TY  - CONF
AU  - Stevanović, Danijela
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Mandić, Miloš
AU  - Harhaji-Trajković, Ljubica
AU  - Janjetović, Kristina
AU  - Kosić, Milica
AU  - Lalošević, Jovan
AU  - Nikolić, Miloš
AU  - Bonači-Nikolić, Branka
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/123456789/6286
AB  - Introduction: Since the interaction between autophagy and virus-induced inflammation is complex,
we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1
cells expressing SARS-Cov2 proteins NSP5 and ORF3a.
Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital
admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants
was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured
by RT-qPCR.
Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time
points, whereasIL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy
markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor
p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a
in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase
of intracellular and secreted p62. This was associated with an NSP5-mediated decrease inTNF/IL-10 mRNA
and an ORF3a-mediated increase inTNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62
mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a.
Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect
SARS-CoV-induced inflammation.
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  - Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19
SP  - 76
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6286
ER  - 

@conference{
author = "Stevanović, Danijela and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Perović, Vladimir and Ristić, Biljana and Bošnjak, Mihajlo and Mandić, Miloš and Harhaji-Trajković, Ljubica and Janjetović, Kristina and Kosić, Milica and Lalošević, Jovan and Nikolić, Miloš and Bonači-Nikolić, Branka and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: Since the interaction between autophagy and virus-induced inflammation is complex,
we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1
cells expressing SARS-Cov2 proteins NSP5 and ORF3a.
Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital
admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants
was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured
by RT-qPCR.
Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time
points, whereasIL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy
markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor
p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a
in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase
of intracellular and secreted p62. This was associated with an NSP5-mediated decrease inTNF/IL-10 mRNA
and an ORF3a-mediated increase inTNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62
mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a.
Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect
SARS-CoV-induced inflammation.",
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 = "Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19",
pages = "76",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6286"
}

Stevanović, D., Paunović, V., Vučićević, L., Misirkić Marjanović, M., Perović, V., Ristić, B., Bošnjak, M., Mandić, M., Harhaji-Trajković, L., Janjetović, K., Kosić, M., Lalošević, J., Nikolić, M., Bonači-Nikolić, B.,& Trajković, V.. (2023). Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19. 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., 76.
https://hdl.handle.net/21.15107/rcub_ibiss_6286

Stevanović D, Paunović V, Vučićević L, Misirkić Marjanović M, Perović V, Ristić B, Bošnjak M, Mandić M, Harhaji-Trajković L, Janjetović K, Kosić M, Lalošević J, Nikolić M, Bonači-Nikolić B, Trajković V. Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:76.
https://hdl.handle.net/21.15107/rcub_ibiss_6286 .

Stevanović, Danijela, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Perović, Vladimir, Ristić, Biljana, Bošnjak, Mihajlo, Mandić, Miloš, Harhaji-Trajković, Ljubica, Janjetović, Kristina, Kosić, Milica, Lalošević, Jovan, Nikolić, Miloš, Bonači-Nikolić, Branka, Trajković, Vladimir, "Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):76,
https://hdl.handle.net/21.15107/rcub_ibiss_6286 .

