TY  - JOUR
AU  - Jevtić, Ivana I.
AU  - Suručić, Relja V.
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Kostić-Rajačić, Slađana V.
AU  - Andrić, Deana
AU  - Penjišević, Jelena Z.
PY  - 2024
UR  - https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4662547
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6648
AB  - Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
T2  - Bioorganic & Medicinal Chemistry
T1  - Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
VL  - 101
DO  - 10.1016/j.bmc.2024.117649
SP  - 117649
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6648
ER  - 

@article{
author = "Jevtić, Ivana I. and Suručić, Relja V. and Tovilović-Kovačević, Gordana and Zogović, Nevena and Kostić-Rajačić, Slađana V. and Andrić, Deana and Penjišević, Jelena Z.",
year = "2024",
abstract = "Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Bioorganic & Medicinal Chemistry",
title = "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study",
volume = "101",
doi = "10.1016/j.bmc.2024.117649",
pages = "117649",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6648"
}

Jevtić, I. I., Suručić, R. V., Tovilović-Kovačević, G., Zogović, N., Kostić-Rajačić, S. V., Andrić, D.,& Penjišević, J. Z.. (2024). Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 101, 117649.
https://doi.org/10.1016/j.bmc.2024.117649
https://hdl.handle.net/21.15107/rcub_ibiss_6648

Jevtić II, Suručić RV, Tovilović-Kovačević G, Zogović N, Kostić-Rajačić SV, Andrić D, Penjišević JZ. Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry. 2024;101:117649.
doi:10.1016/j.bmc.2024.117649
https://hdl.handle.net/21.15107/rcub_ibiss_6648 .

Jevtić, Ivana I., Suručić, Relja V., Tovilović-Kovačević, Gordana, Zogović, Nevena, Kostić-Rajačić, Slađana V., Andrić, Deana, Penjišević, Jelena Z., "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study" in Bioorganic & Medicinal Chemistry, 101 (2024):117649,
https://doi.org/10.1016/j.bmc.2024.117649 .,
https://hdl.handle.net/21.15107/rcub_ibiss_6648 .

TY  - JOUR
AU  - Jevtić, Ivana I.
AU  - Suručić, Relja V.
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Kostić-Rajačić, Slađana V.
AU  - Andrić, Deana
AU  - Penjišević, Jelena Z.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6629
UR  - https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4662547
AB  - Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.
PB  - Amsterdam: Elsevier Ltd
T2  - Bioorganic & Medicinal Chemistry
T1  - Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
VL  - 101
DO  - 10.1016/j.bmc.2024.117649
SP  - 117649
ER  - 

@article{
author = "Jevtić, Ivana I. and Suručić, Relja V. and Tovilović-Kovačević, Gordana and Zogović, Nevena and Kostić-Rajačić, Slađana V. and Andrić, Deana and Penjišević, Jelena Z.",
year = "2024",
abstract = "Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.",
publisher = "Amsterdam: Elsevier Ltd",
journal = "Bioorganic & Medicinal Chemistry",
title = "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study",
volume = "101",
doi = "10.1016/j.bmc.2024.117649",
pages = "117649"
}

Jevtić, I. I., Suručić, R. V., Tovilović-Kovačević, G., Zogović, N., Kostić-Rajačić, S. V., Andrić, D.,& Penjišević, J. Z.. (2024). Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry
Amsterdam: Elsevier Ltd., 101, 117649.
https://doi.org/10.1016/j.bmc.2024.117649

Jevtić II, Suručić RV, Tovilović-Kovačević G, Zogović N, Kostić-Rajačić SV, Andrić D, Penjišević JZ. Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry. 2024;101:117649.
doi:10.1016/j.bmc.2024.117649 .

Jevtić, Ivana I., Suručić, Relja V., Tovilović-Kovačević, Gordana, Zogović, Nevena, Kostić-Rajačić, Slađana V., Andrić, Deana, Penjišević, Jelena Z., "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study" in Bioorganic & Medicinal Chemistry, 101 (2024):117649,
https://doi.org/10.1016/j.bmc.2024.117649 . .

TY  - JOUR
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6302
AB  - Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.
PB  - Basel: MDPI
T2  - Biomedicines
T1  - Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells
IS  - 10
VL  - 11
DO  - 10.3390/biomedicines11102652
SP  - 2652
ER  - 

@article{
author = "Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Tovilović-Kovačević, Gordana",
year = "2023",
abstract = "Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.",
publisher = "Basel: MDPI",
journal = "Biomedicines",
title = "Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells",
number = "10",
volume = "11",
doi = "10.3390/biomedicines11102652",
pages = "2652"
}

Despotović, A., Janjetović, K., Zogović, N.,& Tovilović-Kovačević, G.. (2023). Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells. in Biomedicines
Basel: MDPI., 11(10), 2652.
https://doi.org/10.3390/biomedicines11102652

Despotović A, Janjetović K, Zogović N, Tovilović-Kovačević G. Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells. in Biomedicines. 2023;11(10):2652.
doi:10.3390/biomedicines11102652 .

Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Tovilović-Kovačević, Gordana, "Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells" in Biomedicines, 11, no. 10 (2023):2652,
https://doi.org/10.3390/biomedicines11102652 . .

TY  - JOUR
AU  - Božinović, Nevena
AU  - Savva, Kyriaki
AU  - Rajić, Vladimir
AU  - Popović, Maja
AU  - Tošić, Dragana
AU  - Janjetović, Kristina
AU  - Despotović, Ana
AU  - Zogović, Nevena
AU  - Stratakis, Emmanuel
AU  - Petrović, Suzana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6271
AB  - The creation of novel biocompatible Ti-based thin films with a Zr or Cu sub-layer modified by ultrafast laser processing is studied. To prepare bioactive surfaces, ultrafast laser processing is focused on the formation of laser-induced periodic surface structures (LIPSS) with the production of oxide phases at the surfaces. Two differently designed multilayer thin films Ti/Cu/Ti and Ti/Zr/Ti were deposited on the silicon using the ion sputtering method. The Ti thin film contains Cu or Zr sub-layer (thickness of 10 nm) at the 10 nm below the surface. The composition and surface morphology variations for these systems, deposited and laser-processed under the same experimental conditions, were caused only by different thermo-physical properties of the sub-layer (Cu or Zr). The surface morphology in the form of LIPSS, led to improved cell adhesion and stable cells/thin films interface compared to as-deposited samples. Field-emission scanning electron microscopy and MTT analysis revealed that laser processing of both systems increased cell adhesion, proliferation, and metabolical activity of L929 mouse fibroblast cells compared to non-modified flat surfaces. Overall, the biocompatibility of Zr-containing thin films is better than Ti/Cu/Ti system. Further, laser processing and formation of LIPSS makes Ti/Zr/Ti thin films excellent candidate for biomedical.
PB  - Amsterdam: Elsevier
T2  - Materials Chemistry and Physics
T1  - Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films
VL  - 308
DO  - 10.1016/j.matchemphys.2023.128286
SP  - 128286
ER  - 

@article{
author = "Božinović, Nevena and Savva, Kyriaki and Rajić, Vladimir and Popović, Maja and Tošić, Dragana and Janjetović, Kristina and Despotović, Ana and Zogović, Nevena and Stratakis, Emmanuel and Petrović, Suzana",
year = "2023",
abstract = "The creation of novel biocompatible Ti-based thin films with a Zr or Cu sub-layer modified by ultrafast laser processing is studied. To prepare bioactive surfaces, ultrafast laser processing is focused on the formation of laser-induced periodic surface structures (LIPSS) with the production of oxide phases at the surfaces. Two differently designed multilayer thin films Ti/Cu/Ti and Ti/Zr/Ti were deposited on the silicon using the ion sputtering method. The Ti thin film contains Cu or Zr sub-layer (thickness of 10 nm) at the 10 nm below the surface. The composition and surface morphology variations for these systems, deposited and laser-processed under the same experimental conditions, were caused only by different thermo-physical properties of the sub-layer (Cu or Zr). The surface morphology in the form of LIPSS, led to improved cell adhesion and stable cells/thin films interface compared to as-deposited samples. Field-emission scanning electron microscopy and MTT analysis revealed that laser processing of both systems increased cell adhesion, proliferation, and metabolical activity of L929 mouse fibroblast cells compared to non-modified flat surfaces. Overall, the biocompatibility of Zr-containing thin films is better than Ti/Cu/Ti system. Further, laser processing and formation of LIPSS makes Ti/Zr/Ti thin films excellent candidate for biomedical.",
publisher = "Amsterdam: Elsevier",
journal = "Materials Chemistry and Physics",
title = "Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films",
volume = "308",
doi = "10.1016/j.matchemphys.2023.128286",
pages = "128286"
}

Božinović, N., Savva, K., Rajić, V., Popović, M., Tošić, D., Janjetović, K., Despotović, A., Zogović, N., Stratakis, E.,& Petrović, S.. (2023). Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films. in Materials Chemistry and Physics
Amsterdam: Elsevier., 308, 128286.
https://doi.org/10.1016/j.matchemphys.2023.128286

Božinović N, Savva K, Rajić V, Popović M, Tošić D, Janjetović K, Despotović A, Zogović N, Stratakis E, Petrović S. Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films. in Materials Chemistry and Physics. 2023;308:128286.
doi:10.1016/j.matchemphys.2023.128286 .

Božinović, Nevena, Savva, Kyriaki, Rajić, Vladimir, Popović, Maja, Tošić, Dragana, Janjetović, Kristina, Despotović, Ana, Zogović, Nevena, Stratakis, Emmanuel, Petrović, Suzana, "Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films" in Materials Chemistry and Physics, 308 (2023):128286,
https://doi.org/10.1016/j.matchemphys.2023.128286 . .

TY  - CONF
AU  - Ristić, Biljana
AU  - Krunić, Matija
AU  - Paunović, Verica
AU  - Bošnjak, Mihajlo
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Mirčić, Aleksandar
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://indico.bio.bg.ac.rs/event/4/attachments/6/492/Abstract%20Book-CoMBoS2-TMB.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6284
AB  - Introduction: We examined the molecular mechanisms of graphene quantum dot (GQD)- mediated
protection of SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).
Methods: GQD was produced by electrochemical oxidation of graphite and characterized by AFM, UVVIS and FTIR spectroscopy. The antioxidant activity of GQD in cell-free conditions was assessed by DPPH,
NBT and EPR analysis. The neuroprotective potential of GQD was determined by cell viability assays MTT,
CV. Flow cytometry was used to assess markers of apoptosis and GQD scavenging of intracellular
ROS/RNS as well. Cellular internalization of GQD was determined using TEM.
Results: GQD prevented SNP-induced apoptosis, caspase activation and mitochondrial depolarization
in neuroblastoma cells. Although GQD diminished the NO levelsin SNP-treated cells, NO scavengers displayed only a slight protection. GQD significantly protected SH-SY5Y cells from neurotoxicity of lightexhausted SNP, incapable of producing NO, implying that protective mechanism is independent of
NO-scavenging. GQD reduced SNP-triggered increase in intracellular levels of ROS, particularly •OH, O2•−
in cells and cell-free condition. Nonselective antioxidants, •OH scavengers and iron chelators, mimicked
GQD cytoprotection, indicating that GQD protect cells by neutralizing •OH generated in the Fenton reaction. Cellular GQD internalization wasrequired for optimal protection since the removal of extracellular GQD by extensive washing partly diminished their protective effect, suggesting that GQD exerted
neuroprotective effect intra- and extracellularly.
Conclusion: By demonstrating that GQD protect neuroblastoma cells from SNP-induced apoptosis by
•OH/NO scavenging, our results suggest that GQD could be valuable candidates for treatment of neurodegenerative diseases associated with oxidative/nitrosative stress.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death
SP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6284
ER  - 

@conference{
author = "Ristić, Biljana and Krunić, Matija and Paunović, Verica and Bošnjak, Mihajlo and Tovilović-Kovačević, Gordana and Zogović, Nevena and Mirčić, Aleksandar and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: We examined the molecular mechanisms of graphene quantum dot (GQD)- mediated
protection of SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).
Methods: GQD was produced by electrochemical oxidation of graphite and characterized by AFM, UVVIS and FTIR spectroscopy. The antioxidant activity of GQD in cell-free conditions was assessed by DPPH,
NBT and EPR analysis. The neuroprotective potential of GQD was determined by cell viability assays MTT,
CV. Flow cytometry was used to assess markers of apoptosis and GQD scavenging of intracellular
ROS/RNS as well. Cellular internalization of GQD was determined using TEM.
Results: GQD prevented SNP-induced apoptosis, caspase activation and mitochondrial depolarization
in neuroblastoma cells. Although GQD diminished the NO levelsin SNP-treated cells, NO scavengers displayed only a slight protection. GQD significantly protected SH-SY5Y cells from neurotoxicity of lightexhausted SNP, incapable of producing NO, implying that protective mechanism is independent of
NO-scavenging. GQD reduced SNP-triggered increase in intracellular levels of ROS, particularly •OH, O2•−
in cells and cell-free condition. Nonselective antioxidants, •OH scavengers and iron chelators, mimicked
GQD cytoprotection, indicating that GQD protect cells by neutralizing •OH generated in the Fenton reaction. Cellular GQD internalization wasrequired for optimal protection since the removal of extracellular GQD by extensive washing partly diminished their protective effect, suggesting that GQD exerted
neuroprotective effect intra- and extracellularly.
Conclusion: By demonstrating that GQD protect neuroblastoma cells from SNP-induced apoptosis by
•OH/NO scavenging, our results suggest that GQD could be valuable candidates for treatment of neurodegenerative diseases associated with oxidative/nitrosative stress.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death",
pages = "27",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6284"
}

Ristić, B., Krunić, M., Paunović, V., Bošnjak, M., Tovilović-Kovačević, G., Zogović, N., Mirčić, A., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2023). Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 27.
https://hdl.handle.net/21.15107/rcub_ibiss_6284

Ristić B, Krunić M, Paunović V, Bošnjak M, Tovilović-Kovačević G, Zogović N, Mirčić A, Vuković I, Harhaji-Trajković L, Trajković V. Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:27.
https://hdl.handle.net/21.15107/rcub_ibiss_6284 .

