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  - 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  - 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  - 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  - 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  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0378874119315545?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3390
AB  - ETHNOPHARMACOLOGICAL RELEVANCE Centaurium erythraea Rafn (CE) is used as a traditional medicinal plant in Serbia to treat different ailments due to its antidiabetic, antipyretic, antiflatulent and detoxification effects. AIM OF THE STUDY Elucidation of the mechanisms that underlie the antioxidant and pro-survival effects of the CE extract (CEE) in beta-cells and pancreatic islets from streptozotocin (STZ)-treated diabetic rats. MATERIAL AND METHODS Diabetes was induced in rats by multiple applications of low doses of STZ (40 mg/kg intraperitoneally (i.p.), for five consecutive days). CEE (100 mg/kg) was administered orally, in the pre-treated group for two weeks before diabetes induction, during the treatments with STZ and for four weeks after diabetes onset, and in the post-treatment group for four weeks after diabetes induction. The impact of CEE on diabetic islets was estimated by histological and immunohistochemical examination of the pancreas. Molecular mechanisms of the effects of CEE were also analyzed in insulinoma Rin-5F cells treated with STZ (12 mM) and CEE (0.25 mg/mL). Oxidative stress was evaluated by assessing the levels of DNA damage, lipid peroxidation, protein S-glutathionylation and enzymatic activities and expression of CAT, MnSOD, CuZnSOD, GPx and GR in beta-cells. The presence and activities of the redox-sensitive and islet-enriched regulatory proteins were also analyzed. RESULTS Treatment with CEE ameliorated the insulin level and glycemic control in STZ-induced diabetic rats by improving the structural and functional properties of pancreatic islets through multiple routes of action. The disturbance of islet morphology and islet cell contents in diabetes was reduced by the CEE treatment and was associated with a protective effect of CEE on the levels of insulin, GLUT-2 and p-Akt in diabetic islets. The antioxidant effect of CEE on STZ-treated beta-cells was displayed as reduced DNA damage, lipid peroxidation, protein S-glutathionylation and alleviation of STZ-induced disruption in MnSOD, CuZnSOD and CAT enzyme activities. The oxidative stress-induced disturbance of the transcriptional regulation of CAT, MnSOD, CuZnSOD, GPx and GR enzymes in beta-cells was improved after the CEE treatment, and was observed as readjustment of the presence and activities of redox-sensitive NFκB-p65, FOXO3A, Sp1 and Nrf-2 transcription factors. The observed CEE-mediated induction of proliferative and pro-survival pathways and insulin expression/secretion after STZ-induced oxidative stress in beta-cells could be partially attributed to a fine-tuned modulation of the activities of pro-survival Akt, ERK and p38 kinases and islet-enriched Pdx-1 and MafA regulatory factors. CONCLUSIONS The results of this study provide evidence that CEE improves the structural and functional properties of pancreatic beta-cells by correcting the endogenous antioxidant regulatory mechanisms and by promoting proliferative and pro-survival pathways in beta-cells.
T2  - Journal of Ethnopharmacology
T1  - Centaurium erythraea extract improves survival and functionality of pancreatic beta-cells in diabetes through multiple routes of action.
VL  - 242
DO  - 10.1016/j.jep.2019.112043
SP  - 112043
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 = "2019",
abstract = "ETHNOPHARMACOLOGICAL RELEVANCE Centaurium erythraea Rafn (CE) is used as a traditional medicinal plant in Serbia to treat different ailments due to its antidiabetic, antipyretic, antiflatulent and detoxification effects. AIM OF THE STUDY Elucidation of the mechanisms that underlie the antioxidant and pro-survival effects of the CE extract (CEE) in beta-cells and pancreatic islets from streptozotocin (STZ)-treated diabetic rats. MATERIAL AND METHODS Diabetes was induced in rats by multiple applications of low doses of STZ (40 mg/kg intraperitoneally (i.p.), for five consecutive days). CEE (100 mg/kg) was administered orally, in the pre-treated group for two weeks before diabetes induction, during the treatments with STZ and for four weeks after diabetes onset, and in the post-treatment group for four weeks after diabetes induction. The impact of CEE on diabetic islets was estimated by histological and immunohistochemical examination of the pancreas. Molecular mechanisms of the effects of CEE were also analyzed in insulinoma Rin-5F cells treated with STZ (12 mM) and CEE (0.25 mg/mL). Oxidative stress was evaluated by assessing the levels of DNA damage, lipid peroxidation, protein S-glutathionylation and enzymatic activities and expression of CAT, MnSOD, CuZnSOD, GPx and GR in beta-cells. The presence and activities of the redox-sensitive and islet-enriched regulatory proteins were also analyzed. RESULTS Treatment with CEE ameliorated the insulin level and glycemic control in STZ-induced diabetic rats by improving the structural and functional properties of pancreatic islets through multiple routes of action. The disturbance of islet morphology and islet cell contents in diabetes was reduced by the CEE treatment and was associated with a protective effect of CEE on the levels of insulin, GLUT-2 and p-Akt in diabetic islets. The antioxidant effect of CEE on STZ-treated beta-cells was displayed as reduced DNA damage, lipid peroxidation, protein S-glutathionylation and alleviation of STZ-induced disruption in MnSOD, CuZnSOD and CAT enzyme activities. The oxidative stress-induced disturbance of the transcriptional regulation of CAT, MnSOD, CuZnSOD, GPx and GR enzymes in beta-cells was improved after the CEE treatment, and was observed as readjustment of the presence and activities of redox-sensitive NFκB-p65, FOXO3A, Sp1 and Nrf-2 transcription factors. The observed CEE-mediated induction of proliferative and pro-survival pathways and insulin expression/secretion after STZ-induced oxidative stress in beta-cells could be partially attributed to a fine-tuned modulation of the activities of pro-survival Akt, ERK and p38 kinases and islet-enriched Pdx-1 and MafA regulatory factors. CONCLUSIONS The results of this study provide evidence that CEE improves the structural and functional properties of pancreatic beta-cells by correcting the endogenous antioxidant regulatory mechanisms and by promoting proliferative and pro-survival pathways in beta-cells.",
journal = "Journal of Ethnopharmacology",
title = "Centaurium erythraea extract improves survival and functionality of pancreatic beta-cells in diabetes through multiple routes of action.",
volume = "242",
doi = "10.1016/j.jep.2019.112043",
pages = "112043"
}

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.. (2019). Centaurium erythraea extract improves survival and functionality of pancreatic beta-cells in diabetes through multiple routes of action.. in Journal of Ethnopharmacology, 242, 112043.
https://doi.org/10.1016/j.jep.2019.112043

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 improves survival and functionality of pancreatic beta-cells in diabetes through multiple routes of action.. in Journal of Ethnopharmacology. 2019;242:112043.
doi:10.1016/j.jep.2019.112043 .

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 improves survival and functionality of pancreatic beta-cells in diabetes through multiple routes of action." in Journal of Ethnopharmacology, 242 (2019):112043,
https://doi.org/10.1016/j.jep.2019.112043 . .

TY  - JOUR
AU  - Tolić, Anja
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Rajić, Jovana
AU  - Đorđević, Miloš
AU  - Đorđević, Marija
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Poznanović, Goran
AU  - Uskoković, Aleksandra
AU  - Vidaković, Melita
PY  - 2019
UR  - http://doi.wiley.com/10.1111/jcmm.14154
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3246
AB  - Poly [ADP-ribose] polymerase 1 (PARP-1) has an inhibitory effect on C-X-C motif chemokine 12 gene (Cxcl12) transcription. We examined whether PARP-1 affects the epigenetic control of Cxcl12 expression by changing its DNA methylation pattern. We observed increased expression of Cxcl12 in PARP-1 knock-out mouse embryonic fibroblasts (PARP1-/-) in comparison to wild-type mouse embryonic fibroblasts (NIH3T3). In the Cxcl12 gene, a CpG island is present in the promoter, the 5' untranslated region (5' UTR), the first exon and in the first intron. The methylation state of Cxcl12 in each cell line was investigated by methylation-specific PCR (MSP) and high resolution melting analysis (HRM). Both methods revealed strong demethylation in PARP1-/- compared to NIH3T3 cells in all four DNA regions. Increased expression of the Ten-eleven translocation (Tet) genes in PARP1-/- cells indicated that TETs could be important factors in Cxcl12 demethylation in the absence of PARP-1, accounting for its increased expression. Our results showed that PARP-1 was a potential upstream player in (de)methylation events that modulated Cxcl12 expression.
T2  - Journal of Cellular and Molecular Medicine
T1  - Absence of PARP-1 affects Cxcl12 expression by increasing DNA demethylation
IS  - 4
VL  - 23
DO  - 10.1111/jcmm.14154
SP  - 2610
EP  - 2618
ER  - 

@article{
author = "Tolić, Anja and Grdović, Nevena and Dinić, Svetlana and Rajić, Jovana and Đorđević, Miloš and Đorđević, Marija and Arambašić Jovanović, Jelena and Mihailović, Mirjana and Poznanović, Goran and Uskoković, Aleksandra and Vidaković, Melita",
year = "2019",
abstract = "Poly [ADP-ribose] polymerase 1 (PARP-1) has an inhibitory effect on C-X-C motif chemokine 12 gene (Cxcl12) transcription. We examined whether PARP-1 affects the epigenetic control of Cxcl12 expression by changing its DNA methylation pattern. We observed increased expression of Cxcl12 in PARP-1 knock-out mouse embryonic fibroblasts (PARP1-/-) in comparison to wild-type mouse embryonic fibroblasts (NIH3T3). In the Cxcl12 gene, a CpG island is present in the promoter, the 5' untranslated region (5' UTR), the first exon and in the first intron. The methylation state of Cxcl12 in each cell line was investigated by methylation-specific PCR (MSP) and high resolution melting analysis (HRM). Both methods revealed strong demethylation in PARP1-/- compared to NIH3T3 cells in all four DNA regions. Increased expression of the Ten-eleven translocation (Tet) genes in PARP1-/- cells indicated that TETs could be important factors in Cxcl12 demethylation in the absence of PARP-1, accounting for its increased expression. Our results showed that PARP-1 was a potential upstream player in (de)methylation events that modulated Cxcl12 expression.",
journal = "Journal of Cellular and Molecular Medicine",
title = "Absence of PARP-1 affects Cxcl12 expression by increasing DNA demethylation",
number = "4",
volume = "23",
doi = "10.1111/jcmm.14154",
pages = "2610-2618"
}

Tolić, A., Grdović, N., Dinić, S., Rajić, J., Đorđević, M., Đorđević, M., Arambašić Jovanović, J., Mihailović, M., Poznanović, G., Uskoković, A.,& Vidaković, M.. (2019). Absence of PARP-1 affects Cxcl12 expression by increasing DNA demethylation. in Journal of Cellular and Molecular Medicine, 23(4), 2610-2618.
https://doi.org/10.1111/jcmm.14154

Tolić A, Grdović N, Dinić S, Rajić J, Đorđević M, Đorđević M, Arambašić Jovanović J, Mihailović M, Poznanović G, Uskoković A, Vidaković M. Absence of PARP-1 affects Cxcl12 expression by increasing DNA demethylation. in Journal of Cellular and Molecular Medicine. 2019;23(4):2610-2618.
doi:10.1111/jcmm.14154 .

Tolić, Anja, Grdović, Nevena, Dinić, Svetlana, Rajić, Jovana, Đorđević, Miloš, Đorđević, Marija, Arambašić Jovanović, Jelena, Mihailović, Mirjana, Poznanović, Goran, Uskoković, Aleksandra, Vidaković, Melita, "Absence of PARP-1 affects Cxcl12 expression by increasing DNA demethylation" in Journal of Cellular and Molecular Medicine, 23, no. 4 (2019):2610-2618,
https://doi.org/10.1111/jcmm.14154 . .

