TY  - JOUR
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Grigorov, Ilijana
AU  - Mićanović, Dragica
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Savić, Nevena
AU  - Gudelj, Anđelija
AU  - Otašević, Vesna
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6071
AB  - Introduction: Recently, the involvement of ferroptotic cell death in the reduction of β-cell mass in diabetes has been demonstrated. To elucidate the mechanisms of β-cell ferroptosis and potential antidiabetic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in vivo, a mouse model of type 1 diabetes (T1D) was used.

Methods: Animals were divided into three groups: control (vehicle-treated), diabetic (streptozotocin-treated, 40 mg/kg, from days 1-5), and diabetic treated with Fer-1 (1 mg/kg, from days 1-21). On day 22, glycemia and insulinemia were measured and pancreases were isolated for microscopic analyses.

Results: Diabetes disturbed general parameters of β-cell mass (islet size, β-cell abundance and distribution) and health (insulin and PDX-1 expression), increased lipid peroxidation in islet cells, and phagocytic removal of iron-containing material. It also downregulated the main players of the antiferroptotic pathway - Nrf2, GPX4, and xCT. In contrast, Fer-1 ameliorated the signs of deterioration of β-cell/islets, decreased lipid peroxidation, and reduced phagocytic activity, while upregulated expression of Nrf2 (and its nuclear translocation), GPX4, and xCT in β-cell/islets.

Discussion: Overall, our study confirms ferroptosis as an important mode of β-cell death in T1D and suggests antiferroptotic agents as a promising strategy for the prevention and treatment of diabetes
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Endocrinology
T1  - Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy
VL  - 14
DO  - 10.3389/fendo.2023.1227498
SP  - 1227498
ER  - 

@article{
author = "Markelić, Milica and Stančić, Ana and Saksida, Tamara and Grigorov, Ilijana and Mićanović, Dragica and Veličković, Ksenija and Martinović, Vesna and Savić, Nevena and Gudelj, Anđelija and Otašević, Vesna",
year = "2023",
abstract = "Introduction: Recently, the involvement of ferroptotic cell death in the reduction of β-cell mass in diabetes has been demonstrated. To elucidate the mechanisms of β-cell ferroptosis and potential antidiabetic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in vivo, a mouse model of type 1 diabetes (T1D) was used.

Methods: Animals were divided into three groups: control (vehicle-treated), diabetic (streptozotocin-treated, 40 mg/kg, from days 1-5), and diabetic treated with Fer-1 (1 mg/kg, from days 1-21). On day 22, glycemia and insulinemia were measured and pancreases were isolated for microscopic analyses.

Results: Diabetes disturbed general parameters of β-cell mass (islet size, β-cell abundance and distribution) and health (insulin and PDX-1 expression), increased lipid peroxidation in islet cells, and phagocytic removal of iron-containing material. It also downregulated the main players of the antiferroptotic pathway - Nrf2, GPX4, and xCT. In contrast, Fer-1 ameliorated the signs of deterioration of β-cell/islets, decreased lipid peroxidation, and reduced phagocytic activity, while upregulated expression of Nrf2 (and its nuclear translocation), GPX4, and xCT in β-cell/islets.

Discussion: Overall, our study confirms ferroptosis as an important mode of β-cell death in T1D and suggests antiferroptotic agents as a promising strategy for the prevention and treatment of diabetes",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Endocrinology",
title = "Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy",
volume = "14",
doi = "10.3389/fendo.2023.1227498",
pages = "1227498"
}

Markelić, M., Stančić, A., Saksida, T., Grigorov, I., Mićanović, D., Veličković, K., Martinović, V., Savić, N., Gudelj, A.,& Otašević, V.. (2023). Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy. in Frontiers in Endocrinology
Lausanne: Frontiers Media SA., 14, 1227498.
https://doi.org/10.3389/fendo.2023.1227498

Markelić M, Stančić A, Saksida T, Grigorov I, Mićanović D, Veličković K, Martinović V, Savić N, Gudelj A, Otašević V. Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy. in Frontiers in Endocrinology. 2023;14:1227498.
doi:10.3389/fendo.2023.1227498 .

Markelić, Milica, Stančić, Ana, Saksida, Tamara, Grigorov, Ilijana, Mićanović, Dragica, Veličković, Ksenija, Martinović, Vesna, Savić, Nevena, Gudelj, Anđelija, Otašević, Vesna, "Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy" in Frontiers in Endocrinology, 14 (2023):1227498,
https://doi.org/10.3389/fendo.2023.1227498 . .

TY  - THES
AU  - Đorđević, Marija
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5880
AB  - Ekspresija gena za Arx (engl. Aristaless related homeobox) koji ima glavnu ulogu u održavanju identiteta alfa ćelija endokrinog pankreasa regulisana je metilacijom i predstavlja glavni target za ćelijsko reprogramiranje kao jedna od strategija u terapiji dijabetesa koji u osnovi ima poremećen izvor insulina usled propadanja beta ćelija. Cilj ove doktorske disertacije je podrazumevao ispitivanje sposobnosti transdiferencijacije alfa ćelija pankreasa miša u ćelije koje proizvode insulin nakon uvođenja metilacije u promotoru Arx-a. Nakon tranzijentne transfekcije αTC1-6 ćelijske linije pomoću epigenetičkog alata za ciljanu gensku represiju ispitivani su efekti uvedene metilacije na ekspresiju gena specifičnih za beta ćelije. Optimizacijom nukleofekcije αTC1-6 ćelija uspostavljeni su uslovi pomoću kojih je dostignuta efikasnost od 71,1% pri vijabilnosti ćelija od 80%. Visoka efikasnost uvođenja metilacije dCas9-Dnmt3a3L-KRAB fuzionim (EpiCRISPR) konstruktom je pokazana targetovanim bisulfitnim sekvenciranjem. Utišavanje Arx-a praćeno pokretanjem ekspresije Ins2 na 5. i 7. danu nakon transfekcije detektovano je metodom RT-qPCR-a i analizom transkriptoma. Proteinski nivo insulina detektovan je imunocitohemijskom metodom do 12. dana, a oslobađanje iz ćelija enzimskim imunoesejem na 7. danu nakon transfekcije. Pokretanje procesa transdiferencijacije αTC1-6 ćelija ispitivano je analizom prisustva markera beta ćelija. Rezultati su pokazali da jedna tranzijentna transfekcija može da inicira transdiferencijaciju ~1% alfa ćelija pankreasa u ćelije koje proizvode 35% više insulina u odnosu na lažno transfekovane (Mock) alfa ćelije. Delujući na plastičnu prirodu epigenoma, uspešno je iniciran proces direktnog reprogramiranja alfa ćelija pankreasa u ćelije koje proizvode insulin.
AB  - Aristaless-related homeobox (Arx) gene expression level is regulated by DNA methylation, plaing an important role in the maintenance of pancreatic alpha cell identity. Diabetes is characterized by a disturbed source of insulin, representing a good candidate for cell reprogramming strategy in diabetes therapy by Arx targeting. The aim of this doctoral dissertation was to examine the transdifferentiation ability of murine pancreatic alpha cells into insulin-producing cells induced by the targeted DNA methylation in the Arx promoter. The expression of beta specific marker was analiysed in transiently transfected αTC1-6 cells with a synthetic epigenetic tool for gene repression. The optimization of αTC1-6 cells nucleofection was established conditions by which was achieved an efficiency of 71.1% with an 80% of cell viability. The high efficiency of methylation induction by the dCas9-Dnmt3a3L-KRAB fusion (EpiCRISPR) construct was confirmed by targeted bisulfite sequencing. The Arx silencing followed by induction of Ins2 expression on 5 and 7 days after transfection was detected by RT-qPCR and transcriptome analysis. The insulin protein level was detected immunocytochemicaly until the 12th post-transfection day, and released insulin was detected by the enzyme immunoassay on the 7th post-transfection day. The initiation of the transdifferentiation process of αTC1-6 cells was examined by analyzing the presence of beta cell specific markers. The results showed that a single transient transfection initiate the transdifferentiation of ~1% of alpha cells into cells that produce 35% more insulin compared to mock-transfected cells. Acting on the epigenome plastic nature, the direct reprogramming of pancreatic alpha cells into insulin-producing cells was successfully initiated.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Transdiferencijacija alfa ćelija pankreasa miša u ćelije koje proizvode insulin ciljanom metilacijom DNK primenom Epi-CRISPR sistema
T1  - Transdifferentiation of mouse pancreatic alpha to insulin-producing cells using Epi-CRISPRs directed DNA methylation
SP  - 1
EP  - 92
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5880
ER  - 