Ristić, Biljana, Krunić, Matija, Paunović, Verica, Bošnjak, Mihajlo, Tovilović-Kovačević, Gordana, Zogović, Nevena, Mirčić, Aleksandar, Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):27,
https://hdl.handle.net/21.15107/rcub_ibiss_6284 .

TY  - CONF
AU  - Zeković, Janko
AU  - Vidičević Novaković, Sašenka
AU  - Tasić, Jelena
AU  - Stanojević, Željka
AU  - Milovanović, Andona
AU  - Tomonjić, Nina
AU  - Petričević, Saša
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Trajković, Vladimir
AU  - Isaković, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5839
AB  - Introduction: Cuprizone is a copper chelating agent rensposible for toxic
demyelination. Although its mechanism of demyelination is not fully elucidated, its
toxicity is thought to result, at least partially, from induced autophagy.
The Aim: To examine the effect of cuprizone on autophagy markers in different
neural structures in rats with the assessment of behavior in the open field test.
Material and Methods: This study was performed on 16 female DA rats, 6 weeks
old.The control group (n=8) did not receive cuprizone, while the experimental group
(n=8) received food with 0.6% cuprizone content during 7 weeks. Afterwards,
locomotion and anxiety-like behavior were assessed in the open field test. Imunoblot
technique was performed on: cortex, corpus callosum, cerebellum and spinal cord, in
order to examine the markers of autophagy signaling pathway: pUlk, p62, Beclin1,
LC3II, pAMPK, pmTOR and pRaptor.
Results: Cuprizone-fed animals had a reduced locomotor activity and exhibited an
anxiety-like behavior. In the cortex, p62 and pAMPK were decreased, while pmTOR
tended to be lower. In the corpus callosum, pULK was increased and pmTOR was
decreased. LC3II tended to be increased, while pAMPK tended to be decreased. In the
cerebellum, pAMPK was reduced, while pmTOR was increased. In the spinal cord,
Beclin1 and pRaptor were decreased, while pmTOR, pAMPK, LC3II, p62 tended to
be decreased.
Conclusion: Long-term use of cuprizone leads to impaired locomotor activity and

anxiety-like behavior. Cuprizone-induced damage is most likely due to AMPK-
independent autophagy in the cortex and corpus callosum, while autophagy is

probably inhibited in the cerebellum and spinal cord.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats
SP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5839
ER  - 

@conference{
author = "Zeković, Janko and Vidičević Novaković, Sašenka and Tasić, Jelena and Stanojević, Željka and Milovanović, Andona and Tomonjić, Nina and Petričević, Saša and Zogović, Nevena and Tovilović-Kovačević, Gordana and Trajković, Vladimir and Isaković, Aleksandra",
year = "2023",
abstract = "Introduction: Cuprizone is a copper chelating agent rensposible for toxic
demyelination. Although its mechanism of demyelination is not fully elucidated, its
toxicity is thought to result, at least partially, from induced autophagy.
The Aim: To examine the effect of cuprizone on autophagy markers in different
neural structures in rats with the assessment of behavior in the open field test.
Material and Methods: This study was performed on 16 female DA rats, 6 weeks
old.The control group (n=8) did not receive cuprizone, while the experimental group
(n=8) received food with 0.6% cuprizone content during 7 weeks. Afterwards,
locomotion and anxiety-like behavior were assessed in the open field test. Imunoblot
technique was performed on: cortex, corpus callosum, cerebellum and spinal cord, in
order to examine the markers of autophagy signaling pathway: pUlk, p62, Beclin1,
LC3II, pAMPK, pmTOR and pRaptor.
Results: Cuprizone-fed animals had a reduced locomotor activity and exhibited an
anxiety-like behavior. In the cortex, p62 and pAMPK were decreased, while pmTOR
tended to be lower. In the corpus callosum, pULK was increased and pmTOR was
decreased. LC3II tended to be increased, while pAMPK tended to be decreased. In the
cerebellum, pAMPK was reduced, while pmTOR was increased. In the spinal cord,
Beclin1 and pRaptor were decreased, while pmTOR, pAMPK, LC3II, p62 tended to
be decreased.
Conclusion: Long-term use of cuprizone leads to impaired locomotor activity and

anxiety-like behavior. Cuprizone-induced damage is most likely due to AMPK-
independent autophagy in the cortex and corpus callosum, while autophagy is

probably inhibited in the cerebellum and spinal cord.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5839"
}

Zeković, J., Vidičević Novaković, S., Tasić, J., Stanojević, Ž., Milovanović, A., Tomonjić, N., Petričević, S., Zogović, N., Tovilović-Kovačević, G., Trajković, V.,& Isaković, A.. (2023). Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 80.
https://hdl.handle.net/21.15107/rcub_ibiss_5839

Zeković J, Vidičević Novaković S, Tasić J, Stanojević Ž, Milovanović A, Tomonjić N, Petričević S, Zogović N, Tovilović-Kovačević G, Trajković V, Isaković A. Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:80.
https://hdl.handle.net/21.15107/rcub_ibiss_5839 .

Zeković, Janko, Vidičević Novaković, Sašenka, Tasić, Jelena, Stanojević, Željka, Milovanović, Andona, Tomonjić, Nina, Petričević, Saša, Zogović, Nevena, Tovilović-Kovačević, Gordana, Trajković, Vladimir, Isaković, Aleksandra, "Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):80,
https://hdl.handle.net/21.15107/rcub_ibiss_5839 .

TY  - CONF
AU  - Tovilović-Kovačević, Gordana
AU  - Krstić-Milošević, Dijana
AU  - Vinterhalter, Branka
AU  - Toljić, Mina
AU  - Perović, Vladimir
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
AU  - Zogović, Nevena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5317
AB  - Глиобластом je најчешћи и најагресивнији тип тумора централног нервног система код одраслих. Циљ ове студије је био да се процени антиглиомски потенцијал екстраката коренова Gentiana dinarica у култури U251 ћелија хуманог глиобластома. Метанолни екстракти су добијени из нетрансформисаних коренова G. dinarica (екстракт 1, Е1) и трансгених коренова добијених коришћењем два соја Agrobacterium rhizogenes: A4M70GUS (екстракт 2, Е2) и 15834/PI (екстракт 3, Е3). Трансформацијом коренова са A. rhizogenes стимулисана је продукција ксантона, секундарних метаболита са доказаним антиканцерским ефектом. За разлику од Е1 и Е2, Е3 је снажно инхибирао раст U251 ћелија, изазвао застој ћелијског циклуса у G2/M фази и повећао експресију маркера диференцијације – астроцитног глијалног фибриларног киселог протеина (GFAP) и неуронског β-тубулина. Е3 је стимулисао Akt/mTOR-зависну аутофагију, на шта је указивало повећање нивоа аутофагног маркера LC3-II протеина и појачана деградација селективне аутофагне мете протеина p62. Инхибиција аутофагије је спречила експресију маркера диференцијације, без утицаја на застој у ћелијском циклусу. Е3 је повећао и нивое оксидативног стреса у ћелији, а антиоксиданси N-ацетил цистеин (NAC) и витамин Е су инхибирали и аутофагију и диференцијацију U251 ћелија изазвану Е3. Активна компонента Е3 је највероватније ксантонски агликон норсверцијанин, најзаступљеније једињење у Е3. Норсверцијанин је, као и Е3, зауставио пролиферацију U251 ћелија у G2/M фази ћелијског циклуса и изазвао диференцијацију, аутофагију и оксидативни стрес. Резултати ове студије указују да би Е3 и норсверцијанин могли бити кандидати за диференцијациону терапију глиобластома.
AB  - Glioblastom je najčešći i najagresivniji tip tumora centralnog nervnog sistema kod odraslih. Cilj ove studije je bio da se proceni antigliomski potencijal ekstrakata korenova Gentiana dinarica u kulturi U251 ćelija humanog glioblastoma. Metanolni ekstrakti su dobijeni iz netransformisanih korenova G. dinarica (ekstrakt 1, E1) i transgenih korenova dobijenih korišćenjem dva soja Agrobacterium rhizogenes: A4M70GUS (ekstrakt 2, E2) i 15834/PI (ekstrakt 3, E3). Transformacijom korenova sa A. rhizogenes stimulisana je produkcija ksantona, sekundarnih metabolita sa dokazanim antikancerskim efektom. Za razliku od E1 i E2, E3 je snažno inhibirao rast U251 ćelija, izazvao zastoj ćelijskog ciklusa u G2/M fazi i povećao ekspresiju markera diferencijacije – astrocitnog glijalnog fibrilarnog kiselog proteina (GFAP) i neuronskog β-tubulina. E3 je stimulisao Akt/mTOR-zavisnu autofagiju, na šta je ukazivalo povećanje nivoa autofagnog markera LC3-II proteina i pojačana degradacija selektivne autofagne mete proteina p62. Inhibicija autofagije je sprečila ekspresiju markera diferencijacije, bez uticaja na zastoj u ćelijskom ciklusu. E3 je povećao i nivoe oksidativnog stresa u ćeliji, a antioksidansi N-acetil cistein (NAC) i vitamin E su inhibirali i autofagiju i diferencijaciju U251 ćelija izazvanu E3. Aktivna komponenta E3 je najverovatnije ksantonski aglikon norsvercijanin, najzastupljenije jedinjenje u E3. Norsvercijanin je, kao i E3, zaustavio proliferaciju U251 ćelija u G2/M fazi ćelijskog ciklusa i izazvao diferencijaciju, autofagiju i oksidativni stres. Rezultati ove studije ukazuju da bi E3 i norsvercijanin mogli biti kandidati za diferencijacionu terapiju glioblastoma.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima
T1  - Антиглиомски ефекат екстракта корена Gentiana dinarica Beck. обогаћеног ксантонима
SP  - 280
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5317
ER  - 

@conference{
author = "Tovilović-Kovačević, Gordana and Krstić-Milošević, Dijana and Vinterhalter, Branka and Toljić, Mina and Perović, Vladimir and Trajković, Vladimir and Harhaji-Trajković, Ljubica and Zogović, Nevena",
year = "2022",
abstract = "Глиобластом je најчешћи и најагресивнији тип тумора централног нервног система код одраслих. Циљ ове студије је био да се процени антиглиомски потенцијал екстраката коренова Gentiana dinarica у култури U251 ћелија хуманог глиобластома. Метанолни екстракти су добијени из нетрансформисаних коренова G. dinarica (екстракт 1, Е1) и трансгених коренова добијених коришћењем два соја Agrobacterium rhizogenes: A4M70GUS (екстракт 2, Е2) и 15834/PI (екстракт 3, Е3). Трансформацијом коренова са A. rhizogenes стимулисана је продукција ксантона, секундарних метаболита са доказаним антиканцерским ефектом. За разлику од Е1 и Е2, Е3 је снажно инхибирао раст U251 ћелија, изазвао застој ћелијског циклуса у G2/M фази и повећао експресију маркера диференцијације – астроцитног глијалног фибриларног киселог протеина (GFAP) и неуронског β-тубулина. Е3 је стимулисао Akt/mTOR-зависну аутофагију, на шта је указивало повећање нивоа аутофагног маркера LC3-II протеина и појачана деградација селективне аутофагне мете протеина p62. Инхибиција аутофагије је спречила експресију маркера диференцијације, без утицаја на застој у ћелијском циклусу. Е3 је повећао и нивое оксидативног стреса у ћелији, а антиоксиданси N-ацетил цистеин (NAC) и витамин Е су инхибирали и аутофагију и диференцијацију U251 ћелија изазвану Е3. Активна компонента Е3 је највероватније ксантонски агликон норсверцијанин, најзаступљеније једињење у Е3. Норсверцијанин је, као и Е3, зауставио пролиферацију U251 ћелија у G2/M фази ћелијског циклуса и изазвао диференцијацију, аутофагију и оксидативни стрес. Резултати ове студије указују да би Е3 и норсверцијанин могли бити кандидати за диференцијациону терапију глиобластома., Glioblastom je najčešći i najagresivniji tip tumora centralnog nervnog sistema kod odraslih. Cilj ove studije je bio da se proceni antigliomski potencijal ekstrakata korenova Gentiana dinarica u kulturi U251 ćelija humanog glioblastoma. Metanolni ekstrakti su dobijeni iz netransformisanih korenova G. dinarica (ekstrakt 1, E1) i transgenih korenova dobijenih korišćenjem dva soja Agrobacterium rhizogenes: A4M70GUS (ekstrakt 2, E2) i 15834/PI (ekstrakt 3, E3). Transformacijom korenova sa A. rhizogenes stimulisana je produkcija ksantona, sekundarnih metabolita sa dokazanim antikancerskim efektom. Za razliku od E1 i E2, E3 je snažno inhibirao rast U251 ćelija, izazvao zastoj ćelijskog ciklusa u G2/M fazi i povećao ekspresiju markera diferencijacije – astrocitnog glijalnog fibrilarnog kiselog proteina (GFAP) i neuronskog β-tubulina. E3 je stimulisao Akt/mTOR-zavisnu autofagiju, na šta je ukazivalo povećanje nivoa autofagnog markera LC3-II proteina i pojačana degradacija selektivne autofagne mete proteina p62. Inhibicija autofagije je sprečila ekspresiju markera diferencijacije, bez uticaja na zastoj u ćelijskom ciklusu. E3 je povećao i nivoe oksidativnog stresa u ćeliji, a antioksidansi N-acetil cistein (NAC) i vitamin E su inhibirali i autofagiju i diferencijaciju U251 ćelija izazvanu E3. Aktivna komponenta E3 je najverovatnije ksantonski aglikon norsvercijanin, najzastupljenije jedinjenje u E3. Norsvercijanin je, kao i E3, zaustavio proliferaciju U251 ćelija u G2/M fazi ćelijskog ciklusa i izazvao diferencijaciju, autofagiju i oksidativni stres. Rezultati ove studije ukazuju da bi E3 i norsvercijanin mogli biti kandidati za diferencijacionu terapiju glioblastoma.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima, Антиглиомски ефекат екстракта корена Gentiana dinarica Beck. обогаћеног ксантонима",
pages = "280",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5317"
}

Tovilović-Kovačević, G., Krstić-Milošević, D., Vinterhalter, B., Toljić, M., Perović, V., Trajković, V., Harhaji-Trajković, L.,& Zogović, N.. (2022). Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 280.
https://hdl.handle.net/21.15107/rcub_ibiss_5317

Tovilović-Kovačević G, Krstić-Milošević D, Vinterhalter B, Toljić M, Perović V, Trajković V, Harhaji-Trajković L, Zogović N. Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:280.
https://hdl.handle.net/21.15107/rcub_ibiss_5317 .

