TY  - CHAP
AU  - Đorđević, Marija
AU  - Dinić, Svetlana
AU  - Mihailović, Mirjana
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Arambašić Jovanović, Jelena
AU  - Vidaković, Melita
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2252
AB  - U osnovi dijabetesa se nalazi smanjen broj beta ćelija endokrinog pankreasa, njihovo poremećeno
funkcionisanje ili gubitak identiteta u procesu dediferencijacije. Jedna od aktuelnih strategija za potencijalnu
primenu u terapiji dijabetesa je i direktno ćelijsko reprogramiranje kojim bi se nadomestio
nedostatak funkcionalnih beta ćelija i insulina u organizmu. Ovaj pravac u istraživanjima podrazumeva
transdiferencijaciju somatskih ćelija poreklom iz različitih organa u ćelije koje proizvode insulin
kroz modulaciju ekspresije transkripcionih faktora koji su ključni za održavanje ćelijskog identiteta.
U ovom poglavlju biće predstavljena aktuelna istraživanja koja podrazumevaju ćelijsko reprogramiranje
uz pomoć novih sintetičkih alata koji imaju ulogu da dirigovano uvode izmene u (epi)genom sa
posebnim osvrtom na CRISPR/Cas9 sistem i njegove modifikacije. Alfa ćelije endokrinog pankreasa
predstavljaju atraktivan izvor ćelija za potencijalnu terapiju dijabetesa zato što dele zajedničko poreklo
sa beta ćelijama, imaju visok nivo plastičnosti kao i zbog bliske pozicioniranosti koja obezbeđuje
prirodno okruženje pogodno za njihovo preživljavanje. Jedna od nedavnih studija je podrazumevala
upotrebu EpiCRISPR sistema za ciljano uvođenje metilacije u okviru promotora gena Arx u alfa ćelijama
pankreasa miša u cilju njihove transdiferencijacije. Uvedene izmene na nivou epigenoma su dovele
do pokretanja ekspresije insulina u alfa ćelijama pankreasa miša i inicijacije procesa njihove
transdiferencijacije u ćelije koje produkuju insulin.
AB  - Diabetes is caused by a reduced number of beta cell mass, impaired functioning, or loss of beta cell
identity through the dedifferentiation process. Direct cellular reprogramming is one of the current
strategies in the potential diabetes therapy, which would replace the lack of functional beta cells and
regulate insulin levels. This research approach involves the transdifferentiation of somatic cells from
several organs into insulin-producing cells by modulating the expression pattern of transcription factors
responsible for maintaining cellular identity. This chapter will present current research involving
cellular reprogramming using the new synthetic tools that have ability to introduce targeted (epi)genetic
modifications. Special attention will be paid to the CRISPR/Cas9 system and its modifications.
Pancreatic alpha cells represent an attractive cell source for potential diabetes therapy because they
share a common origin with beta cells, have a high level of plasticity, and provide a natural environment
suitable for cell survival because of their close placement. One of the recent studies involved the
use of the EpiCRISPR system for targeted DNA methylation within the Arx gene promoter in murine
pancreatic alpha cells. The introduced changes at the epigenetic level led to the initiation of insulin
expression in the alpha cells of the mouse pancreas and the initiation of their transdifferentiation process
into insulin-producing cells.
PB  - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
T2  - Trendovi u molekularnoj Biologiji
T1  - Uloga ciljanih (epi)genetičkih modifikacija u potencijalnoj terapiji dijabetesa
T1  - The role of targeted (epi)genetic modifications in potential diabetes therapy
EP  - 150
IS  - 3
SP  - 138
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2252
ER  - 