TY  - CONF
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Janjetović, Kristina
AU  - Paunović, Verica
AU  - Stevanović, Danijela
AU  - Kosić, Milica
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://www.sdir.ac.rs/en/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6301
AB  - Background: Reactive oxygen species (ROS) have been implicated in autophagy induction and mitogen activated protein kinases (MAPK) activation which both participate in the differentiation of hematopoietic and leukemic cells. 
We assessed the role of ROS in MAPK activation and autophagy induction in phorbol myristate acetate-(PMA) induced macrophage differentiation of HL-60 leukemia cells. Material and methods: The macrophage markers CD11b, EGR1, 
CSF1R, and IL-8 were assessed by RT-qPCR and flow cytometry. The activation of MAPK was assessed by ERK and JNK immunoblotting, while autophagy was monitored by LC3-II and p62 immunoblotting. Pharmacological inhibition 
was used to determine the role of MAPK and autophagy in HL60 cell differentiation. Intracellular ROS production was determined by flow cytometric analysis of the green fluorescence emitted by non-selective redox-sensitive dye 2',7'-dichlorodihydrofluorescein diacetate. Antioxidant N-acetylcysteine (NAC) was used to determine the role of ROS in MAPK activation, induction of autophagy and HL-60 macrophage differentiation. Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers 
CD11b, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase of autophagic flux. Pharmacological inhibition of ERK or JNK suppressed PMA-triggered autophagy induction and differentiation of HL-60 cells into macrophage-like cells. PMA increased the intracellular ROS generation and the antioxidant NAC reduced the expression of macrophage markers EGR-1, CSF1R, IL-8 and CD11b in PMA-treated HL-60 cells. NAC also blocked PMA-induced LC3-II and ERK phosphorylation, but only slightly reduced the phosphorylation of JNK and did not affect 
the levels of p62. Conclusion: Our study revealed the partial involvement of ROS in MAPK-dependent autophagy in the differentiation of HL60 cells, indicating ROS/MAPK-mediated autophagy for further investigation in differentiation therapy of AML.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells
SP  - 104
EP  - 105
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6301
ER  - 

@conference{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Bošnjak, Mihajlo and Perović, Vladimir and Janjetović, Kristina and Paunović, Verica and Stevanović, Danijela and Kosić, Milica and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2023",
abstract = "Background: Reactive oxygen species (ROS) have been implicated in autophagy induction and mitogen activated protein kinases (MAPK) activation which both participate in the differentiation of hematopoietic and leukemic cells. 
We assessed the role of ROS in MAPK activation and autophagy induction in phorbol myristate acetate-(PMA) induced macrophage differentiation of HL-60 leukemia cells. Material and methods: The macrophage markers CD11b, EGR1, 
CSF1R, and IL-8 were assessed by RT-qPCR and flow cytometry. The activation of MAPK was assessed by ERK and JNK immunoblotting, while autophagy was monitored by LC3-II and p62 immunoblotting. Pharmacological inhibition 
was used to determine the role of MAPK and autophagy in HL60 cell differentiation. Intracellular ROS production was determined by flow cytometric analysis of the green fluorescence emitted by non-selective redox-sensitive dye 2',7'-dichlorodihydrofluorescein diacetate. Antioxidant N-acetylcysteine (NAC) was used to determine the role of ROS in MAPK activation, induction of autophagy and HL-60 macrophage differentiation. Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers 
CD11b, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase of autophagic flux. Pharmacological inhibition of ERK or JNK suppressed PMA-triggered autophagy induction and differentiation of HL-60 cells into macrophage-like cells. PMA increased the intracellular ROS generation and the antioxidant NAC reduced the expression of macrophage markers EGR-1, CSF1R, IL-8 and CD11b in PMA-treated HL-60 cells. NAC also blocked PMA-induced LC3-II and ERK phosphorylation, but only slightly reduced the phosphorylation of JNK and did not affect 
the levels of p62. Conclusion: Our study revealed the partial involvement of ROS in MAPK-dependent autophagy in the differentiation of HL60 cells, indicating ROS/MAPK-mediated autophagy for further investigation in differentiation therapy of AML.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells",
pages = "104-105",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6301"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Bošnjak, M., Perović, V., Janjetović, K., Paunović, V., Stevanović, D., Kosić, M., Harhaji-Trajković, L.,& Trajković, V.. (2023). The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 104-105.
https://hdl.handle.net/21.15107/rcub_ibiss_6301

Mandić M, Misirkić Marjanović M, Vučićević L, Bošnjak M, Perović V, Janjetović K, Paunović V, Stevanović D, Kosić M, Harhaji-Trajković L, Trajković V. The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:104-105.
https://hdl.handle.net/21.15107/rcub_ibiss_6301 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Bošnjak, Mihajlo, Perović, Vladimir, Janjetović, Kristina, Paunović, Verica, Stevanović, Danijela, Kosić, Milica, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):104-105,
https://hdl.handle.net/21.15107/rcub_ibiss_6301 .

