TY  - JOUR
AU  - Balint, Vanda
AU  - Perić, Mina
AU  - Dačić, Sanja
AU  - Stanisavljević Ninković, Danijela
AU  - Marjanović, Jelena
AU  - Popović, Jelena
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
PY  - 2024
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2340
AB  - Astrocytes are the main homeostatic cells in the central nervous system, with the unique ability to transform from quiescent into a reactive state in response to pathological conditions by reacquiring some precursor properties. This process is known as reactive astrogliosis, a compensatory response that mediates tissue damage and recovery. Although it is well known that SOX transcription factors drive the expression of phenotype-specific genetic programs during neurodevelopment, their roles in mature astrocytes have not been studied extensively. We focused on the transcription factors SOX2 and SOX9, shown to be re-expressed in reactive astrocytes, in order to study the reactivation-related functional properties of astrocytes mediated by those proteins. We performed an initial screening of SOX2 and SOX9 expression after sensorimotor cortex ablation injury in rats and conducted gain-of-function studies in vitro using astrocytes derived from the human NT2/D1 cell line. Our results revealed the direct involvement of SOX2 in the reacquisition of proliferation in mature NT2/D1-derived astrocytes, while SOX9 overexpression increased migratory potential and glutamate uptake in these cells. Our results imply that modulation of SOX gene expression may change the functional properties of astrocytes, which holds promise for the discovery of potential therapeutic targets in the development of novel strategies for tissue regeneration and recovery.
PB  - MDPI
T2  - Biomedicines
T1  - The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes
IS  - 4
SP  - 796
VL  - 12
DO  - 10.3390/biomedicines12040796
ER  - 

@article{
author = "Balint, Vanda and Perić, Mina and Dačić, Sanja and Stanisavljević Ninković, Danijela and Marjanović, Jelena and Popović, Jelena and Stevanović, Milena and Lazić, Andrijana",
year = "2024",
abstract = "Astrocytes are the main homeostatic cells in the central nervous system, with the unique ability to transform from quiescent into a reactive state in response to pathological conditions by reacquiring some precursor properties. This process is known as reactive astrogliosis, a compensatory response that mediates tissue damage and recovery. Although it is well known that SOX transcription factors drive the expression of phenotype-specific genetic programs during neurodevelopment, their roles in mature astrocytes have not been studied extensively. We focused on the transcription factors SOX2 and SOX9, shown to be re-expressed in reactive astrocytes, in order to study the reactivation-related functional properties of astrocytes mediated by those proteins. We performed an initial screening of SOX2 and SOX9 expression after sensorimotor cortex ablation injury in rats and conducted gain-of-function studies in vitro using astrocytes derived from the human NT2/D1 cell line. Our results revealed the direct involvement of SOX2 in the reacquisition of proliferation in mature NT2/D1-derived astrocytes, while SOX9 overexpression increased migratory potential and glutamate uptake in these cells. Our results imply that modulation of SOX gene expression may change the functional properties of astrocytes, which holds promise for the discovery of potential therapeutic targets in the development of novel strategies for tissue regeneration and recovery.",
publisher = "MDPI",
journal = "Biomedicines",
title = "The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes",
number = "4",
pages = "796",
volume = "12",
doi = "10.3390/biomedicines12040796"
}

Balint, V., Perić, M., Dačić, S., Stanisavljević Ninković, D., Marjanović, J., Popović, J., Stevanović, M.,& Lazić, A.. (2024). The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes. in Biomedicines
MDPI., 12(4), 796.
https://doi.org/10.3390/biomedicines12040796

Balint V, Perić M, Dačić S, Stanisavljević Ninković D, Marjanović J, Popović J, Stevanović M, Lazić A. The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes. in Biomedicines. 2024;12(4):796.
doi:10.3390/biomedicines12040796 .