TY  - CONF
AU  - Sarić, Ana
AU  - Tolić, Anja
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Rajić, Jovana
AU  - Đorđević, Miloš
AU  - Đorđević, Marija
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Uskoković, Aleksandra
AU  - Dučić, Tanja
AU  - Vidaković, Melita
PY  - 2019
UR  - https://www.cost.eu/cost-events/the-extracellular-vesicles-paradigm-of-intra-intercellular-communication/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5920
AB  - Double-strand deoxyribonucleic acid (dsDNA) carries the genetic information needed for normal development, growth, survival and reproduction of all living beings (except RNA viruses and other potential DNA-less microorganisms). On top of it, epigenetic processes orchestrate the cell type-specific use of the genetic information essential for normal development and for maintaining the overall integrity of the genome. The alteration of epigenetic marks (e.g. DNA methylation patterns) by hyperglycaemia, oxidative stress and inflammation may have potential epigenetic impacts on gene regulation in diabetic individuals. We used the Fourier transform-infrared (FTIR) spectroscopy (ALBA synchrotron, Cerdanyola del valles, Spain) for qualitative spectral analysis of DNA from mouse fibroblast cells (NIH3T3) and the same cells treated with demetilating agent 5-azacytidine (5-aza). FTIR spectroscopy has the advantage of generating structural information of the entire DNA molecule in a single spectrum, including possible conformational sub-states, present in the sample (methylated/nonmethylated cytosine). The technique is ideal for systematic studies of DNA/RNA sequence variations and covalent modifications, since it is non-destructive and requires only small sample amounts. The FTIR region of interest when studying nucleic acids is 1800–900 cm-1.We obtained the global information regarding the DNA profiles in NIH3T3 with and without 5-aza treatment by FTIR spectroscopy. Some differences in DNA methylation profiles between examined cell lines were qualitatively described by FTIR spectroscopy and compared with restriction analysis method. Using FTIR spectroscopy the most interesting picks were observed approximately at wavelength: 2960-2850 cm-1, 1400-900 cm-1 and 1150 cm-1. These results are in the same time a verification of the proof of principle for synchrotron-based FTIR micro-spectroscopic detection of the differences in the DNA methylation profiles in cells.
PB  - COST Action CellFit
C3  - 3rd CellFit annual meeting: The extracellular vesicles paradigm of intracellular communication; 2019 Oct 10-12; Athens, Greece
T1  - The FTIR spectroscopy as a method of choice for detecting changes in DNA profiles of the mouse embryonic fibroblasts after the treatment with 5-aza
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5920
ER  - 

@conference{
author = "Sarić, Ana and Tolić, Anja and Grdović, Nevena and Dinić, Svetlana and Rajić, Jovana and Đorđević, Miloš and Đorđević, Marija and Arambašić Jovanović, Jelena and Mihailović, Mirjana and Uskoković, Aleksandra and Dučić, Tanja and Vidaković, Melita",
year = "2019",
abstract = "Double-strand deoxyribonucleic acid (dsDNA) carries the genetic information needed for normal development, growth, survival and reproduction of all living beings (except RNA viruses and other potential DNA-less microorganisms). On top of it, epigenetic processes orchestrate the cell type-specific use of the genetic information essential for normal development and for maintaining the overall integrity of the genome. The alteration of epigenetic marks (e.g. DNA methylation patterns) by hyperglycaemia, oxidative stress and inflammation may have potential epigenetic impacts on gene regulation in diabetic individuals. We used the Fourier transform-infrared (FTIR) spectroscopy (ALBA synchrotron, Cerdanyola del valles, Spain) for qualitative spectral analysis of DNA from mouse fibroblast cells (NIH3T3) and the same cells treated with demetilating agent 5-azacytidine (5-aza). FTIR spectroscopy has the advantage of generating structural information of the entire DNA molecule in a single spectrum, including possible conformational sub-states, present in the sample (methylated/nonmethylated cytosine). The technique is ideal for systematic studies of DNA/RNA sequence variations and covalent modifications, since it is non-destructive and requires only small sample amounts. The FTIR region of interest when studying nucleic acids is 1800–900 cm-1.We obtained the global information regarding the DNA profiles in NIH3T3 with and without 5-aza treatment by FTIR spectroscopy. Some differences in DNA methylation profiles between examined cell lines were qualitatively described by FTIR spectroscopy and compared with restriction analysis method. Using FTIR spectroscopy the most interesting picks were observed approximately at wavelength: 2960-2850 cm-1, 1400-900 cm-1 and 1150 cm-1. These results are in the same time a verification of the proof of principle for synchrotron-based FTIR micro-spectroscopic detection of the differences in the DNA methylation profiles in cells.",
publisher = "COST Action CellFit",
journal = "3rd CellFit annual meeting: The extracellular vesicles paradigm of intracellular communication; 2019 Oct 10-12; Athens, Greece",
title = "The FTIR spectroscopy as a method of choice for detecting changes in DNA profiles of the mouse embryonic fibroblasts after the treatment with 5-aza",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5920"
}

Sarić, A., Tolić, A., Grdović, N., Dinić, S., Rajić, J., Đorđević, M., Đorđević, M., Arambašić Jovanović, J., Mihailović, M., Uskoković, A., Dučić, T.,& Vidaković, M.. (2019). The FTIR spectroscopy as a method of choice for detecting changes in DNA profiles of the mouse embryonic fibroblasts after the treatment with 5-aza. in 3rd CellFit annual meeting: The extracellular vesicles paradigm of intracellular communication; 2019 Oct 10-12; Athens, Greece
COST Action CellFit..
https://hdl.handle.net/21.15107/rcub_ibiss_5920

Sarić A, Tolić A, Grdović N, Dinić S, Rajić J, Đorđević M, Đorđević M, Arambašić Jovanović J, Mihailović M, Uskoković A, Dučić T, Vidaković M. The FTIR spectroscopy as a method of choice for detecting changes in DNA profiles of the mouse embryonic fibroblasts after the treatment with 5-aza. in 3rd CellFit annual meeting: The extracellular vesicles paradigm of intracellular communication; 2019 Oct 10-12; Athens, Greece. 2019;.
https://hdl.handle.net/21.15107/rcub_ibiss_5920 .

Sarić, Ana, Tolić, Anja, Grdović, Nevena, Dinić, Svetlana, Rajić, Jovana, Đorđević, Miloš, Đorđević, Marija, Arambašić Jovanović, Jelena, Mihailović, Mirjana, Uskoković, Aleksandra, Dučić, Tanja, Vidaković, Melita, "The FTIR spectroscopy as a method of choice for detecting changes in DNA profiles of the mouse embryonic fibroblasts after the treatment with 5-aza" in 3rd CellFit annual meeting: The extracellular vesicles paradigm of intracellular communication; 2019 Oct 10-12; Athens, Greece (2019),
https://hdl.handle.net/21.15107/rcub_ibiss_5920 .

TY  - CONF
AU  - Rajić, Jovana
AU  - Tolić, Anja
AU  - Đorđević, Marija
AU  - Đorđević, Miloš
AU  - Mihailović, Mirjana
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Poznanović, Goran
AU  - Inić-Kanada, Aleksandra
AU  - Barisani-Asenbauer, Talin
AU  - Grdović, Nevena
AU  - Vidaković, Melita
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5697
AB  - Conjunctival fibrosis often emerges after infections, inflammations and mechanical stresses of the eye and when severe results in impaired vision. Recent data documented unavoidable role of epithelial to mesenchymal transition (EMT) in every fibrotic process including fibrosis-based eye conditions. The aim of this work was to establish whether human conjunctival epithelial (HCjE) cells are prone to EMT induction after prolonged treatment with well-known EMT inducers TGF-β proteins, and to test capabilities of TGF-β1, TGF-β2 and their combination to trigger this process. While TGF-β2 induced only alterations in cell-cell adhesion, TGF-β1 and combination of TGF-β proteins induced prominent change in cell morphology reflected in loss of cell-cell contacts, changes in shape from epithelial polygonal to spindle-like shape typical for mesenchymal phenotype and acquired ability to move. Statistically significant reduction of mRNA expression of epithelial marker genes (CDH1, OCLN, DSP) was observed in all treatment groups, while mRNA expression level of mesenchymal marker genes (CDH2, FN1, VIM) and EMT-related transcription factors (SNAI1, ZEB2, TWIST1) varied among treatment groups. TGF-β1 treatment induced the most pronounced increase in the level of mRNA of genes characteristic for mesenchymal phenotype that was accompanied with corresponding increase in protein level of two mesenchymal markers (CDH2, FN1), in parallel with decrease in protein expression of two epithelial markers (CDH1, DSP). To conclude, HCjE cells are prone to EMT induction and TGF-β1 possesses the highest potential for EMT induction in HCjE cells, suggesting that, in conditions of chronic inflammation, induction of EMT in conjunctival cells could contribute to fibrosis-related eye diseases.
PB  - Belgrade: Faculty of Chemistry
C3  - The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia
T1  - The capability of different TGF-β isoforms to induce EMT in human conjunctival epithelial cells
SP  - 159
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5697
ER  - 

@conference{
author = "Rajić, Jovana and Tolić, Anja and Đorđević, Marija and Đorđević, Miloš and Mihailović, Mirjana and Dinić, Svetlana and Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Poznanović, Goran and Inić-Kanada, Aleksandra and Barisani-Asenbauer, Talin and Grdović, Nevena and Vidaković, Melita",
year = "2019",
abstract = "Conjunctival fibrosis often emerges after infections, inflammations and mechanical stresses of the eye and when severe results in impaired vision. Recent data documented unavoidable role of epithelial to mesenchymal transition (EMT) in every fibrotic process including fibrosis-based eye conditions. The aim of this work was to establish whether human conjunctival epithelial (HCjE) cells are prone to EMT induction after prolonged treatment with well-known EMT inducers TGF-β proteins, and to test capabilities of TGF-β1, TGF-β2 and their combination to trigger this process. While TGF-β2 induced only alterations in cell-cell adhesion, TGF-β1 and combination of TGF-β proteins induced prominent change in cell morphology reflected in loss of cell-cell contacts, changes in shape from epithelial polygonal to spindle-like shape typical for mesenchymal phenotype and acquired ability to move. Statistically significant reduction of mRNA expression of epithelial marker genes (CDH1, OCLN, DSP) was observed in all treatment groups, while mRNA expression level of mesenchymal marker genes (CDH2, FN1, VIM) and EMT-related transcription factors (SNAI1, ZEB2, TWIST1) varied among treatment groups. TGF-β1 treatment induced the most pronounced increase in the level of mRNA of genes characteristic for mesenchymal phenotype that was accompanied with corresponding increase in protein level of two mesenchymal markers (CDH2, FN1), in parallel with decrease in protein expression of two epithelial markers (CDH1, DSP). To conclude, HCjE cells are prone to EMT induction and TGF-β1 possesses the highest potential for EMT induction in HCjE cells, suggesting that, in conditions of chronic inflammation, induction of EMT in conjunctival cells could contribute to fibrosis-related eye diseases.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia",
title = "The capability of different TGF-β isoforms to induce EMT in human conjunctival epithelial cells",
pages = "159",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5697"
}

Rajić, J., Tolić, A., Đorđević, M., Đorđević, M., Mihailović, M., Dinić, S., Uskoković, A., Arambašić Jovanović, J., Poznanović, G., Inić-Kanada, A., Barisani-Asenbauer, T., Grdović, N.,& Vidaković, M.. (2019). The capability of different TGF-β isoforms to induce EMT in human conjunctival epithelial cells. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 159.
https://hdl.handle.net/21.15107/rcub_ibiss_5697

Rajić J, Tolić A, Đorđević M, Đorđević M, Mihailović M, Dinić S, Uskoković A, Arambašić Jovanović J, Poznanović G, Inić-Kanada A, Barisani-Asenbauer T, Grdović N, Vidaković M. The capability of different TGF-β isoforms to induce EMT in human conjunctival epithelial cells. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia. 2019;:159.
https://hdl.handle.net/21.15107/rcub_ibiss_5697 .

Rajić, Jovana, Tolić, Anja, Đorđević, Marija, Đorđević, Miloš, Mihailović, Mirjana, Dinić, Svetlana, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Poznanović, Goran, Inić-Kanada, Aleksandra, Barisani-Asenbauer, Talin, Grdović, Nevena, Vidaković, Melita, "The capability of different TGF-β isoforms to induce EMT in human conjunctival epithelial cells" in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia (2019):159,
https://hdl.handle.net/21.15107/rcub_ibiss_5697 .

