TY  - JOUR
AU  - Ćurčić, Vladimir
AU  - Olszewski, Mateusz
AU  - Maciejewska, Natalia
AU  - Višnjevac, Aleksandar
AU  - Srdić-Rajić, Tatjana
AU  - Dobričić, Vladimir
AU  - García-Sosa, Alfonso T.
AU  - Kokanov, Sanja B.
AU  - Araškov, Jovana B.
AU  - Silvestri, Romano
AU  - Schüle, Roland
AU  - Jung, Manfred
AU  - Nikolić, Milan
AU  - Filipović, Nenad R.
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5298
AB  - Heterocyclic pharmacophores such as thiazole and quinoline rings have a significant role in medicinal chemistry. They are considered privileged structures since they constitute several Food and Drug Administration (FDA)-approved drugs for cancer treatment. Herein, we report the synthesis, in silico evaluation of the ADMET profiles, and in vitro investigation of the anticancer activity of a series of novel thiazolyl-hydrazones based on the 8-quinoline (1a–c), 2-quinoline (2a–c), and 8-hydroxy-2-quinolyl moiety (3a–c). The panel of several human cancer cell lines and the nontumorigenic human embryonic kidney cell line HEK-293 were used to evaluate the compound-mediated in vitro anticancer activities, leading to [2-(2-(quinolyl-8-ol-2-ylmethylene)hydrazinyl)]-4-(4-methoxyphenyl)-1,3-thiazole (3c) as the most promising compound. The study revealed that 3c blocks the cell-cycle progression of a human colon cancer cell line (HCT-116) in the S phase and induces DNA double-strand breaks. Also, our findings demonstrate that 3c accumulates in lysosomes, ultimately leading to the cell death of the hepatocellular carcinoma cell line (Hep-G2) and HCT-116 cells, by the mechanism of autophagy inhibition.
PB  - John Wiley and Sons Inc
T2  - Archiv der Pharmazie
T1  - Quinoline-based thiazolyl-hydrazones target cancer cells through autophagy inhibition
VL  - 357
IS  - 2
SP  - 2300426
DO  - 10.1002/ardp.202300426
ER  - 

@article{
author = "Ćurčić, Vladimir and Olszewski, Mateusz and Maciejewska, Natalia and Višnjevac, Aleksandar and Srdić-Rajić, Tatjana and Dobričić, Vladimir and García-Sosa, Alfonso T. and Kokanov, Sanja B. and Araškov, Jovana B. and Silvestri, Romano and Schüle, Roland and Jung, Manfred and Nikolić, Milan and Filipović, Nenad R.",
year = "2024",
abstract = "Heterocyclic pharmacophores such as thiazole and quinoline rings have a significant role in medicinal chemistry. They are considered privileged structures since they constitute several Food and Drug Administration (FDA)-approved drugs for cancer treatment. Herein, we report the synthesis, in silico evaluation of the ADMET profiles, and in vitro investigation of the anticancer activity of a series of novel thiazolyl-hydrazones based on the 8-quinoline (1a–c), 2-quinoline (2a–c), and 8-hydroxy-2-quinolyl moiety (3a–c). The panel of several human cancer cell lines and the nontumorigenic human embryonic kidney cell line HEK-293 were used to evaluate the compound-mediated in vitro anticancer activities, leading to [2-(2-(quinolyl-8-ol-2-ylmethylene)hydrazinyl)]-4-(4-methoxyphenyl)-1,3-thiazole (3c) as the most promising compound. The study revealed that 3c blocks the cell-cycle progression of a human colon cancer cell line (HCT-116) in the S phase and induces DNA double-strand breaks. Also, our findings demonstrate that 3c accumulates in lysosomes, ultimately leading to the cell death of the hepatocellular carcinoma cell line (Hep-G2) and HCT-116 cells, by the mechanism of autophagy inhibition.",
publisher = "John Wiley and Sons Inc",
journal = "Archiv der Pharmazie",
title = "Quinoline-based thiazolyl-hydrazones target cancer cells through autophagy inhibition",
volume = "357",
number = "2",
pages = "2300426",
doi = "10.1002/ardp.202300426"
}