@phdthesis{
author = "Đorđević, Marija",
year = "2023",
abstract = "Ekspresija gena za Arx (engl. Aristaless related homeobox) koji ima glavnu ulogu u održavanju identiteta alfa ćelija endokrinog pankreasa regulisana je metilacijom i predstavlja glavni target za ćelijsko reprogramiranje kao jedna od strategija u terapiji dijabetesa koji u osnovi ima poremećen izvor insulina usled propadanja beta ćelija. Cilj ove doktorske disertacije je podrazumevao ispitivanje sposobnosti transdiferencijacije alfa ćelija pankreasa miša u ćelije koje proizvode insulin nakon uvođenja metilacije u promotoru Arx-a. Nakon tranzijentne transfekcije αTC1-6 ćelijske linije pomoću epigenetičkog alata za ciljanu gensku represiju ispitivani su efekti uvedene metilacije na ekspresiju gena specifičnih za beta ćelije. Optimizacijom nukleofekcije αTC1-6 ćelija uspostavljeni su uslovi pomoću kojih je dostignuta efikasnost od 71,1% pri vijabilnosti ćelija od 80%. Visoka efikasnost uvođenja metilacije dCas9-Dnmt3a3L-KRAB fuzionim (EpiCRISPR) konstruktom je pokazana targetovanim bisulfitnim sekvenciranjem. Utišavanje Arx-a praćeno pokretanjem ekspresije Ins2 na 5. i 7. danu nakon transfekcije detektovano je metodom RT-qPCR-a i analizom transkriptoma. Proteinski nivo insulina detektovan je imunocitohemijskom metodom do 12. dana, a oslobađanje iz ćelija enzimskim imunoesejem na 7. danu nakon transfekcije. Pokretanje procesa transdiferencijacije αTC1-6 ćelija ispitivano je analizom prisustva markera beta ćelija. Rezultati su pokazali da jedna tranzijentna transfekcija može da inicira transdiferencijaciju ~1% alfa ćelija pankreasa u ćelije koje proizvode 35% više insulina u odnosu na lažno transfekovane (Mock) alfa ćelije. Delujući na plastičnu prirodu epigenoma, uspešno je iniciran proces direktnog reprogramiranja alfa ćelija pankreasa u ćelije koje proizvode insulin., Aristaless-related homeobox (Arx) gene expression level is regulated by DNA methylation, plaing an important role in the maintenance of pancreatic alpha cell identity. Diabetes is characterized by a disturbed source of insulin, representing a good candidate for cell reprogramming strategy in diabetes therapy by Arx targeting. The aim of this doctoral dissertation was to examine the transdifferentiation ability of murine pancreatic alpha cells into insulin-producing cells induced by the targeted DNA methylation in the Arx promoter. The expression of beta specific marker was analiysed in transiently transfected αTC1-6 cells with a synthetic epigenetic tool for gene repression. The optimization of αTC1-6 cells nucleofection was established conditions by which was achieved an efficiency of 71.1% with an 80% of cell viability. The high efficiency of methylation induction by the dCas9-Dnmt3a3L-KRAB fusion (EpiCRISPR) construct was confirmed by targeted bisulfite sequencing. The Arx silencing followed by induction of Ins2 expression on 5 and 7 days after transfection was detected by RT-qPCR and transcriptome analysis. The insulin protein level was detected immunocytochemicaly until the 12th post-transfection day, and released insulin was detected by the enzyme immunoassay on the 7th post-transfection day. The initiation of the transdifferentiation process of αTC1-6 cells was examined by analyzing the presence of beta cell specific markers. The results showed that a single transient transfection initiate the transdifferentiation of ~1% of alpha cells into cells that produce 35% more insulin compared to mock-transfected cells. Acting on the epigenome plastic nature, the direct reprogramming of pancreatic alpha cells into insulin-producing cells was successfully initiated.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Transdiferencijacija alfa ćelija pankreasa miša u ćelije koje proizvode insulin ciljanom metilacijom DNK primenom Epi-CRISPR sistema, Transdifferentiation of mouse pancreatic alpha to insulin-producing cells using Epi-CRISPRs directed DNA methylation",
pages = "1-92",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5880"
}

Đorđević, M.. (2023). Transdiferencijacija alfa ćelija pankreasa miša u ćelije koje proizvode insulin ciljanom metilacijom DNK primenom Epi-CRISPR sistema. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-92.
https://hdl.handle.net/21.15107/rcub_ibiss_5880

Đorđević M. Transdiferencijacija alfa ćelija pankreasa miša u ćelije koje proizvode insulin ciljanom metilacijom DNK primenom Epi-CRISPR sistema. in University of Belgrade, Faculty of Biology. 2023;:1-92.
https://hdl.handle.net/21.15107/rcub_ibiss_5880 .

Đorđević, Marija, "Transdiferencijacija alfa ćelija pankreasa miša u ćelije koje proizvode insulin ciljanom metilacijom DNK primenom Epi-CRISPR sistema" in University of Belgrade, Faculty of Biology (2023):1-92,
https://hdl.handle.net/21.15107/rcub_ibiss_5880 .

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

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

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

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

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

TY  - CONF
AU  - Lakić, Iva
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Grigorov, Ilijana
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Todorović, Zoran
AU  - Đorđević, Jelena
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4896
AB  - Background: Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure.1, 2 Meldonium is an anti-ischemic and anti-inflammatory agent, clinically used to treat myocardial ischemia.3 By shifting energy production from fatty acid oxidation to glycolysis, as an oxygen less consuming pathway, meldonium interferes negatively with lipid metabolism. 
Methods: Thus, we investigated the effects of a 4-week meldonium pre-treatment in 300 mg/kg b.m./day dosage on the course of the sepsis induced by a single intraperitoneal injection of faeces (0.5 g faeces/1 mL saline/100 g b.m.)in Sprague-Dawley male rats. The degree of the heart injury was evaluated by measuring tissue pro-apoptotic Bax and anti-apoptotic Bcl-2 ratio, tissue level of the necrotic marker - high mobility group box 1 protein level (HMGB1), together with the heart histology analysis. Sepsis-associated heart inflammation
was assessed by measuring level of an activated form of NF-kB p65 (phospho-NF-κB p65).
Results: In the heart whole homogenates of the septic group of animals (S) HMGB1 level increased 1.7-fold, in comparison to control rats, while meldonium reduced sepsis-induced increase by 18 % (M+S). The underlying mechanism of the proinflammatory action of HMGB1 includes activation of NF-κB signalling
pathways tissue, so the increased HMGB1 level was followed by a 1.4-fold increase of p-NF-κB p65 in the heart of the S group of rats and a 19 % decreased in the heart of M+S group. The apoptotic marker Bax/Bcl-2 ratio changed in the same manner: 1.4-fold increase in the heart of animals from the S group and a 32 % decrease in the heart of the M+S group. On the other hand, heart histology analysis shows that meldonium worsened the heart histological score, causing the severe and diffuse interstitial mononuclear infiltration along with a greater loss of myocytes and myofibrillar contraction band necrosis. The heart lipidomic analysis suggests that meldonium exhibits potentially harmful effects under septic condition due to the lipid-mobilization impairment.
Conclusion: Meldonium exerted anti-inflammatory, anti-apoptotic, and anti- necrotic effects, while it worsened the septic rat heart histology.
PB  - Banja Luka: Association of Medical Doctors
PB  - Banja Luka: Faculty of Medicine, University of Banja Luka
C3  - 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
T1  - The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury
SP  - 57
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4896
ER  - 