TY  - CONF
AU  - Sarić, Ana
AU  - Tolić, Anja
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Rajić, Jovana
AU  - Đorđević, Miloš
AU  - Đorđević, Marija
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Poznanović, Goran
AU  - Uskoković, Aleksandra
AU  - Vidaković, Melita
AU  - Dučić, Tanja
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5694
AB  - Epigenetic processes orchestrate the cell type-specific use of the genetic information
essential for normal development and for maintaining the overall integrity of the genome.
DNA methylation is probably the most extensively studied epigenetic mark and represents
the covalent attachment of a methyl group to cytosine that is located next to guanine within
the genomic DNA. The alteration of DNA methylation patterns by hyperglycaemia, oxidative
stress and inflammation may have potential epigenetic impacts on gene regulation in diabetic
individuals. Further research devoted to improve the steps that could be undertaken in the
early diagnosis, prevention and treatment of diabetes and its complications is a scientifically
and socially significant task. We used the Fourier transform-infrared (FTIR) spectroscopy
(ALBA synchrotron, Cerdanyola del valles, Spain) for qualitative spectral analysis of
normomethylated DNA from mouse fibroblast cells (NIH3T3) and hypomethylated DNA
from PARP-1 knockout mouse fibroblast cells (PARP-/-). We obtained the global information
regarding the DNA methylation profiles in mouse fibroblast cells by FTIR spectroscopy that
was visualised by immune-fluorescent staining using anti-methyl cytosine (5mC) antibody.
Some differences in DNA methylation profiles between examined cell lines were observed
in spectral region significant for cytosine (990-1250 nm). The most interesting picks were
observed approximately at wavelength: 1240 nm, 1150 nm, 1110 nm and 1010 nm. These
results are in the same time a verification of the proof of principle for FTIR based analysis of
the differences between normomethylated and hypomethylated genomic DNA which could
be set as a potential predictive and diagnostic tool in future. To our knowledge this is a first
time that synchrotron-based FTIR micro-spectroscopy is used for detection of the presence
of 5mC and changes in the DNA methylation profile in cells.
PB  - Belgrade: Serbian Genetic Society
C3  - 6th Congress of the Serbian genetic society: Book of abstracts; 2019 Oct 13-17; Vrnjačka Banja, Serbia
T1  - Detection of DNA methylation profiles in mouse embryonic fibroblasts using Fourier transform-infrared spectroscopy
SP  - 75
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5694
ER  - 

@conference{
author = "Sarić, Ana and Tolić, Anja and Grdović, Nevena and Dinić, Svetlana and Rajić, Jovana and Đorđević, Miloš and Đorđević, Marija and Arambašić Jovanović, Jelena and Mihailović, Mirjana and Poznanović, Goran and Uskoković, Aleksandra and Vidaković, Melita and Dučić, Tanja",
year = "2019",
abstract = "Epigenetic processes orchestrate the cell type-specific use of the genetic information
essential for normal development and for maintaining the overall integrity of the genome.
DNA methylation is probably the most extensively studied epigenetic mark and represents
the covalent attachment of a methyl group to cytosine that is located next to guanine within
the genomic DNA. The alteration of DNA methylation patterns by hyperglycaemia, oxidative
stress and inflammation may have potential epigenetic impacts on gene regulation in diabetic
individuals. Further research devoted to improve the steps that could be undertaken in the
early diagnosis, prevention and treatment of diabetes and its complications is a scientifically
and socially significant task. We used the Fourier transform-infrared (FTIR) spectroscopy
(ALBA synchrotron, Cerdanyola del valles, Spain) for qualitative spectral analysis of
normomethylated DNA from mouse fibroblast cells (NIH3T3) and hypomethylated DNA
from PARP-1 knockout mouse fibroblast cells (PARP-/-). We obtained the global information
regarding the DNA methylation profiles in mouse fibroblast cells by FTIR spectroscopy that
was visualised by immune-fluorescent staining using anti-methyl cytosine (5mC) antibody.
Some differences in DNA methylation profiles between examined cell lines were observed
in spectral region significant for cytosine (990-1250 nm). The most interesting picks were
observed approximately at wavelength: 1240 nm, 1150 nm, 1110 nm and 1010 nm. These
results are in the same time a verification of the proof of principle for FTIR based analysis of
the differences between normomethylated and hypomethylated genomic DNA which could
be set as a potential predictive and diagnostic tool in future. To our knowledge this is a first
time that synchrotron-based FTIR micro-spectroscopy is used for detection of the presence
of 5mC and changes in the DNA methylation profile in cells.",
publisher = "Belgrade: Serbian Genetic Society",
journal = "6th Congress of the Serbian genetic society: Book of abstracts; 2019 Oct 13-17; Vrnjačka Banja, Serbia",
title = "Detection of DNA methylation profiles in mouse embryonic fibroblasts using Fourier transform-infrared spectroscopy",
pages = "75",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5694"
}

Sarić, A., Tolić, A., Grdović, N., Dinić, S., Rajić, J., Đorđević, M., Đorđević, M., Arambašić Jovanović, J., Mihailović, M., Poznanović, G., Uskoković, A., Vidaković, M.,& Dučić, T.. (2019). Detection of DNA methylation profiles in mouse embryonic fibroblasts using Fourier transform-infrared spectroscopy. in 6th Congress of the Serbian genetic society: Book of abstracts; 2019 Oct 13-17; Vrnjačka Banja, Serbia
Belgrade: Serbian Genetic Society., 75.
https://hdl.handle.net/21.15107/rcub_ibiss_5694

Sarić A, Tolić A, Grdović N, Dinić S, Rajić J, Đorđević M, Đorđević M, Arambašić Jovanović J, Mihailović M, Poznanović G, Uskoković A, Vidaković M, Dučić T. Detection of DNA methylation profiles in mouse embryonic fibroblasts using Fourier transform-infrared spectroscopy. in 6th Congress of the Serbian genetic society: Book of abstracts; 2019 Oct 13-17; Vrnjačka Banja, Serbia. 2019;:75.
https://hdl.handle.net/21.15107/rcub_ibiss_5694 .

Sarić, Ana, Tolić, Anja, Grdović, Nevena, Dinić, Svetlana, Rajić, Jovana, Đorđević, Miloš, Đorđević, Marija, Arambašić Jovanović, Jelena, Mihailović, Mirjana, Poznanović, Goran, Uskoković, Aleksandra, Vidaković, Melita, Dučić, Tanja, "Detection of DNA methylation profiles in mouse embryonic fibroblasts using Fourier transform-infrared spectroscopy" in 6th Congress of the Serbian genetic society: Book of abstracts; 2019 Oct 13-17; Vrnjačka Banja, Serbia (2019):75,
https://hdl.handle.net/21.15107/rcub_ibiss_5694 .

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  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5692
AB  - Diabetes is characterized by hyperglycemia resulting from a deficiency in insulin secretion and/or action leading to serve diabetic complications. Despite numerous efforts, recovery, and maintenance of functional beta-cells is still an unresolved task in diabetes therapy. Considering anti-diabetic properties of medicinal herb Centaurium erythraea Rafn (CE), this study aimed to analyze protective effects of the CE extract on Rin-5F beta-cell line exposed to diabetogenic agent streptozotocin (STZ). Cytoprotective concentration of CE extract (0.25 mg/mL) and IC50 dose of STZ (12 mM) were determined using cell viability assay (MTT). The level of insulin mRNA and the concentration of insulin released from beta-cells in a culture medium were analyzed by RT-qPCR and ELISA, respectively. Activity of Akt, ERK and p38 kinases, as well as nuclear levels of islet-enriched Pdx1 and MafA proteins were assessed by Western blot analysis. In comparison to STZ-treated beta-cells, CE extract/STZ co-treatment increased viability of Rin-5F cells for 12%. STZ-treated beta-cells displayed reduction mRNA level of insulin to 63% and reduced insulin secretion to 76% in comparison to control, while application of CE extract improved insulin mRNA level to 77% and insulin secretion to 90% of the control level. Improved viability and functionality of beta-cells could be ascribed to a CE extract-mediated modulation of the activities of pro-survival Akt, ERK and p38 kinases and Pdx1 and MafA factors involved in regulation of beta-cell proliferation and insulin expression/secretion. The results of this study suggest that CE extract promotes proliferative and pro-survival pathways in beta-cells and improves their functional properties.
PB  - Lisboa: Universidade Lusófona
C3  - NutRedOx COST Action CA 16112; 2019 Oct 2-4; Lisboa, Portugal
T1  - Centaurium erithraea extract mediates prosurvival pathways and insulin expression in STZ-treated beta-cells
SP  - 25
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5692
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 = "2019",
abstract = "Diabetes is characterized by hyperglycemia resulting from a deficiency in insulin secretion and/or action leading to serve diabetic complications. Despite numerous efforts, recovery, and maintenance of functional beta-cells is still an unresolved task in diabetes therapy. Considering anti-diabetic properties of medicinal herb Centaurium erythraea Rafn (CE), this study aimed to analyze protective effects of the CE extract on Rin-5F beta-cell line exposed to diabetogenic agent streptozotocin (STZ). Cytoprotective concentration of CE extract (0.25 mg/mL) and IC50 dose of STZ (12 mM) were determined using cell viability assay (MTT). The level of insulin mRNA and the concentration of insulin released from beta-cells in a culture medium were analyzed by RT-qPCR and ELISA, respectively. Activity of Akt, ERK and p38 kinases, as well as nuclear levels of islet-enriched Pdx1 and MafA proteins were assessed by Western blot analysis. In comparison to STZ-treated beta-cells, CE extract/STZ co-treatment increased viability of Rin-5F cells for 12%. STZ-treated beta-cells displayed reduction mRNA level of insulin to 63% and reduced insulin secretion to 76% in comparison to control, while application of CE extract improved insulin mRNA level to 77% and insulin secretion to 90% of the control level. Improved viability and functionality of beta-cells could be ascribed to a CE extract-mediated modulation of the activities of pro-survival Akt, ERK and p38 kinases and Pdx1 and MafA factors involved in regulation of beta-cell proliferation and insulin expression/secretion. The results of this study suggest that CE extract promotes proliferative and pro-survival pathways in beta-cells and improves their functional properties.",
publisher = "Lisboa: Universidade Lusófona",
journal = "NutRedOx COST Action CA 16112; 2019 Oct 2-4; Lisboa, Portugal",
title = "Centaurium erithraea extract mediates prosurvival pathways and insulin expression in STZ-treated beta-cells",
pages = "25",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5692"
}

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.. (2019). Centaurium erithraea extract mediates prosurvival pathways and insulin expression in STZ-treated beta-cells. in NutRedOx COST Action CA 16112; 2019 Oct 2-4; Lisboa, Portugal
Lisboa: Universidade Lusófona., 25.
https://hdl.handle.net/21.15107/rcub_ibiss_5692

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 erithraea extract mediates prosurvival pathways and insulin expression in STZ-treated beta-cells. in NutRedOx COST Action CA 16112; 2019 Oct 2-4; Lisboa, Portugal. 2019;:25.
https://hdl.handle.net/21.15107/rcub_ibiss_5692 .

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 erithraea extract mediates prosurvival pathways and insulin expression in STZ-treated beta-cells" in NutRedOx COST Action CA 16112; 2019 Oct 2-4; Lisboa, Portugal (2019):25,
https://hdl.handle.net/21.15107/rcub_ibiss_5692 .

TY  - CONF
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Uskoković, Aleksandra
AU  - Dinić, Svetlana
AU  - Đorđević, Miloš
AU  - Grdović, Nevena
AU  - Đorđević, Marija
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Poznanović, Goran
AU  - Vidaković, Melita
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5691
AB  - Diabetes is a metabolic disorder characterized by impaired pancreatic insulin production and/or insufficient cell response to insulin and is characterized by chronic hyperglycemia which induces metabolic abnormalities in different cells and tissues. High intracellular glucose concentrations induce the overproduction of reactive oxygen species and activate the formation of advanced glycation end-products, the polyol pathway, the hexosamine pathway and the protein kinase C pathway, influencing gene expression and activity of different regulatory proteins. These changes lead to diabetic end-organ complications affecting vascular system, kidneys, eyes, peripheral nerves, liver and gastrointestinal system. Diabetes represents one example of a disease that has been treated according to the traditional medicine world-wide and as such represents a good model for investigation of beneficial effect of different plant and mushroom extracts and isolated compounds in the management of diabetes and diabetes-related complications. Plants and mushrooms extracts are the source of metabolites such as polyphenols, polysaccharides, terpenes, alkaloids and antibiotics with pronounced biological activities including antioxidant, antitumor, anti-inflammatory, antidiabetic, antimutagenic, anti-hepatotoxic and immunostimulant properties. We provided an overview of the beneficial effects of the examined extracts obtained from flowering plant 
(Centaurium erythraea), sweet chestnut (Castanea sativa), edible mushroom (Lactarius deterrimus) and natural products containing p-glucans (from cereal grains) in the treatment of diabetes. Their antioxidant and antidiabetic properties in vitro and positive effects on different processes involved in the onset and progression of diabetes and its complications in vivo are presented and possible mechanisms that underlie these effects are suggested.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Book of abstracts: The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia
T1  - Plant and mushroom extracts as potential intervening supplements in diabetes and diabetic complications
SP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5691
ER  - 

@conference{
author = "Arambašić Jovanović, Jelena and Mihailović, Mirjana and Uskoković, Aleksandra and Dinić, Svetlana and Đorđević, Miloš and Grdović, Nevena and Đorđević, Marija and Tolić, Anja and Rajić, Jovana and Poznanović, Goran and Vidaković, Melita",
year = "2019",
abstract = "Diabetes is a metabolic disorder characterized by impaired pancreatic insulin production and/or insufficient cell response to insulin and is characterized by chronic hyperglycemia which induces metabolic abnormalities in different cells and tissues. High intracellular glucose concentrations induce the overproduction of reactive oxygen species and activate the formation of advanced glycation end-products, the polyol pathway, the hexosamine pathway and the protein kinase C pathway, influencing gene expression and activity of different regulatory proteins. These changes lead to diabetic end-organ complications affecting vascular system, kidneys, eyes, peripheral nerves, liver and gastrointestinal system. Diabetes represents one example of a disease that has been treated according to the traditional medicine world-wide and as such represents a good model for investigation of beneficial effect of different plant and mushroom extracts and isolated compounds in the management of diabetes and diabetes-related complications. Plants and mushrooms extracts are the source of metabolites such as polyphenols, polysaccharides, terpenes, alkaloids and antibiotics with pronounced biological activities including antioxidant, antitumor, anti-inflammatory, antidiabetic, antimutagenic, anti-hepatotoxic and immunostimulant properties. We provided an overview of the beneficial effects of the examined extracts obtained from flowering plant 
(Centaurium erythraea), sweet chestnut (Castanea sativa), edible mushroom (Lactarius deterrimus) and natural products containing p-glucans (from cereal grains) in the treatment of diabetes. Their antioxidant and antidiabetic properties in vitro and positive effects on different processes involved in the onset and progression of diabetes and its complications in vivo are presented and possible mechanisms that underlie these effects are suggested.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Book of abstracts: The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia",
title = "Plant and mushroom extracts as potential intervening supplements in diabetes and diabetic complications",
pages = "40",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5691"
}

Arambašić Jovanović, J., Mihailović, M., Uskoković, A., Dinić, S., Đorđević, M., Grdović, N., Đorđević, M., Tolić, A., Rajić, J., Poznanović, G.,& Vidaković, M.. (2019). Plant and mushroom extracts as potential intervening supplements in diabetes and diabetic complications. in Book of abstracts: The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 40.
https://hdl.handle.net/21.15107/rcub_ibiss_5691

Arambašić Jovanović J, Mihailović M, Uskoković A, Dinić S, Đorđević M, Grdović N, Đorđević M, Tolić A, Rajić J, Poznanović G, Vidaković M. Plant and mushroom extracts as potential intervening supplements in diabetes and diabetic complications. in Book of abstracts: The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia. 2019;:40.
https://hdl.handle.net/21.15107/rcub_ibiss_5691 .