TY  - CONF
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Ćirić, Darko
AU  - Janjetović, Kristina
AU  - Paunović, Verica
AU  - Stevanović, Danijela
AU  - Kosić, Milica
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/123456789/6285
AB  - Introduction: Autophagy has been shown to participate in the differentiation of hematopoietic and
leukemic cells. We investigated the mechanisms of autophagy action in the differentiation induced by
PKC activator phorbol myristate acetate (PMA) in HL-60 acute myeloid leukemia cells.
Methods: The macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8 were assessed by
flow cytometry and RT-qPCR. Autophagy was monitored by RT-qPCR analysis of autophagy-related (ATG)
gene expression, LC3-II/p62 immunoblotting, beclin-1/Bcl-2 interaction, nuclear translocation of TFEB
and FOXO1/3. The activation of MAP kinases, ERK and JNK was assessed by immunoblotting. Pharmacological inhibition and RNA interference were used to determine the role of MAP kinases and autophagy
in HL60 cell differentiation.
Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by accumulation/punctuation of LC3-II, and the increase in
autophagic flux. PMA also increased nuclear translocation of TFEB, FOXO1/3, as well asthe expression of
several ATG genesin HL-60 cells. PMA stimulated the phosphorylation of ERK and JNK via PKC-dependent
mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear
translocation of TFEB and FOXO1/3, ATG expression, dissociation of beclin-1 from Bcl-2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells.
Conclusion: Our study revealed the involvement of ERK and JNK in TFEB/FOXO-dependent autophagy
and differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target in differentiation therapy of AML.
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  - MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells
SP  - 56
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6285
ER  - 

@conference{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Bošnjak, Mihajlo and Perović, Vladimir and Ristić, Biljana and Ćirić, Darko and Janjetović, Kristina and Paunović, Verica and Stevanović, Danijela and Kosić, Milica and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: Autophagy has been shown to participate in the differentiation of hematopoietic and
leukemic cells. We investigated the mechanisms of autophagy action in the differentiation induced by
PKC activator phorbol myristate acetate (PMA) in HL-60 acute myeloid leukemia cells.
Methods: The macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8 were assessed by
flow cytometry and RT-qPCR. Autophagy was monitored by RT-qPCR analysis of autophagy-related (ATG)
gene expression, LC3-II/p62 immunoblotting, beclin-1/Bcl-2 interaction, nuclear translocation of TFEB
and FOXO1/3. The activation of MAP kinases, ERK and JNK was assessed by immunoblotting. Pharmacological inhibition and RNA interference were used to determine the role of MAP kinases and autophagy
in HL60 cell differentiation.
Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by accumulation/punctuation of LC3-II, and the increase in
autophagic flux. PMA also increased nuclear translocation of TFEB, FOXO1/3, as well asthe expression of
several ATG genesin HL-60 cells. PMA stimulated the phosphorylation of ERK and JNK via PKC-dependent
mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear
translocation of TFEB and FOXO1/3, ATG expression, dissociation of beclin-1 from Bcl-2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells.
Conclusion: Our study revealed the involvement of ERK and JNK in TFEB/FOXO-dependent autophagy
and differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target in differentiation therapy of AML.",
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 = "MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells",
pages = "56",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6285"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Bošnjak, M., Perović, V., Ristić, B., Ćirić, D., Janjetović, K., Paunović, V., Stevanović, D., Kosić, M., Harhaji-Trajković, L.,& Trajković, V.. (2023). MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. 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., 56.
https://hdl.handle.net/21.15107/rcub_ibiss_6285

Mandić M, Misirkić Marjanović M, Vučićević L, Bošnjak M, Perović V, Ristić B, Ćirić D, Janjetović K, Paunović V, Stevanović D, Kosić M, Harhaji-Trajković L, Trajković V. MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:56.
https://hdl.handle.net/21.15107/rcub_ibiss_6285 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Bošnjak, Mihajlo, Perović, Vladimir, Ristić, Biljana, Ćirić, Darko, Janjetović, Kristina, Paunović, Verica, Stevanović, Danijela, Kosić, Milica, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):56,
https://hdl.handle.net/21.15107/rcub_ibiss_6285 .