@conference{
author = "Lakić, Iva and Đurašević, Siniša and Ružičić, Aleksandra and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pavlović, Slađan and Borković Mitić, Slavica and Grigorov, Ilijana and Stanković, Sanja and Jasnić, Nebojša and Todorović, Zoran and Đorđević, Jelena",
year = "2021",
abstract = "Background: Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure.1, 2 Meldonium is an anti-ischemic and anti-inflammatory agent, clinically used to treat myocardial ischemia.3 By shifting energy production from fatty acid oxidation to glycolysis, as an oxygen less consuming pathway, meldonium interferes negatively with lipid metabolism. 
Methods: Thus, we investigated the effects of a 4-week meldonium pre-treatment in 300 mg/kg b.m./day dosage on the course of the sepsis induced by a single intraperitoneal injection of faeces (0.5 g faeces/1 mL saline/100 g b.m.)in Sprague-Dawley male rats. The degree of the heart injury was evaluated by measuring tissue pro-apoptotic Bax and anti-apoptotic Bcl-2 ratio, tissue level of the necrotic marker - high mobility group box 1 protein level (HMGB1), together with the heart histology analysis. Sepsis-associated heart inflammation
was assessed by measuring level of an activated form of NF-kB p65 (phospho-NF-κB p65).
Results: In the heart whole homogenates of the septic group of animals (S) HMGB1 level increased 1.7-fold, in comparison to control rats, while meldonium reduced sepsis-induced increase by 18 % (M+S). The underlying mechanism of the proinflammatory action of HMGB1 includes activation of NF-κB signalling
pathways tissue, so the increased HMGB1 level was followed by a 1.4-fold increase of p-NF-κB p65 in the heart of the S group of rats and a 19 % decreased in the heart of M+S group. The apoptotic marker Bax/Bcl-2 ratio changed in the same manner: 1.4-fold increase in the heart of animals from the S group and a 32 % decrease in the heart of the M+S group. On the other hand, heart histology analysis shows that meldonium worsened the heart histological score, causing the severe and diffuse interstitial mononuclear infiltration along with a greater loss of myocytes and myofibrillar contraction band necrosis. The heart lipidomic analysis suggests that meldonium exhibits potentially harmful effects under septic condition due to the lipid-mobilization impairment.
Conclusion: Meldonium exerted anti-inflammatory, anti-apoptotic, and anti- necrotic effects, while it worsened the septic rat heart histology.",
publisher = "Banja Luka: Association of Medical Doctors, Banja Luka: Faculty of Medicine, University of Banja Luka",
journal = "7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina",
title = "The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury",
pages = "57",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4896"
}

Lakić, I., Đurašević, S., Ružičić, A., Tosti, T., Đurović, S., Glumac, S., Pavlović, S., Borković Mitić, S., Grigorov, I., Stanković, S., Jasnić, N., Todorović, Z.,& Đorđević, J.. (2021). The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
Banja Luka: Association of Medical Doctors., 57.
https://hdl.handle.net/21.15107/rcub_ibiss_4896

Lakić I, Đurašević S, Ružičić A, Tosti T, Đurović S, Glumac S, Pavlović S, Borković Mitić S, Grigorov I, Stanković S, Jasnić N, Todorović Z, Đorđević J. The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina. 2021;:57.
https://hdl.handle.net/21.15107/rcub_ibiss_4896 .

Lakić, Iva, Đurašević, Siniša, Ružičić, Aleksandra, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pavlović, Slađan, Borković Mitić, Slavica, Grigorov, Ilijana, Stanković, Sanja, Jasnić, Nebojša, Todorović, Zoran, Đorđević, Jelena, "The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury" in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina (2021):57,
https://hdl.handle.net/21.15107/rcub_ibiss_4896 .

TY  - CONF
AU  - Todorović, Zoran
AU  - Đurašević, Siniša
AU  - Tosti, Tomislav
AU  - Lakić, Iva
AU  - Grigorov, Ilijana
AU  - Đorđević, Jelena
AU  - Đukanović, Nina
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4895
AB  - Lipidomics deals with small molecules metabolomes with a mass lower than 1500. In recent years, the crucial role of lipidomes in the pathogenesis and therapy of cardiovascular events has become increasingly apparent.1-3 For example, ischemia-reperfusion (IR) injury can initiate oxidative stress that leads to harmful changes in membrane lipids, with an unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of IR disorders and reveals new targets for drug action. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes. Regarding platelet functions, polyunsaturated fatty acids play a role in increasing platelet reactivity, and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies clopidogrel discontinuation in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed “on-demand” in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.
PB  - Banja Luka: Association of Medical Doctors
PB  - Banja Luka: Faculty of Medicine, University of Banja Luka
C3  - 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
T1  - Lipidomics as a Novel Tool in Cardiovascular Research
SP  - 87
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4895
ER  - 

@conference{
author = "Todorović, Zoran and Đurašević, Siniša and Tosti, Tomislav and Lakić, Iva and Grigorov, Ilijana and Đorđević, Jelena and Đukanović, Nina",
year = "2021",
abstract = "Lipidomics deals with small molecules metabolomes with a mass lower than 1500. In recent years, the crucial role of lipidomes in the pathogenesis and therapy of cardiovascular events has become increasingly apparent.1-3 For example, ischemia-reperfusion (IR) injury can initiate oxidative stress that leads to harmful changes in membrane lipids, with an unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of IR disorders and reveals new targets for drug action. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes. Regarding platelet functions, polyunsaturated fatty acids play a role in increasing platelet reactivity, and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies clopidogrel discontinuation in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed “on-demand” in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.",
publisher = "Banja Luka: Association of Medical Doctors, Banja Luka: Faculty of Medicine, University of Banja Luka",
journal = "7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina",
title = "Lipidomics as a Novel Tool in Cardiovascular Research",
pages = "87",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4895"
}

Todorović, Z., Đurašević, S., Tosti, T., Lakić, I., Grigorov, I., Đorđević, J.,& Đukanović, N.. (2021). Lipidomics as a Novel Tool in Cardiovascular Research. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
Banja Luka: Association of Medical Doctors., 87.
https://hdl.handle.net/21.15107/rcub_ibiss_4895

Todorović Z, Đurašević S, Tosti T, Lakić I, Grigorov I, Đorđević J, Đukanović N. Lipidomics as a Novel Tool in Cardiovascular Research. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina. 2021;:87.
https://hdl.handle.net/21.15107/rcub_ibiss_4895 .

Todorović, Zoran, Đurašević, Siniša, Tosti, Tomislav, Lakić, Iva, Grigorov, Ilijana, Đorđević, Jelena, Đukanović, Nina, "Lipidomics as a Novel Tool in Cardiovascular Research" in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina (2021):87,
https://hdl.handle.net/21.15107/rcub_ibiss_4895 .

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

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

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

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

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

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Nikolić, Gorana
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Pejić, Snežana
AU  - Martinović, Vesna
AU  - Mitić-Ćulafić, Dragana
AU  - Milić, Dragana
AU  - Kop, Tatjana J.
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3645
AB  - The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.
T2  - Food and Chemical Toxicology
T1  - Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats
VL  - 140
DO  - 10.1016/j.fct.2020.111302
SP  - 111302
ER  - 

@article{
author = "Đurašević, Siniša and Nikolić, Gorana and Todorović, Ana and Drakulić, Dunja and Pejić, Snežana and Martinović, Vesna and Mitić-Ćulafić, Dragana and Milić, Dragana and Kop, Tatjana J. and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2020",
abstract = "The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.",
journal = "Food and Chemical Toxicology",
title = "Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats",
volume = "140",
doi = "10.1016/j.fct.2020.111302",
pages = "111302"
}

Đurašević, S., Nikolić, G., Todorović, A., Drakulić, D., Pejić, S., Martinović, V., Mitić-Ćulafić, D., Milić, D., Kop, T. J., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2020). Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats. in Food and Chemical Toxicology, 140, 111302.
https://doi.org/10.1016/j.fct.2020.111302

Đurašević S, Nikolić G, Todorović A, Drakulić D, Pejić S, Martinović V, Mitić-Ćulafić D, Milić D, Kop TJ, Jasnić N, Đorđević J, Todorović Z. Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats. in Food and Chemical Toxicology. 2020;140:111302.
doi:10.1016/j.fct.2020.111302 .

