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  - CONF
AU  - Živković, Milica
AU  - Soković Bajić, Svetlana
AU  - Tolinački, Maja
AU  - Brdarić, Emilija
AU  - Đokić, Jelena
AU  - Popović, Nikola
AU  - Rajić, Jovana
AU  - Đorđević, Marija
AU  - Golić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1395
AB  - Objective Our previous studies with Lactobacillus paraplantarum BGCG11 probiotictreatment of diabetic rats showed decreased hyperglycemia and ameliorating effect on diabetes-associated damage of liver and kidneys. Hence, the aim of this study was to reveal the effects of BGCG11 probiotic on gut microbiota composition and monitoring the insulin production in pancreatic islets in diabetic rats. Methods Experiments were performed on albino Wistar rats divided into four groups: ND – non-diabetic control, D – streptozotocin (STZ) induced diabetes; P/D/P – BGCG11 pretreatment; D/P – BGCG11 treatment. The rats were orally administered with BGCG11, one week before (P/D/P) and after the STZ injection, for four weeks (P/D/P and D/P). Total DNA was isolated from all fecal samples and rDNA amplicons were analyzed by DGGE and 16S rDNA genes sequencing. For immunohistochemical analysis, slides were stained with anti-insulin antibody and secondary antibody coupled with horseradish peroxidase. Results The results revealed the higher diversity of gut microbiota in D/P group comparing to D group, as well as the higher prevalence of Flintibacter butyricus (the major butyric producer), Acetatifactor muris (present in obese mouse) and Eisenbergiella massiliensis (found in obese woman), while the lipolytic bacterium Aestuariispira insulae was more prevalent in diabetic rats. In both, P/D/P and D/P group, increased number of positive immunoreactions of β-cells for anti-insulin antibodies was displayed in compare to D group with islet atrophy. Conclusions The results of this study suggest that the positive effect of BGCG11 on STZ-induced diabetes in rats could be annotated to its protective role on the integrity of fecal microbiota.
PB  - Wolters Kluwer Health
C3  - Journal of Clinical Gastroenterology
T1  - The Analysis of Fecal Microbiota and Insulin Production in Diabetic Rats After Oral Administration of Probiotic Lactobacillus Paraplantarum BGCG11
EP  - S12
SP  - S11
VL  - 54
DO  - 10.1097/MCG.0000000000001292
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1395
ER  - 

@conference{
author = "Živković, Milica and Soković Bajić, Svetlana and Tolinački, Maja and Brdarić, Emilija and Đokić, Jelena and Popović, Nikola and Rajić, Jovana and Đorđević, Marija and Golić, Nataša",
year = "2020",
abstract = "Objective Our previous studies with Lactobacillus paraplantarum BGCG11 probiotictreatment of diabetic rats showed decreased hyperglycemia and ameliorating effect on diabetes-associated damage of liver and kidneys. Hence, the aim of this study was to reveal the effects of BGCG11 probiotic on gut microbiota composition and monitoring the insulin production in pancreatic islets in diabetic rats. Methods Experiments were performed on albino Wistar rats divided into four groups: ND – non-diabetic control, D – streptozotocin (STZ) induced diabetes; P/D/P – BGCG11 pretreatment; D/P – BGCG11 treatment. The rats were orally administered with BGCG11, one week before (P/D/P) and after the STZ injection, for four weeks (P/D/P and D/P). Total DNA was isolated from all fecal samples and rDNA amplicons were analyzed by DGGE and 16S rDNA genes sequencing. For immunohistochemical analysis, slides were stained with anti-insulin antibody and secondary antibody coupled with horseradish peroxidase. Results The results revealed the higher diversity of gut microbiota in D/P group comparing to D group, as well as the higher prevalence of Flintibacter butyricus (the major butyric producer), Acetatifactor muris (present in obese mouse) and Eisenbergiella massiliensis (found in obese woman), while the lipolytic bacterium Aestuariispira insulae was more prevalent in diabetic rats. In both, P/D/P and D/P group, increased number of positive immunoreactions of β-cells for anti-insulin antibodies was displayed in compare to D group with islet atrophy. Conclusions The results of this study suggest that the positive effect of BGCG11 on STZ-induced diabetes in rats could be annotated to its protective role on the integrity of fecal microbiota.",
publisher = "Wolters Kluwer Health",
journal = "Journal of Clinical Gastroenterology",
title = "The Analysis of Fecal Microbiota and Insulin Production in Diabetic Rats After Oral Administration of Probiotic Lactobacillus Paraplantarum BGCG11",
pages = "S12-S11",
volume = "54",
doi = "10.1097/MCG.0000000000001292",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1395"
}

Živković, M., Soković Bajić, S., Tolinački, M., Brdarić, E., Đokić, J., Popović, N., Rajić, J., Đorđević, M.,& Golić, N.. (2020). The Analysis of Fecal Microbiota and Insulin Production in Diabetic Rats After Oral Administration of Probiotic Lactobacillus Paraplantarum BGCG11. in Journal of Clinical Gastroenterology
Wolters Kluwer Health., 54, S11-S12.
https://doi.org/10.1097/MCG.0000000000001292
https://hdl.handle.net/21.15107/rcub_imagine_1395

Živković M, Soković Bajić S, Tolinački M, Brdarić E, Đokić J, Popović N, Rajić J, Đorđević M, Golić N. The Analysis of Fecal Microbiota and Insulin Production in Diabetic Rats After Oral Administration of Probiotic Lactobacillus Paraplantarum BGCG11. in Journal of Clinical Gastroenterology. 2020;54:S11-S12.
doi:10.1097/MCG.0000000000001292
https://hdl.handle.net/21.15107/rcub_imagine_1395 .

Živković, Milica, Soković Bajić, Svetlana, Tolinački, Maja, Brdarić, Emilija, Đokić, Jelena, Popović, Nikola, Rajić, Jovana, Đorđević, Marija, Golić, Nataša, "The Analysis of Fecal Microbiota and Insulin Production in Diabetic Rats After Oral Administration of Probiotic Lactobacillus Paraplantarum BGCG11" in Journal of Clinical Gastroenterology, 54 (2020):S11-S12,
https://doi.org/10.1097/MCG.0000000000001292 .,
https://hdl.handle.net/21.15107/rcub_imagine_1395 .