Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200161 (University of Belgrade, Faculty of Pharmacy)

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Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200161 (University of Belgrade, Faculty of Pharmacy) (en)
Ministarstvo prosvete, nauke i tehnološkog razvoja Republike Srbije, Ugovor br. 451-03-68/2020-14/200161 (Univerzitet u Beogradu, Farmaceutski fakultet) (sr_RS)
Министарство просвете, науке и технолошког развоја Републике Србије, Уговор бр. 451-03-68/2020-14/200161 (Универзитет у Београду, Фармацеутски факултет) (sr)
Authors

Publications

Lunić, Tanja; Petković, Miloš; Rakić, Marija; Lađarević, Jelena; Repac, Jelena; Nedeljković, B.B.; Božić-Nedeljković, Biljana

(Elsevier, 2025)

TY  - JOUR
AU  - Lunić, Tanja
AU  - Petković, Miloš
AU  - Rakić, Marija
AU  - Lađarević, Jelena
AU  - Repac, Jelena
AU  - Nedeljković, B.B.
AU  - Božić-Nedeljković, Biljana
PY  - 2025
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5750
AB  - This study explores the anti-neuroinflammatory and antioxidant potential of 42 hydroxybenzoic acid esters and three parent acids. Molecular docking simulations targeted key proteins involved in the lipopolysaccharide (LPS) signaling pathway to identify lead compounds for synthesis and in vitro evaluation. Among the screened esters, the most promising candidates demonstrated antioxidant activity comparable to vitamin C in ABTS and DPPH assays. Additionally, these esters significantly reduced the production of reactive oxygen species (ROS) and nitric oxide (NO) in H2O2- and LPS-stimulated BV2 microglial cells, indicating their ability to attenuate neuroinflammation. Further testing in SH-SY5Y neuronal cells exposed to microglia-derived supernatants confirmed the neuroprotective effects of these esters, reducing microglia-mediated neurotoxicity. These results suggest that hydroxybenzoic acid ester derivatives are promising candidates for mitigating microglia-driven neuroinflammation and protecting neurons, offering potential therapeutic applications for neurodegenerative diseases.
PB  - Elsevier
T2  - Journal of Molecular Structure
VL  - 1321
DO  - 10.1016/j.molstruc.2024.139804
ER  - 
@article{
author = "Lunić, Tanja and Petković, Miloš and Rakić, Marija and Lađarević, Jelena and Repac, Jelena and Nedeljković, B.B. and Božić-Nedeljković, Biljana",
year = "2025",
abstract = "This study explores the anti-neuroinflammatory and antioxidant potential of 42 hydroxybenzoic acid esters and three parent acids. Molecular docking simulations targeted key proteins involved in the lipopolysaccharide (LPS) signaling pathway to identify lead compounds for synthesis and in vitro evaluation. Among the screened esters, the most promising candidates demonstrated antioxidant activity comparable to vitamin C in ABTS and DPPH assays. Additionally, these esters significantly reduced the production of reactive oxygen species (ROS) and nitric oxide (NO) in H2O2- and LPS-stimulated BV2 microglial cells, indicating their ability to attenuate neuroinflammation. Further testing in SH-SY5Y neuronal cells exposed to microglia-derived supernatants confirmed the neuroprotective effects of these esters, reducing microglia-mediated neurotoxicity. These results suggest that hydroxybenzoic acid ester derivatives are promising candidates for mitigating microglia-driven neuroinflammation and protecting neurons, offering potential therapeutic applications for neurodegenerative diseases.",
publisher = "Elsevier",
journal = "Journal of Molecular Structure",
volume = "1321",
doi = "10.1016/j.molstruc.2024.139804"
}
Lunić, T., Petković, M., Rakić, M., Lađarević, J., Repac, J., Nedeljković, B.B.,& Božić-Nedeljković, B.. (2025). in Journal of Molecular Structure
Elsevier., 1321.
https://doi.org/10.1016/j.molstruc.2024.139804
Lunić T, Petković M, Rakić M, Lađarević J, Repac J, Nedeljković B, Božić-Nedeljković B. in Journal of Molecular Structure. 2025;1321.
doi:10.1016/j.molstruc.2024.139804 .
Lunić, Tanja, Petković, Miloš, Rakić, Marija, Lađarević, Jelena, Repac, Jelena, Nedeljković, B.B., Božić-Nedeljković, Biljana, in Journal of Molecular Structure, 1321 (2025),
https://doi.org/10.1016/j.molstruc.2024.139804 . .

Synthesis and in vitro study of redox properties of pyrrole and halogenated pyrrole derivatives

Petković, Miloš; Kotur-Stevuljević, Jelena; Jovanović, Predrag; Jovanović, Miloš; Mitrović, Nikola; Simić, Milena; Tasić, Gordana; Savić, Vladimir

(Serbian Chemical Society., 2024)

TY  - JOUR
AU  - Petković, Miloš
AU  - Kotur-Stevuljević, Jelena
AU  - Jovanović, Predrag
AU  - Jovanović, Miloš
AU  - Mitrović, Nikola
AU  - Simić, Milena
AU  - Tasić, Gordana
AU  - Savić, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5763
AB  - The  redox  balance  plays  a  crucial  role  in  maintaining  biological processes  under  normal  conditions.  Antioxidants  inhibit  and  reduce  harmful oxidation  processes,  while  pro-oxidants  can  act  as  anti-cancer  agents  by promoting  ROS-mediated  cell  death.  The  aim  of  this  study  is  to  compare  the redox  properties  of  seven  newly  synthesised  tribromopyrrole  derivatives  with three novel and four previously synthesized non-halogenated analogues in an in vitro  model  (in  human  serum)  and  with  exogenously  induced oxidative  stress. The  obtained  values  of  their  oxy  scores  (OS)  were  compared  and  the  result showed  that  four  non-halogenated  pyrrole  derivatives  with  secondary  amide group M2, M10,  M11  and M12  have  lower  OS  values  than  Trolox,  a  water-soluble  analogue  of  vitamin  E  with  proven  antioxidant  properties.  All  four compounds show strong resistance to oxidative stress, which is reflected in the maintenance of negative OS values when exposed to exogenous oxidative stress using TBH in the reaction mixture. This capability to resist invading ROS should be  expected  also  in  an  endogenous  environment,  where  constant  prooxidant production  takes  place  at  a  low,  homeostatic  level,  but  even  more  so  in pathological  conditions.  The  tribrominated  derivative M15 showed prooxidant activity  with  a  significantly  higher  OS  value  than  all  other  compounds  tested. The comparison of the dose-response of Trolox and the five compounds with the lowest OS also shows that compounds M2,  M7 and M10 have better antioxidant activity than Trolox.
AB  - Редоксравнотежа игра кључну улогу у одржавању биолошких процеса у нормалним условима.  Антиоксиданси  инхибирају  и  смањују  штетне  процесе  оксидације,  док прооксиданси  могу  деловати  као  антиканцерски  агенси  промовишући  ћелијску  смрт посредовану реактивним кисеоничним врстама. Циљ овог рада је да се упореде редокс својства седам  новосинтетисаних деривата трибромопирола и нехалогенованих аналога(три  новосинтетисанаи  четири  претходно  синтетисана) у in  vitroмоделу  (у  хуманом серуму)  и  са  егзогеноиндукованим  оксидативним  стресом.  Упоређене  су  добијене вредности њихових окси скорова (ОС) и резултат је показао да четири нехалогенована деривата  пирола  са  секундарном  амидном  групом М2,  М10,  М11и М12имају  ниже вредности  ОС  од  Тролокса,  аналога  витамина  Е  растворљивог  у  води  са  доказаним антиоксидативним  својствима.  Сва  четири  једињења  показују  јаку  отпорност  на оксидативни стрес, што се огледа у одржавању негативних вредности ОС када су изложене егзогеном оксидативном стресу коришћењем ТБХ у реакционој смеши. Ову способност да се одупируРОС треба очекивати и у ендогеном окружењу, где се константна производња прооксиданата  одвија  на  ниском,  хомеостатском  нивоу,  али  још  више  у  патолошким стањима.Трибромовани дериват М15је показао прооксидативну активност са значајно вишом ОС вредношћу од свих осталих тестираних једињења. Такође, упоредне анализе доза-одговор тестираних пет једињења са најнижим ОС и Тролокса показују да Тролокс има слабијуантиоксидативну активност од једињења М2,  М7и М10.
PB  - Serbian Chemical Society.
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis and in vitro study of redox properties of pyrrole and halogenated pyrrole derivatives
T1  - Синтеза и in vitro студија редокс особина халогенованих и нехалогенованих деривата пирола
DO  - 10.2298/JSC240515082P
ER  - 
@article{
author = "Petković, Miloš and Kotur-Stevuljević, Jelena and Jovanović, Predrag and Jovanović, Miloš and Mitrović, Nikola and Simić, Milena and Tasić, Gordana and Savić, Vladimir",
year = "2024",
abstract = "The  redox  balance  plays  a  crucial  role  in  maintaining  biological processes  under  normal  conditions.  Antioxidants  inhibit  and  reduce  harmful oxidation  processes,  while  pro-oxidants  can  act  as  anti-cancer  agents  by promoting  ROS-mediated  cell  death.  The  aim  of  this  study  is  to  compare  the redox  properties  of  seven  newly  synthesised  tribromopyrrole  derivatives  with three novel and four previously synthesized non-halogenated analogues in an in vitro  model  (in  human  serum)  and  with  exogenously  induced oxidative  stress. The  obtained  values  of  their  oxy  scores  (OS)  were  compared  and  the  result showed  that  four  non-halogenated  pyrrole  derivatives  with  secondary  amide group M2, M10,  M11  and M12  have  lower  OS  values  than  Trolox,  a  water-soluble  analogue  of  vitamin  E  with  proven  antioxidant  properties.  All  four compounds show strong resistance to oxidative stress, which is reflected in the maintenance of negative OS values when exposed to exogenous oxidative stress using TBH in the reaction mixture. This capability to resist invading ROS should be  expected  also  in  an  endogenous  environment,  where  constant  prooxidant production  takes  place  at  a  low,  homeostatic  level,  but  even  more  so  in pathological  conditions.  The  tribrominated  derivative M15 showed prooxidant activity  with  a  significantly  higher  OS  value  than  all  other  compounds  tested. The comparison of the dose-response of Trolox and the five compounds with the lowest OS also shows that compounds M2,  M7 and M10 have better antioxidant activity than Trolox., Редоксравнотежа игра кључну улогу у одржавању биолошких процеса у нормалним условима.  Антиоксиданси  инхибирају  и  смањују  штетне  процесе  оксидације,  док прооксиданси  могу  деловати  као  антиканцерски  агенси  промовишући  ћелијску  смрт посредовану реактивним кисеоничним врстама. Циљ овог рада је да се упореде редокс својства седам  новосинтетисаних деривата трибромопирола и нехалогенованих аналога(три  новосинтетисанаи  четири  претходно  синтетисана) у in  vitroмоделу  (у  хуманом серуму)  и  са  егзогеноиндукованим  оксидативним  стресом.  Упоређене  су  добијене вредности њихових окси скорова (ОС) и резултат је показао да четири нехалогенована деривата  пирола  са  секундарном  амидном  групом М2,  М10,  М11и М12имају  ниже вредности  ОС  од  Тролокса,  аналога  витамина  Е  растворљивог  у  води  са  доказаним антиоксидативним  својствима.  Сва  четири  једињења  показују  јаку  отпорност  на оксидативни стрес, што се огледа у одржавању негативних вредности ОС када су изложене егзогеном оксидативном стресу коришћењем ТБХ у реакционој смеши. Ову способност да се одупируРОС треба очекивати и у ендогеном окружењу, где се константна производња прооксиданата  одвија  на  ниском,  хомеостатском  нивоу,  али  још  више  у  патолошким стањима.Трибромовани дериват М15је показао прооксидативну активност са значајно вишом ОС вредношћу од свих осталих тестираних једињења. Такође, упоредне анализе доза-одговор тестираних пет једињења са најнижим ОС и Тролокса показују да Тролокс има слабијуантиоксидативну активност од једињења М2,  М7и М10.",
publisher = "Serbian Chemical Society.",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis and in vitro study of redox properties of pyrrole and halogenated pyrrole derivatives, Синтеза и in vitro студија редокс особина халогенованих и нехалогенованих деривата пирола",
doi = "10.2298/JSC240515082P"
}
Petković, M., Kotur-Stevuljević, J., Jovanović, P., Jovanović, M., Mitrović, N., Simić, M., Tasić, G.,& Savić, V.. (2024). Synthesis and in vitro study of redox properties of pyrrole and halogenated pyrrole derivatives. in Journal of the Serbian Chemical Society
Serbian Chemical Society...
https://doi.org/10.2298/JSC240515082P
Petković M, Kotur-Stevuljević J, Jovanović P, Jovanović M, Mitrović N, Simić M, Tasić G, Savić V. Synthesis and in vitro study of redox properties of pyrrole and halogenated pyrrole derivatives. in Journal of the Serbian Chemical Society. 2024;.
doi:10.2298/JSC240515082P .
Petković, Miloš, Kotur-Stevuljević, Jelena, Jovanović, Predrag, Jovanović, Miloš, Mitrović, Nikola, Simić, Milena, Tasić, Gordana, Savić, Vladimir, "Synthesis and in vitro study of redox properties of pyrrole and halogenated pyrrole derivatives" in Journal of the Serbian Chemical Society (2024),
https://doi.org/10.2298/JSC240515082P . .