Đurašević, Siniša, Nikolić, Gorana, Todorović, Ana, Drakulić, Dunja, Pejić, Snežana, Martinović, Vesna, Mitić-Ćulafić, Dragana, Milić, Dragana, Kop, Tatjana J., Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats" in Food and Chemical Toxicology, 140 (2020):111302,
https://doi.org/10.1016/j.fct.2020.111302 . .

TY  - THES
AU  - Rajić, Jovana
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/123456789/3884
AB  - Proces epitelno-mezenhimske tranzicije (EMT) može predstavljati značajan faktor koji doprinosi nastanku fibroznih promena konjuktive u različitim bolestima oka, ali je njegova uloga nedovoljno ispitana. Cilj ove doktorske disertacije podrazumevao je ispitivanje sposobnosti ćelijske linije humanih epitelnih ćelija konjuktive (HCjE) da uđu u proces EMT nakon infekcije uzročnikom trahoma, bakterijom Chlamydia trachomatis, i identifikaciju ključnih faktora povezanih sa pokretanjem i progresijom tranzicije na modelu procesa EMT indukovanog TGF-β proteinima. Posebna pažnja bila je usmerena na rasvetljavanje uloge metilacije DNK u regulaciji ekspresije gena uključenih u tranziciju HCjE ćelija. Praćenjem aktivacije signalnih puteva povezanih sa pokretanjem procesa EMT i ekspresije markera epitelnih/mezenhimskih ćelija pokazano je da HCjE ćelije poseduju sposobnost tranzicije nakon infekcije bakterijom C. trachomatis, praćene promenama u metilacionim profilima gena markera epitelnog/mezenhimskog fenotipa. Praćenjem morfologije, sposobnosti migracije i nivoa ekspresije gena markera uočeno je da dugotrajan tretman TGF-β1 izoformom ima najveći potencijal za pokretanje procesa EMT u HCjE ćelijama, dok su tretmani DNK demetilujućim agensom pokazali da metilacija DNK predstavlja važan mehanizam koji leži u osnovi ovog procesa. Promene profila metilacije DNK, detektovane analizom kriva topljenja i bisulfitnim sekvenciranjem, istakle su ključnu ulogu članova familije miR-200 u pokretanju i reverziji procesa EMT u HCjE ćelijama tretiranim TGF-β1 proteinima. Rezultati dobijeni u ovoj doktorskoj disertaciji ukazuju na mogućnost razvijanja novih selektivnih terapeutskih strategija u lečenju fibroznih promena konjuktive, zasnovanim na reverzibilnosti procesa EMT i epigenetičkih mehanizama.
AB  - The process of epithelial-mesenchymal transition (EMT) could be an important factor in development of fibrosis-related conjunctival eye diseases, but its precise role in these conditions has not been defined yet. The aim of this doctoral dissertation was to examine the ability of human epithelial conjunctival cell line (HCjE) to enter EMT process after infection with trachoma causative agent, bacteria Chlamydia trachomatis, i to identify key factors associated with the initiation i progression of transition in TGF-β-induced EMT model. Special focus was directed to elucidating the role of DNA methylation in the regulation of expression of genes involved in the transition of HCjE cells. Activation of signaling pathways associated with the initiation of the EMT process i the expression level of epithelial/mesenchymal markers revealed that HCjE cells possess the ability to enter the transition after infection with bacteria C. trachomatis, which was associated with changes in the methylation profiles of epithelial/mesenchymal gene markers. Cell morphology, migration ability i expression level of marker genes indicated that long-term treatment with TGF-β1 isoform has the greatest potential to initiate EMT process in HCjE cells, while treatments with DNA demethylating agent suggested that DNA methylation is an important mechanism which underlies this process. Changes in DNA methylation profile, detected by melting curve analysis i bisulfite sequencing, highlighted a key role of miR-200 family members in initiating i reversing TGF-β1-induced EMT process in HCjE cells. The results obtained in this doctoral dissertation indicate the possibility of developing new selective therapeutic strategies in the treatment of fibrosis-related conjunctival diseases, based on the reversibility of both EMT process i epigenetic mechanisms.
PB  - Belgrade: Faculty of Biology, University of Belgrade
T2  - Faculty of Biology, University of Belgrade
T1  - Uloga metilacije DNK u procesu epitelno-mezenhimske tranzicije  humanih epitelnih ćelija konjuktive
T1  - The role of DNA methylation in the process of epithelial-mesenchymal transition of human conjunctival epithelial cells
SP  - 1
EP  - 133
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3884
ER  - 

@phdthesis{
author = "Rajić, Jovana",
year = "2020",
abstract = "Proces epitelno-mezenhimske tranzicije (EMT) može predstavljati značajan faktor koji doprinosi nastanku fibroznih promena konjuktive u različitim bolestima oka, ali je njegova uloga nedovoljno ispitana. Cilj ove doktorske disertacije podrazumevao je ispitivanje sposobnosti ćelijske linije humanih epitelnih ćelija konjuktive (HCjE) da uđu u proces EMT nakon infekcije uzročnikom trahoma, bakterijom Chlamydia trachomatis, i identifikaciju ključnih faktora povezanih sa pokretanjem i progresijom tranzicije na modelu procesa EMT indukovanog TGF-β proteinima. Posebna pažnja bila je usmerena na rasvetljavanje uloge metilacije DNK u regulaciji ekspresije gena uključenih u tranziciju HCjE ćelija. Praćenjem aktivacije signalnih puteva povezanih sa pokretanjem procesa EMT i ekspresije markera epitelnih/mezenhimskih ćelija pokazano je da HCjE ćelije poseduju sposobnost tranzicije nakon infekcije bakterijom C. trachomatis, praćene promenama u metilacionim profilima gena markera epitelnog/mezenhimskog fenotipa. Praćenjem morfologije, sposobnosti migracije i nivoa ekspresije gena markera uočeno je da dugotrajan tretman TGF-β1 izoformom ima najveći potencijal za pokretanje procesa EMT u HCjE ćelijama, dok su tretmani DNK demetilujućim agensom pokazali da metilacija DNK predstavlja važan mehanizam koji leži u osnovi ovog procesa. Promene profila metilacije DNK, detektovane analizom kriva topljenja i bisulfitnim sekvenciranjem, istakle su ključnu ulogu članova familije miR-200 u pokretanju i reverziji procesa EMT u HCjE ćelijama tretiranim TGF-β1 proteinima. Rezultati dobijeni u ovoj doktorskoj disertaciji ukazuju na mogućnost razvijanja novih selektivnih terapeutskih strategija u lečenju fibroznih promena konjuktive, zasnovanim na reverzibilnosti procesa EMT i epigenetičkih mehanizama., The process of epithelial-mesenchymal transition (EMT) could be an important factor in development of fibrosis-related conjunctival eye diseases, but its precise role in these conditions has not been defined yet. The aim of this doctoral dissertation was to examine the ability of human epithelial conjunctival cell line (HCjE) to enter EMT process after infection with trachoma causative agent, bacteria Chlamydia trachomatis, i to identify key factors associated with the initiation i progression of transition in TGF-β-induced EMT model. Special focus was directed to elucidating the role of DNA methylation in the regulation of expression of genes involved in the transition of HCjE cells. Activation of signaling pathways associated with the initiation of the EMT process i the expression level of epithelial/mesenchymal markers revealed that HCjE cells possess the ability to enter the transition after infection with bacteria C. trachomatis, which was associated with changes in the methylation profiles of epithelial/mesenchymal gene markers. Cell morphology, migration ability i expression level of marker genes indicated that long-term treatment with TGF-β1 isoform has the greatest potential to initiate EMT process in HCjE cells, while treatments with DNA demethylating agent suggested that DNA methylation is an important mechanism which underlies this process. Changes in DNA methylation profile, detected by melting curve analysis i bisulfite sequencing, highlighted a key role of miR-200 family members in initiating i reversing TGF-β1-induced EMT process in HCjE cells. The results obtained in this doctoral dissertation indicate the possibility of developing new selective therapeutic strategies in the treatment of fibrosis-related conjunctival diseases, based on the reversibility of both EMT process i epigenetic mechanisms.",
publisher = "Belgrade: Faculty of Biology, University of Belgrade",
journal = "Faculty of Biology, University of Belgrade",
title = "Uloga metilacije DNK u procesu epitelno-mezenhimske tranzicije  humanih epitelnih ćelija konjuktive, The role of DNA methylation in the process of epithelial-mesenchymal transition of human conjunctival epithelial cells",
pages = "1-133",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3884"
}