Ćurčić, V., Olszewski, M., Maciejewska, N., Višnjevac, A., Srdić-Rajić, T., Dobričić, V., García-Sosa, A. T., Kokanov, S. B., Araškov, J. B., Silvestri, R., Schüle, R., Jung, M., Nikolić, M.,& Filipović, N. R.. (2024). Quinoline-based thiazolyl-hydrazones target cancer cells through autophagy inhibition. in Archiv der Pharmazie
John Wiley and Sons Inc., 357(2), 2300426.
https://doi.org/10.1002/ardp.202300426

Ćurčić V, Olszewski M, Maciejewska N, Višnjevac A, Srdić-Rajić T, Dobričić V, García-Sosa AT, Kokanov SB, Araškov JB, Silvestri R, Schüle R, Jung M, Nikolić M, Filipović NR. Quinoline-based thiazolyl-hydrazones target cancer cells through autophagy inhibition. in Archiv der Pharmazie. 2024;357(2):2300426.
doi:10.1002/ardp.202300426 .

Ćurčić, Vladimir, Olszewski, Mateusz, Maciejewska, Natalia, Višnjevac, Aleksandar, Srdić-Rajić, Tatjana, Dobričić, Vladimir, García-Sosa, Alfonso T., Kokanov, Sanja B., Araškov, Jovana B., Silvestri, Romano, Schüle, Roland, Jung, Manfred, Nikolić, Milan, Filipović, Nenad R., "Quinoline-based thiazolyl-hydrazones target cancer cells through autophagy inhibition" in Archiv der Pharmazie, 357, no. 2 (2024):2300426,
https://doi.org/10.1002/ardp.202300426 . .

TY  - CONF
AU  - Ušjak, Dušan
AU  - Novović, Katarina
AU  - Filipić, Brankica
AU  - Kojić, Milan
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena M.
AU  - Arsenović-Ranin, Nevena
AU  - Milenković, Marina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5133
AB  - Colistin is used as a “last resort” drug in the treatment
of carbapenem-resistant Acinetobacter baumannii
infections. Though not the most convenient option due to
the serious side effects, this antibiotic can be very efficient
if administered properly (Garnacho-Montero and Timsit,
2019). However, for several years now, we are witnessing
a steady emergence of colistin-resistant (ColR) strains, with
the constant threat of a sudden burst worldwide (Nowak et
al., 2017). Having in mind that these strains are usually
non-susceptible to any of the existing treatments, i.e.
pandrug-resistant (PDR), the development of new
therapeutic strategies is desperately needed.
In the present study, we showed that colistin
susceptibility of ColR A. baumannii strains can be fully
restored in the presence of very low amounts of selenium
nanoparticles (SeNPs). To demonstrate potent synergistic
interactions between colistin and SeNPs, we performed
checkerboard and time-kill analyses.
PB  - Macedonian Pharmaceutical Association
C3  - Macedonian Pharmaceutical Bulletin
T1  - Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin
VL  - 68
IS  - Suppl. 1
SP  - 295
EP  - 296
DO  - 10.33320/maced.pharm.bull.2022.68.03.142
ER  - 