Tovilović-Kovačević, Gordana, Krstić-Milošević, Dijana, Vinterhalter, Branka, Toljić, Mina, Perović, Vladimir, Trajković, Vladimir, Harhaji-Trajković, Ljubica, Zogović, Nevena, "Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):280,
https://hdl.handle.net/21.15107/rcub_ibiss_5317 .

TY  - JOUR
AU  - Despotović, Ana
AU  - Mirčić, Aleksandar
AU  - Misirlić-Denčić, Sonja
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
PY  - 2022
UR  - https://www.hindawi.com/journals/omcl/2022/2998132/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5078
AB  - We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well-known reactive oxidative species- (ROS-) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis-like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome-associated LC3-II protein, degradation of p62, and increased expression of beclin-1. While both MD and AA+MD increased phosphorylation of AMP-activated protein kinase (AMPK), the well-known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51-like kinase 1 (ULK1), and increased the expression of several autophagy-related genes. Antioxidant N-acetyl cysteine reduced both MD- and AA+MD-induced autophagy, as well as changes in AMPK/mTORC1/ULK1 activity and cell death triggered by the drug combination. Pharmacological and genetic autophagy silencing abolished the toxicity of AA+MD, while autophagy upregulation enhanced the toxicity of both AA+MD and MD. Therefore, by upregulating oxidative stress, inhibiting mTORC1, and activating ULK1, AA converts MD-induced AMPK-dependent autophagy from nontoxic to cytotoxic. These results suggest that AA+MD or MD treatment in combination with autophagy inducers could be further investigated as a novel approach for glioblastoma therapy.
PB  - London: Hindawi Ltd.
T2  - Oxidative Medicine and Cellular Longevity
T1  - Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells
VL  - 2022
DO  - 10.1155/2022/2998132
SP  - 2998132
ER  - 

@article{
author = "Despotović, Ana and Mirčić, Aleksandar and Misirlić-Denčić, Sonja and Harhaji-Trajković, Ljubica and Trajković, Vladimir and Zogović, Nevena and Tovilović-Kovačević, Gordana",
year = "2022",
abstract = "We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well-known reactive oxidative species- (ROS-) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis-like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome-associated LC3-II protein, degradation of p62, and increased expression of beclin-1. While both MD and AA+MD increased phosphorylation of AMP-activated protein kinase (AMPK), the well-known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51-like kinase 1 (ULK1), and increased the expression of several autophagy-related genes. Antioxidant N-acetyl cysteine reduced both MD- and AA+MD-induced autophagy, as well as changes in AMPK/mTORC1/ULK1 activity and cell death triggered by the drug combination. Pharmacological and genetic autophagy silencing abolished the toxicity of AA+MD, while autophagy upregulation enhanced the toxicity of both AA+MD and MD. Therefore, by upregulating oxidative stress, inhibiting mTORC1, and activating ULK1, AA converts MD-induced AMPK-dependent autophagy from nontoxic to cytotoxic. These results suggest that AA+MD or MD treatment in combination with autophagy inducers could be further investigated as a novel approach for glioblastoma therapy.",
publisher = "London: Hindawi Ltd.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells",
volume = "2022",
doi = "10.1155/2022/2998132",
pages = "2998132"
}

Despotović, A., Mirčić, A., Misirlić-Denčić, S., Harhaji-Trajković, L., Trajković, V., Zogović, N.,& Tovilović-Kovačević, G.. (2022). Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells. in Oxidative Medicine and Cellular Longevity
London: Hindawi Ltd.., 2022, 2998132.
https://doi.org/10.1155/2022/2998132

Despotović A, Mirčić A, Misirlić-Denčić S, Harhaji-Trajković L, Trajković V, Zogović N, Tovilović-Kovačević G. Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells. in Oxidative Medicine and Cellular Longevity. 2022;2022:2998132.
doi:10.1155/2022/2998132 .

Despotović, Ana, Mirčić, Aleksandar, Misirlić-Denčić, Sonja, Harhaji-Trajković, Ljubica, Trajković, Vladimir, Zogović, Nevena, Tovilović-Kovačević, Gordana, "Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells" in Oxidative Medicine and Cellular Longevity, 2022 (2022):2998132,
https://doi.org/10.1155/2022/2998132 . .

TY  - CONF
AU  - Dožić, Aleksandra
AU  - Ćetković, Dejan
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Antonijević, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5739
AB  - The aim of this study was to investigate the properties of experimental calcium aluminate (CA) dental cement, synthesized from CaO×Al2O3 and CaCO3. Calcium silicate (Portland cement, PC) served as a control. The elastic modulus and maximum stress obtained using the universal testing machine showed that CA has greater mechanical resistance than the control PC. Scanning electron microscopy (SEM) analysis of cements specimens before and after soaking in phosphate buffer saline showed that hydrated cements exposed crystal particles of calcite and new aluminum containing phases on their surfaces, suggesting their bioactive potential. Biocompatibility of the CA dental cement was evaluated by observing L929 cells morphology using phase-contrast microscopy. Cells treated with CA extract preserved their structural integrity without any changes in cell morphology, but with a slightly inhibited proliferation rate after 24h treatment, while PC induced changes typical for cell death.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
T1  - Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement
SP  - 327
EP  - 330
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5739
ER  - 

@conference{
author = "Dožić, Aleksandra and Ćetković, Dejan and Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Antonijević, Đorđe",
year = "2022",
abstract = "The aim of this study was to investigate the properties of experimental calcium aluminate (CA) dental cement, synthesized from CaO×Al2O3 and CaCO3. Calcium silicate (Portland cement, PC) served as a control. The elastic modulus and maximum stress obtained using the universal testing machine showed that CA has greater mechanical resistance than the control PC. Scanning electron microscopy (SEM) analysis of cements specimens before and after soaking in phosphate buffer saline showed that hydrated cements exposed crystal particles of calcite and new aluminum containing phases on their surfaces, suggesting their bioactive potential. Biocompatibility of the CA dental cement was evaluated by observing L929 cells morphology using phase-contrast microscopy. Cells treated with CA extract preserved their structural integrity without any changes in cell morphology, but with a slightly inhibited proliferation rate after 24h treatment, while PC induced changes typical for cell death.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia",
title = "Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement",
pages = "327-330",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5739"
}

Dožić, A., Ćetković, D., Despotović, A., Janjetović, K., Zogović, N.,& Antonijević, Đ.. (2022). Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 327-330.
https://hdl.handle.net/21.15107/rcub_ibiss_5739

Dožić A, Ćetković D, Despotović A, Janjetović K, Zogović N, Antonijević Đ. Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia. 2022;:327-330.
https://hdl.handle.net/21.15107/rcub_ibiss_5739 .

Dožić, Aleksandra, Ćetković, Dejan, Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Antonijević, Đorđe, "Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement" in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia (2022):327-330,
https://hdl.handle.net/21.15107/rcub_ibiss_5739 .

TY  - CONF
AU  - Janjetović, Kristina
AU  - Stamenković, Marina
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Despotović, Ana
AU  - Stevanović, Danijela
AU  - Mandić, Miloš
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Trajković, Vladimir
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5737
AB  - I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola.
AB  - И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Antikancerski potencijal inhibitora protonske pumpe pantoprazola
T1  - Антиканцерски потенцијал инхибитора протонске пумпе пантопразола
SP  - 285
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5737
ER  - 

@conference{
author = "Janjetović, Kristina and Stamenković, Marina and Tovilović-Kovačević, Gordana and Zogović, Nevena and Despotović, Ana and Stevanović, Danijela and Mandić, Miloš and Kosić, Milica and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Trajković, Vladimir",
year = "2022",
abstract = "I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola., И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Antikancerski potencijal inhibitora protonske pumpe pantoprazola, Антиканцерски потенцијал инхибитора протонске пумпе пантопразола",
pages = "285",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5737"
}

Janjetović, K., Stamenković, M., Tovilović-Kovačević, G., Zogović, N., Despotović, A., Stevanović, D., Mandić, M., Kosić, M., Paunović, V., Vučićević, L., Misirkić Marjanović, M.,& Trajković, V.. (2022). Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737

Janjetović K, Stamenković M, Tovilović-Kovačević G, Zogović N, Despotović A, Stevanović D, Mandić M, Kosić M, Paunović V, Vučićević L, Misirkić Marjanović M, Trajković V. Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

Janjetović, Kristina, Stamenković, Marina, Tovilović-Kovačević, Gordana, Zogović, Nevena, Despotović, Ana, Stevanović, Danijela, Mandić, Miloš, Kosić, Milica, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Trajković, Vladimir, "Antikancerski potencijal inhibitora protonske pumpe pantoprazola" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):285,
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

TY  - CONF
AU  - Ćetković, Dejan
AU  - Dožić, Aleksandra
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Antonijević, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5738
AB  - This study aimed to investigate the influence of ZrO2, Bi2O3 and SrF2 added as radiopacifying agents (30wt.%) into calcium silicate/hydroxyapatite-based dental cement on its physical and biological properties. Among investigated cements, the mixture containing Bi2O3 had the highest values of elastic modules and toughness, similarly to control – mineral trioxide aggregate (MTA). SEM analysis of all hydrated cements has shown that bioactive calcite and tobermorite phases were formed. Crystal violet assay showed that pure (undiluted) extracts of experimental cements did not affect cell viability, while MTA exhibited an extremely cytotoxic effect on L929 cells. In 1:4 dilutions all experimental mixtures significantly increased cell proliferation potential after 72h in comparison to untreated cells and MTA, which cytotoxic effect diminished with dilutions. Further studies are needed to determine which radiopacifyer has the most desirable properties for adequate dental cement fabrication.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
T1  - Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite
SP  - 323
EP  - 326
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5738
ER  - 

@conference{
author = "Ćetković, Dejan and Dožić, Aleksandra and Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Antonijević, Đorđe",
year = "2022",
abstract = "This study aimed to investigate the influence of ZrO2, Bi2O3 and SrF2 added as radiopacifying agents (30wt.%) into calcium silicate/hydroxyapatite-based dental cement on its physical and biological properties. Among investigated cements, the mixture containing Bi2O3 had the highest values of elastic modules and toughness, similarly to control – mineral trioxide aggregate (MTA). SEM analysis of all hydrated cements has shown that bioactive calcite and tobermorite phases were formed. Crystal violet assay showed that pure (undiluted) extracts of experimental cements did not affect cell viability, while MTA exhibited an extremely cytotoxic effect on L929 cells. In 1:4 dilutions all experimental mixtures significantly increased cell proliferation potential after 72h in comparison to untreated cells and MTA, which cytotoxic effect diminished with dilutions. Further studies are needed to determine which radiopacifyer has the most desirable properties for adequate dental cement fabrication.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia",
title = "Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite",
pages = "323-326",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5738"
}

Ćetković, D., Dožić, A., Despotović, A., Janjetović, K., Zogović, N.,& Antonijević, Đ.. (2022). Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 323-326.
https://hdl.handle.net/21.15107/rcub_ibiss_5738

Ćetković D, Dožić A, Despotović A, Janjetović K, Zogović N, Antonijević Đ. Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia. 2022;:323-326.
https://hdl.handle.net/21.15107/rcub_ibiss_5738 .

Ćetković, Dejan, Dožić, Aleksandra, Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Antonijević, Đorđe, "Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite" in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia (2022):323-326,
https://hdl.handle.net/21.15107/rcub_ibiss_5738 .