Rajić, J.. (2020). Uloga metilacije DNK u procesu epitelno-mezenhimske tranzicije  humanih epitelnih ćelija konjuktive. in Faculty of Biology, University of Belgrade
Belgrade: Faculty of Biology, University of Belgrade., 1-133.
https://hdl.handle.net/21.15107/rcub_ibiss_3884

Rajić J. Uloga metilacije DNK u procesu epitelno-mezenhimske tranzicije  humanih epitelnih ćelija konjuktive. in Faculty of Biology, University of Belgrade. 2020;:1-133.
https://hdl.handle.net/21.15107/rcub_ibiss_3884 .

Rajić, Jovana, "Uloga metilacije DNK u procesu epitelno-mezenhimske tranzicije  humanih epitelnih ćelija konjuktive" in Faculty of Biology, University of Belgrade (2020):1-133,
https://hdl.handle.net/21.15107/rcub_ibiss_3884 .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Nikolić, Gorana
AU  - Zaletel, Ivan
AU  - Grigorov, Ilijana
AU  - Memon, Lidija
AU  - Mitić-Ćulafić, Dragana
AU  - Vujović, Predrag
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2020
UR  - https://www.sciencedirect.com/science/article/pii/S1756464619305250?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3512
UR  - https://s100.copyright.com/AppDispatchServlet?publisherName=ELS&contentID=S1756464619305250&orderBeanReset=true
AB  - Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgin coconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to control glycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementation with coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity of steatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on heart histology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither in non-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementation with coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development of severe insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contraindicated in diabetic condition.
T2  - Journal of Functional Foods
T1  - Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats
VL  - 64
DO  - 10.1016/J.JFF.2019.103601
SP  - 103601
ER  - 

@article{
author = "Đurašević, Siniša and Nikolić, Gorana and Zaletel, Ivan and Grigorov, Ilijana and Memon, Lidija and Mitić-Ćulafić, Dragana and Vujović, Predrag and Đorđević, Jelena and Todorović, Zoran",
year = "2020",
abstract = "Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgin coconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to control glycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementation with coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity of steatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on heart histology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither in non-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementation with coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development of severe insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contraindicated in diabetic condition.",
journal = "Journal of Functional Foods",
title = "Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats",
volume = "64",
doi = "10.1016/J.JFF.2019.103601",
pages = "103601"
}

Đurašević, S., Nikolić, G., Zaletel, I., Grigorov, I., Memon, L., Mitić-Ćulafić, D., Vujović, P., Đorđević, J.,& Todorović, Z.. (2020). Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats. in Journal of Functional Foods, 64, 103601.
https://doi.org/10.1016/J.JFF.2019.103601

Đurašević S, Nikolić G, Zaletel I, Grigorov I, Memon L, Mitić-Ćulafić D, Vujović P, Đorđević J, Todorović Z. Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats. in Journal of Functional Foods. 2020;64:103601.
doi:10.1016/J.JFF.2019.103601 .

Đurašević, Siniša, Nikolić, Gorana, Zaletel, Ivan, Grigorov, Ilijana, Memon, Lidija, Mitić-Ćulafić, Dragana, Vujović, Predrag, Đorđević, Jelena, Todorović, Zoran, "Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats" in Journal of Functional Foods, 64 (2020):103601,
https://doi.org/10.1016/J.JFF.2019.103601 . .

TY  - CONF
AU  - Jakubek, Patrycja
AU  - Rajić, Jovana
AU  - Baranowska, Monika
AU  - Vidaković, Melita
AU  - Bartoszek, Agnieszka
AU  - Namiesnik, Jacek
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6319
AB  - The impact of catechins on the expression profile of redox-related genes in HT29 cell line has been studied recently by our group using Oxidative Stress RT2 Profiler PCR Array. Within the examined panel of 84 genes, the down-regulation of SRXN1 gene was unique among other-regulated genes. We hypothesized that the observed down-regulation resulted from DNA methylation and have exploited this observation to choose the proper strategy to monitor the changes in DNA methylation patterns incurred by dietary antioxidants. The current study verified two PCR-based approaches.
PB  - Basel: MDPI
C3  - CA16112—Luxemburg 2019 meeting; 2019 Mar 25-27; Luxemburg, Luxemburg
T1  - DNA Methylation Changes Induced by Redox-Active Compounds—Choosing the Right PCR-Based Method
IS  - 1
VL  - 11
DO  - 10.3390/proceedings2019011020
SP  - 20
ER  - 

@conference{
author = "Jakubek, Patrycja and Rajić, Jovana and Baranowska, Monika and Vidaković, Melita and Bartoszek, Agnieszka and Namiesnik, Jacek",
year = "2019",
abstract = "The impact of catechins on the expression profile of redox-related genes in HT29 cell line has been studied recently by our group using Oxidative Stress RT2 Profiler PCR Array. Within the examined panel of 84 genes, the down-regulation of SRXN1 gene was unique among other-regulated genes. We hypothesized that the observed down-regulation resulted from DNA methylation and have exploited this observation to choose the proper strategy to monitor the changes in DNA methylation patterns incurred by dietary antioxidants. The current study verified two PCR-based approaches.",
publisher = "Basel: MDPI",
journal = "CA16112—Luxemburg 2019 meeting; 2019 Mar 25-27; Luxemburg, Luxemburg",
title = "DNA Methylation Changes Induced by Redox-Active Compounds—Choosing the Right PCR-Based Method",
number = "1",
volume = "11",
doi = "10.3390/proceedings2019011020",
pages = "20"
}

Jakubek, P., Rajić, J., Baranowska, M., Vidaković, M., Bartoszek, A.,& Namiesnik, J.. (2019). DNA Methylation Changes Induced by Redox-Active Compounds—Choosing the Right PCR-Based Method. in CA16112—Luxemburg 2019 meeting; 2019 Mar 25-27; Luxemburg, Luxemburg
Basel: MDPI., 11(1), 20.
https://doi.org/10.3390/proceedings2019011020

Jakubek P, Rajić J, Baranowska M, Vidaković M, Bartoszek A, Namiesnik J. DNA Methylation Changes Induced by Redox-Active Compounds—Choosing the Right PCR-Based Method. in CA16112—Luxemburg 2019 meeting; 2019 Mar 25-27; Luxemburg, Luxemburg. 2019;11(1):20.
doi:10.3390/proceedings2019011020 .