@conference{
author = "Ušjak, Dušan and Novović, Katarina and Filipić, Brankica and Kojić, Milan and Filipović, Nenad and Stevanović, Magdalena M. and Arsenović-Ranin, Nevena and Milenković, Marina",
year = "2022",
abstract = "Colistin is used as a “last resort” drug in the treatment
of carbapenem-resistant Acinetobacter baumannii
infections. Though not the most convenient option due to
the serious side effects, this antibiotic can be very efficient
if administered properly (Garnacho-Montero and Timsit,
2019). However, for several years now, we are witnessing
a steady emergence of colistin-resistant (ColR) strains, with
the constant threat of a sudden burst worldwide (Nowak et
al., 2017). Having in mind that these strains are usually
non-susceptible to any of the existing treatments, i.e.
pandrug-resistant (PDR), the development of new
therapeutic strategies is desperately needed.
In the present study, we showed that colistin
susceptibility of ColR A. baumannii strains can be fully
restored in the presence of very low amounts of selenium
nanoparticles (SeNPs). To demonstrate potent synergistic
interactions between colistin and SeNPs, we performed
checkerboard and time-kill analyses.",
publisher = "Macedonian Pharmaceutical Association",
journal = "Macedonian Pharmaceutical Bulletin",
title = "Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin",
volume = "68",
number = "Suppl. 1",
pages = "295-296",
doi = "10.33320/maced.pharm.bull.2022.68.03.142"
}

Ušjak, D., Novović, K., Filipić, B., Kojić, M., Filipović, N., Stevanović, M. M., Arsenović-Ranin, N.,& Milenković, M.. (2022). Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin. in Macedonian Pharmaceutical Bulletin
Macedonian Pharmaceutical Association., 68(Suppl. 1), 295-296.
https://doi.org/10.33320/maced.pharm.bull.2022.68.03.142

Ušjak D, Novović K, Filipić B, Kojić M, Filipović N, Stevanović MM, Arsenović-Ranin N, Milenković M. Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin. in Macedonian Pharmaceutical Bulletin. 2022;68(Suppl. 1):295-296.
doi:10.33320/maced.pharm.bull.2022.68.03.142 .

Ušjak, Dušan, Novović, Katarina, Filipić, Brankica, Kojić, Milan, Filipović, Nenad, Stevanović, Magdalena M., Arsenović-Ranin, Nevena, Milenković, Marina, "Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin" in Macedonian Pharmaceutical Bulletin, 68, no. Suppl. 1 (2022):295-296,
https://doi.org/10.33320/maced.pharm.bull.2022.68.03.142 . .

TY  - JOUR
AU  - Stevanović, Magdalena M.
AU  - Filipović, Nenad
AU  - Kuzmanović, Maja
AU  - Tomić, Nina
AU  - Ušjak, Dušan
AU  - Milenković, Marina
AU  - Zheng, Kai
AU  - Stampfl, Juergen
AU  - Boccaccini, Aldo R.
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4357
AB  - Multidrug-resistant bacterial strains represent an emerging global health threat and a great obstacle for bone tissue engineering. One of the major components of the extracellular matrix of the bone is a collagen protein, while selenium is an element that has antimicrobial potential, and is also important for bone metabolism and bone health. Here we represent the incorporation of selenium nanoparticles (SeNPs) synthesized by the green chemical reduction method into collagen gels to produce a composite material, collagen/SeNPs, with antimicrobial properties. The samples were comprehensively characterized by zeta potential measurements, dynamic light scattering inductively coupled plasma-mass spectrometry (ICP-MS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), optical microscopy, field-emission scanning electron microscopy (FE-SEM), and differential scanning calorimetry The cytotoxicity of the SeNPS, as well as collagen/SeNPs, was tested on the MRC-5 cells. It was revealed that collagen/SeNPS expressed a lower cytotoxic effect. Collagen/SeNPs showed significant antibacterial activity against all tested Gram-positive strains, the major causative agents of orthopedic infections as well as Candida albicans. Furthermore, three-dimensional β-tricalcium phosphate (3D-TCP) scaffolds were fabricated by a well-established 3D printing (lithography) method, and afterward preliminary coated by newly-synthesized SeNPs or collagen/SeNPs. In addition, uncoated 3D-TCP scaffolds as well as coated by collagen/SeNPs were subjected to biofilm formation. The production of Staphylococcus aureus biofilm on coated scaffolds by collagen/SeNPs was significantly reduced compared to the uncoated ones.
PB  - SAGE Publications Ltd
T2  - Journal of Biomaterials Applications
T1  - Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles
VL  - 36
IS  - 10
SP  - 1800
EP  - 1811
DO  - 10.1177/08853282211073731
ER  - 

