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  - http://radar.ibiss.bg.ac.rs/handle/123456789/6484
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 po-
tencijalnu 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 podrazu-
meva transdiferencijaciju somatskih ćelija poreklom iz različitih organa u ćelije koje proizvode insu-
lin kroz modulaciju ekspresije transkripcionih faktora koji su ključni za održavanje ćelijskog identiteta.
U ovom poglavlju biće predstavljena aktuelna istraživanja koja podrazumevaju ćelijsko reprogrami-
ranje 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 pore-
klo 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 ćeli-
jama pankreasa miša u cilju njihove transdiferencijacije. Uvedene izmene na nivou epigenoma su do-
vele 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 fac-
tors 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)ge-
netic 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 environ-
ment 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 pro-
cess into insulin-producing cells.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
T2  - Trends in Molecular Biology
T1  - Uloga ciljanih (epi)genetičkih modifikacija u potencijalnoj terapiji dijabetesa
T1  - The role of targeted (epi)genetic modifications in potential diabetes therapy
IS  - 3
SP  - 138
EP  - 150
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6484
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 po-
tencijalnu 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 podrazu-
meva transdiferencijaciju somatskih ćelija poreklom iz različitih organa u ćelije koje proizvode insu-
lin kroz modulaciju ekspresije transkripcionih faktora koji su ključni za održavanje ćelijskog identiteta.
U ovom poglavlju biće predstavljena aktuelna istraživanja koja podrazumevaju ćelijsko reprogrami-
ranje 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 pore-
klo 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 ćeli-
jama pankreasa miša u cilju njihove transdiferencijacije. Uvedene izmene na nivou epigenoma su do-
vele 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 fac-
tors 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)ge-
netic 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 environ-
ment 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 pro-
cess into insulin-producing cells.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Trends in Molecular Biology",
booktitle = "Uloga ciljanih (epi)genetičkih modifikacija u potencijalnoj terapiji dijabetesa, The role of targeted (epi)genetic modifications in potential diabetes therapy",
number = "3",
pages = "138-150",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6484"
}

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 Trends in Molecular Biology
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade.(3), 138-150.
https://hdl.handle.net/21.15107/rcub_ibiss_6484

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 Trends in Molecular Biology. 2023;(3):138-150.
https://hdl.handle.net/21.15107/rcub_ibiss_6484 .

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 Trends in Molecular Biology, no. 3 (2023):138-150,
https://hdl.handle.net/21.15107/rcub_ibiss_6484 .

TY  - CONF
AU  - Uskoković, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6308
AB  - Epigenetic editing has a powerful potential to direct reprogramming of cellular phenotype that can be used in disease modeling. The reprogramming of cells from different origin into insulin-producing cells could provide a solution for restoring functional beta cell mass in diabetic patients. We used CRISPR/dCas9-based epigenetic tool for targeted hypermethylation of Arx promoter and its subsequent suppression in mouse pancreatic α cell line. By epigenetic silencing of Arx we successfully triggered a direct, transient switch of pancreatic α- to insulin-producing cells obtaining approximately 1% of transiently transfected cells which were able to produce 35% more insulin than Mock transfected α cells. As a future perspective we intend to address the potential use of epigenetic editing tool as a pre-therapeutic approach in triple-negative breast cancers (TNBCs) with unknown mutational signature of BRCA1. The BRCA1methylation (BRCAness) as a predictor for response to therapeutics such as PARPi would allow direct TNBC treatment without previous screening for BRCA1 mutations. The main objective will be to induce BRCAness by suppressing BRCA1 expression in TNBC cells via targeted DNA methylation of BRCA1 promoter using the synthetic epigenetic editing tool. This approach would enable the faster decision toward the use of newest medicaments to increase cells’ apoptosis and cancer cell diminishment.
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  - Epigenetic editing as a potential therapeutic tool for the treatment of noncommunicable diseases
SP  - 132
EP  - 132
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6308
ER  - 

@conference{
author = "Uskoković, Aleksandra",
year = "2023",
abstract = "Epigenetic editing has a powerful potential to direct reprogramming of cellular phenotype that can be used in disease modeling. The reprogramming of cells from different origin into insulin-producing cells could provide a solution for restoring functional beta cell mass in diabetic patients. We used CRISPR/dCas9-based epigenetic tool for targeted hypermethylation of Arx promoter and its subsequent suppression in mouse pancreatic α cell line. By epigenetic silencing of Arx we successfully triggered a direct, transient switch of pancreatic α- to insulin-producing cells obtaining approximately 1% of transiently transfected cells which were able to produce 35% more insulin than Mock transfected α cells. As a future perspective we intend to address the potential use of epigenetic editing tool as a pre-therapeutic approach in triple-negative breast cancers (TNBCs) with unknown mutational signature of BRCA1. The BRCA1methylation (BRCAness) as a predictor for response to therapeutics such as PARPi would allow direct TNBC treatment without previous screening for BRCA1 mutations. The main objective will be to induce BRCAness by suppressing BRCA1 expression in TNBC cells via targeted DNA methylation of BRCA1 promoter using the synthetic epigenetic editing tool. This approach would enable the faster decision toward the use of newest medicaments to increase cells’ apoptosis and cancer cell diminishment.",
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 = "Epigenetic editing as a potential therapeutic tool for the treatment of noncommunicable diseases",
pages = "132-132",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6308"
}

Uskoković, A.. (2023). Epigenetic editing as a potential therapeutic tool for the treatment of noncommunicable diseases. 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., 132-132.
https://hdl.handle.net/21.15107/rcub_ibiss_6308

Uskoković A. Epigenetic editing as a potential therapeutic tool for the treatment of noncommunicable diseases. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:132-132.
https://hdl.handle.net/21.15107/rcub_ibiss_6308 .

Uskoković, Aleksandra, "Epigenetic editing as a potential therapeutic tool for the treatment of noncommunicable diseases" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):132-132,
https://hdl.handle.net/21.15107/rcub_ibiss_6308 .

TY  - CONF
AU  - Đorđević, Marija
AU  - Feuerstein-Akgoz, Clarissa
AU  - Arambašić Jovanović, Jelena
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Sarić, Ana
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Mihailović, Mirjana
AU  - Gerhauser, Clarissa
AU  - Jurkowski, Tomasz
AU  - Vidaković, Melita
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6307
AB  - Introduction: The Aristaless-related homeobox (Arx) gene plays a key role in the development and maintaining pancreatic alpha cell phenotype, and as such represents an excellent target for alpha cell identity change towards insulin-producing cells. Therefore, this cell switch and increase in beta cell mass could be of potential use in diabetes management.
Methods: On the fifth day after transient transfection with dCas9-Dnmt3a3L-KRAB construct and four gRNAs targeting Arx promoter, αTC1-6 were sorted to collect GFP-positive (transfected) cells (EpiC). The mRNA-seq libraries were pooled in equimolar amounts and sequenced in a single end-setting on the Illumina NextSeq 500 High output machine with 75 bases long reads. KEGG pathway overrepresentation analysis was performed using an application on all significantly up- or downregulated genes using default settings.
Results: Directed induction of DNA methylation on the Arx gene promoter reduces its expression and causes the up-regulation of 357 genes, while 266 genes were down-regulated in EpiC compared to Mock transfected cells. The KEGG pathways analysis of biological processes confirmed several biological pathways associated with genes differentially expressed in EpiC vs. Mock transfected cells at the 5th posttransfection day (pval ≤ 0.05). As the most significant, up-regulated pathways we found Type II diabetes, Insulin secretion, Longevity regulation pathways. As significant, down-regulated pathways pop-up Fatty acid metabolism and PPAR signaling pathway.
Conclusion: Reduction of ArxmRNA level is sufficient to initiate the transdifferentiation process of alpha cells into insulin-producing cells by triggering several biological pathways tight related to insulin secretion and function.
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  - Changes in up and down regulated gene expression after transient suppression of Arx gene in pancreatic alphaTC1-6 cell line
SP  - 151
EP  - 151
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6307
ER  - 

@conference{
author = "Đorđević, Marija and Feuerstein-Akgoz, Clarissa and Arambašić Jovanović, Jelena and Tolić, Anja and Rajić, Jovana and Sarić, Ana and Grdović, Nevena and Dinić, Svetlana and Uskoković, Aleksandra and Mihailović, Mirjana and Gerhauser, Clarissa and Jurkowski, Tomasz and Vidaković, Melita",
year = "2023",
abstract = "Introduction: The Aristaless-related homeobox (Arx) gene plays a key role in the development and maintaining pancreatic alpha cell phenotype, and as such represents an excellent target for alpha cell identity change towards insulin-producing cells. Therefore, this cell switch and increase in beta cell mass could be of potential use in diabetes management.
Methods: On the fifth day after transient transfection with dCas9-Dnmt3a3L-KRAB construct and four gRNAs targeting Arx promoter, αTC1-6 were sorted to collect GFP-positive (transfected) cells (EpiC). The mRNA-seq libraries were pooled in equimolar amounts and sequenced in a single end-setting on the Illumina NextSeq 500 High output machine with 75 bases long reads. KEGG pathway overrepresentation analysis was performed using an application on all significantly up- or downregulated genes using default settings.
Results: Directed induction of DNA methylation on the Arx gene promoter reduces its expression and causes the up-regulation of 357 genes, while 266 genes were down-regulated in EpiC compared to Mock transfected cells. The KEGG pathways analysis of biological processes confirmed several biological pathways associated with genes differentially expressed in EpiC vs. Mock transfected cells at the 5th posttransfection day (pval ≤ 0.05). As the most significant, up-regulated pathways we found Type II diabetes, Insulin secretion, Longevity regulation pathways. As significant, down-regulated pathways pop-up Fatty acid metabolism and PPAR signaling pathway.
Conclusion: Reduction of ArxmRNA level is sufficient to initiate the transdifferentiation process of alpha cells into insulin-producing cells by triggering several biological pathways tight related to insulin secretion and function.",
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 = "Changes in up and down regulated gene expression after transient suppression of Arx gene in pancreatic alphaTC1-6 cell line",
pages = "151-151",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6307"
}

Đorđević, M., Feuerstein-Akgoz, C., Arambašić Jovanović, J., Tolić, A., Rajić, J., Sarić, A., Grdović, N., Dinić, S., Uskoković, A., Mihailović, M., Gerhauser, C., Jurkowski, T.,& Vidaković, M.. (2023). Changes in up and down regulated gene expression after transient suppression of Arx gene in pancreatic alphaTC1-6 cell line. 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., 151-151.
https://hdl.handle.net/21.15107/rcub_ibiss_6307

Đorđević M, Feuerstein-Akgoz C, Arambašić Jovanović J, Tolić A, Rajić J, Sarić A, Grdović N, Dinić S, Uskoković A, Mihailović M, Gerhauser C, Jurkowski T, Vidaković M. Changes in up and down regulated gene expression after transient suppression of Arx gene in pancreatic alphaTC1-6 cell line. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:151-151.
https://hdl.handle.net/21.15107/rcub_ibiss_6307 .

Đorđević, Marija, Feuerstein-Akgoz, Clarissa, Arambašić Jovanović, Jelena, Tolić, Anja, Rajić, Jovana, Sarić, Ana, Grdović, Nevena, Dinić, Svetlana, Uskoković, Aleksandra, Mihailović, Mirjana, Gerhauser, Clarissa, Jurkowski, Tomasz, Vidaković, Melita, "Changes in up and down regulated gene expression after transient suppression of Arx gene in pancreatic alphaTC1-6 cell line" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):151-151,
https://hdl.handle.net/21.15107/rcub_ibiss_6307 .

TY  - CONF
AU  - Sarić, Ana
AU  - Rajić, Jovana
AU  - Tolić, Anja
AU  - Đorđević, Marija
AU  - Grdović, Nevena
AU  - Uskoković, Aleksandra
AU  - Dinić, Svetlana
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Vidaković, Melita
AU  - Dučić, Tanja
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6304
AB  - Introduction: DNA methylation is a major regulator of transcriptional activity and alongside other epigenetic modifications it introduces specific level of chromatin complexity. Fourier transform infrared (FTIR) spectroscopy is a rapid, non-destructive, and label-free technique for identifying subtle changes in all bio-macromolecules, and it has been used as a method of choice for studying DNA conformation. The present study was designed to explore the use of synchrotron-based FTIR spectroscopy to monitor the subtle changes on molecular level regarding the DNA methylation status of cytosine in the whole genome.
Methods: For FTIR-based DNA methylation analysis in situ, DNA-HALO samples were prepared using slightly modified methodology for nuclear HALO preparations where DNA-HALOs are liberated of any protein residues but preserve higher order chromatin structure.
Results: Using FTIR spectroscopy we analysed and compared methylation profiles of isolated genomic DNA and DNA-HALO samples. DNA-HALO structure shows more distinct peaks in fingerprint region of spectra. DNA-HALO structure is more accurate for detecting bonds in unmemthylated cytosine as specific infrared peaks are defined as vibrations of bonds in unmethylated cytosine at 1151 cm-1 and 1357 cm-1. The ratio of integrated area under the peak 1151 cm-1 over integrated area under the peak that represents PO2-backbone vibrations can be used to assess level of unmethylated cytosine and thus methylation rate in the DNA-HALO samples.
Conclusion: This study demonstrates potential of FTIR spectroscopy to detect DNA methylation in DNA-HALO samples more precisely compared to classical DNA extraction procedure that yield unstructured whole genomic DNA.
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  - Methylation profile analysis of Of DNA-HALO structure by synchrotron-based FTIR spectroscopy
SP  - 68
EP  - 68
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6304
ER  - 

@conference{
author = "Sarić, Ana and Rajić, Jovana and Tolić, Anja and Đorđević, Marija and Grdović, Nevena and Uskoković, Aleksandra and Dinić, Svetlana and Arambašić Jovanović, Jelena and Mihailović, Mirjana and Vidaković, Melita and Dučić, Tanja",
year = "2023",
abstract = "Introduction: DNA methylation is a major regulator of transcriptional activity and alongside other epigenetic modifications it introduces specific level of chromatin complexity. Fourier transform infrared (FTIR) spectroscopy is a rapid, non-destructive, and label-free technique for identifying subtle changes in all bio-macromolecules, and it has been used as a method of choice for studying DNA conformation. The present study was designed to explore the use of synchrotron-based FTIR spectroscopy to monitor the subtle changes on molecular level regarding the DNA methylation status of cytosine in the whole genome.
Methods: For FTIR-based DNA methylation analysis in situ, DNA-HALO samples were prepared using slightly modified methodology for nuclear HALO preparations where DNA-HALOs are liberated of any protein residues but preserve higher order chromatin structure.
Results: Using FTIR spectroscopy we analysed and compared methylation profiles of isolated genomic DNA and DNA-HALO samples. DNA-HALO structure shows more distinct peaks in fingerprint region of spectra. DNA-HALO structure is more accurate for detecting bonds in unmemthylated cytosine as specific infrared peaks are defined as vibrations of bonds in unmethylated cytosine at 1151 cm-1 and 1357 cm-1. The ratio of integrated area under the peak 1151 cm-1 over integrated area under the peak that represents PO2-backbone vibrations can be used to assess level of unmethylated cytosine and thus methylation rate in the DNA-HALO samples.
Conclusion: This study demonstrates potential of FTIR spectroscopy to detect DNA methylation in DNA-HALO samples more precisely compared to classical DNA extraction procedure that yield unstructured whole genomic DNA.",
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 = "Methylation profile analysis of Of DNA-HALO structure by synchrotron-based FTIR spectroscopy",
pages = "68-68",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6304"
}

Sarić, A., Rajić, J., Tolić, A., Đorđević, M., Grdović, N., Uskoković, A., Dinić, S., Arambašić Jovanović, J., Mihailović, M., Vidaković, M.,& Dučić, T.. (2023). Methylation profile analysis of Of DNA-HALO structure by synchrotron-based FTIR spectroscopy. 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., 68-68.
https://hdl.handle.net/21.15107/rcub_ibiss_6304

Sarić A, Rajić J, Tolić A, Đorđević M, Grdović N, Uskoković A, Dinić S, Arambašić Jovanović J, Mihailović M, Vidaković M, Dučić T. Methylation profile analysis of Of DNA-HALO structure by synchrotron-based FTIR spectroscopy. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:68-68.
https://hdl.handle.net/21.15107/rcub_ibiss_6304 .