Jelić, Ratomir; Mrkalić, Emina; Ćendić-Serafinović, Marina; Odović, Jadranka; Sovrlić, Miroslav

(John Wiley and Sons Inc, 2024)

TY  - JOUR
AU  - Jelić, Ratomir
AU  - Mrkalić, Emina
AU  - Ćendić-Serafinović, Marina
AU  - Odović, Jadranka
AU  - Sovrlić, Miroslav
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5760
AB  - The interaction between linamarin (LIN), a cyanogenic glycoside, and human serum albumin (HSA) was studied by multiple spectroscopic techniques and molecular docking simulation. All measurements were performed under physiological conditions. The obtained results (including the binding constants, effective quenching constant and a number of binding sites) showed that the complex of HSA-LIN is formed. The values of Stern-Volmer constants (6.70×103, 5.53×103 and 1.95×103) indicate that fluorescence quenching of HSA was static. Results of site marker experiments showed that the binding site of LIN is mainly located in site I (subdomain IIA) of HSA. The thermodynamic parameters showed that binding process occurs spontaneously through hydrophobic interactions. Molecular docking results are in good agreement with experimental data. Furthermore, computational results revealed LIN binds in the cavity of TRP 214, that is, subdomain IIA (site I) of HSA. This comprehensive study provides a deeper insight into ligand binding in HSA which may be useful in drug design and pharmacology.
PB  - John Wiley and Sons Inc
T2  - ChemistrySelect
VL  - 9
IS  - 35
DO  - 10.1002/slct.202401946
ER  - 
@article{
author = "Jelić, Ratomir and Mrkalić, Emina and Ćendić-Serafinović, Marina and Odović, Jadranka and Sovrlić, Miroslav",
year = "2024",
abstract = "The interaction between linamarin (LIN), a cyanogenic glycoside, and human serum albumin (HSA) was studied by multiple spectroscopic techniques and molecular docking simulation. All measurements were performed under physiological conditions. The obtained results (including the binding constants, effective quenching constant and a number of binding sites) showed that the complex of HSA-LIN is formed. The values of Stern-Volmer constants (6.70×103, 5.53×103 and 1.95×103) indicate that fluorescence quenching of HSA was static. Results of site marker experiments showed that the binding site of LIN is mainly located in site I (subdomain IIA) of HSA. The thermodynamic parameters showed that binding process occurs spontaneously through hydrophobic interactions. Molecular docking results are in good agreement with experimental data. Furthermore, computational results revealed LIN binds in the cavity of TRP 214, that is, subdomain IIA (site I) of HSA. This comprehensive study provides a deeper insight into ligand binding in HSA which may be useful in drug design and pharmacology.",
publisher = "John Wiley and Sons Inc",
journal = "ChemistrySelect",
volume = "9",
number = "35",
doi = "10.1002/slct.202401946"
}
Jelić, R., Mrkalić, E., Ćendić-Serafinović, M., Odović, J.,& Sovrlić, M.. (2024). in ChemistrySelect
John Wiley and Sons Inc., 9(35).
https://doi.org/10.1002/slct.202401946
Jelić R, Mrkalić E, Ćendić-Serafinović M, Odović J, Sovrlić M. in ChemistrySelect. 2024;9(35).
doi:10.1002/slct.202401946 .
Jelić, Ratomir, Mrkalić, Emina, Ćendić-Serafinović, Marina, Odović, Jadranka, Sovrlić, Miroslav, in ChemistrySelect, 9, no. 35 (2024),
https://doi.org/10.1002/slct.202401946 . .

Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery

Marinko, Marija; Stojanović, Ivan; Milojević, Predrag; Nenezić, Dragoslav; Kanjuh, Vladimir; Yang, Qin; He, Guo-Wei; Novaković, Aleksandra

(John Wiley and Sons Inc, 2024)

TY  - JOUR
AU  - Marinko, Marija
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
AU  - Novaković, Aleksandra
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5762
AB  - Background: Changes in K+ channel expression/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K+ channels. Their involvement in hydrogen sulfide (H2S)-mediated vasorelaxation is still unclear, and data about human vessels are limited. Objective: To determine the role of K+ channel subtypes in the vasorelaxant mechanism of H2S donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA). Results: NaHS (1 × 10−6–3 × 10−3 mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K+. Among K+ channel blockers, iberiotoxin, glibenclamide, 4-aminopyridine (4-AP), and margatoxin significantly inhibited NaHS-induced relaxation of phenylephrine-contracted HIMA (P < 0.01), whereas in the presence of apamin/1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) combination, the HIMA relaxation was partially reduced (P < 0.05). The effect of NaHS was antagonized by NO pathway inhibitors, L-NAME and KT5823, and by cyclo-oxygenase inhibitor, indomethacin (P < 0.01). Under conditions of blocked NO/prostacyclin synthesis and release, apamin/TRAM-34 and glibenclamide caused further decrease in NaHS-induced vasorelaxation (P < 0.01), while iberiotoxin, 4-AP, and margatoxin were without additional effect (P > 0.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (P < 0.01). Conclusion: Our results demonstrated that H2S donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H2S included direct or indirect opening of different K+ channel subtypes, KATP, BKCa, SKCa/IKCa, and KV (subtype KV1.3), in addition to NO pathway activation and interference with extracellular Ca2+ influx.
PB  - John Wiley and Sons Inc
T2  - Fundamental and Clinical Pharmacology
T1  - Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery
DO  - 10.1111/fcp.13036
ER  - 
@article{
author = "Marinko, Marija and Stojanović, Ivan and Milojević, Predrag and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei and Novaković, Aleksandra",
year = "2024",
abstract = "Background: Changes in K+ channel expression/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K+ channels. Their involvement in hydrogen sulfide (H2S)-mediated vasorelaxation is still unclear, and data about human vessels are limited. Objective: To determine the role of K+ channel subtypes in the vasorelaxant mechanism of H2S donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA). Results: NaHS (1 × 10−6–3 × 10−3 mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K+. Among K+ channel blockers, iberiotoxin, glibenclamide, 4-aminopyridine (4-AP), and margatoxin significantly inhibited NaHS-induced relaxation of phenylephrine-contracted HIMA (P < 0.01), whereas in the presence of apamin/1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) combination, the HIMA relaxation was partially reduced (P < 0.05). The effect of NaHS was antagonized by NO pathway inhibitors, L-NAME and KT5823, and by cyclo-oxygenase inhibitor, indomethacin (P < 0.01). Under conditions of blocked NO/prostacyclin synthesis and release, apamin/TRAM-34 and glibenclamide caused further decrease in NaHS-induced vasorelaxation (P < 0.01), while iberiotoxin, 4-AP, and margatoxin were without additional effect (P > 0.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (P < 0.01). Conclusion: Our results demonstrated that H2S donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H2S included direct or indirect opening of different K+ channel subtypes, KATP, BKCa, SKCa/IKCa, and KV (subtype KV1.3), in addition to NO pathway activation and interference with extracellular Ca2+ influx.",
publisher = "John Wiley and Sons Inc",
journal = "Fundamental and Clinical Pharmacology",
title = "Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery",
doi = "10.1111/fcp.13036"
}
Marinko, M., Stojanović, I., Milojević, P., Nenezić, D., Kanjuh, V., Yang, Q., He, G.,& Novaković, A.. (2024). Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery. in Fundamental and Clinical Pharmacology
John Wiley and Sons Inc..
https://doi.org/10.1111/fcp.13036
Marinko M, Stojanović I, Milojević P, Nenezić D, Kanjuh V, Yang Q, He G, Novaković A. Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery. in Fundamental and Clinical Pharmacology. 2024;.
doi:10.1111/fcp.13036 .
Marinko, Marija, Stojanović, Ivan, Milojević, Predrag, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, Novaković, Aleksandra, "Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery" in Fundamental and Clinical Pharmacology (2024),
https://doi.org/10.1111/fcp.13036 . .

Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis

Vekić, Jelena; Klisić, Aleksandra; Kotur-Stevuljević, Jelena; Milinković, Neda; Gluščević, Sanja; Ciftel, Serpi; Mercantepe, Filiz

(MDPI, 2024)

TY  - JOUR
AU  - Vekić, Jelena
AU  - Klisić, Aleksandra
AU  - Kotur-Stevuljević, Jelena
AU  - Milinković, Neda
AU  - Gluščević, Sanja
AU  - Ciftel, Serpi
AU  - Mercantepe, Filiz
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5751
AB  - Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted “proinflammatory”, “prothrombotic” and “antithrombotic” factors, but the “proinflammatory” factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT.
PB  - MDPI
T2  - Biomedicines
T1  - Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis
VL  - 12
IS  - 8
DO  - 10.3390/biomedicines12081862
ER  - 
@article{
author = "Vekić, Jelena and Klisić, Aleksandra and Kotur-Stevuljević, Jelena and Milinković, Neda and Gluščević, Sanja and Ciftel, Serpi and Mercantepe, Filiz",
year = "2024",
abstract = "Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted “proinflammatory”, “prothrombotic” and “antithrombotic” factors, but the “proinflammatory” factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT.",
publisher = "MDPI",
journal = "Biomedicines",
title = "Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis",
volume = "12",
number = "8",
doi = "10.3390/biomedicines12081862"
}
Vekić, J., Klisić, A., Kotur-Stevuljević, J., Milinković, N., Gluščević, S., Ciftel, S.,& Mercantepe, F.. (2024). Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis. in Biomedicines
MDPI., 12(8).
https://doi.org/10.3390/biomedicines12081862
Vekić J, Klisić A, Kotur-Stevuljević J, Milinković N, Gluščević S, Ciftel S, Mercantepe F. Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis. in Biomedicines. 2024;12(8).
doi:10.3390/biomedicines12081862 .
Vekić, Jelena, Klisić, Aleksandra, Kotur-Stevuljević, Jelena, Milinković, Neda, Gluščević, Sanja, Ciftel, Serpi, Mercantepe, Filiz, "Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis" in Biomedicines, 12, no. 8 (2024),
https://doi.org/10.3390/biomedicines12081862 . .

COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition

Milošević, Tamara; Naumović, Radomir; Sopić, Miron; Vekić, Jelena; Guzonjić, Azra; Pešić, Snežana; Miljković-Trailović, Milica; Kotur-Stevuljević, Jelena

(Springer Nature, 2024)

TY  - JOUR
AU  - Milošević, Tamara
AU  - Naumović, Radomir
AU  - Sopić, Miron
AU  - Vekić, Jelena
AU  - Guzonjić, Azra
AU  - Pešić, Snežana
AU  - Miljković-Trailović, Milica
AU  - Kotur-Stevuljević, Jelena
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5741
AB  - Background and objective: An increased risk of mortality and hospitalization was consistently demonstrated in hemodialysis (HD) patients affected by pandemic coronavirus infection (COVID-19). In this study, we analyzed parameters that may impact mortality in COVID-19 HD patients, including neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP), COVID-19 disease status and telomere length in peripheral blood cells (TL). Materials and methods: A total of 130 chronic hemodialysis patients were enrolled and followed up for 18 months. Patients were categorized into groups based on their COVID-19 disease history and subsequent data about their survival status at the end of the study. Routine laboratory parameters were assessed using standard automated methods and TL was determined using the modified Cawthon method. Survival predictors were analyzed using Kaplan-Meier analysis. Results: Deceased patients (30%) were older with higher body mass index (BMI), higher levels of LDH, NLR index, CRP and lower TL and lymphocytes count compared to survivors. Kaplan-Meier survival analysis showed six parameters were significant mortality predictors in the following order of significance: COVID-19 history, 2-years cardiovascular mortality risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patient’s survival in this group of parameters (log rank 25.4, p < 0.001). Conclusion: Compared to the general population, the mortality rate among HD patients persists at a higher level despite advancements in HD technology and patient care. The situation has been exacerbated by COVID-19, by significant increase in mortality rate among these patients.
PB  - Springer Nature
T2  - Molecular Biology Reports
T1  - COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition
VL  - 51
IS  - 1
DO  - 10.1007/s11033-024-09879-7
ER  - 
@article{
author = "Milošević, Tamara and Naumović, Radomir and Sopić, Miron and Vekić, Jelena and Guzonjić, Azra and Pešić, Snežana and Miljković-Trailović, Milica and Kotur-Stevuljević, Jelena",
year = "2024",
abstract = "Background and objective: An increased risk of mortality and hospitalization was consistently demonstrated in hemodialysis (HD) patients affected by pandemic coronavirus infection (COVID-19). In this study, we analyzed parameters that may impact mortality in COVID-19 HD patients, including neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP), COVID-19 disease status and telomere length in peripheral blood cells (TL). Materials and methods: A total of 130 chronic hemodialysis patients were enrolled and followed up for 18 months. Patients were categorized into groups based on their COVID-19 disease history and subsequent data about their survival status at the end of the study. Routine laboratory parameters were assessed using standard automated methods and TL was determined using the modified Cawthon method. Survival predictors were analyzed using Kaplan-Meier analysis. Results: Deceased patients (30%) were older with higher body mass index (BMI), higher levels of LDH, NLR index, CRP and lower TL and lymphocytes count compared to survivors. Kaplan-Meier survival analysis showed six parameters were significant mortality predictors in the following order of significance: COVID-19 history, 2-years cardiovascular mortality risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patient’s survival in this group of parameters (log rank 25.4, p < 0.001). Conclusion: Compared to the general population, the mortality rate among HD patients persists at a higher level despite advancements in HD technology and patient care. The situation has been exacerbated by COVID-19, by significant increase in mortality rate among these patients.",
publisher = "Springer Nature",
journal = "Molecular Biology Reports",
title = "COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition",
volume = "51",
number = "1",
doi = "10.1007/s11033-024-09879-7"
}
Milošević, T., Naumović, R., Sopić, M., Vekić, J., Guzonjić, A., Pešić, S., Miljković-Trailović, M.,& Kotur-Stevuljević, J.. (2024). COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition. in Molecular Biology Reports
Springer Nature., 51(1).
https://doi.org/10.1007/s11033-024-09879-7
Milošević T, Naumović R, Sopić M, Vekić J, Guzonjić A, Pešić S, Miljković-Trailović M, Kotur-Stevuljević J. COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition. in Molecular Biology Reports. 2024;51(1).
doi:10.1007/s11033-024-09879-7 .
Milošević, Tamara, Naumović, Radomir, Sopić, Miron, Vekić, Jelena, Guzonjić, Azra, Pešić, Snežana, Miljković-Trailović, Milica, Kotur-Stevuljević, Jelena, "COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition" in Molecular Biology Reports, 51, no. 1 (2024),
https://doi.org/10.1007/s11033-024-09879-7 . .

Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation

Bufan, Biljana; Arsenović-Ranin, Nevena; Živković, Irena; Ćuruvija, Ivana; Blagojević, Veljko; Dragačević, Luka; Kovačević, Ana; Kotur-Stevuljević, Jelena; Leposavić, Gordana

(MDPI, 2024)

TY  - JOUR
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Živković, Irena
AU  - Ćuruvija, Ivana
AU  - Blagojević, Veljko
AU  - Dragačević, Luka
AU  - Kovačević, Ana
AU  - Kotur-Stevuljević, Jelena
AU  - Leposavić, Gordana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5721
AB  - Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine.
PB  - MDPI
T2  - Vaccines
T1  - Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation
VL  - 12
IS  - 7
DO  - 10.3390/vaccines12070743
ER  - 
@article{
author = "Bufan, Biljana and Arsenović-Ranin, Nevena and Živković, Irena and Ćuruvija, Ivana and Blagojević, Veljko and Dragačević, Luka and Kovačević, Ana and Kotur-Stevuljević, Jelena and Leposavić, Gordana",
year = "2024",
abstract = "Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine.",
publisher = "MDPI",
journal = "Vaccines",
title = "Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation",
volume = "12",
number = "7",
doi = "10.3390/vaccines12070743"
}
Bufan, B., Arsenović-Ranin, N., Živković, I., Ćuruvija, I., Blagojević, V., Dragačević, L., Kovačević, A., Kotur-Stevuljević, J.,& Leposavić, G.. (2024). Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation. in Vaccines
MDPI., 12(7).
https://doi.org/10.3390/vaccines12070743
Bufan B, Arsenović-Ranin N, Živković I, Ćuruvija I, Blagojević V, Dragačević L, Kovačević A, Kotur-Stevuljević J, Leposavić G. Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation. in Vaccines. 2024;12(7).
doi:10.3390/vaccines12070743 .
Bufan, Biljana, Arsenović-Ranin, Nevena, Živković, Irena, Ćuruvija, Ivana, Blagojević, Veljko, Dragačević, Luka, Kovačević, Ana, Kotur-Stevuljević, Jelena, Leposavić, Gordana, "Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation" in Vaccines, 12, no. 7 (2024),
https://doi.org/10.3390/vaccines12070743 . .