Arambašić Jovanović, Jelena, Mihailović, Mirjana, Uskoković, Aleksandra, Dinić, Svetlana, Đorđević, Miloš, Grdović, Nevena, Đorđević, Marija, Tolić, Anja, Rajić, Jovana, Poznanović, Goran, Vidaković, Melita, "Plant and mushroom extracts as potential intervening supplements in diabetes and diabetic complications" in Book of abstracts: The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia (2019):40,
https://hdl.handle.net/21.15107/rcub_ibiss_5691 .

TY  - JOUR
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Đorđević, Marija
AU  - Đorđević, Miloš
AU  - Dinić, Svetlana
AU  - Grdović, Nevena
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Poznanović, Goran
AU  - Jurkowski, Tomasz P.
AU  - Vidaković, Melita
AU  - Uskoković, Aleksandra
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3460
AB  - Previously, we described the link between C-X-C motif chemokine 12 (Cxcl12) gene induction
and DNA hypomethylation in the absence of poly(ADP-ribose) polymerase 1 (PARP-1). We have now
firmly established that demethylation is the primary cause of gene induction on the basis of Cxcl12 gene
upregulation upon treatment with the demethylating agent 5-azacytidine (5-aza). Since the demethylation
state of Cxcl12 is favored by PARP-1 absence, we investigated the presence of ten-eleven translocation
(TET) proteins on the Cxcl12 promoter in order to corroborate the relationship between the demethylation
process and increased gene expression that occurs in the absence of PARP-1. Analysis was performed on the promoter region within CpG islands of Cxcl12 from control mouse embryonic fibroblasts (NIH3T3)
and PARP-1 knock-out mouse embryonic fibroblasts (PARP1-/-). The lack of PARP-1 increased the abundance of TET2 on the Cxcl12 promoter, suggesting that TET-mediated demethylation provoked by the absence of PARP-1 could account for the observed increased expression of this chemokine. Deciphering the regulation of DNA (de)methylation factors that control Cxcl12 expression may provide an additional therapeutic approach in pharmacological interventions where gene switching on or off based on targeted stimulation or inhibition is necessary.
T2  - Archives of Biological Sciences
T1  - Enrichment of Cxcl12 promoter with TET2: a possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1
IS  - 3
VL  - 71
DO  - 10.2298/ABS190404027T
SP  - 455
EP  - 462
ER  - 

@article{
author = "Tolić, Anja and Rajić, Jovana and Đorđević, Marija and Đorđević, Miloš and Dinić, Svetlana and Grdović, Nevena and Arambašić Jovanović, Jelena and Mihailović, Mirjana and Poznanović, Goran and Jurkowski, Tomasz P. and Vidaković, Melita and Uskoković, Aleksandra",
year = "2019",
abstract = "Previously, we described the link between C-X-C motif chemokine 12 (Cxcl12) gene induction
and DNA hypomethylation in the absence of poly(ADP-ribose) polymerase 1 (PARP-1). We have now
firmly established that demethylation is the primary cause of gene induction on the basis of Cxcl12 gene
upregulation upon treatment with the demethylating agent 5-azacytidine (5-aza). Since the demethylation
state of Cxcl12 is favored by PARP-1 absence, we investigated the presence of ten-eleven translocation
(TET) proteins on the Cxcl12 promoter in order to corroborate the relationship between the demethylation
process and increased gene expression that occurs in the absence of PARP-1. Analysis was performed on the promoter region within CpG islands of Cxcl12 from control mouse embryonic fibroblasts (NIH3T3)
and PARP-1 knock-out mouse embryonic fibroblasts (PARP1-/-). The lack of PARP-1 increased the abundance of TET2 on the Cxcl12 promoter, suggesting that TET-mediated demethylation provoked by the absence of PARP-1 could account for the observed increased expression of this chemokine. Deciphering the regulation of DNA (de)methylation factors that control Cxcl12 expression may provide an additional therapeutic approach in pharmacological interventions where gene switching on or off based on targeted stimulation or inhibition is necessary.",
journal = "Archives of Biological Sciences",
title = "Enrichment of Cxcl12 promoter with TET2: a possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1",
number = "3",
volume = "71",
doi = "10.2298/ABS190404027T",
pages = "455-462"
}

Tolić, A., Rajić, J., Đorđević, M., Đorđević, M., Dinić, S., Grdović, N., Arambašić Jovanović, J., Mihailović, M., Poznanović, G., Jurkowski, T. P., Vidaković, M.,& Uskoković, A.. (2019). Enrichment of Cxcl12 promoter with TET2: a possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1. in Archives of Biological Sciences, 71(3), 455-462.
https://doi.org/10.2298/ABS190404027T

Tolić A, Rajić J, Đorđević M, Đorđević M, Dinić S, Grdović N, Arambašić Jovanović J, Mihailović M, Poznanović G, Jurkowski TP, Vidaković M, Uskoković A. Enrichment of Cxcl12 promoter with TET2: a possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1. in Archives of Biological Sciences. 2019;71(3):455-462.
doi:10.2298/ABS190404027T .

Tolić, Anja, Rajić, Jovana, Đorđević, Marija, Đorđević, Miloš, Dinić, Svetlana, Grdović, Nevena, Arambašić Jovanović, Jelena, Mihailović, Mirjana, Poznanović, Goran, Jurkowski, Tomasz P., Vidaković, Melita, Uskoković, Aleksandra, "Enrichment of Cxcl12 promoter with TET2: a possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1" in Archives of Biological Sciences, 71, no. 3 (2019):455-462,
https://doi.org/10.2298/ABS190404027T . .

TY  - THES
AU  - Đorđević, Miloš
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3475
AB  - Kičica se u Srbiji tradicionalno koristi za lečenje različitih oboljenja, uključujući i dijabetes. Cilj ovog rada bio je rasvetljavanje mehanizama antioksidativnog i protektivnog dejstva ekstrakta kičice (EK) koji doprinose očuvanju strukture i funkcije β-ćelija pankreasa i ublažavanju komplikacija u dijabetesu. Efekti EK analizirani su na eksperimentalnom modelu dijabetesa pacova izazvanom streptozotocinom (STZ) kao i na Rin-5F β-ćelijama izloženim oksidativnom stresu primenom vodonik peroksida, natrijum nitroprusida ili STZ-a. EK je ispoljio antidijabetogeno dejstvo uočeno kao sniženje nivoa glukoze/glikohemoglobina, poboljšanje lipidnog statusa i povećanje nivoa insulina u cirkulaciji dijabetičnih pacova što se može pripisati detektovanom uticaju EK na oc uvanje strukture Langerhansovih ostrvaca i povec anju mase β-c elija koje produkuju insulin. ntioksidativni efekat EK na β-c elije ogledao se u redukovanju oksidativnih os tec enja, modulisanju aktivnosti i ekspresije enzima antioksidativne zaštite (C T, SOD, GPx i GR) i uravnotežavanju aktivnosti redoks-senzitivnih faktora (NFκB, Nrf-2, Sp1, FOXO3 ) uključenih u regulaciju transkripcije gena za antioksidativne enzime. Dodatni doprinos EK boljem preživljavanju β-ćelija i sekreciji/ekspresiji insulina ostvaren je finim promenama u aktivnosti Akt, ERK i p38 kinaza kao i PDX-1 i MafA proteina. Pored toga, antioksidativni efekat EK kod dijabetičnih životinja ogledao se u zaštiti eritrocita, jetre i bubrega od gliko-oksidativnih oštećenja što je doprinelo poboljšanju njihovih funkcionalnih parametara. Opisani efekti EK ukazuju na značaj daljeg razjašnjavanja mehanizama antioksidativnog i protektivnog dejstva EK i njegovih komponenti u cilju potencijalnog terapijskog delovanja u dijabetesu.
AB  - Centaury is traditionally used in Serbia for treating different diseases, including diabetes. This study aimed to elucidate the mechanisms of the antioxidant and protective effects of the centaury extract (CE) that preserve the structure and function of pancreatic β-cells and alleviate diabetic complications. The effects of the CE were analyzed on the experimental model of streptozotocin (STZ)-induced diabetic rats and in Rin-5F β-cells exposed to oxidative stress after exposure to hydrogen peroxide, sodium nitroprusside or STZ. The CE exhibited an anti-diabetic effect, observed as a decrease in hyperglycemia and glycohemoglobin concentration, an improved lipid status, and as increased insulin level in the circulation of diabetic rats. These effects can be attributed to the detected impact of the CE on the preservation of the structure of the islets of Langerhans, and on the increase in insulin producing β-cell mass. The antioxidant effect of the CE on β-cells was manifested as a reduction in oxidative damage, changed activities and expression of antioxidant enzymes, CAT, SOD, GPx and GR, and as a readjustment of the activities of redox-sensitive factors, NFκB, Nrf-2, Sp1, FOXO3A, involved in the regulation of gene transcription of antioxidant enzymes. Additional contributions of the CE to improved β-cell survival and insulin secretion/expression were achieved by the fine-tuning of the activities of Akt, ERK and p38 kinases and transcription regulators, PDX-1 and MafA. The antioxidant effect of the CE in diabetic animals was also reflected on increased protection of erythrocytes, liver and kidneys from glyco-oxidative damage, which contributed to the improvement of their functional parameters in diabetic rats. The described effects of the CE point to the importance of further clarification of the mechanisms of the antioxidant and general protective effects of the CE and its components in view of its potential use for therapeutic intervention in diabetes.
PB  - Belgrade: Faculty of Biology, University of Belgrade
T2  - Faculty of Biology, University of Belgrade
T1  - Molekularni mehanizmi antioksidativnog dejstva ekstrakta kičice (Centaurium erythraea Rafn) u eksperimentalnom modelu dijabetesa pacova
T1  - Molecular mechanisms of the antioxidative effect of centaury (Centaurium erythraea Rafn) extract in the experimental model of diabetes in rats
SP  - 1
EP  - 191
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3475
ER  - 

@phdthesis{
author = "Đorđević, Miloš",
year = "2019",
abstract = "Kičica se u Srbiji tradicionalno koristi za lečenje različitih oboljenja, uključujući i dijabetes. Cilj ovog rada bio je rasvetljavanje mehanizama antioksidativnog i protektivnog dejstva ekstrakta kičice (EK) koji doprinose očuvanju strukture i funkcije β-ćelija pankreasa i ublažavanju komplikacija u dijabetesu. Efekti EK analizirani su na eksperimentalnom modelu dijabetesa pacova izazvanom streptozotocinom (STZ) kao i na Rin-5F β-ćelijama izloženim oksidativnom stresu primenom vodonik peroksida, natrijum nitroprusida ili STZ-a. EK je ispoljio antidijabetogeno dejstvo uočeno kao sniženje nivoa glukoze/glikohemoglobina, poboljšanje lipidnog statusa i povećanje nivoa insulina u cirkulaciji dijabetičnih pacova što se može pripisati detektovanom uticaju EK na oc uvanje strukture Langerhansovih ostrvaca i povec anju mase β-c elija koje produkuju insulin. ntioksidativni efekat EK na β-c elije ogledao se u redukovanju oksidativnih os tec enja, modulisanju aktivnosti i ekspresije enzima antioksidativne zaštite (C T, SOD, GPx i GR) i uravnotežavanju aktivnosti redoks-senzitivnih faktora (NFκB, Nrf-2, Sp1, FOXO3 ) uključenih u regulaciju transkripcije gena za antioksidativne enzime. Dodatni doprinos EK boljem preživljavanju β-ćelija i sekreciji/ekspresiji insulina ostvaren je finim promenama u aktivnosti Akt, ERK i p38 kinaza kao i PDX-1 i MafA proteina. Pored toga, antioksidativni efekat EK kod dijabetičnih životinja ogledao se u zaštiti eritrocita, jetre i bubrega od gliko-oksidativnih oštećenja što je doprinelo poboljšanju njihovih funkcionalnih parametara. Opisani efekti EK ukazuju na značaj daljeg razjašnjavanja mehanizama antioksidativnog i protektivnog dejstva EK i njegovih komponenti u cilju potencijalnog terapijskog delovanja u dijabetesu., Centaury is traditionally used in Serbia for treating different diseases, including diabetes. This study aimed to elucidate the mechanisms of the antioxidant and protective effects of the centaury extract (CE) that preserve the structure and function of pancreatic β-cells and alleviate diabetic complications. The effects of the CE were analyzed on the experimental model of streptozotocin (STZ)-induced diabetic rats and in Rin-5F β-cells exposed to oxidative stress after exposure to hydrogen peroxide, sodium nitroprusside or STZ. The CE exhibited an anti-diabetic effect, observed as a decrease in hyperglycemia and glycohemoglobin concentration, an improved lipid status, and as increased insulin level in the circulation of diabetic rats. These effects can be attributed to the detected impact of the CE on the preservation of the structure of the islets of Langerhans, and on the increase in insulin producing β-cell mass. The antioxidant effect of the CE on β-cells was manifested as a reduction in oxidative damage, changed activities and expression of antioxidant enzymes, CAT, SOD, GPx and GR, and as a readjustment of the activities of redox-sensitive factors, NFκB, Nrf-2, Sp1, FOXO3A, involved in the regulation of gene transcription of antioxidant enzymes. Additional contributions of the CE to improved β-cell survival and insulin secretion/expression were achieved by the fine-tuning of the activities of Akt, ERK and p38 kinases and transcription regulators, PDX-1 and MafA. The antioxidant effect of the CE in diabetic animals was also reflected on increased protection of erythrocytes, liver and kidneys from glyco-oxidative damage, which contributed to the improvement of their functional parameters in diabetic rats. The described effects of the CE point to the importance of further clarification of the mechanisms of the antioxidant and general protective effects of the CE and its components in view of its potential use for therapeutic intervention in diabetes.",
publisher = "Belgrade: Faculty of Biology, University of Belgrade",
journal = "Faculty of Biology, University of Belgrade",
title = "Molekularni mehanizmi antioksidativnog dejstva ekstrakta kičice (Centaurium erythraea Rafn) u eksperimentalnom modelu dijabetesa pacova, Molecular mechanisms of the antioxidative effect of centaury (Centaurium erythraea Rafn) extract in the experimental model of diabetes in rats",
pages = "1-191",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3475"
}