TY  - CONF
AU  - Jeremić, Marija
AU  - Jovanović, Maja
AU  - Tovilović-Kovačević, Gordana
AU  - Harhaji-Trajković, Ljubica
AU  - Zogović, Nevena
AU  - Vukojević, Milica
AU  - Kostić, Vladimir
AU  - Marković, Ivanka D.
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4450
AB  - Alpha-synuclein (ASYN) is regarded as one of the key culprits in
pathogenesis of synucleinopathies, including Parkinson’s disease,
and impaired regulation of autophagy is associated with the
ASYN aggregation. Autophagy is regulated by complex mechanisms,
including AMP activated protein kinase (AMPK), a key
energy sensor regulating cellular metabolism to maintain energy
homeostasis. The aim of our study was to investigate the role of
AMPK and autophagy in neurotoxic effect of secreted ASYN, as
well as dopamine-modified and nitrated recombinant wild-type
ASYN oligomers, on retinoic acid (RA)-differentiated SH-SY5Y
cells. The culture supernatant from neuroblastoma cells stably
expressing wt ASYN was collected and used as conditioned medium (CM). The presence of wt ASYN in CM was confirmed
by immunoblot, following lyophilisation. The CM, as well as
recombinant dopamine-modified or nitrated ASYN, all reduced
viability in differentiated SH-SY5Y cells. This decrease in viability
was accompanied by reduced AMPK activation, increased
conversion of LC3-I to LC3-II and increase in Beclin-1 level, as
demonstrated by immunoblot. Pharmacological activators of
AMPK and autophagy (metformin and AICAR) significantly
increased the cells’ viability in the presence of CM and modified
ASYN forms. Level of AMPK-activated pULK was reduced in
presence of CM, but pharmacological activators of AMPK
reversed that effect. Pharmacological inhibitors of autophagy,
further reduced cell viability in the presence of extracellular
ASYN. The shRNA-mediated LC3 downregulation, as well as
the RNA interference-mediated knockdown of ATG7 gene, both
important for autophagosome biogenesis/maturation, increased
sensitivity of SH-SY5Y cells to the extracellular ASYN-induced
toxicity. These data demonstrate the protective role of AMPK
and autophagy against the toxicity of extracellular ASYN, suggesting
that their modulation may be a promising neuroprotective
strategy in Parkinson’s disease.
PB  - Hoboken: Wiley
C3  - FEBS OpenBio
T1  - Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy
IS  - Supplement 1
VL  - 11
SP  - 463
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4450
ER  - 

@conference{
author = "Jeremić, Marija and Jovanović, Maja and Tovilović-Kovačević, Gordana and Harhaji-Trajković, Ljubica and Zogović, Nevena and Vukojević, Milica and Kostić, Vladimir and Marković, Ivanka D. and Trajković, Vladimir",
year = "2021",
abstract = "Alpha-synuclein (ASYN) is regarded as one of the key culprits in
pathogenesis of synucleinopathies, including Parkinson’s disease,
and impaired regulation of autophagy is associated with the
ASYN aggregation. Autophagy is regulated by complex mechanisms,
including AMP activated protein kinase (AMPK), a key
energy sensor regulating cellular metabolism to maintain energy
homeostasis. The aim of our study was to investigate the role of
AMPK and autophagy in neurotoxic effect of secreted ASYN, as
well as dopamine-modified and nitrated recombinant wild-type
ASYN oligomers, on retinoic acid (RA)-differentiated SH-SY5Y
cells. The culture supernatant from neuroblastoma cells stably
expressing wt ASYN was collected and used as conditioned medium (CM). The presence of wt ASYN in CM was confirmed
by immunoblot, following lyophilisation. The CM, as well as
recombinant dopamine-modified or nitrated ASYN, all reduced
viability in differentiated SH-SY5Y cells. This decrease in viability
was accompanied by reduced AMPK activation, increased
conversion of LC3-I to LC3-II and increase in Beclin-1 level, as
demonstrated by immunoblot. Pharmacological activators of
AMPK and autophagy (metformin and AICAR) significantly
increased the cells’ viability in the presence of CM and modified
ASYN forms. Level of AMPK-activated pULK was reduced in
presence of CM, but pharmacological activators of AMPK
reversed that effect. Pharmacological inhibitors of autophagy,
further reduced cell viability in the presence of extracellular
ASYN. The shRNA-mediated LC3 downregulation, as well as
the RNA interference-mediated knockdown of ATG7 gene, both
important for autophagosome biogenesis/maturation, increased
sensitivity of SH-SY5Y cells to the extracellular ASYN-induced
toxicity. These data demonstrate the protective role of AMPK
and autophagy against the toxicity of extracellular ASYN, suggesting
that their modulation may be a promising neuroprotective
strategy in Parkinson’s disease.",
publisher = "Hoboken: Wiley",
journal = "FEBS OpenBio",
title = "Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy",
number = "Supplement 1",
volume = "11",
pages = "463",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4450"
}

Jeremić, M., Jovanović, M., Tovilović-Kovačević, G., Harhaji-Trajković, L., Zogović, N., Vukojević, M., Kostić, V., Marković, I. D.,& Trajković, V.. (2021). Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy. in FEBS OpenBio
Hoboken: Wiley., 11(Supplement 1), 463.
https://hdl.handle.net/21.15107/rcub_ibiss_4450

Jeremić M, Jovanović M, Tovilović-Kovačević G, Harhaji-Trajković L, Zogović N, Vukojević M, Kostić V, Marković ID, Trajković V. Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy. in FEBS OpenBio. 2021;11(Supplement 1):463.
https://hdl.handle.net/21.15107/rcub_ibiss_4450 .

Jeremić, Marija, Jovanović, Maja, Tovilović-Kovačević, Gordana, Harhaji-Trajković, Ljubica, Zogović, Nevena, Vukojević, Milica, Kostić, Vladimir, Marković, Ivanka D., Trajković, Vladimir, "Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy" in FEBS OpenBio, 11, no. Supplement 1 (2021):463,
https://hdl.handle.net/21.15107/rcub_ibiss_4450 .

TY  - CONF
AU  - Despotović, Ana
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4724
AB  - The aim of this study was to investigate the role of necroptosis inhibitor necrostatin-1
(Nec-1) in death of human glioblastoma U251 cells exposed to ascorbic acid (AA), menadione(MD),
and their combination, in vitro. Nec-1 augmented cytotoxicity of AA+MD, and slightly increased
death of MD-treated U251 cells, as assessed by crystal violet (CV) assay. In line with previous, flow
cytometric analysis of annexin/propidium iodide-stained cells showed that Nec-1 triggered cell
death in MD and significantly enhanced ability of AA+MD to increase number of necrotic cells,
substantiating necrosis as the mechanism of U251 cell death induced by combined treatments
– AA+MD, Nec-1+MD, and Nec-1+AA+MD. Further, Nec-1 elevated mitochondrial and cellular
reactive oxygen species (ROS) generated by both MD and AA+MD co-treatment, as assessed
by flow cytometry analysis of MitoSOX- and DHR-stained cells, respectively. N-acetyl cysteine
(NAC), a well-known antioxidant, opposed U251 cell death induced by AA+MD, Nec-1+MD, and
Nec-1+AA+MD, indicating crucial role of oxidative stress in Nec-1-potentiated cytotoxicity of
MD and AA+MD. Also, Nec-1 activated AMP-activated protein kinase (AMPK), and its effector
molecule ULK1 (Ser317) over the level induced by MD and AA+MD, as showed by immunoblot.
AMPK, highly conserved serine/threonine protein kinase, is activated under the conditions of
oxidative stress probably as a consequence of depleted cellular ATP and elevated AMP levels.
This result implies important role of AMPK in necrosis detected in AA+MD-, Nec-1+MD-, and
Nec-1+AA+MD-treated U251 cells. Therefore, it can be concluded that ability of Nec-1 to enhance
cytotoxic potential of AA+MD co-treatment and trigger cytotoxicity of MD is associated with its
capacity to amplify cellular and mitochondrial ROS production, leading to necrosis-like cell
death of U251 cells. Obtained results reveal potential use of Nec-1 as anti-glioblastoma agent,
especially in combination with AA+MD.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line
DO  - 10.1016/j.freeradbiomed.2021.08.081
SP  - 78
ER  - 

@conference{
author = "Despotović, Ana and Harhaji-Trajković, Ljubica and Trajković, Vladimir and Tovilović-Kovačević, Gordana and Zogović, Nevena",
year = "2021",
abstract = "The aim of this study was to investigate the role of necroptosis inhibitor necrostatin-1
(Nec-1) in death of human glioblastoma U251 cells exposed to ascorbic acid (AA), menadione(MD),
and their combination, in vitro. Nec-1 augmented cytotoxicity of AA+MD, and slightly increased
death of MD-treated U251 cells, as assessed by crystal violet (CV) assay. In line with previous, flow
cytometric analysis of annexin/propidium iodide-stained cells showed that Nec-1 triggered cell
death in MD and significantly enhanced ability of AA+MD to increase number of necrotic cells,
substantiating necrosis as the mechanism of U251 cell death induced by combined treatments
– AA+MD, Nec-1+MD, and Nec-1+AA+MD. Further, Nec-1 elevated mitochondrial and cellular
reactive oxygen species (ROS) generated by both MD and AA+MD co-treatment, as assessed
by flow cytometry analysis of MitoSOX- and DHR-stained cells, respectively. N-acetyl cysteine
(NAC), a well-known antioxidant, opposed U251 cell death induced by AA+MD, Nec-1+MD, and
Nec-1+AA+MD, indicating crucial role of oxidative stress in Nec-1-potentiated cytotoxicity of
MD and AA+MD. Also, Nec-1 activated AMP-activated protein kinase (AMPK), and its effector
molecule ULK1 (Ser317) over the level induced by MD and AA+MD, as showed by immunoblot.
AMPK, highly conserved serine/threonine protein kinase, is activated under the conditions of
oxidative stress probably as a consequence of depleted cellular ATP and elevated AMP levels.
This result implies important role of AMPK in necrosis detected in AA+MD-, Nec-1+MD-, and
Nec-1+AA+MD-treated U251 cells. Therefore, it can be concluded that ability of Nec-1 to enhance
cytotoxic potential of AA+MD co-treatment and trigger cytotoxicity of MD is associated with its
capacity to amplify cellular and mitochondrial ROS production, leading to necrosis-like cell
death of U251 cells. Obtained results reveal potential use of Nec-1 as anti-glioblastoma agent,
especially in combination with AA+MD.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line",
doi = "10.1016/j.freeradbiomed.2021.08.081",
pages = "78"
}

Despotović, A., Harhaji-Trajković, L., Trajković, V., Tovilović-Kovačević, G.,& Zogović, N.. (2021). Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 78.
https://doi.org/10.1016/j.freeradbiomed.2021.08.081

Despotović A, Harhaji-Trajković L, Trajković V, Tovilović-Kovačević G, Zogović N. Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:78.
doi:10.1016/j.freeradbiomed.2021.08.081 .

Despotović, Ana, Harhaji-Trajković, Ljubica, Trajković, Vladimir, Tovilović-Kovačević, Gordana, Zogović, Nevena, "Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):78,
https://doi.org/10.1016/j.freeradbiomed.2021.08.081 . .

TY  - CONF
AU  - Harhaji-Trajković, Ljubica
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Zogović, Nevena
AU  - Mandić, Miloš
AU  - Tovilović-Kovačević, Gordana
AU  - Janjetović, Kristina
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://www.sdir.ac.rs/apstrakti-SDIR-5/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4709
AB  - Background: Intensive proliferation of tumor cells consumes a lot of energy. In nutrient deficiency 
substrates for energy metabolism are obtained by lysosomal degradation of unnecessary/dysfunctional 
intracellular organelles/molecules in the process of autophagy. Leakage of enlarged unstable lysosomes, 
which characterize tumor cells, causes cell death. We investigated antitumor effect of combined targeting 
of lysosomes/autophagy and energy metabolism. Material and Methods: Toxicity against U251 human 
glioma and B16 mouse melanoma cells was measured by viability tests. Type/mechanisms of cell death 
were determined by flow cytometry, immunoblot, fluorescent/electron microscopy and confirmed by 
appropriate genetic/pharmacological inhibitors. Therapeutic potential was estimated in B16 melanoma bearing C57Bl/6 mice. Results: In the first study, lysosomotropic autophagy inhibitor chloroquine (CQ) 
rapidly killed tumor cells incubated in the absence of serum. CQ-induced lysosomal destabilization 
triggered: oxidative stress, mitochondrial depolarization, and mixed apoptosis/necrosis of serum-deprived 
cells. In the second study, lysosomal detergent N-dodecylimidazole (NDI) synergized in antitumor activity 
with the glycolytic inhibitor 2-deoxy-D-glucose (2DG). NDI-triggered release of lysosomal enzymes into the 
cytoplasm caused mitochondrial damage and blocked oxidative phosphorylation, which synergized with 
2DG-mediated glycolysis block in ATP reduction, oxidative stress, and necrosis. Interestingly, although both 
serum deprivation and 2DG stimulated autophagy, CQ- and NDI-induced autophagy suppression was 
irrelevant for their cytotoxicity. Importantly, CQ+food restriction and 2DG+NDI reduced melanoma growth 
in vivo. Conclusion: Autophagy independent antitumor effects of combined energy metabolism suppression 
and lysosomal destabilization might be exploited in cancer therapy.
PB  - Beograd : Srpsko društvo istraživača raka
C3  - 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“
T1  - Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy
SP  - 8
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4709
ER  - 

@conference{
author = "Harhaji-Trajković, Ljubica and Kosić, Milica and Paunović, Verica and Ristić, Biljana and Bošnjak, Mihajlo and Zogović, Nevena and Mandić, Miloš and Tovilović-Kovačević, Gordana and Janjetović, Kristina and Trajković, Vladimir",
year = "2021",
abstract = "Background: Intensive proliferation of tumor cells consumes a lot of energy. In nutrient deficiency 
substrates for energy metabolism are obtained by lysosomal degradation of unnecessary/dysfunctional 
intracellular organelles/molecules in the process of autophagy. Leakage of enlarged unstable lysosomes, 
which characterize tumor cells, causes cell death. We investigated antitumor effect of combined targeting 
of lysosomes/autophagy and energy metabolism. Material and Methods: Toxicity against U251 human 
glioma and B16 mouse melanoma cells was measured by viability tests. Type/mechanisms of cell death 
were determined by flow cytometry, immunoblot, fluorescent/electron microscopy and confirmed by 
appropriate genetic/pharmacological inhibitors. Therapeutic potential was estimated in B16 melanoma bearing C57Bl/6 mice. Results: In the first study, lysosomotropic autophagy inhibitor chloroquine (CQ) 
rapidly killed tumor cells incubated in the absence of serum. CQ-induced lysosomal destabilization 
triggered: oxidative stress, mitochondrial depolarization, and mixed apoptosis/necrosis of serum-deprived 
cells. In the second study, lysosomal detergent N-dodecylimidazole (NDI) synergized in antitumor activity 
with the glycolytic inhibitor 2-deoxy-D-glucose (2DG). NDI-triggered release of lysosomal enzymes into the 
cytoplasm caused mitochondrial damage and blocked oxidative phosphorylation, which synergized with 
2DG-mediated glycolysis block in ATP reduction, oxidative stress, and necrosis. Interestingly, although both 
serum deprivation and 2DG stimulated autophagy, CQ- and NDI-induced autophagy suppression was 
irrelevant for their cytotoxicity. Importantly, CQ+food restriction and 2DG+NDI reduced melanoma growth 
in vivo. Conclusion: Autophagy independent antitumor effects of combined energy metabolism suppression 
and lysosomal destabilization might be exploited in cancer therapy.",
publisher = "Beograd : Srpsko društvo istraživača raka",
journal = "5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“",
title = "Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy",
pages = "8",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4709"
}

Harhaji-Trajković, L., Kosić, M., Paunović, V., Ristić, B., Bošnjak, M., Zogović, N., Mandić, M., Tovilović-Kovačević, G., Janjetović, K.,& Trajković, V.. (2021). Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy. in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“
Beograd : Srpsko društvo istraživača raka., 8.
https://hdl.handle.net/21.15107/rcub_ibiss_4709

Harhaji-Trajković L, Kosić M, Paunović V, Ristić B, Bošnjak M, Zogović N, Mandić M, Tovilović-Kovačević G, Janjetović K, Trajković V. Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy. in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“. 2021;:8.
https://hdl.handle.net/21.15107/rcub_ibiss_4709 .