Jakubek, Patrycja, Rajić, Jovana, Baranowska, Monika, Vidaković, Melita, Bartoszek, Agnieszka, Namiesnik, Jacek, "DNA Methylation Changes Induced by Redox-Active Compounds—Choosing the Right PCR-Based Method" in CA16112—Luxemburg 2019 meeting; 2019 Mar 25-27; Luxemburg, Luxemburg, 11, no. 1 (2019):20,
https://doi.org/10.3390/proceedings2019011020 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Bogdanović, Ljiljana
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3519
AB  - Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to
treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation
to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week
meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our
results showed that meldonium decreased animal body mass gain, food and water intake, and
carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium
increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and
increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1,
causing manganese superoxide dismutase expression and activity to increase, as well as lipid
peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase
activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum
high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in
I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and
serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex
changes in renal lipidomics. Taken together, our results have confirmed that meldonium pretreatment protects against I/R-induced oxidative stress and apoptosis/necrosis.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - The effects of meldonium on the renal acute ischemia/reperfusion injury in rats
IS  - 22
VL  - 20
DO  - 10.3390/ijms20225747
SP  - 5747
ER  - 

@article{
author = "Đurašević, Siniša and Stojković, Maja and Bogdanović, Ljiljana and Pavlović, Slađan and Borković Mitić, Slavica and Grigorov, Ilijana and Bogojević, Desanka and Jasnić, Nebojša and Tosti, Tomislav and Đurović, Saša and Đorđević, Jelena and Todorović, Zoran",
year = "2019",
abstract = "Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to
treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation
to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week
meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our
results showed that meldonium decreased animal body mass gain, food and water intake, and
carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium
increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and
increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1,
causing manganese superoxide dismutase expression and activity to increase, as well as lipid
peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase
activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum
high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in
I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and
serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex
changes in renal lipidomics. Taken together, our results have confirmed that meldonium pretreatment protects against I/R-induced oxidative stress and apoptosis/necrosis.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats",
number = "22",
volume = "20",
doi = "10.3390/ijms20225747",
pages = "5747"
}

Đurašević, S., Stojković, M., Bogdanović, L., Pavlović, S., Borković Mitić, S., Grigorov, I., Bogojević, D., Jasnić, N., Tosti, T., Đurović, S., Đorđević, J.,& Todorović, Z.. (2019). The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences
MDPI., 20(22), 5747.
https://doi.org/10.3390/ijms20225747

Đurašević S, Stojković M, Bogdanović L, Pavlović S, Borković Mitić S, Grigorov I, Bogojević D, Jasnić N, Tosti T, Đurović S, Đorđević J, Todorović Z. The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences. 2019;20(22):5747.
doi:10.3390/ijms20225747 .

Đurašević, Siniša, Stojković, Maja, Bogdanović, Ljiljana, Pavlović, Slađan, Borković Mitić, Slavica, Grigorov, Ilijana, Bogojević, Desanka, Jasnić, Nebojša, Tosti, Tomislav, Đurović, Saša, Đorđević, Jelena, Todorović, Zoran, "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats" in International Journal of Molecular Sciences, 20, no. 22 (2019):5747,
https://doi.org/10.3390/ijms20225747 . .

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  - 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  - 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  - CHAP
AU  - Uskoković, Aleksandra
AU  - Dinić, Svetlana
AU  - Arambašić Jovanović, Jelena
AU  - Poznanović, Goran
AU  - Vidaković, Melita
AU  - Mihailović, Mirjana
PY  - 2019
UR  - http://link.springer.com/10.1007/978-3-319-31143-2_112-1
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2884
AB  - The liver is the central organ for lipid and glucose metabolism. Impaired homeostasis of metabolism promotes the development of nonalcoholic fatty liver disease which is recognized worldwide as the most common liver disease. It covers the entire spectrum of liver disorders, from steatosis which can progress to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease is primarily associated with the metabolic syndrome, which is assumed to represent the hepatic manifestation of the metabolic syndrome. Besides endogenous factors such as the metabolic syndrome, obesity, hypertriglyceridemia, and diabetes, all important risk factors for the development and progression of liver injury, increased alcohol consumption, certain drugs, and environmental contaminants can also induce hepatotoxicity. Epigenetic alterations that are involved in the regulation of hepatic lipid metabolism and the oxidative stress response are important players in the development and progression of liver diseases. Concerning the vital role of oxidative stress in the etiology of liver injury, a number of studies have established the efficacy of antioxidants in the prevention and treatment of liver disease. Alpha-lipoic acid is a naturally occurring compound with a powerful in vivo antioxidant activity that can modulate the redox status of cells and the activities of proteins, thus affecting cell signaling and transcriptional responses involved in glucose and lipid metabolism. This review summarizes the effects of alpha-lipoic acid in liver pathologies related to obesity, metabolic disorders, diabetes, nonalcoholic fatty liver disease, drug toxicity, and radiation. The many beneficial effects of alpha-lipoic acid include improvement of liver transaminases, enhanced scavenging of reactive oxygen species, increased activities of antioxidant enzymes and the resulting decrease in oxidative stress and inflammatory signals, reduced DNA damage, suppression of the fibrotic process, and improved lipid metabolism. In addition, alpha-lipoic acid administration could indirectly prevent epigenetic modifications in the liver by scavenging reactive oxygen species and regulating the NAD+/NADH ratio which is important for NAD+-dependent deacetylase sirtuin activity. Alpha-lipoic acid also mitigates the changes in DNA methylation in rat liver induced by low-density irradiation. However, the majority of alpha-lipoic acid actions have been primarily observed in in vitro and in vivo experimental studies. Translation of this biological knowledge and experimental data to human clinical use warrants further investigation.
PB  - Springer International Publishing, Cham
T2  - Handbook of Nutrition, Diet, and Epigenetics
T1  - Liver Diseases: Epigenetic Mechanisms, Oxidative Stress and Use of Alpha-Lipoic Acid
DO  - 10.1007/978-3-319-31143-2_112-1
SP  - 1121
EP  - 1141
ER  - 

@inbook{
author = "Uskoković, Aleksandra and Dinić, Svetlana and Arambašić Jovanović, Jelena and Poznanović, Goran and Vidaković, Melita and Mihailović, Mirjana",
year = "2019",
abstract = "The liver is the central organ for lipid and glucose metabolism. Impaired homeostasis of metabolism promotes the development of nonalcoholic fatty liver disease which is recognized worldwide as the most common liver disease. It covers the entire spectrum of liver disorders, from steatosis which can progress to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease is primarily associated with the metabolic syndrome, which is assumed to represent the hepatic manifestation of the metabolic syndrome. Besides endogenous factors such as the metabolic syndrome, obesity, hypertriglyceridemia, and diabetes, all important risk factors for the development and progression of liver injury, increased alcohol consumption, certain drugs, and environmental contaminants can also induce hepatotoxicity. Epigenetic alterations that are involved in the regulation of hepatic lipid metabolism and the oxidative stress response are important players in the development and progression of liver diseases. Concerning the vital role of oxidative stress in the etiology of liver injury, a number of studies have established the efficacy of antioxidants in the prevention and treatment of liver disease. Alpha-lipoic acid is a naturally occurring compound with a powerful in vivo antioxidant activity that can modulate the redox status of cells and the activities of proteins, thus affecting cell signaling and transcriptional responses involved in glucose and lipid metabolism. This review summarizes the effects of alpha-lipoic acid in liver pathologies related to obesity, metabolic disorders, diabetes, nonalcoholic fatty liver disease, drug toxicity, and radiation. The many beneficial effects of alpha-lipoic acid include improvement of liver transaminases, enhanced scavenging of reactive oxygen species, increased activities of antioxidant enzymes and the resulting decrease in oxidative stress and inflammatory signals, reduced DNA damage, suppression of the fibrotic process, and improved lipid metabolism. In addition, alpha-lipoic acid administration could indirectly prevent epigenetic modifications in the liver by scavenging reactive oxygen species and regulating the NAD+/NADH ratio which is important for NAD+-dependent deacetylase sirtuin activity. Alpha-lipoic acid also mitigates the changes in DNA methylation in rat liver induced by low-density irradiation. However, the majority of alpha-lipoic acid actions have been primarily observed in in vitro and in vivo experimental studies. Translation of this biological knowledge and experimental data to human clinical use warrants further investigation.",
publisher = "Springer International Publishing, Cham",
journal = "Handbook of Nutrition, Diet, and Epigenetics",
booktitle = "Liver Diseases: Epigenetic Mechanisms, Oxidative Stress and Use of Alpha-Lipoic Acid",
doi = "10.1007/978-3-319-31143-2_112-1",
pages = "1121-1141"
}

Uskoković, A., Dinić, S., Arambašić Jovanović, J., Poznanović, G., Vidaković, M.,& Mihailović, M.. (2019). Liver Diseases: Epigenetic Mechanisms, Oxidative Stress and Use of Alpha-Lipoic Acid. in Handbook of Nutrition, Diet, and Epigenetics
Springer International Publishing, Cham., 1121-1141.
https://doi.org/10.1007/978-3-319-31143-2_112-1

Uskoković A, Dinić S, Arambašić Jovanović J, Poznanović G, Vidaković M, Mihailović M. Liver Diseases: Epigenetic Mechanisms, Oxidative Stress and Use of Alpha-Lipoic Acid. in Handbook of Nutrition, Diet, and Epigenetics. 2019;:1121-1141.
doi:10.1007/978-3-319-31143-2_112-1 .

