Živanović, Jasmina

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

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

(John Wiley and Sons, 2024)

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

Morfofiziološke karakteristike kore nadbubrežne žlezde nakon aplikacije daidzeina u pacovskom modelu uznapredovale andropauze

Ajdžanović, Vladimir; Čukuranović-Kokoris, Jovana; Miler, Marko; Šošić-Jurjević, Branka; Živanović, Jasmina; Marković Filipović, Jelena; Milošević, Verica; Filipović, Branko

(Niš: University of Niš, Faculty of Medicine, 2023)

TY  - CONF
AU  - Ajdžanović, Vladimir
AU  - Čukuranović-Kokoris, Jovana
AU  - Miler, Marko
AU  - Šošić-Jurjević, Branka
AU  - Živanović, Jasmina
AU  - Marković Filipović, Jelena
AU  - Milošević, Verica
AU  - Filipović, Branko
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6405
AB  - Uvod. Aplikacija daidzeina može predstavljati efikasnu i manje rizičnu altemativu indikovanoj, klasičnoj estrogenizaciji starijih muškaraca. Cilj ove studije je podrazumevao morfofiziološku analizu kore nadbubrežne žlezde u pacovskom modelu uznapredovale andropauze, nakon primene daidzeina.
Materijal i metode. Sredovečni (16 meseci stari) pacovi Wistar soja su razdeljeni u
lažno operisanu (SO; n=8), orhidektomisanu (Orx; n=8) i daidzeinom tretiranu orhidektomisanu (Orx+D; n=8) grupu. Daidzein (30 mg/kg t.m./dan) je subkutano davan tri nedelje, dok su SO i Orx grupa dobijale samo rastvarač tokom istog perioda. Ciljevi su realizovani korišćenjem stereologije, histohemije/imunohistohemije, imunoeseja i ultrastruktume analize.
Rezultati. Tretman daidzeinom je značajno uvećao volumene ćelija i jedara zone glomeruloze 
za 32% i 41% tim redom, ali je i snizio (p<0.05) nivo cirkulišućeg aldosterona za 61%, sve u 
poređenju sa odgovarajućim parametrima kod Orx zivotinja. Takođe, daidzein je značajno smanjio 
volumen jedara ćelija zone fascikulate, kao i tkivni i cirkulišući nivo kortikosterona, za 24%, 48% i 33% 
navedenim redom, te izrazito (p<0.05) povisio cirkulišući nivo DHEA za oko 4.6 puta, sve u 
poređenju sa odgovarajućim parametrima kod Orx pacova. Daidzeinom prouzrokovano preusmeravanje 
puteva kortikosteroidogeneze ka produkciji adrenalnih androgena bilo je u skladu sa ultrastruktumim nalazom i rearanžmanima kapilarne rnreže u okviru konkretnih zona kore nadbubrežne zlezde.
Zaključak. Imajući u vidu sklad efekata daidzeina u ispitivanom kontekstu, kao relativnu bezbednost njegove upotrebe, moglo bi se reći da daidzein ima perspektivu u tretrnanu starenjem uzorokovanog gubitka androgena, te hiperfunkcije hipotalamo-hipofizno-adrenalne ose i povezanih metaboličkih poremećaja kod muškaraca.
AB  - Introduction. Daidzein application may represent effective and less harmful alternative to indicated, classical estrogenization of the aging men. The aim of this study was to perform morphophysiological analysis of the adrenal cortex, after daidzein supplementation in a rat model of the severe andropause.
Material and methods. Middle-aged (16 months old) Wistar rats were divided into sham operated (SO; n=8), orchidectomized (Orx; n=8) and daidzein treated orchidectomized (Orx+D; n=8) groups. Daidzein (30 mg/kg b.m./day) was administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using stereology, histochemistry/immunohistochemistry, immunoassays and ultrastructural analysis.
Results. Daidzein treatment significantly increased volumes of the zona glomerulosa cell and nuclei by 32% and 41% respectively, but decreased (p<0.05) circulating aldosterone levels by 61%, all in comparison with the adequate parameters in Orx animals. Also, daidzein significantly decreased zona fasciculata cell nuclei volume, as well as both the adrenal and circulating levels of corticosterone, by 24%, 48% and 33% respectively, but strongly (p<0.05) increased the circulating level of DHEA by about 4.6 times, all when compared to the corresponding parameters of Orx rats. Daidzein-induced shunting of the corticosteroidogenesis pathways towards adrenal androgens production corresponded to the ultrastructural findings and zonal capillary network rearrangements.
Conclusion. Given the coherence of its effects and relative safety, daidzein could be the remedy of choice for the treatment of aging-caused androgen deprivation and the hypothalamo-pituitary-adrenal axis hyperfunction/related metabolic issues in males.
PB  - Niš: University of Niš, Faculty of Medicine
C3  - Abstract Book: 8th Congress of Serbian Anatomical Society of Serbia with international participation; 2023 Sep 21-23; Niš, Serbia
T1  - Morfofiziološke karakteristike kore nadbubrežne žlezde nakon aplikacije daidzeina u pacovskom modelu uznapredovale andropauze
T1  - Morphophysiology of the adrenal cortex after daidzein application in a rat model of the severe andropause
SP  - 166
EP  - 167
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6405
ER  - 
@conference{
author = "Ajdžanović, Vladimir and Čukuranović-Kokoris, Jovana and Miler, Marko and Šošić-Jurjević, Branka and Živanović, Jasmina and Marković Filipović, Jelena and Milošević, Verica and Filipović, Branko",
year = "2023",
abstract = "Uvod. Aplikacija daidzeina može predstavljati efikasnu i manje rizičnu altemativu indikovanoj, klasičnoj estrogenizaciji starijih muškaraca. Cilj ove studije je podrazumevao morfofiziološku analizu kore nadbubrežne žlezde u pacovskom modelu uznapredovale andropauze, nakon primene daidzeina.
Materijal i metode. Sredovečni (16 meseci stari) pacovi Wistar soja su razdeljeni u
lažno operisanu (SO; n=8), orhidektomisanu (Orx; n=8) i daidzeinom tretiranu orhidektomisanu (Orx+D; n=8) grupu. Daidzein (30 mg/kg t.m./dan) je subkutano davan tri nedelje, dok su SO i Orx grupa dobijale samo rastvarač tokom istog perioda. Ciljevi su realizovani korišćenjem stereologije, histohemije/imunohistohemije, imunoeseja i ultrastruktume analize.
Rezultati. Tretman daidzeinom je značajno uvećao volumene ćelija i jedara zone glomeruloze 
za 32% i 41% tim redom, ali je i snizio (p<0.05) nivo cirkulišućeg aldosterona za 61%, sve u 
poređenju sa odgovarajućim parametrima kod Orx zivotinja. Takođe, daidzein je značajno smanjio 
volumen jedara ćelija zone fascikulate, kao i tkivni i cirkulišući nivo kortikosterona, za 24%, 48% i 33% 
navedenim redom, te izrazito (p<0.05) povisio cirkulišući nivo DHEA za oko 4.6 puta, sve u 
poređenju sa odgovarajućim parametrima kod Orx pacova. Daidzeinom prouzrokovano preusmeravanje 
puteva kortikosteroidogeneze ka produkciji adrenalnih androgena bilo je u skladu sa ultrastruktumim nalazom i rearanžmanima kapilarne rnreže u okviru konkretnih zona kore nadbubrežne zlezde.
Zaključak. Imajući u vidu sklad efekata daidzeina u ispitivanom kontekstu, kao relativnu bezbednost njegove upotrebe, moglo bi se reći da daidzein ima perspektivu u tretrnanu starenjem uzorokovanog gubitka androgena, te hiperfunkcije hipotalamo-hipofizno-adrenalne ose i povezanih metaboličkih poremećaja kod muškaraca., Introduction. Daidzein application may represent effective and less harmful alternative to indicated, classical estrogenization of the aging men. The aim of this study was to perform morphophysiological analysis of the adrenal cortex, after daidzein supplementation in a rat model of the severe andropause.
Material and methods. Middle-aged (16 months old) Wistar rats were divided into sham operated (SO; n=8), orchidectomized (Orx; n=8) and daidzein treated orchidectomized (Orx+D; n=8) groups. Daidzein (30 mg/kg b.m./day) was administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using stereology, histochemistry/immunohistochemistry, immunoassays and ultrastructural analysis.
Results. Daidzein treatment significantly increased volumes of the zona glomerulosa cell and nuclei by 32% and 41% respectively, but decreased (p<0.05) circulating aldosterone levels by 61%, all in comparison with the adequate parameters in Orx animals. Also, daidzein significantly decreased zona fasciculata cell nuclei volume, as well as both the adrenal and circulating levels of corticosterone, by 24%, 48% and 33% respectively, but strongly (p<0.05) increased the circulating level of DHEA by about 4.6 times, all when compared to the corresponding parameters of Orx rats. Daidzein-induced shunting of the corticosteroidogenesis pathways towards adrenal androgens production corresponded to the ultrastructural findings and zonal capillary network rearrangements.
Conclusion. Given the coherence of its effects and relative safety, daidzein could be the remedy of choice for the treatment of aging-caused androgen deprivation and the hypothalamo-pituitary-adrenal axis hyperfunction/related metabolic issues in males.",
publisher = "Niš: University of Niš, Faculty of Medicine",
journal = "Abstract Book: 8th Congress of Serbian Anatomical Society of Serbia with international participation; 2023 Sep 21-23; Niš, Serbia",
title = "Morfofiziološke karakteristike kore nadbubrežne žlezde nakon aplikacije daidzeina u pacovskom modelu uznapredovale andropauze, Morphophysiology of the adrenal cortex after daidzein application in a rat model of the severe andropause",
pages = "166-167",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6405"
}
Ajdžanović, V., Čukuranović-Kokoris, J., Miler, M., Šošić-Jurjević, B., Živanović, J., Marković Filipović, J., Milošević, V.,& Filipović, B.. (2023). Morfofiziološke karakteristike kore nadbubrežne žlezde nakon aplikacije daidzeina u pacovskom modelu uznapredovale andropauze. in Abstract Book: 8th Congress of Serbian Anatomical Society of Serbia with international participation; 2023 Sep 21-23; Niš, Serbia
Niš: University of Niš, Faculty of Medicine., 166-167.
https://hdl.handle.net/21.15107/rcub_ibiss_6405
Ajdžanović V, Čukuranović-Kokoris J, Miler M, Šošić-Jurjević B, Živanović J, Marković Filipović J, Milošević V, Filipović B. Morfofiziološke karakteristike kore nadbubrežne žlezde nakon aplikacije daidzeina u pacovskom modelu uznapredovale andropauze. in Abstract Book: 8th Congress of Serbian Anatomical Society of Serbia with international participation; 2023 Sep 21-23; Niš, Serbia. 2023;:166-167.
https://hdl.handle.net/21.15107/rcub_ibiss_6405 .
Ajdžanović, Vladimir, Čukuranović-Kokoris, Jovana, Miler, Marko, Šošić-Jurjević, Branka, Živanović, Jasmina, Marković Filipović, Jelena, Milošević, Verica, Filipović, Branko, "Morfofiziološke karakteristike kore nadbubrežne žlezde nakon aplikacije daidzeina u pacovskom modelu uznapredovale andropauze" in Abstract Book: 8th Congress of Serbian Anatomical Society of Serbia with international participation; 2023 Sep 21-23; Niš, Serbia (2023):166-167,
https://hdl.handle.net/21.15107/rcub_ibiss_6405 .

Adrenocortical vascular network and hormonal output after daidzein application in a rat model of the mild andropause

Čukuranović-Kokoris, Jovana; Đorđević, Miodrag; Miler, Marko; Živanović, Jasmina; Marković Filipović, Jelena; Stanković Đorević, Dobrila; Čukuranović, Rade; Milošević, Verica; Filipović, Branko; Ajdžanović, Vladimir

(bioscientifica, 2023)

TY  - CONF
AU  - Čukuranović-Kokoris, Jovana
AU  - Đorđević, Miodrag
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Marković Filipović, Jelena
AU  - Stanković Đorević, Dobrila
AU  - Čukuranović, Rade
AU  - Milošević, Verica
AU  - Filipović, Branko
AU  - Ajdžanović, Vladimir
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6229
AB  - Soy isoflavone daidzein exerts some beneficial effects in different ageing-related, chronic diseases and may represent a promising alternative to classical estrogenization of the prostate cancer suffering subjects. The aim of this study was to examine the effects of daidzein on the adrenocortical vascular network and hormonal output in a rat model of the mild andropause. Adult (3 months old) Wistar rats were divided into sham-operated (SO; n=7), orchidectomized (Orx; n=7) and daidzein treated orchidectomized (Orx+D; n=7) groups. Daidzein (30 mg/kg b.m./day) was administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Adrenocortical vascular network properties were identified using Novelli histochemical staining, vascular endothelial growth factor (VEGF) immunostaining and the newCast stereological software. Blood concentrations of aldosterone, corticosterone and DHEAS were measured by immunoassays. Volume densities of blood vessels and VEGF depots within the adrenal cortex were not significantly changed after daidzein treatment, although there was a tendency of decrease of these parameters. On the other hand, daidzein application increased (P<0.05) blood concentration of aldosterone by more than 2.5 times and 41%, in comparison with the same parameter in sham-operated and orchidectomized group, respectively. Corticosterone concentration in daidzein-treated, orchidectomized rats showed a tendency of elevation (P>0.05) compared to the both SO animals and orchidectomy alone. DHEAS blood concentration after daidzein application remained at the level of the Orx group, which in both cases ment elevation (P<0.05) by around 80% in comparison with the same parameter in SO group. We conclude that daidzein significantly increases aldosterone and to some lower extent corticosterone output in a rat model of the mild andropause, without significant rearrangements of the entire adrenal cortex vascular network.
PB  - bioscientifica
C3  - 25th European Congress of Endocrinology; 2023 Maz 13-16; Istanbul, Turkey
T1  - Adrenocortical vascular network and hormonal output after daidzein application in a rat model of the mild andropause
DO  - 10.1530/endoabs.90.EP63
SP  - 394
EP  - 395
ER  - 
@conference{
author = "Čukuranović-Kokoris, Jovana and Đorđević, Miodrag and Miler, Marko and Živanović, Jasmina and Marković Filipović, Jelena and Stanković Đorević, Dobrila and Čukuranović, Rade and Milošević, Verica and Filipović, Branko and Ajdžanović, Vladimir",
year = "2023",
abstract = "Soy isoflavone daidzein exerts some beneficial effects in different ageing-related, chronic diseases and may represent a promising alternative to classical estrogenization of the prostate cancer suffering subjects. The aim of this study was to examine the effects of daidzein on the adrenocortical vascular network and hormonal output in a rat model of the mild andropause. Adult (3 months old) Wistar rats were divided into sham-operated (SO; n=7), orchidectomized (Orx; n=7) and daidzein treated orchidectomized (Orx+D; n=7) groups. Daidzein (30 mg/kg b.m./day) was administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Adrenocortical vascular network properties were identified using Novelli histochemical staining, vascular endothelial growth factor (VEGF) immunostaining and the newCast stereological software. Blood concentrations of aldosterone, corticosterone and DHEAS were measured by immunoassays. Volume densities of blood vessels and VEGF depots within the adrenal cortex were not significantly changed after daidzein treatment, although there was a tendency of decrease of these parameters. On the other hand, daidzein application increased (P<0.05) blood concentration of aldosterone by more than 2.5 times and 41%, in comparison with the same parameter in sham-operated and orchidectomized group, respectively. Corticosterone concentration in daidzein-treated, orchidectomized rats showed a tendency of elevation (P>0.05) compared to the both SO animals and orchidectomy alone. DHEAS blood concentration after daidzein application remained at the level of the Orx group, which in both cases ment elevation (P<0.05) by around 80% in comparison with the same parameter in SO group. We conclude that daidzein significantly increases aldosterone and to some lower extent corticosterone output in a rat model of the mild andropause, without significant rearrangements of the entire adrenal cortex vascular network.",
publisher = "bioscientifica",
journal = "25th European Congress of Endocrinology; 2023 Maz 13-16; Istanbul, Turkey",
title = "Adrenocortical vascular network and hormonal output after daidzein application in a rat model of the mild andropause",
doi = "10.1530/endoabs.90.EP63",
pages = "394-395"
}
Čukuranović-Kokoris, J., Đorđević, M., Miler, M., Živanović, J., Marković Filipović, J., Stanković Đorević, D., Čukuranović, R., Milošević, V., Filipović, B.,& Ajdžanović, V.. (2023). Adrenocortical vascular network and hormonal output after daidzein application in a rat model of the mild andropause. in 25th European Congress of Endocrinology; 2023 Maz 13-16; Istanbul, Turkey
bioscientifica., 394-395.
https://doi.org/10.1530/endoabs.90.EP63
Čukuranović-Kokoris J, Đorđević M, Miler M, Živanović J, Marković Filipović J, Stanković Đorević D, Čukuranović R, Milošević V, Filipović B, Ajdžanović V. Adrenocortical vascular network and hormonal output after daidzein application in a rat model of the mild andropause. in 25th European Congress of Endocrinology; 2023 Maz 13-16; Istanbul, Turkey. 2023;:394-395.
doi:10.1530/endoabs.90.EP63 .
Čukuranović-Kokoris, Jovana, Đorđević, Miodrag, Miler, Marko, Živanović, Jasmina, Marković Filipović, Jelena, Stanković Đorević, Dobrila, Čukuranović, Rade, Milošević, Verica, Filipović, Branko, Ajdžanović, Vladimir, "Adrenocortical vascular network and hormonal output after daidzein application in a rat model of the mild andropause" in 25th European Congress of Endocrinology; 2023 Maz 13-16; Istanbul, Turkey (2023):394-395,
https://doi.org/10.1530/endoabs.90.EP63 . .

