TY  - JOUR
AU  - Zakić, Tamara
AU  - Kalezić, Anđelika
AU  - Drvendžija, Zorka
AU  - Udicki, Mirjana
AU  - Ivković Kapicl, Tatjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6528
AB  - The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated β-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.
PB  - Basel: MDPI
T2  - Cells
T1  - Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue
IS  - 2
VL  - 13
DO  - 10.3390/cells13020155
SP  - 155
ER  - 

@article{
author = "Zakić, Tamara and Kalezić, Anđelika and Drvendžija, Zorka and Udicki, Mirjana and Ivković Kapicl, Tatjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2024",
abstract = "The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated β-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue",
number = "2",
volume = "13",
doi = "10.3390/cells13020155",
pages = "155"
}

Zakić, T., Kalezić, A., Drvendžija, Z., Udicki, M., Ivković Kapicl, T., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2024). Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue. in Cells
Basel: MDPI., 13(2), 155.
https://doi.org/10.3390/cells13020155

Zakić T, Kalezić A, Drvendžija Z, Udicki M, Ivković Kapicl T, Srdić Galić B, Korać A, Janković A, Korać B. Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue. in Cells. 2024;13(2):155.
doi:10.3390/cells13020155 .

Zakić, Tamara, Kalezić, Anđelika, Drvendžija, Zorka, Udicki, Mirjana, Ivković Kapicl, Tatjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue" in Cells, 13, no. 2 (2024):155,
https://doi.org/10.3390/cells13020155 . .

TY  - CONF
AU  - Zakić, Tamara
AU  - Budnar-Šoškić, Marta
AU  - Stojanović, Sara
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković-Vaughan, Vanja
AU  - Korać, Bato
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6527
AB  - The precise regulatory mechanisms of interscapular brown adipose tissue (IBAT) thermogenesis are not fully elucidated, especially those in relation to Nuclear factor erythroid 2–related factor 2 (Nrf2). We have recently shown that mice lacking functional Nrf2 (Nrf2KO) at room temperature (RT) depict thermogenic IBAT activity at the structural level. However, gene and protein expression of the main IBAT thermogenic marker uncoupling protein 1 (UCP1), and other redox-metabolic functional parameters, did not align with this apparent thermogenic activation. Here, we investigated the functional activation of IBAT in wild-type (WT) and Nrf2KO mice maintained at RT (24±1°C) or after cold acclimation (45 days, 4±1°C). We performed immunogold labelling of Nrf2 and its closely related transcription factors Nrf1, Nrf3, and nuclear respiratory factor 1 (NRF1) to determine their spatial expression patterns. Next, we measured succinate-based mitochondrial respiration as an indicator of IBAT mitochondrial oxidative function and uncoupling capacity. Electron microscopy confirmed that Nrf2KO mice at RT had the same ultrastructural characteristics as cold-exposed mice, indicating IBAT thermogenic activity. This was associated with increased mitochondrial immunogold reaction of the above redox-sensitive transcription factors indicating their activation in Nrf2KO mice at RT. In contrast to such activated phenotype, respirometry results showed that Nrf2KO mice at RT had no uncoupling activity compared to cold-exposed WT mice. Furthermore, similar respiratory pattern was observed in Nrf2KO mice acclimated to cold, regardless of increased UCP1 expression. These results demonstrate that despite the (ultra)structural recruitment of IBAT in Nrf2KO mice at RT and after cold acclimation, Nrf2 is essential for the full functional thermogenic activation of IBAT and the lack of functional Nrf2 could not be compensated with Nrf1, Nrf3, and NRF1.
PB  - Elsevier
C3  - Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
T1  - The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2
DO  - 10.1016/j.freeradbiomed.2023.03.109
SP  - 25
ER  - 

@conference{
author = "Zakić, Tamara and Budnar-Šoškić, Marta and Stojanović, Sara and Janković, Aleksandra and Korać, Aleksandra and Peković-Vaughan, Vanja and Korać, Bato",
year = "2023",
abstract = "The precise regulatory mechanisms of interscapular brown adipose tissue (IBAT) thermogenesis are not fully elucidated, especially those in relation to Nuclear factor erythroid 2–related factor 2 (Nrf2). We have recently shown that mice lacking functional Nrf2 (Nrf2KO) at room temperature (RT) depict thermogenic IBAT activity at the structural level. However, gene and protein expression of the main IBAT thermogenic marker uncoupling protein 1 (UCP1), and other redox-metabolic functional parameters, did not align with this apparent thermogenic activation. Here, we investigated the functional activation of IBAT in wild-type (WT) and Nrf2KO mice maintained at RT (24±1°C) or after cold acclimation (45 days, 4±1°C). We performed immunogold labelling of Nrf2 and its closely related transcription factors Nrf1, Nrf3, and nuclear respiratory factor 1 (NRF1) to determine their spatial expression patterns. Next, we measured succinate-based mitochondrial respiration as an indicator of IBAT mitochondrial oxidative function and uncoupling capacity. Electron microscopy confirmed that Nrf2KO mice at RT had the same ultrastructural characteristics as cold-exposed mice, indicating IBAT thermogenic activity. This was associated with increased mitochondrial immunogold reaction of the above redox-sensitive transcription factors indicating their activation in Nrf2KO mice at RT. In contrast to such activated phenotype, respirometry results showed that Nrf2KO mice at RT had no uncoupling activity compared to cold-exposed WT mice. Furthermore, similar respiratory pattern was observed in Nrf2KO mice acclimated to cold, regardless of increased UCP1 expression. These results demonstrate that despite the (ultra)structural recruitment of IBAT in Nrf2KO mice at RT and after cold acclimation, Nrf2 is essential for the full functional thermogenic activation of IBAT and the lack of functional Nrf2 could not be compensated with Nrf1, Nrf3, and NRF1.",
publisher = "Elsevier",
journal = "Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria",
title = "The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2",
doi = "10.1016/j.freeradbiomed.2023.03.109",
pages = "25"
}

Zakić, T., Budnar-Šoškić, M., Stojanović, S., Janković, A., Korać, A., Peković-Vaughan, V.,& Korać, B.. (2023). The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
Elsevier., 25.
https://doi.org/10.1016/j.freeradbiomed.2023.03.109

Zakić T, Budnar-Šoškić M, Stojanović S, Janković A, Korać A, Peković-Vaughan V, Korać B. The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria. 2023;:25.
doi:10.1016/j.freeradbiomed.2023.03.109 .

Zakić, Tamara, Budnar-Šoškić, Marta, Stojanović, Sara, Janković, Aleksandra, Korać, Aleksandra, Peković-Vaughan, Vanja, Korać, Bato, "The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2" in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria (2023):25,
https://doi.org/10.1016/j.freeradbiomed.2023.03.109 . .

TY  - CONF
AU  - Budnar Šoškić, Marta
AU  - Zakić, Tamara
AU  - Korać, Aleksandra
AU  - Korać, Bato
AU  - Janković, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6526
AB  - Тight control of the lipid-deposition function of white adipose tissue (WAT) defines the overall metabolic homeostasis and entails coordinated antioxidant response. We aimed to reveal temporal changes in the antioxidant defence (AD) that is a prerequisite for lipid metabolism in the visceral WAT over 45 days of re-acclimation to room temperature (RT, 22±1 °C) in rats pre-acclimated to cold (45 days, 4±1 °C). The Nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant targets, as well as key lipogenic enzymes were examined in epididymal WAT (eWAT) and compared to the RT-maintained control. Upregulation of Nrf2 protein expression observed from the 1-12th day of re-acclimation was followed by an increase in the glutathione level (3-7th day) and the protein expression of copper, zinc superoxide dismutase (3-12th day), manganese superoxide dismutase (1-12th day), thioredoxin (1-45th day), and glutathione peroxidase (1-45th day). Such time-dependent changes in AD during re-acclimation coincided with increases in the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase that were further supported by elevated glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase protein levels. Observed redox-metabolic integration in eWAT resulted in the restitution of relative eWAT mass on the 12th day of re-acclimation. It can be concluded that Nrf2-coordinated redox-metabolic changes drive the restitution of eWAT lipid depot during the re-acclimation of rats after cold. These results show a novel role of Nrf2 in regulating redox-metabolic signaling under homeostatic conditions and its relevance in visceral adiposity in different metabolic diseases.
PB  - Elsevier
C3  - Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
T1  - Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold
DO  - 10.1016/j.freeradbiomed.2023.03.183
SP  - 26
ER  - 

@conference{
author = "Budnar Šoškić, Marta and Zakić, Tamara and Korać, Aleksandra and Korać, Bato and Janković, Aleksandra",
year = "2023",
abstract = "Тight control of the lipid-deposition function of white adipose tissue (WAT) defines the overall metabolic homeostasis and entails coordinated antioxidant response. We aimed to reveal temporal changes in the antioxidant defence (AD) that is a prerequisite for lipid metabolism in the visceral WAT over 45 days of re-acclimation to room temperature (RT, 22±1 °C) in rats pre-acclimated to cold (45 days, 4±1 °C). The Nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant targets, as well as key lipogenic enzymes were examined in epididymal WAT (eWAT) and compared to the RT-maintained control. Upregulation of Nrf2 protein expression observed from the 1-12th day of re-acclimation was followed by an increase in the glutathione level (3-7th day) and the protein expression of copper, zinc superoxide dismutase (3-12th day), manganese superoxide dismutase (1-12th day), thioredoxin (1-45th day), and glutathione peroxidase (1-45th day). Such time-dependent changes in AD during re-acclimation coincided with increases in the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase that were further supported by elevated glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase protein levels. Observed redox-metabolic integration in eWAT resulted in the restitution of relative eWAT mass on the 12th day of re-acclimation. It can be concluded that Nrf2-coordinated redox-metabolic changes drive the restitution of eWAT lipid depot during the re-acclimation of rats after cold. These results show a novel role of Nrf2 in regulating redox-metabolic signaling under homeostatic conditions and its relevance in visceral adiposity in different metabolic diseases.",
publisher = "Elsevier",
journal = "Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria",
title = "Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold",
doi = "10.1016/j.freeradbiomed.2023.03.183",
pages = "26"
}

Budnar Šoškić, M., Zakić, T., Korać, A., Korać, B.,& Janković, A.. (2023). Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
Elsevier., 26.
https://doi.org/10.1016/j.freeradbiomed.2023.03.183

Budnar Šoškić M, Zakić T, Korać A, Korać B, Janković A. Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria. 2023;:26.
doi:10.1016/j.freeradbiomed.2023.03.183 .

Budnar Šoškić, Marta, Zakić, Tamara, Korać, Aleksandra, Korać, Bato, Janković, Aleksandra, "Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold" in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria (2023):26,
https://doi.org/10.1016/j.freeradbiomed.2023.03.183 . .

TY  - JOUR
AU  - Zakić, Tamara
AU  - Peković-Vaughan, Vanja
AU  - Čvoro, Aleksandra
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6519
AB  - Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer-associated adipose tissue (CAAT). Understanding how the redox-metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo-organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell-specific redox-metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.
PB  - John Wiley
T2  - FEBS Letters
T1  - Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue
DO  - 10.1002/1873-3468.14794
ER  - 

@article{
author = "Zakić, Tamara and Peković-Vaughan, Vanja and Čvoro, Aleksandra and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2023",
abstract = "Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer-associated adipose tissue (CAAT). Understanding how the redox-metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo-organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell-specific redox-metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.",
publisher = "John Wiley",
journal = "FEBS Letters",
title = "Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue",
doi = "10.1002/1873-3468.14794"
}

Zakić, T., Peković-Vaughan, V., Čvoro, A., Korać, A., Janković, A.,& Korać, B.. (2023). Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue. in FEBS Letters
John Wiley..
https://doi.org/10.1002/1873-3468.14794

Zakić T, Peković-Vaughan V, Čvoro A, Korać A, Janković A, Korać B. Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue. in FEBS Letters. 2023;.
doi:10.1002/1873-3468.14794 .

Zakić, Tamara, Peković-Vaughan, Vanja, Čvoro, Aleksandra, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue" in FEBS Letters (2023),
https://doi.org/10.1002/1873-3468.14794 . .

