Milenkovic, Dragan

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Author's Bibliography

Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats

Miler, Marko; Živanović, Jasmina; Ajdžanović, Vladimir; Milenkovic, Dragan; Cesar, Thais; Filipović R., Miloš; Milošević, Verica

(John Wiley and Sons, 2024)

TY  - JOUR
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Ajdžanović, Vladimir
AU  - Milenkovic, Dragan
AU  - Cesar, Thais
AU  - Filipović R., Miloš
AU  - Milošević, Verica
PY  - 2024
UR  - https://iubmb.onlinelibrary.wiley.com/journal/18728081
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6462
AB  - Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for four weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate-cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver.
PB  - John Wiley and Sons
T2  - Biofactors
T1  - Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats
DO  - 10.1002/biof.2038
ER  - 
@article{
author = "Miler, Marko and Živanović, Jasmina and Ajdžanović, Vladimir and Milenkovic, Dragan and Cesar, Thais and Filipović R., Miloš and Milošević, Verica",
year = "2024",
abstract = "Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for four weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate-cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver.",
publisher = "John Wiley and Sons",
journal = "Biofactors",
title = "Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats",
doi = "10.1002/biof.2038"
}
Miler, M., Živanović, J., Ajdžanović, V., Milenkovic, D., Cesar, T., Filipović R., M.,& Milošević, V.. (2024). Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats. in Biofactors
John Wiley and Sons..
https://doi.org/10.1002/biof.2038
Miler M, Živanović J, Ajdžanović V, Milenkovic D, Cesar T, Filipović R. M, Milošević V. Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats. in Biofactors. 2024;.
doi:10.1002/biof.2038 .
Miler, Marko, Živanović, Jasmina, Ajdžanović, Vladimir, Milenkovic, Dragan, Cesar, Thais, Filipović R., Miloš, Milošević, Verica, "Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats" in Biofactors (2024),
https://doi.org/10.1002/biof.2038 . .

Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans - Evidence from untargeted mRNA and miRNA studies

Ruskovska, Tatjana; Budić-Leto, Irena; Corral-Jara, Karla Fabiola; Ajdžanović, Vladimir; Arola-Arnal, Anna; Bravo, Francisca Isabel; Deligiannidou, Georgia-Eirini; Havlik, Jaroslav; Janeva, Milkica; Kistanova, Elena; Kontogiorgis, Christos; Krga, Irena; Massaro, Marika; Miler, Marko; Harnafi, Hicham; Milošević, Verica; Morand, Christine; Scoditti, Egeria; Suárez, Manuel; Vauzour, David; Milenkovic, Dragan

(Elsevier B.V., 2022)