Supplementary material for the article: Lemon extract reduces hepatic oxidative stress and persulfidation levels by upregulating Nrf2 and Trx1 expression in old rats

Miler, Marko; Živanović, Jasmina

(2023)

TY  - DATA
AU  - Miler, Marko
AU  - Živanović, Jasmina
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6220
AB  - This dataset is a supplementary document of the research article: Lemon extract reduces hepatic oxidative stress and persulfidation levels by upregulating Nrf2 and Trx1 expression in old rats. It contains Table S1 with data about primer pairs used in qPCR analysis and Table S2 with data about antibodies used for western blot, immunofluorescent, and persulfidation analyses.
T1  - Supplementary material for the article: Lemon extract reduces hepatic oxidative stress and persulfidation levels by upregulating Nrf2 and Trx1 expression in old rats
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6220
ER  - 
@misc{
author = "Miler, Marko and Živanović, Jasmina",
year = "2023",
abstract = "This dataset is a supplementary document of the research article: Lemon extract reduces hepatic oxidative stress and persulfidation levels by upregulating Nrf2 and Trx1 expression in old rats. It contains Table S1 with data about primer pairs used in qPCR analysis and Table S2 with data about antibodies used for western blot, immunofluorescent, and persulfidation analyses.",
title = "Supplementary material for the article: Lemon extract reduces hepatic oxidative stress and persulfidation levels by upregulating Nrf2 and Trx1 expression in old rats",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6220"
}
Miler, M.,& Živanović, J.. (2023). Supplementary material for the article: Lemon extract reduces hepatic oxidative stress and persulfidation levels by upregulating Nrf2 and Trx1 expression in old rats. .
https://hdl.handle.net/21.15107/rcub_ibiss_6220
Miler M, Živanović J. Supplementary material for the article: Lemon extract reduces hepatic oxidative stress and persulfidation levels by upregulating Nrf2 and Trx1 expression in old rats. 2023;.
https://hdl.handle.net/21.15107/rcub_ibiss_6220 .
Miler, Marko, Živanović, Jasmina, "Supplementary material for the article: Lemon extract reduces hepatic oxidative stress and persulfidation levels by upregulating Nrf2 and Trx1 expression in old rats" (2023),
https://hdl.handle.net/21.15107/rcub_ibiss_6220 .

Развој женског репродуктивног система и последице пренаталног излагања дексаметазону

Ristić, Nataša; Nestorović, Nataša; Trifunović, Svetlana; Šošić-Jurjević, Branka; Filipović, Branko; Ajdžanović, Vladimir; Živanović, Jasmina; Miler, Marko; Manojlović-Stojanoski, Milica

(Belgrade: Serbian Biological Society, 2022)

TY  - CONF
AU  - Ristić, Nataša
AU  - Nestorović, Nataša
AU  - Trifunović, Svetlana
AU  - Šošić-Jurjević, Branka
AU  - Filipović, Branko
AU  - Ajdžanović, Vladimir
AU  - Živanović, Jasmina
AU  - Miler, Marko
AU  - Manojlović-Stojanoski, Milica
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6695
AB  - Развој организма и хомеостатски механизми се прилагођавају променљивим условима спољашње средине још током пренаталног периода. Женски репродуктивни систем активно реагује адаптирајући развој и диференцирање гонадотропних ћелија хипофизе и оваријума у складу са условима околине.1,2 Различити типови стреса, укључујући хормонске, нутритивне и психолошке изазове могу проузроковати бројне промене које обликују будући репродуктивни капацитет женке и заправо су део пренаталног програмирања физиологије организма. Третман гравидних женки дексаметазоном (Дк) значајно утиче на развој фетуса и опонаша антенаталну терапију гравидних жена глукокортикоидима као најчешће присутни третман у обстетричкој пракси. Стога су гравидне женке пацова Дк третиране (3 x 0,5 мг/кг/тм Дк) од 16. до 18. дана гестације. Пренатално Дк излагање изазвало је смањење масе фетуса непосредно пред рођење. Забележено је значајно смањење апсолутног броја ФСХ (фоликулостимулирајући хормон) и ЛХ (лутеинизирајући хормон) гонадотропних ћелија хипофизе (p < 0,05) од феталног, преко постнаталног, до пуберталног периода у односу на контролне вредности. Паралелно, Дк излагање током феталног развоја проузроковало је смањење волумена оваријума код потомака старих 16 и 38 дана (p < 0,05). Број фоликула је смањен код 16 дана старих потомака, док су поремећај процеса фоликулогенезе и одложен почетак пубертета забележени код потомака старих 38 дана. Можемо закључити да пренатални период развоја снажно утиче на фертилитет женки током репродуктивног периода.
AB  - Razvoj organizma i homeostatski mehanizmi se prilagođavaju promenljivim uslovima spoljašnje sredine još tokom prenatalnog perioda. Ženski reproduktivni sistem aktivno reaguje adaptirajući razvoj i diferenciranje gonadotropnih ćelija hipofize i ovarijuma u skladu sa uslovima okoline.1,2 Različiti tipovi stresa, uključujući hormonske, nutritivne i psihološke izazove mogu prouzrokovati brojne promene koje oblikuju budući reproduktivni kapacitet ženke i zapravo su deo prenatalnog programiranja fiziologije organizma. Tretman gravidnih ženki deksametazonom (Dk) značajno utiče na razvoj fetusa i oponaša antenatalnu terapiju gravidnih žena glukokortikoidima kao najčešće prisutni tretman u obstetričkoj praksi. Stoga su gravidne ženke pacova Dk tretirane (3 x 0,5 mg/kg/tm Dk) od 16. do 18. dana gestacije. Prenatalno Dk izlaganje izazvalo je smanjenje mase fetusa neposredno pred rođenje. Zabeleženo je značajno smanjenje apsolutnog broja FSH (folikulostimulirajući hormon) i LH (luteinizirajući hormon) gonadotropnih ćelija hipofize (p < 0,05) od fetalnog, preko postnatalnog, do pubertalnog perioda u odnosu na kontrolne vrednosti. Paralelno, Dk izlaganje tokom fetalnog razvoja prouzrokovalo je smanjenje volumena ovarijuma kod potomaka starih 16 i 38 dana (p < 0,05). Broj folikula je smanjen kod 16 dana starih potomaka, dok su poremećaj procesa folikulogeneze i odložen početak puberteta zabeleženi kod potomaka starih 38 dana. Možemo zaključiti da prenatalni period razvoja snažno utiče na fertilitet ženki tokom reproduktivnog perioda.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Развој женског репродуктивног система и последице пренаталног излагања дексаметазону
T1  - Razvoj ženskog reproduktivnog sistema i posledice prenatalnog izlaganja deksametazonu
SP  - 379
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6695
ER  - 
@conference{
author = "Ristić, Nataša and Nestorović, Nataša and Trifunović, Svetlana and Šošić-Jurjević, Branka and Filipović, Branko and Ajdžanović, Vladimir and Živanović, Jasmina and Miler, Marko and Manojlović-Stojanoski, Milica",
year = "2022",
abstract = "Развој организма и хомеостатски механизми се прилагођавају променљивим условима спољашње средине још током пренаталног периода. Женски репродуктивни систем активно реагује адаптирајући развој и диференцирање гонадотропних ћелија хипофизе и оваријума у складу са условима околине.1,2 Различити типови стреса, укључујући хормонске, нутритивне и психолошке изазове могу проузроковати бројне промене које обликују будући репродуктивни капацитет женке и заправо су део пренаталног програмирања физиологије организма. Третман гравидних женки дексаметазоном (Дк) значајно утиче на развој фетуса и опонаша антенаталну терапију гравидних жена глукокортикоидима као најчешће присутни третман у обстетричкој пракси. Стога су гравидне женке пацова Дк третиране (3 x 0,5 мг/кг/тм Дк) од 16. до 18. дана гестације. Пренатално Дк излагање изазвало је смањење масе фетуса непосредно пред рођење. Забележено је значајно смањење апсолутног броја ФСХ (фоликулостимулирајући хормон) и ЛХ (лутеинизирајући хормон) гонадотропних ћелија хипофизе (p < 0,05) од феталног, преко постнаталног, до пуберталног периода у односу на контролне вредности. Паралелно, Дк излагање током феталног развоја проузроковало је смањење волумена оваријума код потомака старих 16 и 38 дана (p < 0,05). Број фоликула је смањен код 16 дана старих потомака, док су поремећај процеса фоликулогенезе и одложен почетак пубертета забележени код потомака старих 38 дана. Можемо закључити да пренатални период развоја снажно утиче на фертилитет женки током репродуктивног периода., Razvoj organizma i homeostatski mehanizmi se prilagođavaju promenljivim uslovima spoljašnje sredine još tokom prenatalnog perioda. Ženski reproduktivni sistem aktivno reaguje adaptirajući razvoj i diferenciranje gonadotropnih ćelija hipofize i ovarijuma u skladu sa uslovima okoline.1,2 Različiti tipovi stresa, uključujući hormonske, nutritivne i psihološke izazove mogu prouzrokovati brojne promene koje oblikuju budući reproduktivni kapacitet ženke i zapravo su deo prenatalnog programiranja fiziologije organizma. Tretman gravidnih ženki deksametazonom (Dk) značajno utiče na razvoj fetusa i oponaša antenatalnu terapiju gravidnih žena glukokortikoidima kao najčešće prisutni tretman u obstetričkoj praksi. Stoga su gravidne ženke pacova Dk tretirane (3 x 0,5 mg/kg/tm Dk) od 16. do 18. dana gestacije. Prenatalno Dk izlaganje izazvalo je smanjenje mase fetusa neposredno pred rođenje. Zabeleženo je značajno smanjenje apsolutnog broja FSH (folikulostimulirajući hormon) i LH (luteinizirajući hormon) gonadotropnih ćelija hipofize (p < 0,05) od fetalnog, preko postnatalnog, do pubertalnog perioda u odnosu na kontrolne vrednosti. Paralelno, Dk izlaganje tokom fetalnog razvoja prouzrokovalo je smanjenje volumena ovarijuma kod potomaka starih 16 i 38 dana (p < 0,05). Broj folikula je smanjen kod 16 dana starih potomaka, dok su poremećaj procesa folikulogeneze i odložen početak puberteta zabeleženi kod potomaka starih 38 dana. Možemo zaključiti da prenatalni period razvoja snažno utiče na fertilitet ženki tokom reproduktivnog perioda.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Развој женског репродуктивног система и последице пренаталног излагања дексаметазону, Razvoj ženskog reproduktivnog sistema i posledice prenatalnog izlaganja deksametazonu",
pages = "379",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6695"
}
Ristić, N., Nestorović, N., Trifunović, S., Šošić-Jurjević, B., Filipović, B., Ajdžanović, V., Živanović, J., Miler, M.,& Manojlović-Stojanoski, M.. (2022). Развој женског репродуктивног система и последице пренаталног излагања дексаметазону. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 379.
https://hdl.handle.net/21.15107/rcub_ibiss_6695
Ristić N, Nestorović N, Trifunović S, Šošić-Jurjević B, Filipović B, Ajdžanović V, Živanović J, Miler M, Manojlović-Stojanoski M. Развој женског репродуктивног система и последице пренаталног излагања дексаметазону. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:379.
https://hdl.handle.net/21.15107/rcub_ibiss_6695 .
Ristić, Nataša, Nestorović, Nataša, Trifunović, Svetlana, Šošić-Jurjević, Branka, Filipović, Branko, Ajdžanović, Vladimir, Živanović, Jasmina, Miler, Marko, Manojlović-Stojanoski, Milica, "Развој женског репродуктивног система и последице пренаталног излагања дексаметазону" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):379,
https://hdl.handle.net/21.15107/rcub_ibiss_6695 .

Age-Related Changes in Calcitonin-Producing Thyroid C-Cells of Male Wistar Rats

Filipović, Branko; Ajdžanović, Vladimir; Živanović, Jasmina; Trifunović, Svetlana; Ristić, Nataša; Milošević, Verica; Šošić-Jurjević, Branka

(New York: Cambridge University Press, 2022)

TY  - JOUR
AU  - Filipović, Branko
AU  - Ajdžanović, Vladimir
AU  - Živanović, Jasmina
AU  - Trifunović, Svetlana
AU  - Ristić, Nataša
AU  - Milošević, Verica
AU  - Šošić-Jurjević, Branka 
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4971
AB  - Thyroid C-cells secrete the hormone calcitonin (CT) which acts as an inhibitor of bone resorption. Our aim was to examine the age-related changes in the structure and function of CT-producing C-cells, using histomorphometric, ultrastructural, and biochemical analyses. We used young adult (3-months-old), middle-aged (16-months-old), and old (24-months-old) male rats. The peroxidase-antiperoxidase method was applied for localization of CT. Stereological analysis was performed using the newCAST stereological software package. Serum samples were analyzed for the determination of CT, testosterone (T), calcium (Ca2+), and phosphorus (P). We found a significant increase in the volume density (Vv) of C-cells in both older groups (p < 0.05). The percentage of smaller volume range C-cells increased (p < 0.0001), while the proportion of greater volume range C-cells decreased (p < 0.05) with ageing. Ultrastructural analysis revealed a larger number of secretory granules in older rats. Serum CT increased (p < 0.001), while serum T and P were reduced (p < 0.01) in older rats. Serum Ca2+ was lower (p < 0.0001) in middle-aged rats compared to young adults. We revealed a 20% incidence of C-cell hyperplasia in older rats and one case of medullary thyroid carcinoma in an old rat. Our findings indicate that the ageing process causes significant histomorphometric changes at the thyroid C-cell level.
PB  - New York: Cambridge University Press
T2  - Microscopy and Microanalysis
T1  - Age-Related Changes in Calcitonin-Producing Thyroid C-Cells of Male Wistar Rats
DO  - 10.1017/S1431927622000721
ER  - 
@article{
author = "Filipović, Branko and Ajdžanović, Vladimir and Živanović, Jasmina and Trifunović, Svetlana and Ristić, Nataša and Milošević, Verica and Šošić-Jurjević, Branka ",
year = "2022",
abstract = "Thyroid C-cells secrete the hormone calcitonin (CT) which acts as an inhibitor of bone resorption. Our aim was to examine the age-related changes in the structure and function of CT-producing C-cells, using histomorphometric, ultrastructural, and biochemical analyses. We used young adult (3-months-old), middle-aged (16-months-old), and old (24-months-old) male rats. The peroxidase-antiperoxidase method was applied for localization of CT. Stereological analysis was performed using the newCAST stereological software package. Serum samples were analyzed for the determination of CT, testosterone (T), calcium (Ca2+), and phosphorus (P). We found a significant increase in the volume density (Vv) of C-cells in both older groups (p < 0.05). The percentage of smaller volume range C-cells increased (p < 0.0001), while the proportion of greater volume range C-cells decreased (p < 0.05) with ageing. Ultrastructural analysis revealed a larger number of secretory granules in older rats. Serum CT increased (p < 0.001), while serum T and P were reduced (p < 0.01) in older rats. Serum Ca2+ was lower (p < 0.0001) in middle-aged rats compared to young adults. We revealed a 20% incidence of C-cell hyperplasia in older rats and one case of medullary thyroid carcinoma in an old rat. Our findings indicate that the ageing process causes significant histomorphometric changes at the thyroid C-cell level.",
publisher = "New York: Cambridge University Press",
journal = "Microscopy and Microanalysis",
title = "Age-Related Changes in Calcitonin-Producing Thyroid C-Cells of Male Wistar Rats",
doi = "10.1017/S1431927622000721"
}
Filipović, B., Ajdžanović, V., Živanović, J., Trifunović, S., Ristić, N., Milošević, V.,& Šošić-Jurjević, B.. (2022). Age-Related Changes in Calcitonin-Producing Thyroid C-Cells of Male Wistar Rats. in Microscopy and Microanalysis
New York: Cambridge University Press..
https://doi.org/10.1017/S1431927622000721
Filipović B, Ajdžanović V, Živanović J, Trifunović S, Ristić N, Milošević V, Šošić-Jurjević B. Age-Related Changes in Calcitonin-Producing Thyroid C-Cells of Male Wistar Rats. in Microscopy and Microanalysis. 2022;.
doi:10.1017/S1431927622000721 .
Filipović, Branko, Ajdžanović, Vladimir, Živanović, Jasmina, Trifunović, Svetlana, Ristić, Nataša, Milošević, Verica, Šošić-Jurjević, Branka , "Age-Related Changes in Calcitonin-Producing Thyroid C-Cells of Male Wistar Rats" in Microscopy and Microanalysis (2022),
https://doi.org/10.1017/S1431927622000721 . .
1

Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis.