TY  - JOUR
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Mandić, Miloš
AU  - Stevanović, Danijela
AU  - Harhaji-Trajković, Ljubica
AU  - Lalošević, Jovan
AU  - Nikolić, Miloš
AU  - Bonači-Nikolić, Branka
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://www.mdpi.com/2073-4409/12/9/1282
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5912
AB  - As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.
PB  - Basel: MDPI
T2  - Cells
T1  - Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19
IS  - 9
VL  - 12
DO  - 10.3390/cells12091282
SP  - 1282
ER  - 

@article{
author = "Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Perović, Vladimir and Ristić, Biljana and Bošnjak, Mihajlo and Mandić, Miloš and Stevanović, Danijela and Harhaji-Trajković, Ljubica and Lalošević, Jovan and Nikolić, Miloš and Bonači-Nikolić, Branka and Trajković, Vladimir",
year = "2023",
abstract = "As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19",
number = "9",
volume = "12",
doi = "10.3390/cells12091282",
pages = "1282"
}

Paunović, V., Vučićević, L., Misirkić Marjanović, M., Perović, V., Ristić, B., Bošnjak, M., Mandić, M., Stevanović, D., Harhaji-Trajković, L., Lalošević, J., Nikolić, M., Bonači-Nikolić, B.,& Trajković, V.. (2023). Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19. in Cells
Basel: MDPI., 12(9), 1282.
https://doi.org/10.3390/cells12091282

Paunović V, Vučićević L, Misirkić Marjanović M, Perović V, Ristić B, Bošnjak M, Mandić M, Stevanović D, Harhaji-Trajković L, Lalošević J, Nikolić M, Bonači-Nikolić B, Trajković V. Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19. in Cells. 2023;12(9):1282.
doi:10.3390/cells12091282 .

Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Perović, Vladimir, Ristić, Biljana, Bošnjak, Mihajlo, Mandić, Miloš, Stevanović, Danijela, Harhaji-Trajković, Ljubica, Lalošević, Jovan, Nikolić, Miloš, Bonači-Nikolić, Branka, Trajković, Vladimir, "Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19" in Cells, 12, no. 9 (2023):1282,
https://doi.org/10.3390/cells12091282 . .

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  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Jovanović, Maja
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Ćirić, Darko
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320522001813
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35304128
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4947
AB  - We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.
PB  - Elsevier Inc.
T2  - Life Sciences
T1  - MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.
VL  - 297
DO  - 10.1016/j.lfs.2022.120481
SP  - 120481
ER  - 

@article{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Jovanović, Maja and Bošnjak, Mihajlo and Perović, Vladimir and Ristić, Biljana and Ćirić, Darko and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2022",
abstract = "We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.",
publisher = "Elsevier Inc.",
journal = "Life Sciences",
title = "MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.",
volume = "297",
doi = "10.1016/j.lfs.2022.120481",
pages = "120481"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Jovanović, M., Bošnjak, M., Perović, V., Ristić, B., Ćirić, D., Harhaji-Trajković, L.,& Trajković, V.. (2022). MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.. in Life Sciences
Elsevier Inc.., 297, 120481.
https://doi.org/10.1016/j.lfs.2022.120481

Mandić M, Misirkić Marjanović M, Vučićević L, Jovanović M, Bošnjak M, Perović V, Ristić B, Ćirić D, Harhaji-Trajković L, Trajković V. MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.. in Life Sciences. 2022;297:120481.
doi:10.1016/j.lfs.2022.120481 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Jovanović, Maja, Bošnjak, Mihajlo, Perović, Vladimir, Ristić, Biljana, Ćirić, Darko, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells." in Life Sciences, 297 (2022):120481,
https://doi.org/10.1016/j.lfs.2022.120481 . .