Harhaji-Trajković, Ljubica, Kosić, Milica, Paunović, Verica, Ristić, Biljana, Bošnjak, Mihajlo, Zogović, Nevena, Mandić, Miloš, Tovilović-Kovačević, Gordana, Janjetović, Kristina, Trajković, Vladimir, "Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy" in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“ (2021):8,
https://hdl.handle.net/21.15107/rcub_ibiss_4709 .

TY  - CONF
AU  - Ristić, Biljana
AU  - Krunić, Matija
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Mirčić, Aleksandar
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Kosić, Milica
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4726
AB  - We here investigated the ability of graphene quantum dots (GQD), graphene nanoparticles with antioxidative capacity, to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). Although GQD diminished the levels of nitric oxide (NO) in both cell free condition and SNPexposed cells, NO scavengers (PTIO and uric acid), displayed only slight protection from SNP, suggesting that NO scavenging was not the main protective mechanism of GQD. Moreover, GQD significantly protected SH-SY5Y cells from neurotoxicity of light exhausted SNP, incapable of producing NO, implying the existence of protective mechanism independent of NO-scavenging. GQD lowered the increase in the concentration of hydroxyl radical (•OH) and superoxide anion (O2•−) caused by SNP both in the cell-free condition and inside cells, as well as ensuing oxidative stress and lipid peroxidation. Nonspecific antioxidants (glutathione, NAC), •OH scavenger (DMSO), and iron chelators (DTPA, BPDSA), but not superoxide dismutase, mimicked the cytoprotective activity of GQD, suggesting that GQD protect cells by neutralizing •OH generated in the presence of iron released from SNP. GQD were readily internalized by SH-SY5Y cells, while extensive washing of cells pre-incubated with GQD only partly reduced their protective activity, suggesting that GQD exerted neuroprotective effect both intra- and extracellularly. By demonstrating that GQD protect neuroblastoma cells from SNP-induced neurotoxicity by both extracellular •OH/NO scavenging and some unknown intracellular mechanism, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative and neuroinflammatory disorders associated with oxidative/nitrosative stress.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging
DO  - 10.1016/j.freeradbiomed.2021.08.167
SP  - 165
ER  - 

@conference{
author = "Ristić, Biljana and Krunić, Matija and Bošnjak, Mihajlo and Paunović, Verica and Zogović, Nevena and Tovilović-Kovačević, Gordana and Mirčić, Aleksandar and Misirkić Marjanović, Maja and Vučićević, Ljubica and Kosić, Milica and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2021",
abstract = "We here investigated the ability of graphene quantum dots (GQD), graphene nanoparticles with antioxidative capacity, to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). Although GQD diminished the levels of nitric oxide (NO) in both cell free condition and SNPexposed cells, NO scavengers (PTIO and uric acid), displayed only slight protection from SNP, suggesting that NO scavenging was not the main protective mechanism of GQD. Moreover, GQD significantly protected SH-SY5Y cells from neurotoxicity of light exhausted SNP, incapable of producing NO, implying the existence of protective mechanism independent of NO-scavenging. GQD lowered the increase in the concentration of hydroxyl radical (•OH) and superoxide anion (O2•−) caused by SNP both in the cell-free condition and inside cells, as well as ensuing oxidative stress and lipid peroxidation. Nonspecific antioxidants (glutathione, NAC), •OH scavenger (DMSO), and iron chelators (DTPA, BPDSA), but not superoxide dismutase, mimicked the cytoprotective activity of GQD, suggesting that GQD protect cells by neutralizing •OH generated in the presence of iron released from SNP. GQD were readily internalized by SH-SY5Y cells, while extensive washing of cells pre-incubated with GQD only partly reduced their protective activity, suggesting that GQD exerted neuroprotective effect both intra- and extracellularly. By demonstrating that GQD protect neuroblastoma cells from SNP-induced neurotoxicity by both extracellular •OH/NO scavenging and some unknown intracellular mechanism, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative and neuroinflammatory disorders associated with oxidative/nitrosative stress.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging",
doi = "10.1016/j.freeradbiomed.2021.08.167",
pages = "165"
}

Ristić, B., Krunić, M., Bošnjak, M., Paunović, V., Zogović, N., Tovilović-Kovačević, G., Mirčić, A., Misirkić Marjanović, M., Vučićević, L., Kosić, M., Trajković, V.,& Harhaji-Trajković, L.. (2021). Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 165.
https://doi.org/10.1016/j.freeradbiomed.2021.08.167

Ristić B, Krunić M, Bošnjak M, Paunović V, Zogović N, Tovilović-Kovačević G, Mirčić A, Misirkić Marjanović M, Vučićević L, Kosić M, Trajković V, Harhaji-Trajković L. Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:165.
doi:10.1016/j.freeradbiomed.2021.08.167 .

Ristić, Biljana, Krunić, Matija, Bošnjak, Mihajlo, Paunović, Verica, Zogović, Nevena, Tovilović-Kovačević, Gordana, Mirčić, Aleksandar, Misirkić Marjanović, Maja, Vučićević, Ljubica, Kosić, Milica, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):165,
https://doi.org/10.1016/j.freeradbiomed.2021.08.167 . .

TY  - CONF
AU  - Stevanović, Danijela
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Paunović, Verica
AU  - Kosić, Milica
AU  - Mandić, Miloš
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4725
AB  - 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) are the most common neurotoxins used to induce experimental model of Parkinson’s disease both in vivo and in vitro. Neurotoxic action of 6-OHDA and MPP+
 is mediated by oxidative stress, mitochondrial damage and induction of apoptotic cell death. Natural disaccharide trehalose exhibits antioxidative properties and stimulates removal of damaged proteins, and thus exhibits powerful
neuroprotective effect in certain brain injury models. We investigated the effects of trehalose in 6-OHDA and MPP+
 - induced oxidative stress and neurotoxicity in human neuroblastoma SH-SY5Y cells. The effects of trehalose on the cell viability and death were assessed by MTT, crystal violet, lactate dehydrogenase assay and AnnexinV-FITC/propidium iodide staining. The production of reactive oxygen species was analyzed by flow cytometry using redox-sensitive dyes dihydrorhodamine 123 (DHR) and MitoSOX Red. Further, activation of stress-related MAP kinases, p38 and JNK were investigated by immunoblot analysis. Our study demonstrated that trehalose pretreatment significantly improved cell viability and reduced neurotoxic effect of 6-OHDA, while slightly decreased cell viability and increased neurotoxic effect of MPP+. Trehalose decreased the number of 6-OHDA-induced apoptotic cells (shown by the reduced % of Annexin V+ and AnnexinV+ PI+ cells) whereas it increased apoptosis in MPP+ treated cells. Flow
cytometric analysis of DHR and MitoSOX stained cells demonstrated that trehalose pretreatment significantly reduced 6-OHDA-triggered ROS and superoxide anion radical generation. However, in MPP+-treated neurons trehalose augmented oxidative stress and production of superoxide anion. Immunoblot analysis showed that trehalose significantly decreased p38 and JNK activation only in 6-OHDA treated cells. These results indicate that trehalose has different effects on oxidative stress induced by two different neurotoxins, 6-OHDA and MPP+, and suggests further
exploration of the mechanism of its antioxidative action.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells
DO  - 10.1016/j.freeradbiomed.2021.08.097
SP  - 94
ER  - 

@conference{
author = "Stevanović, Danijela and Vučićević, Ljubica and Misirkić Marjanović, Maja and Paunović, Verica and Kosić, Milica and Mandić, Miloš and Ristić, Biljana and Bošnjak, Mihajlo and Janjetović, Kristina and Zogović, Nevena and Tovilović-Kovačević, Gordana and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) are the most common neurotoxins used to induce experimental model of Parkinson’s disease both in vivo and in vitro. Neurotoxic action of 6-OHDA and MPP+
 is mediated by oxidative stress, mitochondrial damage and induction of apoptotic cell death. Natural disaccharide trehalose exhibits antioxidative properties and stimulates removal of damaged proteins, and thus exhibits powerful
neuroprotective effect in certain brain injury models. We investigated the effects of trehalose in 6-OHDA and MPP+
 - induced oxidative stress and neurotoxicity in human neuroblastoma SH-SY5Y cells. The effects of trehalose on the cell viability and death were assessed by MTT, crystal violet, lactate dehydrogenase assay and AnnexinV-FITC/propidium iodide staining. The production of reactive oxygen species was analyzed by flow cytometry using redox-sensitive dyes dihydrorhodamine 123 (DHR) and MitoSOX Red. Further, activation of stress-related MAP kinases, p38 and JNK were investigated by immunoblot analysis. Our study demonstrated that trehalose pretreatment significantly improved cell viability and reduced neurotoxic effect of 6-OHDA, while slightly decreased cell viability and increased neurotoxic effect of MPP+. Trehalose decreased the number of 6-OHDA-induced apoptotic cells (shown by the reduced % of Annexin V+ and AnnexinV+ PI+ cells) whereas it increased apoptosis in MPP+ treated cells. Flow
cytometric analysis of DHR and MitoSOX stained cells demonstrated that trehalose pretreatment significantly reduced 6-OHDA-triggered ROS and superoxide anion radical generation. However, in MPP+-treated neurons trehalose augmented oxidative stress and production of superoxide anion. Immunoblot analysis showed that trehalose significantly decreased p38 and JNK activation only in 6-OHDA treated cells. These results indicate that trehalose has different effects on oxidative stress induced by two different neurotoxins, 6-OHDA and MPP+, and suggests further
exploration of the mechanism of its antioxidative action.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells",
doi = "10.1016/j.freeradbiomed.2021.08.097",
pages = "94"
}

Stevanović, D., Vučićević, L., Misirkić Marjanović, M., Paunović, V., Kosić, M., Mandić, M., Ristić, B., Bošnjak, M., Janjetović, K., Zogović, N., Tovilović-Kovačević, G., Harhaji-Trajković, L.,& Trajković, V.. (2021). The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 94.
https://doi.org/10.1016/j.freeradbiomed.2021.08.097

Stevanović D, Vučićević L, Misirkić Marjanović M, Paunović V, Kosić M, Mandić M, Ristić B, Bošnjak M, Janjetović K, Zogović N, Tovilović-Kovačević G, Harhaji-Trajković L, Trajković V. The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:94.
doi:10.1016/j.freeradbiomed.2021.08.097 .

Stevanović, Danijela, Vučićević, Ljubica, Misirkić Marjanović, Maja, Paunović, Verica, Kosić, Milica, Mandić, Miloš, Ristić, Biljana, Bošnjak, Mihajlo, Janjetović, Kristina, Zogović, Nevena, Tovilović-Kovačević, Gordana, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):94,
https://doi.org/10.1016/j.freeradbiomed.2021.08.097 . .