@article{
author = "Stevanović, Magdalena M. and Filipović, Nenad and Kuzmanović, Maja and Tomić, Nina and Ušjak, Dušan and Milenković, Marina and Zheng, Kai and Stampfl, Juergen and Boccaccini, Aldo R.",
year = "2022",
abstract = "Multidrug-resistant bacterial strains represent an emerging global health threat and a great obstacle for bone tissue engineering. One of the major components of the extracellular matrix of the bone is a collagen protein, while selenium is an element that has antimicrobial potential, and is also important for bone metabolism and bone health. Here we represent the incorporation of selenium nanoparticles (SeNPs) synthesized by the green chemical reduction method into collagen gels to produce a composite material, collagen/SeNPs, with antimicrobial properties. The samples were comprehensively characterized by zeta potential measurements, dynamic light scattering inductively coupled plasma-mass spectrometry (ICP-MS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), optical microscopy, field-emission scanning electron microscopy (FE-SEM), and differential scanning calorimetry The cytotoxicity of the SeNPS, as well as collagen/SeNPs, was tested on the MRC-5 cells. It was revealed that collagen/SeNPS expressed a lower cytotoxic effect. Collagen/SeNPs showed significant antibacterial activity against all tested Gram-positive strains, the major causative agents of orthopedic infections as well as Candida albicans. Furthermore, three-dimensional β-tricalcium phosphate (3D-TCP) scaffolds were fabricated by a well-established 3D printing (lithography) method, and afterward preliminary coated by newly-synthesized SeNPs or collagen/SeNPs. In addition, uncoated 3D-TCP scaffolds as well as coated by collagen/SeNPs were subjected to biofilm formation. The production of Staphylococcus aureus biofilm on coated scaffolds by collagen/SeNPs was significantly reduced compared to the uncoated ones.",
publisher = "SAGE Publications Ltd",
journal = "Journal of Biomaterials Applications",
title = "Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles",
volume = "36",
number = "10",
pages = "1800-1811",
doi = "10.1177/08853282211073731"
}

Stevanović, M. M., Filipović, N., Kuzmanović, M., Tomić, N., Ušjak, D., Milenković, M., Zheng, K., Stampfl, J.,& Boccaccini, A. R.. (2022). Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles. in Journal of Biomaterials Applications
SAGE Publications Ltd., 36(10), 1800-1811.
https://doi.org/10.1177/08853282211073731

Stevanović MM, Filipović N, Kuzmanović M, Tomić N, Ušjak D, Milenković M, Zheng K, Stampfl J, Boccaccini AR. Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles. in Journal of Biomaterials Applications. 2022;36(10):1800-1811.
doi:10.1177/08853282211073731 .

Stevanović, Magdalena M., Filipović, Nenad, Kuzmanović, Maja, Tomić, Nina, Ušjak, Dušan, Milenković, Marina, Zheng, Kai, Stampfl, Juergen, Boccaccini, Aldo R., "Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles" in Journal of Biomaterials Applications, 36, no. 10 (2022):1800-1811,
https://doi.org/10.1177/08853282211073731 . .