Uskoković, Aleksandra, Dinić, Svetlana, Arambašić Jovanović, Jelena, Poznanović, Goran, Vidaković, Melita, Mihailović, Mirjana, "Liver Diseases: Epigenetic Mechanisms, Oxidative Stress and Use of Alpha-Lipoic Acid" in Handbook of Nutrition, Diet, and Epigenetics (2019):1121-1141,
https://doi.org/10.1007/978-3-319-31143-2_112-1 . .

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  - THES
AU  - Tolić, Anja
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3474
AB  - Važan aspekt u rasvetljavanju procesa demetilacije DNK predstavlja identifikacija faktora koji regulušu aktivnost TET proteina. Cilj ove doktorske disertacije bio je da se ispita funkcionalna veza između TET-posredovane oksidacije 5mC i PARP-zavisne PARilacije u procesu demetilacije DNK, na globalnom i lokalnom nivou. Rezultati ovog istraživanja ukazuju da PARP-1 interaguje sa TET1 i TET2. Pokazano je i da oba proteina podležu in vitro PARilaciji. PARP-1-zavisna PARilacija TET1 proteina negativno utiče na kinetiku aktivnosti TET1 in vitro. Rezultati in cellulo eksperimenata pokazali su da u odsustvu PARP-1 dolazi do porasta ekspresije Tet1 i Tet2, a da prilikom inhibicije PARilacije i u odsustvu PARP-1 dolazi do pada globalnog nivoa metilacije i porasta hidroksimetilacije DNK. Za analizu lokalnih efekata TET-PARP interakcije izabran je gen za hemokin CXCL12 koji učestvuje u brojnim fiziološkim i patološkim procesima pa je ispitivanje regulacije njegove ekspresije važno za buduće terapijske pristupe. Pokazano je da u odsustvu PARP-1 dolazi do povećane ekspresije kao i do pada u metilaciji Cxcl12. Nakon tretmana aktivatorom/inhibitorom TET aktivnosti, u odsustvu PARP-1, ekpresija Cxcl12 je povećana/smanjena. Prisustvo TET1 i TET2 detektovano je na promotoru Cxcl12 uz povećano regrutovanje TET2 u odsustvu PARP-1. U ovoj disertaciji pokazan je inhibitorni uticaj PARP-1 i PARilacije na aktivnost TET enzima u procesu demetilacije DNK na globalnom nivou, a funkcionalnost lokalnih efekata povezanosti TET i PARP enzima u procesu (de)metilacije ustanovljena je na primeru Cxcl12. Demetilacija DNK nalazi se u osnovi brojnih fizioloških i patoloških stanja, zato rasvetljavanje mehanizama regulacije ovog procesa predstavlja važan korak u potencijalnoj primeni stečenih saznanja u medicini.
AB  - Identification of factors that regulate the activity of TET proteins is important for elucidating the process of DNA demethylation. The aim of this doctoral dissertation was to investigate the functional relationship between TET-mediated oxidation of 5mC and PARP-dependent PARylation in the process of DNA demethylation at both global and local levels. This thesis shows that PARP-1 interacts with TET1 and TET2, and that both TET proteins can undergo in vitro PARylation. PARP-1-dependent PARylation of TET1 negatively affected the kinetics of TET1 activity in vitro. The results of in cellulo experiments revealed that the expression of Tet1 and Tet2 increased in the absence of PARP-1, whereas when PARylation was inhibited or in the absence of PARP-1, there was a decrease in the global level of DNA methylation and an increase in DNA hydroxymethylation. The Cxcl12 gene was selected for the analysis of the local effects of TET-PARP interaction since chemokine CXCL12 participates in numerous physiological and pathological processes, and exploring the regulation of expression of this gene is important for potential clinical intervention. Increased expression and decreased methylation of Cxcl12 were observed in the absence of PARP-1. After treatment with an activator or inhibitor of TET activity in the absence of PARP-1, Cxcl12 expression was respectively increased or decreased. The presence of TET1 and TET2 was detected on the Cxcl12 promoter, with enhanced recruitment of TET2 in the absence of PARP-1. This dissertation describes the inhibitory effects of PARP-1 and PARylation on the activity of TET enzymes in the process of DNA demethylation at the global level, and the local effects of TET-PARP interplay on DNA (de)methylation of Cxcl12 gene. DNA demethylation is at the root of numerous physiological and pathological conditions, and elucidating the mechanisms that regulate this process is an important step in the potential application of acquired knowledge in medicine.
PB  - Belgrade: Faculty of Biology, University of Belgrade
T2  - Faculty of Biology, University of Belgrade
T1  - Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK
T1  - Functional analysis of interactions between TET-mediated oxidation of 5-methylcytosine and PARP-dependent ADP-ribosylation in the process of DNA demethylation
SP  - 1
EP  - 127
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3474
ER  - 