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Korać, Aleksandra
AU  - Korać, Bato
AU  - Janković, Aleksandra
PY  - 2022
UR  - https://www.mdpi.com/1999-4923/14/7/1368
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35890263
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9324995
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5071
AB  - The beneficial effects of l-arginine supplementation in obesity and type II diabetes involve white adipose tissue (WAT) reduction and increased substrate oxidation. We aimed to test the potential of l-arginine to induce WAT browning. Therefore, the molecular basis of browning was investigated in retroperitoneal WAT (rpWAT) of rats exposed to cold or treated with 2.25% l-arginine for 1, 3, and 7 days. Compared to untreated control, levels of inducible nitric oxide (NO) synthase protein expression and NO signaling increased in both cold-exposed and l-arginine-treated groups. These increases coincided with the appearance of multilocular adipocytes and increased expression levels of uncoupling protein 1 (UCP1), thermogenic and beige adipocyte-specific genes (Cidea, Cd137, and Tmem26), mitochondriogenesis markers (peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α, mitochondrial DNA copy number), nuclear respiratory factor 1, PPARα and their respective downstream lipid oxidation enzymes after l-arginine treatment. Such browning phenotype in the l-arginine-treated group was concordant with end-course decreases in leptinaemia, rpWAT mass, and body weight. In conclusion, l-arginine mimics cold-mediated increases in NO signaling in rpWAT and induces molecular and structural fingerprints of rpWAT browning. The results endorse l-arginine as a pharmaceutical alternative to cold exposure, which could be of great interest in obesity and associated metabolic diseases.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.
IS  - 7
VL  - 14
DO  - 10.3390/pharmaceutics14071368
SP  - 1368
ER  - 

@article{
author = "Kalezić, Anđelika and Korać, Aleksandra and Korać, Bato and Janković, Aleksandra",
year = "2022",
abstract = "The beneficial effects of l-arginine supplementation in obesity and type II diabetes involve white adipose tissue (WAT) reduction and increased substrate oxidation. We aimed to test the potential of l-arginine to induce WAT browning. Therefore, the molecular basis of browning was investigated in retroperitoneal WAT (rpWAT) of rats exposed to cold or treated with 2.25% l-arginine for 1, 3, and 7 days. Compared to untreated control, levels of inducible nitric oxide (NO) synthase protein expression and NO signaling increased in both cold-exposed and l-arginine-treated groups. These increases coincided with the appearance of multilocular adipocytes and increased expression levels of uncoupling protein 1 (UCP1), thermogenic and beige adipocyte-specific genes (Cidea, Cd137, and Tmem26), mitochondriogenesis markers (peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α, mitochondrial DNA copy number), nuclear respiratory factor 1, PPARα and their respective downstream lipid oxidation enzymes after l-arginine treatment. Such browning phenotype in the l-arginine-treated group was concordant with end-course decreases in leptinaemia, rpWAT mass, and body weight. In conclusion, l-arginine mimics cold-mediated increases in NO signaling in rpWAT and induces molecular and structural fingerprints of rpWAT browning. The results endorse l-arginine as a pharmaceutical alternative to cold exposure, which could be of great interest in obesity and associated metabolic diseases.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.",
number = "7",
volume = "14",
doi = "10.3390/pharmaceutics14071368",
pages = "1368"
}

Kalezić, A., Korać, A., Korać, B.,& Janković, A.. (2022). l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.. in Pharmaceutics
Basel: MDPI., 14(7), 1368.
https://doi.org/10.3390/pharmaceutics14071368

Kalezić A, Korać A, Korać B, Janković A. l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.. in Pharmaceutics. 2022;14(7):1368.
doi:10.3390/pharmaceutics14071368 .

Kalezić, Anđelika, Korać, Aleksandra, Korać, Bato, Janković, Aleksandra, "l-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold." in Pharmaceutics, 14, no. 7 (2022):1368,
https://doi.org/10.3390/pharmaceutics14071368 . .

TY  - JOUR
AU  - Zakić, Tamara
AU  - Stojanović, Sara
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković‐Vaughan, Vanja
AU  - Korać, Bato
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/biof.1931
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5385
AB  - Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.
T2  - BioFactors
T1  - Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation
DO  - 10.1002/biof.1931
ER  - 

@article{
author = "Zakić, Tamara and Stojanović, Sara and Janković, Aleksandra and Korać, Aleksandra and Peković‐Vaughan, Vanja and Korać, Bato",
year = "2022",
abstract = "Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.",
journal = "BioFactors",
title = "Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation",
doi = "10.1002/biof.1931"
}

Zakić, T., Stojanović, S., Janković, A., Korać, A., Peković‐Vaughan, V.,& Korać, B.. (2022). Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation. in BioFactors.
https://doi.org/10.1002/biof.1931

Zakić T, Stojanović S, Janković A, Korać A, Peković‐Vaughan V, Korać B. Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation. in BioFactors. 2022;.
doi:10.1002/biof.1931 .

Zakić, Tamara, Stojanović, Sara, Janković, Aleksandra, Korać, Aleksandra, Peković‐Vaughan, Vanja, Korać, Bato, "Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation" in BioFactors (2022),
https://doi.org/10.1002/biof.1931 . .

TY  - JOUR
AU  - Protić, Isidora
AU  - Golić, Igor
AU  - Vidaković, Snežana
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2022
UR  - https://www.mdpi.com/1467-3045/44/8/237
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9406340
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5110
AB  - Zinc (in the form of Zn2+) is necessary for male fertility. Both Zn2+ quantity and its localisation have been detected in seminal plasma and ejaculated spermatozoa, suggesting its active uptake via zinc import transporters (ZIPs). Immunofluorescence was used to characterise the expression and localisation of three distinct types of ZIP transporters in ejaculated spermatozoa of normo- and asthenozoospermic sperm samples. ZIP6, ZIP10 and ZIP14 showed heterogeneous sperm cell expression and different compartmental distribution. In both types of sperm samples, ZIP6 and ZIP14 were predominantly localised in the sperm head, while ZIP10 was found along the sperm tail. Compartmental localisation of ZIPs in asthenozoospermia was not changed. However, regarding sub-compartmental localisation in sperm head regions, for ZIP6 asthenozoospermia only decreased its acorn/crescent-like pattern. In contrast, ZIP14 immunostaining was altered in favour of crescent-like, as opposed to acorn-like and acorn/crescent-like patterns. The specific ZIPs localisation may reflect their different roles in sperm cell integrity and motility and may change over time. This is the first report of their specific compartmental and sub-compartmental localisation in ejaculated human sperm cells. Further research will lead to a greater understanding of the roles of ZIPs in sperm cell biology, which could positively influence procedures for human infertility therapy.
PB  - Basel: MDPI
T2  - Current Issues in Molecular Biology
T1  - Heterogeneous Immunolocalisation of Zinc Transporters ZIP6, ZIP10 and ZIP14 in Human Normo- and Asthenozoospermic Spermatozoa.
IS  - 8
VL  - 44
DO  - 10.3390/cimb44080237
SP  - 3444
EP  - 3454
ER  - 

@article{
author = "Protić, Isidora and Golić, Igor and Vidaković, Snežana and Korać, Bato and Korać, Aleksandra",
year = "2022",
abstract = "Zinc (in the form of Zn2+) is necessary for male fertility. Both Zn2+ quantity and its localisation have been detected in seminal plasma and ejaculated spermatozoa, suggesting its active uptake via zinc import transporters (ZIPs). Immunofluorescence was used to characterise the expression and localisation of three distinct types of ZIP transporters in ejaculated spermatozoa of normo- and asthenozoospermic sperm samples. ZIP6, ZIP10 and ZIP14 showed heterogeneous sperm cell expression and different compartmental distribution. In both types of sperm samples, ZIP6 and ZIP14 were predominantly localised in the sperm head, while ZIP10 was found along the sperm tail. Compartmental localisation of ZIPs in asthenozoospermia was not changed. However, regarding sub-compartmental localisation in sperm head regions, for ZIP6 asthenozoospermia only decreased its acorn/crescent-like pattern. In contrast, ZIP14 immunostaining was altered in favour of crescent-like, as opposed to acorn-like and acorn/crescent-like patterns. The specific ZIPs localisation may reflect their different roles in sperm cell integrity and motility and may change over time. This is the first report of their specific compartmental and sub-compartmental localisation in ejaculated human sperm cells. Further research will lead to a greater understanding of the roles of ZIPs in sperm cell biology, which could positively influence procedures for human infertility therapy.",
publisher = "Basel: MDPI",
journal = "Current Issues in Molecular Biology",
title = "Heterogeneous Immunolocalisation of Zinc Transporters ZIP6, ZIP10 and ZIP14 in Human Normo- and Asthenozoospermic Spermatozoa.",
number = "8",
volume = "44",
doi = "10.3390/cimb44080237",
pages = "3444-3454"
}

Protić, I., Golić, I., Vidaković, S., Korać, B.,& Korać, A.. (2022). Heterogeneous Immunolocalisation of Zinc Transporters ZIP6, ZIP10 and ZIP14 in Human Normo- and Asthenozoospermic Spermatozoa.. in Current Issues in Molecular Biology
Basel: MDPI., 44(8), 3444-3454.
https://doi.org/10.3390/cimb44080237

Protić I, Golić I, Vidaković S, Korać B, Korać A. Heterogeneous Immunolocalisation of Zinc Transporters ZIP6, ZIP10 and ZIP14 in Human Normo- and Asthenozoospermic Spermatozoa.. in Current Issues in Molecular Biology. 2022;44(8):3444-3454.
doi:10.3390/cimb44080237 .

Protić, Isidora, Golić, Igor, Vidaković, Snežana, Korać, Bato, Korać, Aleksandra, "Heterogeneous Immunolocalisation of Zinc Transporters ZIP6, ZIP10 and ZIP14 in Human Normo- and Asthenozoospermic Spermatozoa." in Current Issues in Molecular Biology, 44, no. 8 (2022):3444-3454,
https://doi.org/10.3390/cimb44080237 . .

TY  - JOUR
AU  - Protić, Isidora
AU  - Golić, Igor
AU  - Aleksić, Marija
AU  - Vidaković, Snežana
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0306987722000408
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4862
AB  - The global rise in male infertility necessitates a constant search for underlying causes, diagnostics and corrective treatments. Sperm cells are irreplaceable cells for the process of reproduction. Intrauterine insemination (IUI) is a simple and non-invasive technique, most commonly used to overcome both unexplained and mild male-factor infertility. Even though spermatozoa may be classified as “normal” in terms of morphology, motility and concentration, they could be defective at the subcellular level. Protein lysine acetylation within human sperm, a major post-translational modification of tubulin, is suspected to be a cause of sperm abnormality but is not fully understood. An examination of α-tubulin and acetylated α-tubulin immunopresence, spatial distribution and co-localisation in normozoospermic and asthenozoospermic semen samples was conducted to determine if acetylated α-tubulin could be a biomarker of sperm heterogeneity to better predict sperm fertility potential for IUI outcome. Acetylated α-tubulin was present in both sperm subcompartments, tail and nucleus of normozoospermic samples. We found more immunopositivity for acetylated α-tubulin in the sperm tail and less in nucleus of asthenozoospermic compared to normozoospermic samples. Hence, the acetylated α-tubulin in sperm may contribute to sperm nuclei heterogeneity and serve as a novel molecular biomarker.
PB  - Edinburgh: Churchill Livingstone
T2  - Medical Hypotheses
T1  - Presence of acetylated α-tubulin in human sperm nuclei: A contributor to sperm heterogeneity
VL  - 161
DO  - 10.1016/j.mehy.2022.110800
SP  - 110800
ER  - 

@article{
author = "Protić, Isidora and Golić, Igor and Aleksić, Marija and Vidaković, Snežana and Korać, Bato and Korać, Aleksandra",
year = "2022",
abstract = "The global rise in male infertility necessitates a constant search for underlying causes, diagnostics and corrective treatments. Sperm cells are irreplaceable cells for the process of reproduction. Intrauterine insemination (IUI) is a simple and non-invasive technique, most commonly used to overcome both unexplained and mild male-factor infertility. Even though spermatozoa may be classified as “normal” in terms of morphology, motility and concentration, they could be defective at the subcellular level. Protein lysine acetylation within human sperm, a major post-translational modification of tubulin, is suspected to be a cause of sperm abnormality but is not fully understood. An examination of α-tubulin and acetylated α-tubulin immunopresence, spatial distribution and co-localisation in normozoospermic and asthenozoospermic semen samples was conducted to determine if acetylated α-tubulin could be a biomarker of sperm heterogeneity to better predict sperm fertility potential for IUI outcome. Acetylated α-tubulin was present in both sperm subcompartments, tail and nucleus of normozoospermic samples. We found more immunopositivity for acetylated α-tubulin in the sperm tail and less in nucleus of asthenozoospermic compared to normozoospermic samples. Hence, the acetylated α-tubulin in sperm may contribute to sperm nuclei heterogeneity and serve as a novel molecular biomarker.",
publisher = "Edinburgh: Churchill Livingstone",
journal = "Medical Hypotheses",
title = "Presence of acetylated α-tubulin in human sperm nuclei: A contributor to sperm heterogeneity",
volume = "161",
doi = "10.1016/j.mehy.2022.110800",
pages = "110800"
}

Protić, I., Golić, I., Aleksić, M., Vidaković, S., Korać, B.,& Korać, A.. (2022). Presence of acetylated α-tubulin in human sperm nuclei: A contributor to sperm heterogeneity. in Medical Hypotheses
Edinburgh: Churchill Livingstone., 161, 110800.
https://doi.org/10.1016/j.mehy.2022.110800

Protić I, Golić I, Aleksić M, Vidaković S, Korać B, Korać A. Presence of acetylated α-tubulin in human sperm nuclei: A contributor to sperm heterogeneity. in Medical Hypotheses. 2022;161:110800.
doi:10.1016/j.mehy.2022.110800 .

