stevanović, Dejan and Ilić, Nataša and Giebel, Bernd and Kosanović, Maja",
year = "2022",
abstract = "COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13(+) and CD82(+) EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC(+) EVs than sera of the healthy donors and more CD24(+) EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.",
publisher = "Hoboken : Wiley",
journal = "Journal of Extracellular Vesicles",
title = "Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients",
number = "8",
volume = "11",
doi = "10.1002/jev2.12257"
}

Tertel, T., Tomić, S., Đokić, J., Radojević, D., Stevanović, D., Ilić, N., Giebel, B.,& Kosanović, M.. (2022). Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients. in Journal of Extracellular Vesicles
Hoboken : Wiley., 11(8).
https://doi.org/10.1002/jev2.12257

Tertel T, Tomić S, Đokić J, Radojević D, Stevanović D, Ilić N, Giebel B, Kosanović M. Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients. in Journal of Extracellular Vesicles. 2022;11(8).
doi:10.1002/jev2.12257 .

Tertel, Tobias, Tomić, Sergej, Đokić, Jelena, Radojević, Dušan, Stevanović, Dejan, Ilić, Nataša, Giebel, Bernd, Kosanović, Maja, "Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients" in Journal of Extracellular Vesicles, 11, no. 8 (2022),
https://doi.org/10.1002/jev2.12257 . .

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  - 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  - Kosanović, Maja
AU  - Tertel, Tobias
AU  - Đokić, Jelena
AU  - Ilić, Nataša
AU  - Radojević, Dušan
AU  - Stevanović, Dejan
AU  - Movsesijan, Alisa Gruden
AU  - Giebel, Bernd
AU  - Tomić, Sergej
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1434
PB  - Wiley, Hoboken
C3  - European Journal of Immunology
T1  - Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity
EP  - 352
SP  - 352
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1434
ER  - 

@conference{
author = "Kosanović, Maja and Tertel, Tobias and Đokić, Jelena and Ilić, Nataša and Radojević, Dušan and Stevanović, Dejan and Movsesijan, Alisa Gruden and Giebel, Bernd and Tomić, Sergej",
year = "2021",
publisher = "Wiley, Hoboken",
journal = "European Journal of Immunology",
title = "Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity",
pages = "352-352",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1434"
}

Kosanović, M., Tertel, T., Đokić, J., Ilić, N., Radojević, D., Stevanović, D., Movsesijan, A. G., Giebel, B.,& Tomić, S.. (2021). Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity. in European Journal of Immunology
Wiley, Hoboken., 51, 352-352.
https://hdl.handle.net/21.15107/rcub_imagine_1434

Kosanović M, Tertel T, Đokić J, Ilić N, Radojević D, Stevanović D, Movsesijan AG, Giebel B, Tomić S. Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity. in European Journal of Immunology. 2021;51:352-352.
https://hdl.handle.net/21.15107/rcub_imagine_1434 .

Kosanović, Maja, Tertel, Tobias, Đokić, Jelena, Ilić, Nataša, Radojević, Dušan, Stevanović, Dejan, Movsesijan, Alisa Gruden, Giebel, Bernd, Tomić, Sergej, "Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity" in European Journal of Immunology, 51 (2021):352-352,
https://hdl.handle.net/21.15107/rcub_imagine_1434 .

TY  - CONF
AU  - Bekić, Marina
AU  - Dinić, Miroslav
AU  - Radojević, Dušan
AU  - Ilić, Nataša
AU  - Vucević, Dragana
AU  - Vasilev, Sasa
AU  - Đokić, Jelena
AU  - Tomić, Sergej
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1436
PB  - Wiley, Hoboken
C3  - European Journal of Immunology
T1  - Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro
EP  - 179
SP  - 179
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1436
ER  - 

@conference{
author = "Bekić, Marina and Dinić, Miroslav and Radojević, Dušan and Ilić, Nataša and Vucević, Dragana and Vasilev, Sasa and Đokić, Jelena and Tomić, Sergej",
year = "2021",
publisher = "Wiley, Hoboken",
journal = "European Journal of Immunology",
title = "Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro",
pages = "179-179",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1436"
}

Bekić, M., Dinić, M., Radojević, D., Ilić, N., Vucević, D., Vasilev, S., Đokić, J.,& Tomić, S.. (2021). Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro. in European Journal of Immunology
Wiley, Hoboken., 51, 179-179.
https://hdl.handle.net/21.15107/rcub_imagine_1436

Bekić M, Dinić M, Radojević D, Ilić N, Vucević D, Vasilev S, Đokić J, Tomić S. Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro. in European Journal of Immunology. 2021;51:179-179.
https://hdl.handle.net/21.15107/rcub_imagine_1436 .