Sarić, Ana, Rajić, Jovana, Tolić, Anja, Đorđević, Marija, Grdović, Nevena, Uskoković, Aleksandra, Dinić, Svetlana, Arambašić Jovanović, Jelena, Mihailović, Mirjana, Vidaković, Melita, Dučić, Tanja, "Methylation profile analysis of Of DNA-HALO structure by synchrotron-based FTIR spectroscopy" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):68-68,
https://hdl.handle.net/21.15107/rcub_ibiss_6304 .

TY  - DATA
AU  - Đorđević, Marija
AU  - Stepper, Peter
AU  - Feuerstein-Akgoz, Clarissa
AU  - Gerhauser, Clarissa
AU  - Paunović, Verica
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Mihailović, Mirjana
AU  - Jurkowska, Renata
AU  - Jurkowski, Tomasz
AU  - Arambašić Jovanović, Jelena
AU  - Vidaković, Melita
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5669
AB  - Figure 1. UCSC genome browser views of murine Arx gene’s DNA methylation sites in the pancreas and other tissues. If compared with other tissues, Arx gene in pancreatic tissue (young and old) exhibits low DNA methylation. CpG island was shown as a green box. Table 1. Targeted sequences for sgRNAs. Table 2. Primers used for RT-qPCR. Table 3. Primers used for HRM. Table 4. Touchdown PCR program for amplification of bisulfite converted DNA, starting at 55 °C. Table 5. Primers for NGS library preparation. Table 6. Antibodies used for Immunoblot analysis (IBA) and Immunocytochemistry (ICC). Table 7. Primers for PCR reaction after ChIP.
PB  - Frontiers Media S.A.
T2  - Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms
T1  - Supplementary Material for Đorđević M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunović V, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Jurkowska RZ, Jurkowski TP, Jovanović JA, Vidaković M. EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells. Front Endocrinol (Lausanne). 2023;14:1134478.
VL  - 14
SP  - 1134478
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5669
ER  - 

@misc{
author = "Đorđević, Marija and Stepper, Peter and Feuerstein-Akgoz, Clarissa and Gerhauser, Clarissa and Paunović, Verica and Tolić, Anja and Rajić, Jovana and Dinić, Svetlana and Uskoković, Aleksandra and Grdović, Nevena and Mihailović, Mirjana and Jurkowska, Renata and Jurkowski, Tomasz and Arambašić Jovanović, Jelena and Vidaković, Melita",
year = "2023",
abstract = "Figure 1. UCSC genome browser views of murine Arx gene’s DNA methylation sites in the pancreas and other tissues. If compared with other tissues, Arx gene in pancreatic tissue (young and old) exhibits low DNA methylation. CpG island was shown as a green box. Table 1. Targeted sequences for sgRNAs. Table 2. Primers used for RT-qPCR. Table 3. Primers used for HRM. Table 4. Touchdown PCR program for amplification of bisulfite converted DNA, starting at 55 °C. Table 5. Primers for NGS library preparation. Table 6. Antibodies used for Immunoblot analysis (IBA) and Immunocytochemistry (ICC). Table 7. Primers for PCR reaction after ChIP.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms",
title = "Supplementary Material for Đorđević M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunović V, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Jurkowska RZ, Jurkowski TP, Jovanović JA, Vidaković M. EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells. Front Endocrinol (Lausanne). 2023;14:1134478.",
volume = "14",
pages = "1134478",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5669"
}

Đorđević, M., Stepper, P., Feuerstein-Akgoz, C., Gerhauser, C., Paunović, V., Tolić, A., Rajić, J., Dinić, S., Uskoković, A., Grdović, N., Mihailović, M., Jurkowska, R., Jurkowski, T., Arambašić Jovanović, J.,& Vidaković, M.. (2023). Supplementary Material for Đorđević M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunović V, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Jurkowska RZ, Jurkowski TP, Jovanović JA, Vidaković M. EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells. Front Endocrinol (Lausanne). 2023;14:1134478.. in Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms
Frontiers Media S.A.., 14, 1134478.
https://hdl.handle.net/21.15107/rcub_ibiss_5669

Đorđević M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunović V, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Jurkowska R, Jurkowski T, Arambašić Jovanović J, Vidaković M. Supplementary Material for Đorđević M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunović V, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Jurkowska RZ, Jurkowski TP, Jovanović JA, Vidaković M. EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells. Front Endocrinol (Lausanne). 2023;14:1134478.. in Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms. 2023;14:1134478.
https://hdl.handle.net/21.15107/rcub_ibiss_5669 .

Đorđević, Marija, Stepper, Peter, Feuerstein-Akgoz, Clarissa, Gerhauser, Clarissa, Paunović, Verica, Tolić, Anja, Rajić, Jovana, Dinić, Svetlana, Uskoković, Aleksandra, Grdović, Nevena, Mihailović, Mirjana, Jurkowska, Renata, Jurkowski, Tomasz, Arambašić Jovanović, Jelena, Vidaković, Melita, "Supplementary Material for Đorđević M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunović V, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Jurkowska RZ, Jurkowski TP, Jovanović JA, Vidaković M. EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells. Front Endocrinol (Lausanne). 2023;14:1134478." in Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms, 14 (2023):1134478,
https://hdl.handle.net/21.15107/rcub_ibiss_5669 .

TY  - JOUR
AU  - Đorđević, Marija
AU  - Stepper, Peter
AU  - Feuerstein-Akgoz, Clarissa
AU  - Gerhauser, Clarissa
AU  - Paunović, Verica
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Mihailović, Mirjana
AU  - Jurkowska, Renata
AU  - Jurkowski, Tomasz
AU  - Arambašić Jovanović, Jelena
AU  - Vidaković, Melita
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5507
AB  - Introduction: Beta cell dysfunction by loss of beta cell identity, dedifferentiation, and the presence of polyhormonal cells are main characteristics of diabetes. The straightforward strategy for curing diabetes implies reestablishment of pancreatic beta cell function by beta cell replacement therapy. Aristaless-related homeobox (Arx) gene encodes protein which plays an important role in the development of pancreatic alpha cells and is a main target for changing alpha cell identity.

Results: In this study we used CRISPR/dCas9-based epigenetic tools for targeted hypermethylation of Arx gene promoter and its subsequent suppression in mouse pancreatic αTC1-6 cell line. Bisulfite sequencing and methylation profiling revealed that the dCas9-Dnmt3a3L-KRAB single chain fusion constructs (EpiCRISPR) was the most efficient. Epigenetic silencing of Arx expression was accompanied by an increase in transcription of the insulin gene (Ins2) mRNA on 5th and 7th post-transfection day, quantified by both RT-qPCR and RNA-seq. Insulin production and secretion was determined by immunocytochemistry and ELISA assay, respectively. Eventually, we were able to induce switch of approximately 1% of transiently transfected cells which were able to produce 35% more insulin than Mock transfected alpha cells.

Conclusion: In conclusion, we successfully triggered a direct, transient switch of pancreatic alpha to insulin-producing cells opening a future research on promising therapeutic avenue for diabetes management.
PB  - Frontiers Media S.A.
T2  - Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms
T1  - EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells
VL  - 14
DO  - 10.3389/fendo.2023.1134478
SP  - 1134478
ER  - 

@article{
author = "Đorđević, Marija and Stepper, Peter and Feuerstein-Akgoz, Clarissa and Gerhauser, Clarissa and Paunović, Verica and Tolić, Anja and Rajić, Jovana and Dinić, Svetlana and Uskoković, Aleksandra and Grdović, Nevena and Mihailović, Mirjana and Jurkowska, Renata and Jurkowski, Tomasz and Arambašić Jovanović, Jelena and Vidaković, Melita",
year = "2023",
abstract = "Introduction: Beta cell dysfunction by loss of beta cell identity, dedifferentiation, and the presence of polyhormonal cells are main characteristics of diabetes. The straightforward strategy for curing diabetes implies reestablishment of pancreatic beta cell function by beta cell replacement therapy. Aristaless-related homeobox (Arx) gene encodes protein which plays an important role in the development of pancreatic alpha cells and is a main target for changing alpha cell identity.

Results: In this study we used CRISPR/dCas9-based epigenetic tools for targeted hypermethylation of Arx gene promoter and its subsequent suppression in mouse pancreatic αTC1-6 cell line. Bisulfite sequencing and methylation profiling revealed that the dCas9-Dnmt3a3L-KRAB single chain fusion constructs (EpiCRISPR) was the most efficient. Epigenetic silencing of Arx expression was accompanied by an increase in transcription of the insulin gene (Ins2) mRNA on 5th and 7th post-transfection day, quantified by both RT-qPCR and RNA-seq. Insulin production and secretion was determined by immunocytochemistry and ELISA assay, respectively. Eventually, we were able to induce switch of approximately 1% of transiently transfected cells which were able to produce 35% more insulin than Mock transfected alpha cells.

Conclusion: In conclusion, we successfully triggered a direct, transient switch of pancreatic alpha to insulin-producing cells opening a future research on promising therapeutic avenue for diabetes management.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms",
title = "EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells",
volume = "14",
doi = "10.3389/fendo.2023.1134478",
pages = "1134478"
}

Đorđević, M., Stepper, P., Feuerstein-Akgoz, C., Gerhauser, C., Paunović, V., Tolić, A., Rajić, J., Dinić, S., Uskoković, A., Grdović, N., Mihailović, M., Jurkowska, R., Jurkowski, T., Arambašić Jovanović, J.,& Vidaković, M.. (2023). EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells. in Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms
Frontiers Media S.A.., 14, 1134478.
https://doi.org/10.3389/fendo.2023.1134478

Đorđević M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunović V, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Jurkowska R, Jurkowski T, Arambašić Jovanović J, Vidaković M. EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells. in Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms. 2023;14:1134478.
doi:10.3389/fendo.2023.1134478 .

Đorđević, Marija, Stepper, Peter, Feuerstein-Akgoz, Clarissa, Gerhauser, Clarissa, Paunović, Verica, Tolić, Anja, Rajić, Jovana, Dinić, Svetlana, Uskoković, Aleksandra, Grdović, Nevena, Mihailović, Mirjana, Jurkowska, Renata, Jurkowski, Tomasz, Arambašić Jovanović, Jelena, Vidaković, Melita, "EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells" in Frontiers in Endocrinology, Section - Diabetes: Molecular Mechanisms, 14 (2023):1134478,
https://doi.org/10.3389/fendo.2023.1134478 . .

TY  - JOUR
AU  - Jovanović, Aleksandra
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Grdović, Nevena
AU  - Vidaković, Melita
AU  - Mihailović, Mirjana
PY  - 2022
UR  - https://jepm.tfzv.ues.rs.ba/article/190
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6446
AB  - The aim of the present study was the characterization of silymarin and silibinin li-
posomes
via
determination of encapsulation efficiency, particle size, polydispersity
index (PDI), zeta potential, mobility, and conductivity, as well as storage stability
during 28 days at 4ºC and stability after UV irradiation. Encapsulation efficiencies
of silymarin and silibinin were 92.05±1.41% and 87.86±2.06%, respectively. Par-
ticle size and PDI of the liposomes with silymarin were changed from 3541.3±62.5
nm to 2677.0±44.2 nm and from 0.346±0.044 to 0.228±0.036, respectively, dur-
ing the 28-day stability study; particle size and PDI of the liposomes with silibinin
were changed from 2074.7±19.4 nm to 2704.0±35.0 nm and from 0.328±0.030
to 0.456±0.026, respectively. The Zeta potential of the silymarin-loaded liposomes
and silibinin-loaded liposomes was changed from -27.0±0.7 mV to -26.4±0.4 mV
and from -29.4±0.6 mV to -29.0±0.4 mV, respectively. Mobility and conductivity
of the liposomes with silymarin were changed from -2.120±0.057 μmcm/Vs to -
2.067±0.028 μmcm/Vs and from 0.017±0.005 mS/cm to 0.009±0.004 mS/cm,
respectively.  Mobility and conductivity of the liposomal particles with silibinin
were changed from -2.307±0.053 μmcm/Vs to -2.110±0.033 μmcm/Vs and from
0.018±0.003 mS/cm to 0.060±0.001 mS/cm, respectively. UV irradiation did not
affect particle size and PDI of all liposomes, but it caused a decrease in zeta po-
tential: -23.9±0.8 mV for silymarin and -24.5±0.7 mV for silibinin, in mobility: -
1.874±0.064 μmcm/Vs for silymarin and -1.920±0.057 μmcm/Vs for silibinin, and
in conductivity: 0.014±0.001 mS/cm for silymarin and 0.007±0.003 mS/cm for
silibinin. Overall, the obtained results qualify liposomes to be used as silymarin and
silibinin carriers for application in functional foods and pharmaceutical products.
PB  - Faculty of Technology, University of East Sarajevo
T2  - Journal of Engineering and Processing Management
T1  - The characterization of silymarin and silibinin liposomes
IS  - 2
VL  - 14
DO  - 10.7251/JEPM2202040j
SP  - 40
EP  - 45
ER  - 

@article{
author = "Jovanović, Aleksandra and Dinić, Svetlana and Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Grdović, Nevena and Vidaković, Melita and Mihailović, Mirjana",
year = "2022",
abstract = "The aim of the present study was the characterization of silymarin and silibinin li-
posomes
via
determination of encapsulation efficiency, particle size, polydispersity
index (PDI), zeta potential, mobility, and conductivity, as well as storage stability
during 28 days at 4ºC and stability after UV irradiation. Encapsulation efficiencies
of silymarin and silibinin were 92.05±1.41% and 87.86±2.06%, respectively. Par-
ticle size and PDI of the liposomes with silymarin were changed from 3541.3±62.5
nm to 2677.0±44.2 nm and from 0.346±0.044 to 0.228±0.036, respectively, dur-
ing the 28-day stability study; particle size and PDI of the liposomes with silibinin
were changed from 2074.7±19.4 nm to 2704.0±35.0 nm and from 0.328±0.030
to 0.456±0.026, respectively. The Zeta potential of the silymarin-loaded liposomes
and silibinin-loaded liposomes was changed from -27.0±0.7 mV to -26.4±0.4 mV
and from -29.4±0.6 mV to -29.0±0.4 mV, respectively. Mobility and conductivity
of the liposomes with silymarin were changed from -2.120±0.057 μmcm/Vs to -
2.067±0.028 μmcm/Vs and from 0.017±0.005 mS/cm to 0.009±0.004 mS/cm,
respectively.  Mobility and conductivity of the liposomal particles with silibinin
were changed from -2.307±0.053 μmcm/Vs to -2.110±0.033 μmcm/Vs and from
0.018±0.003 mS/cm to 0.060±0.001 mS/cm, respectively. UV irradiation did not
affect particle size and PDI of all liposomes, but it caused a decrease in zeta po-
tential: -23.9±0.8 mV for silymarin and -24.5±0.7 mV for silibinin, in mobility: -
1.874±0.064 μmcm/Vs for silymarin and -1.920±0.057 μmcm/Vs for silibinin, and
in conductivity: 0.014±0.001 mS/cm for silymarin and 0.007±0.003 mS/cm for
silibinin. Overall, the obtained results qualify liposomes to be used as silymarin and
silibinin carriers for application in functional foods and pharmaceutical products.",
publisher = "Faculty of Technology, University of East Sarajevo",
journal = "Journal of Engineering and Processing Management",
title = "The characterization of silymarin and silibinin liposomes",
number = "2",
volume = "14",
doi = "10.7251/JEPM2202040j",
pages = "40-45"
}

Jovanović, A., Dinić, S., Uskoković, A., Arambašić Jovanović, J., Grdović, N., Vidaković, M.,& Mihailović, M.. (2022). The characterization of silymarin and silibinin liposomes. in Journal of Engineering and Processing Management
Faculty of Technology, University of East Sarajevo., 14(2), 40-45.
https://doi.org/10.7251/JEPM2202040j

Jovanović A, Dinić S, Uskoković A, Arambašić Jovanović J, Grdović N, Vidaković M, Mihailović M. The characterization of silymarin and silibinin liposomes. in Journal of Engineering and Processing Management. 2022;14(2):40-45.
doi:10.7251/JEPM2202040j .