Balint, Vanda, Perić, Mina, Dačić, Sanja, Stanisavljević Ninković, Danijela, Marjanović, Jelena, Popović, Jelena, Stevanović, Milena, Lazić, Andrijana, "The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes" in Biomedicines, 12, no. 4 (2024):796,
https://doi.org/10.3390/biomedicines12040796 . .

TY  - CONF
AU  - Balint, Vanda
AU  - Stanisavljević-Ninković, Danijela
AU  - Lazić, Stefan
AU  - Kovačević-Grujičić, Nataša
AU  - Perić, Mina
AU  - Pejić, Jelena
AU  - Mojsin, Marija
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2185
AB  - Astrocytes are the main homeostatic cells in the brain with important roles both in
physiological and pathological conditions. They have a unique ability to become
reactivated in response to different types of brain pathologies, which serves as a
compensatory response that modulates tissue damage and recovery. Also, senescent
astrocytes have profound implications in age-related neurodegenerative disorders. The
molecular mechanisms underlying astrocyte reactivation and senescence are still not
well understood. To investigate the roles of SOX2 and SOX9 transcription factors and
miR-21 in these phenotypic alternations of astroglia, astrocytes derived from NT2/D1
cell line (NT2/A) were used as a model system. Western blot analyses showed that the
expression of both SOX2 and SOX9 decreases during the maturation of NT2/A and
they are re-expressed upon in vitro induced injury. Further modulation of the SOX2
and SOX9 expression will reveal their roles in the regulation of astrocytes
reactivation. Down-regulation of mir-21 in both immature and mature NT2/A by
using the antisense technology, induced the decline in cell proliferation revealed by
Ki67 proliferation marker. Also the premature cellular senescence was induced as
indicated by increase in SA-ß-gal activity and the expression of p21 and p53.
Additionally, in silico analysis predicted many of the genes, previously shown to be
upregulated in senescent astrocytes, as miR-21 targets.
Clarifying the roles of SOX genes and miRNAs in astrocyte reactivation and
senescence would contribute to better understanding of the functions of these cells at
the molecular level, which holds promise for development of new therapeutic
strategies.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of the Serbian Neuroscience Society
T1  - The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells
EP  - 99
SP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2185
ER  - 

@conference{
author = "Balint, Vanda and Stanisavljević-Ninković, Danijela and Lazić, Stefan and Kovačević-Grujičić, Nataša and Perić, Mina and Pejić, Jelena and Mojsin, Marija and Stevanović, Milena and Lazić, Andrijana",
year = "2023",
abstract = "Astrocytes are the main homeostatic cells in the brain with important roles both in
physiological and pathological conditions. They have a unique ability to become
reactivated in response to different types of brain pathologies, which serves as a
compensatory response that modulates tissue damage and recovery. Also, senescent
astrocytes have profound implications in age-related neurodegenerative disorders. The
molecular mechanisms underlying astrocyte reactivation and senescence are still not
well understood. To investigate the roles of SOX2 and SOX9 transcription factors and
miR-21 in these phenotypic alternations of astroglia, astrocytes derived from NT2/D1
cell line (NT2/A) were used as a model system. Western blot analyses showed that the
expression of both SOX2 and SOX9 decreases during the maturation of NT2/A and
they are re-expressed upon in vitro induced injury. Further modulation of the SOX2
and SOX9 expression will reveal their roles in the regulation of astrocytes
reactivation. Down-regulation of mir-21 in both immature and mature NT2/A by
using the antisense technology, induced the decline in cell proliferation revealed by
Ki67 proliferation marker. Also the premature cellular senescence was induced as
indicated by increase in SA-ß-gal activity and the expression of p21 and p53.
Additionally, in silico analysis predicted many of the genes, previously shown to be
upregulated in senescent astrocytes, as miR-21 targets.
Clarifying the roles of SOX genes and miRNAs in astrocyte reactivation and
senescence would contribute to better understanding of the functions of these cells at
the molecular level, which holds promise for development of new therapeutic
strategies.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of the Serbian Neuroscience Society",
title = "The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells",
pages = "99-99",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2185"
}