TY  - JOUR
AU  - Ruskovska, Tatjana
AU  - Budić-Leto, Irena
AU  - Corral-Jara, Karla Fabiola
AU  - Ajdžanović, Vladimir
AU  - Arola-Arnal, Anna
AU  - Bravo, Francisca Isabel
AU  - Deligiannidou, Georgia-Eirini
AU  - Havlik, Jaroslav
AU  - Janeva, Milkica
AU  - Kistanova, Elena
AU  - Kontogiorgis, Christos
AU  - Krga, Irena
AU  - Massaro, Marika
AU  - Miler, Marko
AU  - Harnafi, Hicham
AU  - Milošević, Verica
AU  - Morand, Christine
AU  - Scoditti, Egeria
AU  - Suárez, Manuel
AU  - Vauzour, David
AU  - Milenkovic, Dragan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4977
AB  - Cardiovascular and metabolic disorders present major causes of mortality in the ageing population. Polyphenols present in human diets possess cardiometabolic protective properties, however their underlying molecular mechanisms in humans are still not well identified. Even though preclinical and in vitro studies advocate that these bioactives can modulate gene expression, most studies were performed using targeted approaches. With the objective to decipher the molecular mechanisms underlying polyphenols cardiometabolic preventive properties in humans, we performed integrative multi-omic bioinformatic analyses of published studies which reported improvements of cardiometabolic risk factors following polyphenol intake, together with genomic analyses performed using untargeted approach. We identified 5 studies within our criteria and nearly 5000 differentially expressed genes, both mRNAs and miRNAs, in peripheral blood cells. Integrative bioinformatic analyses (e.g. pathway and gene network analyses, identification of transcription factors, correlation of gene expression profiles with those associated with diseases and drug intake) revealed that these genes are involved in the processes such as cell adhesion and mobility, immune system, metabolism, or cell signaling. We also identified 27 miRNAs known to regulate processes such as cell cytoskeleton, chemotaxis, cell signaling, or cell metabolism. Gene expression profiles negatively correlated with expression profiles of cardiovascular disease patients, while a positive correlation was observed with gene expression profiles following intake of drugs against cardiometabolic disorders. These analyses further advocate for health protective effects of these bioactives against age-associated diseases. In conclusion, polyphenols can exert multi-genomic modifications in humans and use of untargeted methods coupled with bioinformatic analyses represent the best approach to decipher molecular mechanisms underlying healthy-ageing effects of these bioactives.
PB  - Elsevier B.V.
T2  - Ageing Research Reviews
T1  - Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans - Evidence from untargeted mRNA and miRNA studies
VL  - 79:101649
DO  - 10.1016/j.arr.2022.101649
ER  - 
@article{
author = "Ruskovska, Tatjana and Budić-Leto, Irena and Corral-Jara, Karla Fabiola and Ajdžanović, Vladimir and Arola-Arnal, Anna and Bravo, Francisca Isabel and Deligiannidou, Georgia-Eirini and Havlik, Jaroslav and Janeva, Milkica and Kistanova, Elena and Kontogiorgis, Christos and Krga, Irena and Massaro, Marika and Miler, Marko and Harnafi, Hicham and Milošević, Verica and Morand, Christine and Scoditti, Egeria and Suárez, Manuel and Vauzour, David and Milenkovic, Dragan",
year = "2022",
abstract = "Cardiovascular and metabolic disorders present major causes of mortality in the ageing population. Polyphenols present in human diets possess cardiometabolic protective properties, however their underlying molecular mechanisms in humans are still not well identified. Even though preclinical and in vitro studies advocate that these bioactives can modulate gene expression, most studies were performed using targeted approaches. With the objective to decipher the molecular mechanisms underlying polyphenols cardiometabolic preventive properties in humans, we performed integrative multi-omic bioinformatic analyses of published studies which reported improvements of cardiometabolic risk factors following polyphenol intake, together with genomic analyses performed using untargeted approach. We identified 5 studies within our criteria and nearly 5000 differentially expressed genes, both mRNAs and miRNAs, in peripheral blood cells. Integrative bioinformatic analyses (e.g. pathway and gene network analyses, identification of transcription factors, correlation of gene expression profiles with those associated with diseases and drug intake) revealed that these genes are involved in the processes such as cell adhesion and mobility, immune system, metabolism, or cell signaling. We also identified 27 miRNAs known to regulate processes such as cell cytoskeleton, chemotaxis, cell signaling, or cell metabolism. Gene expression profiles negatively correlated with expression profiles of cardiovascular disease patients, while a positive correlation was observed with gene expression profiles following intake of drugs against cardiometabolic disorders. These analyses further advocate for health protective effects of these bioactives against age-associated diseases. In conclusion, polyphenols can exert multi-genomic modifications in humans and use of untargeted methods coupled with bioinformatic analyses represent the best approach to decipher molecular mechanisms underlying healthy-ageing effects of these bioactives.",
publisher = "Elsevier B.V.",
journal = "Ageing Research Reviews",
title = "Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans - Evidence from untargeted mRNA and miRNA studies",
volume = "79:101649",
doi = "10.1016/j.arr.2022.101649"
}
Ruskovska, T., Budić-Leto, I., Corral-Jara, K. F., Ajdžanović, V., Arola-Arnal, A., Bravo, F. I., Deligiannidou, G., Havlik, J., Janeva, M., Kistanova, E., Kontogiorgis, C., Krga, I., Massaro, M., Miler, M., Harnafi, H., Milošević, V., Morand, C., Scoditti, E., Suárez, M., Vauzour, D.,& Milenkovic, D.. (2022). Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans - Evidence from untargeted mRNA and miRNA studies. in Ageing Research Reviews
Elsevier B.V.., 79:101649.
https://doi.org/10.1016/j.arr.2022.101649
Ruskovska T, Budić-Leto I, Corral-Jara KF, Ajdžanović V, Arola-Arnal A, Bravo FI, Deligiannidou G, Havlik J, Janeva M, Kistanova E, Kontogiorgis C, Krga I, Massaro M, Miler M, Harnafi H, Milošević V, Morand C, Scoditti E, Suárez M, Vauzour D, Milenkovic D. Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans - Evidence from untargeted mRNA and miRNA studies. in Ageing Research Reviews. 2022;79:101649.
doi:10.1016/j.arr.2022.101649 .
Ruskovska, Tatjana, Budić-Leto, Irena, Corral-Jara, Karla Fabiola, Ajdžanović, Vladimir, Arola-Arnal, Anna, Bravo, Francisca Isabel, Deligiannidou, Georgia-Eirini, Havlik, Jaroslav, Janeva, Milkica, Kistanova, Elena, Kontogiorgis, Christos, Krga, Irena, Massaro, Marika, Miler, Marko, Harnafi, Hicham, Milošević, Verica, Morand, Christine, Scoditti, Egeria, Suárez, Manuel, Vauzour, David, Milenkovic, Dragan, "Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans - Evidence from untargeted mRNA and miRNA studies" in Ageing Research Reviews, 79:101649 (2022),
https://doi.org/10.1016/j.arr.2022.101649 . .
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Molecular Determinants of the Cardiometabolic Improvements of Dietary Flavanols Identified by an Integrative Analysis of Nutrigenomic Data from a Systematic Review of Animal Studies.