Šošić-Jurjević, Branka ; Trifunović, Svetlana; Živanović, Jasmina; Ajdžanović, Vladimir; Miler, Marko; Ristić, Nataša; Filipović, Branko

(Basel: MDPI, 2022)

TY  - JOUR
AU  - Šošić-Jurjević, Branka 
AU  - Trifunović, Svetlana
AU  - Živanović, Jasmina
AU  - Ajdžanović, Vladimir
AU  - Miler, Marko
AU  - Ristić, Nataša
AU  - Filipović, Branko
PY  - 2022
UR  - https://www.mdpi.com/1422-0067/23/2/791
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35054977
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4769
AB  - Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D3; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D3 group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T4, TSH, and calcitonin in serum remained unaltered. Vit. D3 treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis.
IS  - 2
VL  - 23
DO  - 10.3390/ijms23020791
SP  - 791
ER  - 
@article{
author = "Šošić-Jurjević, Branka  and Trifunović, Svetlana and Živanović, Jasmina and Ajdžanović, Vladimir and Miler, Marko and Ristić, Nataša and Filipović, Branko",
year = "2022",
abstract = "Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D3; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D3 group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T4, TSH, and calcitonin in serum remained unaltered. Vit. D3 treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis.",
number = "2",
volume = "23",
doi = "10.3390/ijms23020791",
pages = "791"
}
Šošić-Jurjević, B., Trifunović, S., Živanović, J., Ajdžanović, V., Miler, M., Ristić, N.,& Filipović, B.. (2022). Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis.. in International Journal of Molecular Sciences
Basel: MDPI., 23(2), 791.
https://doi.org/10.3390/ijms23020791
Šošić-Jurjević B, Trifunović S, Živanović J, Ajdžanović V, Miler M, Ristić N, Filipović B. Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis.. in International Journal of Molecular Sciences. 2022;23(2):791.
doi:10.3390/ijms23020791 .
Šošić-Jurjević, Branka , Trifunović, Svetlana, Živanović, Jasmina, Ajdžanović, Vladimir, Miler, Marko, Ristić, Nataša, Filipović, Branko, "Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis." in International Journal of Molecular Sciences, 23, no. 2 (2022):791,
https://doi.org/10.3390/ijms23020791 . .
1
3
4

Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause

Živanović, Jasmina; Jarić, Ivana; Ajdžanović, Vladimir; Miler, Marko; Stanković, Sanja; Milošević, Verica; Filipović, Branko

(Elsevier GmbH, 2022)

TY  - JOUR
AU  - Živanović, Jasmina
AU  - Jarić, Ivana
AU  - Ajdžanović, Vladimir
AU  - Miler, Marko
AU  - Stanković, Sanja
AU  - Milošević, Verica
AU  - Filipović, Branko
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S094096022100162X
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4499
AB  - Soy isoflavone genistein interplays with numerous physiological or pathophysiological processes during ageing. However, its protective role and underlying mechanisms of action in the regulation of calcium (Ca2+) and phosphate (Pi) homeostasis in an animal model of the andropause are yet to be fully clarified. Wistar male rats (16-month-old) were divided into sham-operated, orchidectomized, orchidectomized estradiol-treated (0.625 mg/kg b.m./day) and orchidectomized genistein-treated (30 mg/kg b.m./day) groups. Treatments were administered subcutaneously for 3 weeks, while the controls received vehicle alone. Estradiol treatment increased the expression level of fibroblast growth factor receptor (FGFR) and parathyroid hormone 1 receptor (PTH1R), and activated mitogen – activated protein kinase kinase 1/2 (MEK 1/2) signaling pathway in the kidneys. Genistein application induced a prominent gene and protein expression of Klotho and downregulated the expression of FGFR and PTH1R in the kidney of andropausal rats. Activation of protein kinase B (Akt) signalling pathway was observed, while MEK 1/2 signaling pathway wasn't altered after genistein treatment. The increase of 25 (OH) vitamin D in the serum and decrease in Ca2+ urine content was observed after genistein application. Our findings strongly suggest genistein as a potent biocompound with beneficial effects on the regulation of Ca2+ and Pi homeostasis, especially during aging process when the balance of mineral metabolism is impaired. These novel data provide closer insights into the physiological roles of genistein in the regulation of mineral homeostasis.
PB  - Elsevier GmbH
T2  - Annals of Anatomy - Anatomischer Anzeiger
T1  - Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause
VL  - 239
DO  - 10.1016/j.aanat.2021.151836
SP  - 151836
ER  - 
@article{
author = "Živanović, Jasmina and Jarić, Ivana and Ajdžanović, Vladimir and Miler, Marko and Stanković, Sanja and Milošević, Verica and Filipović, Branko",
year = "2022",
abstract = "Soy isoflavone genistein interplays with numerous physiological or pathophysiological processes during ageing. However, its protective role and underlying mechanisms of action in the regulation of calcium (Ca2+) and phosphate (Pi) homeostasis in an animal model of the andropause are yet to be fully clarified. Wistar male rats (16-month-old) were divided into sham-operated, orchidectomized, orchidectomized estradiol-treated (0.625 mg/kg b.m./day) and orchidectomized genistein-treated (30 mg/kg b.m./day) groups. Treatments were administered subcutaneously for 3 weeks, while the controls received vehicle alone. Estradiol treatment increased the expression level of fibroblast growth factor receptor (FGFR) and parathyroid hormone 1 receptor (PTH1R), and activated mitogen – activated protein kinase kinase 1/2 (MEK 1/2) signaling pathway in the kidneys. Genistein application induced a prominent gene and protein expression of Klotho and downregulated the expression of FGFR and PTH1R in the kidney of andropausal rats. Activation of protein kinase B (Akt) signalling pathway was observed, while MEK 1/2 signaling pathway wasn't altered after genistein treatment. The increase of 25 (OH) vitamin D in the serum and decrease in Ca2+ urine content was observed after genistein application. Our findings strongly suggest genistein as a potent biocompound with beneficial effects on the regulation of Ca2+ and Pi homeostasis, especially during aging process when the balance of mineral metabolism is impaired. These novel data provide closer insights into the physiological roles of genistein in the regulation of mineral homeostasis.",
publisher = "Elsevier GmbH",
journal = "Annals of Anatomy - Anatomischer Anzeiger",
title = "Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause",
volume = "239",
doi = "10.1016/j.aanat.2021.151836",
pages = "151836"
}
Živanović, J., Jarić, I., Ajdžanović, V., Miler, M., Stanković, S., Milošević, V.,& Filipović, B.. (2022). Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause. in Annals of Anatomy - Anatomischer Anzeiger
Elsevier GmbH., 239, 151836.
https://doi.org/10.1016/j.aanat.2021.151836
Živanović J, Jarić I, Ajdžanović V, Miler M, Stanković S, Milošević V, Filipović B. Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause. in Annals of Anatomy - Anatomischer Anzeiger. 2022;239:151836.
doi:10.1016/j.aanat.2021.151836 .
Živanović, Jasmina, Jarić, Ivana, Ajdžanović, Vladimir, Miler, Marko, Stanković, Sanja, Milošević, Verica, Filipović, Branko, "Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause" in Annals of Anatomy - Anatomischer Anzeiger, 239 (2022):151836,
https://doi.org/10.1016/j.aanat.2021.151836 . .
2
2

Eриоцитрин, полифенол из лимуна, унапређује редокс средину у јетри старих пацова

Miler, Marko; Živanović, Jasmina; Ristić, Nataša; Manojlović-Stojanoski, Milica; Trifunović, Svetlana; Šošić-Jurjević, Branka ; Nestorović, Nataša; Filipović, Branko; Ajdžanović, Vladimir

(Belgrade: Serbian Biological Society, 2022)

TY  - CONF
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Ristić, Nataša
AU  - Manojlović-Stojanoski, Milica
AU  - Trifunović, Svetlana
AU  - Šošić-Jurjević, Branka 
AU  - Nestorović, Nataša
AU  - Filipović, Branko
AU  - Ajdžanović, Vladimir
PY  - 2022
UR  - https://www.serbiosoc.org.rs/?page_id=702
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6034
AB  - Старење доводи до акумулације и смањене елиминације реактивних врста,
стварајући оксидациону средину у јетри. Једна од могућих опција за одлагање овог
догађаја је употреба антиоксиданата из цитруса у склопу процеса здравог старења.
Стога, ова студија je имала за циљ да истражи ефекте ериоцитрина (ЕРИ),
полифенола из лимуна, на редокс средину у јетри код 24-месечних мужјака Wistar
пацова. ЕРИ (30 мг/кг т.м.) је даван орално, једном дневно током четири недеље.
Контролне групе су примиле или носач третмана (сунцокретово уље) или су остале
интактне. Примењена методологија подразумевала је имуноблот и qPCR анализу,
детекцију нивоа персулфидације у гелу и биохемијске анализе. Третман ЕРИ
повећао је експресију гена и протеина за нуклеарни фактор 2 (Nrf2), тиоредоксин
(Trx) 1, глутатион пероксидазу и редуктазу. Експресија гена супероксид дисмутазе
2 (SOD2) и Trx2 је смањена, док је примена ЕРИ повећала експресију протеина
SOD2. Штавише, ЕРИ је смањио концентрацију малондиалдехида, маркера
оксидативног оштећења у ћелији. Показали смо смањење персулфидације протеина
у јетри након третмана ЕРИ, док су генска и протеинска експресија ензима који
производе H2S остале непромењене. У закључку, ЕРИ појачава регулацију редокс
регулатора јетре Nrf2, који активира антиоксидативни одбрамбени систем и Trx1,
што доводи до смањења нивоа персулфидације протеина у јетри. Наши налази
указују на потенцијал ЕРИ у унапређењу редокс средине у јетри старих пацова.
AB  - Starenje dovodi do akumulacije i smanjene eliminacije reaktivnih vrsta,
stvarajući oksidacionu sredinu u jetri. Jedna od mogućih opcija za odlaganje ovog
događaja je upotreba antioksidanata iz citrusa u sklopu procesa zdravog starenja.
Stoga, ova studija je imala za cilj da istraži efekte eriocitrina (ERI),
polifenola iz limuna, na redoks sredinu u jetri kod 24-mesečnih mužjaka Wistar
pacova. ERI (30 mg/kg t.m.) je davan oralno, jednom dnevno tokom četiri nedelje.
Kontrolne grupe su primile ili nosač tretmana (suncokretovo ulje) ili su ostale
intaktne. Primenjena metodologija podrazumevala je imunoblot i qPCR analizu,
detekciju nivoa persulfidacije u gelu i biohemijske analize. Tretman ERI
povećao je ekspresiju gena i proteina za nuklearni faktor 2 (Nrf2), tioredoksin
(Trx) 1, glutation peroksidazu i reduktazu. Ekspresija gena superoksid dismutaze
2 (SOD2) i Trx2 je smanjena, dok je primena ERI povećala ekspresiju proteina
SOD2. Štaviše, ERI je smanjio koncentraciju malondialdehida, markera
oksidativnog oštećenja u ćeliji. Pokazali smo smanjenje persulfidacije proteina
u jetri nakon tretmana ERI, dok su genska i proteinska ekspresija enzima koji
proizvode H2S ostale nepromenjene. U zaključku, ERI pojačava regulaciju redoks
regulatora jetre Nrf2, koji aktivira antioksidativni odbrambeni sistem i Trx1,
što dovodi do smanjenja nivoa persulfidacije proteina u jetri. Naši nalazi
ukazuju na potencijal ERI u unapređenju redoks sredine u jetri starih pacova.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Eриоцитрин, полифенол из лимуна, унапређује редокс средину у јетри старих пацова
T1  - Eriocitrin, polifenol iz limuna, unapređuje redoks sredinu u jetri starih pacova
SP  - 374
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6034
ER  - 
@conference{
author = "Miler, Marko and Živanović, Jasmina and Ristić, Nataša and Manojlović-Stojanoski, Milica and Trifunović, Svetlana and Šošić-Jurjević, Branka  and Nestorović, Nataša and Filipović, Branko and Ajdžanović, Vladimir",
year = "2022",
abstract = "Старење доводи до акумулације и смањене елиминације реактивних врста,
стварајући оксидациону средину у јетри. Једна од могућих опција за одлагање овог
догађаја је употреба антиоксиданата из цитруса у склопу процеса здравог старења.
Стога, ова студија je имала за циљ да истражи ефекте ериоцитрина (ЕРИ),
полифенола из лимуна, на редокс средину у јетри код 24-месечних мужјака Wistar
пацова. ЕРИ (30 мг/кг т.м.) је даван орално, једном дневно током четири недеље.
Контролне групе су примиле или носач третмана (сунцокретово уље) или су остале
интактне. Примењена методологија подразумевала је имуноблот и qPCR анализу,
детекцију нивоа персулфидације у гелу и биохемијске анализе. Третман ЕРИ
повећао је експресију гена и протеина за нуклеарни фактор 2 (Nrf2), тиоредоксин
(Trx) 1, глутатион пероксидазу и редуктазу. Експресија гена супероксид дисмутазе
2 (SOD2) и Trx2 је смањена, док је примена ЕРИ повећала експресију протеина
SOD2. Штавише, ЕРИ је смањио концентрацију малондиалдехида, маркера
оксидативног оштећења у ћелији. Показали смо смањење персулфидације протеина
у јетри након третмана ЕРИ, док су генска и протеинска експресија ензима који
производе H2S остале непромењене. У закључку, ЕРИ појачава регулацију редокс
регулатора јетре Nrf2, који активира антиоксидативни одбрамбени систем и Trx1,
што доводи до смањења нивоа персулфидације протеина у јетри. Наши налази
указују на потенцијал ЕРИ у унапређењу редокс средине у јетри старих пацова., Starenje dovodi do akumulacije i smanjene eliminacije reaktivnih vrsta,
stvarajući oksidacionu sredinu u jetri. Jedna od mogućih opcija za odlaganje ovog
događaja je upotreba antioksidanata iz citrusa u sklopu procesa zdravog starenja.
Stoga, ova studija je imala za cilj da istraži efekte eriocitrina (ERI),
polifenola iz limuna, na redoks sredinu u jetri kod 24-mesečnih mužjaka Wistar
pacova. ERI (30 mg/kg t.m.) je davan oralno, jednom dnevno tokom četiri nedelje.
Kontrolne grupe su primile ili nosač tretmana (suncokretovo ulje) ili su ostale
intaktne. Primenjena metodologija podrazumevala je imunoblot i qPCR analizu,
detekciju nivoa persulfidacije u gelu i biohemijske analize. Tretman ERI
povećao je ekspresiju gena i proteina za nuklearni faktor 2 (Nrf2), tioredoksin
(Trx) 1, glutation peroksidazu i reduktazu. Ekspresija gena superoksid dismutaze
2 (SOD2) i Trx2 je smanjena, dok je primena ERI povećala ekspresiju proteina
SOD2. Štaviše, ERI je smanjio koncentraciju malondialdehida, markera
oksidativnog oštećenja u ćeliji. Pokazali smo smanjenje persulfidacije proteina
u jetri nakon tretmana ERI, dok su genska i proteinska ekspresija enzima koji
proizvode H2S ostale nepromenjene. U zaključku, ERI pojačava regulaciju redoks
regulatora jetre Nrf2, koji aktivira antioksidativni odbrambeni sistem i Trx1,
što dovodi do smanjenja nivoa persulfidacije proteina u jetri. Naši nalazi
ukazuju na potencijal ERI u unapređenju redoks sredine u jetri starih pacova.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Eриоцитрин, полифенол из лимуна, унапређује редокс средину у јетри старих пацова, Eriocitrin, polifenol iz limuna, unapređuje redoks sredinu u jetri starih pacova",
pages = "374",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6034"
}
Miler, M., Živanović, J., Ristić, N., Manojlović-Stojanoski, M., Trifunović, S., Šošić-Jurjević, B., Nestorović, N., Filipović, B.,& Ajdžanović, V.. (2022). Eриоцитрин, полифенол из лимуна, унапређује редокс средину у јетри старих пацова. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 374.
https://hdl.handle.net/21.15107/rcub_ibiss_6034
Miler M, Živanović J, Ristić N, Manojlović-Stojanoski M, Trifunović S, Šošić-Jurjević B, Nestorović N, Filipović B, Ajdžanović V. Eриоцитрин, полифенол из лимуна, унапређује редокс средину у јетри старих пацова. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:374.
https://hdl.handle.net/21.15107/rcub_ibiss_6034 .
Miler, Marko, Živanović, Jasmina, Ristić, Nataša, Manojlović-Stojanoski, Milica, Trifunović, Svetlana, Šošić-Jurjević, Branka , Nestorović, Nataša, Filipović, Branko, Ajdžanović, Vladimir, "Eриоцитрин, полифенол из лимуна, унапређује редокс средину у јетри старих пацова" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):374,
https://hdl.handle.net/21.15107/rcub_ibiss_6034 .