Balint, V., Stanisavljević-Ninković, D., Lazić, S., Kovačević-Grujičić, N., Perić, M., Pejić, J., Mojsin, M., Stevanović, M.,& Lazić, A.. (2023). The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells. in 8th Congress of the Serbian Neuroscience Society
Belgrade : Serbian Neuroscience Society., 99-99.
https://hdl.handle.net/21.15107/rcub_imagine_2185

Balint V, Stanisavljević-Ninković D, Lazić S, Kovačević-Grujičić N, Perić M, Pejić J, Mojsin M, Stevanović M, Lazić A. The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells. in 8th Congress of the Serbian Neuroscience Society. 2023;:99-99.
https://hdl.handle.net/21.15107/rcub_imagine_2185 .

Balint, Vanda, Stanisavljević-Ninković, Danijela, Lazić, Stefan, Kovačević-Grujičić, Nataša, Perić, Mina, Pejić, Jelena, Mojsin, Marija, Stevanović, Milena, Lazić, Andrijana, "The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells" in 8th Congress of the Serbian Neuroscience Society (2023):99-99,
https://hdl.handle.net/21.15107/rcub_imagine_2185 .

TY  - CONF
AU  - Bojić, Luka
AU  - Schwirtlich, Marija
AU  - Lazić, Stefan
AU  - Stanisavljević Ninković, Danijela
AU  - Balint, Vanda
AU  - Stevanović, Milena
AU  - Milivojević, Milena
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2133
AB  - Introduction: Prolonged exposure to sunlight, has a harmful effect on skin cells encompassing reduced
viability, morphological changes, and altered gene expression. The two most prevalent types ofskin cancer,squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), arise from malignant transformation
of keratinocytes. UV radiation, among other factors, serves as the primary cause of these tumors. Previous data hasshown that changesin different SOX genes expression in these cancer types correlates with
disease progression, suggesting their role as oncogenes/tumor suppressors. The presented work is focused on examining the impact of UVB radiation on the expression of SOX2 and SOX9 genesin HaCaT cells
derived from human keratinocytes.
Methods: Using a custom-made UV solarsimulator for the irradiation of HaCaT cells with 150 mJ/cm2 or
300 mJ/cm2
, we analyzed SOX2 and SOX9 gene expression. In order to determine the protective effects
of quercetin, anti-inflammatory bioflavonoid, we treated irradiated HaCaT with quercetin, and analyzed
SOX gene expression.
Results: Our resultsindicate that UVB radiation induces a dose dependent decrease of SOX2 expression
while expression of SOX9 was increased at the dose of 150 mJ/cm2 in HaCaT. Treatment of cells with
quercetin increased the expression of both SOX2 and SOX9 genesin HaCaT cellsfollowing UVB radiation
at both doses compared to irradiated cells.
Conclusions: Further research is needed to understand the molecular mechanisms and significance of
SOX2 and SOX9 in UVB-induced cellular responses, in the context of nonmelanoma cancers with potential implications for targeted therapeutic strategies for nonmelanoma cancers
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro
EP  - 143
SP  - 143
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2133
ER  - 