Monfoulet, Laurent‐Emmanuel; Ruskovska, Tatjana; Ajdžanović, Vladimir; Havlik, Jaroslav; Vauzour, David; Bayram, Banu; Krga, Irena; Corral-Jara, Karla-Fabiola; Kistanova, Elena; Abadjieva, Desislava; Massaro, Marika; Scoditti, Egeria; Deligiannidou, Eirini; Kontogiorgis, Christos; Arola-Arnal, Anna; van Schothorst, Evert M; Morand, Christine; Milenkovic, Dragan

(John Wiley and Sons, 2021)

TY  - JOUR
AU  - Monfoulet, Laurent‐Emmanuel
AU  - Ruskovska, Tatjana
AU  - Ajdžanović, Vladimir
AU  - Havlik, Jaroslav
AU  - Vauzour, David
AU  - Bayram, Banu
AU  - Krga, Irena
AU  - Corral-Jara, Karla-Fabiola
AU  - Kistanova, Elena
AU  - Abadjieva, Desislava
AU  - Massaro, Marika
AU  - Scoditti, Egeria
AU  - Deligiannidou, Eirini
AU  - Kontogiorgis, Christos
AU  - Arola-Arnal, Anna
AU  - van Schothorst, Evert M
AU  - Morand, Christine
AU  - Milenkovic, Dragan
PY  - 2021
UR  - https://onlinelibrary.wiley.com/doi/10.1002/mnfr.202100227
UR  - http://www.ncbi.nlm.nih.gov/pubmed/34048642
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4437
AB  - SCOPE Flavanols are important polyphenols of the human diet with extensive demonstrations of their beneficial effects on cardiometabolic health. They contribute to preserve health acting on a large range of cellular processes. The underlying mechanisms of action of flavanols are not fully understood but involve a nutrigenomic regulation. METHODS AND RESULTS To further capture how the intake of dietary flavanols results in the modulation of gene expression, nutrigenomics data in response to dietary flavanols obtained from animal models of cardiometabolic diseases have been collected and submitted to a bioinformatics analysis. This systematic analysis shows that dietary flavanols modulate a large range of genes mainly involved in endocrine function, fatty acid metabolism, and inflammation. Several regulators of the gene expression have been predicted and include transcription factors, miRNAs and epigenetic factors. CONCLUSION This review highlights the complex and multilevel action of dietary flavanols contributing to their strong potential to preserve cardiometabolic health. The identification of the potential molecular mediators and of the flavanol metabolites driving the nutrigenomic response in the target organs is still a pending question which the answer will contribute to optimize the beneficial health effects of dietary bioactives.
PB  - John Wiley and Sons
T2  - Molecular Nutrition & Food Research
T2  - Molecular Nutrition & Food Research
T1  - Molecular Determinants of the Cardiometabolic Improvements of Dietary Flavanols Identified by an Integrative Analysis of Nutrigenomic Data from a Systematic Review of Animal Studies.
IS  - 16
VL  - 65
DO  - 10.1002/mnfr.202100227
SP  - e2100227
ER  - 
@article{
author = "Monfoulet, Laurent‐Emmanuel and Ruskovska, Tatjana and Ajdžanović, Vladimir and Havlik, Jaroslav and Vauzour, David and Bayram, Banu and Krga, Irena and Corral-Jara, Karla-Fabiola and Kistanova, Elena and Abadjieva, Desislava and Massaro, Marika and Scoditti, Egeria and Deligiannidou, Eirini and Kontogiorgis, Christos and Arola-Arnal, Anna and van Schothorst, Evert M and Morand, Christine and Milenkovic, Dragan",
year = "2021",