TY  - CONF
AU  - Despotović, Ana
AU  - Zogović, Nevena
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
AU  - Tovilović-Kovačević, Gordana
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4723
AB  - Glioblastoma multiforme (GBM) represents the most common and aggressive brain tumor that still lacks effective treatment options. Tumorigenesis and progression of GBM is tightly connected with over-activation of PI3K/Akt pathway, as well as with perturbed reactive oxygen species (ROS) generation in tumor cells and microenvironment. Breaking the redox balance within the tumor cells by enhancing ROS production is one of the proposed strategies for the treatment of malignancies. The aim of this study was to investigate potential antiglioma effect of ascorbic acid (AA) and menadione (MD) combination (AA+MD), the well-known oxidative stress inducer, and determine the interplay between Akt kinase activity and ROS generation in AA+MD-treated human U251 glioblastoma cells. To this end, U251 cells were treated with AA, MD and AA+MD, in the presence or absence of antioxidant N-acetylcysteine (NAC) or selective Akt inhibitor 10-DEBC hydrochloride (DEBC). Cell viability was assessed using crystal violet and MTT assays, ROS production was evaluated by flow cytometry of dihydrorhodamine-labeled cells, while Akt activity was determined using immunoblot. In contrast to AA and MD alone, combined treatment significantly decreased viability of U251 cells. The prominent toxicity of AA+MD was accompanied by an increase in ROS generation and Akt inhibition. ROS scavenger NAC diminished both Akt inhibition and cytotoxic effect of AA+MD, suggesting that Akt inactivation and cell death induced by AA+MD are ROS-dependent. Additionally, specific Akt inhibitor DEBC further enhanced death of U251 cells and elevated AA+MD-induced ROS production. Collectively, these results suggest that PI3K/Akt serves as pro-survival pathway, and its abolishing due to excessive ROS accumulation leads to glioblastoma cell death. Further, a pro-survival role of PI3K/Akt might encompass ROS removal. In conclusion, treatment with AA and MD, particularly in combination with Akt-targeted therapy, has great potential in combating GBM which is worthy of further investigation.
PB  - Amsterdam : Elsevier
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt
DO  - 10.1016/j.freeradbiomed.2021.08.072
SP  - 69
ER  - 

@conference{
author = "Despotović, Ana and Zogović, Nevena and Trajković, Vladimir and Harhaji-Trajković, Ljubica and Tovilović-Kovačević, Gordana",
year = "2021",
abstract = "Glioblastoma multiforme (GBM) represents the most common and aggressive brain tumor that still lacks effective treatment options. Tumorigenesis and progression of GBM is tightly connected with over-activation of PI3K/Akt pathway, as well as with perturbed reactive oxygen species (ROS) generation in tumor cells and microenvironment. Breaking the redox balance within the tumor cells by enhancing ROS production is one of the proposed strategies for the treatment of malignancies. The aim of this study was to investigate potential antiglioma effect of ascorbic acid (AA) and menadione (MD) combination (AA+MD), the well-known oxidative stress inducer, and determine the interplay between Akt kinase activity and ROS generation in AA+MD-treated human U251 glioblastoma cells. To this end, U251 cells were treated with AA, MD and AA+MD, in the presence or absence of antioxidant N-acetylcysteine (NAC) or selective Akt inhibitor 10-DEBC hydrochloride (DEBC). Cell viability was assessed using crystal violet and MTT assays, ROS production was evaluated by flow cytometry of dihydrorhodamine-labeled cells, while Akt activity was determined using immunoblot. In contrast to AA and MD alone, combined treatment significantly decreased viability of U251 cells. The prominent toxicity of AA+MD was accompanied by an increase in ROS generation and Akt inhibition. ROS scavenger NAC diminished both Akt inhibition and cytotoxic effect of AA+MD, suggesting that Akt inactivation and cell death induced by AA+MD are ROS-dependent. Additionally, specific Akt inhibitor DEBC further enhanced death of U251 cells and elevated AA+MD-induced ROS production. Collectively, these results suggest that PI3K/Akt serves as pro-survival pathway, and its abolishing due to excessive ROS accumulation leads to glioblastoma cell death. Further, a pro-survival role of PI3K/Akt might encompass ROS removal. In conclusion, treatment with AA and MD, particularly in combination with Akt-targeted therapy, has great potential in combating GBM which is worthy of further investigation.",
publisher = "Amsterdam : Elsevier",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt",
doi = "10.1016/j.freeradbiomed.2021.08.072",
pages = "69"
}

Despotović, A., Zogović, N., Trajković, V., Harhaji-Trajković, L.,& Tovilović-Kovačević, G.. (2021). Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Amsterdam : Elsevier., 69.
https://doi.org/10.1016/j.freeradbiomed.2021.08.072

Despotović A, Zogović N, Trajković V, Harhaji-Trajković L, Tovilović-Kovačević G. Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:69.
doi:10.1016/j.freeradbiomed.2021.08.072 .

Despotović, Ana, Zogović, Nevena, Trajković, Vladimir, Harhaji-Trajković, Ljubica, Tovilović-Kovačević, Gordana, "Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):69,
https://doi.org/10.1016/j.freeradbiomed.2021.08.072 . .

TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović-Marković, Biljana
AU  - Jovanović, Svetlana
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0891584921007760
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4655
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•-), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy-limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.
PB  - Elsevier Inc.
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.
VL  - 177
DO  - 10.1016/j.freeradbiomed.2021.10.025
SP  - 167
EP  - 180
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zogović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović-Marković, Biljana and Jovanović, Svetlana and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•-), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy-limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.",
publisher = "Elsevier Inc.",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.",
volume = "177",
doi = "10.1016/j.freeradbiomed.2021.10.025",
pages = "167-180"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zogović, N., Mirčić, A., Marković, Z., Todorović-Marković, B., Jovanović, S., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.. in Free Radical Biology and Medicine
Elsevier Inc.., 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zogović N, Mirčić A, Marković Z, Todorović-Marković B, Jovanović S, Kleut D, Mojović M, Nakarada Đ, Marković O, Vuković I, Harhaji-Trajković L, Trajković V. Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zogović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović-Marković, Biljana, Jovanović, Svetlana, Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera, Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death." in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .

TY  - JOUR
AU  - Despotović, Ana
AU  - Antonijević, Đorđe M
AU  - Ilić, Dragan
AU  - Zogović, Nevena
AU  - Jokanović, Vukoman R
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4430
AB  - Introduction Calcium silicate (CS) dental cements have numerous clinical indications in dentistry including pulp capping, root end surgery, perforation repair and apexification/apexogenesis treatment. Materials and methods Novel CS based dental cement with incorporation of SrCO3 radiopacifier named ALBO-DENT was used as an experimental cement material while Portland cement (Aalborg, Denmark) and ProRoot MTA (Tulsa Dental, USA) were used as controls. The radiopacity evaluation was performed using digital Trophy Radiographic system with an intention to precisely determine the minimum of radiopaque agent needed to confer to ISO radiopacity requirement. Thereafter, biocompatibility of material was tested in in vitro conditions in mouse fibrosarcoma L929 cell culture treated with materials’ extracts. Cell morphology was observed using phase-contrast microscopy, while cell viability was measured using crystal violet (CV) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assays. Results Radiopacity evaluation revealed that 30%wt addition of SrCO3 was necessary to achieve satisfactory radiopacity (3.45 mm Al). Cytotoxicity analysis using CV and MTT assays revealed that pure extracts of ALBO-DENT presented superior biocompatibility when compared to PC and MTA controls while serial dilutions of experimental cements’ extracts as well as that of PC and MTA did not influence L929 cell viability. Conclusions Novel formulation of CS cement – ALBO-DENT presented satisfactory radiopacity and adequate biocompatibility.
AB  - Uvod Kalcijum-silikatni (KS) dentalni cementi se koriste u brojnim kliničkim indikacijama u stomatologiji koje uključuju direktno prekrivanje pulpe, retrogradnu hirurgiju korena zuba, lečenje perforacija i apeksogenezu/apeksifikaciju. Materijali i metode U istraživanju je korišćen novosintetisani cement na bazi KS sa dodatkom SrCO3 kao kontrastnog agensa ALBO-DENTA, dok su kao kontrola korišćeni cement Portland (PC, Aalborg, Denmark) i ProRoot MTA (MTA, Tulsa Dental, USA). Rendgenokontrasnost je ispitivana digitalnom radiografijom primenom aparata Trophy, sa namerom da se precizno odredi minimum
kontrastnog agensa koji zadovoljava zahteve standarda ISO za rendgenkontrastnost. Biokompatibilnost materijala je ispitana in vitro, u kulturi ćelija mišjeg fibrosarkoma L929 tretiranoj ekstraktima ispitivanih materijala. Ćelijska morfologija je praćena upotrebom fazno-kontrastne mikroskopije, dok je vijabilnost ćelija utvrđivana kristal violet (KV) i 3-(4,5-dimetiltiazol-2-yl)-2,5-difenfl-tetrazolium bromid (MTT) esejima.
Rezultati Ispitivanje rendgenkontrastnosti je pokazalo da dodatak 30% SrCO3 dovodi do zadovoljavajućeg kontrasta materijala (3,45 mm Al). Analiza citotoksičnosti KV i MTT metodom je pokazala da čisti ekstrakt ALBO-DENTA pokazuje bolju biokompatibilnost u poređenju sa PC i MTA, dok serijska razblaženja ekstrakta ispitivanog cementa, kao i PC i MTA, nisu uticala na vijabilitet ćelija L929. Zaključci Novi cement na bazi KS – ALBO-DENT pokazao je zavodovoljavajuću rendgenkontrastnost i odgovarajuću biokompatibilnost.
PB  - Belgrade: Serbian Dental Journal
T2  - Serbian Dental Journal
T1  - Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement
T1  - Ispitivanje rendgenkontrastnosti i citotoksičnosti ALBO-DENTA – novog kalcijum-silikatnog cementa sa dodatkom stroncijumkarbonata
IS  - 2
VL  - 68
DO  - 10.2298/SGS2102068D
SP  - 68
EP  - 78
ER  - 

@article{
author = "Despotović, Ana and Antonijević, Đorđe M and Ilić, Dragan and Zogović, Nevena and Jokanović, Vukoman R",
year = "2021",
abstract = "Introduction Calcium silicate (CS) dental cements have numerous clinical indications in dentistry including pulp capping, root end surgery, perforation repair and apexification/apexogenesis treatment. Materials and methods Novel CS based dental cement with incorporation of SrCO3 radiopacifier named ALBO-DENT was used as an experimental cement material while Portland cement (Aalborg, Denmark) and ProRoot MTA (Tulsa Dental, USA) were used as controls. The radiopacity evaluation was performed using digital Trophy Radiographic system with an intention to precisely determine the minimum of radiopaque agent needed to confer to ISO radiopacity requirement. Thereafter, biocompatibility of material was tested in in vitro conditions in mouse fibrosarcoma L929 cell culture treated with materials’ extracts. Cell morphology was observed using phase-contrast microscopy, while cell viability was measured using crystal violet (CV) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assays. Results Radiopacity evaluation revealed that 30%wt addition of SrCO3 was necessary to achieve satisfactory radiopacity (3.45 mm Al). Cytotoxicity analysis using CV and MTT assays revealed that pure extracts of ALBO-DENT presented superior biocompatibility when compared to PC and MTA controls while serial dilutions of experimental cements’ extracts as well as that of PC and MTA did not influence L929 cell viability. Conclusions Novel formulation of CS cement – ALBO-DENT presented satisfactory radiopacity and adequate biocompatibility., Uvod Kalcijum-silikatni (KS) dentalni cementi se koriste u brojnim kliničkim indikacijama u stomatologiji koje uključuju direktno prekrivanje pulpe, retrogradnu hirurgiju korena zuba, lečenje perforacija i apeksogenezu/apeksifikaciju. Materijali i metode U istraživanju je korišćen novosintetisani cement na bazi KS sa dodatkom SrCO3 kao kontrastnog agensa ALBO-DENTA, dok su kao kontrola korišćeni cement Portland (PC, Aalborg, Denmark) i ProRoot MTA (MTA, Tulsa Dental, USA). Rendgenokontrasnost je ispitivana digitalnom radiografijom primenom aparata Trophy, sa namerom da se precizno odredi minimum
kontrastnog agensa koji zadovoljava zahteve standarda ISO za rendgenkontrastnost. Biokompatibilnost materijala je ispitana in vitro, u kulturi ćelija mišjeg fibrosarkoma L929 tretiranoj ekstraktima ispitivanih materijala. Ćelijska morfologija je praćena upotrebom fazno-kontrastne mikroskopije, dok je vijabilnost ćelija utvrđivana kristal violet (KV) i 3-(4,5-dimetiltiazol-2-yl)-2,5-difenfl-tetrazolium bromid (MTT) esejima.
Rezultati Ispitivanje rendgenkontrastnosti je pokazalo da dodatak 30% SrCO3 dovodi do zadovoljavajućeg kontrasta materijala (3,45 mm Al). Analiza citotoksičnosti KV i MTT metodom je pokazala da čisti ekstrakt ALBO-DENTA pokazuje bolju biokompatibilnost u poređenju sa PC i MTA, dok serijska razblaženja ekstrakta ispitivanog cementa, kao i PC i MTA, nisu uticala na vijabilitet ćelija L929. Zaključci Novi cement na bazi KS – ALBO-DENT pokazao je zavodovoljavajuću rendgenkontrastnost i odgovarajuću biokompatibilnost.",
publisher = "Belgrade: Serbian Dental Journal",
journal = "Serbian Dental Journal",
title = "Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement, Ispitivanje rendgenkontrastnosti i citotoksičnosti ALBO-DENTA – novog kalcijum-silikatnog cementa sa dodatkom stroncijumkarbonata",
number = "2",
volume = "68",
doi = "10.2298/SGS2102068D",
pages = "68-78"
}

Despotović, A., Antonijević, Đ. M., Ilić, D., Zogović, N.,& Jokanović, V. R.. (2021). Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement. in Serbian Dental Journal
Belgrade: Serbian Dental Journal., 68(2), 68-78.
https://doi.org/10.2298/SGS2102068D

Despotović A, Antonijević ĐM, Ilić D, Zogović N, Jokanović VR. Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement. in Serbian Dental Journal. 2021;68(2):68-78.
doi:10.2298/SGS2102068D .

Despotović, Ana, Antonijević, Đorđe M, Ilić, Dragan, Zogović, Nevena, Jokanović, Vukoman R, "Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement" in Serbian Dental Journal, 68, no. 2 (2021):68-78,
https://doi.org/10.2298/SGS2102068D . .