@conference{
author = "Bojić, Luka and Schwirtlich, Marija and Lazić, Stefan and Stanisavljević Ninković, Danijela and Balint, Vanda and Stevanović, Milena and Milivojević, Milena",
year = "2023",
abstract = "Introduction: Prolonged exposure to sunlight, has a harmful effect on skin cells encompassing reduced
viability, morphological changes, and altered gene expression. The two most prevalent types ofskin cancer,squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), arise from malignant transformation
of keratinocytes. UV radiation, among other factors, serves as the primary cause of these tumors. Previous data hasshown that changesin different SOX genes expression in these cancer types correlates with
disease progression, suggesting their role as oncogenes/tumor suppressors. The presented work is focused on examining the impact of UVB radiation on the expression of SOX2 and SOX9 genesin HaCaT cells
derived from human keratinocytes.
Methods: Using a custom-made UV solarsimulator for the irradiation of HaCaT cells with 150 mJ/cm2 or
300 mJ/cm2
, we analyzed SOX2 and SOX9 gene expression. In order to determine the protective effects
of quercetin, anti-inflammatory bioflavonoid, we treated irradiated HaCaT with quercetin, and analyzed
SOX gene expression.
Results: Our resultsindicate that UVB radiation induces a dose dependent decrease of SOX2 expression
while expression of SOX9 was increased at the dose of 150 mJ/cm2 in HaCaT. Treatment of cells with
quercetin increased the expression of both SOX2 and SOX9 genesin HaCaT cellsfollowing UVB radiation
at both doses compared to irradiated cells.
Conclusions: Further research is needed to understand the molecular mechanisms and significance of
SOX2 and SOX9 in UVB-induced cellular responses, in the context of nonmelanoma cancers with potential implications for targeted therapeutic strategies for nonmelanoma cancers",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro",
pages = "143-143",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2133"
}

Bojić, L., Schwirtlich, M., Lazić, S., Stanisavljević Ninković, D., Balint, V., Stevanović, M.,& Milivojević, M.. (2023). The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 143-143.
https://hdl.handle.net/21.15107/rcub_imagine_2133

Bojić L, Schwirtlich M, Lazić S, Stanisavljević Ninković D, Balint V, Stevanović M, Milivojević M. The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:143-143.
https://hdl.handle.net/21.15107/rcub_imagine_2133 .

Bojić, Luka, Schwirtlich, Marija, Lazić, Stefan, Stanisavljević Ninković, Danijela, Balint, Vanda, Stevanović, Milena, Milivojević, Milena, "The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):143-143,
https://hdl.handle.net/21.15107/rcub_imagine_2133 .

TY  - CONF
AU  - Krstić, Aleksandra
AU  - Pavić, Aleksandar
AU  - Balint, Vanda
AU  - Lazić, Stefan
AU  - Avdović, Edina
AU  - Marković, Zoran
AU  - Pejić, Jelena
AU  - Stevanović, Milena
AU  - Petrović, Isidora
PY  - 2022
UR  - https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1866
AB  - Pancreatic carcinoma represents one of the most lethal malignant diseases in the world although some
progress has been made in treating the disease in the past decades. Current multi-agent treatment options
have improved the overall survival of patients, but more effective treatment strategies are still needed. In this
paper we have characterized anticancer potential of coumarin-palladium(II) complex against pancreatic
carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were
assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented
results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being
effective at micromolar concentrations (0.5 M). Treatments induced apoptosis, increased BAX/BCL-2 ratio
and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in
pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma
xenografts resulted in significant reduction of tumor mass, while did not provoke any adverse toxic effects
including hepatotoxicity. Presented results indicate the great potential of tested compound and the
perspective of its further development towards pancreatic cancer therapy.
C3  - RAD International concerence on radiation in various fields of research
T1  - Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells
IS  - Spring Edition
SP  - 34
DO  - 10.21175/rad.spr.abstr.book.2022.9.3
ER  - 

@conference{
author = "Krstić, Aleksandra and Pavić, Aleksandar and Balint, Vanda and Lazić, Stefan and Avdović, Edina and Marković, Zoran and Pejić, Jelena and Stevanović, Milena and Petrović, Isidora",
year = "2022",
abstract = "Pancreatic carcinoma represents one of the most lethal malignant diseases in the world although some
progress has been made in treating the disease in the past decades. Current multi-agent treatment options
have improved the overall survival of patients, but more effective treatment strategies are still needed. In this
paper we have characterized anticancer potential of coumarin-palladium(II) complex against pancreatic
carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were
assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented
results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being
effective at micromolar concentrations (0.5 M). Treatments induced apoptosis, increased BAX/BCL-2 ratio
and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in
pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma
xenografts resulted in significant reduction of tumor mass, while did not provoke any adverse toxic effects
including hepatotoxicity. Presented results indicate the great potential of tested compound and the
perspective of its further development towards pancreatic cancer therapy.",
journal = "RAD International concerence on radiation in various fields of research",
title = "Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells",
number = "Spring Edition",
pages = "34",
doi = "10.21175/rad.spr.abstr.book.2022.9.3"
}