Biochemistry and laboratory diagnosis of obesity

Milinković, Neda; Bogavac-Stanojević, Nataša; Vekić, Jelena; Jovičić, Snežana; Kotur-Stevuljević, Jelena

(Savez farmaceutskih udruženja Srbije, Beograd, 2024)

TY  - JOUR
AU  - Milinković, Neda
AU  - Bogavac-Stanojević, Nataša
AU  - Vekić, Jelena
AU  - Jovičić, Snežana
AU  - Kotur-Stevuljević, Jelena
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5714
AB  - Until now, a lot of research has been carried out which significantly helped in
understanding and solving the problem of obesity. Despite this, there has been an upward in
obesity trend at the global level. The role of laboratory diagnostics in the field of obesity is of
great importance to doctors for establishing a diagnosis and monitoring the effects of therapy.
Determining biochemical parameters also contributes to practical usefulness in the prevention of
this disease, and prevention of consequent complications. Routinely available biochemical
analyses are usually used to diagnose and monitor the effects of obesity therapy. The initial
association related to laboratory analyses refers to parameters of lipid status, but there are a variety
of routine laboratory parameters that can help in understanding and monitoring obesity from
different angles. Timely and adequate management of obesity is also of interest from an economic
aspect. For this reason, the topic of this research is to summarize the latest aspects of the concept
of obesity, specifically from the point of view of biochemistry and laboratory diagnostics. Taking
into account the complexity of this disease, it is important to point out the future perspectives and
challenges that inevitably arise before both laboratory professionals and healthcare providers in
general.
AB  - Do sada je sprovedeno dosta istraživanja koja su značajno pomogla u sagledavanju i rešavanju problema gojaznosti. I pored toga, gojaznost ima trend porasta na globalnom nivou. Uloga laboratorijske dijagnostike u oblasti gojaznosti je od velikog značaja lekarima za postavljanje dijagnoze i praćenje efekata terapije. Određivanje biohemijskih parametara takođe doprinosi praktičnoj korisnosti u prevenciji ovog oboljenja, kao i predupređenju posledičnih komplikacija. Obično se za postavljanje dijagnoze i praćenje efekata terapije gojaznosti određuju rutinski dostupne biohemijske analize. Prvobitna asocijacija vezana za laboratorijske analize odnosi se na parametre lipidnog statusa, ali jako je veliki broj rutinskih analiza koje mogu pomoći u sagledavanju i praćenju gojaznosti iz različitih uglova. Dodatno, pravovremeno i adekvatno upravljanje gojaznošću je od interesa i sa ekonomskog aspekta. Iz tog razloga, tema ovog istraživanja je sumiranje najnovijih aspekata koncepta gojaznosti, posebno sa stanovišta biohemije i laboratorijske dijagnostike. Uzimajući u obzir složenost ove bolesti, važno je ukazati na buduće perspektive i izazove koji se neizbežno javljaju kako pred laboratorijskim stručnjacima, tako i pred zdravstvenim radnicima uopšte.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
PB  - Univerzitet u Beogradu - Farmaceutski fakultet
T2  - Arhiv za farmaciju
T1  - Biochemistry and laboratory diagnosis of obesity
T1  - Biohemija i laboratorijska dijagnostika gojaznosti
VL  - 74
IS  - 3
SP  - 348
EP  - 374
DO  - 10.5937/arhfarm74-50458
ER  - 
@article{
author = "Milinković, Neda and Bogavac-Stanojević, Nataša and Vekić, Jelena and Jovičić, Snežana and Kotur-Stevuljević, Jelena",
year = "2024",
abstract = "Until now, a lot of research has been carried out which significantly helped in
understanding and solving the problem of obesity. Despite this, there has been an upward in
obesity trend at the global level. The role of laboratory diagnostics in the field of obesity is of
great importance to doctors for establishing a diagnosis and monitoring the effects of therapy.
Determining biochemical parameters also contributes to practical usefulness in the prevention of
this disease, and prevention of consequent complications. Routinely available biochemical
analyses are usually used to diagnose and monitor the effects of obesity therapy. The initial
association related to laboratory analyses refers to parameters of lipid status, but there are a variety
of routine laboratory parameters that can help in understanding and monitoring obesity from
different angles. Timely and adequate management of obesity is also of interest from an economic
aspect. For this reason, the topic of this research is to summarize the latest aspects of the concept
of obesity, specifically from the point of view of biochemistry and laboratory diagnostics. Taking
into account the complexity of this disease, it is important to point out the future perspectives and
challenges that inevitably arise before both laboratory professionals and healthcare providers in
general., Do sada je sprovedeno dosta istraživanja koja su značajno pomogla u sagledavanju i rešavanju problema gojaznosti. I pored toga, gojaznost ima trend porasta na globalnom nivou. Uloga laboratorijske dijagnostike u oblasti gojaznosti je od velikog značaja lekarima za postavljanje dijagnoze i praćenje efekata terapije. Određivanje biohemijskih parametara takođe doprinosi praktičnoj korisnosti u prevenciji ovog oboljenja, kao i predupređenju posledičnih komplikacija. Obično se za postavljanje dijagnoze i praćenje efekata terapije gojaznosti određuju rutinski dostupne biohemijske analize. Prvobitna asocijacija vezana za laboratorijske analize odnosi se na parametre lipidnog statusa, ali jako je veliki broj rutinskih analiza koje mogu pomoći u sagledavanju i praćenju gojaznosti iz različitih uglova. Dodatno, pravovremeno i adekvatno upravljanje gojaznošću je od interesa i sa ekonomskog aspekta. Iz tog razloga, tema ovog istraživanja je sumiranje najnovijih aspekata koncepta gojaznosti, posebno sa stanovišta biohemije i laboratorijske dijagnostike. Uzimajući u obzir složenost ove bolesti, važno je ukazati na buduće perspektive i izazove koji se neizbežno javljaju kako pred laboratorijskim stručnjacima, tako i pred zdravstvenim radnicima uopšte.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd, Univerzitet u Beogradu - Farmaceutski fakultet",
journal = "Arhiv za farmaciju",
title = "Biochemistry and laboratory diagnosis of obesity, Biohemija i laboratorijska dijagnostika gojaznosti",
volume = "74",
number = "3",
pages = "348-374",
doi = "10.5937/arhfarm74-50458"
}
Milinković, N., Bogavac-Stanojević, N., Vekić, J., Jovičić, S.,& Kotur-Stevuljević, J.. (2024). Biochemistry and laboratory diagnosis of obesity. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 74(3), 348-374.
https://doi.org/10.5937/arhfarm74-50458
Milinković N, Bogavac-Stanojević N, Vekić J, Jovičić S, Kotur-Stevuljević J. Biochemistry and laboratory diagnosis of obesity. in Arhiv za farmaciju. 2024;74(3):348-374.
doi:10.5937/arhfarm74-50458 .
Milinković, Neda, Bogavac-Stanojević, Nataša, Vekić, Jelena, Jovičić, Snežana, Kotur-Stevuljević, Jelena, "Biochemistry and laboratory diagnosis of obesity" in Arhiv za farmaciju, 74, no. 3 (2024):348-374,
https://doi.org/10.5937/arhfarm74-50458 . .

Childhood obesity accelerates biological ageing: is oxidative stress a link?

Subošić, Branko; Zdravković, Vera; Ješić, Maja; Munjas, Jelena; Kovačević, Smiljka; Guzonjić, Azra; Mitrović, Jadranka; Saso, Luciano; Đuričić, Ivana; Kotur-Stevuljević, Jelena

(Cambridge University Press, 2024)

TY  - JOUR
AU  - Subošić, Branko
AU  - Zdravković, Vera
AU  - Ješić, Maja
AU  - Munjas, Jelena
AU  - Kovačević, Smiljka
AU  - Guzonjić, Azra
AU  - Mitrović, Jadranka
AU  - Saso, Luciano
AU  - Đuričić, Ivana
AU  - Kotur-Stevuljević, Jelena
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5654
AB  - Obesity is multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed estimate connection between relative leukocyte telomere lengths (rLRL) - biomarker of cellular aging with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both genders. The results suggested that rLTL are significantly shorter in obese, compared to lean group (p<0,01). Negative correlation of rLTL with total oxidant status, TOS (Spearman's ρ = -0.365, p<0.001) as well as with C reactive protein (Spearman's ρ= -0,363, p<0.001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35% of total variability; antioxidant factor with 30% of total variability and lipid antioxidant - biological ageing factor with 12% of the total variability. The most important predictor of body mass index (BMI) >30kg/m2 according to logistic regression analysis was PCA derived antioxidant factor's score (OR: 1.66, 95th Cl: 1.05-2.6, p=0.029). PCA analysis confirmed oxidative stress importance in biological ageing caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homeostasis deepness, even before any overt disease occurrence.
PB  - Cambridge University Press
T2  - British Journal of Nutrition
T1  - Childhood obesity accelerates biological ageing: is oxidative stress a link?
DO  - 10.1017/S0007114524000898
ER  - 
@article{
author = "Subošić, Branko and Zdravković, Vera and Ješić, Maja and Munjas, Jelena and Kovačević, Smiljka and Guzonjić, Azra and Mitrović, Jadranka and Saso, Luciano and Đuričić, Ivana and Kotur-Stevuljević, Jelena",
year = "2024",
abstract = "Obesity is multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed estimate connection between relative leukocyte telomere lengths (rLRL) - biomarker of cellular aging with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both genders. The results suggested that rLTL are significantly shorter in obese, compared to lean group (p<0,01). Negative correlation of rLTL with total oxidant status, TOS (Spearman's ρ = -0.365, p<0.001) as well as with C reactive protein (Spearman's ρ= -0,363, p<0.001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35% of total variability; antioxidant factor with 30% of total variability and lipid antioxidant - biological ageing factor with 12% of the total variability. The most important predictor of body mass index (BMI) >30kg/m2 according to logistic regression analysis was PCA derived antioxidant factor's score (OR: 1.66, 95th Cl: 1.05-2.6, p=0.029). PCA analysis confirmed oxidative stress importance in biological ageing caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homeostasis deepness, even before any overt disease occurrence.",
publisher = "Cambridge University Press",
journal = "British Journal of Nutrition",
title = "Childhood obesity accelerates biological ageing: is oxidative stress a link?",
doi = "10.1017/S0007114524000898"
}
Subošić, B., Zdravković, V., Ješić, M., Munjas, J., Kovačević, S., Guzonjić, A., Mitrović, J., Saso, L., Đuričić, I.,& Kotur-Stevuljević, J.. (2024). Childhood obesity accelerates biological ageing: is oxidative stress a link?. in British Journal of Nutrition
Cambridge University Press..
https://doi.org/10.1017/S0007114524000898
Subošić B, Zdravković V, Ješić M, Munjas J, Kovačević S, Guzonjić A, Mitrović J, Saso L, Đuričić I, Kotur-Stevuljević J. Childhood obesity accelerates biological ageing: is oxidative stress a link?. in British Journal of Nutrition. 2024;.
doi:10.1017/S0007114524000898 .
Subošić, Branko, Zdravković, Vera, Ješić, Maja, Munjas, Jelena, Kovačević, Smiljka, Guzonjić, Azra, Mitrović, Jadranka, Saso, Luciano, Đuričić, Ivana, Kotur-Stevuljević, Jelena, "Childhood obesity accelerates biological ageing: is oxidative stress a link?" in British Journal of Nutrition (2024),
https://doi.org/10.1017/S0007114524000898 . .

Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity

Subošić, Branko; Kotur-Stevuljević, Jelena; Bogavac-Stanojević, Nataša; Zdravković, Vera; Ješić, Maja; Kovačević, Smiljka; Đuričić, Ivana

(MDPI, 2024)

TY  - JOUR
AU  - Subošić, Branko
AU  - Kotur-Stevuljević, Jelena
AU  - Bogavac-Stanojević, Nataša
AU  - Zdravković, Vera
AU  - Ješić, Maja
AU  - Kovačević, Smiljka
AU  - Đuričić, Ivana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5625
AB  - Fatty acids play a crucial role in obesity development and in the comorbidities of obesity in both adults and children. This study aimed to assess the impact of circulating fatty acids on biomarkers of metabolic health of adolescents living with obesity. Parameters such as blood lipids, redox status, and leukocyte telomere length (rLTL) were measured alongside the proportions of individual fatty acids. The Mann–Whitney U test revealed that individuals with obesity exhibited an unfavorable lipid and redox status compared to the control normal weight group. The group with obesity also had lower plasma n-3 polyunsaturated fatty acids (PUFAs) and a higher ratio of n-6 to n-3 PUFAs than the control group. They also had a shorter rLTL, indicating accelerated biological aging. There was an inverse association of rLTL and plasma n-6-to-n-3 PUFA ratio. Future studies should explore the impact of recommended nutrition plans and increased physical activity on these parameters to determine if these interventions can enhance the health and well-being of adolescents with obesity, knowing that early obesity can track into adulthood.
PB  - MDPI
T2  - Biomedicines
T1  - Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity
VL  - 12
IS  - 4
DO  - 10.3390/biomedicines12040883
ER  - 
@article{
author = "Subošić, Branko and Kotur-Stevuljević, Jelena and Bogavac-Stanojević, Nataša and Zdravković, Vera and Ješić, Maja and Kovačević, Smiljka and Đuričić, Ivana",
year = "2024",
abstract = "Fatty acids play a crucial role in obesity development and in the comorbidities of obesity in both adults and children. This study aimed to assess the impact of circulating fatty acids on biomarkers of metabolic health of adolescents living with obesity. Parameters such as blood lipids, redox status, and leukocyte telomere length (rLTL) were measured alongside the proportions of individual fatty acids. The Mann–Whitney U test revealed that individuals with obesity exhibited an unfavorable lipid and redox status compared to the control normal weight group. The group with obesity also had lower plasma n-3 polyunsaturated fatty acids (PUFAs) and a higher ratio of n-6 to n-3 PUFAs than the control group. They also had a shorter rLTL, indicating accelerated biological aging. There was an inverse association of rLTL and plasma n-6-to-n-3 PUFA ratio. Future studies should explore the impact of recommended nutrition plans and increased physical activity on these parameters to determine if these interventions can enhance the health and well-being of adolescents with obesity, knowing that early obesity can track into adulthood.",
publisher = "MDPI",
journal = "Biomedicines",
title = "Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity",
volume = "12",
number = "4",
doi = "10.3390/biomedicines12040883"
}
Subošić, B., Kotur-Stevuljević, J., Bogavac-Stanojević, N., Zdravković, V., Ješić, M., Kovačević, S.,& Đuričić, I.. (2024). Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity. in Biomedicines
MDPI., 12(4).
https://doi.org/10.3390/biomedicines12040883
Subošić B, Kotur-Stevuljević J, Bogavac-Stanojević N, Zdravković V, Ješić M, Kovačević S, Đuričić I. Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity. in Biomedicines. 2024;12(4).
doi:10.3390/biomedicines12040883 .
Subošić, Branko, Kotur-Stevuljević, Jelena, Bogavac-Stanojević, Nataša, Zdravković, Vera, Ješić, Maja, Kovačević, Smiljka, Đuričić, Ivana, "Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity" in Biomedicines, 12, no. 4 (2024),
https://doi.org/10.3390/biomedicines12040883 . .

Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach

Živančević, Katarina; Baralić, Katarina; Vukelić, Dragana; Marić, Đurđica; Kotur-Stevuljević, Jelena; Ivanišević, Jasmina; Savić, Miroslav; Batinić, Bojan; Janković, Radmila; Buha-Đorđević, Aleksandra; Antonijević-Miljaković, Evica; Ćurčić, Marijana; Bulat, Zorica; Antonijević, Biljana; Đukić-Ćosić, Danijela

(Elsevier Inc., 2024)

TY  - JOUR
AU  - Živančević, Katarina
AU  - Baralić, Katarina
AU  - Vukelić, Dragana
AU  - Marić, Đurđica
AU  - Kotur-Stevuljević, Jelena
AU  - Ivanišević, Jasmina
AU  - Savić, Miroslav
AU  - Batinić, Bojan
AU  - Janković, Radmila
AU  - Buha-Đorđević, Aleksandra
AU  - Antonijević-Miljaković, Evica
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5614
AB  - Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dismutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting “no-threshold” concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies.
PB  - Elsevier Inc.
T2  - Environmental Research
T1  - Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach
VL  - 252
IS  - 1
SP  - 118680
DO  - 10.1016/j.envres.2024.118680
ER  - 
@article{
author = "Živančević, Katarina and Baralić, Katarina and Vukelić, Dragana and Marić, Đurđica and Kotur-Stevuljević, Jelena and Ivanišević, Jasmina and Savić, Miroslav and Batinić, Bojan and Janković, Radmila and Buha-Đorđević, Aleksandra and Antonijević-Miljaković, Evica and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela",
year = "2024",
abstract = "Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dismutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting “no-threshold” concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies.",
publisher = "Elsevier Inc.",
journal = "Environmental Research",
title = "Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach",
volume = "252",
number = "1",
pages = "118680",
doi = "10.1016/j.envres.2024.118680"
}
Živančević, K., Baralić, K., Vukelić, D., Marić, Đ., Kotur-Stevuljević, J., Ivanišević, J., Savić, M., Batinić, B., Janković, R., Buha-Đorđević, A., Antonijević-Miljaković, E., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2024). Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach. in Environmental Research
Elsevier Inc.., 252(1), 118680.
https://doi.org/10.1016/j.envres.2024.118680
Živančević K, Baralić K, Vukelić D, Marić Đ, Kotur-Stevuljević J, Ivanišević J, Savić M, Batinić B, Janković R, Buha-Đorđević A, Antonijević-Miljaković E, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach. in Environmental Research. 2024;252(1):118680.
doi:10.1016/j.envres.2024.118680 .
Živančević, Katarina, Baralić, Katarina, Vukelić, Dragana, Marić, Đurđica, Kotur-Stevuljević, Jelena, Ivanišević, Jasmina, Savić, Miroslav, Batinić, Bojan, Janković, Radmila, Buha-Đorđević, Aleksandra, Antonijević-Miljaković, Evica, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach" in Environmental Research, 252, no. 1 (2024):118680,
https://doi.org/10.1016/j.envres.2024.118680 . .
1

Facile and Low-Cost Electrochemical Synthesis of Zinc Alginate Hydrogel Films for Biomedical Applications

Rupar, Jelena; Marković, Mihajlo; Božić, Dragana; Antić-Stanković, Jelena; Mijailović, Nataša; Gavrilov, Nemanja; Bajuk-Bogdanović, Danica; Milojević-Rakić, Maja; Janošević-Ležaić, Aleksandra

(John Wiley and Sons Ltd, 2024)


                                            

                                            
Rupar, J., Marković, M., Božić, D., Antić-Stanković, J., Mijailović, N., Gavrilov, N., Bajuk-Bogdanović, D., Milojević-Rakić, M.,& Janošević-Ležaić, A.. (2024). Facile and Low-Cost Electrochemical Synthesis of Zinc
Alginate Hydrogel Films for Biomedical Applications. in Applied Organometallic Chemistry
John Wiley and Sons Ltd..
https://doi.org/10.1002/aoc.7732
Rupar J, Marković M, Božić D, Antić-Stanković J, Mijailović N, Gavrilov N, Bajuk-Bogdanović D, Milojević-Rakić M, Janošević-Ležaić A. Facile and Low-Cost Electrochemical Synthesis of Zinc
Alginate Hydrogel Films for Biomedical Applications. in Applied Organometallic Chemistry. 2024;.
doi:10.1002/aoc.7732 .
Rupar, Jelena, Marković, Mihajlo, Božić, Dragana, Antić-Stanković, Jelena, Mijailović, Nataša, Gavrilov, Nemanja, Bajuk-Bogdanović, Danica, Milojević-Rakić, Maja, Janošević-Ležaić, Aleksandra, "Facile and Low-Cost Electrochemical Synthesis of Zinc
Alginate Hydrogel Films for Biomedical Applications" in Applied Organometallic Chemistry (2024),
https://doi.org/10.1002/aoc.7732 . .

From Field to Pharmacy: Isolation, Characterization and Tableting Behaviour of Microcrystalline Cellulose from Wheat and Corn Harvest Residues

Medarević, Đorđe; Čežek, Maša; Knežević, Aleksandar; Turković, Erna; Barudžija, Tanja; Samardžić, Stevan; Maksimović, Zoran

(MDPI, 2024)

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Čežek, Maša
AU  - Knežević, Aleksandar
AU  - Turković, Erna
AU  - Barudžija, Tanja
AU  - Samardžić, Stevan
AU  - Maksimović, Zoran
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5733
AB  - A lack of strategies for the utilization of harvest residues (HRs) has led to serious environmental problems due to an accumulation of these residues or their burning in the field. In this study, wheat and corn HRs were used as feedstock for the production of microcrystalline cellulose (MCC) by treatment with 2–8% sodium hydroxide, 10% hydrogen peroxide and further hydrolysis with 1–2 M hydrochloric acid. The changes in the FT-IR spectra and PXRD diffractograms after chemical treatment confirmed the removal of most of the lignin, hemicellulose and amorphous fraction of cellulose. A higher degree of crystallinity was observed for MCC obtained from corn HRs, which was attributed to a more efficient removal of lignin and hemicellulose by a higher sodium hydroxide concentration, which facilitates the dissolution of amorphous cellulose during acid hydrolysis. MCC obtained from HRs exhibited lower bulk density and poorer flow properties but similar or better tableting properties compared to commercial MCC (CeolusTM PH101). The lower ejection and detachment stress suggests that MCC isolated from HRs requires less lubricant compared to commercial MCC. This study showed that MCC isolated from wheat and corn HRs exhibits comparable tableting behaviour like commercial sample, further supporting this type of agricultural waste utilization.
PB  - MDPI
T2  - Pharmaceutics
T1  - From Field to Pharmacy: Isolation, Characterization and Tableting Behaviour of Microcrystalline Cellulose from Wheat and Corn Harvest Residues
VL  - 16
IS  - 8
SP  - 1090
DO  - 10.3390/pharmaceutics16081090
ER  - 
@article{
author = "Medarević, Đorđe and Čežek, Maša and Knežević, Aleksandar and Turković, Erna and Barudžija, Tanja and Samardžić, Stevan and Maksimović, Zoran",
year = "2024",
abstract = "A lack of strategies for the utilization of harvest residues (HRs) has led to serious environmental problems due to an accumulation of these residues or their burning in the field. In this study, wheat and corn HRs were used as feedstock for the production of microcrystalline cellulose (MCC) by treatment with 2–8% sodium hydroxide, 10% hydrogen peroxide and further hydrolysis with 1–2 M hydrochloric acid. The changes in the FT-IR spectra and PXRD diffractograms after chemical treatment confirmed the removal of most of the lignin, hemicellulose and amorphous fraction of cellulose. A higher degree of crystallinity was observed for MCC obtained from corn HRs, which was attributed to a more efficient removal of lignin and hemicellulose by a higher sodium hydroxide concentration, which facilitates the dissolution of amorphous cellulose during acid hydrolysis. MCC obtained from HRs exhibited lower bulk density and poorer flow properties but similar or better tableting properties compared to commercial MCC (CeolusTM PH101). The lower ejection and detachment stress suggests that MCC isolated from HRs requires less lubricant compared to commercial MCC. This study showed that MCC isolated from wheat and corn HRs exhibits comparable tableting behaviour like commercial sample, further supporting this type of agricultural waste utilization.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "From Field to Pharmacy: Isolation, Characterization and Tableting Behaviour of Microcrystalline Cellulose from Wheat and Corn Harvest Residues",
volume = "16",
number = "8",
pages = "1090",
doi = "10.3390/pharmaceutics16081090"
}
Medarević, Đ., Čežek, M., Knežević, A., Turković, E., Barudžija, T., Samardžić, S.,& Maksimović, Z.. (2024). From Field to Pharmacy: Isolation, Characterization and Tableting Behaviour of Microcrystalline Cellulose from Wheat and Corn Harvest Residues. in Pharmaceutics
MDPI., 16(8), 1090.
https://doi.org/10.3390/pharmaceutics16081090
Medarević Đ, Čežek M, Knežević A, Turković E, Barudžija T, Samardžić S, Maksimović Z. From Field to Pharmacy: Isolation, Characterization and Tableting Behaviour of Microcrystalline Cellulose from Wheat and Corn Harvest Residues. in Pharmaceutics. 2024;16(8):1090.
doi:10.3390/pharmaceutics16081090 .
Medarević, Đorđe, Čežek, Maša, Knežević, Aleksandar, Turković, Erna, Barudžija, Tanja, Samardžić, Stevan, Maksimović, Zoran, "From Field to Pharmacy: Isolation, Characterization and Tableting Behaviour of Microcrystalline Cellulose from Wheat and Corn Harvest Residues" in Pharmaceutics, 16, no. 8 (2024):1090,
https://doi.org/10.3390/pharmaceutics16081090 . .

Cardiometabolic Risk Factors Related to Atrial Fibrillation and Metabolic Syndrome in the Pakistani Population

Rafaqat, Saira; Sharif, Saima; Naz, Shagufta; Gluščević, Sanja; Mercantepe, Mercantepe; Ninić, Ana; Klisić, Aleksandra

(MDPI, 2024)

TY  - JOUR
AU  - Rafaqat, Saira
AU  - Sharif, Saima
AU  - Naz, Shagufta
AU  - Gluščević, Sanja
AU  - Mercantepe, Mercantepe
AU  - Ninić, Ana
AU  - Klisić, Aleksandra
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5756
AB  - Background and Objectives: This study aimed to examine the relationship between cardiometabolic risk factors and atrial fibrillation (AF) and the simultaneous presence of AF and metabolic syndrome (MetS) in the Pakistani population. Materials and Methods: A total of 690 subjects were enrolled (n = 230 patients with AF, n = 230 patients with AF and MetS, and n = 230 controls). The associations between cardiometabolic parameters and AF with and without MetS were analyzed by univariable and multivariable binary regression analyses. Results: Body mass index (BMI), fasting blood glucose (FBG), and triglycerides (TG) were independently positively correlated, but the glomerular filtration rate (GFR) and sodium were independently negatively correlated with AF. An increase in BMI, FBG, and TG levels by one unit measure increased the probability by 55.1%, 20.6%, and 1.3%, respectively, for the AF occurrence. A decrease in GFR and sodium levels increased the probability by 4.3% and 33.6%, respectively, for the AF occurrence. On the other hand, uric acid was independently negatively correlated, whereas sodium was independently positively correlated, with MetS and AF. A decrease in uric acid levels and an increase in sodium levels by 1 unit measure increased the probability for MetS and AF by 23.2% and 7.5%, respectively. Conclusions: Cost-effective and routinely measured parameters, i.e., BMI, FBG TG, GFR, and sodium levels, can be reliable indicators of AF, whereas serum uric acid and sodium levels are independently associated with AF and MetS in the Pakistani population. Timely recognition and the control of modifiable cardiometabolic risk factors are of great significance in the prevention of AF development.
PB  - MDPI
T2  - Medicina (Lithuania)
T1  - Cardiometabolic Risk Factors Related to Atrial Fibrillation and Metabolic Syndrome in the Pakistani Population
VL  - 60
IS  - 8
DO  - 10.3390/medicina60081190
ER  - 
@article{
author = "Rafaqat, Saira and Sharif, Saima and Naz, Shagufta and Gluščević, Sanja and Mercantepe, Mercantepe and Ninić, Ana and Klisić, Aleksandra",
year = "2024",
abstract = "Background and Objectives: This study aimed to examine the relationship between cardiometabolic risk factors and atrial fibrillation (AF) and the simultaneous presence of AF and metabolic syndrome (MetS) in the Pakistani population. Materials and Methods: A total of 690 subjects were enrolled (n = 230 patients with AF, n = 230 patients with AF and MetS, and n = 230 controls). The associations between cardiometabolic parameters and AF with and without MetS were analyzed by univariable and multivariable binary regression analyses. Results: Body mass index (BMI), fasting blood glucose (FBG), and triglycerides (TG) were independently positively correlated, but the glomerular filtration rate (GFR) and sodium were independently negatively correlated with AF. An increase in BMI, FBG, and TG levels by one unit measure increased the probability by 55.1%, 20.6%, and 1.3%, respectively, for the AF occurrence. A decrease in GFR and sodium levels increased the probability by 4.3% and 33.6%, respectively, for the AF occurrence. On the other hand, uric acid was independently negatively correlated, whereas sodium was independently positively correlated, with MetS and AF. A decrease in uric acid levels and an increase in sodium levels by 1 unit measure increased the probability for MetS and AF by 23.2% and 7.5%, respectively. Conclusions: Cost-effective and routinely measured parameters, i.e., BMI, FBG TG, GFR, and sodium levels, can be reliable indicators of AF, whereas serum uric acid and sodium levels are independently associated with AF and MetS in the Pakistani population. Timely recognition and the control of modifiable cardiometabolic risk factors are of great significance in the prevention of AF development.",
publisher = "MDPI",
journal = "Medicina (Lithuania)",
title = "Cardiometabolic Risk Factors Related to Atrial Fibrillation and Metabolic Syndrome in the Pakistani Population",
volume = "60",
number = "8",
doi = "10.3390/medicina60081190"
}
Rafaqat, S., Sharif, S., Naz, S., Gluščević, S., Mercantepe, M., Ninić, A.,& Klisić, A.. (2024). Cardiometabolic Risk Factors Related to Atrial Fibrillation and Metabolic Syndrome in the Pakistani Population. in Medicina (Lithuania)
MDPI., 60(8).
https://doi.org/10.3390/medicina60081190
Rafaqat S, Sharif S, Naz S, Gluščević S, Mercantepe M, Ninić A, Klisić A. Cardiometabolic Risk Factors Related to Atrial Fibrillation and Metabolic Syndrome in the Pakistani Population. in Medicina (Lithuania). 2024;60(8).
doi:10.3390/medicina60081190 .
Rafaqat, Saira, Sharif, Saima, Naz, Shagufta, Gluščević, Sanja, Mercantepe, Mercantepe, Ninić, Ana, Klisić, Aleksandra, "Cardiometabolic Risk Factors Related to Atrial Fibrillation and Metabolic Syndrome in the Pakistani Population" in Medicina (Lithuania), 60, no. 8 (2024),
https://doi.org/10.3390/medicina60081190 . .