Protić, Isidora, Golić, Igor, Aleksić, Marija, Vidaković, Snežana, Korać, Bato, Korać, Aleksandra, "Presence of acetylated α-tubulin in human sperm nuclei: A contributor to sperm heterogeneity" in Medical Hypotheses, 161 (2022):110800,
https://doi.org/10.1016/j.mehy.2022.110800 . .

TY  - CONF
AU  - Zakić, Tamara
AU  - Ninković, Anastasija
AU  - Stojanović, Sara
AU  - Budnar Šoškić, Marta
AU  - Kalezić, Anđelika
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković-Vaughan, Vanja
AU  - Korać, Bato
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5128
AB  - Interscapular brown adipose tissue (IBAT) is a highly metabolically active, thermogenic tissue essential for the maintenance of total energy homeostasis, with a remarkable ability for remodelling in response to exogenous stimuli. Given that nuclear factor erythroid 2-related factor 2 (NRF2) has a pivotal role in redox-metabolic homeostasis, we aimed to investigate its role in IBAT homeostasis under basal conditions or upon cold stimulation. Therefore, we analysed structural and redox-metabolic profiles of IBAT in wild-type (WT) and mice lacking functional Nrf2 (Nrf2KO) maintained at room (RT, 24±1°C) or low temperature (4±1°C). Our results show that both WT and Nrf2KO mice appear to be acclimated to cold, showing characteristics of thermogenically active IBAT, including increased gene and protein expression of uncoupling protein 1 (UCP1). Surprisingly, light and electron microscopy revealed that Nrf2KO mice at RT displayed distinct structural features of activated IBAT, together with the presence of vasodilated blood vessels, while the expression of thermogenic marker UCP1 did not show a corresponding cold-induced change, thus indicating IBAT functional inactivity. This lack of IBAT thermogenic activity in Nrf2KO mice at RT is consistent with its altered redox-metabolic profile, whereby protein expression of the main antioxidant defence and key metabolic enzymes either remained the same or was decreased compared to WT mice at RT. Accordingly, circulatory levels of triglycerides and cholesterol were decreased while glucose, urea and creatinine remained unchanged. Moreover, gene and/or protein expression of important redox-metabolic transcriptional factors – erythroid NRF1, NFkB, PGC-1α and PPARγ, as well as eNOS and AMPKα were increased, suggesting compensatory molecular mechanisms leading to altered IBAT phenotype in Nrf2KO mice at RT. In conclusion, the lack of functional Nrf2 leads to marked structural characteristics of active IBAT in Nrf2KO mice at RT, which are only followed by its functional activation through distinct redox-metabolic reprogramming after cold stimulation.
PB  - Society for Free Radical Research-Europe
C3  - Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
T1  - Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation
DO  - 10.1016/j.freeradbiomed.2022.06.035
SP  - 5
ER  - 

@conference{
author = "Zakić, Tamara and Ninković, Anastasija and Stojanović, Sara and Budnar Šoškić, Marta and Kalezić, Anđelika and Janković, Aleksandra and Korać, Aleksandra and Peković-Vaughan, Vanja and Korać, Bato",
year = "2022",
abstract = "Interscapular brown adipose tissue (IBAT) is a highly metabolically active, thermogenic tissue essential for the maintenance of total energy homeostasis, with a remarkable ability for remodelling in response to exogenous stimuli. Given that nuclear factor erythroid 2-related factor 2 (NRF2) has a pivotal role in redox-metabolic homeostasis, we aimed to investigate its role in IBAT homeostasis under basal conditions or upon cold stimulation. Therefore, we analysed structural and redox-metabolic profiles of IBAT in wild-type (WT) and mice lacking functional Nrf2 (Nrf2KO) maintained at room (RT, 24±1°C) or low temperature (4±1°C). Our results show that both WT and Nrf2KO mice appear to be acclimated to cold, showing characteristics of thermogenically active IBAT, including increased gene and protein expression of uncoupling protein 1 (UCP1). Surprisingly, light and electron microscopy revealed that Nrf2KO mice at RT displayed distinct structural features of activated IBAT, together with the presence of vasodilated blood vessels, while the expression of thermogenic marker UCP1 did not show a corresponding cold-induced change, thus indicating IBAT functional inactivity. This lack of IBAT thermogenic activity in Nrf2KO mice at RT is consistent with its altered redox-metabolic profile, whereby protein expression of the main antioxidant defence and key metabolic enzymes either remained the same or was decreased compared to WT mice at RT. Accordingly, circulatory levels of triglycerides and cholesterol were decreased while glucose, urea and creatinine remained unchanged. Moreover, gene and/or protein expression of important redox-metabolic transcriptional factors – erythroid NRF1, NFkB, PGC-1α and PPARγ, as well as eNOS and AMPKα were increased, suggesting compensatory molecular mechanisms leading to altered IBAT phenotype in Nrf2KO mice at RT. In conclusion, the lack of functional Nrf2 leads to marked structural characteristics of active IBAT in Nrf2KO mice at RT, which are only followed by its functional activation through distinct redox-metabolic reprogramming after cold stimulation.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation",
doi = "10.1016/j.freeradbiomed.2022.06.035",
pages = "5"
}

Zakić, T., Ninković, A., Stojanović, S., Budnar Šoškić, M., Kalezić, A., Janković, A., Korać, A., Peković-Vaughan, V.,& Korać, B.. (2022). Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
Society for Free Radical Research-Europe., 5.
https://doi.org/10.1016/j.freeradbiomed.2022.06.035

Zakić T, Ninković A, Stojanović S, Budnar Šoškić M, Kalezić A, Janković A, Korać A, Peković-Vaughan V, Korać B. Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. 2022;:5.
doi:10.1016/j.freeradbiomed.2022.06.035 .

Zakić, Tamara, Ninković, Anastasija, Stojanović, Sara, Budnar Šoškić, Marta, Kalezić, Anđelika, Janković, Aleksandra, Korać, Aleksandra, Peković-Vaughan, Vanja, Korać, Bato, "Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation" in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium (2022):5,
https://doi.org/10.1016/j.freeradbiomed.2022.06.035 . .

TY  - CONF
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5126
AB  - Altered redox homeostasis is recognized as a hallmark of neoplastic transformation. However, data from various in vitro and in vivo studies often show increased or decreased transcriptional and translational levels of antioxidant defense (AD) enzymes. One of the underlying causes for such conflicting reports is cell heterogeneity within the complex tumor microenvironment, especially in breast cancer. To overcome barriers associated with bulk tissue gene and protein expression analysis, we choose an immunohistochemical approach. We cross-examined serial tissue sections of tumor and adipose tissue from premenopausal women with malignant invasive ductal carcinoma and benign fibroadenoma to gain a comprehensive overview of cell-specific AD enzymes expression and localization patterns. At the level of overall tissue architecture, malignant tumor tissue shows significantly higher immunopositivity for copper, zinc- and manganese- superoxide dismutase, catalase, and glutathione peroxidase compared to benign tumor tissue. Generally, AD enzymes are specifically localized in the cytoplasm (copper, zinc superoxide dismutase, catalase, glutathione peroxidase) and mitochondria (manganese superoxide dismutase, glutathione peroxidase) of cancer cells and cancer-associated adipocytes. Detailed analysis of different regions of the tumor tissue revealed significant heterogeneity in the degree of immunopositivity along the axis of tumor center–invasive front–adipose tissue. Clusters of cancer cells at the invasive front of the tumor often show a higher degree of immunopositivity for AD enzymes compared to cancer cells in the center of the tumor mass. Similarly, cancer-associated adipocytes that are in close proximity to cancer cells at the invasive front of the tumor show a higher degree of immunopositivity for AD enzymes compared to adipocytes from distant peritumoral adipose tissue. In conclusion, immunohistochemical approach confirms high AD enzymes expression in breast cancer and further reveals distinct regional mosaicism consistent with cell heterogeneity within the tumor microenvironment. This research was supported by the Science Fund of the Republic of Serbia, #7750238-REFRAME.
PB  - Society for Free Radical Research-Europe
C3  - Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
T1  - Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue
DO  - 10.1016/j.freeradbiomed.2022.06.154
ER  - 

@conference{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2022",
abstract = "Altered redox homeostasis is recognized as a hallmark of neoplastic transformation. However, data from various in vitro and in vivo studies often show increased or decreased transcriptional and translational levels of antioxidant defense (AD) enzymes. One of the underlying causes for such conflicting reports is cell heterogeneity within the complex tumor microenvironment, especially in breast cancer. To overcome barriers associated with bulk tissue gene and protein expression analysis, we choose an immunohistochemical approach. We cross-examined serial tissue sections of tumor and adipose tissue from premenopausal women with malignant invasive ductal carcinoma and benign fibroadenoma to gain a comprehensive overview of cell-specific AD enzymes expression and localization patterns. At the level of overall tissue architecture, malignant tumor tissue shows significantly higher immunopositivity for copper, zinc- and manganese- superoxide dismutase, catalase, and glutathione peroxidase compared to benign tumor tissue. Generally, AD enzymes are specifically localized in the cytoplasm (copper, zinc superoxide dismutase, catalase, glutathione peroxidase) and mitochondria (manganese superoxide dismutase, glutathione peroxidase) of cancer cells and cancer-associated adipocytes. Detailed analysis of different regions of the tumor tissue revealed significant heterogeneity in the degree of immunopositivity along the axis of tumor center–invasive front–adipose tissue. Clusters of cancer cells at the invasive front of the tumor often show a higher degree of immunopositivity for AD enzymes compared to cancer cells in the center of the tumor mass. Similarly, cancer-associated adipocytes that are in close proximity to cancer cells at the invasive front of the tumor show a higher degree of immunopositivity for AD enzymes compared to adipocytes from distant peritumoral adipose tissue. In conclusion, immunohistochemical approach confirms high AD enzymes expression in breast cancer and further reveals distinct regional mosaicism consistent with cell heterogeneity within the tumor microenvironment. This research was supported by the Science Fund of the Republic of Serbia, #7750238-REFRAME.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue",
doi = "10.1016/j.freeradbiomed.2022.06.154"
}

Kalezić, A., Udički, M., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2022). Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
Society for Free Radical Research-Europe..
https://doi.org/10.1016/j.freeradbiomed.2022.06.154

Kalezić A, Udički M, Srdić Galić B, Korać A, Janković A, Korać B. Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. 2022;.
doi:10.1016/j.freeradbiomed.2022.06.154 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue" in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium (2022),
https://doi.org/10.1016/j.freeradbiomed.2022.06.154 . .