The effects of aging on thyroid C-cells in male rats

Filipović, Branko; Ajdžanović, Vladimir; Živanović, Jasmina; Manojlović-Stojanoski, Milica; Trifunović, Svetlana; Nestorović, Nataša; Šošić-Jurjević, Branka

(bioscientifica, 2022)

TY  - CONF
AU  - Filipović, Branko
AU  - Ajdžanović, Vladimir
AU  - Živanović, Jasmina
AU  - Manojlović-Stojanoski, Milica
AU  - Trifunović, Svetlana
AU  - Nestorović, Nataša
AU  - Šošić-Jurjević, Branka 
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4976
AB  - Thyroid C-cells, as a second type of endocrine cell population within thyroid, produce and secrete peptide hormone calcitonin (CT). This hypocalcemic hormone acts as an inhibitor of bone resorption. The aging is a complex process that alters various cellular functions. Therefore, the aim of this study was to examine the aging-related changes in the structure and function of CT-producing thyroid C-cells in male Wistar rats, using histomorphometric, ultrastructural and biochemical analysis. The investigation was performed on three groups of male rats: adult (3-months old), middle-aged (16-months old) and old (24-months old). The peroxidase-antiperoxidase method was applied for localization of CT in the C-cells. Stereological analysis was performed using Olimpus microscope (BX-51), equipped with a microcator, a motorised stage and a CCD video camera, and controlled by the newCAST stereological software package. Blood serum samples were analyzed for determination of CT, testosterone (T), calcium (Ca2+) and phosphorus (P) concentrations. We found a significant increase in the volume density (Vv) of thyroid C-cells in both middle-aged and old rats, all compared to adult animals. The percentage of smaller volume range C-cells (<500 μm3) increases, while the proportion of greater volume rang C-cells (both 500-1000 μm3 and >1000 μm3) markedly decreases with aging. By ultrastructural analysis we found that the average number of secretory granules per C-cell was significantly increased in both middle-aged and aged rats, all compared to adults. Unlike the C-cells of adult rats, these granules in older, especially in old animals, had a content of fairly low density. By the biochemical analysis, we detected a significant increase in serum CT levels, while serum T was markedly reduced in both middle aged and old rats, all in comparison with adults. Serum Ca2+ concentration significantly decreased in middle-aged rats compared to adults, while concentration of serum Pwas lower in both middle-aged and old rats, all related to adult group. Our findings show that aging process increases the Vv of thyroid C-cells, with a simultaneous change in percentage of cells with larger and smaller volume rang, and an increase in the number of both cell types. These changes, accompanied by modulation of the cellular ultrastructure and an increase in serum CT levels, reflect the structure and function of CT-producing thyroid C-cells in our aging model.
PB  - bioscientifica
C3  - European Congress of Endocrinology 2022; 2022 May 21-24; Milan, Italy
T1  - The effects of aging on thyroid C-cells in male rats
DO  - 10.1530/endoabs.81.P477
SP  - P477
ER  - 
@conference{
author = "Filipović, Branko and Ajdžanović, Vladimir and Živanović, Jasmina and Manojlović-Stojanoski, Milica and Trifunović, Svetlana and Nestorović, Nataša and Šošić-Jurjević, Branka ",
year = "2022",
abstract = "Thyroid C-cells, as a second type of endocrine cell population within thyroid, produce and secrete peptide hormone calcitonin (CT). This hypocalcemic hormone acts as an inhibitor of bone resorption. The aging is a complex process that alters various cellular functions. Therefore, the aim of this study was to examine the aging-related changes in the structure and function of CT-producing thyroid C-cells in male Wistar rats, using histomorphometric, ultrastructural and biochemical analysis. The investigation was performed on three groups of male rats: adult (3-months old), middle-aged (16-months old) and old (24-months old). The peroxidase-antiperoxidase method was applied for localization of CT in the C-cells. Stereological analysis was performed using Olimpus microscope (BX-51), equipped with a microcator, a motorised stage and a CCD video camera, and controlled by the newCAST stereological software package. Blood serum samples were analyzed for determination of CT, testosterone (T), calcium (Ca2+) and phosphorus (P) concentrations. We found a significant increase in the volume density (Vv) of thyroid C-cells in both middle-aged and old rats, all compared to adult animals. The percentage of smaller volume range C-cells (<500 μm3) increases, while the proportion of greater volume rang C-cells (both 500-1000 μm3 and >1000 μm3) markedly decreases with aging. By ultrastructural analysis we found that the average number of secretory granules per C-cell was significantly increased in both middle-aged and aged rats, all compared to adults. Unlike the C-cells of adult rats, these granules in older, especially in old animals, had a content of fairly low density. By the biochemical analysis, we detected a significant increase in serum CT levels, while serum T was markedly reduced in both middle aged and old rats, all in comparison with adults. Serum Ca2+ concentration significantly decreased in middle-aged rats compared to adults, while concentration of serum Pwas lower in both middle-aged and old rats, all related to adult group. Our findings show that aging process increases the Vv of thyroid C-cells, with a simultaneous change in percentage of cells with larger and smaller volume rang, and an increase in the number of both cell types. These changes, accompanied by modulation of the cellular ultrastructure and an increase in serum CT levels, reflect the structure and function of CT-producing thyroid C-cells in our aging model.",
publisher = "bioscientifica",
journal = "European Congress of Endocrinology 2022; 2022 May 21-24; Milan, Italy",
title = "The effects of aging on thyroid C-cells in male rats",
doi = "10.1530/endoabs.81.P477",
pages = "P477"
}
Filipović, B., Ajdžanović, V., Živanović, J., Manojlović-Stojanoski, M., Trifunović, S., Nestorović, N.,& Šošić-Jurjević, B.. (2022). The effects of aging on thyroid C-cells in male rats. in European Congress of Endocrinology 2022; 2022 May 21-24; Milan, Italy
bioscientifica., P477.
https://doi.org/10.1530/endoabs.81.P477
Filipović B, Ajdžanović V, Živanović J, Manojlović-Stojanoski M, Trifunović S, Nestorović N, Šošić-Jurjević B. The effects of aging on thyroid C-cells in male rats. in European Congress of Endocrinology 2022; 2022 May 21-24; Milan, Italy. 2022;:P477.
doi:10.1530/endoabs.81.P477 .
Filipović, Branko, Ajdžanović, Vladimir, Živanović, Jasmina, Manojlović-Stojanoski, Milica, Trifunović, Svetlana, Nestorović, Nataša, Šošić-Jurjević, Branka , "The effects of aging on thyroid C-cells in male rats" in European Congress of Endocrinology 2022; 2022 May 21-24; Milan, Italy (2022):P477,
https://doi.org/10.1530/endoabs.81.P477 . .

Thyroid Gland Alterations in Old-Aged Wistar Rats: A Comprehensive Stereological, Ultrastructural, Hormonal, and Gene Expression Study

Miler, Marko; Ajdžanović, Vladimir; Živanović, Jasmina; Marković Filipović, Jelena; Šošić-Jurjević, Branka ; Milošević, Verica

(Cambridge University Press, 2021)

TY  - JOUR
AU  - Miler, Marko
AU  - Ajdžanović, Vladimir
AU  - Živanović, Jasmina
AU  - Marković Filipović, Jelena
AU  - Šošić-Jurjević, Branka 
AU  - Milošević, Verica
PY  - 2021
UR  - https://www.cambridge.org/core/journals/microscopy-and-microanalysis/article/abs/thyroid-gland-alterations-in-oldaged-wistar-rats-a-comprehensive-stereological-ultrastructural-hormonal-and-gene-expression-study/4C35B9A6AFED404C65272C08C8C2DC27
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4143
AB  - The aim of the present study was to determine and elaborate on all changes in old-aged (OA) versus young-aged (YA) rat thyroids by using
stereological, ultrastructural, hormonal, and gene expression analyses. We used 4- and 24-month-old male Wistar rats in our evaluation,
presenting all changes in comparison with YA rats. Results showed that the thyroid parenchyma was characterized by higher absolute
volumes of the gland, colloid, epithelium, and interstitium by 135, 135, 140, and 142% ( p < 0.05) respectively, while the relative volumes
of colloid and glands were unchanged. Ultrastructural analysis revealed less active glands, with smaller amounts of lysosomes, thyroglobulin
(Tg) granules, and microvilli in the luminal colloid. Optical density values for thyroid peroxidase (TPO), Tg, and vascular-endothelial
growth factor immunostaining remained unchanged; however, TPO and Tg exhibited visually stronger expression in small active follicles.
Thyroxine (T4)-Tg, the relative intensity of fluorescence (RIF), serum T4, and the sodium-iodide symporter immunohistochemical and gene
expressions decreased by 20, 40, 29, and 31% ( p < 0.05), respectively, in OA thyroids. Pituitary thyroid-stimulating hormone (TSH) RIF
increased by 44% ( p < 0.05), but the TSH serum concentration remained unchanged. In conclusion, the obtained results indicate depression
of the thyroid gland synthetic and secretory capacity with advanced age.
PB  - Cambridge University Press
T2  - Microscopy and Microanalysis
T1  - Thyroid Gland Alterations in Old-Aged Wistar Rats: A Comprehensive Stereological, Ultrastructural, Hormonal, and Gene Expression Study
DO  - 10.1017/S1431927621000064
ER  - 
@article{
author = "Miler, Marko and Ajdžanović, Vladimir and Živanović, Jasmina and Marković Filipović, Jelena and Šošić-Jurjević, Branka  and Milošević, Verica",
year = "2021",
abstract = "The aim of the present study was to determine and elaborate on all changes in old-aged (OA) versus young-aged (YA) rat thyroids by using
stereological, ultrastructural, hormonal, and gene expression analyses. We used 4- and 24-month-old male Wistar rats in our evaluation,
presenting all changes in comparison with YA rats. Results showed that the thyroid parenchyma was characterized by higher absolute
volumes of the gland, colloid, epithelium, and interstitium by 135, 135, 140, and 142% ( p < 0.05) respectively, while the relative volumes
of colloid and glands were unchanged. Ultrastructural analysis revealed less active glands, with smaller amounts of lysosomes, thyroglobulin
(Tg) granules, and microvilli in the luminal colloid. Optical density values for thyroid peroxidase (TPO), Tg, and vascular-endothelial
growth factor immunostaining remained unchanged; however, TPO and Tg exhibited visually stronger expression in small active follicles.
Thyroxine (T4)-Tg, the relative intensity of fluorescence (RIF), serum T4, and the sodium-iodide symporter immunohistochemical and gene
expressions decreased by 20, 40, 29, and 31% ( p < 0.05), respectively, in OA thyroids. Pituitary thyroid-stimulating hormone (TSH) RIF
increased by 44% ( p < 0.05), but the TSH serum concentration remained unchanged. In conclusion, the obtained results indicate depression
of the thyroid gland synthetic and secretory capacity with advanced age.",
publisher = "Cambridge University Press",
journal = "Microscopy and Microanalysis",
title = "Thyroid Gland Alterations in Old-Aged Wistar Rats: A Comprehensive Stereological, Ultrastructural, Hormonal, and Gene Expression Study",
doi = "10.1017/S1431927621000064"
}
Miler, M., Ajdžanović, V., Živanović, J., Marković Filipović, J., Šošić-Jurjević, B.,& Milošević, V.. (2021). Thyroid Gland Alterations in Old-Aged Wistar Rats: A Comprehensive Stereological, Ultrastructural, Hormonal, and Gene Expression Study. in Microscopy and Microanalysis
Cambridge University Press..
https://doi.org/10.1017/S1431927621000064
Miler M, Ajdžanović V, Živanović J, Marković Filipović J, Šošić-Jurjević B, Milošević V. Thyroid Gland Alterations in Old-Aged Wistar Rats: A Comprehensive Stereological, Ultrastructural, Hormonal, and Gene Expression Study. in Microscopy and Microanalysis. 2021;.
doi:10.1017/S1431927621000064 .
Miler, Marko, Ajdžanović, Vladimir, Živanović, Jasmina, Marković Filipović, Jelena, Šošić-Jurjević, Branka , Milošević, Verica, "Thyroid Gland Alterations in Old-Aged Wistar Rats: A Comprehensive Stereological, Ultrastructural, Hormonal, and Gene Expression Study" in Microscopy and Microanalysis (2021),
https://doi.org/10.1017/S1431927621000064 . .
1
1
1

The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study.

Ajdžanović, Vladimir; Miler, Marko; Živanović, Jasmina; Filipović, Branko; Šošić-Jurjević, Branka ; Popovska-Perčinić, Florina; Milošević, Verica

(2020)

TY  - JOUR
AU  - Ajdžanović, Vladimir
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Filipović, Branko
AU  - Šošić-Jurjević, Branka 
AU  - Popovska-Perčinić, Florina
AU  - Milošević, Verica
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32120001
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3627
AB  - INTRODUCTION AND AIM Daidzein application may represent an effective and less harmful alternative to indicated, classical estrogenization of ageing men. The aim of this study was to perform structural and hormonal analysis of the adrenal cortex, after estradiol or daidzein supplementation in a rat model of the andropause. MATERIAL AND METHODS Middle-aged Wistar rats were divided into sham operated (SO; n = 8), orchidectomized (Orx; n = 8), estradiol treated orchidectomized (Orx + E; n = 8) and daidzein treated orchidectomized (Orx + D; n = 8) groups. Estradiol (0.625 mg/kg b.m./day) or daidzein (30 mg/kg b.m./day) were administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using stereology, histochemistry/immunohistochemistry, immunoassays and ultrastructural analysis. RESULTS Both estradiol and daidzein treatment significantly increased volumes of the zona glomerulosa cell and nuclei, but decreased circulating aldosterone levels. Estradiol markedly increased volumes of the zona fasciculata cell and nuclei in parallel with significant decrease of the adrenal tissue level of corticosterone, while daidzein significantly decreased both the adrenal and circulating levels of corticosterone. Serum DHEA level and volumes of the zona reticularis cell and nuclei significantly increased upon estradiol treatment, whereas daidzein even stronger increased the circulating level of DHEA. Shunting of the corticosteroidogenesis pathways towards adrenal androgens production, after the treatments, corresponded to the ultrastructural findings and zonal capillary network rearrangements. CONCLUSIONS Given the coherence of its effects and relative safety, daidzein could be the remedy of choice for the treatment of ageing-caused androgen deprivation and the hypothalamo-pituitary-adrenal axis hyperfunction/related metabolic issues in males.
T2  - Annals of Anatomy
T1  - The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study.
VL  - 230
DO  - 10.1016/j.aanat.2020.151487
SP  - 151487
ER  - 
@article{
author = "Ajdžanović, Vladimir and Miler, Marko and Živanović, Jasmina and Filipović, Branko and Šošić-Jurjević, Branka  and Popovska-Perčinić, Florina and Milošević, Verica",
year = "2020",
abstract = "INTRODUCTION AND AIM Daidzein application may represent an effective and less harmful alternative to indicated, classical estrogenization of ageing men. The aim of this study was to perform structural and hormonal analysis of the adrenal cortex, after estradiol or daidzein supplementation in a rat model of the andropause. MATERIAL AND METHODS Middle-aged Wistar rats were divided into sham operated (SO; n = 8), orchidectomized (Orx; n = 8), estradiol treated orchidectomized (Orx + E; n = 8) and daidzein treated orchidectomized (Orx + D; n = 8) groups. Estradiol (0.625 mg/kg b.m./day) or daidzein (30 mg/kg b.m./day) were administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using stereology, histochemistry/immunohistochemistry, immunoassays and ultrastructural analysis. RESULTS Both estradiol and daidzein treatment significantly increased volumes of the zona glomerulosa cell and nuclei, but decreased circulating aldosterone levels. Estradiol markedly increased volumes of the zona fasciculata cell and nuclei in parallel with significant decrease of the adrenal tissue level of corticosterone, while daidzein significantly decreased both the adrenal and circulating levels of corticosterone. Serum DHEA level and volumes of the zona reticularis cell and nuclei significantly increased upon estradiol treatment, whereas daidzein even stronger increased the circulating level of DHEA. Shunting of the corticosteroidogenesis pathways towards adrenal androgens production, after the treatments, corresponded to the ultrastructural findings and zonal capillary network rearrangements. CONCLUSIONS Given the coherence of its effects and relative safety, daidzein could be the remedy of choice for the treatment of ageing-caused androgen deprivation and the hypothalamo-pituitary-adrenal axis hyperfunction/related metabolic issues in males.",
journal = "Annals of Anatomy",
title = "The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study.",
volume = "230",
doi = "10.1016/j.aanat.2020.151487",
pages = "151487"
}
Ajdžanović, V., Miler, M., Živanović, J., Filipović, B., Šošić-Jurjević, B., Popovska-Perčinić, F.,& Milošević, V.. (2020). The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study.. in Annals of Anatomy, 230, 151487.
https://doi.org/10.1016/j.aanat.2020.151487
Ajdžanović V, Miler M, Živanović J, Filipović B, Šošić-Jurjević B, Popovska-Perčinić F, Milošević V. The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study.. in Annals of Anatomy. 2020;230:151487.
doi:10.1016/j.aanat.2020.151487 .
Ajdžanović, Vladimir, Miler, Marko, Živanović, Jasmina, Filipović, Branko, Šošić-Jurjević, Branka , Popovska-Perčinić, Florina, Milošević, Verica, "The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study." in Annals of Anatomy, 230 (2020):151487,
https://doi.org/10.1016/j.aanat.2020.151487 . .
5
3
5