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  - CONF
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Jovanović, Maja
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2019
UR  - https://nordicautophagy.org
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6597
AB  - We investigated the mechanism and the role of autophagy in phorbol myristate acetate (PMA)-induced myeloid differentiation of human acute myeloid leukemia HL-60 cells. Methods: The mRNA levels of myeloid differentiation markers colony stimulating factor 1 receptor (CSF1R), early growth response protein 1 (EGR1), and interleukin 8 (IL-8), were assessed by real-time RT-PCR. Cell cycle arrest and the expression of surface myeloid marker CD11b were analyzed by flow cytometry. Autophagy was monitored by acridine orange staining, RT-PCR analysis of autophagy-related (ATG) gene expression, LC3-II/p62 immunoblotting, Beclin-1/Bcl-2 interaction, nuclear translocation of transcription factor EB (TFEB). The activation of MAP kinases extracelluar signal-regulated kinase (ERK) and c-Jun-N terminal kinase (JNK) was assessed by immunoblotting. Pharmacological inhibition and RNA interference (RNAi) were used to determine the role of MAP kinases in autophagy and HL60 cell differentiation, while the role of autophagy in HL60 differentiation was analyzed using RNAi-mediated knockdown of ATG5 and p62. Results: PMA-induced differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of p21, CD11b, CSF1R, EGR1, and IL-8. The induction of autophagy was demonstrated by accumulation of LC3-II, the increase in autophagic flux, the increase in expression of ATG genes, nuclear translocation of TFEB and dissociation of Beclin1from Bcl-2.The suppression of autophagy by RNAi–mediated knockdown of ATG5 or p62 counteracted myeloid differentiation of HL60 cells. Both ERK and JNK were activated by PMA, and their pharmacological and genetic inhibition decreased PMA-induced autophagy and differentiation of HL60 cells. Conclusion: Our study revealed the involvement of JNK and ERK in autophagy-dependent myeloid differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target for treatment of acute myeloid leukemia
PB  - Nordic Autophagy Society
C3  - 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands
T1  - MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells
SP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6597
ER  - 

@conference{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Jovanović, Maja and Bošnjak, Mihajlo and Perović, Vladimir and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2019",
abstract = "We investigated the mechanism and the role of autophagy in phorbol myristate acetate (PMA)-induced myeloid differentiation of human acute myeloid leukemia HL-60 cells. Methods: The mRNA levels of myeloid differentiation markers colony stimulating factor 1 receptor (CSF1R), early growth response protein 1 (EGR1), and interleukin 8 (IL-8), were assessed by real-time RT-PCR. Cell cycle arrest and the expression of surface myeloid marker CD11b were analyzed by flow cytometry. Autophagy was monitored by acridine orange staining, RT-PCR analysis of autophagy-related (ATG) gene expression, LC3-II/p62 immunoblotting, Beclin-1/Bcl-2 interaction, nuclear translocation of transcription factor EB (TFEB). The activation of MAP kinases extracelluar signal-regulated kinase (ERK) and c-Jun-N terminal kinase (JNK) was assessed by immunoblotting. Pharmacological inhibition and RNA interference (RNAi) were used to determine the role of MAP kinases in autophagy and HL60 cell differentiation, while the role of autophagy in HL60 differentiation was analyzed using RNAi-mediated knockdown of ATG5 and p62. Results: PMA-induced differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of p21, CD11b, CSF1R, EGR1, and IL-8. The induction of autophagy was demonstrated by accumulation of LC3-II, the increase in autophagic flux, the increase in expression of ATG genes, nuclear translocation of TFEB and dissociation of Beclin1from Bcl-2.The suppression of autophagy by RNAi–mediated knockdown of ATG5 or p62 counteracted myeloid differentiation of HL60 cells. Both ERK and JNK were activated by PMA, and their pharmacological and genetic inhibition decreased PMA-induced autophagy and differentiation of HL60 cells. Conclusion: Our study revealed the involvement of JNK and ERK in autophagy-dependent myeloid differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target for treatment of acute myeloid leukemia",
publisher = "Nordic Autophagy Society",
journal = "3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands",
title = "MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells",
pages = "33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6597"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Jovanović, M., Bošnjak, M., Perović, V., Harhaji-Trajković, L.,& Trajković, V.. (2019). MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands
Nordic Autophagy Society., 33.
https://hdl.handle.net/21.15107/rcub_ibiss_6597