@inbook{
author = "Đorđević, Marija and Dinić, Svetlana and Mihailović, Mirjana and Uskoković, Aleksandra and Grdović, Nevena and Arambašić Jovanović, Jelena and Vidaković, Melita",
year = "2023",
abstract = "U osnovi dijabetesa se nalazi smanjen broj beta ćelija endokrinog pankreasa, njihovo poremećeno
funkcionisanje ili gubitak identiteta u procesu dediferencijacije. Jedna od aktuelnih strategija za potencijalnu
primenu u terapiji dijabetesa je i direktno ćelijsko reprogramiranje kojim bi se nadomestio
nedostatak funkcionalnih beta ćelija i insulina u organizmu. Ovaj pravac u istraživanjima podrazumeva
transdiferencijaciju somatskih ćelija poreklom iz različitih organa u ćelije koje proizvode insulin
kroz modulaciju ekspresije transkripcionih faktora koji su ključni za održavanje ćelijskog identiteta.
U ovom poglavlju biće predstavljena aktuelna istraživanja koja podrazumevaju ćelijsko reprogramiranje
uz pomoć novih sintetičkih alata koji imaju ulogu da dirigovano uvode izmene u (epi)genom sa
posebnim osvrtom na CRISPR/Cas9 sistem i njegove modifikacije. Alfa ćelije endokrinog pankreasa
predstavljaju atraktivan izvor ćelija za potencijalnu terapiju dijabetesa zato što dele zajedničko poreklo
sa beta ćelijama, imaju visok nivo plastičnosti kao i zbog bliske pozicioniranosti koja obezbeđuje
prirodno okruženje pogodno za njihovo preživljavanje. Jedna od nedavnih studija je podrazumevala
upotrebu EpiCRISPR sistema za ciljano uvođenje metilacije u okviru promotora gena Arx u alfa ćelijama
pankreasa miša u cilju njihove transdiferencijacije. Uvedene izmene na nivou epigenoma su dovele
do pokretanja ekspresije insulina u alfa ćelijama pankreasa miša i inicijacije procesa njihove
transdiferencijacije u ćelije koje produkuju insulin., Diabetes is caused by a reduced number of beta cell mass, impaired functioning, or loss of beta cell
identity through the dedifferentiation process. Direct cellular reprogramming is one of the current
strategies in the potential diabetes therapy, which would replace the lack of functional beta cells and
regulate insulin levels. This research approach involves the transdifferentiation of somatic cells from
several organs into insulin-producing cells by modulating the expression pattern of transcription factors
responsible for maintaining cellular identity. This chapter will present current research involving
cellular reprogramming using the new synthetic tools that have ability to introduce targeted (epi)genetic
modifications. Special attention will be paid to the CRISPR/Cas9 system and its modifications.
Pancreatic alpha cells represent an attractive cell source for potential diabetes therapy because they
share a common origin with beta cells, have a high level of plasticity, and provide a natural environment
suitable for cell survival because of their close placement. One of the recent studies involved the
use of the EpiCRISPR system for targeted DNA methylation within the Arx gene promoter in murine
pancreatic alpha cells. The introduced changes at the epigenetic level led to the initiation of insulin
expression in the alpha cells of the mouse pancreas and the initiation of their transdifferentiation process
into insulin-producing cells.",
publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo",
journal = "Trendovi u molekularnoj Biologiji",
booktitle = "Uloga ciljanih (epi)genetičkih modifikacija u potencijalnoj terapiji dijabetesa, The role of targeted (epi)genetic modifications in potential diabetes therapy",
pages = "150-138",
number = "3",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2252"
}

Đorđević, M., Dinić, S., Mihailović, M., Uskoković, A., Grdović, N., Arambašić Jovanović, J.,& Vidaković, M.. (2023). Uloga ciljanih (epi)genetičkih modifikacija u potencijalnoj terapiji dijabetesa. in Trendovi u molekularnoj Biologiji
Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo.(3), 138-150.
https://hdl.handle.net/21.15107/rcub_imagine_2252

Đorđević M, Dinić S, Mihailović M, Uskoković A, Grdović N, Arambašić Jovanović J, Vidaković M. Uloga ciljanih (epi)genetičkih modifikacija u potencijalnoj terapiji dijabetesa. in Trendovi u molekularnoj Biologiji. 2023;(3):138-150.
https://hdl.handle.net/21.15107/rcub_imagine_2252 .

Đorđević, Marija, Dinić, Svetlana, Mihailović, Mirjana, Uskoković, Aleksandra, Grdović, Nevena, Arambašić Jovanović, Jelena, Vidaković, Melita, "Uloga ciljanih (epi)genetičkih modifikacija u potencijalnoj terapiji dijabetesa" in Trendovi u molekularnoj Biologiji, no. 3 (2023):138-150,
https://hdl.handle.net/21.15107/rcub_imagine_2252 .

TY  - JOUR
AU  - Mihailović, Mirjana
AU  - Živković, Milica
AU  - Arambasić-Jovanović, Jelena
AU  - Tolinački, Maja
AU  - Sinadinović, Marija
AU  - Rajić, Jovana
AU  - Uskoković, Aleksandra
AU  - Dinić, Svetlana
AU  - Grdović, Nevena
AU  - Golić, Nataša
AU  - Vidaković, Melita
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1039
AB  - The aim of this study was to assess the effect of the probiotic Lactobacillus paraplantarum BGCG11 on the regulatory pathways that underlie the defense responses of the liver and kidney in diabetic rats. Probiotic-treated diabetic rats exhibited decreased hyperglycemia, glycated hemoglobin, triacylglycerols and a reduction in advanced glycation end products of serum proteins. The probiotic treatment adjusted the redox imbalance in the liver and kidney of diabetic rats, reduced the level of DNA damage, increased the activity of the pro-survival Akt kinase, decreased procaspase 3 degradation and lowered the level of inflammatory mediator C/EBP beta. Administration of probiotic to diabetic rats attenuated fibrotic process activated in the liver and kidneys as judged by the increase in E-cadherin and decreases in alpha-smooth muscle actin and fibronectin. In summary, the probiotic administration had an ameliorating effect on diabetes-associated disturbed redox homeostasis, inflammation and fibrosis, which underline the development of diabetic complications.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Functional Foods
T1  - Oral administration of probiotic Lactobacillus paraplantarum BGCG11 attenuates diabetes-induced liver and kidney damage in rats
EP  - 437
SP  - 427
VL  - 38
DO  - 10.1016/j.jff.2017.09.033
ER  - 

