TY  - JOUR
AU  - Vasović, Dolika D.
AU  - Ivković, Sanja
AU  - Živanović, Ana
AU  - Major, Tamara
AU  - Milašin, Jelena M.
AU  - Nikolić, Nađa S.
AU  - Simonović, Jelena
AU  - Šutulović, Nikola
AU  - Hrnčić, Dragan
AU  - Stanojlović, Olivera
AU  - Vesković, Milena
AU  - Rašić, Dejan M.
AU  - Mladenović, Dušan
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5611
AB  - Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in
diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular
changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual
cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided
into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group
exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18).
Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in
the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure
alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular
Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly
up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly
higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its
anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T1  - Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover
VL  - 394
SP  - 110996
DO  - 10.1016/j.cbi.2024.110996
ER  - 

@article{
author = "Vasović, Dolika D. and Ivković, Sanja and Živanović, Ana and Major, Tamara and Milašin, Jelena M. and Nikolić, Nađa S. and Simonović, Jelena and Šutulović, Nikola and Hrnčić, Dragan and Stanojlović, Olivera and Vesković, Milena and Rašić, Dejan M. and Mladenović, Dušan",
year = "2024",
abstract = "Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in
diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular
changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual
cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided
into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group
exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18).
Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in
the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure
alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular
Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly
up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly
higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its
anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions",
title = "Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover",
volume = "394",
pages = "110996",
doi = "10.1016/j.cbi.2024.110996"
}

Vasović, D. D., Ivković, S., Živanović, A., Major, T., Milašin, J. M., Nikolić, N. S., Simonović, J., Šutulović, N., Hrnčić, D., Stanojlović, O., Vesković, M., Rašić, D. M.,& Mladenović, D.. (2024). Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover. in Chemico-Biological Interactions
Elsevier., 394, 110996.
https://doi.org/10.1016/j.cbi.2024.110996

Vasović DD, Ivković S, Živanović A, Major T, Milašin JM, Nikolić NS, Simonović J, Šutulović N, Hrnčić D, Stanojlović O, Vesković M, Rašić DM, Mladenović D. Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover. in Chemico-Biological Interactions. 2024;394:110996.
doi:10.1016/j.cbi.2024.110996 .

Vasović, Dolika D., Ivković, Sanja, Živanović, Ana, Major, Tamara, Milašin, Jelena M., Nikolić, Nađa S., Simonović, Jelena, Šutulović, Nikola, Hrnčić, Dragan, Stanojlović, Olivera, Vesković, Milena, Rašić, Dejan M., Mladenović, Dušan, "Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover" in Chemico-Biological Interactions, 394 (2024):110996,
https://doi.org/10.1016/j.cbi.2024.110996 . .

TY  - CONF
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Vesović, Marina
AU  - Živanović, Ana
AU  - Radić, Gordana
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5475
AB  - Design of dual COX-2/5-LOX inhibitors can be considered an adequate approach in the development of new anti-inflammatory drugs with less pronounced side effects. The aim of the present research was to examine the binding potential of the seven newly designed thiourea derivatives of naproxen towards COX-2 and 5-LOX. The binding analysis of ligand conformations was performed by OEDocking 3.2.0.2 software. The binding potential assessment revealed that thiourea derivatives of naproxen exhibited a comparable binding affinity as naproxen towards COX-2. The highest number of key binding interactions with 5-LOX was formed by compound 5, whereas compound 6 established the most stable complex (-9.29 kcal/mol). According to the obtained results, derivatives 5 and 6 can be considered as dual COX-2/5-LOX inhibitors with potential anti-inflammatory activity. However, none of the investigated compounds were able to form three hydrogen bonds with the binding site of COX-2, as well as three key hydrogen bonds with the active site of 5-LOX.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings
T1  - In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen
SP  - 475
EP  - 478
DO  - 10.46793/ICCBI23.475N
ER  - 

@conference{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Vesović, Marina and Živanović, Ana and Radić, Gordana and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "Design of dual COX-2/5-LOX inhibitors can be considered an adequate approach in the development of new anti-inflammatory drugs with less pronounced side effects. The aim of the present research was to examine the binding potential of the seven newly designed thiourea derivatives of naproxen towards COX-2 and 5-LOX. The binding analysis of ligand conformations was performed by OEDocking 3.2.0.2 software. The binding potential assessment revealed that thiourea derivatives of naproxen exhibited a comparable binding affinity as naproxen towards COX-2. The highest number of key binding interactions with 5-LOX was formed by compound 5, whereas compound 6 established the most stable complex (-9.29 kcal/mol). According to the obtained results, derivatives 5 and 6 can be considered as dual COX-2/5-LOX inhibitors with potential anti-inflammatory activity. However, none of the investigated compounds were able to form three hydrogen bonds with the binding site of COX-2, as well as three key hydrogen bonds with the active site of 5-LOX.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings",
title = "In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen",
pages = "475-478",
doi = "10.46793/ICCBI23.475N"
}

Nedeljković, N., Dobričić, V., Vesović, M., Živanović, A., Radić, G., Vujić, Z.,& Nikolić, M.. (2023). In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen. in 2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings
Institute for Information Technologies, University of Kragujevac, Serbia., 475-478.
https://doi.org/10.46793/ICCBI23.475N

Nedeljković N, Dobričić V, Vesović M, Živanović A, Radić G, Vujić Z, Nikolić M. In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen. in 2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings. 2023;:475-478.
doi:10.46793/ICCBI23.475N .

Nedeljković, Nikola, Dobričić, Vladimir, Vesović, Marina, Živanović, Ana, Radić, Gordana, Vujić, Zorica, Nikolić, Miloš, "In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen" in 2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings (2023):475-478,
https://doi.org/10.46793/ICCBI23.475N . .

TY  - JOUR
AU  - Jovanović Macura, Irena
AU  - Živanović, Ana
AU  - Perović, Milka
AU  - Ćirić, Jelena
AU  - Major, Tamara
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5121
AB  - Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease
VL  - 24
IS  - 18
DO  - 10.3390/ijms241814092
ER  - 

@article{
author = "Jovanović Macura, Irena and Živanović, Ana and Perović, Milka and Ćirić, Jelena and Major, Tamara and Kanazir, Selma and Ivković, Sanja",
year = "2023",
abstract = "Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease",
volume = "24",
number = "18",
doi = "10.3390/ijms241814092"
}

Jovanović Macura, I., Živanović, A., Perović, M., Ćirić, J., Major, T., Kanazir, S.,& Ivković, S.. (2023). The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease. in International Journal of Molecular Sciences
MDPI., 24(18).
https://doi.org/10.3390/ijms241814092

Jovanović Macura I, Živanović A, Perović M, Ćirić J, Major T, Kanazir S, Ivković S. The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease. in International Journal of Molecular Sciences. 2023;24(18).
doi:10.3390/ijms241814092 .

Jovanović Macura, Irena, Živanović, Ana, Perović, Milka, Ćirić, Jelena, Major, Tamara, Kanazir, Selma, Ivković, Sanja, "The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease" in International Journal of Molecular Sciences, 24, no. 18 (2023),
https://doi.org/10.3390/ijms241814092 . .