Krstić, A., Pavić, A., Balint, V., Lazić, S., Avdović, E., Marković, Z., Pejić, J., Stevanović, M.,& Petrović, I.. (2022). Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells. in RAD International concerence on radiation in various fields of research(Spring Edition), 34.
https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3

Krstić A, Pavić A, Balint V, Lazić S, Avdović E, Marković Z, Pejić J, Stevanović M, Petrović I. Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells. in RAD International concerence on radiation in various fields of research. 2022;(Spring Edition):34.
doi:10.21175/rad.spr.abstr.book.2022.9.3 .

Krstić, Aleksandra, Pavić, Aleksandar, Balint, Vanda, Lazić, Stefan, Avdović, Edina, Marković, Zoran, Pejić, Jelena, Stevanović, Milena, Petrović, Isidora, "Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells" in RAD International concerence on radiation in various fields of research, no. Spring Edition (2022):34,
https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3 . .

TY  - CONF
AU  - Balint, Vanda
AU  - Stanisavljević Ninković, Danijela
AU  - Anastasov, Nataša
AU  - Lazić, Stefan
AU  - Kovačević-Grujičić, Nataša
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
AU  - Krstić, Aleksandra
AU  - Pejić, Jelena
PY  - 2022
UR  - https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1864
AB  - Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical,
metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of
senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular
mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have
shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms.
Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link
between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21
in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1
cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense
technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence
hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescenceassociated
β-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously
shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken
together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our
knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes.
Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic
strategies based on miRNA manipulation could prevent senescence and may improve the physiological
outcome.
C3  - RAD International concerence on radiation in various fields of research
T1  - Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes
IS  - Spring Edition
SP  - 90
DO  - 10.21175/rad.spr.abstr.book.2022.22.1
ER  - 

@conference{
author = "Balint, Vanda and Stanisavljević Ninković, Danijela and Anastasov, Nataša and Lazić, Stefan and Kovačević-Grujičić, Nataša and Stevanović, Milena and Lazić, Andrijana and Krstić, Aleksandra and Pejić, Jelena",
year = "2022",
abstract = "Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical,
metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of
senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular
mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have
shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms.
Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link
between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21
in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1
cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense
technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence
hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescenceassociated
β-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously
shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken
together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our
knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes.
Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic
strategies based on miRNA manipulation could prevent senescence and may improve the physiological
outcome.",
journal = "RAD International concerence on radiation in various fields of research",
title = "Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes",
number = "Spring Edition",
pages = "90",
doi = "10.21175/rad.spr.abstr.book.2022.22.1"
}

Balint, V., Stanisavljević Ninković, D., Anastasov, N., Lazić, S., Kovačević-Grujičić, N., Stevanović, M., Lazić, A., Krstić, A.,& Pejić, J.. (2022). Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes. in RAD International concerence on radiation in various fields of research(Spring Edition), 90.
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1

Balint V, Stanisavljević Ninković D, Anastasov N, Lazić S, Kovačević-Grujičić N, Stevanović M, Lazić A, Krstić A, Pejić J. Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes. in RAD International concerence on radiation in various fields of research. 2022;(Spring Edition):90.
doi:10.21175/rad.spr.abstr.book.2022.22.1 .