The effects of naringenin on NRF2 and antioxidant enzymes expressions in the thyroids of the old-aged Wistar rats

Miler, Marko; Živanović, Jasmina; Ajdžanović, Vladimir; Šošić-Jurjević, Branka ; Marković, Zorica; Milošević, Verica

(European Society of Endocrinology, 2020)

TY  - CONF
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Ajdžanović, Vladimir
AU  - Šošić-Jurjević, Branka 
AU  - Marković, Zorica
AU  - Milošević, Verica
PY  - 2020
UR  - https://www.endocrine-abstracts.org/ea/0070/abstract-book/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4110
AB  - Citrus flavanone naringenin (NAR) is a potent antioxidant with ability to
change pituitary-thyroid function. NAR increases concentration of thyroid-
stimulating hormone (TSH) in serum by increasing Sirtuin1 expression
in the pituitary thyrotrophs and improves thyroid hormonogenesis capacity
in old-aged rats. Thyroid hormone production is followed by generation of
large quantities of reactive oxygen species (ROS) which are essential for
iodine organification. A master regulator of redox status, NRF2 protein,
together with antioxidant enzymes (AOE), is responsible for maintenance
of redox/antioxidant balance in the cell. Considering that NRF2 expression
can be affected by NAR, besides TSH, the study aim is to analyze gene and
protein expressions of NRF2 and AOE in the thyroids of 24-month-old male
Wistar rats. NAR was suspended in sunflower oil (vehicle) and administrated
directly to the oral cavity, at a dose of 15 mg/kg b.m., during 4 weeks.
Control group received vehicle only. We performed qPCR and immunoblot
analyses for gene and protein expressions, respectively. Obtained results
showed that NAR treatment lowered (P < 0.05) mRNA levels of Nrf2, superoxide
dismutase 1 and 2 (Sod1, Sod2) and catalase (Cat) for 42%, 32%, 45%
and 35%, respectively, while it only increased (P < 0.05) expression of glutathione
peroxidase (Gpx) for 54%, all in comparison with the controls. Gene
expression of glutathione reductase (Gr) remained unchanged. Also, NAR
up-regulated (P < 0.05) protein expression of NRF2 and SOD2 for 58% and
50%, respectively, and down-regulated (P < 0.05) SOD1 expression for 48%,
all when compared to the adequate control values. CAT, GR and GPx protein
expressions didn’t change after NAR treatment. It can be concluded that
NAR changes gene and protein expression of NRF2 in old-aged rat model.
Down-regulation in Nrf2 gene expression, and some AOE, is in line with
previously observed TSH stimulation after NAR. Antioxidant protection in
thyroid needs to be lowered in order to ensure sufficient ROS for adequate
thyroid hormones production. However, due to NAR prooxidant properties,
redox status in thyroid upon its application was changed, inducing accumulation
of NRF2 protein in the thyrocytes. This led to increment of Gpx
gene and SOD2 protein expression, helping in maintenance of fundamental
antioxidant protection and disposal of excessive ROS in the thyroid gland
of old-aged rats.
PB  - European Society of Endocrinology
C3  - 22nd European Congress of Endocrinology; 2020 Sep 5-9
T1  - The effects of naringenin on NRF2 and antioxidant enzymes expressions in the thyroids of the old-aged Wistar rats
DO  - 10.1530/endoabs.70.AEP919
SP  - 372
ER  - 
@conference{
author = "Miler, Marko and Živanović, Jasmina and Ajdžanović, Vladimir and Šošić-Jurjević, Branka  and Marković, Zorica and Milošević, Verica",
year = "2020",
abstract = "Citrus flavanone naringenin (NAR) is a potent antioxidant with ability to
change pituitary-thyroid function. NAR increases concentration of thyroid-
stimulating hormone (TSH) in serum by increasing Sirtuin1 expression
in the pituitary thyrotrophs and improves thyroid hormonogenesis capacity
in old-aged rats. Thyroid hormone production is followed by generation of
large quantities of reactive oxygen species (ROS) which are essential for
iodine organification. A master regulator of redox status, NRF2 protein,
together with antioxidant enzymes (AOE), is responsible for maintenance
of redox/antioxidant balance in the cell. Considering that NRF2 expression
can be affected by NAR, besides TSH, the study aim is to analyze gene and
protein expressions of NRF2 and AOE in the thyroids of 24-month-old male
Wistar rats. NAR was suspended in sunflower oil (vehicle) and administrated
directly to the oral cavity, at a dose of 15 mg/kg b.m., during 4 weeks.
Control group received vehicle only. We performed qPCR and immunoblot
analyses for gene and protein expressions, respectively. Obtained results
showed that NAR treatment lowered (P < 0.05) mRNA levels of Nrf2, superoxide
dismutase 1 and 2 (Sod1, Sod2) and catalase (Cat) for 42%, 32%, 45%
and 35%, respectively, while it only increased (P < 0.05) expression of glutathione
peroxidase (Gpx) for 54%, all in comparison with the controls. Gene
expression of glutathione reductase (Gr) remained unchanged. Also, NAR
up-regulated (P < 0.05) protein expression of NRF2 and SOD2 for 58% and
50%, respectively, and down-regulated (P < 0.05) SOD1 expression for 48%,
all when compared to the adequate control values. CAT, GR and GPx protein
expressions didn’t change after NAR treatment. It can be concluded that
NAR changes gene and protein expression of NRF2 in old-aged rat model.
Down-regulation in Nrf2 gene expression, and some AOE, is in line with
previously observed TSH stimulation after NAR. Antioxidant protection in
thyroid needs to be lowered in order to ensure sufficient ROS for adequate
thyroid hormones production. However, due to NAR prooxidant properties,
redox status in thyroid upon its application was changed, inducing accumulation
of NRF2 protein in the thyrocytes. This led to increment of Gpx
gene and SOD2 protein expression, helping in maintenance of fundamental
antioxidant protection and disposal of excessive ROS in the thyroid gland
of old-aged rats.",
publisher = "European Society of Endocrinology",
journal = "22nd European Congress of Endocrinology; 2020 Sep 5-9",
title = "The effects of naringenin on NRF2 and antioxidant enzymes expressions in the thyroids of the old-aged Wistar rats",
doi = "10.1530/endoabs.70.AEP919",
pages = "372"
}
Miler, M., Živanović, J., Ajdžanović, V., Šošić-Jurjević, B., Marković, Z.,& Milošević, V.. (2020). The effects of naringenin on NRF2 and antioxidant enzymes expressions in the thyroids of the old-aged Wistar rats. in 22nd European Congress of Endocrinology; 2020 Sep 5-9
European Society of Endocrinology., 372.
https://doi.org/10.1530/endoabs.70.AEP919
Miler M, Živanović J, Ajdžanović V, Šošić-Jurjević B, Marković Z, Milošević V. The effects of naringenin on NRF2 and antioxidant enzymes expressions in the thyroids of the old-aged Wistar rats. in 22nd European Congress of Endocrinology; 2020 Sep 5-9. 2020;:372.
doi:10.1530/endoabs.70.AEP919 .
Miler, Marko, Živanović, Jasmina, Ajdžanović, Vladimir, Šošić-Jurjević, Branka , Marković, Zorica, Milošević, Verica, "The effects of naringenin on NRF2 and antioxidant enzymes expressions in the thyroids of the old-aged Wistar rats" in 22nd European Congress of Endocrinology; 2020 Sep 5-9 (2020):372,
https://doi.org/10.1530/endoabs.70.AEP919 . .

Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats

Miler, Marko; Živanović, Jasmina; Ajdžanović, Vladimir; Milenković, Dragan; Jarić, Ivana; Šošić-Jurjević, Branka ; Milošević, Verica

(NLM (Medline), 2020)

TY  - JOUR
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Ajdžanović, Vladimir
AU  - Milenković, Dragan
AU  - Jarić, Ivana
AU  - Šošić-Jurjević, Branka 
AU  - Milošević, Verica
PY  - 2020
UR  - https://dx.doi.org/10.1021/acs.jafc.0c03079
UR  - https://radar.ibiss.bg.ac.rs/123456789/3860
AB  - A growing population of elderly people consume citrus flavanones, naringenin, and hesperetin in the form of fruits or juices. Flavanones are bioactives with potent antioxidant properties and have potential in slowing down the aging process. Because flavanones exert controversial effects on pituitary-thyroid functioning, our study on the old-aged rat model aimed to elucidate the mechanism by which naringenin and hesperetin affect this axis. Naringenin and hesperetin increased the Sirt1 mRNA level by 91 and 71% (p < 0.05), which was followed by increased Sirt1 expression by 20 and 15% (p < 0.05), respectively. Only naringenin decreased thyroid-stimulating hormone expression by 20% (p < 0.05). Thyroid peroxidase protein expression was upregulated after naringenin or hesperetin by 62 and 43% (p < 0.05), respectively. Naringenin lowered mRNA levels of Tpo, Sod1, Sod2, Cat, and Nrf2 by 50, 32, 45, 35, and 42% (p < 0.05), respectively, and increased Gpx by 54% (p < 0.05), while hesperetin decreased Sod1 and Sod2 mRNA levels by 46 and 55% (p < 0.05), respectively. Naringenin increased the protein expressions of Nrf2 and SOD2 by 58 and 50% (p < 0.05), respectively, and decreased SOD1 expression by 48% (p < 0.05), while hesperetin protein decreased expressions of SOD1 and Nrf2 by 63 and 32% (p < 0.05), respectively. Altogether, our findings suggest that citrus flavanones contribute to restoring the impaired thyroid functioning in the old-aged rats.
PB  - NLM (Medline)
T2  - Journal of Agricultural and Food Chemistry
T1  - Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats
IS  - 31
VL  - 68
DO  - 10.1021/acs.jafc.0c03079
SP  - 8242
EP  - 8254
ER  - 
@article{
author = "Miler, Marko and Živanović, Jasmina and Ajdžanović, Vladimir and Milenković, Dragan and Jarić, Ivana and Šošić-Jurjević, Branka  and Milošević, Verica",
year = "2020",
abstract = "A growing population of elderly people consume citrus flavanones, naringenin, and hesperetin in the form of fruits or juices. Flavanones are bioactives with potent antioxidant properties and have potential in slowing down the aging process. Because flavanones exert controversial effects on pituitary-thyroid functioning, our study on the old-aged rat model aimed to elucidate the mechanism by which naringenin and hesperetin affect this axis. Naringenin and hesperetin increased the Sirt1 mRNA level by 91 and 71% (p < 0.05), which was followed by increased Sirt1 expression by 20 and 15% (p < 0.05), respectively. Only naringenin decreased thyroid-stimulating hormone expression by 20% (p < 0.05). Thyroid peroxidase protein expression was upregulated after naringenin or hesperetin by 62 and 43% (p < 0.05), respectively. Naringenin lowered mRNA levels of Tpo, Sod1, Sod2, Cat, and Nrf2 by 50, 32, 45, 35, and 42% (p < 0.05), respectively, and increased Gpx by 54% (p < 0.05), while hesperetin decreased Sod1 and Sod2 mRNA levels by 46 and 55% (p < 0.05), respectively. Naringenin increased the protein expressions of Nrf2 and SOD2 by 58 and 50% (p < 0.05), respectively, and decreased SOD1 expression by 48% (p < 0.05), while hesperetin protein decreased expressions of SOD1 and Nrf2 by 63 and 32% (p < 0.05), respectively. Altogether, our findings suggest that citrus flavanones contribute to restoring the impaired thyroid functioning in the old-aged rats.",
publisher = "NLM (Medline)",
journal = "Journal of Agricultural and Food Chemistry",
title = "Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats",
number = "31",
volume = "68",
doi = "10.1021/acs.jafc.0c03079",
pages = "8242-8254"
}
Miler, M., Živanović, J., Ajdžanović, V., Milenković, D., Jarić, I., Šošić-Jurjević, B.,& Milošević, V.. (2020). Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats. in Journal of Agricultural and Food Chemistry
NLM (Medline)., 68(31), 8242-8254.
https://doi.org/10.1021/acs.jafc.0c03079
Miler M, Živanović J, Ajdžanović V, Milenković D, Jarić I, Šošić-Jurjević B, Milošević V. Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats. in Journal of Agricultural and Food Chemistry. 2020;68(31):8242-8254.
doi:10.1021/acs.jafc.0c03079 .
Miler, Marko, Živanović, Jasmina, Ajdžanović, Vladimir, Milenković, Dragan, Jarić, Ivana, Šošić-Jurjević, Branka , Milošević, Verica, "Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats" in Journal of Agricultural and Food Chemistry, 68, no. 31 (2020):8242-8254,
https://doi.org/10.1021/acs.jafc.0c03079 . .
15
5
14

Old age-associated impairment of the rat liver antioxidant defense system: the basis for affirmation of the experimental model

Miler, Marko; Ajdžanović, Vladimir; Živanović, Jasmina; Jarić, Ivana; Šošić-Jurjević, Branka; Potrebić, Milica; Milošević, Verica

(2019)

TY  - JOUR
AU  - Miler, Marko
AU  - Ajdžanović, Vladimir
AU  - Živanović, Jasmina
AU  - Jarić, Ivana
AU  - Šošić-Jurjević, Branka
AU  - Potrebić, Milica
AU  - Milošević, Verica
PY  - 2019
UR  - http://online.journals.tubitak.gov.tr/openDoiPdf.htm?mKodu=vet-1812-39
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3402
AB  - Letter to the Editor
T2  - Turkish Journal of Veterinary and Animal Sciences
T1  - Old age-associated impairment of the rat liver antioxidant defense system: the basis for affirmation of the experimental model
IS  - 3
VL  - 43
DO  - 10.3906/vet-1812-39
SP  - 423
EP  - 426
ER  - 
@article{
author = "Miler, Marko and Ajdžanović, Vladimir and Živanović, Jasmina and Jarić, Ivana and Šošić-Jurjević, Branka and Potrebić, Milica and Milošević, Verica",
year = "2019",
abstract = "Letter to the Editor",
journal = "Turkish Journal of Veterinary and Animal Sciences",
title = "Old age-associated impairment of the rat liver antioxidant defense system: the basis for affirmation of the experimental model",
number = "3",
volume = "43",
doi = "10.3906/vet-1812-39",
pages = "423-426"
}
Miler, M., Ajdžanović, V., Živanović, J., Jarić, I., Šošić-Jurjević, B., Potrebić, M.,& Milošević, V.. (2019). Old age-associated impairment of the rat liver antioxidant defense system: the basis for affirmation of the experimental model. in Turkish Journal of Veterinary and Animal Sciences, 43(3), 423-426.
https://doi.org/10.3906/vet-1812-39
Miler M, Ajdžanović V, Živanović J, Jarić I, Šošić-Jurjević B, Potrebić M, Milošević V. Old age-associated impairment of the rat liver antioxidant defense system: the basis for affirmation of the experimental model. in Turkish Journal of Veterinary and Animal Sciences. 2019;43(3):423-426.
doi:10.3906/vet-1812-39 .
Miler, Marko, Ajdžanović, Vladimir, Živanović, Jasmina, Jarić, Ivana, Šošić-Jurjević, Branka, Potrebić, Milica, Milošević, Verica, "Old age-associated impairment of the rat liver antioxidant defense system: the basis for affirmation of the experimental model" in Turkish Journal of Veterinary and Animal Sciences, 43, no. 3 (2019):423-426,
https://doi.org/10.3906/vet-1812-39 . .
3
1
2

Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration

Živanović, Jasmina; Kouroussis, Emilia; Kohl, Joshua B.; Adhikari, Bikash; Bursać, Biljana; Schott-Roux, Sonia; Petrović, Dunja; Miljković, Jan Lj.; Thomas-Lopez, Daniel; Jung, Youngeun; Miler, Marko; Mitchell, Sarah; Milošević, Verica; Gomes, Jose Eduardo; Benhar, Moran; Gonzales-Zorn, Bruno; Ivanović-Burmazović, Ivana; Torregrossa, Roberta; Mitchell, James R.; Whiteman, Matthew; Schwarz, Guenter; Snyder, Solomon H.; Paul, Bindu D.; Carroll, Kate S.; Filipović, Miloš R.