Đorđević, M.. (2019). Molekularni mehanizmi antioksidativnog dejstva ekstrakta kičice (Centaurium erythraea Rafn) u eksperimentalnom modelu dijabetesa pacova. in Faculty of Biology, University of Belgrade
Belgrade: Faculty of Biology, University of Belgrade., 1-191.
https://hdl.handle.net/21.15107/rcub_ibiss_3475

Đorđević M. Molekularni mehanizmi antioksidativnog dejstva ekstrakta kičice (Centaurium erythraea Rafn) u eksperimentalnom modelu dijabetesa pacova. in Faculty of Biology, University of Belgrade. 2019;:1-191.
https://hdl.handle.net/21.15107/rcub_ibiss_3475 .

Đorđević, Miloš, "Molekularni mehanizmi antioksidativnog dejstva ekstrakta kičice (Centaurium erythraea Rafn) u eksperimentalnom modelu dijabetesa pacova" in Faculty of Biology, University of Belgrade (2019):1-191,
https://hdl.handle.net/21.15107/rcub_ibiss_3475 .

TY  - JOUR
AU  - Vidaković, Melita
AU  - Mihailović, Mirjana
AU  - Đorđević, Marija
AU  - Rajić, Jovana
AU  - Uskoković, Aleksandra
AU  - Dinić, Svetlana
AU  - Grdović, Nevena
AU  - Đorđević, Miloš
AU  - Tolić, Anja
AU  - Poznanović, Goran
AU  - Caballero, Garrido
AU  - Arambašić Jovanović, Jelena
PY  - 2018
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641700040V
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2886
AB  - We examined whether CXCL12α improves insulin secretion by influencing the Ca2+ oscillation pattern and Ca2+ influx ([Ca2+]i), thereby enhancing the viability of pancreatic islet cells in oxidative stress. The islets of Langerhans were isolated from male OF1 mice and pretreated with 40 ng/mL of CXCL12α prior to exposure to 7.5 μM hydrogen peroxide, which served to induce oxidative stress. Incubation of islets with CXCL12α induced pancreatic β-cell proliferation and improved the ability of β-cells to withstand oxidative stress. Consecutive treatments of isolated islets with hydrogen peroxide caused a decline in β-cell functioning over time, while the CXCL12α pretreatment of islets exhibited a physiological response to high glucose that was comparable to control islets. The attenuated response of islets to a high D-glucose challenge was observed as a partial to complete abolishment of [Ca2+]i. Treatments with increasing concentrations of CXCL12α decreased the number of Ca2+ oscillations that lasted longer, thus pointing to an overall increase in [Ca2+]i, which was followed by increased insulin secretion. In addition, treatment of islets with CXCL12α enhanced the transcription rate for insulin and the CXCR4 gene, pointing to the importance of CXCL12/CXCR4 signaling in the regulation of Ca2+ intake and insulin secretion in pancreatic islet cells. We propose that a potential treatment with CXCL12α could help to remove preexisting glucotoxicity and associated temporary β-cell stunning that might be present at the time of diabetes diagnosis in vivo.
T2  - Archives of Biological Sciences
T1  - CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake
IS  - 1
VL  - 70
DO  - 10.2298/ABS170711040V
SP  - 191
EP  - 204
ER  - 

@article{
author = "Vidaković, Melita and Mihailović, Mirjana and Đorđević, Marija and Rajić, Jovana and Uskoković, Aleksandra and Dinić, Svetlana and Grdović, Nevena and Đorđević, Miloš and Tolić, Anja and Poznanović, Goran and Caballero, Garrido and Arambašić Jovanović, Jelena",
year = "2018",
abstract = "We examined whether CXCL12α improves insulin secretion by influencing the Ca2+ oscillation pattern and Ca2+ influx ([Ca2+]i), thereby enhancing the viability of pancreatic islet cells in oxidative stress. The islets of Langerhans were isolated from male OF1 mice and pretreated with 40 ng/mL of CXCL12α prior to exposure to 7.5 μM hydrogen peroxide, which served to induce oxidative stress. Incubation of islets with CXCL12α induced pancreatic β-cell proliferation and improved the ability of β-cells to withstand oxidative stress. Consecutive treatments of isolated islets with hydrogen peroxide caused a decline in β-cell functioning over time, while the CXCL12α pretreatment of islets exhibited a physiological response to high glucose that was comparable to control islets. The attenuated response of islets to a high D-glucose challenge was observed as a partial to complete abolishment of [Ca2+]i. Treatments with increasing concentrations of CXCL12α decreased the number of Ca2+ oscillations that lasted longer, thus pointing to an overall increase in [Ca2+]i, which was followed by increased insulin secretion. In addition, treatment of islets with CXCL12α enhanced the transcription rate for insulin and the CXCR4 gene, pointing to the importance of CXCL12/CXCR4 signaling in the regulation of Ca2+ intake and insulin secretion in pancreatic islet cells. We propose that a potential treatment with CXCL12α could help to remove preexisting glucotoxicity and associated temporary β-cell stunning that might be present at the time of diabetes diagnosis in vivo.",
journal = "Archives of Biological Sciences",
title = "CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake",
number = "1",
volume = "70",
doi = "10.2298/ABS170711040V",
pages = "191-204"
}

Vidaković, M., Mihailović, M., Đorđević, M., Rajić, J., Uskoković, A., Dinić, S., Grdović, N., Đorđević, M., Tolić, A., Poznanović, G., Caballero, G.,& Arambašić Jovanović, J.. (2018). CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake. in Archives of Biological Sciences, 70(1), 191-204.
https://doi.org/10.2298/ABS170711040V

Vidaković M, Mihailović M, Đorđević M, Rajić J, Uskoković A, Dinić S, Grdović N, Đorđević M, Tolić A, Poznanović G, Caballero G, Arambašić Jovanović J. CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake. in Archives of Biological Sciences. 2018;70(1):191-204.
doi:10.2298/ABS170711040V .

Vidaković, Melita, Mihailović, Mirjana, Đorđević, Marija, Rajić, Jovana, Uskoković, Aleksandra, Dinić, Svetlana, Grdović, Nevena, Đorđević, Miloš, Tolić, Anja, Poznanović, Goran, Caballero, Garrido, Arambašić Jovanović, Jelena, "CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake" in Archives of Biological Sciences, 70, no. 1 (2018):191-204,
https://doi.org/10.2298/ABS170711040V . .

TY  - JOUR
AU  - Vidaković, Melita
AU  - Caballero, Garrido
AU  - Mihailović, Mirjana
AU  - Arambašić Jovanović, Jelena
AU  - Đorđević, Marija
AU  - Rajić, Jovana
AU  - Uskoković, Aleksandra
AU  - Dinić, Svetlana
AU  - Grdović, Nevena
AU  - Đorđević, Miloš
AU  - Tolić, Anja
AU  - Poznanović, Goran
PY  - 2018
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641700040V
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3023
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/1940
AB  - We examined whether CXCL12α improves insulin secretion by influencing the Ca2+ oscillation pattern and Ca2+ influx ([Ca2+]i), thereby enhancing the viability of pancreatic islet cells in oxidative stress. The islets of Langerhans were isolated from male OF1 mice and pretreated with 40 ng/mL of CXCL12α prior to exposure to 7.5 μM hydrogen peroxide, which served to induce oxidative stress. Incubation of islets with CXCL12α induced pancreatic β-cell proliferation and improved the ability of β-cells to withstand oxidative stress. Consecutive treatments of isolated islets with hydrogen peroxide caused a decline in β-cell functioning over time, while the CXCL12α pretreatment of islets exhibited a physiological response to high glucose that was comparable to control islets. The attenuated response of islets to a high D-glucose challenge was observed as a partial to complete abolishment of [Ca2+]i. Treatments with increasing concentrations of CXCL12α decreased the number of Ca2+ oscillations that lasted longer, thus pointing to an overall increase in [Ca2+]i, which was followed by increased insulin secretion. In addition, treatment of islets with CXCL12α enhanced the transcription rate for insulin and the CXCR4 gene, pointing to the importance of CXCL12/CXCR4 signaling in the regulation of Ca2+ intake and insulin secretion in pancreatic islet cells. We propose that a potential treatment with CXCL12α could help to remove preexisting glucotoxicity and associated temporary β-cell stunning that might be present at the time of diabetes diagnosis in vivo.
PB  - Belgrade: Serbian Biological Society
T2  - Archives of Biological Sciences
T1  - CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake
IS  - 1
VL  - 70
DO  - 10.2298/ABS170711040V
SP  - 191
EP  - 204
ER  - 

@article{
author = "Vidaković, Melita and Caballero, Garrido and Mihailović, Mirjana and Arambašić Jovanović, Jelena and Đorđević, Marija and Rajić, Jovana and Uskoković, Aleksandra and Dinić, Svetlana and Grdović, Nevena and Đorđević, Miloš and Tolić, Anja and Poznanović, Goran",
year = "2018",
abstract = "We examined whether CXCL12α improves insulin secretion by influencing the Ca2+ oscillation pattern and Ca2+ influx ([Ca2+]i), thereby enhancing the viability of pancreatic islet cells in oxidative stress. The islets of Langerhans were isolated from male OF1 mice and pretreated with 40 ng/mL of CXCL12α prior to exposure to 7.5 μM hydrogen peroxide, which served to induce oxidative stress. Incubation of islets with CXCL12α induced pancreatic β-cell proliferation and improved the ability of β-cells to withstand oxidative stress. Consecutive treatments of isolated islets with hydrogen peroxide caused a decline in β-cell functioning over time, while the CXCL12α pretreatment of islets exhibited a physiological response to high glucose that was comparable to control islets. The attenuated response of islets to a high D-glucose challenge was observed as a partial to complete abolishment of [Ca2+]i. Treatments with increasing concentrations of CXCL12α decreased the number of Ca2+ oscillations that lasted longer, thus pointing to an overall increase in [Ca2+]i, which was followed by increased insulin secretion. In addition, treatment of islets with CXCL12α enhanced the transcription rate for insulin and the CXCR4 gene, pointing to the importance of CXCL12/CXCR4 signaling in the regulation of Ca2+ intake and insulin secretion in pancreatic islet cells. We propose that a potential treatment with CXCL12α could help to remove preexisting glucotoxicity and associated temporary β-cell stunning that might be present at the time of diabetes diagnosis in vivo.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Archives of Biological Sciences",
title = "CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake",
number = "1",
volume = "70",
doi = "10.2298/ABS170711040V",
pages = "191-204"
}

Vidaković, M., Caballero, G., Mihailović, M., Arambašić Jovanović, J., Đorđević, M., Rajić, J., Uskoković, A., Dinić, S., Grdović, N., Đorđević, M., Tolić, A.,& Poznanović, G.. (2018). CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake. in Archives of Biological Sciences
Belgrade: Serbian Biological Society., 70(1), 191-204.
https://doi.org/10.2298/ABS170711040V

Vidaković M, Caballero G, Mihailović M, Arambašić Jovanović J, Đorđević M, Rajić J, Uskoković A, Dinić S, Grdović N, Đorđević M, Tolić A, Poznanović G. CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake. in Archives of Biological Sciences. 2018;70(1):191-204.
doi:10.2298/ABS170711040V .