Increased Odds of Metabolic Dysfunction-Associated Steatotic Liver Disease Are Linked to Reduced n-6, but Not n-3 Polyunsaturated Fatty Acids in Plasma

Franković, Irena; Đuričić, Ivana; Ninić, Ana; Vekić, Jelena; Vorkapić, Tara; Erceg, Sanja; Gojković, Tamara; Tomašević, Ratko; Mamić, Milica; Mitrović, Miloš; Zeljković, Aleksandra

(MDPI, 2024)

TY  - JOUR
AU  - Franković, Irena
AU  - Đuričić, Ivana
AU  - Ninić, Ana
AU  - Vekić, Jelena
AU  - Vorkapić, Tara
AU  - Erceg, Sanja
AU  - Gojković, Tamara
AU  - Tomašević, Ratko
AU  - Mamić, Milica
AU  - Mitrović, Miloš
AU  - Zeljković, Aleksandra
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5755
AB  - The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need for better understanding of its complex pathogenesis. Lipid accumulation in hepatocytes is among principal mechanisms contributing to MASLD development. While routine lipid parameters are well studied, the profile of circulating fatty acids in MASLD patients remains less explored. This study aimed to assess relative proportions of individual fatty acids in plasma of MASLD patients and to explore their associations with other biochemical markers of MASLD. Ninety-one patients and 48 healthy individuals were enrolled. The relative proportions of fatty acids in plasma were determined using gas chromatography with FID detection. Proportions of total n-6 polyunsaturated fatty acids (PUFAs) and linoleic acid (LA) in plasma were lower in MASLD patients (p = 0.001 and p = 0.004, respectively), with no differences observed in n-3 PUFAs. Total plasma n-6 PUFAs correlated negatively with body mass index, hepatic steatosis indices, triglyceride concentration and coronary risk index. Decreased prevalence of n-6 PUFAs in plasma was independently associated with higher odds of MASLD (OR = 0.769; CI: 0.611–0.968; p = 0.025). Our findings indicate an altered circulatory fatty acid distribution in MASLD, characterized by a reduced amount of n-6 PUFAs, particularly LA, which may have significant implications for the prevention and treatment of MASLD.
PB  - MDPI
T2  - Biomolecules
T1  - Increased Odds of Metabolic Dysfunction-Associated Steatotic
Liver Disease Are Linked to Reduced n-6, but Not n-3
Polyunsaturated Fatty Acids in Plasma
VL  - 14
IS  - 8
DO  - 10.3390/biom14080902
ER  - 
@article{
author = "Franković, Irena and Đuričić, Ivana and Ninić, Ana and Vekić, Jelena and Vorkapić, Tara and Erceg, Sanja and Gojković, Tamara and Tomašević, Ratko and Mamić, Milica and Mitrović, Miloš and Zeljković, Aleksandra",
year = "2024",
abstract = "The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need for better understanding of its complex pathogenesis. Lipid accumulation in hepatocytes is among principal mechanisms contributing to MASLD development. While routine lipid parameters are well studied, the profile of circulating fatty acids in MASLD patients remains less explored. This study aimed to assess relative proportions of individual fatty acids in plasma of MASLD patients and to explore their associations with other biochemical markers of MASLD. Ninety-one patients and 48 healthy individuals were enrolled. The relative proportions of fatty acids in plasma were determined using gas chromatography with FID detection. Proportions of total n-6 polyunsaturated fatty acids (PUFAs) and linoleic acid (LA) in plasma were lower in MASLD patients (p = 0.001 and p = 0.004, respectively), with no differences observed in n-3 PUFAs. Total plasma n-6 PUFAs correlated negatively with body mass index, hepatic steatosis indices, triglyceride concentration and coronary risk index. Decreased prevalence of n-6 PUFAs in plasma was independently associated with higher odds of MASLD (OR = 0.769; CI: 0.611–0.968; p = 0.025). Our findings indicate an altered circulatory fatty acid distribution in MASLD, characterized by a reduced amount of n-6 PUFAs, particularly LA, which may have significant implications for the prevention and treatment of MASLD.",
publisher = "MDPI",
journal = "Biomolecules",
title = "Increased Odds of Metabolic Dysfunction-Associated Steatotic
Liver Disease Are Linked to Reduced n-6, but Not n-3
Polyunsaturated Fatty Acids in Plasma",
volume = "14",
number = "8",
doi = "10.3390/biom14080902"
}
Franković, I., Đuričić, I., Ninić, A., Vekić, J., Vorkapić, T., Erceg, S., Gojković, T., Tomašević, R., Mamić, M., Mitrović, M.,& Zeljković, A.. (2024). Increased Odds of Metabolic Dysfunction-Associated Steatotic
Liver Disease Are Linked to Reduced n-6, but Not n-3
Polyunsaturated Fatty Acids in Plasma. in Biomolecules
MDPI., 14(8).
https://doi.org/10.3390/biom14080902
Franković I, Đuričić I, Ninić A, Vekić J, Vorkapić T, Erceg S, Gojković T, Tomašević R, Mamić M, Mitrović M, Zeljković A. Increased Odds of Metabolic Dysfunction-Associated Steatotic
Liver Disease Are Linked to Reduced n-6, but Not n-3
Polyunsaturated Fatty Acids in Plasma. in Biomolecules. 2024;14(8).
doi:10.3390/biom14080902 .
Franković, Irena, Đuričić, Ivana, Ninić, Ana, Vekić, Jelena, Vorkapić, Tara, Erceg, Sanja, Gojković, Tamara, Tomašević, Ratko, Mamić, Milica, Mitrović, Miloš, Zeljković, Aleksandra, "Increased Odds of Metabolic Dysfunction-Associated Steatotic
Liver Disease Are Linked to Reduced n-6, but Not n-3
Polyunsaturated Fatty Acids in Plasma" in Biomolecules, 14, no. 8 (2024),
https://doi.org/10.3390/biom14080902 . .

Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides

Anić-Marković, Bojana; Marinković, Aleksandar; Antić-Stanković, Jelena; Mijatović, Stefan; Cvijetić, Ilija; Simić, Milena; Aranđelović, Irena

(MDPI, 2024)

TY  - JOUR
AU  - Anić-Marković, Bojana
AU  - Marinković, Aleksandar
AU  - Antić-Stanković, Jelena
AU  - Mijatović, Stefan
AU  - Cvijetić, Ilija
AU  - Simić, Milena
AU  - Aranđelović, Irena
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5754
AB  - Antioxidants are promising compounds with antimicrobial activity against drug-resistant pathogens, especially when combined with conventional antimicrobials. Our study aimed to characterize the structure of nicotinamides synthesized from nicotinic acid and thiocarbohydrazones and to evaluate their antibacterial and antifungal activity. Seven nicotinic acid hydrazides (NC 1–7) were synthesized using mono-thiocarbohydrazones with hydroxyl group substituents, along with quinolone, phenolic, and pyridine rings known for their antimicrobial activity. The in vitro antimicrobial activity of NC 1–7, at concentrations ranging from 0.001 to 1 mM, was tested against Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (NCIMB 9111), and Candida albicans (ATCC 24433) using the broth microdilution method per EUCAST 2024 guidelines. Microorganism survival percentages were calculated based on optical density, and target fishing using the PharmMapper database identified potential molecular targets. The results showed that P. aeruginosa was most susceptible to the compounds, while C. albicans was the least susceptible. NC 3 significantly inhibited P. aeruginosa and K. pneumoniae growth at 0.016 mM, while higher concentrations were required for S. aureus, E. faecalis, and C. albicans. NC 5 was most effective against gram-positive bacteria at 0.03 mM. Only NC 4 completely inhibited C. albicans below 1 mM. NC 3, with the lowest concentration for 50% growth inhibition (0.016–0.064 mM), showed promising antibacterial potential against specific AMR-related proteins (bleomycin resistance protein, HTH-type transcriptional regulator QacR, and streptogramin A acetyltransferase), suggesting that this class of compounds could enhance or restore the activity of established antibiotics.
PB  - MDPI
T2  - Pharmaceutics
T1  - Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides
VL  - 16
IS  - 8
DO  - 10.3390/pharmaceutics16081084
ER  - 
@article{
author = "Anić-Marković, Bojana and Marinković, Aleksandar and Antić-Stanković, Jelena and Mijatović, Stefan and Cvijetić, Ilija and Simić, Milena and Aranđelović, Irena",
year = "2024",
abstract = "Antioxidants are promising compounds with antimicrobial activity against drug-resistant pathogens, especially when combined with conventional antimicrobials. Our study aimed to characterize the structure of nicotinamides synthesized from nicotinic acid and thiocarbohydrazones and to evaluate their antibacterial and antifungal activity. Seven nicotinic acid hydrazides (NC 1–7) were synthesized using mono-thiocarbohydrazones with hydroxyl group substituents, along with quinolone, phenolic, and pyridine rings known for their antimicrobial activity. The in vitro antimicrobial activity of NC 1–7, at concentrations ranging from 0.001 to 1 mM, was tested against Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (NCIMB 9111), and Candida albicans (ATCC 24433) using the broth microdilution method per EUCAST 2024 guidelines. Microorganism survival percentages were calculated based on optical density, and target fishing using the PharmMapper database identified potential molecular targets. The results showed that P. aeruginosa was most susceptible to the compounds, while C. albicans was the least susceptible. NC 3 significantly inhibited P. aeruginosa and K. pneumoniae growth at 0.016 mM, while higher concentrations were required for S. aureus, E. faecalis, and C. albicans. NC 5 was most effective against gram-positive bacteria at 0.03 mM. Only NC 4 completely inhibited C. albicans below 1 mM. NC 3, with the lowest concentration for 50% growth inhibition (0.016–0.064 mM), showed promising antibacterial potential against specific AMR-related proteins (bleomycin resistance protein, HTH-type transcriptional regulator QacR, and streptogramin A acetyltransferase), suggesting that this class of compounds could enhance or restore the activity of established antibiotics.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides",
volume = "16",
number = "8",
doi = "10.3390/pharmaceutics16081084"
}
Anić-Marković, B., Marinković, A., Antić-Stanković, J., Mijatović, S., Cvijetić, I., Simić, M.,& Aranđelović, I.. (2024). Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides. in Pharmaceutics
MDPI., 16(8).
https://doi.org/10.3390/pharmaceutics16081084
Anić-Marković B, Marinković A, Antić-Stanković J, Mijatović S, Cvijetić I, Simić M, Aranđelović I. Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides. in Pharmaceutics. 2024;16(8).
doi:10.3390/pharmaceutics16081084 .
Anić-Marković, Bojana, Marinković, Aleksandar, Antić-Stanković, Jelena, Mijatović, Stefan, Cvijetić, Ilija, Simić, Milena, Aranđelović, Irena, "Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides" in Pharmaceutics, 16, no. 8 (2024),
https://doi.org/10.3390/pharmaceutics16081084 . .

Stanković, Marko; Zeljković, Aleksandra; Vekić, Jelena; Antonić, Tamara; Ardalić, Daniela; Miljković-Trailović, Milica; Munjas, Jelena; Sarić-Matutinović, Marija; Gojković, Tamara; Jovičić, Snežana; Miković, Željko; Stefanović, Aleksandra

(MDPI, 2024)

TY  - JOUR
AU  - Stanković, Marko
AU  - Zeljković, Aleksandra
AU  - Vekić, Jelena
AU  - Antonić, Tamara
AU  - Ardalić, Daniela
AU  - Miljković-Trailović, Milica
AU  - Munjas, Jelena
AU  - Sarić-Matutinović, Marija
AU  - Gojković, Tamara
AU  - Jovičić, Snežana
AU  - Miković, Željko
AU  - Stefanović, Aleksandra
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5753
AB  - This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.
PB  - MDPI
T2  - Antioxidants
VL  - 13
IS  - 8
DO  - 10.3390/antiox13080948
ER  - 
@article{
author = "Stanković, Marko and Zeljković, Aleksandra and Vekić, Jelena and Antonić, Tamara and Ardalić, Daniela and Miljković-Trailović, Milica and Munjas, Jelena and Sarić-Matutinović, Marija and Gojković, Tamara and Jovičić, Snežana and Miković, Željko and Stefanović, Aleksandra",
year = "2024",
abstract = "This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.",
publisher = "MDPI",
journal = "Antioxidants",
volume = "13",
number = "8",
doi = "10.3390/antiox13080948"
}
Stanković, M., Zeljković, A., Vekić, J., Antonić, T., Ardalić, D., Miljković-Trailović, M., Munjas, J., Sarić-Matutinović, M., Gojković, T., Jovičić, S., Miković, Ž.,& Stefanović, A.. (2024). in Antioxidants
MDPI., 13(8).
https://doi.org/10.3390/antiox13080948
Stanković M, Zeljković A, Vekić J, Antonić T, Ardalić D, Miljković-Trailović M, Munjas J, Sarić-Matutinović M, Gojković T, Jovičić S, Miković Ž, Stefanović A. in Antioxidants. 2024;13(8).
doi:10.3390/antiox13080948 .
Stanković, Marko, Zeljković, Aleksandra, Vekić, Jelena, Antonić, Tamara, Ardalić, Daniela, Miljković-Trailović, Milica, Munjas, Jelena, Sarić-Matutinović, Marija, Gojković, Tamara, Jovičić, Snežana, Miković, Željko, Stefanović, Aleksandra, in Antioxidants, 13, no. 8 (2024),
https://doi.org/10.3390/antiox13080948 . .

Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches

Radosavljević, Tatjana; Branković, Marija; Samardžić, Janko; Đuretić, Jasmina; Vukičević, Dušan; Vučević, Danijela; Jakovljević, Vladimir

(MDPI, 2024)

TY  - JOUR
AU  - Radosavljević, Tatjana
AU  - Branković, Marija
AU  - Samardžić, Janko
AU  - Đuretić, Jasmina
AU  - Vukičević, Dušan
AU  - Vučević, Danijela
AU  - Jakovljević, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5752
AB  - Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), encompasses a range of liver conditions from steatosis to nonalcoholic steatohepatitis (NASH). Its prevalence, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis of MASLD involves metabolic dysregulation, inflammation, oxidative stress, genetic factors and, notably, mitochondrial dysfunction. Recent studies underscore the critical role of mitochondrial dysfunction in MASLD’s progression. Therapeutically, enhancing mitochondrial function has gained interest, along with lifestyle changes and pharmacological interventions targeting mitochondrial processes. The FDA’s approval of resmetirom for metabolic-associated steatohepatitis (MASH) with fibrosis marks a significant step. While resmetirom represents progress, further research is essential to understand MASLD-related mitochondrial dysfunction fully. Innovative strategies like gene editing and small-molecule modulators, alongside lifestyle interventions, can potentially improve MASLD treatment. Drug repurposing and new targets will advance MASLD therapy, addressing its increasing global burden. Therefore, this review aims to provide a better understanding of the role of mitochondrial dysfunction in MASLD and identify more effective preventive and treatment strategies.
PB  - MDPI
T2  - Antioxidants
T1  - Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches
VL  - 13
IS  - 8
DO  - 10.3390/antiox13080906
ER  - 
@article{
author = "Radosavljević, Tatjana and Branković, Marija and Samardžić, Janko and Đuretić, Jasmina and Vukičević, Dušan and Vučević, Danijela and Jakovljević, Vladimir",
year = "2024",
abstract = "Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), encompasses a range of liver conditions from steatosis to nonalcoholic steatohepatitis (NASH). Its prevalence, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis of MASLD involves metabolic dysregulation, inflammation, oxidative stress, genetic factors and, notably, mitochondrial dysfunction. Recent studies underscore the critical role of mitochondrial dysfunction in MASLD’s progression. Therapeutically, enhancing mitochondrial function has gained interest, along with lifestyle changes and pharmacological interventions targeting mitochondrial processes. The FDA’s approval of resmetirom for metabolic-associated steatohepatitis (MASH) with fibrosis marks a significant step. While resmetirom represents progress, further research is essential to understand MASLD-related mitochondrial dysfunction fully. Innovative strategies like gene editing and small-molecule modulators, alongside lifestyle interventions, can potentially improve MASLD treatment. Drug repurposing and new targets will advance MASLD therapy, addressing its increasing global burden. Therefore, this review aims to provide a better understanding of the role of mitochondrial dysfunction in MASLD and identify more effective preventive and treatment strategies.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches",
volume = "13",
number = "8",
doi = "10.3390/antiox13080906"
}
Radosavljević, T., Branković, M., Samardžić, J., Đuretić, J., Vukičević, D., Vučević, D.,& Jakovljević, V.. (2024). Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches. in Antioxidants
MDPI., 13(8).
https://doi.org/10.3390/antiox13080906
Radosavljević T, Branković M, Samardžić J, Đuretić J, Vukičević D, Vučević D, Jakovljević V. Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches. in Antioxidants. 2024;13(8).
doi:10.3390/antiox13080906 .
Radosavljević, Tatjana, Branković, Marija, Samardžić, Janko, Đuretić, Jasmina, Vukičević, Dušan, Vučević, Danijela, Jakovljević, Vladimir, "Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches" in Antioxidants, 13, no. 8 (2024),
https://doi.org/10.3390/antiox13080906 . .

Three Component Cascade Processes Involving Palladium Catalyzed Transformations/Dipolar Cycloadditions for the Synthesis of Angular Heterotriquinane Derivatives

Jovanović, Predrag; Jovanović, Miloš; Petković, Miloš; Simić, Milena; Tasić, Gordana; Rodić, Marko; Rakić, Srđan; Vlahović, Filip; Savić, Vladimir

(John Wiley and Sons Inc, 2024)

TY  - JOUR
AU  - Jovanović, Predrag
AU  - Jovanović, Miloš
AU  - Petković, Miloš
AU  - Simić, Milena
AU  - Tasić, Gordana
AU  - Rodić, Marko
AU  - Rakić, Srđan
AU  - Vlahović, Filip
AU  - Savić, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5704
AB  - Combining chemical reactivities of allenes and oximes created a methodology for the preparation of heterocyclic triquinane-type skeletons via a cascade process constructing four bonds in a single step. The initial reaction of allene moiety promoted by Pd-catalysis, affording π-allyl Pd-species, was followed by two additional transformations - nucleophilic displacement and dipolar cycloaddition - to furnish the product highly stereoselectively in moderate to good yields. For the process to be efficient, it was necessary to use a dipolarophilic component as a solvent. Intriguingly, while the reaction with cyclopentanone derived oxime progressed through the whole cascade, with cyclohexanone analogue it stopped at the nitrone stage, requiring an additional step to yield similar type of products. Some aspects of the studied cascade were examined by DFT.
PB  - John Wiley and Sons Inc
T2  - Advanced Synthesis and Catalysis
T1  - Three Component Cascade Processes Involving Palladium Catalyzed Transformations/Dipolar Cycloadditions for the Synthesis of Angular Heterotriquinane Derivatives
DO  - 10.1002/adsc.202400253
ER  - 
@article{
author = "Jovanović, Predrag and Jovanović, Miloš and Petković, Miloš and Simić, Milena and Tasić, Gordana and Rodić, Marko and Rakić, Srđan and Vlahović, Filip and Savić, Vladimir",
year = "2024",
abstract = "Combining chemical reactivities of allenes and oximes created a methodology for the preparation of heterocyclic triquinane-type skeletons via a cascade process constructing four bonds in a single step. The initial reaction of allene moiety promoted by Pd-catalysis, affording π-allyl Pd-species, was followed by two additional transformations - nucleophilic displacement and dipolar cycloaddition - to furnish the product highly stereoselectively in moderate to good yields. For the process to be efficient, it was necessary to use a dipolarophilic component as a solvent. Intriguingly, while the reaction with cyclopentanone derived oxime progressed through the whole cascade, with cyclohexanone analogue it stopped at the nitrone stage, requiring an additional step to yield similar type of products. Some aspects of the studied cascade were examined by DFT.",
publisher = "John Wiley and Sons Inc",
journal = "Advanced Synthesis and Catalysis",
title = "Three Component Cascade Processes Involving Palladium Catalyzed Transformations/Dipolar Cycloadditions for the Synthesis of Angular Heterotriquinane Derivatives",
doi = "10.1002/adsc.202400253"
}
Jovanović, P., Jovanović, M., Petković, M., Simić, M., Tasić, G., Rodić, M., Rakić, S., Vlahović, F.,& Savić, V.. (2024). Three Component Cascade Processes Involving Palladium Catalyzed Transformations/Dipolar Cycloadditions for the Synthesis of Angular Heterotriquinane Derivatives. in Advanced Synthesis and Catalysis
John Wiley and Sons Inc..
https://doi.org/10.1002/adsc.202400253
Jovanović P, Jovanović M, Petković M, Simić M, Tasić G, Rodić M, Rakić S, Vlahović F, Savić V. Three Component Cascade Processes Involving Palladium Catalyzed Transformations/Dipolar Cycloadditions for the Synthesis of Angular Heterotriquinane Derivatives. in Advanced Synthesis and Catalysis. 2024;.
doi:10.1002/adsc.202400253 .
Jovanović, Predrag, Jovanović, Miloš, Petković, Miloš, Simić, Milena, Tasić, Gordana, Rodić, Marko, Rakić, Srđan, Vlahović, Filip, Savić, Vladimir, "Three Component Cascade Processes Involving Palladium Catalyzed Transformations/Dipolar Cycloadditions for the Synthesis of Angular Heterotriquinane Derivatives" in Advanced Synthesis and Catalysis (2024),
https://doi.org/10.1002/adsc.202400253 . .
11

Cytotoxic prenylated phenols of false indigo-bush (Amorpha fruticosa L.)

Samardžić, Stevan; Đorđić Crnogorac, Marija; Petković, Miloš; Arsenijević, Jelena; Stanojković, Tatjana; Maksimović, Zoran

(Taylor & Francis Ltd., 2024)

TY  - JOUR
AU  - Samardžić, Stevan
AU  - Đorđić Crnogorac, Marija
AU  - Petković, Miloš
AU  - Arsenijević, Jelena
AU  - Stanojković, Tatjana
AU  - Maksimović, Zoran
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5636
AB  - This study employed the MTT assay to assess the cytotoxicity of one flavan and two stilbene derivatives isolated from the false indigo-bush (Amorpha fruticosa L.) fruits: 5,7-dihydroxy-8-geranylflavanone (1), 2-carboxy-3,5-dihydroxy-4-geranylbibenzyl (2), and 2-carboxy-3-hydroxy-
4-prenyl-5-methoxybibenzyl (3). The examined compounds reduced the survival of human cervical and colon tumour cells (HeLa, HT-29, HCT-116, and LS174) with IC50 values ranging from 10.55 to 147.09 μg/mL, except for 1, which did not affect LS174 cells within the tested concentrations. The highest activity was observed for 1 against HeLa cells, and 1 also exhibited the weakest effect against normal foetal lung fibroblasts (IC50 = 166.11 μg/mL), demonstrating good potency and selectivity. Stilbenes 2 and 3 proved efficacious, but lacked selectivity compared to 1. Our findings revealed the cytotoxicity of false indigo-bush constituents, justifying further mechanistic and in vivo investigations, particularly on 5,7-dihydroxy-8-geranylflavanone, which displayed considerable in vitro anticancer capacity and a potentially favourable safety profile.
PB  - Taylor & Francis Ltd.
T2  - Natural Product Research
T1  - Cytotoxic prenylated phenols of false indigo-bush (Amorpha fruticosa L.)
DO  - 10.1080/14786419.2024.2353912
ER  - 
@article{
author = "Samardžić, Stevan and Đorđić Crnogorac, Marija and Petković, Miloš and Arsenijević, Jelena and Stanojković, Tatjana and Maksimović, Zoran",
year = "2024",
abstract = "This study employed the MTT assay to assess the cytotoxicity of one flavan and two stilbene derivatives isolated from the false indigo-bush (Amorpha fruticosa L.) fruits: 5,7-dihydroxy-8-geranylflavanone (1), 2-carboxy-3,5-dihydroxy-4-geranylbibenzyl (2), and 2-carboxy-3-hydroxy-
4-prenyl-5-methoxybibenzyl (3). The examined compounds reduced the survival of human cervical and colon tumour cells (HeLa, HT-29, HCT-116, and LS174) with IC50 values ranging from 10.55 to 147.09 μg/mL, except for 1, which did not affect LS174 cells within the tested concentrations. The highest activity was observed for 1 against HeLa cells, and 1 also exhibited the weakest effect against normal foetal lung fibroblasts (IC50 = 166.11 μg/mL), demonstrating good potency and selectivity. Stilbenes 2 and 3 proved efficacious, but lacked selectivity compared to 1. Our findings revealed the cytotoxicity of false indigo-bush constituents, justifying further mechanistic and in vivo investigations, particularly on 5,7-dihydroxy-8-geranylflavanone, which displayed considerable in vitro anticancer capacity and a potentially favourable safety profile.",
publisher = "Taylor & Francis Ltd.",
journal = "Natural Product Research",
title = "Cytotoxic prenylated phenols of false indigo-bush (Amorpha fruticosa L.)",
doi = "10.1080/14786419.2024.2353912"
}
Samardžić, S., Đorđić Crnogorac, M., Petković, M., Arsenijević, J., Stanojković, T.,& Maksimović, Z.. (2024). Cytotoxic prenylated phenols of false indigo-bush (Amorpha fruticosa L.). in Natural Product Research
Taylor & Francis Ltd...
https://doi.org/10.1080/14786419.2024.2353912
Samardžić S, Đorđić Crnogorac M, Petković M, Arsenijević J, Stanojković T, Maksimović Z. Cytotoxic prenylated phenols of false indigo-bush (Amorpha fruticosa L.). in Natural Product Research. 2024;.
doi:10.1080/14786419.2024.2353912 .
Samardžić, Stevan, Đorđić Crnogorac, Marija, Petković, Miloš, Arsenijević, Jelena, Stanojković, Tatjana, Maksimović, Zoran, "Cytotoxic prenylated phenols of false indigo-bush (Amorpha fruticosa L.)" in Natural Product Research (2024),
https://doi.org/10.1080/14786419.2024.2353912 . .

Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent

Tasić, Gordana; Mitrović, Nikola; Simić, Milena; Koravović, Mladen; Jovanović, Predrag; Petković, Miloš; Jovanović, Miloš; Ivković, Branka; Savić, Vladimir

(Wiley Periodicals LLC., 2024)

TY  - JOUR
AU  - Tasić, Gordana
AU  - Mitrović, Nikola
AU  - Simić, Milena
AU  - Koravović, Mladen
AU  - Jovanović, Predrag
AU  - Petković, Miloš
AU  - Jovanović, Miloš
AU  - Ivković, Branka
AU  - Savić, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5556
AB  - Hydantoin derivatives are versatile structural motifs found in natural products
and various compounds with different biological or other properties. Due to
their importance in both organic and medicinal chemistry, a number of synthetic procedures have been developed. In this article, a novel methodology
utilizing N-Boc protected amino acid amides for their preparation has been
described. The cyclisation process was accomplished using solid supported
PPh3 and CBr 4 as reagents affording substituted hydantoins in moderate to
good yields (40%–77%).
PB  - Wiley Periodicals LLC.
T2  - Journal Heterocyclic Chemistry
T1  - Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent
DO  - 10.1002/jhet.4802
ER  - 
@article{
author = "Tasić, Gordana and Mitrović, Nikola and Simić, Milena and Koravović, Mladen and Jovanović, Predrag and Petković, Miloš and Jovanović, Miloš and Ivković, Branka and Savić, Vladimir",
year = "2024",
abstract = "Hydantoin derivatives are versatile structural motifs found in natural products
and various compounds with different biological or other properties. Due to
their importance in both organic and medicinal chemistry, a number of synthetic procedures have been developed. In this article, a novel methodology
utilizing N-Boc protected amino acid amides for their preparation has been
described. The cyclisation process was accomplished using solid supported
PPh3 and CBr 4 as reagents affording substituted hydantoins in moderate to
good yields (40%–77%).",
publisher = "Wiley Periodicals LLC.",
journal = "Journal Heterocyclic Chemistry",
title = "Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent",
doi = "10.1002/jhet.4802"
}
Tasić, G., Mitrović, N., Simić, M., Koravović, M., Jovanović, P., Petković, M., Jovanović, M., Ivković, B.,& Savić, V.. (2024). Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent. in Journal Heterocyclic Chemistry
Wiley Periodicals LLC...
https://doi.org/10.1002/jhet.4802
Tasić G, Mitrović N, Simić M, Koravović M, Jovanović P, Petković M, Jovanović M, Ivković B, Savić V. Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent. in Journal Heterocyclic Chemistry. 2024;.
doi:10.1002/jhet.4802 .
Tasić, Gordana, Mitrović, Nikola, Simić, Milena, Koravović, Mladen, Jovanović, Predrag, Petković, Miloš, Jovanović, Miloš, Ivković, Branka, Savić, Vladimir, "Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent" in Journal Heterocyclic Chemistry (2024),
https://doi.org/10.1002/jhet.4802 . .