(2019)

TY  - JOUR
AU  - Živanović, Jasmina
AU  - Kouroussis, Emilia
AU  - Kohl, Joshua B.
AU  - Adhikari, Bikash
AU  - Bursać, Biljana
AU  - Schott-Roux, Sonia
AU  - Petrović, Dunja
AU  - Miljković, Jan Lj.
AU  - Thomas-Lopez, Daniel
AU  - Jung, Youngeun
AU  - Miler, Marko
AU  - Mitchell, Sarah
AU  - Milošević, Verica
AU  - Gomes, Jose Eduardo
AU  - Benhar, Moran
AU  - Gonzales-Zorn, Bruno
AU  - Ivanović-Burmazović, Ivana
AU  - Torregrossa, Roberta
AU  - Mitchell, James R.
AU  - Whiteman, Matthew
AU  - Schwarz, Guenter
AU  - Snyder, Solomon H.
AU  - Paul, Bindu D.
AU  - Carroll, Kate S.
AU  - Filipović, Miloš R.
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/abs/pii/S1550413119305625
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3518
AB  - Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure and/or function. Persulfides are difficult to label and study due to their reactivity and similarity with cysteine. Here, we report a facile strategy for chemoselective persulfide bioconjugation using dimedone-based probes, to achieve highly selective, rapid, and robust persulfide labeling in biological samples with broad utility. Using this method, we show persulfidation is an evolutionarily conserved modification and waves of persulfidation are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function. We report an age-associated decline in persulfidation that is conserved across evolutionary boundaries. Accordingly, dietary or pharmacological interventions to increase persulfidation associate with increased longevity and improved capacity to cope with stress stimuli.
T2  - Cell Metabolism
T1  - Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration
IS  - 6
VL  - 30
DO  - 10.1016/J.CMET.2019.10.007
SP  - 1152
EP  - 1170.e13
ER  - 
@article{
author = "Živanović, Jasmina and Kouroussis, Emilia and Kohl, Joshua B. and Adhikari, Bikash and Bursać, Biljana and Schott-Roux, Sonia and Petrović, Dunja and Miljković, Jan Lj. and Thomas-Lopez, Daniel and Jung, Youngeun and Miler, Marko and Mitchell, Sarah and Milošević, Verica and Gomes, Jose Eduardo and Benhar, Moran and Gonzales-Zorn, Bruno and Ivanović-Burmazović, Ivana and Torregrossa, Roberta and Mitchell, James R. and Whiteman, Matthew and Schwarz, Guenter and Snyder, Solomon H. and Paul, Bindu D. and Carroll, Kate S. and Filipović, Miloš R.",
year = "2019",
abstract = "Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure and/or function. Persulfides are difficult to label and study due to their reactivity and similarity with cysteine. Here, we report a facile strategy for chemoselective persulfide bioconjugation using dimedone-based probes, to achieve highly selective, rapid, and robust persulfide labeling in biological samples with broad utility. Using this method, we show persulfidation is an evolutionarily conserved modification and waves of persulfidation are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function. We report an age-associated decline in persulfidation that is conserved across evolutionary boundaries. Accordingly, dietary or pharmacological interventions to increase persulfidation associate with increased longevity and improved capacity to cope with stress stimuli.",
journal = "Cell Metabolism",
title = "Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration",
number = "6",
volume = "30",
doi = "10.1016/J.CMET.2019.10.007",
pages = "1152-1170.e13"
}
Živanović, J., Kouroussis, E., Kohl, J. B., Adhikari, B., Bursać, B., Schott-Roux, S., Petrović, D., Miljković, J. Lj., Thomas-Lopez, D., Jung, Y., Miler, M., Mitchell, S., Milošević, V., Gomes, J. E., Benhar, M., Gonzales-Zorn, B., Ivanović-Burmazović, I., Torregrossa, R., Mitchell, J. R., Whiteman, M., Schwarz, G., Snyder, S. H., Paul, B. D., Carroll, K. S.,& Filipović, M. R.. (2019). Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration. in Cell Metabolism, 30(6), 1152-1170.e13.
https://doi.org/10.1016/J.CMET.2019.10.007
Živanović J, Kouroussis E, Kohl JB, Adhikari B, Bursać B, Schott-Roux S, Petrović D, Miljković JL, Thomas-Lopez D, Jung Y, Miler M, Mitchell S, Milošević V, Gomes JE, Benhar M, Gonzales-Zorn B, Ivanović-Burmazović I, Torregrossa R, Mitchell JR, Whiteman M, Schwarz G, Snyder SH, Paul BD, Carroll KS, Filipović MR. Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration. in Cell Metabolism. 2019;30(6):1152-1170.e13.
doi:10.1016/J.CMET.2019.10.007 .
Živanović, Jasmina, Kouroussis, Emilia, Kohl, Joshua B., Adhikari, Bikash, Bursać, Biljana, Schott-Roux, Sonia, Petrović, Dunja, Miljković, Jan Lj., Thomas-Lopez, Daniel, Jung, Youngeun, Miler, Marko, Mitchell, Sarah, Milošević, Verica, Gomes, Jose Eduardo, Benhar, Moran, Gonzales-Zorn, Bruno, Ivanović-Burmazović, Ivana, Torregrossa, Roberta, Mitchell, James R., Whiteman, Matthew, Schwarz, Guenter, Snyder, Solomon H., Paul, Bindu D., Carroll, Kate S., Filipović, Miloš R., "Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration" in Cell Metabolism, 30, no. 6 (2019):1152-1170.e13,
https://doi.org/10.1016/J.CMET.2019.10.007 . .
124
234
105
216

The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.

Šošić-Jurjević, Branka ; Lütjohann, Dieter; Renko, Kostja; Filipović, Branko; Radulović, Niko; Ajdžanović, Vladimir; Trifunović, Svetlana; Nestorović, Nataša; Živanović, Jasmina; Manojlović-Stojanoski, Milica; Kӧhrle, Josef; Milošević, Verica

(2019)

TY  - JOUR
AU  - Šošić-Jurjević, Branka 
AU  - Lütjohann, Dieter
AU  - Renko, Kostja
AU  - Filipović, Branko
AU  - Radulović, Niko
AU  - Ajdžanović, Vladimir
AU  - Trifunović, Svetlana
AU  - Nestorović, Nataša
AU  - Živanović, Jasmina
AU  - Manojlović-Stojanoski, Milica
AU  - Kӧhrle, Josef
AU  - Milošević, Verica
PY  - 2019
UR  - internal-pdf://Šošić-Jurjević et al. - 2019 - The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Chol.pdf
UR  - https://www.sciencedirect.com/science/article/pii/S0960076018307507
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3290
AB  - We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.
T2  - The Journal of Steroid Biochemistry and Molecular Biology
T1  - The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.
VL  - 190
DO  - 10.1016/j.jsbmb.2019.03.009
SP  - 1
EP  - 10
ER  - 
@article{
author = "Šošić-Jurjević, Branka  and Lütjohann, Dieter and Renko, Kostja and Filipović, Branko and Radulović, Niko and Ajdžanović, Vladimir and Trifunović, Svetlana and Nestorović, Nataša and Živanović, Jasmina and Manojlović-Stojanoski, Milica and Kӧhrle, Josef and Milošević, Verica",
year = "2019",
abstract = "We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.",
journal = "The Journal of Steroid Biochemistry and Molecular Biology",
title = "The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.",
volume = "190",
doi = "10.1016/j.jsbmb.2019.03.009",
pages = "1-10"
}
Šošić-Jurjević, B., Lütjohann, D., Renko, K., Filipović, B., Radulović, N., Ajdžanović, V., Trifunović, S., Nestorović, N., Živanović, J., Manojlović-Stojanoski, M., Kӧhrle, J.,& Milošević, V.. (2019). The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.. in The Journal of Steroid Biochemistry and Molecular Biology, 190, 1-10.
https://doi.org/10.1016/j.jsbmb.2019.03.009
Šošić-Jurjević B, Lütjohann D, Renko K, Filipović B, Radulović N, Ajdžanović V, Trifunović S, Nestorović N, Živanović J, Manojlović-Stojanoski M, Kӧhrle J, Milošević V. The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats.. in The Journal of Steroid Biochemistry and Molecular Biology. 2019;190:1-10.
doi:10.1016/j.jsbmb.2019.03.009 .
Šošić-Jurjević, Branka , Lütjohann, Dieter, Renko, Kostja, Filipović, Branko, Radulović, Niko, Ajdžanović, Vladimir, Trifunović, Svetlana, Nestorović, Nataša, Živanović, Jasmina, Manojlović-Stojanoski, Milica, Kӧhrle, Josef, Milošević, Verica, "The Isoflavones Genistein and Daidzein Increase Hepatic Concentration of Thyroid Hormones and Affect Cholesterol Metabolism in Middle-Aged Male Rats." in The Journal of Steroid Biochemistry and Molecular Biology, 190 (2019):1-10,
https://doi.org/10.1016/j.jsbmb.2019.03.009 . .
43
23
39

Naringenin increases pituitary Sirt1/TSH ratio and induces ultrastructural changes in the thyroids of old-aged male Wistar rats

Miler, Marko; Živanović, Jasmina; Ajdžanović, Vladimir; Jarić, Ivana; Šošić-Jurjević, Branka ; Milošević, Verica

(Basel: S. Karger AG, 2019)

TY  - CONF
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Ajdžanović, Vladimir
AU  - Jarić, Ivana
AU  - Šošić-Jurjević, Branka 
AU  - Milošević, Verica
PY  - 2019
UR  - https://www.karger.com/Journal/Issue/278476
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3500
AB  - Objectives: Fruit-derived polyphenols can affect pituitary thyroid stimulating hormone (TSH) secretion, which is mediated by Sirt1 protein. Recently, we have shown that citrus polyphenol naringenin (NAR) increases serum TSH level and modify thyroid structure in terms of increased hormone biosynthesis. Keeping in mind that higher serum TSH level and elevated Sirt1 expression are tightly connected with longevity, we wanted to test whetherNAR administration affects pituitary TSH and Sirt1 immunofluorescent expression and changes thyroid ultrastructure in 24-month-old male Wistar rats.
Methods: NAR was administrated orally (15 mg/kg b.m.) during 4 weeks, while the control group received vehicle, sunflower oil. Quantitative analysis of labeled TSH and Sirt1 proteins in TSH cells considered the relative intensity of fluorescence (RIF) measurements, while ultrastructural analysis was performed in the thyroids. Results: Increased (p<0.05) Sirt1 RIF as well as Sirt1/TSH ratio were observed, while TSH content-reflecting RIF decreased (p<0.05), all after NAR treatment. In line with this effect of NAR, thyroids of the same group responded to direct TSH stimulation in comparison with the controls. Namely, ultrastructural analysis showed higher thyroid epithelium, well developed
rough endoplasmic reticulum and polymorphic lysosomes which were more abundant than in the control group. Some lysosomes were attached to colloid droplets, unequivocally indicating the gland secretory activity. Conclusion: Citrus flavanone NAR increases pituitary Sirt1/TSH expression ratio in old rats. This corresponds with decreased thyrotrope TSH content/increased secretion, while ultrastructure of the thyroids follows direct TSH stimulation. These results, for the first time, show potency of NAR to positively interfere with TSH secretion in old-aged rats, which may contribute to the healthy aging and longevity.
PB  - Basel: S. Karger AG
C3  - 42nd Annual Meeting of the European Thyroid Association Abstracts; 2019 Sep 7-10; Budapest, Hungary (European Thyroid Journal; Vol. 1; No. 1)
T1  - Naringenin increases pituitary Sirt1/TSH ratio and induces ultrastructural changes in the thyroids of old-aged male Wistar rats
DO  - 10.1159/000501012
SP  - 15
EP  - 16
ER  - 
@conference{
author = "Miler, Marko and Živanović, Jasmina and Ajdžanović, Vladimir and Jarić, Ivana and Šošić-Jurjević, Branka  and Milošević, Verica",
year = "2019",
abstract = "Objectives: Fruit-derived polyphenols can affect pituitary thyroid stimulating hormone (TSH) secretion, which is mediated by Sirt1 protein. Recently, we have shown that citrus polyphenol naringenin (NAR) increases serum TSH level and modify thyroid structure in terms of increased hormone biosynthesis. Keeping in mind that higher serum TSH level and elevated Sirt1 expression are tightly connected with longevity, we wanted to test whetherNAR administration affects pituitary TSH and Sirt1 immunofluorescent expression and changes thyroid ultrastructure in 24-month-old male Wistar rats.
Methods: NAR was administrated orally (15 mg/kg b.m.) during 4 weeks, while the control group received vehicle, sunflower oil. Quantitative analysis of labeled TSH and Sirt1 proteins in TSH cells considered the relative intensity of fluorescence (RIF) measurements, while ultrastructural analysis was performed in the thyroids. Results: Increased (p<0.05) Sirt1 RIF as well as Sirt1/TSH ratio were observed, while TSH content-reflecting RIF decreased (p<0.05), all after NAR treatment. In line with this effect of NAR, thyroids of the same group responded to direct TSH stimulation in comparison with the controls. Namely, ultrastructural analysis showed higher thyroid epithelium, well developed
rough endoplasmic reticulum and polymorphic lysosomes which were more abundant than in the control group. Some lysosomes were attached to colloid droplets, unequivocally indicating the gland secretory activity. Conclusion: Citrus flavanone NAR increases pituitary Sirt1/TSH expression ratio in old rats. This corresponds with decreased thyrotrope TSH content/increased secretion, while ultrastructure of the thyroids follows direct TSH stimulation. These results, for the first time, show potency of NAR to positively interfere with TSH secretion in old-aged rats, which may contribute to the healthy aging and longevity.",
publisher = "Basel: S. Karger AG",
journal = "42nd Annual Meeting of the European Thyroid Association Abstracts; 2019 Sep 7-10; Budapest, Hungary (European Thyroid Journal; Vol. 1; No. 1)",
title = "Naringenin increases pituitary Sirt1/TSH ratio and induces ultrastructural changes in the thyroids of old-aged male Wistar rats",
doi = "10.1159/000501012",
pages = "15-16"
}
Miler, M., Živanović, J., Ajdžanović, V., Jarić, I., Šošić-Jurjević, B.,& Milošević, V.. (2019). Naringenin increases pituitary Sirt1/TSH ratio and induces ultrastructural changes in the thyroids of old-aged male Wistar rats. in 42nd Annual Meeting of the European Thyroid Association Abstracts; 2019 Sep 7-10; Budapest, Hungary (European Thyroid Journal; Vol. 1; No. 1)
Basel: S. Karger AG., 15-16.
https://doi.org/10.1159/000501012
Miler M, Živanović J, Ajdžanović V, Jarić I, Šošić-Jurjević B, Milošević V. Naringenin increases pituitary Sirt1/TSH ratio and induces ultrastructural changes in the thyroids of old-aged male Wistar rats. in 42nd Annual Meeting of the European Thyroid Association Abstracts; 2019 Sep 7-10; Budapest, Hungary (European Thyroid Journal; Vol. 1; No. 1). 2019;:15-16.
doi:10.1159/000501012 .
Miler, Marko, Živanović, Jasmina, Ajdžanović, Vladimir, Jarić, Ivana, Šošić-Jurjević, Branka , Milošević, Verica, "Naringenin increases pituitary Sirt1/TSH ratio and induces ultrastructural changes in the thyroids of old-aged male Wistar rats" in 42nd Annual Meeting of the European Thyroid Association Abstracts; 2019 Sep 7-10; Budapest, Hungary (European Thyroid Journal; Vol. 1; No. 1) (2019):15-16,
https://doi.org/10.1159/000501012 . .
6
14

Protein Persulfidation Protects Against Aging

Živanović, Jasmina; Kouroussis, Emilia; Kohl, Joshua; Miler, Marko; Mitchell, Sarah; Mitchell, James; Schwartz, Guenter; Milošević, Verica; Filipović R., Miloš

(Berlin: Freie Universität Berlin, 2019)