Vidaković, Melita, Caballero, Garrido, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Đorđević, Marija, Rajić, Jovana, Uskoković, Aleksandra, Dinić, Svetlana, Grdović, Nevena, Đorđević, Miloš, Tolić, Anja, Poznanović, Goran, "CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake" in Archives of Biological Sciences, 70, no. 1 (2018):191-204,
https://doi.org/10.2298/ABS170711040V . .

TY  - CONF
AU  - Tolić, Anja
AU  - Ninković, Niccoleta Aleksandra
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  - Okamoto, Akimitsu
AU  - Vidaković, Melita
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5799
AB  - Objectives: This study aim to implement a novel method, methylation-specific fluorescence in situ hybridization (MeFISH), based on microscopic visualization of DNA methylation/hydroxymethylation status at specific DNA regions in individual nuclei after pancreatic cell treatment with different compounds that possess a pronounced DNA (de)methylation capacity.
Methods: The DNA (de)methylating properties of two selected compounds caffeine (Co) and azacitidine (A) were evaluated in a Rin-5F pancreatic beta-cell line. Rin-5F cells were spin down on microscopic slides and further processed for preparing HALOs (relaxed DNA with preserved contacts with non-soluble nuclear proteins). The fluorescent visualization was achieved using ICON probe that covers region of interest in the promoter of the CXCL12 gene and target C positioned on the +26 bp, osmium for methylated cytosine (5mC)-dependent crosslinking and Tyramide Signal Amplification Systems for enhanced fluorescent staining.
Results: In control and Rin-5F cells treated with Co we were able to detect clear, single fluorescent signal that correspond to 5mC positioned on the +26 bp within the promoter region of the CXCL12 gene using MeFISH. Confirmation for the in situ hybridization specificity was achieved by omitting the crosslinking reaction with osmium. We observed a clear difference between control and Co treated samples, indicating that Co acts as pronounced DNA methylating compound. Treatment of cells with A lead to the appearance of a specific signal in a limited number of HALO preparations confirming demethylating property of A.
Conclusions: The Co acts as a pronounced DNA methylating agent in contrast to A, which demethylates CXCL12 gene and subsequently promotes higher gene expression. Higher methylation of the CXCL12 gene after cell treatment with Co leads to suppression of the gene which was observed by RT-qPCR. The analysed C, positioned on the +26 bp, may represent one of the major sites whose methylation is important for the regulation of the CXCL12 gene expression in vivo.
PB  - Karger Publishers
C3  - Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy
T1  - MeFISH: Fluorescent detection of Target Methylated Cytosines within the Genome
DO  - 10.1159/000490753
SP  - 16
ER  - 

@conference{
author = "Tolić, Anja and Ninković, Niccoleta Aleksandra 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 Okamoto, Akimitsu and Vidaković, Melita",
year = "2018",
abstract = "Objectives: This study aim to implement a novel method, methylation-specific fluorescence in situ hybridization (MeFISH), based on microscopic visualization of DNA methylation/hydroxymethylation status at specific DNA regions in individual nuclei after pancreatic cell treatment with different compounds that possess a pronounced DNA (de)methylation capacity.
Methods: The DNA (de)methylating properties of two selected compounds caffeine (Co) and azacitidine (A) were evaluated in a Rin-5F pancreatic beta-cell line. Rin-5F cells were spin down on microscopic slides and further processed for preparing HALOs (relaxed DNA with preserved contacts with non-soluble nuclear proteins). The fluorescent visualization was achieved using ICON probe that covers region of interest in the promoter of the CXCL12 gene and target C positioned on the +26 bp, osmium for methylated cytosine (5mC)-dependent crosslinking and Tyramide Signal Amplification Systems for enhanced fluorescent staining.
Results: In control and Rin-5F cells treated with Co we were able to detect clear, single fluorescent signal that correspond to 5mC positioned on the +26 bp within the promoter region of the CXCL12 gene using MeFISH. Confirmation for the in situ hybridization specificity was achieved by omitting the crosslinking reaction with osmium. We observed a clear difference between control and Co treated samples, indicating that Co acts as pronounced DNA methylating compound. Treatment of cells with A lead to the appearance of a specific signal in a limited number of HALO preparations confirming demethylating property of A.
Conclusions: The Co acts as a pronounced DNA methylating agent in contrast to A, which demethylates CXCL12 gene and subsequently promotes higher gene expression. Higher methylation of the CXCL12 gene after cell treatment with Co leads to suppression of the gene which was observed by RT-qPCR. The analysed C, positioned on the +26 bp, may represent one of the major sites whose methylation is important for the regulation of the CXCL12 gene expression in vivo.",
publisher = "Karger Publishers",
journal = "Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy",
title = "MeFISH: Fluorescent detection of Target Methylated Cytosines within the Genome",
doi = "10.1159/000490753",
pages = "16"
}

Tolić, A., Ninković, N. A., Rajić, J., Đorđević, M., Đorđević, M., Uskoković, A., Grdović, N., Mihailović, M., Arambašić Jovanović, J., Dinić, S., Okamoto, A.,& Vidaković, M.. (2018). MeFISH: Fluorescent detection of Target Methylated Cytosines within the Genome. in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy
Karger Publishers., 16.
https://doi.org/10.1159/000490753

Tolić A, Ninković NA, Rajić J, Đorđević M, Đorđević M, Uskoković A, Grdović N, Mihailović M, Arambašić Jovanović J, Dinić S, Okamoto A, Vidaković M. MeFISH: Fluorescent detection of Target Methylated Cytosines within the Genome. in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy. 2018;:16.
doi:10.1159/000490753 .

Tolić, Anja, Ninković, Niccoleta Aleksandra, Rajić, Jovana, Đorđević, Miloš, Đorđević, Marija, Uskoković, Aleksandra, Grdović, Nevena, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Dinić, Svetlana, Okamoto, Akimitsu, Vidaković, Melita, "MeFISH: Fluorescent detection of Target Methylated Cytosines within the Genome" in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy (2018):16,
https://doi.org/10.1159/000490753 . .

TY  - CONF
AU  - Rajić, Jovana
AU  - Grdović, Nevena
AU  - Petrović Matić, Sanja
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Mihailović, Mirjana
AU  - Arambašić Jovanović, Jelena
AU  - Tolić, Anja
AU  - Đorđević, Marija
AU  - Đorđević, Miloš
AU  - Poznanović, Goran
AU  - Pucar, Ana
AU  - Vidaković, Melita
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5800
AB  - Objectives: Procalcitonin (PCT) has recently emerged as an important biomarker for an early and accurate diagnosis of bacte­rial infection, hence suggested as biomarker of periodontal disease caused by oral pathogenic microorganisms. Altered DNA meth­ylation of PCT coding gene - calcitonin-related polypeptide a (CALCA) has been shown during systemic inflammation. The aim of this study was to evaluate the influence oflocal and/or systemic inflammation present during periodontitis and diabetes on DNA methylation status of CALCA and its potential use as epigenetic­based biomarker of these chronic inflammatory conditions. 
Methods: The study included 65 individuals divided in three groups: healthy control (n = 17), periodontitis (n = 27) and diabe­tes/periodontitis group (n = 21). Periodontitis was diagnosed us­ing International Workshop for a Classification of Periodontal Diseases and Conditions criteria (1999) while type 2 diabetes as­sessment was performed according to WHO criteria (2013). DNA methylation profile of CALCA promoter in buccal epithelial cells was analyzed by methylation specific polymerase chain reaction (MSP). 
Results: Decrease in DNA methylation of CALCA promoter was observed in periodontitis and even more pronounced in dia­betes/periodontitis compared to control group, although without statistical significance. Correlation analysis revealed statistically significant relationship between the extent of DNA methylation of the CALCA promoter and glycosylated hemoglobin. Even though it is known that life style affects DNA methylation patterns, there was no difference in DNA methylation of CALCA promoter be­tween smokers/non-smokers and normal/overweight individuals. 
Conclusions: Presented results suggest that local periodontal inflammation contributes to the change, but that only systemic inflammation significantly alters the DNA methylation profile of CALCA in buccal cells. Those results imply that DNA methylation status of CALCA reflects systemic inflammation, but additional studies are needed to estimate usefulness of this epigenetic-based biomarker for periodontal disease.
PB  - Krager Publishers
C3  - Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy
T1  - Evaluation of the DNA Methylation Status of Procalcitonin Gene as a Biomarker of Local and Systemic Inflammation
DO  - 10.1159/000490753
SP  - 12
ER  - 

@conference{
author = "Rajić, Jovana and Grdović, Nevena and Petrović Matić, Sanja and Dinić, Svetlana and Uskoković, Aleksandra and Mihailović, Mirjana and Arambašić Jovanović, Jelena and Tolić, Anja and Đorđević, Marija and Đorđević, Miloš and Poznanović, Goran and Pucar, Ana and Vidaković, Melita",
year = "2018",
abstract = "Objectives: Procalcitonin (PCT) has recently emerged as an important biomarker for an early and accurate diagnosis of bacte­rial infection, hence suggested as biomarker of periodontal disease caused by oral pathogenic microorganisms. Altered DNA meth­ylation of PCT coding gene - calcitonin-related polypeptide a (CALCA) has been shown during systemic inflammation. The aim of this study was to evaluate the influence oflocal and/or systemic inflammation present during periodontitis and diabetes on DNA methylation status of CALCA and its potential use as epigenetic­based biomarker of these chronic inflammatory conditions. 
Methods: The study included 65 individuals divided in three groups: healthy control (n = 17), periodontitis (n = 27) and diabe­tes/periodontitis group (n = 21). Periodontitis was diagnosed us­ing International Workshop for a Classification of Periodontal Diseases and Conditions criteria (1999) while type 2 diabetes as­sessment was performed according to WHO criteria (2013). DNA methylation profile of CALCA promoter in buccal epithelial cells was analyzed by methylation specific polymerase chain reaction (MSP). 
Results: Decrease in DNA methylation of CALCA promoter was observed in periodontitis and even more pronounced in dia­betes/periodontitis compared to control group, although without statistical significance. Correlation analysis revealed statistically significant relationship between the extent of DNA methylation of the CALCA promoter and glycosylated hemoglobin. Even though it is known that life style affects DNA methylation patterns, there was no difference in DNA methylation of CALCA promoter be­tween smokers/non-smokers and normal/overweight individuals. 
Conclusions: Presented results suggest that local periodontal inflammation contributes to the change, but that only systemic inflammation significantly alters the DNA methylation profile of CALCA in buccal cells. Those results imply that DNA methylation status of CALCA reflects systemic inflammation, but additional studies are needed to estimate usefulness of this epigenetic-based biomarker for periodontal disease.",
publisher = "Krager Publishers",
journal = "Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy",
title = "Evaluation of the DNA Methylation Status of Procalcitonin Gene as a Biomarker of Local and Systemic Inflammation",
doi = "10.1159/000490753",
pages = "12"
}

Rajić, J., Grdović, N., Petrović Matić, S., Dinić, S., Uskoković, A., Mihailović, M., Arambašić Jovanović, J., Tolić, A., Đorđević, M., Đorđević, M., Poznanović, G., Pucar, A.,& Vidaković, M.. (2018). Evaluation of the DNA Methylation Status of Procalcitonin Gene as a Biomarker of Local and Systemic Inflammation. in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy
Krager Publishers., 12.
https://doi.org/10.1159/000490753

Rajić J, Grdović N, Petrović Matić S, Dinić S, Uskoković A, Mihailović M, Arambašić Jovanović J, Tolić A, Đorđević M, Đorđević M, Poznanović G, Pucar A, Vidaković M. Evaluation of the DNA Methylation Status of Procalcitonin Gene as a Biomarker of Local and Systemic Inflammation. in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy. 2018;:12.
doi:10.1159/000490753 .

Rajić, Jovana, Grdović, Nevena, Petrović Matić, Sanja, Dinić, Svetlana, Uskoković, Aleksandra, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Tolić, Anja, Đorđević, Marija, Đorđević, Miloš, Poznanović, Goran, Pucar, Ana, Vidaković, Melita, "Evaluation of the DNA Methylation Status of Procalcitonin Gene as a Biomarker of Local and Systemic Inflammation" in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy (2018):12,
https://doi.org/10.1159/000490753 . .