TY  - JOUR
AU  - Korać, Bato
AU  - Kalezić, Anđelika
AU  - Peković-Vaughan, Vanja
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S2213231721000355
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33579666
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4152
AB  - "Life is an instantaneous encounter of circulating matter and flowing energy" (Jean Giaja, Serbian physiologist), is one of the most elegant definitions not only of life but the relationship of redox biology and metabolism. Their evolutionary liaison has created inseparable yet dynamic homeostasis in health, which, when disrupted, leads to disease. This interconnection is even more pertinent today, in an era of increasing metabolic diseases of epidemic proportions such as obesity, metabolic syndrome, and diabetes. Despite great advances in understanding the molecular mechanisms of redox and metabolic regulation, we face significant challenges in preventing, diagnosing, and treating metabolic diseases. The etiological association and temporal overlap of these syndromes present significant challenges for the discrimination of appropriate clinical biomarkers for diagnosis, treatment, and outcome prediction. These multifactorial, multiorgan metabolic syndromes with complex etiopathogenic mechanisms are accompanied by disturbed redox equilibrium in target tissues and circulation. Free radicals and reactive species are considered both a causal factor and a consequence of disease status. Thus, determining the subtypes and levels of free radicals and reactive species, oxidatively damaged biomolecules (lipids, proteins, and nucleic acids) and antioxidant defense components as well as redox-sensitive transcription factors and fluxes of redox-dependent metabolic pathways will help define existing and establish novel redox biomarkers for stratifying metabolic diseases. This review aims to discuss diverse redox/metabolic aspects in obesity, metabolic syndrome, and diabetes, with the imperative to help establish a platform for emerging and future redox-metabolic biomarkers research in precision medicine. Future research warrants detailed investigations into the status of redox biomarkers in healthy subjects and patients, including the use of emerging 'omic' profiling technologies (e.g., redox proteomes, lipidomes, metabolomes, and transcriptomes), taking into account the influence of lifestyle (diet, physical activity, sleep, work patterns) as well as circadian ~24h fluctuations in circulatory factors and metabolites.
PB  - Elsevier BV
T2  - Redox Biology
T1  - Redox changes in obesity, metabolic syndrome, and diabetes.
DO  - 10.1016/j.redox.2021.101887
SP  - 101887
ER  - 

@article{
author = "Korać, Bato and Kalezić, Anđelika and Peković-Vaughan, Vanja and Korać, Aleksandra and Janković, Aleksandra",
year = "2021",
abstract = ""Life is an instantaneous encounter of circulating matter and flowing energy" (Jean Giaja, Serbian physiologist), is one of the most elegant definitions not only of life but the relationship of redox biology and metabolism. Their evolutionary liaison has created inseparable yet dynamic homeostasis in health, which, when disrupted, leads to disease. This interconnection is even more pertinent today, in an era of increasing metabolic diseases of epidemic proportions such as obesity, metabolic syndrome, and diabetes. Despite great advances in understanding the molecular mechanisms of redox and metabolic regulation, we face significant challenges in preventing, diagnosing, and treating metabolic diseases. The etiological association and temporal overlap of these syndromes present significant challenges for the discrimination of appropriate clinical biomarkers for diagnosis, treatment, and outcome prediction. These multifactorial, multiorgan metabolic syndromes with complex etiopathogenic mechanisms are accompanied by disturbed redox equilibrium in target tissues and circulation. Free radicals and reactive species are considered both a causal factor and a consequence of disease status. Thus, determining the subtypes and levels of free radicals and reactive species, oxidatively damaged biomolecules (lipids, proteins, and nucleic acids) and antioxidant defense components as well as redox-sensitive transcription factors and fluxes of redox-dependent metabolic pathways will help define existing and establish novel redox biomarkers for stratifying metabolic diseases. This review aims to discuss diverse redox/metabolic aspects in obesity, metabolic syndrome, and diabetes, with the imperative to help establish a platform for emerging and future redox-metabolic biomarkers research in precision medicine. Future research warrants detailed investigations into the status of redox biomarkers in healthy subjects and patients, including the use of emerging 'omic' profiling technologies (e.g., redox proteomes, lipidomes, metabolomes, and transcriptomes), taking into account the influence of lifestyle (diet, physical activity, sleep, work patterns) as well as circadian ~24h fluctuations in circulatory factors and metabolites.",
publisher = "Elsevier BV",
journal = "Redox Biology",
title = "Redox changes in obesity, metabolic syndrome, and diabetes.",
doi = "10.1016/j.redox.2021.101887",
pages = "101887"
}

Korać, B., Kalezić, A., Peković-Vaughan, V., Korać, A.,& Janković, A.. (2021). Redox changes in obesity, metabolic syndrome, and diabetes.. in Redox Biology
Elsevier BV., 101887.
https://doi.org/10.1016/j.redox.2021.101887

Korać B, Kalezić A, Peković-Vaughan V, Korać A, Janković A. Redox changes in obesity, metabolic syndrome, and diabetes.. in Redox Biology. 2021;:101887.
doi:10.1016/j.redox.2021.101887 .

Korać, Bato, Kalezić, Anđelika, Peković-Vaughan, Vanja, Korać, Aleksandra, Janković, Aleksandra, "Redox changes in obesity, metabolic syndrome, and diabetes." in Redox Biology (2021):101887,
https://doi.org/10.1016/j.redox.2021.101887 . .

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Aleksić, Marija
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33765617
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4175
AB  - One of the underlying mechanisms that could link breast cancer and obesity is shifted redox homeostasis in the tumor microenvironment. To reveal the relationship between the malignant phenotype and obesity, we compared redox profiles of breast tumor and tumor-associated adipose tissue from premenopausal women: normal-weight with benign tumors, overweight/obese with benign tumors, normal-weight with malignant tumors, and overweight/obese with malignant tumors. Namely, we examined the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression and activity of main antioxidant defense (AD) enzymes: copper, zinc- and manganese superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of 4-hydroxy-2-nonenal (4-HNE) modified proteins. Higher protein expression and activity of AD enzymes were found in malignant tumor tissue than benign tumor tissue, irrespective of obesity. Nevertheless, malignant tumor tissue of overweight/obese women was characterized by higher protein expression of Nrf2 and weaker immunopositivity for 4-HNE modified proteins. In malignant tumor-associated adipose tissue, the redox profile was clearly related to obesity. Higher Nrf2 protein expression and higher AD enzyme levels were observed in normal-weight women, while stronger immunopositivity for 4-HNE modified proteins was found in overweight/obese women. The results suggest that the complex interplay between obesity and malignancy involves redox-sensitive pathways in breast tumor and tumor-associated adipose tissue.
PB  - Elsevier BV
T2  - Redox Biology
T1  - Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.
VL  - 41
DO  - 10.1016/j.redox.2021.101939
SP  - 101939
ER  - 

@article{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Aleksić, Marija and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "One of the underlying mechanisms that could link breast cancer and obesity is shifted redox homeostasis in the tumor microenvironment. To reveal the relationship between the malignant phenotype and obesity, we compared redox profiles of breast tumor and tumor-associated adipose tissue from premenopausal women: normal-weight with benign tumors, overweight/obese with benign tumors, normal-weight with malignant tumors, and overweight/obese with malignant tumors. Namely, we examined the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression and activity of main antioxidant defense (AD) enzymes: copper, zinc- and manganese superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of 4-hydroxy-2-nonenal (4-HNE) modified proteins. Higher protein expression and activity of AD enzymes were found in malignant tumor tissue than benign tumor tissue, irrespective of obesity. Nevertheless, malignant tumor tissue of overweight/obese women was characterized by higher protein expression of Nrf2 and weaker immunopositivity for 4-HNE modified proteins. In malignant tumor-associated adipose tissue, the redox profile was clearly related to obesity. Higher Nrf2 protein expression and higher AD enzyme levels were observed in normal-weight women, while stronger immunopositivity for 4-HNE modified proteins was found in overweight/obese women. The results suggest that the complex interplay between obesity and malignancy involves redox-sensitive pathways in breast tumor and tumor-associated adipose tissue.",
publisher = "Elsevier BV",
journal = "Redox Biology",
title = "Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.",
volume = "41",
doi = "10.1016/j.redox.2021.101939",
pages = "101939"
}

Kalezić, A., Udički, M., Srdić Galić, B., Aleksić, M., Korać, A., Janković, A.,& Korać, B.. (2021). Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.. in Redox Biology
Elsevier BV., 41, 101939.
https://doi.org/10.1016/j.redox.2021.101939

Kalezić A, Udički M, Srdić Galić B, Aleksić M, Korać A, Janković A, Korać B. Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.. in Redox Biology. 2021;41:101939.
doi:10.1016/j.redox.2021.101939 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Aleksić, Marija, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy." in Redox Biology, 41 (2021):101939,
https://doi.org/10.1016/j.redox.2021.101939 . .

TY  - JOUR
AU  - Korać, Aleksandra
AU  - Srdić-Galić, Biljana
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Korać, Bato
AU  - Janković, Aleksandra
PY  - 2021
UR  - https://doi.org/10.5114/aoms/92118
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4197
AB  - Introduction: Metabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lip-id storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT). Material and methods: Gene and protein expression levels of leptin, adi-ponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and "at risk" groups. Results: Compared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of "at risk" groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of "at risk" obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin. Conclusions: Low adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.
PB  - Termedia Sp. z.o.o.
T2  - Archives of Medical Science
T1  - Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles
IS  - 2
VL  - 17
DO  - 10.5114/aoms/92118
SP  - 323
EP  - 336
ER  - 

@article{
author = "Korać, Aleksandra and Srdić-Galić, Biljana and Stančić, Ana and Otašević, Vesna and Korać, Bato and Janković, Aleksandra",
year = "2021",
abstract = "Introduction: Metabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lip-id storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT). Material and methods: Gene and protein expression levels of leptin, adi-ponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and "at risk" groups. Results: Compared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of "at risk" groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of "at risk" obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin. Conclusions: Low adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.",
publisher = "Termedia Sp. z.o.o.",
journal = "Archives of Medical Science",
title = "Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles",
number = "2",
volume = "17",
doi = "10.5114/aoms/92118",
pages = "323-336"
}

Korać, A., Srdić-Galić, B., Stančić, A., Otašević, V., Korać, B.,& Janković, A.. (2021). Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles. in Archives of Medical Science
Termedia Sp. z.o.o.., 17(2), 323-336.
https://doi.org/10.5114/aoms/92118

Korać A, Srdić-Galić B, Stančić A, Otašević V, Korać B, Janković A. Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles. in Archives of Medical Science. 2021;17(2):323-336.
doi:10.5114/aoms/92118 .

Korać, Aleksandra, Srdić-Galić, Biljana, Stančić, Ana, Otašević, Vesna, Korać, Bato, Janković, Aleksandra, "Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles" in Archives of Medical Science, 17, no. 2 (2021):323-336,
https://doi.org/10.5114/aoms/92118 . .

TY  - JOUR
AU  - Aleksić, Marija
AU  - Kalezić, Anđelika
AU  - Saso, Luciano
AU  - Janković, Aleksandra
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4216
AB  - Brown adipose tissue (BAT) is important for maintaining whole-body metabolic and energy homeostasis. However, the effects of hypothyroidism, one of the most common diseases worldwide, which increases the risk of several metabolic disorders, on BAT redox and metabolic homeostasis remain mostly unknown. We aimed to investigate the dynamics of protein expression, enzyme activity, and localization of antioxidant defense (AD) enzymes in rat interscapular BAT upon induction of hypothyroidism by antithyroid drug methimazole for 7, 15, and 21 days. Our results showed an increased protein expression of CuZn-and Mn-superoxide dismutase, catalase, glutamyl– cysteine ligase, thioredoxin, total glutathione content, and activity of catalase and thioredoxin reductase in hypothyroid rats, compared to euthyroid control. Concomitant with the increase in AD, newly established nuclear, mitochondrial, and peroxisomal localization of AD enzymes was found. Hypothyroidism also potentiated associations between mitochondria, peroxisomes, and lipid bodies, creating specific structural–functional units. Moreover, hypothyroidism induced protein expression and nuclear translocation of a master regulator of redox-metabolic homeostasis, nuclear factor erythroid 2-related factor 2 (Nrf2), and an increased amount of 4-hydroxynonenal (4-HNE) protein adducts. The results indicate that spatiotemporal overlap in the remodeling of AD is orchestrated by Nrf2, implicating the role of 4-HNE in this process and suggesting the potential mechanism of redox-structural remodeling during BAT adaptation in hypothyroidism.
PB  - MDPI AG
T2  - Antioxidants
T1  - The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism
IS  - 4
VL  - 10
DO  - 10.3390/antiox10040591
SP  - 591
ER  - 

@article{
author = "Aleksić, Marija and Kalezić, Anđelika and Saso, Luciano and Janković, Aleksandra and Korać, Bato and Korać, Aleksandra",
year = "2021",
abstract = "Brown adipose tissue (BAT) is important for maintaining whole-body metabolic and energy homeostasis. However, the effects of hypothyroidism, one of the most common diseases worldwide, which increases the risk of several metabolic disorders, on BAT redox and metabolic homeostasis remain mostly unknown. We aimed to investigate the dynamics of protein expression, enzyme activity, and localization of antioxidant defense (AD) enzymes in rat interscapular BAT upon induction of hypothyroidism by antithyroid drug methimazole for 7, 15, and 21 days. Our results showed an increased protein expression of CuZn-and Mn-superoxide dismutase, catalase, glutamyl– cysteine ligase, thioredoxin, total glutathione content, and activity of catalase and thioredoxin reductase in hypothyroid rats, compared to euthyroid control. Concomitant with the increase in AD, newly established nuclear, mitochondrial, and peroxisomal localization of AD enzymes was found. Hypothyroidism also potentiated associations between mitochondria, peroxisomes, and lipid bodies, creating specific structural–functional units. Moreover, hypothyroidism induced protein expression and nuclear translocation of a master regulator of redox-metabolic homeostasis, nuclear factor erythroid 2-related factor 2 (Nrf2), and an increased amount of 4-hydroxynonenal (4-HNE) protein adducts. The results indicate that spatiotemporal overlap in the remodeling of AD is orchestrated by Nrf2, implicating the role of 4-HNE in this process and suggesting the potential mechanism of redox-structural remodeling during BAT adaptation in hypothyroidism.",
publisher = "MDPI AG",
journal = "Antioxidants",
title = "The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism",
number = "4",
volume = "10",
doi = "10.3390/antiox10040591",
pages = "591"
}

Aleksić, M., Kalezić, A., Saso, L., Janković, A., Korać, B.,& Korać, A.. (2021). The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism. in Antioxidants
MDPI AG., 10(4), 591.
https://doi.org/10.3390/antiox10040591

Aleksić M, Kalezić A, Saso L, Janković A, Korać B, Korać A. The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism. in Antioxidants. 2021;10(4):591.
doi:10.3390/antiox10040591 .