TY  - CONF
AU  - Živanović, Jasmina
AU  - Kouroussis, Emilia
AU  - Kohl, Joshua
AU  - Miler, Marko
AU  - Mitchell, Sarah
AU  - Mitchell, James
AU  - Schwartz, Guenter
AU  - Milošević, Verica
AU  - Filipović R., Miloš
PY  - 2019
UR  - https://www.bcp.fu-berlin.de/en/biologie/arbeitsgruppen/mikrobiologie/ag_antelmann/meetings/190915_redox_res/Flyer-Sant-Feliu-2019-final6.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6039
AB  - For couple of decades aging is believed to be a consequence of damages accumulated by increased production of reactive oxygen species (ROS). Opposite to that, dietary restriction attempts to extend life have been linked to increased H2S production. We hypothesized that reacting with sulfenic acids (formed by ROS) H2S would rescue cysteine residue by forming persulfides. Persulfides are better ROS scavengers and could form protein S-sulfonates that could be cleaved back by disulfide reductase to restore free thiolate. This rescue loop would thus prevent irreversible thiol hyperoxidation. Using dimedone switch method we could first show that persulfidation is a posttranslational modification that is evolutionarily conserved (bacteria, flies, worms, mice and humans). Then we could also observe that thioredoxin readily catalyzes the reduction of cysteine S-sulfonate, two orders of magnitude faster than the reduction of corresponding disulfide. The persulfidation levels/H2S producing ability positively correlated with the ability of yeast, worms and mammalian cells to resist stress caused by ROS. Persulfidation declines with aging in worms, rats and mice, due to the downregulation of H2S producing enzymes, but dietary restriction in mice and worms restores persulfide levels and improves their lifespan. Based on these data we suggest that persulfidation represents an evolutionarily conserved anti-aging mechanism.
PB  - Berlin: Freie Universität Berlin
C3  - SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain
T1  - Protein Persulfidation Protects Against Aging
SP  - 169
EP  - 169
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6039
ER  - 
@conference{
author = "Živanović, Jasmina and Kouroussis, Emilia and Kohl, Joshua and Miler, Marko and Mitchell, Sarah and Mitchell, James and Schwartz, Guenter and Milošević, Verica and Filipović R., Miloš",
year = "2019",
abstract = "For couple of decades aging is believed to be a consequence of damages accumulated by increased production of reactive oxygen species (ROS). Opposite to that, dietary restriction attempts to extend life have been linked to increased H2S production. We hypothesized that reacting with sulfenic acids (formed by ROS) H2S would rescue cysteine residue by forming persulfides. Persulfides are better ROS scavengers and could form protein S-sulfonates that could be cleaved back by disulfide reductase to restore free thiolate. This rescue loop would thus prevent irreversible thiol hyperoxidation. Using dimedone switch method we could first show that persulfidation is a posttranslational modification that is evolutionarily conserved (bacteria, flies, worms, mice and humans). Then we could also observe that thioredoxin readily catalyzes the reduction of cysteine S-sulfonate, two orders of magnitude faster than the reduction of corresponding disulfide. The persulfidation levels/H2S producing ability positively correlated with the ability of yeast, worms and mammalian cells to resist stress caused by ROS. Persulfidation declines with aging in worms, rats and mice, due to the downregulation of H2S producing enzymes, but dietary restriction in mice and worms restores persulfide levels and improves their lifespan. Based on these data we suggest that persulfidation represents an evolutionarily conserved anti-aging mechanism.",
publisher = "Berlin: Freie Universität Berlin",
journal = "SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain",
title = "Protein Persulfidation Protects Against Aging",
pages = "169-169",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6039"
}
Živanović, J., Kouroussis, E., Kohl, J., Miler, M., Mitchell, S., Mitchell, J., Schwartz, G., Milošević, V.,& Filipović R., M.. (2019). Protein Persulfidation Protects Against Aging. in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain
Berlin: Freie Universität Berlin., 169-169.
https://hdl.handle.net/21.15107/rcub_ibiss_6039
Živanović J, Kouroussis E, Kohl J, Miler M, Mitchell S, Mitchell J, Schwartz G, Milošević V, Filipović R. M. Protein Persulfidation Protects Against Aging. in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain. 2019;:169-169.
https://hdl.handle.net/21.15107/rcub_ibiss_6039 .
Živanović, Jasmina, Kouroussis, Emilia, Kohl, Joshua, Miler, Marko, Mitchell, Sarah, Mitchell, James, Schwartz, Guenter, Milošević, Verica, Filipović R., Miloš, "Protein Persulfidation Protects Against Aging" in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain (2019):169-169,
https://hdl.handle.net/21.15107/rcub_ibiss_6039 .

The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.

Šošić-Jurjević, Branka ; Lütjohann, Dieter; Renko, Kostja; Filipović, Branko; Radulović, Niko; Ajdžanović, Vladimir; Trifunović, Svetlana; Nestorović, Nataša; Živanović, Jasmina; Manojlović-Stojanoski, Milica; Kӧhrle, Josef; Milošević, Verica

(2019)

TY  - JOUR
AU  - Šošić-Jurjević, Branka 
AU  - Lütjohann, Dieter
AU  - Renko, Kostja
AU  - Filipović, Branko
AU  - Radulović, Niko
AU  - Ajdžanović, Vladimir
AU  - Trifunović, Svetlana
AU  - Nestorović, Nataša
AU  - Živanović, Jasmina
AU  - Manojlović-Stojanoski, Milica
AU  - Kӧhrle, Josef
AU  - Milošević, Verica
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0960076018307507
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3305
AB  - We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.
T2  - The Journal of Steroid Biochemistry and Molecular Miology
T1  - The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.
VL  - 190
DO  - 10.1016/j.jsbmb.2019.03.009
SP  - 1
EP  - 10
ER  - 
@article{
author = "Šošić-Jurjević, Branka  and Lütjohann, Dieter and Renko, Kostja and Filipović, Branko and Radulović, Niko and Ajdžanović, Vladimir and Trifunović, Svetlana and Nestorović, Nataša and Živanović, Jasmina and Manojlović-Stojanoski, Milica and Kӧhrle, Josef and Milošević, Verica",
year = "2019",
abstract = "We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.",
journal = "The Journal of Steroid Biochemistry and Molecular Miology",
title = "The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.",
volume = "190",
doi = "10.1016/j.jsbmb.2019.03.009",
pages = "1-10"
}
Šošić-Jurjević, B., Lütjohann, D., Renko, K., Filipović, B., Radulović, N., Ajdžanović, V., Trifunović, S., Nestorović, N., Živanović, J., Manojlović-Stojanoski, M., Kӧhrle, J.,& Milošević, V.. (2019). The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.. in The Journal of Steroid Biochemistry and Molecular Miology, 190, 1-10.
https://doi.org/10.1016/j.jsbmb.2019.03.009
Šošić-Jurjević B, Lütjohann D, Renko K, Filipović B, Radulović N, Ajdžanović V, Trifunović S, Nestorović N, Živanović J, Manojlović-Stojanoski M, Kӧhrle J, Milošević V. The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.. in The Journal of Steroid Biochemistry and Molecular Miology. 2019;190:1-10.
doi:10.1016/j.jsbmb.2019.03.009 .
Šošić-Jurjević, Branka , Lütjohann, Dieter, Renko, Kostja, Filipović, Branko, Radulović, Niko, Ajdžanović, Vladimir, Trifunović, Svetlana, Nestorović, Nataša, Živanović, Jasmina, Manojlović-Stojanoski, Milica, Kӧhrle, Josef, Milošević, Verica, "The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats." in The Journal of Steroid Biochemistry and Molecular Miology, 190 (2019):1-10,
https://doi.org/10.1016/j.jsbmb.2019.03.009 . .
43
23
39

Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause.

Živanović, Jasmina; Jarić, Ivana; Ajdžanović, Vladimir; Mojić, Marija; Miler, Marko; Šošić-Jurjević, Branka ; Milošević, Verica; Filipović, Branko

(2019)

TY  - JOUR
AU  - Živanović, Jasmina
AU  - Jarić, Ivana
AU  - Ajdžanović, Vladimir
AU  - Mojić, Marija
AU  - Miler, Marko
AU  - Šošić-Jurjević, Branka 
AU  - Milošević, Verica
AU  - Filipović, Branko
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0940960218301080?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3150
AB  - In a rat model of the andropause we aimed to examine the influence of daidzein, soy isoflavone, on the structure and function of parathyroid glands (PTG) and the expression levels of some of the crucial regulators of Ca2+ and Pi homeostasis in the kidney, and to compare these effects with the effects of estradiol, serving as a positive control. Middle-aged (16-month-old) male Wistar rats were divided into the following groups: sham-operated (SO), orchidectomized (Orx), orchidectomized and estradiol-treated (Orx+E; 0.625mg/kg b.w./day, s.c.) as well as orchidectomized and daidzein-treated (Orx+D; 30mg/kg b.w./day, s.c.) group. Every treated group had a corresponding control group. PTH serum concentration was decreased in Orx+E and Orx+D groups by 10% and 21% (p<0.05) respectively, in comparison with the Orx. PTG volume was decreased in Orx+E group by 16% (p<0.05), when compared to the Orx. In Orx+E group expression of NaPi 2a was lower (p<0.05), while NaPi 2a abundance in Orx+D animals was increased (p<0.05), when compared to Orx. Expression of PTH1R was increased (p<0.05) in Orx+E group, while in Orx+D animals the same parameter was decreased (p<0.05), in comparison with Orx. Klotho expression was elevated (p<0.05) in Orx+D rats, in regard to Orx. Orx+D induced reduction in Ca2+/creatinine and Pi/creatinine ratio in urine by 32% and 16% (p<0.05) respectively, in comparison with Orx. In conclusion, presented results indicate the more coherent beneficial effects of daidzein compared to estradiol, on disturbed Ca2+ and Pi homeostasis, and presumably on bone health, in the aging male rats.
T2  - Annals of Anatomy = Anatomischer Anzeiger
T1  - Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause.
VL  - 221
DO  - 10.1016/j.aanat.2018.08.001
SP  - 27
EP  - 37
ER  - 
@article{
author = "Živanović, Jasmina and Jarić, Ivana and Ajdžanović, Vladimir and Mojić, Marija and Miler, Marko and Šošić-Jurjević, Branka  and Milošević, Verica and Filipović, Branko",
year = "2019",
abstract = "In a rat model of the andropause we aimed to examine the influence of daidzein, soy isoflavone, on the structure and function of parathyroid glands (PTG) and the expression levels of some of the crucial regulators of Ca2+ and Pi homeostasis in the kidney, and to compare these effects with the effects of estradiol, serving as a positive control. Middle-aged (16-month-old) male Wistar rats were divided into the following groups: sham-operated (SO), orchidectomized (Orx), orchidectomized and estradiol-treated (Orx+E; 0.625mg/kg b.w./day, s.c.) as well as orchidectomized and daidzein-treated (Orx+D; 30mg/kg b.w./day, s.c.) group. Every treated group had a corresponding control group. PTH serum concentration was decreased in Orx+E and Orx+D groups by 10% and 21% (p<0.05) respectively, in comparison with the Orx. PTG volume was decreased in Orx+E group by 16% (p<0.05), when compared to the Orx. In Orx+E group expression of NaPi 2a was lower (p<0.05), while NaPi 2a abundance in Orx+D animals was increased (p<0.05), when compared to Orx. Expression of PTH1R was increased (p<0.05) in Orx+E group, while in Orx+D animals the same parameter was decreased (p<0.05), in comparison with Orx. Klotho expression was elevated (p<0.05) in Orx+D rats, in regard to Orx. Orx+D induced reduction in Ca2+/creatinine and Pi/creatinine ratio in urine by 32% and 16% (p<0.05) respectively, in comparison with Orx. In conclusion, presented results indicate the more coherent beneficial effects of daidzein compared to estradiol, on disturbed Ca2+ and Pi homeostasis, and presumably on bone health, in the aging male rats.",
journal = "Annals of Anatomy = Anatomischer Anzeiger",
title = "Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause.",
volume = "221",
doi = "10.1016/j.aanat.2018.08.001",
pages = "27-37"
}
Živanović, J., Jarić, I., Ajdžanović, V., Mojić, M., Miler, M., Šošić-Jurjević, B., Milošević, V.,& Filipović, B.. (2019). Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause.. in Annals of Anatomy = Anatomischer Anzeiger, 221, 27-37.
https://doi.org/10.1016/j.aanat.2018.08.001
Živanović J, Jarić I, Ajdžanović V, Mojić M, Miler M, Šošić-Jurjević B, Milošević V, Filipović B. Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause.. in Annals of Anatomy = Anatomischer Anzeiger. 2019;221:27-37.
doi:10.1016/j.aanat.2018.08.001 .
Živanović, Jasmina, Jarić, Ivana, Ajdžanović, Vladimir, Mojić, Marija, Miler, Marko, Šošić-Jurjević, Branka , Milošević, Verica, Filipović, Branko, "Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause." in Annals of Anatomy = Anatomischer Anzeiger, 221 (2019):27-37,
https://doi.org/10.1016/j.aanat.2018.08.001 . .
8
8
8

The effects of Vitex agnus castus L. essential oil on the pituitary cells in middle aged rats

Milošević, Verica; Filipović, Branko; Živanović, Jasmina; Miler, Marko; Manojlović-Stojanoski, Milica; Ušćebrka, gordana; Ajdžanović, Vladimir

(Saint-Petersburg: Eco-Vector, 2019)

TY  - CONF
AU  - Milošević, Verica
AU  - Filipović, Branko
AU  - Živanović, Jasmina
AU  - Miler, Marko
AU  - Manojlović-Stojanoski, Milica
AU  - Ušćebrka, gordana
AU  - Ajdžanović, Vladimir
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5927
AB  - In traditional medicine, the Mediterranean plant Vitex after the last injection. Pituitary glands were excised, agnus-castus L., Familia Verbenacee (Vac) has been weighed and processed for the stereological analysis. used since ancient times to alleviate the symptoms of ACTH-, TSH- and PRL-producing cells were identified with aging. We have already shown that the essential oil of polyclonal rabbit antisera (ACTH, TSHß, PRL respectively).
Vac stimulates thyroid C cells activity and decreases bone ACTH and TSH blood levels were determined using the turnover in middle-aged male rats [1). Herein, essential immunoassays. The stereological analysis, after treatment oil isolated by hydrodistillation from ripe Vac barriers was with Vac, showed that the immunopositive ACTH and applied to middle aged male rats with aim to evaluate its PRL cells had decreased (p<0.05) relative volume density effects on the pituitary hormone producing cells. Animals by 18 and 36% respectively, while the same parameter were divided into two groups. The first group was treated was significantly increased by 73% in TSH cells, all in subcutaneously with Vac essential oil (60 mg/kg b.m.), comparison with the values obtained for the controls. once a day for 3 weeks, while the second one was treated
Circulating concentration of ACTH decreased (p<0.05) by
with sterile olive oil by the same schedule, and served as 52%, while the level of TSH increased (p<0.01) for 45%, the control. The administered dose of Vac essential oil had all compared to the adequate parameters in control rats. bone-protective and sedative effects, as well as analgesic These results show that Vac essential oil differently affects effect in our and other researchers' studies, with absolute the stereological parameters and hormonal output of rate of survival [1, 2]. Decapitatation was performed 24h various pituitary cells.
PB  - Saint-Petersburg: Eco-Vector
C3  - 23th International Congress Phytopharm; 2019 Jul 1-3; Saint-Petersburg, Russia
T1  - The effects of Vitex agnus castus L. essential oil on the pituitary cells in middle aged rats
SP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5927
ER  - 
@conference{
author = "Milošević, Verica and Filipović, Branko and Živanović, Jasmina and Miler, Marko and Manojlović-Stojanoski, Milica and Ušćebrka, gordana and Ajdžanović, Vladimir",
year = "2019",
abstract = "In traditional medicine, the Mediterranean plant Vitex after the last injection. Pituitary glands were excised, agnus-castus L., Familia Verbenacee (Vac) has been weighed and processed for the stereological analysis. used since ancient times to alleviate the symptoms of ACTH-, TSH- and PRL-producing cells were identified with aging. We have already shown that the essential oil of polyclonal rabbit antisera (ACTH, TSHß, PRL respectively).
Vac stimulates thyroid C cells activity and decreases bone ACTH and TSH blood levels were determined using the turnover in middle-aged male rats [1). Herein, essential immunoassays. The stereological analysis, after treatment oil isolated by hydrodistillation from ripe Vac barriers was with Vac, showed that the immunopositive ACTH and applied to middle aged male rats with aim to evaluate its PRL cells had decreased (p<0.05) relative volume density effects on the pituitary hormone producing cells. Animals by 18 and 36% respectively, while the same parameter were divided into two groups. The first group was treated was significantly increased by 73% in TSH cells, all in subcutaneously with Vac essential oil (60 mg/kg b.m.), comparison with the values obtained for the controls. once a day for 3 weeks, while the second one was treated
Circulating concentration of ACTH decreased (p<0.05) by
with sterile olive oil by the same schedule, and served as 52%, while the level of TSH increased (p<0.01) for 45%, the control. The administered dose of Vac essential oil had all compared to the adequate parameters in control rats. bone-protective and sedative effects, as well as analgesic These results show that Vac essential oil differently affects effect in our and other researchers' studies, with absolute the stereological parameters and hormonal output of rate of survival [1, 2]. Decapitatation was performed 24h various pituitary cells.",
publisher = "Saint-Petersburg: Eco-Vector",
journal = "23th International Congress Phytopharm; 2019 Jul 1-3; Saint-Petersburg, Russia",
title = "The effects of Vitex agnus castus L. essential oil on the pituitary cells in middle aged rats",
pages = "40",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5927"
}
Milošević, V., Filipović, B., Živanović, J., Miler, M., Manojlović-Stojanoski, M., Ušćebrka, g.,& Ajdžanović, V.. (2019). The effects of Vitex agnus castus L. essential oil on the pituitary cells in middle aged rats. in 23th International Congress Phytopharm; 2019 Jul 1-3; Saint-Petersburg, Russia
Saint-Petersburg: Eco-Vector., 40.
https://hdl.handle.net/21.15107/rcub_ibiss_5927
Milošević V, Filipović B, Živanović J, Miler M, Manojlović-Stojanoski M, Ušćebrka G, Ajdžanović V. The effects of Vitex agnus castus L. essential oil on the pituitary cells in middle aged rats. in 23th International Congress Phytopharm; 2019 Jul 1-3; Saint-Petersburg, Russia. 2019;:40.
https://hdl.handle.net/21.15107/rcub_ibiss_5927 .
Milošević, Verica, Filipović, Branko, Živanović, Jasmina, Miler, Marko, Manojlović-Stojanoski, Milica, Ušćebrka, gordana, Ajdžanović, Vladimir, "The effects of Vitex agnus castus L. essential oil on the pituitary cells in middle aged rats" in 23th International Congress Phytopharm; 2019 Jul 1-3; Saint-Petersburg, Russia (2019):40,
https://hdl.handle.net/21.15107/rcub_ibiss_5927 .