TY  - CONF
AU  - Đorđević, Miloš
AU  - Mihailović, Mirjana
AU  - Arambašić Jovanović, Jelena
AU  - Grdović, Nevena
AU  - Uskoković, Aleksandra
AU  - Đorđević, Marija
AU  - Rajić, Jovana
AU  - Tolić, Anja
AU  - Poznanović, Goran
AU  - Vidaković, Melita
AU  - Dinić, Svetlana
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5801
AB  - Objectives: Centaurium erythraea ( CE) is traditionally used in Serbia for diabetes management. Since oxidative stress represents one of the major pathogenic factors that lead to diabetes and its complications, this study investigated protective effect of CE methanol extract against oxidative stress-induced pancreatic P-cell death. 
Methods: Rin-SF, rat insulinoma pancreatic P-cells, were incu­bated for 24 h with 1.25 mM sodium nitroprusside (SNP) with/ without CE extract (0.2 mg/mL) and processed immediately. Rin­SF cell viability was estimated using the MTT viability assay. Lipid peroxidation was assessed using the thiobarbituric acid-reactive substance (TBARS) assay, while the DNA damage was estimated by alkaline comet assay. Catalase (CAT) activity was determined by the rate ofH202 decomposition, whereas superoxide dismutase (SOD) activity was estimated by the epinephrine method. The ac­tivities of glutathione peroxidase (GPx) and glutathione reductase ( GR) were determined by monitoring NADPH oxidation. Relative gene expression of CAT, MnSOD, CuZnSOD, GPx, GR and insu­lin was determined by RT-qPCR. Relative protein level of antioxi­dant enzymes was estimated using immunoblot analysis. 
Results: CE methanol extract enhanced p-cell viability and in­sulin gene expression by reducing oxidative stress in SNP-treated cells. CE extract lowered DNA damage and lipid peroxidation pro­voked by SNP treatment and adjusted antioxidant enzyme activi­ties. CE treatment increased SNP-mediated attenuation of CAT, GPx and GR activities and reduced CuZnSOD and MnSOD ac­tivities that were stimulated in SNP treated cells. SNP-induced in­crease in gene expression of CAT, GPx, GR, MnSOD and CuZn­SOD was accompanied by decrease of CAT, GPx and CuZnSOD mRNA level after CE treatment. In addition, SNP treatment in­creased protein levels of CAT, GR, GPx and MnSOD and de­creased CuZnSO D protein level. CE extract reduced CAT and Mn­SOD and partially restored CuZnSOD protein level. 
Conclusions: The CE methanol extract protects pancreatic p-cells from oxidative damage by improving antioxidant defence system. Detected attenuation of oxidative stress in P-cells in vitro provide a useful platform for in vivo investigation of antioxidant and antidiabetic effect of CE extract and its potential usage as an effective supplement for diabetes treatment.
PB  - Krager Publishers
C3  - Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy
T1  - Centaurium erythraea Methanol Extract Attenuates SNP-lnduced Oxidative Stress in Pancreatic B-Cells
DO  - 10.1159/000490753
SP  - 7
ER  - 

@conference{
author = "Đorđević, Miloš and Mihailović, Mirjana and Arambašić Jovanović, Jelena and Grdović, Nevena and Uskoković, Aleksandra and Đorđević, Marija and Rajić, Jovana and Tolić, Anja and Poznanović, Goran and Vidaković, Melita and Dinić, Svetlana",
year = "2018",
abstract = "Objectives: Centaurium erythraea ( CE) is traditionally used in Serbia for diabetes management. Since oxidative stress represents one of the major pathogenic factors that lead to diabetes and its complications, this study investigated protective effect of CE methanol extract against oxidative stress-induced pancreatic P-cell death. 
Methods: Rin-SF, rat insulinoma pancreatic P-cells, were incu­bated for 24 h with 1.25 mM sodium nitroprusside (SNP) with/ without CE extract (0.2 mg/mL) and processed immediately. Rin­SF cell viability was estimated using the MTT viability assay. Lipid peroxidation was assessed using the thiobarbituric acid-reactive substance (TBARS) assay, while the DNA damage was estimated by alkaline comet assay. Catalase (CAT) activity was determined by the rate ofH202 decomposition, whereas superoxide dismutase (SOD) activity was estimated by the epinephrine method. The ac­tivities of glutathione peroxidase (GPx) and glutathione reductase ( GR) were determined by monitoring NADPH oxidation. Relative gene expression of CAT, MnSOD, CuZnSOD, GPx, GR and insu­lin was determined by RT-qPCR. Relative protein level of antioxi­dant enzymes was estimated using immunoblot analysis. 
Results: CE methanol extract enhanced p-cell viability and in­sulin gene expression by reducing oxidative stress in SNP-treated cells. CE extract lowered DNA damage and lipid peroxidation pro­voked by SNP treatment and adjusted antioxidant enzyme activi­ties. CE treatment increased SNP-mediated attenuation of CAT, GPx and GR activities and reduced CuZnSOD and MnSOD ac­tivities that were stimulated in SNP treated cells. SNP-induced in­crease in gene expression of CAT, GPx, GR, MnSOD and CuZn­SOD was accompanied by decrease of CAT, GPx and CuZnSOD mRNA level after CE treatment. In addition, SNP treatment in­creased protein levels of CAT, GR, GPx and MnSOD and de­creased CuZnSO D protein level. CE extract reduced CAT and Mn­SOD and partially restored CuZnSOD protein level. 
Conclusions: The CE methanol extract protects pancreatic p-cells from oxidative damage by improving antioxidant defence system. Detected attenuation of oxidative stress in P-cells in vitro provide a useful platform for in vivo investigation of antioxidant and antidiabetic effect of CE extract and its potential usage as an effective supplement for diabetes treatment.",
publisher = "Krager Publishers",
journal = "Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy",
title = "Centaurium erythraea Methanol Extract Attenuates SNP-lnduced Oxidative Stress in Pancreatic B-Cells",
doi = "10.1159/000490753",
pages = "7"
}

Đorđević, M., Mihailović, M., Arambašić Jovanović, J., Grdović, N., Uskoković, A., Đorđević, M., Rajić, J., Tolić, A., Poznanović, G., Vidaković, M.,& Dinić, S.. (2018). Centaurium erythraea Methanol Extract Attenuates SNP-lnduced Oxidative Stress in Pancreatic B-Cells. in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy
Krager Publishers., 7.
https://doi.org/10.1159/000490753

Đorđević M, Mihailović M, Arambašić Jovanović J, Grdović N, Uskoković A, Đorđević M, Rajić J, Tolić A, Poznanović G, Vidaković M, Dinić S. Centaurium erythraea Methanol Extract Attenuates SNP-lnduced Oxidative Stress in Pancreatic B-Cells. in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy. 2018;:7.
doi:10.1159/000490753 .

Đorđević, Miloš, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Grdović, Nevena, Uskoković, Aleksandra, Đorđević, Marija, Rajić, Jovana, Tolić, Anja, Poznanović, Goran, Vidaković, Melita, Dinić, Svetlana, "Centaurium erythraea Methanol Extract Attenuates SNP-lnduced Oxidative Stress in Pancreatic B-Cells" in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy (2018):7,
https://doi.org/10.1159/000490753 . .

TY  - CONF
AU  - Đorđević, Marija
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Dinić, Svetlana
AU  - Đorđević, Miloš
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Hunyadi, Attila
AU  - Vidaković, Melita
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5802
AB  - Objective: 20-hydroxyecdysone (20HE), a steroid hormone that modulates molting response in insects exerts many pharma­cological effects in mammals, most of which appear beneficial. The aim of this study was to investigate whether 20HE is able to reduce the destruction of beta-cells of the islets of Langerhans and ame­liorate hyperglycemia induced changes in liver tissue in strepto­zotocin (STZ)-induced rat model of diabetes. 
Methods: An experimental model of diabetes was induced in rats by the administration of 35 mg/kg STZ intraperitoneally for 4 consecutive days. 20HE was administered orally at a dose of20 mg/ kg body weight for four weeks, starting from the last day of STZ administration. Pancreas tissue sections were analyzed by hema­toxylin and eosin staining and immunohistochemical staining with insulin. Estimation of oxidative damage of DNA and lipids in the liver were detected by comet assay and thiobarbituric acid-re­active substance assay, respectively. Liver sections were analyzed by hematoxylin/eosin and Masson's trichrome staining. 
Results: Diabetic rats treated with the 20HE displayed several improved biochemical parameters in the circulation: reduced hy­perglycemia, lower triglyceride concentration and reduced glycat­ed hemoglobin. The administration of 20HE to diabetic rats also led to positive histological changes of pancreatic islets and increase in the number of insulin-positive cells in the islets which was ac­companied by increased serum insulin level. These results show that 20HE administration to diabetic rats restrained islet destruc­tion and partially restored the number of insulin-positive cells. In addition, treatment of 20HE attenuated diabetes-induced liver damage in rats according to lower level of DNA damage and reduc­tion of oxidative damage oflipids. This result is in accordance with observed improvement of liver architecture in 20HE treated dia­betic rats. Staining of collagen and increase in E-cadherin and de­creases in a-smooth muscle actin revealed that administration of 20HE to diabetic rats attenuated fibrotic process in the liver. 
Conclusions: 20HE administration seems to be beneficial for improving the hyperglycemia by increasing beta-cell mass and preventing diabetic complications in liver by attenuating fibrotic process.
PB  - Krager Publishers
C3  - Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy
T1  - 20-Hydroxyecdysone Protects Pancreatic Islets and Liver in Streptozotocin-lnduced Diabetic Rats
DO  - 10.1159/000490753
SP  - 14
ER  - 

@conference{
author = "Đorđević, Marija and Arambašić Jovanović, Jelena and Mihailović, Mirjana and Uskoković, Aleksandra and Grdović, Nevena and Dinić, Svetlana and Đorđević, Miloš and Tolić, Anja and Rajić, Jovana and Hunyadi, Attila and Vidaković, Melita",
year = "2018",
abstract = "Objective: 20-hydroxyecdysone (20HE), a steroid hormone that modulates molting response in insects exerts many pharma­cological effects in mammals, most of which appear beneficial. The aim of this study was to investigate whether 20HE is able to reduce the destruction of beta-cells of the islets of Langerhans and ame­liorate hyperglycemia induced changes in liver tissue in strepto­zotocin (STZ)-induced rat model of diabetes. 
Methods: An experimental model of diabetes was induced in rats by the administration of 35 mg/kg STZ intraperitoneally for 4 consecutive days. 20HE was administered orally at a dose of20 mg/ kg body weight for four weeks, starting from the last day of STZ administration. Pancreas tissue sections were analyzed by hema­toxylin and eosin staining and immunohistochemical staining with insulin. Estimation of oxidative damage of DNA and lipids in the liver were detected by comet assay and thiobarbituric acid-re­active substance assay, respectively. Liver sections were analyzed by hematoxylin/eosin and Masson's trichrome staining. 
Results: Diabetic rats treated with the 20HE displayed several improved biochemical parameters in the circulation: reduced hy­perglycemia, lower triglyceride concentration and reduced glycat­ed hemoglobin. The administration of 20HE to diabetic rats also led to positive histological changes of pancreatic islets and increase in the number of insulin-positive cells in the islets which was ac­companied by increased serum insulin level. These results show that 20HE administration to diabetic rats restrained islet destruc­tion and partially restored the number of insulin-positive cells. In addition, treatment of 20HE attenuated diabetes-induced liver damage in rats according to lower level of DNA damage and reduc­tion of oxidative damage oflipids. This result is in accordance with observed improvement of liver architecture in 20HE treated dia­betic rats. Staining of collagen and increase in E-cadherin and de­creases in a-smooth muscle actin revealed that administration of 20HE to diabetic rats attenuated fibrotic process in the liver. 
Conclusions: 20HE administration seems to be beneficial for improving the hyperglycemia by increasing beta-cell mass and preventing diabetic complications in liver by attenuating fibrotic process.",
publisher = "Krager Publishers",
journal = "Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy",
title = "20-Hydroxyecdysone Protects Pancreatic Islets and Liver in Streptozotocin-lnduced Diabetic Rats",
doi = "10.1159/000490753",
pages = "14"
}

Đorđević, M., Arambašić Jovanović, J., Mihailović, M., Uskoković, A., Grdović, N., Dinić, S., Đorđević, M., Tolić, A., Rajić, J., Hunyadi, A.,& Vidaković, M.. (2018). 20-Hydroxyecdysone Protects Pancreatic Islets and Liver in Streptozotocin-lnduced Diabetic Rats. in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy
Krager Publishers., 14.
https://doi.org/10.1159/000490753

Đorđević M, Arambašić Jovanović J, Mihailović M, Uskoković A, Grdović N, Dinić S, Đorđević M, Tolić A, Rajić J, Hunyadi A, Vidaković M. 20-Hydroxyecdysone Protects Pancreatic Islets and Liver in Streptozotocin-lnduced Diabetic Rats. in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy. 2018;:14.
doi:10.1159/000490753 .

Đorđević, Marija, Arambašić Jovanović, Jelena, Mihailović, Mirjana, Uskoković, Aleksandra, Grdović, Nevena, Dinić, Svetlana, Đorđević, Miloš, Tolić, Anja, Rajić, Jovana, Hunyadi, Attila, Vidaković, Melita, "20-Hydroxyecdysone Protects Pancreatic Islets and Liver in Streptozotocin-lnduced Diabetic Rats" in Selected Abstracts from the 3rd European Summer School on Nutrigenomics; 2018 Jun 25-29; Jesi, italy (2018):14,
https://doi.org/10.1159/000490753 . .