abstract = "SCOPE Flavanols are important polyphenols of the human diet with extensive demonstrations of their beneficial effects on cardiometabolic health. They contribute to preserve health acting on a large range of cellular processes. The underlying mechanisms of action of flavanols are not fully understood but involve a nutrigenomic regulation. METHODS AND RESULTS To further capture how the intake of dietary flavanols results in the modulation of gene expression, nutrigenomics data in response to dietary flavanols obtained from animal models of cardiometabolic diseases have been collected and submitted to a bioinformatics analysis. This systematic analysis shows that dietary flavanols modulate a large range of genes mainly involved in endocrine function, fatty acid metabolism, and inflammation. Several regulators of the gene expression have been predicted and include transcription factors, miRNAs and epigenetic factors. CONCLUSION This review highlights the complex and multilevel action of dietary flavanols contributing to their strong potential to preserve cardiometabolic health. The identification of the potential molecular mediators and of the flavanol metabolites driving the nutrigenomic response in the target organs is still a pending question which the answer will contribute to optimize the beneficial health effects of dietary bioactives.",
publisher = "John Wiley and Sons",
journal = "Molecular Nutrition & Food Research, Molecular Nutrition & Food Research",
title = "Molecular Determinants of the Cardiometabolic Improvements of Dietary Flavanols Identified by an Integrative Analysis of Nutrigenomic Data from a Systematic Review of Animal Studies.",
number = "16",
volume = "65",
doi = "10.1002/mnfr.202100227",
pages = "e2100227"
}
Monfoulet, L., Ruskovska, T., Ajdžanović, V., Havlik, J., Vauzour, D., Bayram, B., Krga, I., Corral-Jara, K., Kistanova, E., Abadjieva, D., Massaro, M., Scoditti, E., Deligiannidou, E., Kontogiorgis, C., Arola-Arnal, A., van Schothorst, E. M., Morand, C.,& Milenkovic, D.. (2021). Molecular Determinants of the Cardiometabolic Improvements of Dietary Flavanols Identified by an Integrative Analysis of Nutrigenomic Data from a Systematic Review of Animal Studies.. in Molecular Nutrition & Food Research
John Wiley and Sons., 65(16), e2100227.
https://doi.org/10.1002/mnfr.202100227
Monfoulet L, Ruskovska T, Ajdžanović V, Havlik J, Vauzour D, Bayram B, Krga I, Corral-Jara K, Kistanova E, Abadjieva D, Massaro M, Scoditti E, Deligiannidou E, Kontogiorgis C, Arola-Arnal A, van Schothorst EM, Morand C, Milenkovic D. Molecular Determinants of the Cardiometabolic Improvements of Dietary Flavanols Identified by an Integrative Analysis of Nutrigenomic Data from a Systematic Review of Animal Studies.. in Molecular Nutrition & Food Research. 2021;65(16):e2100227.
doi:10.1002/mnfr.202100227 .
Monfoulet, Laurent‐Emmanuel, Ruskovska, Tatjana, Ajdžanović, Vladimir, Havlik, Jaroslav, Vauzour, David, Bayram, Banu, Krga, Irena, Corral-Jara, Karla-Fabiola, Kistanova, Elena, Abadjieva, Desislava, Massaro, Marika, Scoditti, Egeria, Deligiannidou, Eirini, Kontogiorgis, Christos, Arola-Arnal, Anna, van Schothorst, Evert M, Morand, Christine, Milenkovic, Dragan, "Molecular Determinants of the Cardiometabolic Improvements of Dietary Flavanols Identified by an Integrative Analysis of Nutrigenomic Data from a Systematic Review of Animal Studies." in Molecular Nutrition & Food Research, 65, no. 16 (2021):e2100227,
https://doi.org/10.1002/mnfr.202100227 . .
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