Jovanović, Aleksandra, Dinić, Svetlana, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Grdović, Nevena, Vidaković, Melita, Mihailović, Mirjana, "The characterization of silymarin and silibinin liposomes" in Journal of Engineering and Processing Management, 14, no. 2 (2022):40-45,
https://doi.org/10.7251/JEPM2202040j . .

TY  - JOUR
AU  - Dinić, Svetlana
AU  - Arambašić Jovanović, Jelena
AU  - Uskoković, Aleksandra
AU  - Mihailović, Mirjana
AU  - Grdović, Nevena
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Đorđević, Marija
AU  - Vidaković, Melita
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5125
AB  - The biggest drawback of a current diabetes therapy is the treatment of the consequences not the cause of the disease. Regardless of the diabetes type, preservation and recovery of functional pancreatic beta cells stands as the biggest challenge in the treatment of diabetes. Free radicals and oxidative stress are among the major mediators of autoimmune destruction of beta cells in type 1 diabetes (T1D) or beta cell malfunction and death provoked by glucotoxicity and insulin resistance in type 2 diabetes (T2D). Additionally, oxidative stress reduces functionality of beta cells in T2D by stimulating their de-/trans-differentiation through the loss of transcription factors critical for beta cell development, maturity and regeneration. This review summarizes up to date clarified redox-related mechanisms involved in regulating beta cell identity and death, underlining similarities and differences between T1D and T2D. The protective effects of natural antioxidants on the oxidative stress-induced beta cell failure were also discussed. Considering that oxidative stress affects epigenetic regulatory mechanisms involved in the regulation of pancreatic beta cell survival and insulin secretion, this review highlighted huge potential of epigenetic therapy. Special attention was paid on application of the state-of-the-art CRISPR/Cas9 technology, based on targeted epigenome editing with the purpose of changing the differentiation state of different cell types, making them insulin-producing with ability to attenuate diabetes. Clarification of the above-mentioned mechanisms could provide better insight into diabetes etiology and pathogenesis, which would allow development of novel, potentially more efficient therapeutic strategies for the prevention or reversion of beta cell loss.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Endocrinology
T1  - Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management
VL  - 13
DO  - 10.3389/fendo.2022.1006376
SP  - 1006376
ER  - 

@article{
author = "Dinić, Svetlana and Arambašić Jovanović, Jelena and Uskoković, Aleksandra and Mihailović, Mirjana and Grdović, Nevena and Tolić, Anja and Rajić, Jovana and Đorđević, Marija and Vidaković, Melita",
year = "2022",
abstract = "The biggest drawback of a current diabetes therapy is the treatment of the consequences not the cause of the disease. Regardless of the diabetes type, preservation and recovery of functional pancreatic beta cells stands as the biggest challenge in the treatment of diabetes. Free radicals and oxidative stress are among the major mediators of autoimmune destruction of beta cells in type 1 diabetes (T1D) or beta cell malfunction and death provoked by glucotoxicity and insulin resistance in type 2 diabetes (T2D). Additionally, oxidative stress reduces functionality of beta cells in T2D by stimulating their de-/trans-differentiation through the loss of transcription factors critical for beta cell development, maturity and regeneration. This review summarizes up to date clarified redox-related mechanisms involved in regulating beta cell identity and death, underlining similarities and differences between T1D and T2D. The protective effects of natural antioxidants on the oxidative stress-induced beta cell failure were also discussed. Considering that oxidative stress affects epigenetic regulatory mechanisms involved in the regulation of pancreatic beta cell survival and insulin secretion, this review highlighted huge potential of epigenetic therapy. Special attention was paid on application of the state-of-the-art CRISPR/Cas9 technology, based on targeted epigenome editing with the purpose of changing the differentiation state of different cell types, making them insulin-producing with ability to attenuate diabetes. Clarification of the above-mentioned mechanisms could provide better insight into diabetes etiology and pathogenesis, which would allow development of novel, potentially more efficient therapeutic strategies for the prevention or reversion of beta cell loss.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Endocrinology",
title = "Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management",
volume = "13",
doi = "10.3389/fendo.2022.1006376",
pages = "1006376"
}

Dinić, S., Arambašić Jovanović, J., Uskoković, A., Mihailović, M., Grdović, N., Tolić, A., Rajić, J., Đorđević, M.,& Vidaković, M.. (2022). Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management. in Frontiers in Endocrinology
Lausanne: Frontiers Media SA., 13, 1006376.
https://doi.org/10.3389/fendo.2022.1006376

Dinić S, Arambašić Jovanović J, Uskoković A, Mihailović M, Grdović N, Tolić A, Rajić J, Đorđević M, Vidaković M. Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management. in Frontiers in Endocrinology. 2022;13:1006376.
doi:10.3389/fendo.2022.1006376 .

Dinić, Svetlana, Arambašić Jovanović, Jelena, Uskoković, Aleksandra, Mihailović, Mirjana, Grdović, Nevena, Tolić, Anja, Rajić, Jovana, Đorđević, Marija, Vidaković, Melita, "Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management" in Frontiers in Endocrinology, 13 (2022):1006376,
https://doi.org/10.3389/fendo.2022.1006376 . .

TY  - JOUR
AU  - Đorđević, Marija
AU  - Paunović, Verica
AU  - Jovanović Tucović, Maja
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Mihailović, Mirjana
AU  - Marković, Ivanka
AU  - Arambašić Jovanović, Jelena
AU  - Vidaković, Melita
PY  - 2022
UR  - https://www.mdpi.com/2076-3417/12/15/7938
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5102
AB  - An efficient transfection is a crucial step for the introduction of epigenetic modification in host cells, and there is a need for an optimized transfection process for individual model systems separately. Mouse pancreatic αTC1-6 cells, which act as an attractive model system for epigenetic cell reprogramming and diabetes treatment, were transiently transfected with two different transfection methods: the chemical method with polyethyleneimine (PEI) and nucleofection as a physical transfection method. Flow cytometry and fluorescent microscopy examination of GFP expression showed that transfection efficiency was affected by the size of plasmids using both transfection methods. Subsequently, the Cas9 mRNA expression confirmed successful transfection with EpiCRISPR plasmid, whereas the cell physiology remained unchanged. The adjusted nucleofection protocol for αTC1-6 cells transfected with an EpiCRISPR mix of plasmids reached 71.1% of GFP-positive transfected cells on the fifth post-transfection day and proved to be much more efficient than the 3.8% GFP-positive PEI transfected cells. Modifying the protocol, we finally specify CM-156 program and SF 4D-Nucleofector X Solutions for Amaxa™ nucleofection as a method of choice for alpha TC1-6 cell line transfection.
PB  - Basel: MDPI
T2  - Applied Sciences
T1  - Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection
IS  - 15
VL  - 12
DO  - 10.3390/app12157938
SP  - 7938
ER  - 

@article{
author = "Đorđević, Marija and Paunović, Verica and Jovanović Tucović, Maja and Tolić, Anja and Rajić, Jovana and Dinić, Svetlana and Uskoković, Aleksandra and Grdović, Nevena and Mihailović, Mirjana and Marković, Ivanka and Arambašić Jovanović, Jelena and Vidaković, Melita",
year = "2022",
abstract = "An efficient transfection is a crucial step for the introduction of epigenetic modification in host cells, and there is a need for an optimized transfection process for individual model systems separately. Mouse pancreatic αTC1-6 cells, which act as an attractive model system for epigenetic cell reprogramming and diabetes treatment, were transiently transfected with two different transfection methods: the chemical method with polyethyleneimine (PEI) and nucleofection as a physical transfection method. Flow cytometry and fluorescent microscopy examination of GFP expression showed that transfection efficiency was affected by the size of plasmids using both transfection methods. Subsequently, the Cas9 mRNA expression confirmed successful transfection with EpiCRISPR plasmid, whereas the cell physiology remained unchanged. The adjusted nucleofection protocol for αTC1-6 cells transfected with an EpiCRISPR mix of plasmids reached 71.1% of GFP-positive transfected cells on the fifth post-transfection day and proved to be much more efficient than the 3.8% GFP-positive PEI transfected cells. Modifying the protocol, we finally specify CM-156 program and SF 4D-Nucleofector X Solutions for Amaxa™ nucleofection as a method of choice for alpha TC1-6 cell line transfection.",
publisher = "Basel: MDPI",
journal = "Applied Sciences",
title = "Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection",
number = "15",
volume = "12",
doi = "10.3390/app12157938",
pages = "7938"
}

Đorđević, M., Paunović, V., Jovanović Tucović, M., Tolić, A., Rajić, J., Dinić, S., Uskoković, A., Grdović, N., Mihailović, M., Marković, I., Arambašić Jovanović, J.,& Vidaković, M.. (2022). Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection. in Applied Sciences
Basel: MDPI., 12(15), 7938.
https://doi.org/10.3390/app12157938

Đorđević M, Paunović V, Jovanović Tucović M, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Marković I, Arambašić Jovanović J, Vidaković M. Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection. in Applied Sciences. 2022;12(15):7938.
doi:10.3390/app12157938 .

Đorđević, Marija, Paunović, Verica, Jovanović Tucović, Maja, Tolić, Anja, Rajić, Jovana, Dinić, Svetlana, Uskoković, Aleksandra, Grdović, Nevena, Mihailović, Mirjana, Marković, Ivanka, Arambašić Jovanović, Jelena, Vidaković, Melita, "Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection" in Applied Sciences, 12, no. 15 (2022):7938,
https://doi.org/10.3390/app12157938 . .

TY  - JOUR
AU  - Tolić, Anja
AU  - Ravichandran, Mirunalini
AU  - Rajić, Jovana
AU  - Đorđević, Marija
AU  - Đorđević, Miloš
AU  - Dinić, Svetlana
AU  - Grdović, Nevena
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Nestorović, Nataša
AU  - Jurkowski, Tomasz P.
AU  - Uskoković, Aleksandra
AU  - Vidaković, Melita
PY  - 2022
UR  - https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-022-00445-8
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8985375
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4957
AB  - BACKGROUND Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA-the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP-TET interplay. RESULTS Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo. CONCLUSIONS According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine.
PB  - London: BioMed Central Ltd
T2  - Epigenetics & Chromatin
T1  - TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.
IS  - 1
VL  - 15
DO  - 10.1186/s13072-022-00445-8
SP  - 11
ER  - 

@article{
author = "Tolić, Anja and Ravichandran, Mirunalini and Rajić, Jovana and Đorđević, Marija and Đorđević, Miloš and Dinić, Svetlana and Grdović, Nevena and Arambašić Jovanović, Jelena and Mihailović, Mirjana and Nestorović, Nataša and Jurkowski, Tomasz P. and Uskoković, Aleksandra and Vidaković, Melita",
year = "2022",
abstract = "BACKGROUND Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA-the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP-TET interplay. RESULTS Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo. CONCLUSIONS According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine.",
publisher = "London: BioMed Central Ltd",
journal = "Epigenetics & Chromatin",
title = "TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.",
number = "1",
volume = "15",
doi = "10.1186/s13072-022-00445-8",
pages = "11"
}

Tolić, A., Ravichandran, M., Rajić, J., Đorđević, M., Đorđević, M., Dinić, S., Grdović, N., Arambašić Jovanović, J., Mihailović, M., Nestorović, N., Jurkowski, T. P., Uskoković, A.,& Vidaković, M.. (2022). TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.. in Epigenetics & Chromatin
London: BioMed Central Ltd., 15(1), 11.
https://doi.org/10.1186/s13072-022-00445-8

Tolić A, Ravichandran M, Rajić J, Đorđević M, Đorđević M, Dinić S, Grdović N, Arambašić Jovanović J, Mihailović M, Nestorović N, Jurkowski TP, Uskoković A, Vidaković M. TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.. in Epigenetics & Chromatin. 2022;15(1):11.
doi:10.1186/s13072-022-00445-8 .

Tolić, Anja, Ravichandran, Mirunalini, Rajić, Jovana, Đorđević, Marija, Đorđević, Miloš, Dinić, Svetlana, Grdović, Nevena, Arambašić Jovanović, Jelena, Mihailović, Mirjana, Nestorović, Nataša, Jurkowski, Tomasz P., Uskoković, Aleksandra, Vidaković, Melita, "TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation." in Epigenetics & Chromatin, 15, no. 1 (2022):11,
https://doi.org/10.1186/s13072-022-00445-8 . .

TY  - JOUR
AU  - Đorđević, Miloš
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Mihailović, Mirjana
AU  - Arambašić Jovanović, Jelena
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Đorđević, Marija
AU  - Mišić, Danijela
AU  - Šiler, Branislav
AU  - Vidaković, Melita
AU  - Dinić, Svetlana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4782
AB  - The use of medicinal herbs can mitigate oxidative stress-induced diabetic complications and organ failure. This study investigated hepato- and reno-protective effects of methanol extract of Centaurium erythraea Rafn (CEE) in STZ-diabetic rats pre-treated (2 weeks) and/or post-treated (4 weeks) with CEE (orally, 100 mg/kg/day). Both CEE treatments markedly improved liver and kidney functionality in diabetic rats observed as reduced aspartate and alanine aminotransferase activities and decreased creatinine and blood urea nitrogen levels. CEE pre-treatment reduced the level of glycosylated proteins in diabetic liver more efficiently than post-treatment. Lowered levels of lipid peroxidation, DNA damage and protein glutathionylation, elevated ratio of reduced to oxidized glutathione, and mitigated disturbance of antioxidant enzyme activities reflected the antioxidant effect of CEE in diabetic liver and kidney. Although CEE pre-treatment was more effective, the obtained results indicate that both treatments protect the liver and kidney from oxidative damage by boosting the endogenous antioxidant defense system.
PB  - Elsevier
T2  - Journal of Functional Foods
T1  - Centaurium erythraea methanol extract improves the functionality of diabetic liver and kidney by mitigating hyperglycemia-induced oxidative stress
VL  - 90
DO  - 10.1016/j.jff.2022.104975
SP  - 104975
ER  - 

@article{
author = "Đorđević, Miloš and Tolić, Anja and Rajić, Jovana and Mihailović, Mirjana and Arambašić Jovanović, Jelena and Uskoković, Aleksandra and Grdović, Nevena and Đorđević, Marija and Mišić, Danijela and Šiler, Branislav and Vidaković, Melita and Dinić, Svetlana",
year = "2022",
abstract = "The use of medicinal herbs can mitigate oxidative stress-induced diabetic complications and organ failure. This study investigated hepato- and reno-protective effects of methanol extract of Centaurium erythraea Rafn (CEE) in STZ-diabetic rats pre-treated (2 weeks) and/or post-treated (4 weeks) with CEE (orally, 100 mg/kg/day). Both CEE treatments markedly improved liver and kidney functionality in diabetic rats observed as reduced aspartate and alanine aminotransferase activities and decreased creatinine and blood urea nitrogen levels. CEE pre-treatment reduced the level of glycosylated proteins in diabetic liver more efficiently than post-treatment. Lowered levels of lipid peroxidation, DNA damage and protein glutathionylation, elevated ratio of reduced to oxidized glutathione, and mitigated disturbance of antioxidant enzyme activities reflected the antioxidant effect of CEE in diabetic liver and kidney. Although CEE pre-treatment was more effective, the obtained results indicate that both treatments protect the liver and kidney from oxidative damage by boosting the endogenous antioxidant defense system.",
publisher = "Elsevier",
journal = "Journal of Functional Foods",
title = "Centaurium erythraea methanol extract improves the functionality of diabetic liver and kidney by mitigating hyperglycemia-induced oxidative stress",
volume = "90",
doi = "10.1016/j.jff.2022.104975",
pages = "104975"
}

Đorđević, M., Tolić, A., Rajić, J., Mihailović, M., Arambašić Jovanović, J., Uskoković, A., Grdović, N., Đorđević, M., Mišić, D., Šiler, B., Vidaković, M.,& Dinić, S.. (2022). Centaurium erythraea methanol extract improves the functionality of diabetic liver and kidney by mitigating hyperglycemia-induced oxidative stress. in Journal of Functional Foods
Elsevier., 90, 104975.
https://doi.org/10.1016/j.jff.2022.104975

Đorđević M, Tolić A, Rajić J, Mihailović M, Arambašić Jovanović J, Uskoković A, Grdović N, Đorđević M, Mišić D, Šiler B, Vidaković M, Dinić S. Centaurium erythraea methanol extract improves the functionality of diabetic liver and kidney by mitigating hyperglycemia-induced oxidative stress. in Journal of Functional Foods. 2022;90:104975.
doi:10.1016/j.jff.2022.104975 .