Aleksić, Marija, Kalezić, Anđelika, Saso, Luciano, Janković, Aleksandra, Korać, Bato, Korać, Aleksandra, "The unity of redox and structural remodeling of brown adipose tissue in hypothyroidism" in Antioxidants, 10, no. 4 (2021):591,
https://doi.org/10.3390/antiox10040591 . .

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Aleksić, Marija
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/11/2731
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4407
AB  - Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.
T2  - Cancers
T1  - Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis
IS  - 11
VL  - 13
DO  - 10.3390/cancers13112731
SP  - 2731
ER  - 

@article{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Aleksić, Marija and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.",
journal = "Cancers",
title = "Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis",
number = "11",
volume = "13",
doi = "10.3390/cancers13112731",
pages = "2731"
}

Kalezić, A., Udički, M., Srdić Galić, B., Aleksić, M., Korać, A., Janković, A.,& Korać, B.. (2021). Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis. in Cancers, 13(11), 2731.
https://doi.org/10.3390/cancers13112731

Kalezić A, Udički M, Srdić Galić B, Aleksić M, Korać A, Janković A, Korać B. Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis. in Cancers. 2021;13(11):2731.
doi:10.3390/cancers13112731 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Aleksić, Marija, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis" in Cancers, 13, no. 11 (2021):2731,
https://doi.org/10.3390/cancers13112731 . .

TY  - JOUR
AU  - Aleksić, Marija
AU  - Golić, Igor
AU  - Kalezić, Anđelika
AU  - Janković, Aleksandra
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2021
UR  - https://www.mdpi.com/2073-4409/10/9/2248
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8472630
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4491
AB  - Despite peroxisomes being important partners of mitochondria by carrying out fatty acid oxidation in brown adipocytes, no clear evidence concerning peroxisome origin and way(s) of biogenesis exists. Herein we used methimazole-induced hypothyroidism for 7, 15, and 21 days to study peroxisomal remodeling and origin in rat brown adipocytes. We found that peroxisomes originated via both canonic, and de novo pathways. Each pathway operates in euthyroid control and over the course of hypothyroidism, in a time-dependent manner. Hypothyroidism increased the peroxisomal number by 1.8-, 3.6- and 5.8-fold on days 7, 15, and 21. Peroxisomal presence, their distribution, and their degree of maturation were heterogeneous in brown adipocytes in a Harlequin-like manner, reflecting differences in their origin. The canonic pathway, through numerous dumbbell-like and "pearls on strings" structures, supported by high levels of Pex11β and Drp1, prevailed on day 7. The de novo pathway of peroxisomal biogenesis started on day 15 and became dominant by day 21. The transition of peroxisomal biogenesis from canonic to the de novo pathway was driven by increased levels of Pex19, PMP70, Pex5S, and Pex26 and characterized by numerous tubular structures. Furthermore, specific peroxisomal origin from mitochondria, regardless of thyroid status, indicates their mutual regulation in rat brown adipocytes.
PB  - Basel: MDPI
T2  - Cells
T1  - Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.
IS  - 9
VL  - 10
DO  - 10.3390/cells10092248
SP  - 2248
ER  - 

@article{
author = "Aleksić, Marija and Golić, Igor and Kalezić, Anđelika and Janković, Aleksandra and Korać, Bato and Korać, Aleksandra",
year = "2021",
abstract = "Despite peroxisomes being important partners of mitochondria by carrying out fatty acid oxidation in brown adipocytes, no clear evidence concerning peroxisome origin and way(s) of biogenesis exists. Herein we used methimazole-induced hypothyroidism for 7, 15, and 21 days to study peroxisomal remodeling and origin in rat brown adipocytes. We found that peroxisomes originated via both canonic, and de novo pathways. Each pathway operates in euthyroid control and over the course of hypothyroidism, in a time-dependent manner. Hypothyroidism increased the peroxisomal number by 1.8-, 3.6- and 5.8-fold on days 7, 15, and 21. Peroxisomal presence, their distribution, and their degree of maturation were heterogeneous in brown adipocytes in a Harlequin-like manner, reflecting differences in their origin. The canonic pathway, through numerous dumbbell-like and "pearls on strings" structures, supported by high levels of Pex11β and Drp1, prevailed on day 7. The de novo pathway of peroxisomal biogenesis started on day 15 and became dominant by day 21. The transition of peroxisomal biogenesis from canonic to the de novo pathway was driven by increased levels of Pex19, PMP70, Pex5S, and Pex26 and characterized by numerous tubular structures. Furthermore, specific peroxisomal origin from mitochondria, regardless of thyroid status, indicates their mutual regulation in rat brown adipocytes.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.",
number = "9",
volume = "10",
doi = "10.3390/cells10092248",
pages = "2248"
}

Aleksić, M., Golić, I., Kalezić, A., Janković, A., Korać, B.,& Korać, A.. (2021). Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.. in Cells
Basel: MDPI., 10(9), 2248.
https://doi.org/10.3390/cells10092248

Aleksić M, Golić I, Kalezić A, Janković A, Korać B, Korać A. Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner.. in Cells. 2021;10(9):2248.
doi:10.3390/cells10092248 .

Aleksić, Marija, Golić, Igor, Kalezić, Anđelika, Janković, Aleksandra, Korać, Bato, Korać, Aleksandra, "Hypothyroidism Intensifies Both Canonic and the De Novo Pathway of Peroxisomal Biogenesis in Rat Brown Adipocytes in a Time-Dependent Manner." in Cells, 10, no. 9 (2021):2248,
https://doi.org/10.3390/cells10092248 . .

TY  - JOUR
AU  - Janković, Aleksandra
AU  - Zakić, Tamara
AU  - Miličić, Miroslav
AU  - Unić-Stojanović, Dragana
AU  - Kalezić, Anđelika
AU  - Korać, Aleksandra
AU  - Jović, Miomir
AU  - Korać, Bato
PY  - 2021
UR  - https://www.mdpi.com/2076-3921/10/12/1910
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8750270
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4740
AB  - Remote ischaemic preconditioning (RIPC) is a medical procedure that consists of repeated brief periods of transient ischaemia and reperfusion of distant organs (limbs) with the ability to provide internal organ protection from ischaemia. Even though RIPC has been successfully applied in patients with myocardial infarction during coronary revascularization (surgery/percutaneous angioplasty), the underlying molecular mechanisms are yet to be clarified. Thus, our study aimed to determine the role of nitric oxide synthase (NOS) isoforms in RIPC-induced protection (3 × 5 min of forearm ischaemia with 5 min of reperfusion) of arterial graft in patients undergoing urgent coronary artery bypass grafting (CABG). We examined RIPC effects on specific expression and immunolocalization of three NOS isoforms - endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) in patients' internal thoracic artery (ITA) used as a graft. We found that the application of RIPC protocol leads to an increased protein expression of eNOS, which was further confirmed with strong eNOS immunopositivity, especially in the endothelium and smooth muscle cells of ITA. The same analysis of two other NOS isoforms, iNOS and nNOS, showed no significant differences between patients undergoing CABG with or without RIPC. Our results demonstrate RIPC-induced upregulation of eNOS in human ITA, pointing to its significance in achieving protective phenotype on a systemic level with important implications for graft patency.
PB  - Basel: MDPI
T2  - Antioxidants (Basel, Switzerland)
T1  - Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.
IS  - 12
VL  - 10
DO  - 10.3390/antiox10121910
SP  - 1910
ER  - 

@article{
author = "Janković, Aleksandra and Zakić, Tamara and Miličić, Miroslav and Unić-Stojanović, Dragana and Kalezić, Anđelika and Korać, Aleksandra and Jović, Miomir and Korać, Bato",
year = "2021",
abstract = "Remote ischaemic preconditioning (RIPC) is a medical procedure that consists of repeated brief periods of transient ischaemia and reperfusion of distant organs (limbs) with the ability to provide internal organ protection from ischaemia. Even though RIPC has been successfully applied in patients with myocardial infarction during coronary revascularization (surgery/percutaneous angioplasty), the underlying molecular mechanisms are yet to be clarified. Thus, our study aimed to determine the role of nitric oxide synthase (NOS) isoforms in RIPC-induced protection (3 × 5 min of forearm ischaemia with 5 min of reperfusion) of arterial graft in patients undergoing urgent coronary artery bypass grafting (CABG). We examined RIPC effects on specific expression and immunolocalization of three NOS isoforms - endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) in patients' internal thoracic artery (ITA) used as a graft. We found that the application of RIPC protocol leads to an increased protein expression of eNOS, which was further confirmed with strong eNOS immunopositivity, especially in the endothelium and smooth muscle cells of ITA. The same analysis of two other NOS isoforms, iNOS and nNOS, showed no significant differences between patients undergoing CABG with or without RIPC. Our results demonstrate RIPC-induced upregulation of eNOS in human ITA, pointing to its significance in achieving protective phenotype on a systemic level with important implications for graft patency.",
publisher = "Basel: MDPI",
journal = "Antioxidants (Basel, Switzerland)",
title = "Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.",
number = "12",
volume = "10",
doi = "10.3390/antiox10121910",
pages = "1910"
}

Janković, A., Zakić, T., Miličić, M., Unić-Stojanović, D., Kalezić, A., Korać, A., Jović, M.,& Korać, B.. (2021). Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.. in Antioxidants (Basel, Switzerland)
Basel: MDPI., 10(12), 1910.
https://doi.org/10.3390/antiox10121910

Janković A, Zakić T, Miličić M, Unić-Stojanović D, Kalezić A, Korać A, Jović M, Korać B. Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.. in Antioxidants (Basel, Switzerland). 2021;10(12):1910.
doi:10.3390/antiox10121910 .

Janković, Aleksandra, Zakić, Tamara, Miličić, Miroslav, Unić-Stojanović, Dragana, Kalezić, Anđelika, Korać, Aleksandra, Jović, Miomir, Korać, Bato, "Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting." in Antioxidants (Basel, Switzerland), 10, no. 12 (2021):1910,
https://doi.org/10.3390/antiox10121910 . .