TY  - JOUR
AU  - Ušjak, Dušan
AU  - Novović, Katarina
AU  - Filipić, Brankica
AU  - Kojić, Milan
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
AU  - Milenković, Marina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4177
AB  - Aims: To investigate the synergistic activity of colistin and selenium nanoparticles (SeNPs) against pandrug-resistant (PDR) Ac. baumannii. Methods and Results: Chequerboard and time-kill assays were employed to ex- plore the potential synergistic interactions between colistin and SeNPs against Ac. baumannii isolates (8), previously determined as colistin-resistant (MIC range 16– 256 μg ml−1 ). Also, whole-genome sequencing (WGS) and gene expression analyses were used to elucidate the mechanisms of colistin resistance. Exceptionally strong synergistic activity (FICI range 0.004–0.035) of colistin and SeNPs against colistin- resistant isolates was revealed. Colistin (0.5 or 1 μg ml −1 ) used in combination with SeNPs (0.5 μg ml−1 ) was able to reduce initial inoculum during the first 4 h of incuba- tion, in contrast to colistin (0.5, 1 or 2 μg ml−1 ) alone. Conclusions: These findings propose colistin/SeNPs combination as a new option to fight PDR Ac. baumannii, the therapeutic possibilities of which should be proved in future in vivo studies. Significance and Impact of Study: Here we present the first evidence of synergy between colistin and selenium compounds against bacteria in general. Also, WGS and gene expression analyses provide some new insights into Ac. baumannii colistin resistance mechanisms.
PB  - John Wiley and Sons Inc
T2  - Journal of Applied Microbiology
T1  - In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles
VL  - 133
IS  - 3
SP  - 1197
SP  - 1197
EP  - 1206
DO  - 10.1111/jam.15638
ER  - 

@article{
author = "Ušjak, Dušan and Novović, Katarina and Filipić, Brankica and Kojić, Milan and Filipović, Nenad and Stevanović, Magdalena and Milenković, Marina",
year = "2022",
abstract = "Aims: To investigate the synergistic activity of colistin and selenium nanoparticles (SeNPs) against pandrug-resistant (PDR) Ac. baumannii. Methods and Results: Chequerboard and time-kill assays were employed to ex- plore the potential synergistic interactions between colistin and SeNPs against Ac. baumannii isolates (8), previously determined as colistin-resistant (MIC range 16– 256 μg ml−1 ). Also, whole-genome sequencing (WGS) and gene expression analyses were used to elucidate the mechanisms of colistin resistance. Exceptionally strong synergistic activity (FICI range 0.004–0.035) of colistin and SeNPs against colistin- resistant isolates was revealed. Colistin (0.5 or 1 μg ml −1 ) used in combination with SeNPs (0.5 μg ml−1 ) was able to reduce initial inoculum during the first 4 h of incuba- tion, in contrast to colistin (0.5, 1 or 2 μg ml−1 ) alone. Conclusions: These findings propose colistin/SeNPs combination as a new option to fight PDR Ac. baumannii, the therapeutic possibilities of which should be proved in future in vivo studies. Significance and Impact of Study: Here we present the first evidence of synergy between colistin and selenium compounds against bacteria in general. Also, WGS and gene expression analyses provide some new insights into Ac. baumannii colistin resistance mechanisms.",
publisher = "John Wiley and Sons Inc",
journal = "Journal of Applied Microbiology",
title = "In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles",
volume = "133",
number = "3",
pages = "1197-1197-1206",
doi = "10.1111/jam.15638"
}

Ušjak, D., Novović, K., Filipić, B., Kojić, M., Filipović, N., Stevanović, M.,& Milenković, M.. (2022). In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles. in Journal of Applied Microbiology
John Wiley and Sons Inc., 133(3), 1197-1206.
https://doi.org/10.1111/jam.15638

Ušjak D, Novović K, Filipić B, Kojić M, Filipović N, Stevanović M, Milenković M. In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles. in Journal of Applied Microbiology. 2022;133(3):1197-1206.
doi:10.1111/jam.15638 .