Prostate cancer metastasis and soy isoflavones: a dogfight over a bone

Ajdžanović, Vladimir; Filipović, Branko; Miljić, Dragana; Mijatović, Sanja; Maksimović-Ivanić, Danijela; Miler, Marko; Živanović, Jasmina; Milošević, Verica

(2019)

TY  - JOUR
AU  - Ajdžanović, Vladimir
AU  - Filipović, Branko
AU  - Miljić, Dragana
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Milošević, Verica
PY  - 2019
UR  - http://www.excli.de/vol18/Ajdzanovic_19022019_proof.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3293
AB  - Prostate cancer is a complex, progressive, bone-tropic disease, which is usually associated with skeletal issues, poor mobility and a fatal outcome when it reaches the metastatic phase. Soy isoflavones, steroid-like compounds from soy-based food/dietary supplements, have been found to decrease the risk of prostate cancer in frequent consumers. Herein, we present a systematization of the data on soy isoflavone effects at different stages of metastatic prostate cancer progression, with a particular interest in the context of bone-related molecular events. Specifically, soy isoflavones have been determined to downregulate the prostate cancer cell androgen receptors, reverse the epithelial to mesenchymal transition of these cells, decrease the expressions of prostate-specific antigen, matrix metalloproteinase and serine proteinase, and reduce the superficial membrane fluidity in prostate cancer cells. In addition, soy isoflavones suppress the angiogenesis that follows prostate cancer growth, obstruct prostate cancer cells adhesion to the vascular endothelium and their extravasation in the area of future bone lesions, improve the general bone morphofunctional status, have a beneficial effect on prostate cancer metastasiscaused osteolytic/osteoblastic lesions and possibly affect the pre-metastatic niche formation. The observed, multilevel antimetastatic properties of soy isoflavones imply that they should be considered as promising components of combined therapeutic approaches to advanced prostate cancer.
T2  - EXCLI Journal
T1  - Prostate cancer metastasis and soy isoflavones: a dogfight over a bone
VL  - 18
DO  - 10.17179/excli2018-1836
SP  - 106
EP  - 126
ER  - 
@article{
author = "Ajdžanović, Vladimir and Filipović, Branko and Miljić, Dragana and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Miler, Marko and Živanović, Jasmina and Milošević, Verica",
year = "2019",
abstract = "Prostate cancer is a complex, progressive, bone-tropic disease, which is usually associated with skeletal issues, poor mobility and a fatal outcome when it reaches the metastatic phase. Soy isoflavones, steroid-like compounds from soy-based food/dietary supplements, have been found to decrease the risk of prostate cancer in frequent consumers. Herein, we present a systematization of the data on soy isoflavone effects at different stages of metastatic prostate cancer progression, with a particular interest in the context of bone-related molecular events. Specifically, soy isoflavones have been determined to downregulate the prostate cancer cell androgen receptors, reverse the epithelial to mesenchymal transition of these cells, decrease the expressions of prostate-specific antigen, matrix metalloproteinase and serine proteinase, and reduce the superficial membrane fluidity in prostate cancer cells. In addition, soy isoflavones suppress the angiogenesis that follows prostate cancer growth, obstruct prostate cancer cells adhesion to the vascular endothelium and their extravasation in the area of future bone lesions, improve the general bone morphofunctional status, have a beneficial effect on prostate cancer metastasiscaused osteolytic/osteoblastic lesions and possibly affect the pre-metastatic niche formation. The observed, multilevel antimetastatic properties of soy isoflavones imply that they should be considered as promising components of combined therapeutic approaches to advanced prostate cancer.",
journal = "EXCLI Journal",
title = "Prostate cancer metastasis and soy isoflavones: a dogfight over a bone",
volume = "18",
doi = "10.17179/excli2018-1836",
pages = "106-126"
}
Ajdžanović, V., Filipović, B., Miljić, D., Mijatović, S., Maksimović-Ivanić, D., Miler, M., Živanović, J.,& Milošević, V.. (2019). Prostate cancer metastasis and soy isoflavones: a dogfight over a bone. in EXCLI Journal, 18, 106-126.
https://doi.org/10.17179/excli2018-1836
Ajdžanović V, Filipović B, Miljić D, Mijatović S, Maksimović-Ivanić D, Miler M, Živanović J, Milošević V. Prostate cancer metastasis and soy isoflavones: a dogfight over a bone. in EXCLI Journal. 2019;18:106-126.
doi:10.17179/excli2018-1836 .
Ajdžanović, Vladimir, Filipović, Branko, Miljić, Dragana, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Miler, Marko, Živanović, Jasmina, Milošević, Verica, "Prostate cancer metastasis and soy isoflavones: a dogfight over a bone" in EXCLI Journal, 18 (2019):106-126,
https://doi.org/10.17179/excli2018-1836 . .
4
10

The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.

Filipović, Branko; Šošić-Jurjević, Branka ; Ajdžanović, Vladimir; Živanović, Jasmina; Manojlović-Stojanoski, Milica; Nestorović, Nataša; Ristić, Nataša; Trifunović, Svetlana; Milošević, Verica

(2018)

TY  - JOUR
AU  - Filipović, Branko
AU  - Šošić-Jurjević, Branka 
AU  - Ajdžanović, Vladimir
AU  - Živanović, Jasmina
AU  - Manojlović-Stojanoski, Milica
AU  - Nestorović, Nataša
AU  - Ristić, Nataša
AU  - Trifunović, Svetlana
AU  - Milošević, Verica
PY  - 2018
UR  - http://doi.wiley.com/10.1111/joa.12828
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3079
AB  - As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg-1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C-cells by immunohistochemical staining for thyroglobulin and CT. Thyroid follicular epithelium, interstitium, colloid and CT-immunopositive C-cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T3 ), thyroxine (T4 ) and CT were determined as well as urinary calcium (Ca2+ ) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P < 0.05), but trabecular separation (Tb.Sp) was decreased (P < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P < 0.05) compared with Orx, whereas Vv of the colloid was lower (P < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC, T3 , T4 and urinary Ca2+ concentrations (P < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.
T2  - Journal of Anatomy
T2  - Journal of Anatomy
T1  - The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.
IS  - 2
VL  - 233
DO  - 10.1111/joa.12828
SP  - 204
EP  - 212
ER  - 
@article{
author = "Filipović, Branko and Šošić-Jurjević, Branka  and Ajdžanović, Vladimir and Živanović, Jasmina and Manojlović-Stojanoski, Milica and Nestorović, Nataša and Ristić, Nataša and Trifunović, Svetlana and Milošević, Verica",
year = "2018",
abstract = "As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg-1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C-cells by immunohistochemical staining for thyroglobulin and CT. Thyroid follicular epithelium, interstitium, colloid and CT-immunopositive C-cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T3 ), thyroxine (T4 ) and CT were determined as well as urinary calcium (Ca2+ ) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P < 0.05), but trabecular separation (Tb.Sp) was decreased (P < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P < 0.05) compared with Orx, whereas Vv of the colloid was lower (P < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC, T3 , T4 and urinary Ca2+ concentrations (P < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.",
journal = "Journal of Anatomy, Journal of Anatomy",
title = "The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.",
number = "2",
volume = "233",
doi = "10.1111/joa.12828",
pages = "204-212"
}
Filipović, B., Šošić-Jurjević, B., Ajdžanović, V., Živanović, J., Manojlović-Stojanoski, M., Nestorović, N., Ristić, N., Trifunović, S.,& Milošević, V.. (2018). The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.. in Journal of Anatomy, 233(2), 204-212.
https://doi.org/10.1111/joa.12828
Filipović B, Šošić-Jurjević B, Ajdžanović V, Živanović J, Manojlović-Stojanoski M, Nestorović N, Ristić N, Trifunović S, Milošević V. The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.. in Journal of Anatomy. 2018;233(2):204-212.
doi:10.1111/joa.12828 .
Filipović, Branko, Šošić-Jurjević, Branka , Ajdžanović, Vladimir, Živanović, Jasmina, Manojlović-Stojanoski, Milica, Nestorović, Nataša, Ristić, Nataša, Trifunović, Svetlana, Milošević, Verica, "The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis." in Journal of Anatomy, 233, no. 2 (2018):204-212,
https://doi.org/10.1111/joa.12828 . .
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Diosgenin Affects Steroid Hormone Production and Gene Expression of Antioxidative Enzymes in the Ovary of Middle-aged Rats

Jarić, Ivana; Miler, Marko; Ajdžanović, Vladimir; Živanović, Jasmina; Pendoski, Laze; Žikić, Dragan; Ušćebrka, Gordana; Milošević, Verica

(Skopje: Faculty of Veterinary Medicine, 2018)

TY  - CONF
AU  - Jarić, Ivana
AU  - Miler, Marko
AU  - Ajdžanović, Vladimir
AU  - Živanović, Jasmina
AU  - Pendoski, Laze
AU  - Žikić, Dragan
AU  - Ušćebrka, Gordana
AU  - Milošević, Verica
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6037
AB  - Diosgenin is bioactive, steroidal saponin from Dioscorea viliosa (Wild Yam) and appears to be novel promising substance for the treatment of menopausal symptoms. In addition, diosgenin may manipulate the endogenous steroid hormone levels and may affect the numerous oxidative stress pathways/molecules. Since decline in the steroid hormone levels as well as increase in oxidative stress in the ovaries play an integral part of the menopause, this study aimed to investigate the effects of diosgenin on production of estradiol and progesterone, as well as to investigated the effects of diosgenin on the expression of genes encoding the antioxidant enzymes (Cu, Zn-superoxide dismutase (CuZnSOD), Mn-superoxide dismutase (MnSOD), glutathione peroxidase (GPX), and catalase (CAD) in ovary of acyclic-middle aged female rats. Middle-aged (l3-months-old) acyclic female Wistar rats in constant diestrus stage, which represent tractable model to human menopause, were divided into control and diosgenin treated groups.Diosgenin (100 mgfl<g b.w.lday) was orally applied for 4 weeks, while C group received the vehicle alone. In our experimental model, diosgenin administration to acyclic middle-aged rats significantly increased estradiol and progesterone serum concentrations when compared to the corresponding control. Gene expression analysis revealed that diosgenin significantly down-regulate all examined enzymes involved in antioxidative defense. The down-regulation were especially pronounced in CuZnSOD and CAT, indicating that the diosgenin may decrease the pool of reactive oxygen species in the ovary directly due and may act as free radical scavengers. Therefore, our results indicate beneficial potential of diosgenin in the middle-aged rat ovary.
PB  - Skopje: Faculty of Veterinary Medicine
C3  - Book of abstracts: join meeting: 5th International Vet-Istanbul group congress and 8th International scientific meeting days of veterinary medicine; 2018, Sep 23-27; Ohrid, Macedonia
T1  - Diosgenin Affects Steroid Hormone Production and Gene Expression of Antioxidative Enzymes in the Ovary of Middle-aged Rats
SP  - 147
EP  - 147
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6037
ER  - 
@conference{
author = "Jarić, Ivana and Miler, Marko and Ajdžanović, Vladimir and Živanović, Jasmina and Pendoski, Laze and Žikić, Dragan and Ušćebrka, Gordana and Milošević, Verica",
year = "2018",
abstract = "Diosgenin is bioactive, steroidal saponin from Dioscorea viliosa (Wild Yam) and appears to be novel promising substance for the treatment of menopausal symptoms. In addition, diosgenin may manipulate the endogenous steroid hormone levels and may affect the numerous oxidative stress pathways/molecules. Since decline in the steroid hormone levels as well as increase in oxidative stress in the ovaries play an integral part of the menopause, this study aimed to investigate the effects of diosgenin on production of estradiol and progesterone, as well as to investigated the effects of diosgenin on the expression of genes encoding the antioxidant enzymes (Cu, Zn-superoxide dismutase (CuZnSOD), Mn-superoxide dismutase (MnSOD), glutathione peroxidase (GPX), and catalase (CAD) in ovary of acyclic-middle aged female rats. Middle-aged (l3-months-old) acyclic female Wistar rats in constant diestrus stage, which represent tractable model to human menopause, were divided into control and diosgenin treated groups.Diosgenin (100 mgfl<g b.w.lday) was orally applied for 4 weeks, while C group received the vehicle alone. In our experimental model, diosgenin administration to acyclic middle-aged rats significantly increased estradiol and progesterone serum concentrations when compared to the corresponding control. Gene expression analysis revealed that diosgenin significantly down-regulate all examined enzymes involved in antioxidative defense. The down-regulation were especially pronounced in CuZnSOD and CAT, indicating that the diosgenin may decrease the pool of reactive oxygen species in the ovary directly due and may act as free radical scavengers. Therefore, our results indicate beneficial potential of diosgenin in the middle-aged rat ovary.",
publisher = "Skopje: Faculty of Veterinary Medicine",
journal = "Book of abstracts: join meeting: 5th International Vet-Istanbul group congress and 8th International scientific meeting days of veterinary medicine; 2018, Sep 23-27; Ohrid, Macedonia",
title = "Diosgenin Affects Steroid Hormone Production and Gene Expression of Antioxidative Enzymes in the Ovary of Middle-aged Rats",
pages = "147-147",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6037"
}
Jarić, I., Miler, M., Ajdžanović, V., Živanović, J., Pendoski, L., Žikić, D., Ušćebrka, G.,& Milošević, V.. (2018). Diosgenin Affects Steroid Hormone Production and Gene Expression of Antioxidative Enzymes in the Ovary of Middle-aged Rats. in Book of abstracts: join meeting: 5th International Vet-Istanbul group congress and 8th International scientific meeting days of veterinary medicine; 2018, Sep 23-27; Ohrid, Macedonia
Skopje: Faculty of Veterinary Medicine., 147-147.
https://hdl.handle.net/21.15107/rcub_ibiss_6037
Jarić I, Miler M, Ajdžanović V, Živanović J, Pendoski L, Žikić D, Ušćebrka G, Milošević V. Diosgenin Affects Steroid Hormone Production and Gene Expression of Antioxidative Enzymes in the Ovary of Middle-aged Rats. in Book of abstracts: join meeting: 5th International Vet-Istanbul group congress and 8th International scientific meeting days of veterinary medicine; 2018, Sep 23-27; Ohrid, Macedonia. 2018;:147-147.
https://hdl.handle.net/21.15107/rcub_ibiss_6037 .
Jarić, Ivana, Miler, Marko, Ajdžanović, Vladimir, Živanović, Jasmina, Pendoski, Laze, Žikić, Dragan, Ušćebrka, Gordana, Milošević, Verica, "Diosgenin Affects Steroid Hormone Production and Gene Expression of Antioxidative Enzymes in the Ovary of Middle-aged Rats" in Book of abstracts: join meeting: 5th International Vet-Istanbul group congress and 8th International scientific meeting days of veterinary medicine; 2018, Sep 23-27; Ohrid, Macedonia (2018):147-147,
https://hdl.handle.net/21.15107/rcub_ibiss_6037 .