TY  - CONF
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4859
AB  - Breast cancer behaves as a complex pseudo-organ where the adaptive behavior of cancer cells is deeply context-dependent, reflecting various local and systemic influences. Recently, cancer-associated adipocytes emerged as critical players in cancer progression, adapting to metabolic demands of proliferating cancer cells and responding through the supply of diverse energy substrates. To decipher underlying mechanisms that enable such plastic response, we cross-examined biopsies of cancer-associated adipose tissue from normal-weight and overweight women with invasive ductal carcinoma compared to mammary adipose tissue of weight-matched women with benign fibroadenoma. To that end, we analyzed mitochondrial copy number and master regulators of energy and redox homeostasis (AMP-activated protein kinase – AMPK and nuclear factor erythroid 2-related factor 2 – Nrf2), followed by key enzymes in their downstream pathways such as glycolysis, pentose phosphate pathway, fatty acid oxidation, and antioxidant defense. Compared to mammary adipose tissue, cancer-associated adipose tissue showed concomitantly higher AMPK and Nrf2 protein expression followed by overexpression of hexokinase 2, glucose-6-phosphate dehydrogenase, peroxisomal acyl-coenzyme A oxidase 1, first-line antioxidant defense enzymes (CuZn- and Mn- superoxide dismutase and catalase), as well as higher mitochondrial copy number. In contrast, in cancer-associated adipose tissue of obese women, a sole increase in AMPK protein expression without Nrf2 was followed by increased protein expression of analyzed metabolic enzymes but not antioxidant defense enzymes or mitochondrial copy number. The results indicate that simultaneous activation of AMPK and Nrf2 signaling promotes a specific metabolic phenotype of cancer-associated adipose tissue, resembling the Warburg effect with high mitochondrial content and increased redox homeostasis threshold. Moreover, context-dependent disruption of the AMPK–Nrf2 axis could prevent the establishment of such phenotype in obesity
PB  - Elsevier BV
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer
VL  - 177
DO  - 10.1016/j.freeradbiomed.2021.08.086
SP  - S76
EP  - S77
ER  - 

@conference{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Breast cancer behaves as a complex pseudo-organ where the adaptive behavior of cancer cells is deeply context-dependent, reflecting various local and systemic influences. Recently, cancer-associated adipocytes emerged as critical players in cancer progression, adapting to metabolic demands of proliferating cancer cells and responding through the supply of diverse energy substrates. To decipher underlying mechanisms that enable such plastic response, we cross-examined biopsies of cancer-associated adipose tissue from normal-weight and overweight women with invasive ductal carcinoma compared to mammary adipose tissue of weight-matched women with benign fibroadenoma. To that end, we analyzed mitochondrial copy number and master regulators of energy and redox homeostasis (AMP-activated protein kinase – AMPK and nuclear factor erythroid 2-related factor 2 – Nrf2), followed by key enzymes in their downstream pathways such as glycolysis, pentose phosphate pathway, fatty acid oxidation, and antioxidant defense. Compared to mammary adipose tissue, cancer-associated adipose tissue showed concomitantly higher AMPK and Nrf2 protein expression followed by overexpression of hexokinase 2, glucose-6-phosphate dehydrogenase, peroxisomal acyl-coenzyme A oxidase 1, first-line antioxidant defense enzymes (CuZn- and Mn- superoxide dismutase and catalase), as well as higher mitochondrial copy number. In contrast, in cancer-associated adipose tissue of obese women, a sole increase in AMPK protein expression without Nrf2 was followed by increased protein expression of analyzed metabolic enzymes but not antioxidant defense enzymes or mitochondrial copy number. The results indicate that simultaneous activation of AMPK and Nrf2 signaling promotes a specific metabolic phenotype of cancer-associated adipose tissue, resembling the Warburg effect with high mitochondrial content and increased redox homeostasis threshold. Moreover, context-dependent disruption of the AMPK–Nrf2 axis could prevent the establishment of such phenotype in obesity",
publisher = "Elsevier BV, Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer",
volume = "177",
doi = "10.1016/j.freeradbiomed.2021.08.086",
pages = "S76-S77"
}

Kalezić, A., Udički, M., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2021). AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier BV., 177, S76-S77.
https://doi.org/10.1016/j.freeradbiomed.2021.08.086

Kalezić A, Udički M, Srdić Galić B, Korać A, Janković A, Korać B. AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;177:S76-S77.
doi:10.1016/j.freeradbiomed.2021.08.086 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia, 177 (2021):S76-S77,
https://doi.org/10.1016/j.freeradbiomed.2021.08.086 . .

TY  - CONF
AU  - Budnar, Marta
AU  - Zakić, Tamara
AU  - Ćirović, Duško
AU  - Kalezić, Anđelika
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4805
AB  - Hibernators enter into an extreme state of prolonged torpor characterized by hypometabolism (over 95% metabolic suppression), significant suppression of vital functions, and hypothermia. Specific regulatory mechanisms control physiological processes and metabolic functions that allow hibernators to survive challenging environmental conditions. Skin is one of the most metabolically active organs with intense fluctuations in metabolic rates that are accompanied by adequate changes in the antioxidant status. However, there is little data concerning redox-metabolic-related changes in hibernators skin. This study aimed to investigate nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent control of redox and metabolic responses in the skin (epidermis and dermis) of ground squirrel (Spermophilus citellus) in pre-hibernation, hibernation (torpor), and post-hibernation. To that end, we examined the protein expression of Nrf2, hypoxia-inducible factor 1 alpha (HIF-1α), and key antioxidant defense (AD) and metabolic enzymes. Our results showed no change in HIF-1α protein expression during circannual phases, indicating that skin is not hypoxic during hibernation. Moreover, Nrf2 was strongly elevated in hibernation and post-hibernation, accompanied by higher methionine sulfoxide reductase A protein expression in hibernation. Interestingly, in hibernation protein levels of most AD enzymes remain on pre-hibernation level, while post-hibernation was characterized by high expression of manganese superoxide dismutase and glutathione peroxidase, indicating a possible role of Nrf2 in preconditioning during hibernation. Indeed, such AD and Nrf2 increases correlated with upregulation of pyruvate dehydrogenase, citrate synthase, complex III of the mitochondrial electron transport chain, and fatty acid synthase in hibernation and post-hibernation, and with an additional increase in enzymes of mitochondrial and peroxisomal β-oxidation in post-hibernation. The results suggest that Nrf2 is involved in the regulation of complex antioxidant response concerning changes in metabolic activity in the skin of ground squirrel in hibernation and post-hibernation to maintain optimal conditions for surviving.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus)
DO  - 10.1016/j.freeradbiomed.2021.08.060
SP  - S65
ER  - 

@conference{
author = "Budnar, Marta and Zakić, Tamara and Ćirović, Duško and Kalezić, Anđelika and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Hibernators enter into an extreme state of prolonged torpor characterized by hypometabolism (over 95% metabolic suppression), significant suppression of vital functions, and hypothermia. Specific regulatory mechanisms control physiological processes and metabolic functions that allow hibernators to survive challenging environmental conditions. Skin is one of the most metabolically active organs with intense fluctuations in metabolic rates that are accompanied by adequate changes in the antioxidant status. However, there is little data concerning redox-metabolic-related changes in hibernators skin. This study aimed to investigate nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent control of redox and metabolic responses in the skin (epidermis and dermis) of ground squirrel (Spermophilus citellus) in pre-hibernation, hibernation (torpor), and post-hibernation. To that end, we examined the protein expression of Nrf2, hypoxia-inducible factor 1 alpha (HIF-1α), and key antioxidant defense (AD) and metabolic enzymes. Our results showed no change in HIF-1α protein expression during circannual phases, indicating that skin is not hypoxic during hibernation. Moreover, Nrf2 was strongly elevated in hibernation and post-hibernation, accompanied by higher methionine sulfoxide reductase A protein expression in hibernation. Interestingly, in hibernation protein levels of most AD enzymes remain on pre-hibernation level, while post-hibernation was characterized by high expression of manganese superoxide dismutase and glutathione peroxidase, indicating a possible role of Nrf2 in preconditioning during hibernation. Indeed, such AD and Nrf2 increases correlated with upregulation of pyruvate dehydrogenase, citrate synthase, complex III of the mitochondrial electron transport chain, and fatty acid synthase in hibernation and post-hibernation, and with an additional increase in enzymes of mitochondrial and peroxisomal β-oxidation in post-hibernation. The results suggest that Nrf2 is involved in the regulation of complex antioxidant response concerning changes in metabolic activity in the skin of ground squirrel in hibernation and post-hibernation to maintain optimal conditions for surviving.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus)",
doi = "10.1016/j.freeradbiomed.2021.08.060",
pages = "S65"
}

Budnar, M., Zakić, T., Ćirović, D., Kalezić, A., Korać, A., Janković, A.,& Korać, B.. (2021). Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus). in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., S65.
https://doi.org/10.1016/j.freeradbiomed.2021.08.060

Budnar M, Zakić T, Ćirović D, Kalezić A, Korać A, Janković A, Korać B. Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus). in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:S65.
doi:10.1016/j.freeradbiomed.2021.08.060 .

Budnar, Marta, Zakić, Tamara, Ćirović, Duško, Kalezić, Anđelika, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus)" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):S65,
https://doi.org/10.1016/j.freeradbiomed.2021.08.060 . .

TY  - CONF
AU  - Golić, Igor
AU  - Aleksić, Marija
AU  - Kalezić, Anđelika
AU  - Janković, Aleksandra
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4803
AB  - The disequilibrium of reactive oxygen/nitrogen species (ROS/RNS) is one of the causes of male infertility. To examine the role of ROS/RNS in reproduction, we modulated the cell concentration of О2•– and NO using the superoxide dismutase (SOD) mimic, M40403, which selectively removes О2•– and consequently increases the NO bioavailability. The fine chromatin changes are difficult to observe via routine light/electron microscopy, therefore we used fractal analysis to analyze DNA compaction. We used normospermic semen samples from ten human subjects. After purification in Cook density gradient, the sperm-rich fraction was rinsed in modified Tyrod medium (TM). Purified samples were divided into three groups. One group was evaluated immediately after resuspension in TM and served as the control. For the other two groups, untreated and SOD mimic-treated group (50 μM), the sperm was resuspended in TM and evaluated after incubation at 37 ºC / 6% CO2 for 3 hours. Air-dried and methanol fixed sperm smears were stained with toluidine blue and analyzed on Leica DMLB microscope. Images from ten randomly selected fields were analyzed in ImageJ plugin FracLac to get fractal dimension defined as a measure of complexity. Average values of fractal dimensions (mean ± SEM) are: control group – 1.016 ± 0.553; untreated group – 0.955 ± 0.291; treated group – 1.146 ± 0.096. Also, average values of lacunarity are: control group – 0.734 ± 0.129; untreated group – 0.727 ± 0.129; treated group – 0.901 ± 0.297. Results show that SOD mimic remodels chromatin condensation by increasing the euchromatin area, potentially leading to a resume in transcriptional activity. This hypothesis would be consistent with our published findings of up-regulated mRNA expression of eNOS, MnSOD, and catalase in SOD mimic-treated spermatozoa ex vivo (Otasevic et al., 2013). Therefore, SOD mimic modulates the redox environment via direct chromatin remodeling in spermatozoa. Fractal analysis has proven to be a good method for the analysis of chromatin condensation in human sperm nuclei. Ref: Otasevic V, Korac A, Vucetic M, Macanovic B, Garalejic E, Ivanovic-Burmazovic I, Filipovic MR, Buzadzic B, Stancic A, Jankovic A, Velickovic K, Golic I, Markelic M, Korac B. Is manganese (II) pentaazamacrocyclic superoxide dismutase mimic beneficial for human sperm mitochondria function and motility? Antioxid Redox Signal. 2013 Jan 10;18(2):170-8. doi: 10.1089/ars.2012.4684. Epub 2012 Jun 12. PMID: 22563824; PMCID: PMC3513981
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Fractal analysis of chromatin condensation in the human sperm nuclei
DO  - 10.1016/j.freeradbiomed.2021.08.178
SP  - S114
ER  - 