TY  - CONF
AU  - Grdović, Nevena
AU  - Mihailović, Mirjana
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Arambašić Jovanović, Jelena
AU  - Rajić, Jovana
AU  - Đorđević, Miloš
AU  - Đorđević, Marija
AU  - Tolić, Anja
AU  - Poznanović, Goran
AU  - Vidaković, Melita
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5695
AB  - Dijabetična nefropatija je praćena nagomilavanjem kolagena i drugih proteina
ekstracelularnog matriksa (ECM) u mezangijumu glomerula i tubulointersticijumu,
odnosno fibrozom bubrega. Kombinacijom hipoglikemijskog i antioksidativnog efekta
alfa-lipoinska kiselina (ALA) deluje protektivno na nefropatiju i ostale komplikacije u
dijabetesu. Imajući to u vidu cilj ovog rada je bio da se ispita uticaj ALA na procese
fibroze u bubrezima pacova kod kojih je dijabetes indukovan streptozotocinom.
Svakodnevna aplikacija ALA u trajanju od četiri i osam nedelja nakon indukcije
dijabetesa dovela je do značajnog smanjenja nivoa glukoze, dok je nivo uree u krvi
smanjen neznatno. PAS bojenje histoloških preparata ukazalo je na protektivni efekat
ALA na strukturu korteksa bubrega kod dijabetičnih životinja, ali na osnovu
trihromatskog bojenja nisu detektovani pozitivni efekti ALA na nagomilavanja ECM
proteina. Naprotiv, pojačano prisustvo ECM proteina je uočeno i kod nedijabetičnih
životinja tretiranih ALA. Analiza ekspresije iRNK za kolagene I i IV potvrdila je da
tretman ALA kod nedijabetičnih životinja indukuje povećanje ekspresije oba tipa
kolagena i da tretman ALA dijabetičnih životinja dovodi do određenog smanjenja u
nivou ekspresije kolagena tipa I ali nema uticaj na ekspresiju kolagena tipa IV. Imajući u
vidu direktnu povezanost fibroznih promena i funkcionalnosti bubrega ovi rezultati
sugerišu potencijalno kontraindikovano dejstvo ALA kod dijabetične nefropatije.
PB  - Belgrade: Serbian Biological Society
C3  - Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija
T1  - Efekat alfa-lipoinske kiseline na fibrozu bubrega kod dijabetičnih pacova
SP  - 152
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5695
ER  - 

@conference{
author = "Grdović, Nevena and Mihailović, Mirjana and Dinić, Svetlana and Uskoković, Aleksandra and Arambašić Jovanović, Jelena and Rajić, Jovana and Đorđević, Miloš and Đorđević, Marija and Tolić, Anja and Poznanović, Goran and Vidaković, Melita",
year = "2018",
abstract = "Dijabetična nefropatija je praćena nagomilavanjem kolagena i drugih proteina
ekstracelularnog matriksa (ECM) u mezangijumu glomerula i tubulointersticijumu,
odnosno fibrozom bubrega. Kombinacijom hipoglikemijskog i antioksidativnog efekta
alfa-lipoinska kiselina (ALA) deluje protektivno na nefropatiju i ostale komplikacije u
dijabetesu. Imajući to u vidu cilj ovog rada je bio da se ispita uticaj ALA na procese
fibroze u bubrezima pacova kod kojih je dijabetes indukovan streptozotocinom.
Svakodnevna aplikacija ALA u trajanju od četiri i osam nedelja nakon indukcije
dijabetesa dovela je do značajnog smanjenja nivoa glukoze, dok je nivo uree u krvi
smanjen neznatno. PAS bojenje histoloških preparata ukazalo je na protektivni efekat
ALA na strukturu korteksa bubrega kod dijabetičnih životinja, ali na osnovu
trihromatskog bojenja nisu detektovani pozitivni efekti ALA na nagomilavanja ECM
proteina. Naprotiv, pojačano prisustvo ECM proteina je uočeno i kod nedijabetičnih
životinja tretiranih ALA. Analiza ekspresije iRNK za kolagene I i IV potvrdila je da
tretman ALA kod nedijabetičnih životinja indukuje povećanje ekspresije oba tipa
kolagena i da tretman ALA dijabetičnih životinja dovodi do određenog smanjenja u
nivou ekspresije kolagena tipa I ali nema uticaj na ekspresiju kolagena tipa IV. Imajući u
vidu direktnu povezanost fibroznih promena i funkcionalnosti bubrega ovi rezultati
sugerišu potencijalno kontraindikovano dejstvo ALA kod dijabetične nefropatije.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija",
title = "Efekat alfa-lipoinske kiseline na fibrozu bubrega kod dijabetičnih pacova",
pages = "152",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5695"
}

Grdović, N., Mihailović, M., Dinić, S., Uskoković, A., Arambašić Jovanović, J., Rajić, J., Đorđević, M., Đorđević, M., Tolić, A., Poznanović, G.,& Vidaković, M.. (2018). Efekat alfa-lipoinske kiseline na fibrozu bubrega kod dijabetičnih pacova. in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija
Belgrade: Serbian Biological Society., 152.
https://hdl.handle.net/21.15107/rcub_ibiss_5695

Grdović N, Mihailović M, Dinić S, Uskoković A, Arambašić Jovanović J, Rajić J, Đorđević M, Đorđević M, Tolić A, Poznanović G, Vidaković M. Efekat alfa-lipoinske kiseline na fibrozu bubrega kod dijabetičnih pacova. in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija. 2018;:152.
https://hdl.handle.net/21.15107/rcub_ibiss_5695 .

Grdović, Nevena, Mihailović, Mirjana, Dinić, Svetlana, Uskoković, Aleksandra, Arambašić Jovanović, Jelena, Rajić, Jovana, Đorđević, Miloš, Đorđević, Marija, Tolić, Anja, Poznanović, Goran, Vidaković, Melita, "Efekat alfa-lipoinske kiseline na fibrozu bubrega kod dijabetičnih pacova" in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija (2018):152,
https://hdl.handle.net/21.15107/rcub_ibiss_5695 .

TY  - CONF
AU  - Đorđević, Miloš
AU  - Mihailović, Mirjana
AU  - Arambašić Jovanović, Jelena
AU  - Grdović, Nevena
AU  - Uskoković, Aleksandra
AU  - Đorđević, Marija
AU  - Rajić, Jovana
AU  - Tolić, Anja
AU  - Poznanović, Goran
AU  - Vidaković, Melita
AU  - Dinić, Svetlana
PY  - 2018
UR  - http://blog.u-bourgogne.fr/cost-nutredox/wp-content/uploads/sites/81/2018/02/Mallorca-COST-meeting-2018-Final-Program.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3461
AB  - In light of increasing prevalence of diabetes over the past few decades and increasing lifespan of human population, there is a need to better monitor the quality of life of diabetic patients. Epidemiological evidence shows protective effect of regular consumption of diets rich in plant polyphenols against development of diabetes. Centaurium erythraea Rafn (CE) is traditionally used in Serbia for diabetes treatment. Previous phytochemical studies with aerial parts of CE showed it can substantially alleviate oxidative stress, one of the major pathogenic factors that lead to diabetes and its complications. Chronic hyperglycemia, the hallmark of diabetes, leads to increased production of free radicals which affect red blood cells (RBCs) structure and function. Considering RBCs role as oxygen transporters and consequences of impaired oxygen delivery in diabetes, the main goal of this research was to evaluate the protective effect of the methanol extract of aerial parts of CE against oxidative challenge in RBCs of rats with streptozotocin (STZ)-induced diabetes. The CE extract (100 mg/kg) was given daily and orally two weeks before, during diabetes induction (i.p. injection of STZ (40 mg/kg) for five consecutive days), and for four weeks after the STZ injections (animals designated as pre-treated group), or for four weeks after diabetes induction (post-treated group). Daily application of CE extract to STZ-induced diabetic rats improved the redox status of RBCs, observed as reduced lipid peroxidation and alleviated oxidative damage due to improved glutathione system and antioxidant enzyme activity, such as catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR). Ameliorated RBCs’ redox status was accompanied with improvement of major biochemical indicators of diabetes. CE extract increased serum insulin level, reduced blood glucose and glycated hemoglobin concentrations and improved lipid profile of diabetic rats. Furthermore, the CE extract reduced non-enzymatic glycation and enzymatic glycosylation and improved parameters which correlate with RBC aggregation and deformability. The protective effect of CE extract was more pronounced in pre-treated diabetic group. According to these results, Centaurium erythraea methanol extract has a great potential for use as dietary supplement in diabetes management. Since plenty of bioactive compounds, including polyphenols were determined in CE extract, identification of active metabolites from CE and their tissue distribution after intake could provide a useful source of potential novel antidiabetic pharmaceutical entities.
C3  - Towards a Redox Healthy Aging. WGs Meeting of the NutRedOx COST Action CA16112. 2018 Feb 15–16;  Palma, Mallorca
T1  - Protective effect of Centaurium erythraea methanol extract against oxidative challenge in red blood cells of diabetic rats
SP  - 23
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3461
ER  - 

@conference{
author = "Đorđević, Miloš and Mihailović, Mirjana and Arambašić Jovanović, Jelena and Grdović, Nevena and Uskoković, Aleksandra and Đorđević, Marija and Rajić, Jovana and Tolić, Anja and Poznanović, Goran and Vidaković, Melita and Dinić, Svetlana",
year = "2018",
abstract = "In light of increasing prevalence of diabetes over the past few decades and increasing lifespan of human population, there is a need to better monitor the quality of life of diabetic patients. Epidemiological evidence shows protective effect of regular consumption of diets rich in plant polyphenols against development of diabetes. Centaurium erythraea Rafn (CE) is traditionally used in Serbia for diabetes treatment. Previous phytochemical studies with aerial parts of CE showed it can substantially alleviate oxidative stress, one of the major pathogenic factors that lead to diabetes and its complications. Chronic hyperglycemia, the hallmark of diabetes, leads to increased production of free radicals which affect red blood cells (RBCs) structure and function. Considering RBCs role as oxygen transporters and consequences of impaired oxygen delivery in diabetes, the main goal of this research was to evaluate the protective effect of the methanol extract of aerial parts of CE against oxidative challenge in RBCs of rats with streptozotocin (STZ)-induced diabetes. The CE extract (100 mg/kg) was given daily and orally two weeks before, during diabetes induction (i.p. injection of STZ (40 mg/kg) for five consecutive days), and for four weeks after the STZ injections (animals designated as pre-treated group), or for four weeks after diabetes induction (post-treated group). Daily application of CE extract to STZ-induced diabetic rats improved the redox status of RBCs, observed as reduced lipid peroxidation and alleviated oxidative damage due to improved glutathione system and antioxidant enzyme activity, such as catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR). Ameliorated RBCs’ redox status was accompanied with improvement of major biochemical indicators of diabetes. CE extract increased serum insulin level, reduced blood glucose and glycated hemoglobin concentrations and improved lipid profile of diabetic rats. Furthermore, the CE extract reduced non-enzymatic glycation and enzymatic glycosylation and improved parameters which correlate with RBC aggregation and deformability. The protective effect of CE extract was more pronounced in pre-treated diabetic group. According to these results, Centaurium erythraea methanol extract has a great potential for use as dietary supplement in diabetes management. Since plenty of bioactive compounds, including polyphenols were determined in CE extract, identification of active metabolites from CE and their tissue distribution after intake could provide a useful source of potential novel antidiabetic pharmaceutical entities.",
journal = "Towards a Redox Healthy Aging. WGs Meeting of the NutRedOx COST Action CA16112. 2018 Feb 15–16;  Palma, Mallorca",
title = "Protective effect of Centaurium erythraea methanol extract against oxidative challenge in red blood cells of diabetic rats",
pages = "23",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3461"
}

Đorđević, M., Mihailović, M., Arambašić Jovanović, J., Grdović, N., Uskoković, A., Đorđević, M., Rajić, J., Tolić, A., Poznanović, G., Vidaković, M.,& Dinić, S.. (2018). Protective effect of Centaurium erythraea methanol extract against oxidative challenge in red blood cells of diabetic rats. in Towards a Redox Healthy Aging. WGs Meeting of the NutRedOx COST Action CA16112. 2018 Feb 15–16;  Palma, Mallorca, 23.
https://hdl.handle.net/21.15107/rcub_ibiss_3461

Đorđević M, Mihailović M, Arambašić Jovanović J, Grdović N, Uskoković A, Đorđević M, Rajić J, Tolić A, Poznanović G, Vidaković M, Dinić S. Protective effect of Centaurium erythraea methanol extract against oxidative challenge in red blood cells of diabetic rats. in Towards a Redox Healthy Aging. WGs Meeting of the NutRedOx COST Action CA16112. 2018 Feb 15–16;  Palma, Mallorca. 2018;:23.
https://hdl.handle.net/21.15107/rcub_ibiss_3461 .

Đorđević, Miloš, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Grdović, Nevena, Uskoković, Aleksandra, Đorđević, Marija, Rajić, Jovana, Tolić, Anja, Poznanović, Goran, Vidaković, Melita, Dinić, Svetlana, "Protective effect of Centaurium erythraea methanol extract against oxidative challenge in red blood cells of diabetic rats" in Towards a Redox Healthy Aging. WGs Meeting of the NutRedOx COST Action CA16112. 2018 Feb 15–16;  Palma, Mallorca (2018):23,
https://hdl.handle.net/21.15107/rcub_ibiss_3461 .