Đorđević, Miloš, Tolić, Anja, Rajić, Jovana, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Uskoković, Aleksandra, Grdović, Nevena, Đorđević, Marija, Mišić, Danijela, Šiler, Branislav, Vidaković, Melita, Dinić, Svetlana, "Centaurium erythraea methanol extract improves the functionality of diabetic liver and kidney by mitigating hyperglycemia-induced oxidative stress" in Journal of Functional Foods, 90 (2022):104975,
https://doi.org/10.1016/j.jff.2022.104975 . .

TY  - CONF
AU  - Sarić, Ana
AU  - Rajić, Jovana
AU  - Đorđević, Marija
AU  - Jovanović, Mirna
AU  - Podolski-Renić, Ana
AU  - Pešić, Milica
AU  - Uskoković, Aleksandra
AU  - Tolić, Anja
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5918
AB  - 5-hydroxymethylcytosine (5-hmC) is formed through the oxidation of 5-methylcytosine (5-mC) by the catalytic activity of TET enzymes. It has been proposed to have regulatory functions as an independent epigenetic mark and it might have diagnostic potential as global loss of 5hmC level is commonly observed in cancers.
We have recently shown the inhibitory influence of PARP-1 dependent PARylation on TET1 hydroxylase activity in DNA demethylation. These findings could provide the rationale for using PARP inhibitors in cancers that are characterised by the 5hmC loss, other than cancer where treatment with PARP inhibitors exploited homologues repair (HR) defects on the basis of the synthetic lethality phenomenon. The activating effects of PARP inhibition on TET activity could provide the additional mechanism of action of PARP inhibitors (which are less cytotoxic than standard chemotherapeutic agents) in the treatment of cancers characterised by diminishing levels of 5hmC.
In our study, we have tested the effects of PARP inhibition on 5-hmC levels in non-small cell lung cancer. First, we analysed global levels of 5-hmC in several non-small cell lung cancer cell lines (NCI-H460 sensitive and resistant to doxorubicin, A549, NCI-H661) in comparison to normal fetal lung fibroblast cells MRC-5. Since both slot-blot and confocal microscopy analyses have shown that the A549 cell line has the lowest level of 5-hmC this cell line was selected for further experiments in which we set out to raise DNA hydroxymethylation levels by inhibiting PARP activity. After 72h treatment of A549 cells with PARylation inhibitor niraparib (IC50= 10 μM), we indeed observed an increase in 5-hmC level while 5-mC level did not change. This is a promising start to our investigation of alternative mechanisms of action of PARP inhibition in the treatment of cancers. Through this research, we hope to expand the range of cancer types that would be treated with PARP inhibitors, regardless of the HR status.
PB  - Josep Carreras Leukaemia Research Institute (IJC)
PB  - Innovative Training Network (ITN) INTERCEPT-MDS
C3  - Spetses summer school: Cancer epigenetics: Principles, Applications and Single-cell resolution; 2022 Aug 28 - Sep 3; Spteses Island, Greece
T1  - Influence of PARP inhibition on 5-hmC level in NSCLC
SP  - 116
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5918
ER  - 

@conference{
author = "Sarić, Ana and Rajić, Jovana and Đorđević, Marija and Jovanović, Mirna and Podolski-Renić, Ana and Pešić, Milica and Uskoković, Aleksandra and Tolić, Anja",
year = "2022",
abstract = "5-hydroxymethylcytosine (5-hmC) is formed through the oxidation of 5-methylcytosine (5-mC) by the catalytic activity of TET enzymes. It has been proposed to have regulatory functions as an independent epigenetic mark and it might have diagnostic potential as global loss of 5hmC level is commonly observed in cancers.
We have recently shown the inhibitory influence of PARP-1 dependent PARylation on TET1 hydroxylase activity in DNA demethylation. These findings could provide the rationale for using PARP inhibitors in cancers that are characterised by the 5hmC loss, other than cancer where treatment with PARP inhibitors exploited homologues repair (HR) defects on the basis of the synthetic lethality phenomenon. The activating effects of PARP inhibition on TET activity could provide the additional mechanism of action of PARP inhibitors (which are less cytotoxic than standard chemotherapeutic agents) in the treatment of cancers characterised by diminishing levels of 5hmC.
In our study, we have tested the effects of PARP inhibition on 5-hmC levels in non-small cell lung cancer. First, we analysed global levels of 5-hmC in several non-small cell lung cancer cell lines (NCI-H460 sensitive and resistant to doxorubicin, A549, NCI-H661) in comparison to normal fetal lung fibroblast cells MRC-5. Since both slot-blot and confocal microscopy analyses have shown that the A549 cell line has the lowest level of 5-hmC this cell line was selected for further experiments in which we set out to raise DNA hydroxymethylation levels by inhibiting PARP activity. After 72h treatment of A549 cells with PARylation inhibitor niraparib (IC50= 10 μM), we indeed observed an increase in 5-hmC level while 5-mC level did not change. This is a promising start to our investigation of alternative mechanisms of action of PARP inhibition in the treatment of cancers. Through this research, we hope to expand the range of cancer types that would be treated with PARP inhibitors, regardless of the HR status.",
publisher = "Josep Carreras Leukaemia Research Institute (IJC), Innovative Training Network (ITN) INTERCEPT-MDS",
journal = "Spetses summer school: Cancer epigenetics: Principles, Applications and Single-cell resolution; 2022 Aug 28 - Sep 3; Spteses Island, Greece",
title = "Influence of PARP inhibition on 5-hmC level in NSCLC",
pages = "116",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5918"
}

Sarić, A., Rajić, J., Đorđević, M., Jovanović, M., Podolski-Renić, A., Pešić, M., Uskoković, A.,& Tolić, A.. (2022). Influence of PARP inhibition on 5-hmC level in NSCLC. in Spetses summer school: Cancer epigenetics: Principles, Applications and Single-cell resolution; 2022 Aug 28 - Sep 3; Spteses Island, Greece
Josep Carreras Leukaemia Research Institute (IJC)., 116.
https://hdl.handle.net/21.15107/rcub_ibiss_5918

Sarić A, Rajić J, Đorđević M, Jovanović M, Podolski-Renić A, Pešić M, Uskoković A, Tolić A. Influence of PARP inhibition on 5-hmC level in NSCLC. in Spetses summer school: Cancer epigenetics: Principles, Applications and Single-cell resolution; 2022 Aug 28 - Sep 3; Spteses Island, Greece. 2022;:116.
https://hdl.handle.net/21.15107/rcub_ibiss_5918 .

Sarić, Ana, Rajić, Jovana, Đorđević, Marija, Jovanović, Mirna, Podolski-Renić, Ana, Pešić, Milica, Uskoković, Aleksandra, Tolić, Anja, "Influence of PARP inhibition on 5-hmC level in NSCLC" in Spetses summer school: Cancer epigenetics: Principles, Applications and Single-cell resolution; 2022 Aug 28 - Sep 3; Spteses Island, Greece (2022):116,
https://hdl.handle.net/21.15107/rcub_ibiss_5918 .

TY  - CONF
AU  - Jovanović, Aleksandra
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Grdović, Nevena
AU  - Vidaković, Melita
AU  - Mihailović, Mirjana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5255
AB  - The aim of the present study was the characterization of silymarin and silibinin loaded liposomes via determination of encapsulation efficiency, particle size, polydispersity index (PDI), zeta potential, mobility, and conductivity, as well as storage stability during 28 days at 4ºC and stability after UV irradiation. Encapsulation efficiency of silymarin and silibinin were 92.05±1.41% and 87.86±2.06%, respectively. Particle size and PDI of the liposomes with silymarin were changed from 3541.3±62.5 nm to 2677.0±44.2 nm and from 0.346±0.044 to 0.228±0.036, respectively, during the 28-days stability study; particle size and PDI of the liposomes with silibinin were changed from 2074.7±19.4 nm to 2704.0±35.0 nm and from 0.328±0.030 to 0.456±0.026, respectively. Zeta potential of the silymarin-liposomes and silibinin-liposomes was changed from -27.0±0.7 mV to -26.4±0.4 mV and from -29.4±0.6 mV to -29.0±0.4 mV, respectively. Mobility and conductivity of the liposomes with silymarin were changed from -2.120±0.057 µmcm/Vs to -2.067±0.028 µmcm/Vs and from 0.017±0.005 mS/cm to 0.009±0.004 mS/cm, respectively. Mobility and conductivity of the liposomal particles with silibinin were changed from -2.307±0.053 µmcm/Vs to -2.110±0.033 µmcm/Vs and from 0.018±0.003 mS/cm to 0.060±0.001 mS/cm, respectively. UV irradiation did not affect particle size and PDI of all liposomes, but it caused a decrease in zeta potential: -23.9±0.8 mV for silymarin and -24.5±0.7 mV for silibinin, in mobility: -1.874±0.064 µmcm/Vs for silymarin and -1.920±0.057 µmcm/Vs for silibinin, and in conductivity: 0.014±0.001 mS/cm for silymarin and 0.007±0.003 mS/cm for silibinin. Overall, the obtained results qualify liposomes to be used as silymarin and silibinin carriers for application in functional foods and pharmaceutical products.
PB  - Banja Luka: University of Banja Luka
C3  - XIV conference of chemists, technologists and environmentalists of Republic of Srpska; 2022 Oct 21-2; Banja Luka, Bosnia and Herzegovinia
T1  - The characterisation of silymarin and silibinin loaded liposomes
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5255
ER  - 

@conference{
editor = "Malinović, Borislav",
author = "Jovanović, Aleksandra and Dinić, Svetlana and Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Grdović, Nevena and Vidaković, Melita and Mihailović, Mirjana",
year = "2022",
abstract = "The aim of the present study was the characterization of silymarin and silibinin loaded liposomes via determination of encapsulation efficiency, particle size, polydispersity index (PDI), zeta potential, mobility, and conductivity, as well as storage stability during 28 days at 4ºC and stability after UV irradiation. Encapsulation efficiency of silymarin and silibinin were 92.05±1.41% and 87.86±2.06%, respectively. Particle size and PDI of the liposomes with silymarin were changed from 3541.3±62.5 nm to 2677.0±44.2 nm and from 0.346±0.044 to 0.228±0.036, respectively, during the 28-days stability study; particle size and PDI of the liposomes with silibinin were changed from 2074.7±19.4 nm to 2704.0±35.0 nm and from 0.328±0.030 to 0.456±0.026, respectively. Zeta potential of the silymarin-liposomes and silibinin-liposomes was changed from -27.0±0.7 mV to -26.4±0.4 mV and from -29.4±0.6 mV to -29.0±0.4 mV, respectively. Mobility and conductivity of the liposomes with silymarin were changed from -2.120±0.057 µmcm/Vs to -2.067±0.028 µmcm/Vs and from 0.017±0.005 mS/cm to 0.009±0.004 mS/cm, respectively. Mobility and conductivity of the liposomal particles with silibinin were changed from -2.307±0.053 µmcm/Vs to -2.110±0.033 µmcm/Vs and from 0.018±0.003 mS/cm to 0.060±0.001 mS/cm, respectively. UV irradiation did not affect particle size and PDI of all liposomes, but it caused a decrease in zeta potential: -23.9±0.8 mV for silymarin and -24.5±0.7 mV for silibinin, in mobility: -1.874±0.064 µmcm/Vs for silymarin and -1.920±0.057 µmcm/Vs for silibinin, and in conductivity: 0.014±0.001 mS/cm for silymarin and 0.007±0.003 mS/cm for silibinin. Overall, the obtained results qualify liposomes to be used as silymarin and silibinin carriers for application in functional foods and pharmaceutical products.",
publisher = "Banja Luka: University of Banja Luka",
journal = "XIV conference of chemists, technologists and environmentalists of Republic of Srpska; 2022 Oct 21-2; Banja Luka, Bosnia and Herzegovinia",
title = "The characterisation of silymarin and silibinin loaded liposomes",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5255"
}

Malinović, B., Jovanović, A., Dinić, S., Uskoković, A., Arambašić Jovanović, J., Grdović, N., Vidaković, M.,& Mihailović, M.. (2022). The characterisation of silymarin and silibinin loaded liposomes. in XIV conference of chemists, technologists and environmentalists of Republic of Srpska; 2022 Oct 21-2; Banja Luka, Bosnia and Herzegovinia
Banja Luka: University of Banja Luka..
https://hdl.handle.net/21.15107/rcub_ibiss_5255

Malinović B, Jovanović A, Dinić S, Uskoković A, Arambašić Jovanović J, Grdović N, Vidaković M, Mihailović M. The characterisation of silymarin and silibinin loaded liposomes. in XIV conference of chemists, technologists and environmentalists of Republic of Srpska; 2022 Oct 21-2; Banja Luka, Bosnia and Herzegovinia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5255 .

Malinović, Borislav, Jovanović, Aleksandra, Dinić, Svetlana, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Grdović, Nevena, Vidaković, Melita, Mihailović, Mirjana, "The characterisation of silymarin and silibinin loaded liposomes" in XIV conference of chemists, technologists and environmentalists of Republic of Srpska; 2022 Oct 21-2; Banja Luka, Bosnia and Herzegovinia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5255 .