Mandić M, Misirkić Marjanović M, Vučićević L, Jovanović M, Bošnjak M, Perović V, Harhaji-Trajković L, Trajković V. MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands. 2019;:33.
https://hdl.handle.net/21.15107/rcub_ibiss_6597 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Jovanović, Maja, Bošnjak, Mihajlo, Perović, Vladimir, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells" in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands (2019):33,
https://hdl.handle.net/21.15107/rcub_ibiss_6597 .

TY  - JOUR
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  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S0944711318300874?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3125
AB  - BACKGROUND Glioblastoma multiforme (GMB) is the most malignant of all brain tumors with poor prognosis. Anticancer potential of xanthones, bioactive compounds found in Gentiana dinarica, is well-documented. Transformation of G. dinarica roots with Agrobacterium rhizogenes provides higher xanthones accumulation, which enables better exploitation of these anticancer compounds. HYPOTHESIS/PURPOSE The aim of this study was to investigate antiglioma effect of three different G. dinarica extracts: E1—derived from untransformed roots, E2—derived from roots transformed using A. rhizogenes strain A4M70GUS, and E3—derived from roots transformed using A. rhizogenes strain 15834/PI. Further, mechanisms involved in anticancer potential of the most potent extract were examined in detail, and its active component was determined. METHODS The cell viability was assessed using MTT and crystal violet test. Cell cycle analysis, the expression of differentiation markers, the levels of autophagy, and oxidative stress were analyzed by flow cytometry. Autophagy and related signaling pathways were assessed by immunoblotting. RESULTS E3, in contrast to E1 and E2, strongly reduced growth of U251 human glioblastoma cells, triggered cell cycle arrest in G2/M phase, changed cellular morphology, and increased expression of markers of differentiated astrocytes (glial fibrillary acidic protein) and neurons (β-tubulin). E3 stimulated autophagy, as demonstrated by enhanced intracellular acidification, increased microtubule-associated light chain 3B (LC3-I) conversion to autophagosome associated LC3-II, and decreased level of selective autophagy target p62. Induction of autophagy was associated with Akt-dependent inhibition of main autophagy suppressor mammalian target of rapamycin (mTOR). Both genetic and pharmacological inhibition of autophagy suppressed the expression of differentiation markers, but had no effect on cell cycle arrest in E3-treated cells. E3 stimulated oxidative stress, and antioxidants vitamin E and N-acetyl cysteine inhibited autophagy and differentiation of E3-treated U251 cells. The most prevalent compound of E3, xanthone aglycone norswertianin, also arrested glioblastoma cell proliferation in G2/M phase and induced glioblastoma cell differentiation through induction of autophagy and oxidative stress. CONCLUSION These results indicate that E3 and its main active component norswertianin may serve as a potential candidate for differentiation therapy of glioblastoma.
T2  - Phytomedicine
T1  - Xanthone-rich extract from Gentiana dinarica transformed roots and its active component norswertianin induce autophagy and ROS-dependent differentiation of human glioblastoma cell line
VL  - 47
DO  - 10.1016/J.PHYMED.2018.03.052
SP  - 151
EP  - 160
ER  - 