TY  - JOUR
AU  - Antonijević, Đorđe
AU  - Despotović, Ana
AU  - Biočanin, Vladimir
AU  - Milošević, Miloš
AU  - Trišić, Dijana
AU  - Lazović, Vladimir
AU  - Zogović, Nevena
AU  - Milašin, Jelena
AU  - Ilić, Dragan
PY  - 2021
UR  - https://www.sciencedirect.com/science/article/pii/S0272884221020794
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4464
AB  - The purpose of this study was to investigate the influence of different radiopacifiers on the physicochemical and biological properties of novel calcium silicate based endodontic ceramic enriched with bioactive nano-particulated hydroxyapatite – ECHA. Namely, ECHA was used as a basis for mixing with the following radiopacifiers: strontium fluoride (SrF2), zirconium dioxide (ZrO2) and bismuth oxide (Bi2O3). For comparison, Portland cement (PC) and mineral trioxide aggregate (MTA) were used. The following physicochemical characteristics were examined: the radiopacity, setting time, compressive strength, porosity, wettability and pH value. The biocompatibility of the cements was assessed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and cell adhesion assays. The highest radiopacity was obtained for the ECHA + Bi2O3 mixture and MTA that were statistically significant in comparison to other materials (p < 0.05). Both initial and final setting times as well as compressive strengths were statistically lower for experimental cements than for PC and MTA (p < 0.05). The lowest total porosity was observed in the ECHA + ZrO2 group when compared with the other two experimental cements (p < 0.05), but not when compared with PC and MTA (p > 0.05). Experimental cements exhibited statistically higher contact angles of glycerol than PC and MTA (p < 0.05). For blood plasma, a statistical difference was found only between ECHA + Bi2O3 and PC (p < 0.05). All investigated materials had alkalization ability. Cell viability assays revealed that the extracts of tested cements did not exhibit cytotoxic effect on L929 cells. Scanning electron microscopy had shown a high degree of cell proliferation and adhesion of cells from apical papilla on experimental cements’ surfaces. Novel endodontic ceramics with nano-hydroxyapatite addition have satisfactory biological and physicochemical properties when compared to MTA and PC controls. Considerable lower setting time of experimental cements might present a huge advantage of these synthesized materials in clinical practice. SrF2 presents a novel promising radiopacifying agent for dental cements manufacturing.
PB  - Oxford : Elsevier
T2  - Ceramics International
T1  - Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic
IS  - 20
VL  - 47
DO  - 10.1016/j.ceramint.2021.07.052
SP  - 28913
EP  - 28923
ER  - 

@article{
author = "Antonijević, Đorđe and Despotović, Ana and Biočanin, Vladimir and Milošević, Miloš and Trišić, Dijana and Lazović, Vladimir and Zogović, Nevena and Milašin, Jelena and Ilić, Dragan",
year = "2021",
abstract = "The purpose of this study was to investigate the influence of different radiopacifiers on the physicochemical and biological properties of novel calcium silicate based endodontic ceramic enriched with bioactive nano-particulated hydroxyapatite – ECHA. Namely, ECHA was used as a basis for mixing with the following radiopacifiers: strontium fluoride (SrF2), zirconium dioxide (ZrO2) and bismuth oxide (Bi2O3). For comparison, Portland cement (PC) and mineral trioxide aggregate (MTA) were used. The following physicochemical characteristics were examined: the radiopacity, setting time, compressive strength, porosity, wettability and pH value. The biocompatibility of the cements was assessed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and cell adhesion assays. The highest radiopacity was obtained for the ECHA + Bi2O3 mixture and MTA that were statistically significant in comparison to other materials (p < 0.05). Both initial and final setting times as well as compressive strengths were statistically lower for experimental cements than for PC and MTA (p < 0.05). The lowest total porosity was observed in the ECHA + ZrO2 group when compared with the other two experimental cements (p < 0.05), but not when compared with PC and MTA (p > 0.05). Experimental cements exhibited statistically higher contact angles of glycerol than PC and MTA (p < 0.05). For blood plasma, a statistical difference was found only between ECHA + Bi2O3 and PC (p < 0.05). All investigated materials had alkalization ability. Cell viability assays revealed that the extracts of tested cements did not exhibit cytotoxic effect on L929 cells. Scanning electron microscopy had shown a high degree of cell proliferation and adhesion of cells from apical papilla on experimental cements’ surfaces. Novel endodontic ceramics with nano-hydroxyapatite addition have satisfactory biological and physicochemical properties when compared to MTA and PC controls. Considerable lower setting time of experimental cements might present a huge advantage of these synthesized materials in clinical practice. SrF2 presents a novel promising radiopacifying agent for dental cements manufacturing.",
publisher = "Oxford : Elsevier",
journal = "Ceramics International",
title = "Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic",
number = "20",
volume = "47",
doi = "10.1016/j.ceramint.2021.07.052",
pages = "28913-28923"
}

Antonijević, Đ., Despotović, A., Biočanin, V., Milošević, M., Trišić, D., Lazović, V., Zogović, N., Milašin, J.,& Ilić, D.. (2021). Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic. in Ceramics International
Oxford : Elsevier., 47(20), 28913-28923.
https://doi.org/10.1016/j.ceramint.2021.07.052

Antonijević Đ, Despotović A, Biočanin V, Milošević M, Trišić D, Lazović V, Zogović N, Milašin J, Ilić D. Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic. in Ceramics International. 2021;47(20):28913-28923.
doi:10.1016/j.ceramint.2021.07.052 .

Antonijević, Đorđe, Despotović, Ana, Biočanin, Vladimir, Milošević, Miloš, Trišić, Dijana, Lazović, Vladimir, Zogović, Nevena, Milašin, Jelena, Ilić, Dragan, "Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic" in Ceramics International, 47, no. 20 (2021):28913-28923,
https://doi.org/10.1016/j.ceramint.2021.07.052 . .

TY  - JOUR
AU  - Antonijević, Đorđe
AU  - Despotović, Ana
AU  - Biočanin, Vladimir
AU  - Milošević, Miloš
AU  - Trišić, Dijana
AU  - Lazović, Vladimir
AU  - Zogović, Nevena
AU  - Milašin, Jelena
AU  - Ilić, Dragan
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0272884221020794
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4445
AB  - The purpose of this study was to investigate the influence of different radiopacifiers on the physicochemical and biological properties of novel calcium silicate based endodontic ceramic enriched with bioactive nano-particulated hydroxyapatite – ECHA. Namely, ECHA was used as a basis for mixing with the following radiopacifiers: strontium fluoride (SrF2), zirconium dioxide (ZrO2) and bismuth oxide (Bi2O3). For comparison, Portland cement (PC) and mineral trioxide aggregate (MTA) were used. The following physicochemical characteristics were examined: the radiopacity, setting time, compressive strength, porosity, wettability and pH value. The biocompatibility of the cements was assessed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and cell adhesion assays. The highest radiopacity was obtained for the ECHA + Bi2O3 mixture and MTA that were statistically significant in comparison to other materials (p < 0.05). Both initial and final setting times as well as compressive strengths were statistically lower for experimental cements than for PC and MTA (p < 0.05). The lowest total porosity was observed in the ECHA + ZrO2 group when compared with the other two experimental cements (p < 0.05), but not when compared with PC and MTA (p > 0.05). Experimental cements exhibited statistically higher contact angles of glycerol than PC and MTA (p < 0.05). For blood plasma, a statistical difference was found only between ECHA + Bi2O3 and PC (p < 0.05). All investigated materials had alkalization ability. Cell viability assays revealed that the extracts of tested cements did not exhibit cytotoxic effect on L929 cells. Scanning electron microscopy had shown a high degree of cell proliferation and adhesion of cells from apical papilla on experimental cements’ surfaces. Novel endodontic ceramics with nano-hydroxyapatite addition have satisfactory biological and physicochemical properties when compared to MTA and PC controls. Considerable lower setting time of experimental cements might present a huge advantage of these synthesized materials in clinical practice. SrF2 presents a novel promising radiopacifying agent for dental cements manufacturing.
PB  - Oxford: Elsevier Ltd
T2  - Ceramics International
T1  - Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic
IS  - 20
VL  - 47
DO  - 10.1016/j.ceramint.2021.07.052
SP  - 28913
EP  - 28923
ER  - 

@article{
author = "Antonijević, Đorđe and Despotović, Ana and Biočanin, Vladimir and Milošević, Miloš and Trišić, Dijana and Lazović, Vladimir and Zogović, Nevena and Milašin, Jelena and Ilić, Dragan",
year = "2021",
abstract = "The purpose of this study was to investigate the influence of different radiopacifiers on the physicochemical and biological properties of novel calcium silicate based endodontic ceramic enriched with bioactive nano-particulated hydroxyapatite – ECHA. Namely, ECHA was used as a basis for mixing with the following radiopacifiers: strontium fluoride (SrF2), zirconium dioxide (ZrO2) and bismuth oxide (Bi2O3). For comparison, Portland cement (PC) and mineral trioxide aggregate (MTA) were used. The following physicochemical characteristics were examined: the radiopacity, setting time, compressive strength, porosity, wettability and pH value. The biocompatibility of the cements was assessed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and cell adhesion assays. The highest radiopacity was obtained for the ECHA + Bi2O3 mixture and MTA that were statistically significant in comparison to other materials (p < 0.05). Both initial and final setting times as well as compressive strengths were statistically lower for experimental cements than for PC and MTA (p < 0.05). The lowest total porosity was observed in the ECHA + ZrO2 group when compared with the other two experimental cements (p < 0.05), but not when compared with PC and MTA (p > 0.05). Experimental cements exhibited statistically higher contact angles of glycerol than PC and MTA (p < 0.05). For blood plasma, a statistical difference was found only between ECHA + Bi2O3 and PC (p < 0.05). All investigated materials had alkalization ability. Cell viability assays revealed that the extracts of tested cements did not exhibit cytotoxic effect on L929 cells. Scanning electron microscopy had shown a high degree of cell proliferation and adhesion of cells from apical papilla on experimental cements’ surfaces. Novel endodontic ceramics with nano-hydroxyapatite addition have satisfactory biological and physicochemical properties when compared to MTA and PC controls. Considerable lower setting time of experimental cements might present a huge advantage of these synthesized materials in clinical practice. SrF2 presents a novel promising radiopacifying agent for dental cements manufacturing.",
publisher = "Oxford: Elsevier Ltd",
journal = "Ceramics International",
title = "Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic",
number = "20",
volume = "47",
doi = "10.1016/j.ceramint.2021.07.052",
pages = "28913-28923"
}

Antonijević, Đ., Despotović, A., Biočanin, V., Milošević, M., Trišić, D., Lazović, V., Zogović, N., Milašin, J.,& Ilić, D.. (2021). Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic. in Ceramics International
Oxford: Elsevier Ltd., 47(20), 28913-28923.
https://doi.org/10.1016/j.ceramint.2021.07.052

Antonijević Đ, Despotović A, Biočanin V, Milošević M, Trišić D, Lazović V, Zogović N, Milašin J, Ilić D. Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic. in Ceramics International. 2021;47(20):28913-28923.
doi:10.1016/j.ceramint.2021.07.052 .

Antonijević, Đorđe, Despotović, Ana, Biočanin, Vladimir, Milošević, Miloš, Trišić, Dijana, Lazović, Vladimir, Zogović, Nevena, Milašin, Jelena, Ilić, Dragan, "Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic" in Ceramics International, 47, no. 20 (2021):28913-28923,
https://doi.org/10.1016/j.ceramint.2021.07.052 . .

TY  - JOUR
AU  - Tešić, Vesna
AU  - Ćirić, Jelena
AU  - Jovanović Macura, Irena
AU  - Zogović, Nevena
AU  - Milanović, Desanka
AU  - Kanazir, Selma
AU  - Perović, Milka
PY  - 2021
UR  - https://www.mdpi.com/2072-6643/13/12/4526
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8703853
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4760
AB  - Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats. Corticosterone level was increased in the cortex of aged ad libitum-fed rats. Food restriction induced its further increase, accompanied with an increase in the level of 11β-hydroxysteroid dehydrogenase type 1. However, alterations in the level of GR phosphorylated at Ser232 were not detected in animals on food restriction, in line with unaltered CDK5 level, the decrease of Hsp90, and an increase in a negative regulator of GR function, FKBP51. Moreover, our data revealed that reduced food intake prevented age-related increase in the levels of NFκB, gfap, and bax, confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of c-fos, our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging.
PB  - Basel: MDPI
T2  - Nutrients
T1  - Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging-The Effects of Long-Term Food Restriction.
IS  - 12
VL  - 13
DO  - 10.3390/nu13124526
SP  - 4526
ER  - 

@article{
author = "Tešić, Vesna and Ćirić, Jelena and Jovanović Macura, Irena and Zogović, Nevena and Milanović, Desanka and Kanazir, Selma and Perović, Milka",
year = "2021",
abstract = "Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats. Corticosterone level was increased in the cortex of aged ad libitum-fed rats. Food restriction induced its further increase, accompanied with an increase in the level of 11β-hydroxysteroid dehydrogenase type 1. However, alterations in the level of GR phosphorylated at Ser232 were not detected in animals on food restriction, in line with unaltered CDK5 level, the decrease of Hsp90, and an increase in a negative regulator of GR function, FKBP51. Moreover, our data revealed that reduced food intake prevented age-related increase in the levels of NFκB, gfap, and bax, confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of c-fos, our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging.",
publisher = "Basel: MDPI",
journal = "Nutrients",
title = "Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging-The Effects of Long-Term Food Restriction.",
number = "12",
volume = "13",
doi = "10.3390/nu13124526",
pages = "4526"
}

Tešić, V., Ćirić, J., Jovanović Macura, I., Zogović, N., Milanović, D., Kanazir, S.,& Perović, M.. (2021). Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging-The Effects of Long-Term Food Restriction.. in Nutrients
Basel: MDPI., 13(12), 4526.
https://doi.org/10.3390/nu13124526

Tešić V, Ćirić J, Jovanović Macura I, Zogović N, Milanović D, Kanazir S, Perović M. Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging-The Effects of Long-Term Food Restriction.. in Nutrients. 2021;13(12):4526.
doi:10.3390/nu13124526 .

Tešić, Vesna, Ćirić, Jelena, Jovanović Macura, Irena, Zogović, Nevena, Milanović, Desanka, Kanazir, Selma, Perović, Milka, "Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging-The Effects of Long-Term Food Restriction." in Nutrients, 13, no. 12 (2021):4526,
https://doi.org/10.3390/nu13124526 . .