Balint, Vanda, Stanisavljević Ninković, Danijela, Anastasov, Nataša, Lazić, Stefan, Kovačević-Grujičić, Nataša, Stevanović, Milena, Lazić, Andrijana, Krstić, Aleksandra, Pejić, Jelena, "Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes" in RAD International concerence on radiation in various fields of research, no. Spring Edition (2022):90,
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1 . .

TY  - JOUR
AU  - Lazić, Andrijana
AU  - Balint, Vanda
AU  - Stanisavljević Ninković, Danijela
AU  - Perić, Mina
AU  - Stevanović, Milena
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1602
AB  - Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies
IS  - 9
VL  - 23
DO  - 10.3390/ijms23094995
ER  - 

@article{
author = "Lazić, Andrijana and Balint, Vanda and Stanisavljević Ninković, Danijela and Perić, Mina and Stevanović, Milena",
year = "2022",
abstract = "Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies",
number = "9",
volume = "23",
doi = "10.3390/ijms23094995"
}

Lazić, A., Balint, V., Stanisavljević Ninković, D., Perić, M.,& Stevanović, M.. (2022). Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies. in International Journal of Molecular Sciences
MDPI, Basel., 23(9).
https://doi.org/10.3390/ijms23094995

Lazić A, Balint V, Stanisavljević Ninković D, Perić M, Stevanović M. Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies. in International Journal of Molecular Sciences. 2022;23(9).
doi:10.3390/ijms23094995 .

Lazić, Andrijana, Balint, Vanda, Stanisavljević Ninković, Danijela, Perić, Mina, Stevanović, Milena, "Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies" in International Journal of Molecular Sciences, 23, no. 9 (2022),
https://doi.org/10.3390/ijms23094995 . .

TY  - JOUR
AU  - Balint, Vanda
AU  - Stanisavljević Ninković, Danijela
AU  - Anastasov, Nataša
AU  - Lazić, Stefan
AU  - Kovačević Grujičić, Nataša
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1472
AB  - Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical, metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms. Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21 in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1 cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescence-associated beta-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes. Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic strategies based on miRNA manipulation could prevent senescence and may improve the physiological outcome.
PB  - Maik Nauka/Interperiodica/Springer, New York
T2  - Biochemistry-Moscow
T1  - Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes
EP  - 1445
IS  - 11
SP  - 1434
VL  - 86
DO  - 10.1134/S0006297921110079
ER  - 

@article{
author = "Balint, Vanda and Stanisavljević Ninković, Danijela and Anastasov, Nataša and Lazić, Stefan and Kovačević Grujičić, Nataša and Stevanović, Milena and Lazić, Andrijana",
year = "2021",
abstract = "Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical, metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms. Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21 in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1 cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescence-associated beta-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes. Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic strategies based on miRNA manipulation could prevent senescence and may improve the physiological outcome.",
publisher = "Maik Nauka/Interperiodica/Springer, New York",
journal = "Biochemistry-Moscow",
title = "Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes",
pages = "1445-1434",
number = "11",
volume = "86",
doi = "10.1134/S0006297921110079"
}

Balint, V., Stanisavljević Ninković, D., Anastasov, N., Lazić, S., Kovačević Grujičić, N., Stevanović, M.,& Lazić, A.. (2021). Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes. in Biochemistry-Moscow
Maik Nauka/Interperiodica/Springer, New York., 86(11), 1434-1445.
https://doi.org/10.1134/S0006297921110079

Balint V, Stanisavljević Ninković D, Anastasov N, Lazić S, Kovačević Grujičić N, Stevanović M, Lazić A. Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes. in Biochemistry-Moscow. 2021;86(11):1434-1445.
doi:10.1134/S0006297921110079 .

Balint, Vanda, Stanisavljević Ninković, Danijela, Anastasov, Nataša, Lazić, Stefan, Kovačević Grujičić, Nataša, Stevanović, Milena, Lazić, Andrijana, "Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes" in Biochemistry-Moscow, 86, no. 11 (2021):1434-1445,
https://doi.org/10.1134/S0006297921110079 . .