Nutritional Value, Phytochemical Composition and Biological Activities of Lycium barbarum L. fruits from Serbia

Ilić, Tijana; Đuričić, Ivana; Kodranov, Igor; Ušjak, Ljuboš; Kolašinac, Stefan; Milenković, Marina; Marčetić, Mirjana; Božić, Dragana; Vidović, Bojana

(Springer, 2024)

TY  - JOUR
AU  - Ilić, Tijana
AU  - Đuričić, Ivana
AU  - Kodranov, Igor
AU  - Ušjak, Ljuboš
AU  - Kolašinac, Stefan
AU  - Milenković, Marina
AU  - Marčetić, Mirjana
AU  - Božić, Dragana
AU  - Vidović, Bojana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5705
AB  - Cultivation of goji berries (GB), fruits of Lycium barbarum L. (Solanaceae), is expanding worldwide, including in Europe. In this study, a comparative analysis of the nutritional value, chemical composition and in vitro biological activities of GB from different locations in Serbia was performed. Proximate compositions were evaluated according to standard methods. Minerals were assessed by inductively coupled plasma techniques, while fatty acids, sterols, and phenolic profiles were analyzed by gas- and liquid chromatography-based techniques coupled with flame-ionization, mass spectrometry, or diode array detection. The total content of phenolics, flavonoids, carotenoids, and polysaccharides was assessed using spectrophotometric methods. Methanol extracts from GB were examined for their antioxidant, enzyme inhibitory (α-amylase, α-glucosidase, acetylcholinesterase and tyrosinase) and antibacterial activities. Despite significant variations among samples from different locations, the results confirmed that GB are a valuable source of dietary fiber and protein and are characterized by favorable fatty acid profiles. Phytochemical analysis revealed that β-sitosterol, Δ5-avenasterol, and 24-methyldesmosterol are the predominant sterols and caffeic acid, gallic acid, quercetin and rutin are the main phenols. All GB samples showed both antioxidant and mild antimicrobial activity. A dose-dependent anti-enzymatic activity (IC50 ranging 1.68–6.88 mg/mL) was demonstrated. The results support further promotion of GB cultivation in Serbia and further investigations on their potential applications in various industries.
PB  - Springer
T2  - Plant Foods for Human Nutrition
T1  - Nutritional Value, Phytochemical Composition and Biological Activities of Lycium barbarum L. fruits from Serbia
DO  - 10.1007/s11130-024-01208-4
ER  - 
@article{
author = "Ilić, Tijana and Đuričić, Ivana and Kodranov, Igor and Ušjak, Ljuboš and Kolašinac, Stefan and Milenković, Marina and Marčetić, Mirjana and Božić, Dragana and Vidović, Bojana",
year = "2024",
abstract = "Cultivation of goji berries (GB), fruits of Lycium barbarum L. (Solanaceae), is expanding worldwide, including in Europe. In this study, a comparative analysis of the nutritional value, chemical composition and in vitro biological activities of GB from different locations in Serbia was performed. Proximate compositions were evaluated according to standard methods. Minerals were assessed by inductively coupled plasma techniques, while fatty acids, sterols, and phenolic profiles were analyzed by gas- and liquid chromatography-based techniques coupled with flame-ionization, mass spectrometry, or diode array detection. The total content of phenolics, flavonoids, carotenoids, and polysaccharides was assessed using spectrophotometric methods. Methanol extracts from GB were examined for their antioxidant, enzyme inhibitory (α-amylase, α-glucosidase, acetylcholinesterase and tyrosinase) and antibacterial activities. Despite significant variations among samples from different locations, the results confirmed that GB are a valuable source of dietary fiber and protein and are characterized by favorable fatty acid profiles. Phytochemical analysis revealed that β-sitosterol, Δ5-avenasterol, and 24-methyldesmosterol are the predominant sterols and caffeic acid, gallic acid, quercetin and rutin are the main phenols. All GB samples showed both antioxidant and mild antimicrobial activity. A dose-dependent anti-enzymatic activity (IC50 ranging 1.68–6.88 mg/mL) was demonstrated. The results support further promotion of GB cultivation in Serbia and further investigations on their potential applications in various industries.",
publisher = "Springer",
journal = "Plant Foods for Human Nutrition",
title = "Nutritional Value, Phytochemical Composition and Biological Activities of Lycium barbarum L. fruits from Serbia",
doi = "10.1007/s11130-024-01208-4"
}
Ilić, T., Đuričić, I., Kodranov, I., Ušjak, L., Kolašinac, S., Milenković, M., Marčetić, M., Božić, D.,& Vidović, B.. (2024). Nutritional Value, Phytochemical Composition and Biological Activities of Lycium barbarum L. fruits from Serbia. in Plant Foods for Human Nutrition
Springer..
https://doi.org/10.1007/s11130-024-01208-4
Ilić T, Đuričić I, Kodranov I, Ušjak L, Kolašinac S, Milenković M, Marčetić M, Božić D, Vidović B. Nutritional Value, Phytochemical Composition and Biological Activities of Lycium barbarum L. fruits from Serbia. in Plant Foods for Human Nutrition. 2024;.
doi:10.1007/s11130-024-01208-4 .
Ilić, Tijana, Đuričić, Ivana, Kodranov, Igor, Ušjak, Ljuboš, Kolašinac, Stefan, Milenković, Marina, Marčetić, Mirjana, Božić, Dragana, Vidović, Bojana, "Nutritional Value, Phytochemical Composition and Biological Activities of Lycium barbarum L. fruits from Serbia" in Plant Foods for Human Nutrition (2024),
https://doi.org/10.1007/s11130-024-01208-4 . .

Discovery of dual-acting HDAC inhibitors for the treatment of pancreatic cancer by combining drug synergy and molecular modeling

Đoković, Nemanja; Ilić, Aleksandra; Čebzan, Alen; Radović, Branko; Ružić, Dušan; Beljkaš, Milan; Đurić, Ana; Srdić-Rajić, Tatjana; Oljačić, Slavica; Nikolić, Katarina

(EFMC, 2024)

TY  - CONF
AU  - Đoković, Nemanja
AU  - Ilić, Aleksandra
AU  - Čebzan, Alen
AU  - Radović, Branko
AU  - Ružić, Dušan
AU  - Beljkaš, Milan
AU  - Đurić, Ana
AU  - Srdić-Rajić, Tatjana
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5747
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most threatening and deadly cancers. The occurrence of
chemoresistance in PDAC plays an important role in the unfavorable survival rates, so there is an urgent need to
rapidly develop new pharmaceutical strategies to address this problem and improve treatment outcomes for
PDAC (1). Considering the numerous epigenetic alterations observed in PDAC, the use of epigenetic drugs, such
as histone deacetylase (HDAC) inhibitors, is a promising approach, especially when used in combination
therapies (2).
In this study, we investigated the potential of using drug sensitivity and basal gene expression data from
pancreatic cancer cell lines to develop a bioinformatic screening protocol to predict the available combinatorial
options for HDAC inhibitors, including sirtuin (SIRT) inhibitors. Experimental validation of the protocol in two
pancreatic cancer cell lines (MIA PaCa-2 cells and PANC-1) confirmed the identified synergies between HDAC
inhibitors and the sphingosine-1-phosphate (S1P) receptor agonist – fingolimod or HDAC inhibitors and the
Rho-associated protein kinase (ROCK) inhibitor – RKI-1447 (3).
The bioinformatic screening protocol developed to predict synergistic drug combinations in PDAC identified
several previously unknown interaction partners of HDAC inhibitors. The predicted interaction partners of
HDAC inhibitors, including ROCK, aurora kinase A inhibitor (AURKA), glutaminase inhibitor (GLS) and
WEE1 kinase inhibitor, were selected using structure-based molecular modeling for the development of novel
classes of dual-acting HDAC inhibitors. The novel dual inhibitors (HDAC/ROCK, SIRT/AURKA, HDAC/GLS
and HDAC/WEE1) were designed based on the known pharmacophore properties and molecular docking models
developed for the respective targets. The molecular docking study was performed using GOLD software. The
enzymes were prepared for the docking study using the online software Play Molecule-ProteinPrepare. The
docking results of the developed inhibitors showed a remarkable affinity to the specific targets. The critical parts
of the structures that produce the interactions crucial for the inhibition of HDAC1, HDAC6, ROCK1, ROCK2,
AURKA, GLS and WEE1 were identified. In conjunction with the drug synergy predictions, these designed
molecules also show great potential as promising structures for subsequent experimental evaluation. Taking all
these findings into account, the most aactive compounds were selected to be further synthesized and evaluated
using in vitro enzyme and cell assays.
References
1) A. McGuigan et al., World J Gastroenterol. 24, 4846–4861 (2018).
2) X.-S. Xiang, P.-C. Li, W.-Q. Wang, L. Liu, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1877, 188676
(2022).
3) N. Djokovic, A. Djuric, D. Ruzic, T. Srdic-Rajic, K. Nikolic, Pharmaceuticals. 16, 294 (2023).
PB  - EFMC
PB  - Societa Chimica Italiana
C3  - EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts
T1  - Discovery of dual-acting HDAC inhibitors for the treatment of pancreatic cancer by combining drug synergy and molecular modeling
SP  - 463
EP  - 463
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5747
ER  - 
@conference{
author = "Đoković, Nemanja and Ilić, Aleksandra and Čebzan, Alen and Radović, Branko and Ružić, Dušan and Beljkaš, Milan and Đurić, Ana and Srdić-Rajić, Tatjana and Oljačić, Slavica and Nikolić, Katarina",
year = "2024",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is one of the most threatening and deadly cancers. The occurrence of
chemoresistance in PDAC plays an important role in the unfavorable survival rates, so there is an urgent need to
rapidly develop new pharmaceutical strategies to address this problem and improve treatment outcomes for
PDAC (1). Considering the numerous epigenetic alterations observed in PDAC, the use of epigenetic drugs, such
as histone deacetylase (HDAC) inhibitors, is a promising approach, especially when used in combination
therapies (2).
In this study, we investigated the potential of using drug sensitivity and basal gene expression data from
pancreatic cancer cell lines to develop a bioinformatic screening protocol to predict the available combinatorial
options for HDAC inhibitors, including sirtuin (SIRT) inhibitors. Experimental validation of the protocol in two
pancreatic cancer cell lines (MIA PaCa-2 cells and PANC-1) confirmed the identified synergies between HDAC
inhibitors and the sphingosine-1-phosphate (S1P) receptor agonist – fingolimod or HDAC inhibitors and the
Rho-associated protein kinase (ROCK) inhibitor – RKI-1447 (3).
The bioinformatic screening protocol developed to predict synergistic drug combinations in PDAC identified
several previously unknown interaction partners of HDAC inhibitors. The predicted interaction partners of
HDAC inhibitors, including ROCK, aurora kinase A inhibitor (AURKA), glutaminase inhibitor (GLS) and
WEE1 kinase inhibitor, were selected using structure-based molecular modeling for the development of novel
classes of dual-acting HDAC inhibitors. The novel dual inhibitors (HDAC/ROCK, SIRT/AURKA, HDAC/GLS
and HDAC/WEE1) were designed based on the known pharmacophore properties and molecular docking models
developed for the respective targets. The molecular docking study was performed using GOLD software. The
enzymes were prepared for the docking study using the online software Play Molecule-ProteinPrepare. The
docking results of the developed inhibitors showed a remarkable affinity to the specific targets. The critical parts
of the structures that produce the interactions crucial for the inhibition of HDAC1, HDAC6, ROCK1, ROCK2,
AURKA, GLS and WEE1 were identified. In conjunction with the drug synergy predictions, these designed
molecules also show great potential as promising structures for subsequent experimental evaluation. Taking all
these findings into account, the most aactive compounds were selected to be further synthesized and evaluated
using in vitro enzyme and cell assays.
References
1) A. McGuigan et al., World J Gastroenterol. 24, 4846–4861 (2018).
2) X.-S. Xiang, P.-C. Li, W.-Q. Wang, L. Liu, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1877, 188676
(2022).
3) N. Djokovic, A. Djuric, D. Ruzic, T. Srdic-Rajic, K. Nikolic, Pharmaceuticals. 16, 294 (2023).",
publisher = "EFMC, Societa Chimica Italiana",
journal = "EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts",
title = "Discovery of dual-acting HDAC inhibitors for the treatment of pancreatic cancer by combining drug synergy and molecular modeling",
pages = "463-463",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5747"
}
Đoković, N., Ilić, A., Čebzan, A., Radović, B., Ružić, D., Beljkaš, M., Đurić, A., Srdić-Rajić, T., Oljačić, S.,& Nikolić, K.. (2024). Discovery of dual-acting HDAC inhibitors for the treatment of pancreatic cancer by combining drug synergy and molecular modeling. in EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts
EFMC., 463-463.
https://hdl.handle.net/21.15107/rcub_farfar_5747
Đoković N, Ilić A, Čebzan A, Radović B, Ružić D, Beljkaš M, Đurić A, Srdić-Rajić T, Oljačić S, Nikolić K. Discovery of dual-acting HDAC inhibitors for the treatment of pancreatic cancer by combining drug synergy and molecular modeling. in EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts. 2024;:463-463.
https://hdl.handle.net/21.15107/rcub_farfar_5747 .
Đoković, Nemanja, Ilić, Aleksandra, Čebzan, Alen, Radović, Branko, Ružić, Dušan, Beljkaš, Milan, Đurić, Ana, Srdić-Rajić, Tatjana, Oljačić, Slavica, Nikolić, Katarina, "Discovery of dual-acting HDAC inhibitors for the treatment of pancreatic cancer by combining drug synergy and molecular modeling" in EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts (2024):463-463,
https://hdl.handle.net/21.15107/rcub_farfar_5747 .