@conference{
author = "Golić, Igor and Aleksić, Marija and Kalezić, Anđelika and Janković, Aleksandra and Korać, Bato and Korać, Aleksandra",
year = "2021",
abstract = "The disequilibrium of reactive oxygen/nitrogen species (ROS/RNS) is one of the causes of male infertility. To examine the role of ROS/RNS in reproduction, we modulated the cell concentration of О2•– and NO using the superoxide dismutase (SOD) mimic, M40403, which selectively removes О2•– and consequently increases the NO bioavailability. The fine chromatin changes are difficult to observe via routine light/electron microscopy, therefore we used fractal analysis to analyze DNA compaction. We used normospermic semen samples from ten human subjects. After purification in Cook density gradient, the sperm-rich fraction was rinsed in modified Tyrod medium (TM). Purified samples were divided into three groups. One group was evaluated immediately after resuspension in TM and served as the control. For the other two groups, untreated and SOD mimic-treated group (50 μM), the sperm was resuspended in TM and evaluated after incubation at 37 ºC / 6% CO2 for 3 hours. Air-dried and methanol fixed sperm smears were stained with toluidine blue and analyzed on Leica DMLB microscope. Images from ten randomly selected fields were analyzed in ImageJ plugin FracLac to get fractal dimension defined as a measure of complexity. Average values of fractal dimensions (mean ± SEM) are: control group – 1.016 ± 0.553; untreated group – 0.955 ± 0.291; treated group – 1.146 ± 0.096. Also, average values of lacunarity are: control group – 0.734 ± 0.129; untreated group – 0.727 ± 0.129; treated group – 0.901 ± 0.297. Results show that SOD mimic remodels chromatin condensation by increasing the euchromatin area, potentially leading to a resume in transcriptional activity. This hypothesis would be consistent with our published findings of up-regulated mRNA expression of eNOS, MnSOD, and catalase in SOD mimic-treated spermatozoa ex vivo (Otasevic et al., 2013). Therefore, SOD mimic modulates the redox environment via direct chromatin remodeling in spermatozoa. Fractal analysis has proven to be a good method for the analysis of chromatin condensation in human sperm nuclei. Ref: Otasevic V, Korac A, Vucetic M, Macanovic B, Garalejic E, Ivanovic-Burmazovic I, Filipovic MR, Buzadzic B, Stancic A, Jankovic A, Velickovic K, Golic I, Markelic M, Korac B. Is manganese (II) pentaazamacrocyclic superoxide dismutase mimic beneficial for human sperm mitochondria function and motility? Antioxid Redox Signal. 2013 Jan 10;18(2):170-8. doi: 10.1089/ars.2012.4684. Epub 2012 Jun 12. PMID: 22563824; PMCID: PMC3513981",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Fractal analysis of chromatin condensation in the human sperm nuclei",
doi = "10.1016/j.freeradbiomed.2021.08.178",
pages = "S114"
}

Golić, I., Aleksić, M., Kalezić, A., Janković, A., Korać, B.,& Korać, A.. (2021). Fractal analysis of chromatin condensation in the human sperm nuclei. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., S114.
https://doi.org/10.1016/j.freeradbiomed.2021.08.178

Golić I, Aleksić M, Kalezić A, Janković A, Korać B, Korać A. Fractal analysis of chromatin condensation in the human sperm nuclei. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:S114.
doi:10.1016/j.freeradbiomed.2021.08.178 .

Golić, Igor, Aleksić, Marija, Kalezić, Anđelika, Janković, Aleksandra, Korać, Bato, Korać, Aleksandra, "Fractal analysis of chromatin condensation in the human sperm nuclei" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):S114,
https://doi.org/10.1016/j.freeradbiomed.2021.08.178 . .

TY  - CONF
AU  - Kalezić, Anđelika
AU  - Udicki, Mirjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4681
AB  - Global trends of increasing caloric consumption and decreasing physical activity have given rise to metabolic diseases in epidemic proportions. As a chronic state of altered metabolic and energy homeostasis,obesity is associated with various chronic diseases, including cancer. Alongside obesity, breast cancer incidence is also on the rise,even among premenopausal women. Acting through systemic and local influences, obesity could be viewed as a potential driving force for breast cancer development; however, this relationship seems rather complex. Accumulating evidence indicates that obesity decreasesthe incidence of breast cancer but increases rates of mortality,metastasis and therapeutic resistance in premenopausal women. We aim to provide an in-depth insight into the molecular mechanisms underlying the intriguing relationship between breast cancer and obesity by focusing on cross-examinationof metabolic alterations in breast cancer and cancer-associated adipose tissue. Metabolic reprogramming will be discussed through the potential influences obesityexerts on major pathways in glucose, lipid, and mitochondrial metabolism in breast cancer and cancer-associated adipose tissue. An overview of the wide-ranging implications of context-dependent metabolic reprogramming for personalized diagnostic and therapeutic approaches will be given.
PB  - Belgrade: Serbian Nutrition Society
C3  - 14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia
T1  - Molecular basis of obesity and cancer
SP  - 55
EP  - 55
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4681
ER  - 

@conference{
author = "Kalezić, Anđelika and Udicki, Mirjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Global trends of increasing caloric consumption and decreasing physical activity have given rise to metabolic diseases in epidemic proportions. As a chronic state of altered metabolic and energy homeostasis,obesity is associated with various chronic diseases, including cancer. Alongside obesity, breast cancer incidence is also on the rise,even among premenopausal women. Acting through systemic and local influences, obesity could be viewed as a potential driving force for breast cancer development; however, this relationship seems rather complex. Accumulating evidence indicates that obesity decreasesthe incidence of breast cancer but increases rates of mortality,metastasis and therapeutic resistance in premenopausal women. We aim to provide an in-depth insight into the molecular mechanisms underlying the intriguing relationship between breast cancer and obesity by focusing on cross-examinationof metabolic alterations in breast cancer and cancer-associated adipose tissue. Metabolic reprogramming will be discussed through the potential influences obesityexerts on major pathways in glucose, lipid, and mitochondrial metabolism in breast cancer and cancer-associated adipose tissue. An overview of the wide-ranging implications of context-dependent metabolic reprogramming for personalized diagnostic and therapeutic approaches will be given.",
publisher = "Belgrade: Serbian Nutrition Society",
journal = "14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia",
title = "Molecular basis of obesity and cancer",
pages = "55-55",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4681"
}

Kalezić, A., Udicki, M., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2021). Molecular basis of obesity and cancer. in 14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia
Belgrade: Serbian Nutrition Society., 55-55.
https://hdl.handle.net/21.15107/rcub_ibiss_4681

Kalezić A, Udicki M, Srdić Galić B, Korać A, Janković A, Korać B. Molecular basis of obesity and cancer. in 14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia. 2021;:55-55.
https://hdl.handle.net/21.15107/rcub_ibiss_4681 .

Kalezić, Anđelika, Udicki, Mirjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Molecular basis of obesity and cancer" in 14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia (2021):55-55,
https://hdl.handle.net/21.15107/rcub_ibiss_4681 .

TY  - JOUR
AU  - Zakić, Tamara
AU  - Budnar, Marta
AU  - Kalezić, Anđelika
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2020
UR  - http://hrana-ishrana.org/wp-content/uploads/2021/03/Broj-2-Vol-61-2020-1.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4179
AB  - Priča o vitaminu C (L-askorbinska kiselina), antioksidansu i kofaktoru u brojnim
biohemijskim reakcijama, deo je njegove duge istorije danas dobro poznata.
Međutim, mnoga pitanja o mehanizmima njegovog delovanja i koristima
koje on ostvaruje po ljudsko zdravlje se kontinuirano nameću. Ovo se
odnosi ne samo na preporučene doze vitamina C, već i na način njegove primene.
Pored toga, postoje brojna pitanja o efikasnosti vitamina C u terapiji
različitih humanih infektivnih bolesti, njegovom antivirusnom potencijalu,
kao i ulozi u funkcionisanju imunskog sistema. Činjenica da vitamin C može
delovati kao redukciono sredstvo (antioksidant) i pro-oksidativno, dodatno
naglašava njegov oksidaciono-redukcioni (redoks) potencijal u fiziološkim
uslovima. Danas posebnu pažnja zahteva pitanje efekta intravenske primene
vitamina C kod pacijenata sa SARS-CoV-2. Ovaj pregled ima za cilj da
prikaže poznate činjenice o vitaminu C i njegovim mehanizmima delovanja
kako bi se bolje razumeli novi izazovi povezani sa vitaminom C.
AB  - The story of vitamin C (L-ascorbic acid) as an antioxidant and a cofactor
in numerous biochemical reactions is a part of its long history and
it is well known today. However, many questions of its mechanism of
action and the benefits that it has on human health are still emerging.
This applies not only to the recommended doses but also to the route
of its administration. Besides, there are numerous questions about the
therapeutic efficacy of vitamin C in various human (infectious) diseases,
as well as its immune system function and antiviral potential.
The fact that vitamin C can act as a reductant (antioxidant) and a prooxidant
further emphasizes its oxidation-reduction (redox) potential
in real physiological conditions. Today, the question of the intravenous
administration of vitamin C effect in patients with SARS-CoV-2
requires special attention. This review aims to showcase known facts
about vitamin C and its mechanisms of action to better understand
the current new challenges related to vitamin C.
PB  - Belgrade: Serbian Nutrition Society
T2  - Hrana i ishrana
T1  - Vitamin C biochemistry: From scurvy to COVID-19 treatment
T1  - Biohemija vitamina C: Od skorbuta do COVID-19 tretmana
IS  - 2
VL  - 61
DO  - 10.5937/hraIsh2002059Z
SP  - 59
EP  - 70
ER  - 

@article{
author = "Zakić, Tamara and Budnar, Marta and Kalezić, Anđelika and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2020",
abstract = "Priča o vitaminu C (L-askorbinska kiselina), antioksidansu i kofaktoru u brojnim
biohemijskim reakcijama, deo je njegove duge istorije danas dobro poznata.
Međutim, mnoga pitanja o mehanizmima njegovog delovanja i koristima
koje on ostvaruje po ljudsko zdravlje se kontinuirano nameću. Ovo se
odnosi ne samo na preporučene doze vitamina C, već i na način njegove primene.
Pored toga, postoje brojna pitanja o efikasnosti vitamina C u terapiji
različitih humanih infektivnih bolesti, njegovom antivirusnom potencijalu,
kao i ulozi u funkcionisanju imunskog sistema. Činjenica da vitamin C može
delovati kao redukciono sredstvo (antioksidant) i pro-oksidativno, dodatno
naglašava njegov oksidaciono-redukcioni (redoks) potencijal u fiziološkim
uslovima. Danas posebnu pažnja zahteva pitanje efekta intravenske primene
vitamina C kod pacijenata sa SARS-CoV-2. Ovaj pregled ima za cilj da
prikaže poznate činjenice o vitaminu C i njegovim mehanizmima delovanja
kako bi se bolje razumeli novi izazovi povezani sa vitaminom C., The story of vitamin C (L-ascorbic acid) as an antioxidant and a cofactor
in numerous biochemical reactions is a part of its long history and
it is well known today. However, many questions of its mechanism of
action and the benefits that it has on human health are still emerging.
This applies not only to the recommended doses but also to the route
of its administration. Besides, there are numerous questions about the
therapeutic efficacy of vitamin C in various human (infectious) diseases,
as well as its immune system function and antiviral potential.
The fact that vitamin C can act as a reductant (antioxidant) and a prooxidant
further emphasizes its oxidation-reduction (redox) potential
in real physiological conditions. Today, the question of the intravenous
administration of vitamin C effect in patients with SARS-CoV-2
requires special attention. This review aims to showcase known facts
about vitamin C and its mechanisms of action to better understand
the current new challenges related to vitamin C.",
publisher = "Belgrade: Serbian Nutrition Society",
journal = "Hrana i ishrana",
title = "Vitamin C biochemistry: From scurvy to COVID-19 treatment, Biohemija vitamina C: Od skorbuta do COVID-19 tretmana",
number = "2",
volume = "61",
doi = "10.5937/hraIsh2002059Z",
pages = "59-70"
}

Zakić, T., Budnar, M., Kalezić, A., Korać, A., Janković, A.,& Korać, B.. (2020). Vitamin C biochemistry: From scurvy to COVID-19 treatment. in Hrana i ishrana
Belgrade: Serbian Nutrition Society., 61(2), 59-70.
https://doi.org/10.5937/hraIsh2002059Z

Zakić T, Budnar M, Kalezić A, Korać A, Janković A, Korać B. Vitamin C biochemistry: From scurvy to COVID-19 treatment. in Hrana i ishrana. 2020;61(2):59-70.
doi:10.5937/hraIsh2002059Z .

Zakić, Tamara, Budnar, Marta, Kalezić, Anđelika, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Vitamin C biochemistry: From scurvy to COVID-19 treatment" in Hrana i ishrana, 61, no. 2 (2020):59-70,
https://doi.org/10.5937/hraIsh2002059Z . .