TY  - JOUR
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Vidaković, Melita
PY  - 2021
UR  - https://www.mdpi.com/2309-608X/7/1/58
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4141
AB  - Diabetes mellitus is a life-threatening multifactorial metabolic disorder characterized by high level of glucose in the blood. Diabetes and its chronic complications have a significant impact on human life, health systems, and countries’ economies. Currently, there are many commercial hypoglycemic drugs that are effective in controlling hyperglycemia but with several serious side-effects and without a sufficient capacity to significantly alter the course of diabetic complications. Over many centuries mushrooms and their bioactive compounds have been used in the treatment of diabetes mellitus, especially polysaccharides and terpenoids derived from various mushroom species. This review summarizes the effects of these main mushroom secondary metabolites on diabetes and underlying molecular mechanisms responsible for lowering blood glucose. In vivo and in vitro data revealed that treatment with mushroom polysaccharides displayed an anti-hyperglycemic effect by inhibiting glucose absorption efficacy, enhancing pancreatic β-cell mass, and increasing insulin-signaling pathways. Mushroom terpenoids act as inhibitors of α-glucosidase and as insulin sensitizers through activation of PPARγ in order to reduce hyperglycemia in animal models of diabetes. In conclusion, mushroom polysaccharides and terpenoids can effectively ameliorate hyperglycemia by various mechanisms and can be used as supportive candidates for prevention and control of diabetes in the future.
PB  - MDPI AG
T2  - Journal of Fungi
T1  - The Effects of Major Mushroom Bioactive Compounds on Mechanisms That Control Blood Glucose Level
IS  - 1
VL  - 7
DO  - 10.3390/jof7010058
SP  - 58
ER  - 

@article{
author = "Arambašić Jovanović, Jelena and Mihailović, Mirjana and Uskoković, Aleksandra and Grdović, Nevena and Dinić, Svetlana and Vidaković, Melita",
year = "2021",
abstract = "Diabetes mellitus is a life-threatening multifactorial metabolic disorder characterized by high level of glucose in the blood. Diabetes and its chronic complications have a significant impact on human life, health systems, and countries’ economies. Currently, there are many commercial hypoglycemic drugs that are effective in controlling hyperglycemia but with several serious side-effects and without a sufficient capacity to significantly alter the course of diabetic complications. Over many centuries mushrooms and their bioactive compounds have been used in the treatment of diabetes mellitus, especially polysaccharides and terpenoids derived from various mushroom species. This review summarizes the effects of these main mushroom secondary metabolites on diabetes and underlying molecular mechanisms responsible for lowering blood glucose. In vivo and in vitro data revealed that treatment with mushroom polysaccharides displayed an anti-hyperglycemic effect by inhibiting glucose absorption efficacy, enhancing pancreatic β-cell mass, and increasing insulin-signaling pathways. Mushroom terpenoids act as inhibitors of α-glucosidase and as insulin sensitizers through activation of PPARγ in order to reduce hyperglycemia in animal models of diabetes. In conclusion, mushroom polysaccharides and terpenoids can effectively ameliorate hyperglycemia by various mechanisms and can be used as supportive candidates for prevention and control of diabetes in the future.",
publisher = "MDPI AG",
journal = "Journal of Fungi",
title = "The Effects of Major Mushroom Bioactive Compounds on Mechanisms That Control Blood Glucose Level",
number = "1",
volume = "7",
doi = "10.3390/jof7010058",
pages = "58"
}

Arambašić Jovanović, J., Mihailović, M., Uskoković, A., Grdović, N., Dinić, S.,& Vidaković, M.. (2021). The Effects of Major Mushroom Bioactive Compounds on Mechanisms That Control Blood Glucose Level. in Journal of Fungi
MDPI AG., 7(1), 58.
https://doi.org/10.3390/jof7010058

Arambašić Jovanović J, Mihailović M, Uskoković A, Grdović N, Dinić S, Vidaković M. The Effects of Major Mushroom Bioactive Compounds on Mechanisms That Control Blood Glucose Level. in Journal of Fungi. 2021;7(1):58.
doi:10.3390/jof7010058 .

Arambašić Jovanović, Jelena, Mihailović, Mirjana, Uskoković, Aleksandra, Grdović, Nevena, Dinić, Svetlana, Vidaković, Melita, "The Effects of Major Mushroom Bioactive Compounds on Mechanisms That Control Blood Glucose Level" in Journal of Fungi, 7, no. 1 (2021):58,
https://doi.org/10.3390/jof7010058 . .

TY  - JOUR
AU  - Grdović, Nevena
AU  - Rajić, Jovana
AU  - Arambašić Jovanović, Jelena
AU  - Dinić, Svetlana
AU  - Tolić, Anja
AU  - Đorđević, Miloš
AU  - Đorđević, Marija
AU  - Trifunović, Svetlana
AU  - Vidaković, Melita
AU  - Uskoković, Aleksandra
AU  - Mihailović, Mirjana
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4190
AB  - α-Lipoic acid (ALA) is widely used as a nutritional supplement and therapeutic agent in diabetes management. Well-established antioxidant and hypoglycemic effects of ALA were considered to be particularly important in combating diabetic complications including renal injury. The present study evaluated the potential of ALA to affect profibrotic events in kidney that could alter its structure and functioning. ALA was administered intraperitoneally (10 mg/kg) to nondiabetic and streptozotocin-induced diabetic male Wistar rats for 4 and 8 weeks. The effects of ALA were assessed starting from structural/morphological alterations through changes that characterize profibrotic processes, to regulation of collagen gene expression in kidney. Here, we demonstrated that ALA improved systemic glucose and urea level, reduced formation of renal advanced glycation end products (AGEs), and maintained renal structural integrity in diabetic rats. However, profibrotic events provoked in diabetes were not alleviated by ALA since collagen synthesis/deposition and expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) remained elevated in ALA-treated diabetic rats, especially after 8 weeks of diabetes onset. Moreover, 8 weeks treatment of nondiabetic rats with ALA led to the development of profibrotic features reflected in increased collagen synthesis/deposition. Besides the TGF-β1 downstream signaling, the additional mechanism underlying the upregulation of collagen IV in nondiabetic rats treated with ALA involves decreased DNA methylation of its promoter that could arise from increased Tet1 expression. These findings emphasize the therapeutic caution in the use of ALA, especially in patients with renal diabetic complication.
PB  - Hindawi Limited
T2  - Oxidative Medicine and Cellular Longevity
T1  - α-Lipoic Acid Increases Collagen Synthesis and Deposition in Nondiabetic and Diabetic Rat Kidneys
VL  - 2021
DO  - 10.1155/2021/6669352
SP  - 6669352
ER  - 

@article{
author = "Grdović, Nevena and Rajić, Jovana and Arambašić Jovanović, Jelena and Dinić, Svetlana and Tolić, Anja and Đorđević, Miloš and Đorđević, Marija and Trifunović, Svetlana and Vidaković, Melita and Uskoković, Aleksandra and Mihailović, Mirjana",
year = "2021",
abstract = "α-Lipoic acid (ALA) is widely used as a nutritional supplement and therapeutic agent in diabetes management. Well-established antioxidant and hypoglycemic effects of ALA were considered to be particularly important in combating diabetic complications including renal injury. The present study evaluated the potential of ALA to affect profibrotic events in kidney that could alter its structure and functioning. ALA was administered intraperitoneally (10 mg/kg) to nondiabetic and streptozotocin-induced diabetic male Wistar rats for 4 and 8 weeks. The effects of ALA were assessed starting from structural/morphological alterations through changes that characterize profibrotic processes, to regulation of collagen gene expression in kidney. Here, we demonstrated that ALA improved systemic glucose and urea level, reduced formation of renal advanced glycation end products (AGEs), and maintained renal structural integrity in diabetic rats. However, profibrotic events provoked in diabetes were not alleviated by ALA since collagen synthesis/deposition and expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) remained elevated in ALA-treated diabetic rats, especially after 8 weeks of diabetes onset. Moreover, 8 weeks treatment of nondiabetic rats with ALA led to the development of profibrotic features reflected in increased collagen synthesis/deposition. Besides the TGF-β1 downstream signaling, the additional mechanism underlying the upregulation of collagen IV in nondiabetic rats treated with ALA involves decreased DNA methylation of its promoter that could arise from increased Tet1 expression. These findings emphasize the therapeutic caution in the use of ALA, especially in patients with renal diabetic complication.",
publisher = "Hindawi Limited",
journal = "Oxidative Medicine and Cellular Longevity",
title = "α-Lipoic Acid Increases Collagen Synthesis and Deposition in Nondiabetic and Diabetic Rat Kidneys",
volume = "2021",
doi = "10.1155/2021/6669352",
pages = "6669352"
}

Grdović, N., Rajić, J., Arambašić Jovanović, J., Dinić, S., Tolić, A., Đorđević, M., Đorđević, M., Trifunović, S., Vidaković, M., Uskoković, A.,& Mihailović, M.. (2021). α-Lipoic Acid Increases Collagen Synthesis and Deposition in Nondiabetic and Diabetic Rat Kidneys. in Oxidative Medicine and Cellular Longevity
Hindawi Limited., 2021, 6669352.
https://doi.org/10.1155/2021/6669352

Grdović N, Rajić J, Arambašić Jovanović J, Dinić S, Tolić A, Đorđević M, Đorđević M, Trifunović S, Vidaković M, Uskoković A, Mihailović M. α-Lipoic Acid Increases Collagen Synthesis and Deposition in Nondiabetic and Diabetic Rat Kidneys. in Oxidative Medicine and Cellular Longevity. 2021;2021:6669352.
doi:10.1155/2021/6669352 .

Grdović, Nevena, Rajić, Jovana, Arambašić Jovanović, Jelena, Dinić, Svetlana, Tolić, Anja, Đorđević, Miloš, Đorđević, Marija, Trifunović, Svetlana, Vidaković, Melita, Uskoković, Aleksandra, Mihailović, Mirjana, "α-Lipoic Acid Increases Collagen Synthesis and Deposition in Nondiabetic and Diabetic Rat Kidneys" in Oxidative Medicine and Cellular Longevity, 2021 (2021):6669352,
https://doi.org/10.1155/2021/6669352 . .

TY  - JOUR
AU  - Mihailović, Mirjana
AU  - Dinić, Svetlana
AU  - Arambašić Jovanović, Jelena
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Vidaković, Melita
PY  - 2021
UR  - https://www.mdpi.com/2076-3921/10/3/480
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4172
AB  - Diabetes is a complex metabolic disorder resulting either from insulin resistance or an impaired insulin secretion. Prolonged elevated blood glucose concentration, the key clinical sign of diabetes, initiates an enhancement of reactive oxygen species derived from glucose autoxidation and glycosylation of proteins. Consequently, chronic oxidative stress overwhelms cellular endogenous antioxidant defenses and leads to the acute and long-standing structural and functional changes of macromolecules resulting in impaired cellular functioning, cell death and organ dysfunction. The oxidative stress provoked chain of pathological events over time cause diabetic complications such as nephropathy, peripheral neuropathy, cardiomyopathy, retinopathy, hypertension, and liver disease. Under diabetic conditions, accompanying genome/epigenome and metabolite markers alterations may also affect glucose homeostasis, pancreatic β-cells, muscle, liver, and adipose tissue. By providing deeper genetic/epigenetic insight of direct or indirect dietary effects, nutrigenomics offers a promising opportunity to improve the quality of life of diabetic patients. Natural plant extracts, or their naturally occurring compounds, were shown to be very proficient in the prevention and treatment of different pathologies associated with oxidative stress including diabetes and its complications. Considering that food intake is one of the crucial components in diabetes’ prevalence, progression and complications, this review summarizes the effect of the major plant secondary metabolite and phytoconstituents on the antioxidant enzymes activity and gene expression under diabetic conditions.
PB  - MDPI AG
T2  - Antioxidants
T2  - Antioxidants
T1  - The Influence of Plant Extracts and Phytoconstituents on Antioxidant Enzymes Activity and Gene Expression in the Prevention and Treatment of Impaired Glucose Homeostasis and Diabetes Complications
IS  - 3
VL  - 10
DO  - 10.3390/antiox10030480
SP  - 480
ER  - 

@article{
author = "Mihailović, Mirjana and Dinić, Svetlana and Arambašić Jovanović, Jelena and Uskoković, Aleksandra and Grdović, Nevena and Vidaković, Melita",
year = "2021",
abstract = "Diabetes is a complex metabolic disorder resulting either from insulin resistance or an impaired insulin secretion. Prolonged elevated blood glucose concentration, the key clinical sign of diabetes, initiates an enhancement of reactive oxygen species derived from glucose autoxidation and glycosylation of proteins. Consequently, chronic oxidative stress overwhelms cellular endogenous antioxidant defenses and leads to the acute and long-standing structural and functional changes of macromolecules resulting in impaired cellular functioning, cell death and organ dysfunction. The oxidative stress provoked chain of pathological events over time cause diabetic complications such as nephropathy, peripheral neuropathy, cardiomyopathy, retinopathy, hypertension, and liver disease. Under diabetic conditions, accompanying genome/epigenome and metabolite markers alterations may also affect glucose homeostasis, pancreatic β-cells, muscle, liver, and adipose tissue. By providing deeper genetic/epigenetic insight of direct or indirect dietary effects, nutrigenomics offers a promising opportunity to improve the quality of life of diabetic patients. Natural plant extracts, or their naturally occurring compounds, were shown to be very proficient in the prevention and treatment of different pathologies associated with oxidative stress including diabetes and its complications. Considering that food intake is one of the crucial components in diabetes’ prevalence, progression and complications, this review summarizes the effect of the major plant secondary metabolite and phytoconstituents on the antioxidant enzymes activity and gene expression under diabetic conditions.",
publisher = "MDPI AG",
journal = "Antioxidants, Antioxidants",
title = "The Influence of Plant Extracts and Phytoconstituents on Antioxidant Enzymes Activity and Gene Expression in the Prevention and Treatment of Impaired Glucose Homeostasis and Diabetes Complications",
number = "3",
volume = "10",
doi = "10.3390/antiox10030480",
pages = "480"
}

Mihailović, M., Dinić, S., Arambašić Jovanović, J., Uskoković, A., Grdović, N.,& Vidaković, M.. (2021). The Influence of Plant Extracts and Phytoconstituents on Antioxidant Enzymes Activity and Gene Expression in the Prevention and Treatment of Impaired Glucose Homeostasis and Diabetes Complications. in Antioxidants
MDPI AG., 10(3), 480.
https://doi.org/10.3390/antiox10030480

Mihailović M, Dinić S, Arambašić Jovanović J, Uskoković A, Grdović N, Vidaković M. The Influence of Plant Extracts and Phytoconstituents on Antioxidant Enzymes Activity and Gene Expression in the Prevention and Treatment of Impaired Glucose Homeostasis and Diabetes Complications. in Antioxidants. 2021;10(3):480.
doi:10.3390/antiox10030480 .

Mihailović, Mirjana, Dinić, Svetlana, Arambašić Jovanović, Jelena, Uskoković, Aleksandra, Grdović, Nevena, Vidaković, Melita, "The Influence of Plant Extracts and Phytoconstituents on Antioxidant Enzymes Activity and Gene Expression in the Prevention and Treatment of Impaired Glucose Homeostasis and Diabetes Complications" in Antioxidants, 10, no. 3 (2021):480,
https://doi.org/10.3390/antiox10030480 . .