Bekić, Marina, Dinić, Miroslav, Radojević, Dušan, Ilić, Nataša, Vucević, Dragana, Vasilev, Sasa, Đokić, Jelena, Tomić, Sergej, "Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro" in European Journal of Immunology, 51 (2021):179-179,
https://hdl.handle.net/21.15107/rcub_imagine_1436 .

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  - Soković Bajić, Svetlana
AU  - Đokić, Jelena
AU  - Dinić, Miroslav
AU  - Tomić, Sergej
AU  - Popović, Nikola
AU  - Brdarić, Emilija
AU  - Golić, Nataša
AU  - Tolinački, Maja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1318
AB  - The characterization of mechanisms involved in the positive effects of probiotic bacteria in various pathophysiological conditions is a prerogative for their safe and efficient application in biomedicine. We have investigated the immunological effects of live bacteria-free supernatant collected from GABA-producing Lactobacillus brevis BGZLS10-17 on Concanavalin A-stimulated mesenteric lymph node cells (MLNC), an in vitro model of activated immune cells. We have shown that GABA containing and GABA-free supernatant of Lactobacillus brevis BGZLS10-17 have strong immunoregulatory effects on MLNC. Further, GABA produced by this strain exhibit additional inhibitory effects on proliferation, IFN-gamma and IL-17 production by MLNC, and the expression of MHCII and CD80 on antigen presenting cells. At the other hand, GABA-containing supernatants displayed the strongest stimulatory effects on the expression of immunoregulatory molecules, such as Foxp3(+), IL-10, TGF-beta, CTLA4 and SIRP-alpha. By looking for the mechanisms of actions, we found that supernatants produced by BGZLS10-17 induce autophagy in different MLNC, such as CD4(+) and CD8(+) T lymphocytes, NK and NKT cells, as well as antigen presenting cells. Further, we showed that the stimulation of Foxp3(+), IL-10 and TGF-beta expression by BGZLS10-17 produced GABA is completely mediated by the induction of ATG5 dependent autophagy, and that other molecules in the supernatants display GABA-, ATG5-, Foxp3(+)-, IL-10- and TGF-beta- independent, immunoregulatory effects.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro
SP  - 1347
VL  - 10
DO  - 10.1038/s41598-020-58177-2
ER  - 

@article{
author = "Soković Bajić, Svetlana and Đokić, Jelena and Dinić, Miroslav and Tomić, Sergej and Popović, Nikola and Brdarić, Emilija and Golić, Nataša and Tolinački, Maja",
year = "2020",
abstract = "The characterization of mechanisms involved in the positive effects of probiotic bacteria in various pathophysiological conditions is a prerogative for their safe and efficient application in biomedicine. We have investigated the immunological effects of live bacteria-free supernatant collected from GABA-producing Lactobacillus brevis BGZLS10-17 on Concanavalin A-stimulated mesenteric lymph node cells (MLNC), an in vitro model of activated immune cells. We have shown that GABA containing and GABA-free supernatant of Lactobacillus brevis BGZLS10-17 have strong immunoregulatory effects on MLNC. Further, GABA produced by this strain exhibit additional inhibitory effects on proliferation, IFN-gamma and IL-17 production by MLNC, and the expression of MHCII and CD80 on antigen presenting cells. At the other hand, GABA-containing supernatants displayed the strongest stimulatory effects on the expression of immunoregulatory molecules, such as Foxp3(+), IL-10, TGF-beta, CTLA4 and SIRP-alpha. By looking for the mechanisms of actions, we found that supernatants produced by BGZLS10-17 induce autophagy in different MLNC, such as CD4(+) and CD8(+) T lymphocytes, NK and NKT cells, as well as antigen presenting cells. Further, we showed that the stimulation of Foxp3(+), IL-10 and TGF-beta expression by BGZLS10-17 produced GABA is completely mediated by the induction of ATG5 dependent autophagy, and that other molecules in the supernatants display GABA-, ATG5-, Foxp3(+)-, IL-10- and TGF-beta- independent, immunoregulatory effects.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro",
pages = "1347",
volume = "10",
doi = "10.1038/s41598-020-58177-2"
}

Soković Bajić, S., Đokić, J., Dinić, M., Tomić, S., Popović, N., Brdarić, E., Golić, N.,& Tolinački, M.. (2020). GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro. in Scientific Reports
Nature Publishing Group, London., 10, 1347.
https://doi.org/10.1038/s41598-020-58177-2

Soković Bajić S, Đokić J, Dinić M, Tomić S, Popović N, Brdarić E, Golić N, Tolinački M. GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro. in Scientific Reports. 2020;10:1347.
doi:10.1038/s41598-020-58177-2 .

Soković Bajić, Svetlana, Đokić, Jelena, Dinić, Miroslav, Tomić, Sergej, Popović, Nikola, Brdarić, Emilija, Golić, Nataša, Tolinački, Maja, "GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro" in Scientific Reports, 10 (2020):1347,
https://doi.org/10.1038/s41598-020-58177-2 . .

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 . .