TY  - JOUR
AU  - Miler, Irena
AU  - Rabasović, Mihailo D.
AU  - Aleksić, Marija
AU  - Krmpot, Aleksandar J.
AU  - Kalezić, Anđelika
AU  - Janković, Aleksandra
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/10.1002/jbio.202000362
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4072
AB  - Our previous study on rat skin showed that cumulative oxidative pressure induces profound structural and ultrastructural alterations in both rat skin epidermis and dermis during aging. Here, we aimed to investigate the biophotonic properties of collagen as a main dermal component in the function of chronological aging. We used second harmonic generation (SHG) and two‐photon excited fluorescence (TPEF) on 5 μm thick skin paraffin sections from 15‐day‐, 1‐month‐ and 21‐month‐old rats, respectively, to analyze collagen alterations, in comparison to conventional light and electron microscopy methods. Obtained results show that polarization‐resolved SHG (PSHG) images can detect collagen fiber alterations in line with chronological aging and that this method is consistent with light and electron microscopy. Moreover, the β coefficient calculated from PSHG images points out that delicate alterations lead to a more ordered structure of collagen molecules due to oxidative damage. The results of this study also open the possibility of successfully applying this fast and label‐free method to previously fixed samples.image
PB  - Wiley
T2  - Journal of Biophotonics
T1  - Polarization‐resolved SHG imaging as a fast screening method for collagen alterations during aging: Comparison with light and electron microscopy
DO  - 10.1002/jbio.202000362
ER  - 

@article{
author = "Miler, Irena and Rabasović, Mihailo D. and Aleksić, Marija and Krmpot, Aleksandar J. and Kalezić, Anđelika and Janković, Aleksandra and Korać, Bato and Korać, Aleksandra",
year = "2020",
abstract = "Our previous study on rat skin showed that cumulative oxidative pressure induces profound structural and ultrastructural alterations in both rat skin epidermis and dermis during aging. Here, we aimed to investigate the biophotonic properties of collagen as a main dermal component in the function of chronological aging. We used second harmonic generation (SHG) and two‐photon excited fluorescence (TPEF) on 5 μm thick skin paraffin sections from 15‐day‐, 1‐month‐ and 21‐month‐old rats, respectively, to analyze collagen alterations, in comparison to conventional light and electron microscopy methods. Obtained results show that polarization‐resolved SHG (PSHG) images can detect collagen fiber alterations in line with chronological aging and that this method is consistent with light and electron microscopy. Moreover, the β coefficient calculated from PSHG images points out that delicate alterations lead to a more ordered structure of collagen molecules due to oxidative damage. The results of this study also open the possibility of successfully applying this fast and label‐free method to previously fixed samples.image",
publisher = "Wiley",
journal = "Journal of Biophotonics",
title = "Polarization‐resolved SHG imaging as a fast screening method for collagen alterations during aging: Comparison with light and electron microscopy",
doi = "10.1002/jbio.202000362"
}

Miler, I., Rabasović, M. D., Aleksić, M., Krmpot, A. J., Kalezić, A., Janković, A., Korać, B.,& Korać, A.. (2020). Polarization‐resolved SHG imaging as a fast screening method for collagen alterations during aging: Comparison with light and electron microscopy. in Journal of Biophotonics
Wiley..
https://doi.org/10.1002/jbio.202000362

Miler I, Rabasović MD, Aleksić M, Krmpot AJ, Kalezić A, Janković A, Korać B, Korać A. Polarization‐resolved SHG imaging as a fast screening method for collagen alterations during aging: Comparison with light and electron microscopy. in Journal of Biophotonics. 2020;.
doi:10.1002/jbio.202000362 .

Miler, Irena, Rabasović, Mihailo D., Aleksić, Marija, Krmpot, Aleksandar J., Kalezić, Anđelika, Janković, Aleksandra, Korać, Bato, Korać, Aleksandra, "Polarization‐resolved SHG imaging as a fast screening method for collagen alterations during aging: Comparison with light and electron microscopy" in Journal of Biophotonics (2020),
https://doi.org/10.1002/jbio.202000362 . .

TY  - JOUR
AU  - Vujačić-Mirski, Ksenija
AU  - Bruns, Kai
AU  - Kalinović, Sanela
AU  - Oelze, Matthias
AU  - Kröller-Schön, Swenja
AU  - Steven, Sebastian
AU  - Mojović, Miloš
AU  - Korać, Bato
AU  - Münzel, Thomas
AU  - Daiber, Andreas
PY  - 2020
UR  - https://www.mdpi.com/2076-3921/9/5/388
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32384768
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3672
AB  - Reactive oxygen and nitrogen species (RONS) cause oxidative damage, which is associated with endothelial dysfunction and cardiovascular disease, but may also contribute to redox signaling. Therefore, their precise detection is important for the evaluation of disease mechanisms. Here, we compared three different methods for the detection of 3-nitrotyrosine (3-NT), a marker of nitro-oxidative stress, in biological samples. Nitrated proteins were generated by incubation with peroxynitrite or 3-morpholino sydnonimine (Sin-1) and subjected to total hydrolysis using pronase, a mixture of different proteases. The 3-NT was then separated by high performance liquid chromatography (HPLC) and quantified by electrochemical detection (ECD, CoulArray) and compared to classical methods, namely enzyme-linked immunosorbent assay (ELISA) and dot blot analysis using specific 3-NT antibodies. Calibration curves for authentic 3-NT (detection limit 10 nM) and a concentration-response pattern for 3-NT obtained from digested nitrated bovine serum albumin (BSA) were highly linear over a wide 3-NT concentration range. Also, ex vivo nitration of protein from heart, isolated mitochondria, and serum/plasma could be quantified using the HPLC/ECD method and was confirmed by LC-MS/MS. Of note, nitro-oxidative damage of mitochondria results in increased superoxide (O2•-) formation rates (measured by dihydroethidium-based HPLC assay), pointing to a self-amplification mechanism of oxidative stress. Based on our ex vivo data, the CoulArray quantification method for 3-NT seems to have some advantages regarding sensitivity and selectivity. Establishing a reliable automated HPLC assay for the routine quantification of 3-NT in biological samples of cell culture, of animal and human origin seems to be more sophisticated than expected.
T2  - Antioxidants (Basel, Switzerland)
T2  - Antioxidants (Basel, Switzerland)
T1  - Development of an Analytical Assay for Electrochemical Detection and Quantification of Protein-Bound 3-Nitrotyrosine in Biological Samples and Comparison with Classical, Antibody-Based Methods.
IS  - 5
VL  - 9
DO  - 10.3390/antiox9050388
SP  - 388
ER  - 

@article{
author = "Vujačić-Mirski, Ksenija and Bruns, Kai and Kalinović, Sanela and Oelze, Matthias and Kröller-Schön, Swenja and Steven, Sebastian and Mojović, Miloš and Korać, Bato and Münzel, Thomas and Daiber, Andreas",
year = "2020",
abstract = "Reactive oxygen and nitrogen species (RONS) cause oxidative damage, which is associated with endothelial dysfunction and cardiovascular disease, but may also contribute to redox signaling. Therefore, their precise detection is important for the evaluation of disease mechanisms. Here, we compared three different methods for the detection of 3-nitrotyrosine (3-NT), a marker of nitro-oxidative stress, in biological samples. Nitrated proteins were generated by incubation with peroxynitrite or 3-morpholino sydnonimine (Sin-1) and subjected to total hydrolysis using pronase, a mixture of different proteases. The 3-NT was then separated by high performance liquid chromatography (HPLC) and quantified by electrochemical detection (ECD, CoulArray) and compared to classical methods, namely enzyme-linked immunosorbent assay (ELISA) and dot blot analysis using specific 3-NT antibodies. Calibration curves for authentic 3-NT (detection limit 10 nM) and a concentration-response pattern for 3-NT obtained from digested nitrated bovine serum albumin (BSA) were highly linear over a wide 3-NT concentration range. Also, ex vivo nitration of protein from heart, isolated mitochondria, and serum/plasma could be quantified using the HPLC/ECD method and was confirmed by LC-MS/MS. Of note, nitro-oxidative damage of mitochondria results in increased superoxide (O2•-) formation rates (measured by dihydroethidium-based HPLC assay), pointing to a self-amplification mechanism of oxidative stress. Based on our ex vivo data, the CoulArray quantification method for 3-NT seems to have some advantages regarding sensitivity and selectivity. Establishing a reliable automated HPLC assay for the routine quantification of 3-NT in biological samples of cell culture, of animal and human origin seems to be more sophisticated than expected.",
journal = "Antioxidants (Basel, Switzerland), Antioxidants (Basel, Switzerland)",
title = "Development of an Analytical Assay for Electrochemical Detection and Quantification of Protein-Bound 3-Nitrotyrosine in Biological Samples and Comparison with Classical, Antibody-Based Methods.",
number = "5",
volume = "9",
doi = "10.3390/antiox9050388",
pages = "388"
}

Vujačić-Mirski, K., Bruns, K., Kalinović, S., Oelze, M., Kröller-Schön, S., Steven, S., Mojović, M., Korać, B., Münzel, T.,& Daiber, A.. (2020). Development of an Analytical Assay for Electrochemical Detection and Quantification of Protein-Bound 3-Nitrotyrosine in Biological Samples and Comparison with Classical, Antibody-Based Methods.. in Antioxidants (Basel, Switzerland), 9(5), 388.
https://doi.org/10.3390/antiox9050388

Vujačić-Mirski K, Bruns K, Kalinović S, Oelze M, Kröller-Schön S, Steven S, Mojović M, Korać B, Münzel T, Daiber A. Development of an Analytical Assay for Electrochemical Detection and Quantification of Protein-Bound 3-Nitrotyrosine in Biological Samples and Comparison with Classical, Antibody-Based Methods.. in Antioxidants (Basel, Switzerland). 2020;9(5):388.
doi:10.3390/antiox9050388 .

Vujačić-Mirski, Ksenija, Bruns, Kai, Kalinović, Sanela, Oelze, Matthias, Kröller-Schön, Swenja, Steven, Sebastian, Mojović, Miloš, Korać, Bato, Münzel, Thomas, Daiber, Andreas, "Development of an Analytical Assay for Electrochemical Detection and Quantification of Protein-Bound 3-Nitrotyrosine in Biological Samples and Comparison with Classical, Antibody-Based Methods." in Antioxidants (Basel, Switzerland), 9, no. 5 (2020):388,
https://doi.org/10.3390/antiox9050388 . .

TY  - JOUR
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/biof.1535
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3385
AB  - Infertility is a significant global health problem that currently affects one of six couples in reproductive age. The quality of male reproductive cells dramatically decreased over the last years and almost every aspect of modern life additionally worsen sperm functional parameters that consequently markedly increase male infertility. This clearly points out the importance of finding a new approach to treat male infertility. Redox signaling mediated by reactive oxygen, nitrogen and sulfur species (ROS, RNS, and RSS respectively), has appeared important for sperm reproductive function. Present review summarizes the current knowledge of ROS, RNS, and RSS in male reproductive biology and identifies potential targets for development of novel pharmacological and therapeutic approaches for male infertility by targeted therapeutic modulation of redox signaling.
T2  - BioFactors (Oxford, England)
T1  - Reactive oxygen, nitrogen, and sulfur species in human male fertility. A crossroad of cellular signaling and pathology.
IS  - 2
VL  - 46
DO  - 10.1002/biof.1535
SP  - 206
EP  - 219
ER  - 

@article{
author = "Otašević, Vesna and Stančić, Ana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2020",
abstract = "Infertility is a significant global health problem that currently affects one of six couples in reproductive age. The quality of male reproductive cells dramatically decreased over the last years and almost every aspect of modern life additionally worsen sperm functional parameters that consequently markedly increase male infertility. This clearly points out the importance of finding a new approach to treat male infertility. Redox signaling mediated by reactive oxygen, nitrogen and sulfur species (ROS, RNS, and RSS respectively), has appeared important for sperm reproductive function. Present review summarizes the current knowledge of ROS, RNS, and RSS in male reproductive biology and identifies potential targets for development of novel pharmacological and therapeutic approaches for male infertility by targeted therapeutic modulation of redox signaling.",
journal = "BioFactors (Oxford, England)",
title = "Reactive oxygen, nitrogen, and sulfur species in human male fertility. A crossroad of cellular signaling and pathology.",
number = "2",
volume = "46",
doi = "10.1002/biof.1535",
pages = "206-219"
}

Otašević, V., Stančić, A., Korać, A., Janković, A.,& Korać, B.. (2020). Reactive oxygen, nitrogen, and sulfur species in human male fertility. A crossroad of cellular signaling and pathology.. in BioFactors (Oxford, England), 46(2), 206-219.
https://doi.org/10.1002/biof.1535

Otašević V, Stančić A, Korać A, Janković A, Korać B. Reactive oxygen, nitrogen, and sulfur species in human male fertility. A crossroad of cellular signaling and pathology.. in BioFactors (Oxford, England). 2020;46(2):206-219.
doi:10.1002/biof.1535 .

Otašević, Vesna, Stančić, Ana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Reactive oxygen, nitrogen, and sulfur species in human male fertility. A crossroad of cellular signaling and pathology." in BioFactors (Oxford, England), 46, no. 2 (2020):206-219,
https://doi.org/10.1002/biof.1535 . .