TY  - CONF
AU  - Perović, Vladimir
AU  - Zogović, Nikola
AU  - Zogović, Nevena
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4720
AB  - Renal failure represents a growing clinical problem around the world. Although dialysis is a short-term solution, kidney transplantation confers better survival and quality-of-life outcomes for most patients with end-stage kidney disease. A major limitation to renal transplantation is the supply of donor kidneys. Determining eligibility for a kidney transplantation is one of the most difficult decisions facing clinicians. Clinical practice guidelines have been implemented in many countries for the evaluation and acceptance of patients for the kidney transplantation waiting list in order to provide explicit recommendations to guide clinical decision making. The most important determinants of the outcome of renal transplantation are the degree of HLA matching, the cold ischemia time (total time between removal of the kidney from the donor and its transplantation into the recipient), blood group matching, number of prior grafts, presence of donor-specific antibodies, age of donor and recipient, time on dialysis prior to transplantation, diabetes in the recipient, race, living or cadaver donor, and transplant center. Kidney allocation algorithms vary both within and between countries. Most methods of donor organ allocation involve the use of simple algorithms designed to take into account major factors thought to influence graft outcome. The aim of this study is to improve the existing decision support system for Kidney Exchange Program (KEP) in the Serbian healthcare system by applying complex multicriteria optimization (CMCO) methods. Also, the goal is to determine the framework for harmonization of KEP in Serbia with the corresponding programs in European countries. In this study, we present the objectives and constraints in the Serbian KEP, determined by the medical aspects of kidney transplantation process and the Serbian law on human organ transplantation. We will then compare them with the corresponding KEP objectives and constraints in European countries. Based on the comparison and analysis of the applied CMCO algorithms in European countries with developed KEP, we intend to determine the guidelines for the CMCO algorithm in the Serbian KEP.
PB  - Novi Sad: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad
C3  - Biologia Serbica
T1  - Innovative bioinformatic approach to kidney transplant wait-list management in the Republic of Serbia
SP  - 90
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4720
ER  - 

@conference{
author = "Perović, Vladimir and Zogović, Nikola and Zogović, Nevena",
year = "2021",
abstract = "Renal failure represents a growing clinical problem around the world. Although dialysis is a short-term solution, kidney transplantation confers better survival and quality-of-life outcomes for most patients with end-stage kidney disease. A major limitation to renal transplantation is the supply of donor kidneys. Determining eligibility for a kidney transplantation is one of the most difficult decisions facing clinicians. Clinical practice guidelines have been implemented in many countries for the evaluation and acceptance of patients for the kidney transplantation waiting list in order to provide explicit recommendations to guide clinical decision making. The most important determinants of the outcome of renal transplantation are the degree of HLA matching, the cold ischemia time (total time between removal of the kidney from the donor and its transplantation into the recipient), blood group matching, number of prior grafts, presence of donor-specific antibodies, age of donor and recipient, time on dialysis prior to transplantation, diabetes in the recipient, race, living or cadaver donor, and transplant center. Kidney allocation algorithms vary both within and between countries. Most methods of donor organ allocation involve the use of simple algorithms designed to take into account major factors thought to influence graft outcome. The aim of this study is to improve the existing decision support system for Kidney Exchange Program (KEP) in the Serbian healthcare system by applying complex multicriteria optimization (CMCO) methods. Also, the goal is to determine the framework for harmonization of KEP in Serbia with the corresponding programs in European countries. In this study, we present the objectives and constraints in the Serbian KEP, determined by the medical aspects of kidney transplantation process and the Serbian law on human organ transplantation. We will then compare them with the corresponding KEP objectives and constraints in European countries. Based on the comparison and analysis of the applied CMCO algorithms in European countries with developed KEP, we intend to determine the guidelines for the CMCO algorithm in the Serbian KEP.",
publisher = "Novi Sad: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad",
journal = "Biologia Serbica",
title = "Innovative bioinformatic approach to kidney transplant wait-list management in the Republic of Serbia",
pages = "90",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4720"
}

Perović, V., Zogović, N.,& Zogović, N.. (2021). Innovative bioinformatic approach to kidney transplant wait-list management in the Republic of Serbia. in Biologia Serbica
Novi Sad: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad., 90.
https://hdl.handle.net/21.15107/rcub_ibiss_4720

Perović V, Zogović N, Zogović N. Innovative bioinformatic approach to kidney transplant wait-list management in the Republic of Serbia. in Biologia Serbica. 2021;:90.
https://hdl.handle.net/21.15107/rcub_ibiss_4720 .

Perović, Vladimir, Zogović, Nikola, Zogović, Nevena, "Innovative bioinformatic approach to kidney transplant wait-list management in the Republic of Serbia" in Biologia Serbica (2021):90,
https://hdl.handle.net/21.15107/rcub_ibiss_4720 .

TY  - CHAP
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Krstić Milošević, Dijana
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/123456789/3896
AB  - Gentianaceae have a long history of use as traditional remedies for treatment of various ailments. The medicinal properties of crude herbal drug are attributed to bitter glycosides, flavonoids, and xanthones, the main plant secondary metabolites. These plant-derived molecules, especially naturally occurring xanthones, possess a broad spectrum of bioactivity like anticarcinogenic, antimicrobial, neuroprotective, antidiabetic, cardio-protective. The most of Gentianaceae species are rare and endangered by uncontrolled overharvesting and influences of various environmental factors (habitat loss, climate change, and invasive species spreading). Decline of Gentianaceae species poses a high risk to the loss of enormous diversity of potentially bioactive compounds. In this chapter we will summarize pharmacological activities of identified secondary metabolites from endangered species belonging to four Gentianaceae genera (Gentiana, Gentianella, Centaurium, Swertia), as well as importance of biodiversity conservation in context of their biotherapeutic potential.
PB  - Academic Press
T2  - Biodiversity and Biomedicine Our Future
T1  - Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics
DO  - 10.1016/B978-0-12-819541-3.00019-0
SP  - 335
EP  - 384
ER  - 

@inbook{
author = "Tovilović-Kovačević, Gordana and Zogović, Nevena and Krstić Milošević, Dijana",
year = "2020",
abstract = "Gentianaceae have a long history of use as traditional remedies for treatment of various ailments. The medicinal properties of crude herbal drug are attributed to bitter glycosides, flavonoids, and xanthones, the main plant secondary metabolites. These plant-derived molecules, especially naturally occurring xanthones, possess a broad spectrum of bioactivity like anticarcinogenic, antimicrobial, neuroprotective, antidiabetic, cardio-protective. The most of Gentianaceae species are rare and endangered by uncontrolled overharvesting and influences of various environmental factors (habitat loss, climate change, and invasive species spreading). Decline of Gentianaceae species poses a high risk to the loss of enormous diversity of potentially bioactive compounds. In this chapter we will summarize pharmacological activities of identified secondary metabolites from endangered species belonging to four Gentianaceae genera (Gentiana, Gentianella, Centaurium, Swertia), as well as importance of biodiversity conservation in context of their biotherapeutic potential.",
publisher = "Academic Press",
journal = "Biodiversity and Biomedicine Our Future",
booktitle = "Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics",
doi = "10.1016/B978-0-12-819541-3.00019-0",
pages = "335-384"
}

Tovilović-Kovačević, G., Zogović, N.,& Krstić Milošević, D.. (2020). Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics. in Biodiversity and Biomedicine Our Future
Academic Press., 335-384.
https://doi.org/10.1016/B978-0-12-819541-3.00019-0

Tovilović-Kovačević G, Zogović N, Krstić Milošević D. Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics. in Biodiversity and Biomedicine Our Future. 2020;:335-384.
doi:10.1016/B978-0-12-819541-3.00019-0 .

Tovilović-Kovačević, Gordana, Zogović, Nevena, Krstić Milošević, Dijana, "Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics" in Biodiversity and Biomedicine Our Future (2020):335-384,
https://doi.org/10.1016/B978-0-12-819541-3.00019-0 . .

TY  - CONF
AU  - Ristić, Biljana
AU  - Krunić, Matija
AU  - Bošnjak, Mihajlo
AU  - Mirčić, Aleksandar
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Paunović, Verica
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2019
UR  - https://nordicautophagy.org/
UR  - https://nordicautophagy.org/report-3rd-nordic-autophagy-society-conference-in-utrecht/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6718
AB  - We investigated the ability of nano-sized graphen layers graphen quantum dots (GQD) to protect human neuroblastoma SH-SY5Y cells from toxicity of NO donor sodium nitroprusside (SNP). GQD prevented SNP induced mitochondrial depolarization and caspase dependent apoptosis. GQD partly suppressed neurotoxicity of NO donor DEA-NONOate and reduced SNP induced NO release in cells and cell-free system, suggesting that neuroprotective effects of GQD were partly mediated by their NO-scavanging capacity. However, GQD significantly preserved SH-SY5Y cells from light exhausted SNP, which was unable to produce NO, implying the existence of protective mechanism independent of NO-scavenging. Unspecific antioxidant, as well as hydroxyl radical (.OH) scavengers DMSO, vitamin E and gluthatione mimicked neuroprotective activity of GQD, while GQD diminished concentration of reactive oxygen species (ROS), especially .OH, in cells and cell culture medium, suggesting important role of .OH scavenging in neuroprotective activity of GQD. However ability of GQD to protect SH-SY5Y cells from SNP was not exclusively mediated by their ability to scavenge NO and ROS from medium, since it persisted after washing of GQD preincubated cells. Interestingly, GQD were found to be present in autophagosome-like vacuoles. Both SNP and GQD, and especially their combination, increased intracellular acidity characteristic for presence of autophagosomes, concentration of proautophagic protein beclin-1, while deacreased level of specific substrate of autophagic proteolysis p62. Moreover, SNP and GQD, and above all their combination, increased concentration of autophagosome-associated protein LC3 II in the presence of inhibitor of autophagic proteolysis bafilomycin A1. Finally, autophagy inhibitors 3-methzladenine, wortmannin and NH4Cl prevented neuroprotective ability of GQD, implying that GQD stimulated prosurvival autophagy in SNP treated neurons. Therefore, by demonstrating ability of GQD to protect SH-SY5Y neurons from SNP induced apoptosis by scavenging NO/ROS and stimulation of cytoprotective autophagy, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative disorders.
PB  - Nordic Autophagy Society
C3  - 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands
T1  - Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction
SP  - 40
EP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6718
ER  - 

@conference{
author = "Ristić, Biljana and Krunić, Matija and Bošnjak, Mihajlo and Mirčić, Aleksandar and Tovilović-Kovačević, Gordana and Zogović, Nevena and Paunović, Verica and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2019",
abstract = "We investigated the ability of nano-sized graphen layers graphen quantum dots (GQD) to protect human neuroblastoma SH-SY5Y cells from toxicity of NO donor sodium nitroprusside (SNP). GQD prevented SNP induced mitochondrial depolarization and caspase dependent apoptosis. GQD partly suppressed neurotoxicity of NO donor DEA-NONOate and reduced SNP induced NO release in cells and cell-free system, suggesting that neuroprotective effects of GQD were partly mediated by their NO-scavanging capacity. However, GQD significantly preserved SH-SY5Y cells from light exhausted SNP, which was unable to produce NO, implying the existence of protective mechanism independent of NO-scavenging. Unspecific antioxidant, as well as hydroxyl radical (.OH) scavengers DMSO, vitamin E and gluthatione mimicked neuroprotective activity of GQD, while GQD diminished concentration of reactive oxygen species (ROS), especially .OH, in cells and cell culture medium, suggesting important role of .OH scavenging in neuroprotective activity of GQD. However ability of GQD to protect SH-SY5Y cells from SNP was not exclusively mediated by their ability to scavenge NO and ROS from medium, since it persisted after washing of GQD preincubated cells. Interestingly, GQD were found to be present in autophagosome-like vacuoles. Both SNP and GQD, and especially their combination, increased intracellular acidity characteristic for presence of autophagosomes, concentration of proautophagic protein beclin-1, while deacreased level of specific substrate of autophagic proteolysis p62. Moreover, SNP and GQD, and above all their combination, increased concentration of autophagosome-associated protein LC3 II in the presence of inhibitor of autophagic proteolysis bafilomycin A1. Finally, autophagy inhibitors 3-methzladenine, wortmannin and NH4Cl prevented neuroprotective ability of GQD, implying that GQD stimulated prosurvival autophagy in SNP treated neurons. Therefore, by demonstrating ability of GQD to protect SH-SY5Y neurons from SNP induced apoptosis by scavenging NO/ROS and stimulation of cytoprotective autophagy, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative disorders.",
publisher = "Nordic Autophagy Society",
journal = "3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands",
title = "Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction",
pages = "40-40",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6718"
}

Ristić, B., Krunić, M., Bošnjak, M., Mirčić, A., Tovilović-Kovačević, G., Zogović, N., Paunović, V., Trajković, V.,& Harhaji-Trajković, L.. (2019). Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands
Nordic Autophagy Society., 40-40.
https://hdl.handle.net/21.15107/rcub_ibiss_6718

Ristić B, Krunić M, Bošnjak M, Mirčić A, Tovilović-Kovačević G, Zogović N, Paunović V, Trajković V, Harhaji-Trajković L. Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands. 2019;:40-40.
https://hdl.handle.net/21.15107/rcub_ibiss_6718 .

Ristić, Biljana, Krunić, Matija, Bošnjak, Mihajlo, Mirčić, Aleksandar, Tovilović-Kovačević, Gordana, Zogović, Nevena, Paunović, Verica, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction" in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands (2019):40-40,
https://hdl.handle.net/21.15107/rcub_ibiss_6718 .