@phdthesis{
author = "Tolić, Anja",
year = "2019",
abstract = "Važan aspekt u rasvetljavanju procesa demetilacije DNK predstavlja identifikacija faktora koji regulušu aktivnost TET proteina. Cilj ove doktorske disertacije bio je da se ispita funkcionalna veza između TET-posredovane oksidacije 5mC i PARP-zavisne PARilacije u procesu demetilacije DNK, na globalnom i lokalnom nivou. Rezultati ovog istraživanja ukazuju da PARP-1 interaguje sa TET1 i TET2. Pokazano je i da oba proteina podležu in vitro PARilaciji. PARP-1-zavisna PARilacija TET1 proteina negativno utiče na kinetiku aktivnosti TET1 in vitro. Rezultati in cellulo eksperimenata pokazali su da u odsustvu PARP-1 dolazi do porasta ekspresije Tet1 i Tet2, a da prilikom inhibicije PARilacije i u odsustvu PARP-1 dolazi do pada globalnog nivoa metilacije i porasta hidroksimetilacije DNK. Za analizu lokalnih efekata TET-PARP interakcije izabran je gen za hemokin CXCL12 koji učestvuje u brojnim fiziološkim i patološkim procesima pa je ispitivanje regulacije njegove ekspresije važno za buduće terapijske pristupe. Pokazano je da u odsustvu PARP-1 dolazi do povećane ekspresije kao i do pada u metilaciji Cxcl12. Nakon tretmana aktivatorom/inhibitorom TET aktivnosti, u odsustvu PARP-1, ekpresija Cxcl12 je povećana/smanjena. Prisustvo TET1 i TET2 detektovano je na promotoru Cxcl12 uz povećano regrutovanje TET2 u odsustvu PARP-1. U ovoj disertaciji pokazan je inhibitorni uticaj PARP-1 i PARilacije na aktivnost TET enzima u procesu demetilacije DNK na globalnom nivou, a funkcionalnost lokalnih efekata povezanosti TET i PARP enzima u procesu (de)metilacije ustanovljena je na primeru Cxcl12. Demetilacija DNK nalazi se u osnovi brojnih fizioloških i patoloških stanja, zato rasvetljavanje mehanizama regulacije ovog procesa predstavlja važan korak u potencijalnoj primeni stečenih saznanja u medicini., Identification of factors that regulate the activity of TET proteins is important for elucidating the process of DNA demethylation. The aim of this doctoral dissertation was to investigate the functional relationship between TET-mediated oxidation of 5mC and PARP-dependent PARylation in the process of DNA demethylation at both global and local levels. This thesis shows that PARP-1 interacts with TET1 and TET2, and that both TET proteins can undergo in vitro PARylation. PARP-1-dependent PARylation of TET1 negatively affected the kinetics of TET1 activity in vitro. The results of in cellulo experiments revealed that the expression of Tet1 and Tet2 increased in the absence of PARP-1, whereas when PARylation was inhibited or in the absence of PARP-1, there was a decrease in the global level of DNA methylation and an increase in DNA hydroxymethylation. The Cxcl12 gene was selected for the analysis of the local effects of TET-PARP interaction since chemokine CXCL12 participates in numerous physiological and pathological processes, and exploring the regulation of expression of this gene is important for potential clinical intervention. Increased expression and decreased methylation of Cxcl12 were observed in the absence of PARP-1. After treatment with an activator or inhibitor of TET activity in the absence of PARP-1, Cxcl12 expression was respectively increased or decreased. The presence of TET1 and TET2 was detected on the Cxcl12 promoter, with enhanced recruitment of TET2 in the absence of PARP-1. This dissertation describes the inhibitory effects of PARP-1 and PARylation on the activity of TET enzymes in the process of DNA demethylation at the global level, and the local effects of TET-PARP interplay on DNA (de)methylation of Cxcl12 gene. DNA demethylation is at the root of numerous physiological and pathological conditions, and elucidating the mechanisms that regulate this process is an important step in the potential application of acquired knowledge in medicine.",
publisher = "Belgrade: Faculty of Biology, University of Belgrade",
journal = "Faculty of Biology, University of Belgrade",
title = "Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK, Functional analysis of interactions between TET-mediated oxidation of 5-methylcytosine and PARP-dependent ADP-ribosylation in the process of DNA demethylation",
pages = "1-127",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3474"
}

Tolić, A.. (2019). Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK. in Faculty of Biology, University of Belgrade
Belgrade: Faculty of Biology, University of Belgrade., 1-127.
https://hdl.handle.net/21.15107/rcub_ibiss_3474

Tolić A. Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK. in Faculty of Biology, University of Belgrade. 2019;:1-127.
https://hdl.handle.net/21.15107/rcub_ibiss_3474 .

Tolić, Anja, "Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK" in Faculty of Biology, University of Belgrade (2019):1-127,
https://hdl.handle.net/21.15107/rcub_ibiss_3474 .

TY  - CONF
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović-Matić, Svetlana
AU  - Martinović, Vesna
AU  - Korać, Aleksandra
AU  - Jovanović-Stojanov, Sofija
AU  - Grigorov, Ilijana
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5660
AB  - Oxidative stress. cell damage and cell death underlies the etiology of liver damage/dysfunction  in  diabetes.  Bigh  Mobility  Group  Box 1 (HMGB1) is a nuclear protein that is  released  from damaged/stressed  liver cells during, diabetes and  contributes to oxidative  stresse-mediated autophagy  an cell death/survival. Since ethyl pyruvate (EP) an HMGB1 relase/expession and autophagy in the liver of diabetic rats. Diabetes was indused by streptozotocin(65mg/kg). Pretreated group of diabetes rats- (EP+D) startedl treatment  with EP (80mg/kg/daily) three·days before
diabetes induction,  while  in  the  second  group  (D+EP}  treatment  start   ten  days after diabetes induuction. In compcarison with D+EP group, EP+D group had better glycemic  status  and  higher  activity  of  antioxidative enzyme  SOD  and CAT in diabetic  liver.  According  to  western  immunoblot   analyses,  EP+D  group   sliowed higher     expression     of     extracellular    HMGB l     in    comparison      with D+EP. Consequently  detected increase in HMGB1/RAGE interactions in EP+D group were followed  by higher expression of LC3-II, HMGB1/Beclin 1 interaction and activation  of  autophagy.  Expression  of  LC3-II  and   HMGB1/Beclin 1 interaction were  at  the  control  level  in  D+EP.  Preserved  liver   morphology  in  both  EP   treated groups, observed  by  electron  microscopy,   implicated  existence   of   adaptive mechanisms  in EP+D  group.  Further  analyses  showed that  protective autophagy (mitophagy) was enhanced in EP+D group compared with diabetic and D+EP groups. Thus treatment of  diabetic  patients  with  EP  may  constitute  a  new strategy for the treatment  of  diabetes related  tissue  injury.
PB  - Belgrade: Serbian Physiological Society
C3  - Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
T1  - Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver
SP  - 108
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5660
ER  - 

@conference{
author = "Petrović, Anja and Bogojević, Desanka and Ivanović-Matić, Svetlana and Martinović, Vesna and Korać, Aleksandra and Jovanović-Stojanov, Sofija and Grigorov, Ilijana",
year = "2018",
abstract = "Oxidative stress. cell damage and cell death underlies the etiology of liver damage/dysfunction  in  diabetes.  Bigh  Mobility  Group  Box 1 (HMGB1) is a nuclear protein that is  released  from damaged/stressed  liver cells during, diabetes and  contributes to oxidative  stresse-mediated autophagy  an cell death/survival. Since ethyl pyruvate (EP) an HMGB1 relase/expession and autophagy in the liver of diabetic rats. Diabetes was indused by streptozotocin(65mg/kg). Pretreated group of diabetes rats- (EP+D) startedl treatment  with EP (80mg/kg/daily) three·days before
diabetes induction,  while  in  the  second  group  (D+EP}  treatment  start   ten  days after diabetes induuction. In compcarison with D+EP group, EP+D group had better glycemic  status  and  higher  activity  of  antioxidative enzyme  SOD  and CAT in diabetic  liver.  According  to  western  immunoblot   analyses,  EP+D  group   sliowed higher     expression     of     extracellular    HMGB l     in    comparison      with D+EP. Consequently  detected increase in HMGB1/RAGE interactions in EP+D group were followed  by higher expression of LC3-II, HMGB1/Beclin 1 interaction and activation  of  autophagy.  Expression  of  LC3-II  and   HMGB1/Beclin 1 interaction were  at  the  control  level  in  D+EP.  Preserved  liver   morphology  in  both  EP   treated groups, observed  by  electron  microscopy,   implicated  existence   of   adaptive mechanisms  in EP+D  group.  Further  analyses  showed that  protective autophagy (mitophagy) was enhanced in EP+D group compared with diabetic and D+EP groups. Thus treatment of  diabetic  patients  with  EP  may  constitute  a  new strategy for the treatment  of  diabetes related  tissue  injury.",
publisher = "Belgrade: Serbian Physiological Society",
journal = "Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia",
title = "Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver",
pages = "108",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5660"
}

Petrović, A., Bogojević, D., Ivanović-Matić, S., Martinović, V., Korać, A., Jovanović-Stojanov, S.,& Grigorov, I.. (2018). Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
Belgrade: Serbian Physiological Society., 108.
https://hdl.handle.net/21.15107/rcub_ibiss_5660

Petrović A, Bogojević D, Ivanović-Matić S, Martinović V, Korać A, Jovanović-Stojanov S, Grigorov I. Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia. 2018;:108.
https://hdl.handle.net/21.15107/rcub_ibiss_5660 .

Petrović, Anja, Bogojević, Desanka, Ivanović-Matić, Svetlana, Martinović, Vesna, Korać, Aleksandra, Jovanović-Stojanov, Sofija, Grigorov, Ilijana, "Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver" in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia (2018):108,
https://hdl.handle.net/21.15107/rcub_ibiss_5660 .

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 . .