TY  - JOUR
AU  - Rajić, Jovana
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Tolić, Anja
AU  - Đorđević, Marija
AU  - Đorđević, Miloš
AU  - Poznanović, Goran
AU  - Mihailović, Mirjana
AU  - Inic-Kanada, Aleksandra
AU  - Barisani-Asenbauer, Talin
AU  - Grdović, Nevena
AU  - Vidaković, Melita
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32387379
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3687
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3695
AB  - Epithelial to mesenchymal transition (EMT) contributes to fibrosis associated pathologies including scarring of different ocular tissues. Recently targeting EMT is seen as an appropriate therapeutic approach for different fibrosis related eye diseases such as macular degeneration or glaucoma surgery related fibrosis. Nevertheless, for ocular surface diseases, target genes specific for particular cell type or condition are still undefined. This study aimed to expose the complex regulatory mechanisms that trigger EMT in human conjunctival epithelial (HCjE) cells. EMT was induced by prolonged treatment with two TGF-β isoforms, TGF-β1 and TGF-β2, and their combination. TGF-β1 showed the strongest potential for initiating EMT in HCjE cells, reflected on morphological changes, cell migration and the levels of mRNA expression of different epithelial (CDH1, OCLN, DSP) and mesenchymal (CDH2, FN1, VIM, SNAI1, ZEB2, TWIST1) marker genes. Co-treatment with the DNA demethylating agent 5-Azacytidine (5-AzaC) was capable of stopping the transition of HCjE cells towards a mesenchymal phenotype, based on morphological features, reduced cell mobility and mRNA and protein expression levels of epithelial and mesenchymal marker genes. An EMT qRT-PCR-based array revealed that EMT induced considerable alterations in gene expression, with downregulation of the majority of epithelial marker genes and upregulation of genes specific for the mesenchymal state. The major effect of 5-AzaC treatment was observed as a suppression of mesenchymal marker genes, suggesting the involvement of upstream negative regulator(s) whose promoter demethylation and subsequent expression will in turn promote EMT switch off. The expression level of miRNAs potentially important for EMT induction was determined using qRT-PCR-based array which pointed at members of miR-200 family as main regulators of EMT process in HCjE cells. 5-AzaC treatment induced increased expression of miR-200a, -200b, -200c and miR-141 towards the control level, indicating important role of DNA methylation in their regulation. The DNA methylation status of both miR-200 family clusters, analyzed with high-resolution melting (HRM) and bisulfite sequencing (Bis-Seq), revealed that TGF-β1-induced EMT was accompanied by increase in promoter CpG methylation of both miR-200 loci, which was reverted after 5-AzaC treatment. In conclusion, our results indicate that DNA demethylation of promoters of miR-200 loci is critically important for stopping and reverting the EMT in human conjunctival epithelial cells, suggesting the potential for the development of novel epigenetic-based therapeutic strategies for treating conjunctival conditions associated with EMT.
PB  - Elsevier BV
T2  - Experimental Eye Research
T1  - DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells.
VL  - 197
DO  - 10.1016/j.exer.2020.108047
SP  - 108047
ER  - 

@article{
author = "Rajić, Jovana and Dinić, Svetlana and Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Tolić, Anja and Đorđević, Marija and Đorđević, Miloš and Poznanović, Goran and Mihailović, Mirjana and Inic-Kanada, Aleksandra and Barisani-Asenbauer, Talin and Grdović, Nevena and Vidaković, Melita",
year = "2020",
abstract = "Epithelial to mesenchymal transition (EMT) contributes to fibrosis associated pathologies including scarring of different ocular tissues. Recently targeting EMT is seen as an appropriate therapeutic approach for different fibrosis related eye diseases such as macular degeneration or glaucoma surgery related fibrosis. Nevertheless, for ocular surface diseases, target genes specific for particular cell type or condition are still undefined. This study aimed to expose the complex regulatory mechanisms that trigger EMT in human conjunctival epithelial (HCjE) cells. EMT was induced by prolonged treatment with two TGF-β isoforms, TGF-β1 and TGF-β2, and their combination. TGF-β1 showed the strongest potential for initiating EMT in HCjE cells, reflected on morphological changes, cell migration and the levels of mRNA expression of different epithelial (CDH1, OCLN, DSP) and mesenchymal (CDH2, FN1, VIM, SNAI1, ZEB2, TWIST1) marker genes. Co-treatment with the DNA demethylating agent 5-Azacytidine (5-AzaC) was capable of stopping the transition of HCjE cells towards a mesenchymal phenotype, based on morphological features, reduced cell mobility and mRNA and protein expression levels of epithelial and mesenchymal marker genes. An EMT qRT-PCR-based array revealed that EMT induced considerable alterations in gene expression, with downregulation of the majority of epithelial marker genes and upregulation of genes specific for the mesenchymal state. The major effect of 5-AzaC treatment was observed as a suppression of mesenchymal marker genes, suggesting the involvement of upstream negative regulator(s) whose promoter demethylation and subsequent expression will in turn promote EMT switch off. The expression level of miRNAs potentially important for EMT induction was determined using qRT-PCR-based array which pointed at members of miR-200 family as main regulators of EMT process in HCjE cells. 5-AzaC treatment induced increased expression of miR-200a, -200b, -200c and miR-141 towards the control level, indicating important role of DNA methylation in their regulation. The DNA methylation status of both miR-200 family clusters, analyzed with high-resolution melting (HRM) and bisulfite sequencing (Bis-Seq), revealed that TGF-β1-induced EMT was accompanied by increase in promoter CpG methylation of both miR-200 loci, which was reverted after 5-AzaC treatment. In conclusion, our results indicate that DNA demethylation of promoters of miR-200 loci is critically important for stopping and reverting the EMT in human conjunctival epithelial cells, suggesting the potential for the development of novel epigenetic-based therapeutic strategies for treating conjunctival conditions associated with EMT.",
publisher = "Elsevier BV",
journal = "Experimental Eye Research",
title = "DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells.",
volume = "197",
doi = "10.1016/j.exer.2020.108047",
pages = "108047"
}

Rajić, J., Dinić, S., Uskoković, A., Arambašić Jovanović, J., Tolić, A., Đorđević, M., Đorđević, M., Poznanović, G., Mihailović, M., Inic-Kanada, A., Barisani-Asenbauer, T., Grdović, N.,& Vidaković, M.. (2020). DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells.. in Experimental Eye Research
Elsevier BV., 197, 108047.
https://doi.org/10.1016/j.exer.2020.108047

Rajić J, Dinić S, Uskoković A, Arambašić Jovanović J, Tolić A, Đorđević M, Đorđević M, Poznanović G, Mihailović M, Inic-Kanada A, Barisani-Asenbauer T, Grdović N, Vidaković M. DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells.. in Experimental Eye Research. 2020;197:108047.
doi:10.1016/j.exer.2020.108047 .

Rajić, Jovana, Dinić, Svetlana, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Tolić, Anja, Đorđević, Marija, Đorđević, Miloš, Poznanović, Goran, Mihailović, Mirjana, Inic-Kanada, Aleksandra, Barisani-Asenbauer, Talin, Grdović, Nevena, Vidaković, Melita, "DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells." in Experimental Eye Research, 197 (2020):108047,
https://doi.org/10.1016/j.exer.2020.108047 . .

TY  - JOUR
AU  - Rajić, Jovana
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Tolić, Anja
AU  - Đorđević, Marija
AU  - Đorđević, Miloš
AU  - Poznanović, Goran
AU  - Mihailović, Mirjana
AU  - Inic-Kanada, Aleksandra
AU  - Barisani-Asenbauer, Talin
AU  - Grdović, Nevena
AU  - Vidaković, Melita
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32387379
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3687
UR  - https://radar.ibiss.bg.ac.rs/handle/handle/123456789/3695
AB  - Epithelial to mesenchymal transition (EMT) contributes to fibrosis associated pathologies including scarring of different ocular tissues. Recently targeting EMT is seen as an appropriate therapeutic approach for different fibrosis related eye diseases such as macular degeneration or glaucoma surgery related fibrosis. Nevertheless, for ocular surface diseases, target genes specific for particular cell type or condition are still undefined. This study aimed to expose the complex regulatory mechanisms that trigger EMT in human conjunctival epithelial (HCjE) cells. EMT was induced by prolonged treatment with two TGF-β isoforms, TGF-β1 and TGF-β2, and their combination. TGF-β1 showed the strongest potential for initiating EMT in HCjE cells, reflected on morphological changes, cell migration and the levels of mRNA expression of different epithelial (CDH1, OCLN, DSP) and mesenchymal (CDH2, FN1, VIM, SNAI1, ZEB2, TWIST1) marker genes. Co-treatment with the DNA demethylating agent 5-Azacytidine (5-AzaC) was capable of stopping the transition of HCjE cells towards a mesenchymal phenotype, based on morphological features, reduced cell mobility and mRNA and protein expression levels of epithelial and mesenchymal marker genes. An EMT qRT-PCR-based array revealed that EMT induced considerable alterations in gene expression, with downregulation of the majority of epithelial marker genes and upregulation of genes specific for the mesenchymal state. The major effect of 5-AzaC treatment was observed as a suppression of mesenchymal marker genes, suggesting the involvement of upstream negative regulator(s) whose promoter demethylation and subsequent expression will in turn promote EMT switch off. The expression level of miRNAs potentially important for EMT induction was determined using qRT-PCR-based array which pointed at members of miR-200 family as main regulators of EMT process in HCjE cells. 5-AzaC treatment induced increased expression of miR-200a, -200b, -200c and miR-141 towards the control level, indicating important role of DNA methylation in their regulation. The DNA methylation status of both miR-200 family clusters, analyzed with high-resolution melting (HRM) and bisulfite sequencing (Bis-Seq), revealed that TGF-β1-induced EMT was accompanied by increase in promoter CpG methylation of both miR-200 loci, which was reverted after 5-AzaC treatment. In conclusion, our results indicate that DNA demethylation of promoters of miR-200 loci is critically important for stopping and reverting the EMT in human conjunctival epithelial cells, suggesting the potential for the development of novel epigenetic-based therapeutic strategies for treating conjunctival conditions associated with EMT.
PB  - Elsevier BV
T2  - Experimental Eye Research
T1  - DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells.
VL  - 197
DO  - 10.1016/j.exer.2020.108047
SP  - 108047
ER  - 

@article{
author = "Rajić, Jovana and Dinić, Svetlana and Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Tolić, Anja and Đorđević, Marija and Đorđević, Miloš and Poznanović, Goran and Mihailović, Mirjana and Inic-Kanada, Aleksandra and Barisani-Asenbauer, Talin and Grdović, Nevena and Vidaković, Melita",
year = "2020",
abstract = "Epithelial to mesenchymal transition (EMT) contributes to fibrosis associated pathologies including scarring of different ocular tissues. Recently targeting EMT is seen as an appropriate therapeutic approach for different fibrosis related eye diseases such as macular degeneration or glaucoma surgery related fibrosis. Nevertheless, for ocular surface diseases, target genes specific for particular cell type or condition are still undefined. This study aimed to expose the complex regulatory mechanisms that trigger EMT in human conjunctival epithelial (HCjE) cells. EMT was induced by prolonged treatment with two TGF-β isoforms, TGF-β1 and TGF-β2, and their combination. TGF-β1 showed the strongest potential for initiating EMT in HCjE cells, reflected on morphological changes, cell migration and the levels of mRNA expression of different epithelial (CDH1, OCLN, DSP) and mesenchymal (CDH2, FN1, VIM, SNAI1, ZEB2, TWIST1) marker genes. Co-treatment with the DNA demethylating agent 5-Azacytidine (5-AzaC) was capable of stopping the transition of HCjE cells towards a mesenchymal phenotype, based on morphological features, reduced cell mobility and mRNA and protein expression levels of epithelial and mesenchymal marker genes. An EMT qRT-PCR-based array revealed that EMT induced considerable alterations in gene expression, with downregulation of the majority of epithelial marker genes and upregulation of genes specific for the mesenchymal state. The major effect of 5-AzaC treatment was observed as a suppression of mesenchymal marker genes, suggesting the involvement of upstream negative regulator(s) whose promoter demethylation and subsequent expression will in turn promote EMT switch off. The expression level of miRNAs potentially important for EMT induction was determined using qRT-PCR-based array which pointed at members of miR-200 family as main regulators of EMT process in HCjE cells. 5-AzaC treatment induced increased expression of miR-200a, -200b, -200c and miR-141 towards the control level, indicating important role of DNA methylation in their regulation. The DNA methylation status of both miR-200 family clusters, analyzed with high-resolution melting (HRM) and bisulfite sequencing (Bis-Seq), revealed that TGF-β1-induced EMT was accompanied by increase in promoter CpG methylation of both miR-200 loci, which was reverted after 5-AzaC treatment. In conclusion, our results indicate that DNA demethylation of promoters of miR-200 loci is critically important for stopping and reverting the EMT in human conjunctival epithelial cells, suggesting the potential for the development of novel epigenetic-based therapeutic strategies for treating conjunctival conditions associated with EMT.",
publisher = "Elsevier BV",
journal = "Experimental Eye Research",
title = "DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells.",
volume = "197",
doi = "10.1016/j.exer.2020.108047",
pages = "108047"
}

Rajić, J., Dinić, S., Uskoković, A., Arambašić Jovanović, J., Tolić, A., Đorđević, M., Đorđević, M., Poznanović, G., Mihailović, M., Inic-Kanada, A., Barisani-Asenbauer, T., Grdović, N.,& Vidaković, M.. (2020). DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells.. in Experimental Eye Research
Elsevier BV., 197, 108047.
https://doi.org/10.1016/j.exer.2020.108047

Rajić J, Dinić S, Uskoković A, Arambašić Jovanović J, Tolić A, Đorđević M, Đorđević M, Poznanović G, Mihailović M, Inic-Kanada A, Barisani-Asenbauer T, Grdović N, Vidaković M. DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells.. in Experimental Eye Research. 2020;197:108047.
doi:10.1016/j.exer.2020.108047 .

Rajić, Jovana, Dinić, Svetlana, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Tolić, Anja, Đorđević, Marija, Đorđević, Miloš, Poznanović, Goran, Mihailović, Mirjana, Inic-Kanada, Aleksandra, Barisani-Asenbauer, Talin, Grdović, Nevena, Vidaković, Melita, "DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells." in Experimental Eye Research, 197 (2020):108047,
https://doi.org/10.1016/j.exer.2020.108047 . .

TY  - JOUR
AU  - Đorđević, Miloš
AU  - Grdović, Nevena
AU  - Mihailović, Mirjana
AU  - Arambašić Jovanović, Jelena
AU  - Uskoković, Aleksandra
AU  - Rajić, Jovana
AU  - Đorđević, Marija
AU  - Tolić, Anja
AU  - Mišić, Danijela
AU  - Šiler, Branislav
AU  - Poznanović, Goran
AU  - Vidaković, Melita
AU  - Dinić, Svetlana
PY  - 2020
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/5029
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3651
AB  - Oxidative stress is one of the major mechanisms that underlies the damage of pancreatic b-cells and defects in insulin secretion in diabetes. As herbal preparations can alleviate oxidative stress through their redox-active secondary metabolites, in this study we investigated the cytoprotective effects of Centaurium erythraea extract (CEe) against H2O2- and SNP-induced oxidative/nitrosative stress in Rin-5F b-cells. The antioxidant activity of CEe and its effect on cell survival and insulin expression/secretion were evaluated. The CEe increased cell viability and ameliorated the disturbance of redox homeostasis in H2O2- and SNP-treated cells by decreasing DNA damage, lipid peroxidation and protein S-glutathionylation. The CEe restored GSH homeostasis in H2O2-treated b-cells and attenuated the SNP-induced disturbance of the GSH/GSSG ratio. The H2O2- and SNP-induced disruption of CAT, GPx, GR, MnSOD and CuZnSOD activities was adjusted by the CEe towards control values, as well as mRNA and protein levels of GPx, MnSOD and CAT. The CEe increased insulin expression/secretion particularly in H2O2-treated b-cells, which was in accordance with the more pronounced antioxidant effect of the CEe observed in H2O2-treated b-cells as compared to SNP-treated cells. These findings support the beneficial effect of the CEe in preventing or slowing down b-cell damage and dysfunction caused by oxidative/nitrosative stress during diabetes development.
T2  - Archives of Biological Sciences
T1  - Centaurium erythraea extract reduces redox imbalance and improves insulin expression and secretion in pancreatic β-cells exposed to oxidative and nitrosative stress
IS  - 1
VL  - 72
DO  - 10.2298/abs200127005d
SP  - 117
EP  - 128
ER  - 

@article{
author = "Đorđević, Miloš and Grdović, Nevena and Mihailović, Mirjana and Arambašić Jovanović, Jelena and Uskoković, Aleksandra and Rajić, Jovana and Đorđević, Marija and Tolić, Anja and Mišić, Danijela and Šiler, Branislav and Poznanović, Goran and Vidaković, Melita and Dinić, Svetlana",
year = "2020",
abstract = "Oxidative stress is one of the major mechanisms that underlies the damage of pancreatic b-cells and defects in insulin secretion in diabetes. As herbal preparations can alleviate oxidative stress through their redox-active secondary metabolites, in this study we investigated the cytoprotective effects of Centaurium erythraea extract (CEe) against H2O2- and SNP-induced oxidative/nitrosative stress in Rin-5F b-cells. The antioxidant activity of CEe and its effect on cell survival and insulin expression/secretion were evaluated. The CEe increased cell viability and ameliorated the disturbance of redox homeostasis in H2O2- and SNP-treated cells by decreasing DNA damage, lipid peroxidation and protein S-glutathionylation. The CEe restored GSH homeostasis in H2O2-treated b-cells and attenuated the SNP-induced disturbance of the GSH/GSSG ratio. The H2O2- and SNP-induced disruption of CAT, GPx, GR, MnSOD and CuZnSOD activities was adjusted by the CEe towards control values, as well as mRNA and protein levels of GPx, MnSOD and CAT. The CEe increased insulin expression/secretion particularly in H2O2-treated b-cells, which was in accordance with the more pronounced antioxidant effect of the CEe observed in H2O2-treated b-cells as compared to SNP-treated cells. These findings support the beneficial effect of the CEe in preventing or slowing down b-cell damage and dysfunction caused by oxidative/nitrosative stress during diabetes development.",
journal = "Archives of Biological Sciences",
title = "Centaurium erythraea extract reduces redox imbalance and improves insulin expression and secretion in pancreatic β-cells exposed to oxidative and nitrosative stress",
number = "1",
volume = "72",
doi = "10.2298/abs200127005d",
pages = "117-128"
}

Đorđević, M., Grdović, N., Mihailović, M., Arambašić Jovanović, J., Uskoković, A., Rajić, J., Đorđević, M., Tolić, A., Mišić, D., Šiler, B., Poznanović, G., Vidaković, M.,& Dinić, S.. (2020). Centaurium erythraea extract reduces redox imbalance and improves insulin expression and secretion in pancreatic β-cells exposed to oxidative and nitrosative stress. in Archives of Biological Sciences, 72(1), 117-128.
https://doi.org/10.2298/abs200127005d

Đorđević M, Grdović N, Mihailović M, Arambašić Jovanović J, Uskoković A, Rajić J, Đorđević M, Tolić A, Mišić D, Šiler B, Poznanović G, Vidaković M, Dinić S. Centaurium erythraea extract reduces redox imbalance and improves insulin expression and secretion in pancreatic β-cells exposed to oxidative and nitrosative stress. in Archives of Biological Sciences. 2020;72(1):117-128.
doi:10.2298/abs200127005d .

