TY  - JOUR
AU  - Grigorov, Ilijana
AU  - Pejić, Snežana
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Veljković, Filip
AU  - Miletić Vukajlović, Jadranka
AU  - Bobić, Katarina
AU  - Soldatović, Ivan
AU  - Đurašević, Siniša
AU  - Jasnić, Nebojša
AU  - Stanković, Sanja
AU  - Glumac, Sofija
AU  - Mihailović-Vučinić, Violeta
AU  - Milenković, Branislava
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11550
AB  - The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.
T2  - International Journal of Molecular Sciences
T1  - Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission
VL  - 24
IS  - 17
SP  - 13164
DO  - 10.3390/ijms241713164
ER  - 

@article{
author = "Grigorov, Ilijana and Pejić, Snežana and Todorović, Ana and Drakulić, Dunja and Veljković, Filip and Miletić Vukajlović, Jadranka and Bobić, Katarina and Soldatović, Ivan and Đurašević, Siniša and Jasnić, Nebojša and Stanković, Sanja and Glumac, Sofija and Mihailović-Vučinić, Violeta and Milenković, Branislava",
year = "2023",
abstract = "The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.",
journal = "International Journal of Molecular Sciences",
title = "Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission",
volume = "24",
number = "17",
pages = "13164",
doi = "10.3390/ijms241713164"
}

Grigorov, I., Pejić, S., Todorović, A., Drakulić, D., Veljković, F., Miletić Vukajlović, J., Bobić, K., Soldatović, I., Đurašević, S., Jasnić, N., Stanković, S., Glumac, S., Mihailović-Vučinić, V.,& Milenković, B.. (2023). Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission. in International Journal of Molecular Sciences, 24(17), 13164.
https://doi.org/10.3390/ijms241713164

Grigorov I, Pejić S, Todorović A, Drakulić D, Veljković F, Miletić Vukajlović J, Bobić K, Soldatović I, Đurašević S, Jasnić N, Stanković S, Glumac S, Mihailović-Vučinić V, Milenković B. Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission. in International Journal of Molecular Sciences. 2023;24(17):13164.
doi:10.3390/ijms241713164 .

Grigorov, Ilijana, Pejić, Snežana, Todorović, Ana, Drakulić, Dunja, Veljković, Filip, Miletić Vukajlović, Jadranka, Bobić, Katarina, Soldatović, Ivan, Đurašević, Siniša, Jasnić, Nebojša, Stanković, Sanja, Glumac, Sofija, Mihailović-Vučinić, Violeta, Milenković, Branislava, "Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission" in International Journal of Molecular Sciences, 24, no. 17 (2023):13164,
https://doi.org/10.3390/ijms241713164 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Lakić, Iva
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pejić, Snežana
AU  - Todorović, Ana
AU  - Drakulić, Dunja R.
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10173
AB  - A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.
T2  - International Journal of Molecular Sciences
T1  - The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats
VL  - 23
IS  - 4
SP  - 2395
DO  - 10.3390/ijms23042395
ER  - 

@article{
author = "Đurašević, Siniša and Ružičić, Aleksandra and Lakić, Iva and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pejić, Snežana and Todorović, Ana and Drakulić, Dunja R. and Stanković, Sanja and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2022",
abstract = "A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.",
journal = "International Journal of Molecular Sciences",
title = "The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats",
volume = "23",
number = "4",
pages = "2395",
doi = "10.3390/ijms23042395"
}

Đurašević, S., Ružičić, A., Lakić, I., Tosti, T., Đurović, S., Glumac, S., Pejić, S., Todorović, A., Drakulić, D. R., Stanković, S., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2022). The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences, 23(4), 2395.
https://doi.org/10.3390/ijms23042395

Đurašević S, Ružičić A, Lakić I, Tosti T, Đurović S, Glumac S, Pejić S, Todorović A, Drakulić DR, Stanković S, Jasnić N, Đorđević J, Todorović Z. The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences. 2022;23(4):2395.
doi:10.3390/ijms23042395 .

Đurašević, Siniša, Ružičić, Aleksandra, Lakić, Iva, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pejić, Snežana, Todorović, Ana, Drakulić, Dunja R., Stanković, Sanja, Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats" in International Journal of Molecular Sciences, 23, no. 4 (2022):2395,
https://doi.org/10.3390/ijms23042395 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Pejić, Snežana
AU  - Grigorov, Ilijana
AU  - Nikolić, Gorana
AU  - Mitić-Ćulafić, Dragana
AU  - Dragićević, Milan
AU  - Đorđević, Jelena
AU  - Todorović Vukotić, Nevena
AU  - Đorđević, Neda O.
AU  - Todorović, Ana
AU  - Drakulić, Dunja R.
AU  - Veljković, Filip M.
AU  - Pajović, Snežana B.
AU  - Todorović, Zoran
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9831
AB  - Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.
T2  - Antioxidants
T1  - Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes
VL  - 10
IS  - 6
SP  - 911
DO  - 10.3390/antiox10060911
ER  - 

@article{
author = "Đurašević, Siniša and Pejić, Snežana and Grigorov, Ilijana and Nikolić, Gorana and Mitić-Ćulafić, Dragana and Dragićević, Milan and Đorđević, Jelena and Todorović Vukotić, Nevena and Đorđević, Neda O. and Todorović, Ana and Drakulić, Dunja R. and Veljković, Filip M. and Pajović, Snežana B. and Todorović, Zoran",
year = "2021",
abstract = "Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.",
journal = "Antioxidants",
title = "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes",
volume = "10",
number = "6",
pages = "911",
doi = "10.3390/antiox10060911"
}

Đurašević, S., Pejić, S., Grigorov, I., Nikolić, G., Mitić-Ćulafić, D., Dragićević, M., Đorđević, J., Todorović Vukotić, N., Đorđević, N. O., Todorović, A., Drakulić, D. R., Veljković, F. M., Pajović, S. B.,& Todorović, Z.. (2021). Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants, 10(6), 911.
https://doi.org/10.3390/antiox10060911

Đurašević S, Pejić S, Grigorov I, Nikolić G, Mitić-Ćulafić D, Dragićević M, Đorđević J, Todorović Vukotić N, Đorđević NO, Todorović A, Drakulić DR, Veljković FM, Pajović SB, Todorović Z. Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants. 2021;10(6):911.
doi:10.3390/antiox10060911 .

Đurašević, Siniša, Pejić, Snežana, Grigorov, Ilijana, Nikolić, Gorana, Mitić-Ćulafić, Dragana, Dragićević, Milan, Đorđević, Jelena, Todorović Vukotić, Nevena, Đorđević, Neda O., Todorović, Ana, Drakulić, Dunja R., Veljković, Filip M., Pajović, Snežana B., Todorović, Zoran, "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes" in Antioxidants, 10, no. 6 (2021):911,
https://doi.org/10.3390/antiox10060911 . .