Application of membrane mimetic systems approach in investigation of ionizable drugs: a case of cetirizine

Popović-Nikolić, Marija; Oljačić, Slavica; Popović, Gordana; Nikolić, Katarina

(EFMC, 2024)

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Oljačić, Slavica
AU  - Popović, Gordana
AU  - Nikolić, Katarina
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5746
AB  - Membrane mimicking approach is based on the philosophy of compartmentalization of molecules in systems
which may affect reaction rates, properties and stereochemistry that, in turn, differ from those observed in “pure”
aqueous solutions [1]. There is no ideal model that fully reproduces all the complexities of biomembranes, but a
large variety of membrane mimetics are available [2]. Since their properties are well understood at the chemical
level, micellar solutions of differently charged surfactants are systems the most commonly used to mimic the
desired functions of cells membranes [1]. In our previous studies we showed that protolytic equilibria of
ionizable drugs may significantly shift in micellar solutions [3, 4]. Our results suggest that is not possible to
predict the direction and intensity of the shift which requires comprehensive experimental consideration of every
single compound. Drug compounds containing two or more ionizable centers represent the greatest challenge,
especially if the pKa values are close and the ionization processes are overlapped. Estimation of the
pharmacological behavior and pharmacokinetic properties of these drugs, based on the pKa values exclusively
defined in “pure” aqueous solution, can be misleading, as possible interactions with biomolecules may
significantly change the assumed ionization patterns. In this study, the protolytic equilibria of cetirizine, a
second-generation antihistamine used to treat various allergy symptoms has been examined in micellar solutions
of differently charged surfactants, anionic (SDS), cationic (CTAB), and nonionic (TX-100). The pKa values of
cetirizine were determined potentiometrically under the same conditions in the “pure” water and in the micellar
solutions. Complex system of protolytic equilibria which includes 3 ionizable centers was resolved by program
HYPERQUAD [5]. The shift in equilibria affected by the presence of micelles was observed from (- 1.41) pKa
unit (cationic micelles) to (+ 2.01) pKa unit (anionic micelles). Interaction with micelles indicates on possible
interactions with biomolecules which may affect assumed distribution of equilibrium forms under the conditions
of absorption.
References
1) Fendler, J.H., Chem Rev., 1987, 87(5):877-899.
2) Klöpfer, K., Hagn, F., Prog Nucl Magn Reson Spectrosc., 2019, 114:271-283.
3) Popović-Nikolić, M.R., et al., J Chem Eng Data., 2018, 63(8):3150-3156.
4) Popović, M. R., et al., J ChemEng Data., 2013, 58(9):2567-2573.
5) Gans, P., et al., Talanta., 1996:43:1739.
PB  - EFMC
PB  - Societa Chimica Italiana
C3  - EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts
T1  - Application of membrane mimetic systems approach in investigation of ionizable drugs: a case of cetirizine
SP  - 468
EP  - 468
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5746
ER  - 
@conference{
author = "Popović-Nikolić, Marija and Oljačić, Slavica and Popović, Gordana and Nikolić, Katarina",
year = "2024",
abstract = "Membrane mimicking approach is based on the philosophy of compartmentalization of molecules in systems
which may affect reaction rates, properties and stereochemistry that, in turn, differ from those observed in “pure”
aqueous solutions [1]. There is no ideal model that fully reproduces all the complexities of biomembranes, but a
large variety of membrane mimetics are available [2]. Since their properties are well understood at the chemical
level, micellar solutions of differently charged surfactants are systems the most commonly used to mimic the
desired functions of cells membranes [1]. In our previous studies we showed that protolytic equilibria of
ionizable drugs may significantly shift in micellar solutions [3, 4]. Our results suggest that is not possible to
predict the direction and intensity of the shift which requires comprehensive experimental consideration of every
single compound. Drug compounds containing two or more ionizable centers represent the greatest challenge,
especially if the pKa values are close and the ionization processes are overlapped. Estimation of the
pharmacological behavior and pharmacokinetic properties of these drugs, based on the pKa values exclusively
defined in “pure” aqueous solution, can be misleading, as possible interactions with biomolecules may
significantly change the assumed ionization patterns. In this study, the protolytic equilibria of cetirizine, a
second-generation antihistamine used to treat various allergy symptoms has been examined in micellar solutions
of differently charged surfactants, anionic (SDS), cationic (CTAB), and nonionic (TX-100). The pKa values of
cetirizine were determined potentiometrically under the same conditions in the “pure” water and in the micellar
solutions. Complex system of protolytic equilibria which includes 3 ionizable centers was resolved by program
HYPERQUAD [5]. The shift in equilibria affected by the presence of micelles was observed from (- 1.41) pKa
unit (cationic micelles) to (+ 2.01) pKa unit (anionic micelles). Interaction with micelles indicates on possible
interactions with biomolecules which may affect assumed distribution of equilibrium forms under the conditions
of absorption.
References
1) Fendler, J.H., Chem Rev., 1987, 87(5):877-899.
2) Klöpfer, K., Hagn, F., Prog Nucl Magn Reson Spectrosc., 2019, 114:271-283.
3) Popović-Nikolić, M.R., et al., J Chem Eng Data., 2018, 63(8):3150-3156.
4) Popović, M. R., et al., J ChemEng Data., 2013, 58(9):2567-2573.
5) Gans, P., et al., Talanta., 1996:43:1739.",
publisher = "EFMC, Societa Chimica Italiana",
journal = "EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts",
title = "Application of membrane mimetic systems approach in investigation of ionizable drugs: a case of cetirizine",
pages = "468-468",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5746"
}
Popović-Nikolić, M., Oljačić, S., Popović, G.,& Nikolić, K.. (2024). Application of membrane mimetic systems approach in investigation of ionizable drugs: a case of cetirizine. in EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts
EFMC., 468-468.
https://hdl.handle.net/21.15107/rcub_farfar_5746
Popović-Nikolić M, Oljačić S, Popović G, Nikolić K. Application of membrane mimetic systems approach in investigation of ionizable drugs: a case of cetirizine. in EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts. 2024;:468-468.
https://hdl.handle.net/21.15107/rcub_farfar_5746 .
Popović-Nikolić, Marija, Oljačić, Slavica, Popović, Gordana, Nikolić, Katarina, "Application of membrane mimetic systems approach in investigation of ionizable drugs: a case of cetirizine" in EFMC-ISMC 2024,  XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts (2024):468-468,
https://hdl.handle.net/21.15107/rcub_farfar_5746 .

Determination of physicochemical quality parameters of fruit wines produced in Republic of Serbia

Čakar, Uroš; Stanković, Ivan; Đorđević, Brižita

(Savez farmaceutskih udruženja Srbije, Beograd, 2024)

TY  - JOUR
AU  - Čakar, Uroš
AU  - Stanković, Ivan
AU  - Đorđević, Brižita
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5745
AB  - Fruit wines are products obtained after the processing of fruit crops which are not grapes.
Water and alcohol are the most abundant constituents of fruit wines, along with biologically active
compounds which are present in small amounts. Taken together, they significantly affect the
physicochemical quality parameters. Before market placement, it is important to determine the
physicochemical quality parameters of fruit wines.
This study deals with the determination of physicochemical quality parameters in
blackberry and sour cherry fruit wines produced in Serbia. The total content of acids determined
by titration was in the interval from 7.37 to 9.05 g/L express to mallic acid. The pH values were
from 2.75 to 3.57. The content of free SO2 is important to prevent spoilage induced by
microorganisms, and it was in the range from 12.52 to 15.21 mg/L. The ethanol content of samples
was in the interval from 6.87 to 13.57 % v/v. The obtained values for ethanol content were in
accordance with the initial content of sugar in vinification, which was in the range from 13.8 to
24.2 ° Brix. Total phenolic content of fruit wines was from 1895.77 to 2417.21 mg/L expressed
as gallic acid equivalents.
All the investigated physicochemical parameters of the analyzed fruit wines, except ethanol
content, were in line with the National Regulations for Quality and Other Demands for Grape
Wine (National Regulations). The obtained results indicate the quality of fruit and demonstrate
that all the procedures applied during wine production were conducted properly to obtain a quality
final product. Ethanol content was below the minimal limit in 5 of 11 analyzed samples according
to the National Regulations. This can be explained by the fact that every fruit has a different
composition of natural constituents, which is a crucial reason to adopt specific regulations related
to quality and other requirements for fruit wines.
AB  - Voćna vina su proizvodi koji se dobijaju preradom voća koje nije grožđe. Voda i alkohol su najzastupljeniji u sastavu, dok su u malim količinama prisutna i biološki aktivna jedinjenja. Svi oni zajedno utiču na fizičko-hemijske parametre kvaliteta. Da bi voćna vina mogla da se nađu na tržištu, bitno je da se ispitaju fizičko-hemijski parametri kvaliteta. U ovom radu ispitani su fizičko-hemijski parametri kvaliteta voćnih vina od kupine i višnje koja su proizvedena u Srbiji. Sadržaj ukupnih kiselina određen titracijom je bio od 7.37 do 9.05 g/L jabučne kiseline. Vrednosti za pH vina su bile u intervalu od 2.75 do 3.57. Količina slobodnog SO2, koji je važan da zaštiti vino od mikrobiološkog kvarenja, bila je 12.52 do 15.21 mg/L. Količina alkohola u vinima bila je u intervalu od 6.87 do 13.57 % v/v. Upravo ove vrednosti su bile u skladu sa inicijalnim sadržajem šećera u vinifikacijama, koji je bio od 13.8 do 24.2 ° Brix. Sadržaj ukupnih polifenola u vinima je bio 1895.77 do 2417.21 mg/L ekvivalenata galne kiseline. Svi rezultati analize kvaliteta voćnih vina, osim sadržaja alkohola, bili su u skladu sa Pravilnikom o kvalitetu i drugim zahtevima za vino od grožđa (Pravilnik), što ukazuje na kvalitet voća i na to da je postupak proizvodnje sproveden tako da se dobije dobar krajnji proizvod. Sadržaj alkohola u 5 od 11 uzoraka analiziranih vina je bio ispod najniže vrednosti propisane Pravilnikom, što se može objasniti različitom prirodom samog voća u odnosu na grožđe. Upravo to je glavni razlog da se usvoje posebni zakonski propisi koji će se odnositi na kvalitet i druge zahteve za voćna vina.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
PB  - Univerzitet u Beogradu - Farmaceutski fakultet
T2  - Arhiv za farmaciju
T1  - Determination of physicochemical quality parameters of fruit wines produced in Republic of Serbia
T1  - Ispitivanje fizičko-hemijskih parametara kvaliteta voćnih vina proizvedenih u Republici Srbiji
VL  - 74
IS  - 4
SP  - 582
EP  - 597
DO  - 10.5937/arhfarm74-50304
ER  - 
@article{
author = "Čakar, Uroš and Stanković, Ivan and Đorđević, Brižita",
year = "2024",
abstract = "Fruit wines are products obtained after the processing of fruit crops which are not grapes.
Water and alcohol are the most abundant constituents of fruit wines, along with biologically active
compounds which are present in small amounts. Taken together, they significantly affect the
physicochemical quality parameters. Before market placement, it is important to determine the
physicochemical quality parameters of fruit wines.
This study deals with the determination of physicochemical quality parameters in
blackberry and sour cherry fruit wines produced in Serbia. The total content of acids determined
by titration was in the interval from 7.37 to 9.05 g/L express to mallic acid. The pH values were
from 2.75 to 3.57. The content of free SO2 is important to prevent spoilage induced by
microorganisms, and it was in the range from 12.52 to 15.21 mg/L. The ethanol content of samples
was in the interval from 6.87 to 13.57 % v/v. The obtained values for ethanol content were in
accordance with the initial content of sugar in vinification, which was in the range from 13.8 to
24.2 ° Brix. Total phenolic content of fruit wines was from 1895.77 to 2417.21 mg/L expressed
as gallic acid equivalents.
All the investigated physicochemical parameters of the analyzed fruit wines, except ethanol
content, were in line with the National Regulations for Quality and Other Demands for Grape
Wine (National Regulations). The obtained results indicate the quality of fruit and demonstrate
that all the procedures applied during wine production were conducted properly to obtain a quality
final product. Ethanol content was below the minimal limit in 5 of 11 analyzed samples according
to the National Regulations. This can be explained by the fact that every fruit has a different
composition of natural constituents, which is a crucial reason to adopt specific regulations related
to quality and other requirements for fruit wines., Voćna vina su proizvodi koji se dobijaju preradom voća koje nije grožđe. Voda i alkohol su najzastupljeniji u sastavu, dok su u malim količinama prisutna i biološki aktivna jedinjenja. Svi oni zajedno utiču na fizičko-hemijske parametre kvaliteta. Da bi voćna vina mogla da se nađu na tržištu, bitno je da se ispitaju fizičko-hemijski parametri kvaliteta. U ovom radu ispitani su fizičko-hemijski parametri kvaliteta voćnih vina od kupine i višnje koja su proizvedena u Srbiji. Sadržaj ukupnih kiselina određen titracijom je bio od 7.37 do 9.05 g/L jabučne kiseline. Vrednosti za pH vina su bile u intervalu od 2.75 do 3.57. Količina slobodnog SO2, koji je važan da zaštiti vino od mikrobiološkog kvarenja, bila je 12.52 do 15.21 mg/L. Količina alkohola u vinima bila je u intervalu od 6.87 do 13.57 % v/v. Upravo ove vrednosti su bile u skladu sa inicijalnim sadržajem šećera u vinifikacijama, koji je bio od 13.8 do 24.2 ° Brix. Sadržaj ukupnih polifenola u vinima je bio 1895.77 do 2417.21 mg/L ekvivalenata galne kiseline. Svi rezultati analize kvaliteta voćnih vina, osim sadržaja alkohola, bili su u skladu sa Pravilnikom o kvalitetu i drugim zahtevima za vino od grožđa (Pravilnik), što ukazuje na kvalitet voća i na to da je postupak proizvodnje sproveden tako da se dobije dobar krajnji proizvod. Sadržaj alkohola u 5 od 11 uzoraka analiziranih vina je bio ispod najniže vrednosti propisane Pravilnikom, što se može objasniti različitom prirodom samog voća u odnosu na grožđe. Upravo to je glavni razlog da se usvoje posebni zakonski propisi koji će se odnositi na kvalitet i druge zahteve za voćna vina.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd, Univerzitet u Beogradu - Farmaceutski fakultet",
journal = "Arhiv za farmaciju",
title = "Determination of physicochemical quality parameters of fruit wines produced in Republic of Serbia, Ispitivanje fizičko-hemijskih parametara kvaliteta voćnih vina proizvedenih u Republici Srbiji",
volume = "74",
number = "4",
pages = "582-597",
doi = "10.5937/arhfarm74-50304"
}
Čakar, U., Stanković, I.,& Đorđević, B.. (2024). Determination of physicochemical quality parameters of fruit wines produced in Republic of Serbia. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 74(4), 582-597.
https://doi.org/10.5937/arhfarm74-50304
Čakar U, Stanković I, Đorđević B. Determination of physicochemical quality parameters of fruit wines produced in Republic of Serbia. in Arhiv za farmaciju. 2024;74(4):582-597.
doi:10.5937/arhfarm74-50304 .
Čakar, Uroš, Stanković, Ivan, Đorđević, Brižita, "Determination of physicochemical quality parameters of fruit wines produced in Republic of Serbia" in Arhiv za farmaciju, 74, no. 4 (2024):582-597,
https://doi.org/10.5937/arhfarm74-50304 . .