Đorđević, Miloš, Grdović, Nevena, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Uskoković, Aleksandra, Rajić, Jovana, Đorđević, Marija, Tolić, Anja, Mišić, Danijela, Šiler, Branislav, Poznanović, Goran, Vidaković, Melita, Dinić, Svetlana, "Centaurium erythraea extract reduces redox imbalance and improves insulin expression and secretion in pancreatic β-cells exposed to oxidative and nitrosative stress" in Archives of Biological Sciences, 72, no. 1 (2020):117-128,
https://doi.org/10.2298/abs200127005d . .

TY  - CONF
AU  - Đorđević, Miloš
AU  - Grdović, Nevena
AU  - Mihailović, Mirjana
AU  - Arambašić Jovanović, Jelena
AU  - Uskoković, Aleksandra
AU  - Rajić, Jovana
AU  - Đorđević, Marija
AU  - Tolić, Anja
AU  - Mišić, Danijela
AU  - Šiler, Branislav
AU  - Poznanović, Goran
AU  - Vidaković, Melita
AU  - Dinić, Svetlana
PY  - 2020
UR  - https://blog.u-bourgogne.fr/cost-nutredox/wp-content/uploads/sites/81/2020/03/NutRedOX-Belgrade-2020-Abstract-book.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4107
AB  - Centaurium erythraea (CE) is traditionally used for diabetes treatment due to its anti-diabetic properties. Previously we have reported that the major constituents of CE methanol extract (CEE) are secoiridoids and polyphenols. Here we analyzed the protective effect of CEE on pancreatic β-cells in streptozotocin (STZ)-induced diabetic rats. CEE (100 mg/kg) was administered daily and orally to control or diabetic rats for two weeks before diabetes induction, during five days of STZ treatment (40 mg/kg/day), and for four weeks after last STZ injection (pre-treated group), or for four weeks after diabetes induction (post-treated group). Histological and immunohistochemical examination of the pancreas revealed disturbed morphology of pancreatic islets, a decrease in their number and size which was accompanied by the reduction of insulin-positive β-cells in diabetic rats when compared to control or control/CEE-treated rats. Islet morphology and mass, as well as the number of insulin-positive β-cells, were improved in CEE-treated diabetic rats, particularly in a pre-treated group. In pre- and post-treated groups we observed the increase of GLUT-2 transporter and p-Akt kinase, that were absent in diabetic pancreas pointing to impaired glucose-stimulated insulin secretion in remnant β-cells. CEE-mediated increase of β-cell mass, GLUT-2 and p-Akt levels in diabetic rats contributed to the elevation of serum insulin level and reduction of glucose level which was more prominent in pre- than in a post-treated group. The results of this study suggest that improved insulin production and glycemic control in CEE-treated diabetic rats may result from the structural/functional preservation of pancreatic islets.
PB  - NutRedox, COST Action CA16112
C3  - WGs Meeting of the NutRedOx COST Action CA16112 Belgrade, March 2-3, 2020
T1  - Beneficial effects of Centaurium erythraea extract on glycemic control and insulin  level in diabetic rats
SP  - 9
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4107
ER  - 

@conference{
author = "Đorđević, Miloš and Grdović, Nevena and Mihailović, Mirjana and Arambašić Jovanović, Jelena and Uskoković, Aleksandra and Rajić, Jovana and Đorđević, Marija and Tolić, Anja and Mišić, Danijela and Šiler, Branislav and Poznanović, Goran and Vidaković, Melita and Dinić, Svetlana",
year = "2020",
abstract = "Centaurium erythraea (CE) is traditionally used for diabetes treatment due to its anti-diabetic properties. Previously we have reported that the major constituents of CE methanol extract (CEE) are secoiridoids and polyphenols. Here we analyzed the protective effect of CEE on pancreatic β-cells in streptozotocin (STZ)-induced diabetic rats. CEE (100 mg/kg) was administered daily and orally to control or diabetic rats for two weeks before diabetes induction, during five days of STZ treatment (40 mg/kg/day), and for four weeks after last STZ injection (pre-treated group), or for four weeks after diabetes induction (post-treated group). Histological and immunohistochemical examination of the pancreas revealed disturbed morphology of pancreatic islets, a decrease in their number and size which was accompanied by the reduction of insulin-positive β-cells in diabetic rats when compared to control or control/CEE-treated rats. Islet morphology and mass, as well as the number of insulin-positive β-cells, were improved in CEE-treated diabetic rats, particularly in a pre-treated group. In pre- and post-treated groups we observed the increase of GLUT-2 transporter and p-Akt kinase, that were absent in diabetic pancreas pointing to impaired glucose-stimulated insulin secretion in remnant β-cells. CEE-mediated increase of β-cell mass, GLUT-2 and p-Akt levels in diabetic rats contributed to the elevation of serum insulin level and reduction of glucose level which was more prominent in pre- than in a post-treated group. The results of this study suggest that improved insulin production and glycemic control in CEE-treated diabetic rats may result from the structural/functional preservation of pancreatic islets.",
publisher = "NutRedox, COST Action CA16112",
journal = "WGs Meeting of the NutRedOx COST Action CA16112 Belgrade, March 2-3, 2020",
title = "Beneficial effects of Centaurium erythraea extract on glycemic control and insulin  level in diabetic rats",
pages = "9",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4107"
}

Đorđević, M., Grdović, N., Mihailović, M., Arambašić Jovanović, J., Uskoković, A., Rajić, J., Đorđević, M., Tolić, A., Mišić, D., Šiler, B., Poznanović, G., Vidaković, M.,& Dinić, S.. (2020). Beneficial effects of Centaurium erythraea extract on glycemic control and insulin  level in diabetic rats. in WGs Meeting of the NutRedOx COST Action CA16112 Belgrade, March 2-3, 2020
NutRedox, COST Action CA16112., 9.
https://hdl.handle.net/21.15107/rcub_ibiss_4107

Đorđević M, Grdović N, Mihailović M, Arambašić Jovanović J, Uskoković A, Rajić J, Đorđević M, Tolić A, Mišić D, Šiler B, Poznanović G, Vidaković M, Dinić S. Beneficial effects of Centaurium erythraea extract on glycemic control and insulin  level in diabetic rats. in WGs Meeting of the NutRedOx COST Action CA16112 Belgrade, March 2-3, 2020. 2020;:9.
https://hdl.handle.net/21.15107/rcub_ibiss_4107 .

Đorđević, Miloš, Grdović, Nevena, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Uskoković, Aleksandra, Rajić, Jovana, Đorđević, Marija, Tolić, Anja, Mišić, Danijela, Šiler, Branislav, Poznanović, Goran, Vidaković, Melita, Dinić, Svetlana, "Beneficial effects of Centaurium erythraea extract on glycemic control and insulin  level in diabetic rats" in WGs Meeting of the NutRedOx COST Action CA16112 Belgrade, March 2-3, 2020 (2020):9,
https://hdl.handle.net/21.15107/rcub_ibiss_4107 .

TY  - DATA
AU  - Mihailović, Mirjana
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Poznanović, Goran
AU  - Franić, Aida
AU  - Đorđević, Marija
AU  - Vidaković, Melita
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3715
AB  - Supplementary Table S1. The  effects  of administration  of  extracts  of Castanea  sativa, Lactarius deterrimusand the combination of theseextracts on the change in body weight and biochemical parameters in seraof diabetic rats.
T2  - Archives of Biological Sciences
T1  - Supplementary data for the article: Mihailović M, Uskoković A, Arambašić-Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, Vidaković M. Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. Arch Biol Sci. 2020;72(2):233-42.
IS  - 2
VL  - 72
SP  - 233
EP  - 242
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3715
ER  - 

@misc{
author = "Mihailović, Mirjana and Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Grdović, Nevena and Dinić, Svetlana and Poznanović, Goran and Franić, Aida and Đorđević, Marija and Vidaković, Melita",
year = "2020",
abstract = "Supplementary Table S1. The  effects  of administration  of  extracts  of Castanea  sativa, Lactarius deterrimusand the combination of theseextracts on the change in body weight and biochemical parameters in seraof diabetic rats.",
journal = "Archives of Biological Sciences",
title = "Supplementary data for the article: Mihailović M, Uskoković A, Arambašić-Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, Vidaković M. Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. Arch Biol Sci. 2020;72(2):233-42.",
number = "2",
volume = "72",
pages = "233-242",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3715"
}

Mihailović, M., Uskoković, A., Arambašić Jovanović, J., Grdović, N., Dinić, S., Poznanović, G., Franić, A., Đorđević, M.,& Vidaković, M.. (2020). Supplementary data for the article: Mihailović M, Uskoković A, Arambašić-Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, Vidaković M. Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. Arch Biol Sci. 2020;72(2):233-42.. in Archives of Biological Sciences, 72(2), 233-242.
https://hdl.handle.net/21.15107/rcub_ibiss_3715

Mihailović M, Uskoković A, Arambašić Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, Vidaković M. Supplementary data for the article: Mihailović M, Uskoković A, Arambašić-Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, Vidaković M. Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. Arch Biol Sci. 2020;72(2):233-42.. in Archives of Biological Sciences. 2020;72(2):233-242.
https://hdl.handle.net/21.15107/rcub_ibiss_3715 .

Mihailović, Mirjana, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Grdović, Nevena, Dinić, Svetlana, Poznanović, Goran, Franić, Aida, Đorđević, Marija, Vidaković, Melita, "Supplementary data for the article: Mihailović M, Uskoković A, Arambašić-Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, Vidaković M. Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. Arch Biol Sci. 2020;72(2):233-42." in Archives of Biological Sciences, 72, no. 2 (2020):233-242,
https://hdl.handle.net/21.15107/rcub_ibiss_3715 .

TY  - CONF
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Đorđević, Miloš
AU  - Đorđević, Marija
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Mihailović, Mirjana
AU  - Arambašić Jovanović, Jelena
AU  - Dinić, Svetlana
AU  - Nestorović, Nataša
AU  - Jurkowski, Tomasz
AU  - Vidaković, Melita
PY  - 2020
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4783
AB  - Since our previous work indicated interplay of Ten-eleven translocation (TET) and Poly (ADP-ribose) polymerase (PARP) proteins our aim was to further study the effects of their interaction. 
The ability of recombinant PARP-1 to poly ADP-ribosylate (PARylate) catalytic domains of TET proteins was examined in vitro. It was observed that all TETs (TET1, TET2, TET3) readily undergo PARylation. To our knowledge, this is the first report of PARP-1 PARylation of TET2 and TET3 while TET1 PARylation has been previously documented. PARylation of TET proteins was evidenced by western blot signal stretching from the position of unmodified TET. This type of signal is characteristic for PARylation since proteins are modified to varying degrees by covalently attached negatively charged PAR polymers. This slows their movement during electrophoresis and individual molecules are expected to stop at different positions resulting in signal stretching upwards.  PARylation can introduce electrostatic and topological changes in modified proteins, resulting in altered enzymatic activity. Therefore we evaluated TET1 activity in vitro using an ELISA type in-house assay, which showed that PARP-1-dependent PARylation lowers the ability of TET1 catalytic domain to oxidize 5mC to 5hmC. 
To corroborate these results in cellulo, we examined changes in DNA methylation in mouse embryonic fibroblasts (NIH3T3) compared to a PARP-1 knock out mouse embryonic fibroblast cell line (P ARP-/-). Lower methylation was observed in PARP-/- cells by immunocytochemical staining. Next, we analyzed global DNA methylation by ELISA assay and we again detected lower methylation levels in PARP-/- and also in NIH3T3 cells treated by a PARP inhibitor niraparib. Finally, DNA hydroxymethylation was assessed by immunocytochemistry and stronger signal was observed in PARP-/- cells and NIH3T3 cells treated by niraparib, compared to control NIH3T3 cells. 
In summary, inhibition of PARylation or absence of PARP-1 lead to decreased methylation and increased hydroxymethylation of DNA in cellulo. Together, our results point to the inhibitory influence that PARP-1 and PARylation exert on TET1 activity. Further studies are needed to evaluate the effects of PARylation of other TET proteins as well as to examine potential influence of other PARPs.
PB  - Cold Spring Harbor Laboratory
C3  - 2020 virtual meeting on EPIGENETICS & CHROMATIN; 2020 Sep 15-18; Virtual meeting
T1  - PARP-1 and PARylation inhibit TET1 demethylation activity
SP  - 286
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4783
ER  - 