@article{
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 = "2018",
abstract = "BACKGROUND Glioblastoma multiforme (GMB) is the most malignant of all brain tumors with poor prognosis. Anticancer potential of xanthones, bioactive compounds found in Gentiana dinarica, is well-documented. Transformation of G. dinarica roots with Agrobacterium rhizogenes provides higher xanthones accumulation, which enables better exploitation of these anticancer compounds. HYPOTHESIS/PURPOSE The aim of this study was to investigate antiglioma effect of three different G. dinarica extracts: E1—derived from untransformed roots, E2—derived from roots transformed using A. rhizogenes strain A4M70GUS, and E3—derived from roots transformed using A. rhizogenes strain 15834/PI. Further, mechanisms involved in anticancer potential of the most potent extract were examined in detail, and its active component was determined. METHODS The cell viability was assessed using MTT and crystal violet test. Cell cycle analysis, the expression of differentiation markers, the levels of autophagy, and oxidative stress were analyzed by flow cytometry. Autophagy and related signaling pathways were assessed by immunoblotting. RESULTS E3, in contrast to E1 and E2, strongly reduced growth of U251 human glioblastoma cells, triggered cell cycle arrest in G2/M phase, changed cellular morphology, and increased expression of markers of differentiated astrocytes (glial fibrillary acidic protein) and neurons (β-tubulin). E3 stimulated autophagy, as demonstrated by enhanced intracellular acidification, increased microtubule-associated light chain 3B (LC3-I) conversion to autophagosome associated LC3-II, and decreased level of selective autophagy target p62. Induction of autophagy was associated with Akt-dependent inhibition of main autophagy suppressor mammalian target of rapamycin (mTOR). Both genetic and pharmacological inhibition of autophagy suppressed the expression of differentiation markers, but had no effect on cell cycle arrest in E3-treated cells. E3 stimulated oxidative stress, and antioxidants vitamin E and N-acetyl cysteine inhibited autophagy and differentiation of E3-treated U251 cells. The most prevalent compound of E3, xanthone aglycone norswertianin, also arrested glioblastoma cell proliferation in G2/M phase and induced glioblastoma cell differentiation through induction of autophagy and oxidative stress. CONCLUSION These results indicate that E3 and its main active component norswertianin may serve as a potential candidate for differentiation therapy of glioblastoma.",
journal = "Phytomedicine",
title = "Xanthone-rich extract from Gentiana dinarica transformed roots and its active component norswertianin induce autophagy and ROS-dependent differentiation of human glioblastoma cell line",
volume = "47",
doi = "10.1016/J.PHYMED.2018.03.052",
pages = "151-160"
}

Tovilović-Kovačević, G., Krstić Milošević, D., Vinterhalter, B., Toljić, M., Perović, V., Trajković, V., Harhaji-Trajković, L.,& Zogović, N.. (2018). Xanthone-rich extract from Gentiana dinarica transformed roots and its active component norswertianin induce autophagy and ROS-dependent differentiation of human glioblastoma cell line. in Phytomedicine, 47, 151-160.
https://doi.org/10.1016/J.PHYMED.2018.03.052

Tovilović-Kovačević G, Krstić Milošević D, Vinterhalter B, Toljić M, Perović V, Trajković V, Harhaji-Trajković L, Zogović N. Xanthone-rich extract from Gentiana dinarica transformed roots and its active component norswertianin induce autophagy and ROS-dependent differentiation of human glioblastoma cell line. in Phytomedicine. 2018;47:151-160.
doi:10.1016/J.PHYMED.2018.03.052 .

Tovilović-Kovačević, Gordana, Krstić Milošević, Dijana, Vinterhalter, Branka, Toljić, Mina, Perović, Vladimir, Trajković, Vladimir, Harhaji-Trajković, Ljubica, Zogović, Nevena, "Xanthone-rich extract from Gentiana dinarica transformed roots and its active component norswertianin induce autophagy and ROS-dependent differentiation of human glioblastoma cell line" in Phytomedicine, 47 (2018):151-160,
https://doi.org/10.1016/J.PHYMED.2018.03.052 . .