@article{
author = "Mihailović, Mirjana and Živković, Milica and Arambasić-Jovanović, Jelena and Tolinački, Maja and Sinadinović, Marija and Rajić, Jovana and Uskoković, Aleksandra and Dinić, Svetlana and Grdović, Nevena and Golić, Nataša and Vidaković, Melita",
year = "2017",
abstract = "The aim of this study was to assess the effect of the probiotic Lactobacillus paraplantarum BGCG11 on the regulatory pathways that underlie the defense responses of the liver and kidney in diabetic rats. Probiotic-treated diabetic rats exhibited decreased hyperglycemia, glycated hemoglobin, triacylglycerols and a reduction in advanced glycation end products of serum proteins. The probiotic treatment adjusted the redox imbalance in the liver and kidney of diabetic rats, reduced the level of DNA damage, increased the activity of the pro-survival Akt kinase, decreased procaspase 3 degradation and lowered the level of inflammatory mediator C/EBP beta. Administration of probiotic to diabetic rats attenuated fibrotic process activated in the liver and kidneys as judged by the increase in E-cadherin and decreases in alpha-smooth muscle actin and fibronectin. In summary, the probiotic administration had an ameliorating effect on diabetes-associated disturbed redox homeostasis, inflammation and fibrosis, which underline the development of diabetic complications.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Functional Foods",
title = "Oral administration of probiotic Lactobacillus paraplantarum BGCG11 attenuates diabetes-induced liver and kidney damage in rats",
pages = "437-427",
volume = "38",
doi = "10.1016/j.jff.2017.09.033"
}

Mihailović, M., Živković, M., Arambasić-Jovanović, J., Tolinački, M., Sinadinović, M., Rajić, J., Uskoković, A., Dinić, S., Grdović, N., Golić, N.,& Vidaković, M.. (2017). Oral administration of probiotic Lactobacillus paraplantarum BGCG11 attenuates diabetes-induced liver and kidney damage in rats. in Journal of Functional Foods
Elsevier Science Bv, Amsterdam., 38, 427-437.
https://doi.org/10.1016/j.jff.2017.09.033

Mihailović M, Živković M, Arambasić-Jovanović J, Tolinački M, Sinadinović M, Rajić J, Uskoković A, Dinić S, Grdović N, Golić N, Vidaković M. Oral administration of probiotic Lactobacillus paraplantarum BGCG11 attenuates diabetes-induced liver and kidney damage in rats. in Journal of Functional Foods. 2017;38:427-437.
doi:10.1016/j.jff.2017.09.033 .

Mihailović, Mirjana, Živković, Milica, Arambasić-Jovanović, Jelena, Tolinački, Maja, Sinadinović, Marija, Rajić, Jovana, Uskoković, Aleksandra, Dinić, Svetlana, Grdović, Nevena, Golić, Nataša, Vidaković, Melita, "Oral administration of probiotic Lactobacillus paraplantarum BGCG11 attenuates diabetes-induced liver and kidney damage in rats" in Journal of Functional Foods, 38 (2017):427-437,
https://doi.org/10.1016/j.jff.2017.09.033 . .

TY  - JOUR
AU  - Marković, Jelena
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Karan-Đurašević, Teodora
AU  - Uskoković, Aleksandra
AU  - Arambasić, Jelena
AU  - Mihailović, Mirjana
AU  - Pavlović, Sonja
AU  - Poznanović, Goran
AU  - Vidaković, Melita
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/661
AB  - Despite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12) transcription. The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ)-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells
IS  - 3
VL  - 8
DO  - 10.1371/journal.pone.0059679
ER  - 

@article{
author = "Marković, Jelena and Grdović, Nevena and Dinić, Svetlana and Karan-Đurašević, Teodora and Uskoković, Aleksandra and Arambasić, Jelena and Mihailović, Mirjana and Pavlović, Sonja and Poznanović, Goran and Vidaković, Melita",
year = "2013",
abstract = "Despite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12) transcription. The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ)-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells",
number = "3",
volume = "8",
doi = "10.1371/journal.pone.0059679"
}

Marković, J., Grdović, N., Dinić, S., Karan-Đurašević, T., Uskoković, A., Arambasić, J., Mihailović, M., Pavlović, S., Poznanović, G.,& Vidaković, M.. (2013). PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells. in PLoS One
Public Library Science, San Francisco., 8(3).
https://doi.org/10.1371/journal.pone.0059679

Marković J, Grdović N, Dinić S, Karan-Đurašević T, Uskoković A, Arambasić J, Mihailović M, Pavlović S, Poznanović G, Vidaković M. PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells. in PLoS One. 2013;8(3).
doi:10.1371/journal.pone.0059679 .

Marković, Jelena, Grdović, Nevena, Dinić, Svetlana, Karan-Đurašević, Teodora, Uskoković, Aleksandra, Arambasić, Jelena, Mihailović, Mirjana, Pavlović, Sonja, Poznanović, Goran, Vidaković, Melita, "PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells" in PLoS One, 8, no. 3 (2013),
https://doi.org/10.1371/journal.pone.0059679 . .