@conference{
author = "Tolić, Anja and Rajić, Jovana and Đorđević, Miloš and Đorđević, Marija and Uskoković, Aleksandra and Grdović, Nevena and Mihailović, Mirjana and Arambašić Jovanović, Jelena and Dinić, Svetlana and Nestorović, Nataša and Jurkowski, Tomasz and Vidaković, Melita",
year = "2020",
abstract = "Since our previous work indicated interplay of Ten-eleven translocation (TET) and Poly (ADP-ribose) polymerase (PARP) proteins our aim was to further study the effects of their interaction. 
The ability of recombinant PARP-1 to poly ADP-ribosylate (PARylate) catalytic domains of TET proteins was examined in vitro. It was observed that all TETs (TET1, TET2, TET3) readily undergo PARylation. To our knowledge, this is the first report of PARP-1 PARylation of TET2 and TET3 while TET1 PARylation has been previously documented. PARylation of TET proteins was evidenced by western blot signal stretching from the position of unmodified TET. This type of signal is characteristic for PARylation since proteins are modified to varying degrees by covalently attached negatively charged PAR polymers. This slows their movement during electrophoresis and individual molecules are expected to stop at different positions resulting in signal stretching upwards.  PARylation can introduce electrostatic and topological changes in modified proteins, resulting in altered enzymatic activity. Therefore we evaluated TET1 activity in vitro using an ELISA type in-house assay, which showed that PARP-1-dependent PARylation lowers the ability of TET1 catalytic domain to oxidize 5mC to 5hmC. 
To corroborate these results in cellulo, we examined changes in DNA methylation in mouse embryonic fibroblasts (NIH3T3) compared to a PARP-1 knock out mouse embryonic fibroblast cell line (P ARP-/-). Lower methylation was observed in PARP-/- cells by immunocytochemical staining. Next, we analyzed global DNA methylation by ELISA assay and we again detected lower methylation levels in PARP-/- and also in NIH3T3 cells treated by a PARP inhibitor niraparib. Finally, DNA hydroxymethylation was assessed by immunocytochemistry and stronger signal was observed in PARP-/- cells and NIH3T3 cells treated by niraparib, compared to control NIH3T3 cells. 
In summary, inhibition of PARylation or absence of PARP-1 lead to decreased methylation and increased hydroxymethylation of DNA in cellulo. Together, our results point to the inhibitory influence that PARP-1 and PARylation exert on TET1 activity. Further studies are needed to evaluate the effects of PARylation of other TET proteins as well as to examine potential influence of other PARPs.",
publisher = "Cold Spring Harbor Laboratory",
journal = "2020 virtual meeting on EPIGENETICS & CHROMATIN; 2020 Sep 15-18; Virtual meeting",
title = "PARP-1 and PARylation inhibit TET1 demethylation activity",
pages = "286",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4783"
}

Tolić, A., Rajić, J., Đorđević, M., Đorđević, M., Uskoković, A., Grdović, N., Mihailović, M., Arambašić Jovanović, J., Dinić, S., Nestorović, N., Jurkowski, T.,& Vidaković, M.. (2020). PARP-1 and PARylation inhibit TET1 demethylation activity. in 2020 virtual meeting on EPIGENETICS & CHROMATIN; 2020 Sep 15-18; Virtual meeting
Cold Spring Harbor Laboratory., 286.
https://hdl.handle.net/21.15107/rcub_ibiss_4783

Tolić A, Rajić J, Đorđević M, Đorđević M, Uskoković A, Grdović N, Mihailović M, Arambašić Jovanović J, Dinić S, Nestorović N, Jurkowski T, Vidaković M. PARP-1 and PARylation inhibit TET1 demethylation activity. in 2020 virtual meeting on EPIGENETICS & CHROMATIN; 2020 Sep 15-18; Virtual meeting. 2020;:286.
https://hdl.handle.net/21.15107/rcub_ibiss_4783 .

Tolić, Anja, Rajić, Jovana, Đorđević, Miloš, Đorđević, Marija, Uskoković, Aleksandra, Grdović, Nevena, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Dinić, Svetlana, Nestorović, Nataša, Jurkowski, Tomasz, Vidaković, Melita, "PARP-1 and PARylation inhibit TET1 demethylation activity" in 2020 virtual meeting on EPIGENETICS & CHROMATIN; 2020 Sep 15-18; Virtual meeting (2020):286,
https://hdl.handle.net/21.15107/rcub_ibiss_4783 .

TY  - CHAP
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Dinić, Svetlana
AU  - Vidaković, Melita
AU  - Mihailović, Mirjana
AU  - Poznanović, Goran
AU  - Grdović, Nevena
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3947
AB  - Diabetes is a group of metabolic diseases, characterized by impaired pancreatic insulin production or insufficient cell response to insulin, which lead to hyperglycemia-induced end-organ complications. Hyperglycemia-induced imbalance between reactive oxygen species overproduction and antioxidant defense leads to oxidative stress resulting in modification of proteins, lipids, and DNA and consequently impaired cellular function. The formation of advanced glycation end products is also an important factor that contributes to chronic stress conditions and diabetic complications. Plants and mushrooms have been used as alternative medicines in the treatment of diabetes. Their extracts are sources of metabolites such as polyphenols, polysaccharides, terpenes, alkaloids, and antibiotics with pronounced biological activities, including antioxidant, antitumor, antiinflammatory, antidiabetic, antimutagenic, antihepatotoxic, and immunostimulant properties. The purpose of this review is to summarize the available treatments and beneficial effects of Centaurium erythraea, Castanea sativa, Lactarius deterrimus, and β-glucan-enriched cereal grain extracts in the treatment of diabetes-induced complications.
PB  - Academic Press - Elsevier
T2  - Biodiversity and Biomedicine
T1  - Mushroom and plant extracts as potential intervention supplements in diabetes management
DO  - 10.1016/b978-0-12-819541-3.00013-x
SP  - 247
EP  - 256
ER  - 

@inbook{
editor = "Ozturk, Munir, Egamberdieva, Dilfuza, Pešić, Milica",
author = "Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Dinić, Svetlana and Vidaković, Melita and Mihailović, Mirjana and Poznanović, Goran and Grdović, Nevena",
year = "2020",
abstract = "Diabetes is a group of metabolic diseases, characterized by impaired pancreatic insulin production or insufficient cell response to insulin, which lead to hyperglycemia-induced end-organ complications. Hyperglycemia-induced imbalance between reactive oxygen species overproduction and antioxidant defense leads to oxidative stress resulting in modification of proteins, lipids, and DNA and consequently impaired cellular function. The formation of advanced glycation end products is also an important factor that contributes to chronic stress conditions and diabetic complications. Plants and mushrooms have been used as alternative medicines in the treatment of diabetes. Their extracts are sources of metabolites such as polyphenols, polysaccharides, terpenes, alkaloids, and antibiotics with pronounced biological activities, including antioxidant, antitumor, antiinflammatory, antidiabetic, antimutagenic, antihepatotoxic, and immunostimulant properties. The purpose of this review is to summarize the available treatments and beneficial effects of Centaurium erythraea, Castanea sativa, Lactarius deterrimus, and β-glucan-enriched cereal grain extracts in the treatment of diabetes-induced complications.",
publisher = "Academic Press - Elsevier",
journal = "Biodiversity and Biomedicine",
booktitle = "Mushroom and plant extracts as potential intervention supplements in diabetes management",
doi = "10.1016/b978-0-12-819541-3.00013-x",
pages = "247-256"
}

Ozturk, M., Egamberdieva, D., Pešić, M., Uskoković, A., Arambašić Jovanović, J., Dinić, S., Vidaković, M., Mihailović, M., Poznanović, G.,& Grdović, N.. (2020). Mushroom and plant extracts as potential intervention supplements in diabetes management. in Biodiversity and Biomedicine
Academic Press - Elsevier., 247-256.
https://doi.org/10.1016/b978-0-12-819541-3.00013-x

Ozturk M, Egamberdieva D, Pešić M, Uskoković A, Arambašić Jovanović J, Dinić S, Vidaković M, Mihailović M, Poznanović G, Grdović N. Mushroom and plant extracts as potential intervention supplements in diabetes management. in Biodiversity and Biomedicine. 2020;:247-256.
doi:10.1016/b978-0-12-819541-3.00013-x .

Ozturk, Munir, Egamberdieva, Dilfuza, Pešić, Milica, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Dinić, Svetlana, Vidaković, Melita, Mihailović, Mirjana, Poznanović, Goran, Grdović, Nevena, "Mushroom and plant extracts as potential intervention supplements in diabetes management" in Biodiversity and Biomedicine (2020):247-256,
https://doi.org/10.1016/b978-0-12-819541-3.00013-x . .

TY  - CHAP
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Dinić, Svetlana
AU  - Grdović, Nevena
AU  - Uskoković, Aleksandra
AU  - Poznanović, Goran
AU  - Vidaković, Melita
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3750
AB  - Diabetes is characterized by impaired pancreatic insulin production or an insufficient cellular response to insulin. Hyperglycemia is the main cause of diabetic complications affecting vascular system, kidneys, eyes, peripheral nerves, liver and gastrointestinal system. Hyperglycemia induces overproduction of reactive oxygen species, resulting in impaired cellular function and altered cell signaling. High intracellular glucose levels activate the formation of advanced glycation end-products, the polyol pathway, the hexosamine pathway, and the protein kinase C pathway, affecting gene expression and activity of different regulator proteins. Medicinal mushrooms as source of metabolites (minerals, vitamins, polyphenols, flavonoids, terpenes, alkaloids) have been used in traditional medicine in diabetes treatment for centuries. Lactarius species exhibit a variety of biological activities, including antioxidant, antitumor, and immunostimulatory actions. In this chapter the antioxidant capacity of Lactarius deterrimus and its potential to attenuate the processes that underlie the development and progression of diabetes and diabetes-induced complications will be examined.
PB  - Academic Press
T2  - DIABETES Oxidative Stress and Dietary Antioxidants SECOND EDITION
T1  - The antioxidant potential of Lactarius deterrimus in diabetes
DO  - 10.1016/B978-0-12-815776-3.00026-7
SP  - 265
EP  - 273
ER  - 

@inbook{
author = "Arambašić Jovanović, Jelena and Mihailović, Mirjana and Dinić, Svetlana and Grdović, Nevena and Uskoković, Aleksandra and Poznanović, Goran and Vidaković, Melita",
year = "2020",
abstract = "Diabetes is characterized by impaired pancreatic insulin production or an insufficient cellular response to insulin. Hyperglycemia is the main cause of diabetic complications affecting vascular system, kidneys, eyes, peripheral nerves, liver and gastrointestinal system. Hyperglycemia induces overproduction of reactive oxygen species, resulting in impaired cellular function and altered cell signaling. High intracellular glucose levels activate the formation of advanced glycation end-products, the polyol pathway, the hexosamine pathway, and the protein kinase C pathway, affecting gene expression and activity of different regulator proteins. Medicinal mushrooms as source of metabolites (minerals, vitamins, polyphenols, flavonoids, terpenes, alkaloids) have been used in traditional medicine in diabetes treatment for centuries. Lactarius species exhibit a variety of biological activities, including antioxidant, antitumor, and immunostimulatory actions. In this chapter the antioxidant capacity of Lactarius deterrimus and its potential to attenuate the processes that underlie the development and progression of diabetes and diabetes-induced complications will be examined.",
publisher = "Academic Press",
journal = "DIABETES Oxidative Stress and Dietary Antioxidants SECOND EDITION",
booktitle = "The antioxidant potential of Lactarius deterrimus in diabetes",
doi = "10.1016/B978-0-12-815776-3.00026-7",
pages = "265-273"
}

Arambašić Jovanović, J., Mihailović, M., Dinić, S., Grdović, N., Uskoković, A., Poznanović, G.,& Vidaković, M.. (2020). The antioxidant potential of Lactarius deterrimus in diabetes. in DIABETES Oxidative Stress and Dietary Antioxidants SECOND EDITION
Academic Press., 265-273.
https://doi.org/10.1016/B978-0-12-815776-3.00026-7

Arambašić Jovanović J, Mihailović M, Dinić S, Grdović N, Uskoković A, Poznanović G, Vidaković M. The antioxidant potential of Lactarius deterrimus in diabetes. in DIABETES Oxidative Stress and Dietary Antioxidants SECOND EDITION. 2020;:265-273.
doi:10.1016/B978-0-12-815776-3.00026-7 .

Arambašić Jovanović, Jelena, Mihailović, Mirjana, Dinić, Svetlana, Grdović, Nevena, Uskoković, Aleksandra, Poznanović, Goran, Vidaković, Melita, "The antioxidant potential of Lactarius deterrimus in diabetes" in DIABETES Oxidative Stress and Dietary Antioxidants SECOND EDITION (2020):265-273,
https://doi.org/10.1016/B978-0-12-815776-3.00026-7 . .

TY  - JOUR
AU  - Mihailović, Mirjana
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Poznanović, Goran
AU  - Franić, Aida
AU  - Đorđević, Marija
AU  - Vidaković, Melita
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3658
AB  - Diabetes is the most important non-infectious disease affecting 5% of the general population. Different plant and mushroom extracts with hypoglycemic and antioxidant properties have been used traditionally as antidiabetic herbal medicines. The aim of this study was to study the in vivo effect of extracts obtained from the edible mushroom, Lactarius deterrimus (Ld), and chestnut, Castanea sativa (Cs), on the alleviation of liver damage in streptozotocin (STZ)-induced diabetic rats. The extracts were applied, either alone or in combination, for four weeks, starting from the last day of STZ administration. Diabetic rats treated with the extracts exhibited reduced hyperglycemia and lower hepatic oxidative stress. Extract treatment decreased the level of O-linkage of N-acetylglucosamine modified superoxide dismutase, catalase and NF-κB. Masson trichrome staining showed a decrease in collagen fiber deposition in the liver. Immunoblot analysis revealed the activation of the prosurvival Akt kinase after extract application. The obtained results revealed that the hyperglycemia-reducing and antioxidant effects of the Ld and Cs extracts suppressed cytotoxic signaling pathways, attenuating the negative effects of diabetes on the liver. The examined extracts are beneficial in the prevention of liver damage and could be considered for prediabetes and diabetes management after a definitive phytochemical description of extract constituents and subsequent evaluation in preclinical and clinical studies.
T2  - Archives of Biological Sciences
T1  - Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase
IS  - 2
VL  - 72
DO  - 10.2298/ABS200410017M
SP  - 233
EP  - 242
ER  - 

@article{
author = "Mihailović, Mirjana and Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Grdović, Nevena and Dinić, Svetlana and Poznanović, Goran and Franić, Aida and Đorđević, Marija and Vidaković, Melita",
year = "2020",
abstract = "Diabetes is the most important non-infectious disease affecting 5% of the general population. Different plant and mushroom extracts with hypoglycemic and antioxidant properties have been used traditionally as antidiabetic herbal medicines. The aim of this study was to study the in vivo effect of extracts obtained from the edible mushroom, Lactarius deterrimus (Ld), and chestnut, Castanea sativa (Cs), on the alleviation of liver damage in streptozotocin (STZ)-induced diabetic rats. The extracts were applied, either alone or in combination, for four weeks, starting from the last day of STZ administration. Diabetic rats treated with the extracts exhibited reduced hyperglycemia and lower hepatic oxidative stress. Extract treatment decreased the level of O-linkage of N-acetylglucosamine modified superoxide dismutase, catalase and NF-κB. Masson trichrome staining showed a decrease in collagen fiber deposition in the liver. Immunoblot analysis revealed the activation of the prosurvival Akt kinase after extract application. The obtained results revealed that the hyperglycemia-reducing and antioxidant effects of the Ld and Cs extracts suppressed cytotoxic signaling pathways, attenuating the negative effects of diabetes on the liver. The examined extracts are beneficial in the prevention of liver damage and could be considered for prediabetes and diabetes management after a definitive phytochemical description of extract constituents and subsequent evaluation in preclinical and clinical studies.",
journal = "Archives of Biological Sciences",
title = "Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase",
number = "2",
volume = "72",
doi = "10.2298/ABS200410017M",
pages = "233-242"
}

Mihailović, M., Uskoković, A., Arambašić Jovanović, J., Grdović, N., Dinić, S., Poznanović, G., Franić, A., Đorđević, M.,& Vidaković, M.. (2020). Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. in Archives of Biological Sciences, 72(2), 233-242.
https://doi.org/10.2298/ABS200410017M

Mihailović M, Uskoković A, Arambašić Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, Vidaković M. Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. in Archives of Biological Sciences. 2020;72(2):233-242.
doi:10.2298/ABS200410017M .

Mihailović, Mirjana, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Grdović, Nevena, Dinić, Svetlana, Poznanović, Goran, Franić, Aida, Đorđević, Marija, Vidaković, Melita, "Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase" in Archives of Biological Sciences, 72, no. 2 (2020):233-242,
https://doi.org/10.2298/ABS200410017M . .