Ušjak, Dušan, Novović, Katarina, Filipić, Brankica, Kojić, Milan, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina, "In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles" in Journal of Applied Microbiology, 133, no. 3 (2022):1197-1206,
https://doi.org/10.1111/jam.15638 . .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Ušjak, Dušan
AU  - Milenković, Marina
AU  - Zheng, Kai
AU  - Liverani, Liliana
AU  - Boccaccini, Aldo R.
AU  - Stevanović, Magdalena
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3787
AB  - Although selenium nanoparticles (SeNPs) have gained attention in the scientific community mostly through investigation of their anticancer activity, a great potential of this nanomaterial was recognized recently regarding its antimicrobial activity. The particle form, size, and surface chemistry have been recognized as crucial parameters determining the interaction of nanomaterials with biological entities. Furthermore, considering a narrow boundary between beneficial and toxic effects for selenium per se, it is clear that investigations of biomedical applications of SeNPs are very demanding and must be done with great precautions. The goal of this work is to evaluate the effects of SeNPs surface chemistry and structure on antimicrobial activity against several common bacterial strains, including Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 6633), and Kocuria rhizophila (ATCC 9341), as well as Escherichia coli (ATCC 8739), Salmonella Abony (NCTC 6017), Klebsiella pneumoniae (NCIMB 9111) and Pseudomonas aeruginosa (ATCC 9027), and the standard yeast strain Candida albicans (ATCC 10231). Three types of SeNPs were synthesized by chemical reduction approach using different stabilizers and reducing agents: (i) bovine serum albumin (BSA) + ascorbic acid, (ii) chitosan + ascorbic acid, and (iii) with glucose. A thorough physicochemical characterization of the obtained SeNPs was performed to determine the effects of varying synthesis parameters on their morphology, size, structure, and surface chemistry. All SeNPs were amorphous, with spherical morphology and size in the range 70–300 nm. However, the SeNPs obtained under different synthesis conditions, i.e. by using different stabilizers as well as reducing agents, exhibited different antimicrobial activity as well as cytotoxicity which are crucial for their applications. In this paper, the antimicrobial screening of the selected systems is presented, which was determined by the broth microdilution method, and inhibitory influence on the production of monomicrobial and dual-species biofilm was evaluated. The potential mechanism of action of different systems is proposed. Additionally, the cytotoxicity of SeNPs was examined on the MRC-5 cell line, in the same concentration interval as for antimicrobial testing. It was shown that formulation SeNPs-BSA expressed a significantly lower cytotoxic effect than the other two formulations.
PB  - Frontiers Media S.A.
T2  - Frontiers in Bioengineering and Biotechnology
T1  - Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure
VL  - 8
DO  - 10.3389/fbioe.2020.624621
ER  - 

@article{
author = "Filipović, Nenad and Ušjak, Dušan and Milenković, Marina and Zheng, Kai and Liverani, Liliana and Boccaccini, Aldo R. and Stevanović, Magdalena",
year = "2021",
abstract = "Although selenium nanoparticles (SeNPs) have gained attention in the scientific community mostly through investigation of their anticancer activity, a great potential of this nanomaterial was recognized recently regarding its antimicrobial activity. The particle form, size, and surface chemistry have been recognized as crucial parameters determining the interaction of nanomaterials with biological entities. Furthermore, considering a narrow boundary between beneficial and toxic effects for selenium per se, it is clear that investigations of biomedical applications of SeNPs are very demanding and must be done with great precautions. The goal of this work is to evaluate the effects of SeNPs surface chemistry and structure on antimicrobial activity against several common bacterial strains, including Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 6633), and Kocuria rhizophila (ATCC 9341), as well as Escherichia coli (ATCC 8739), Salmonella Abony (NCTC 6017), Klebsiella pneumoniae (NCIMB 9111) and Pseudomonas aeruginosa (ATCC 9027), and the standard yeast strain Candida albicans (ATCC 10231). Three types of SeNPs were synthesized by chemical reduction approach using different stabilizers and reducing agents: (i) bovine serum albumin (BSA) + ascorbic acid, (ii) chitosan + ascorbic acid, and (iii) with glucose. A thorough physicochemical characterization of the obtained SeNPs was performed to determine the effects of varying synthesis parameters on their morphology, size, structure, and surface chemistry. All SeNPs were amorphous, with spherical morphology and size in the range 70–300 nm. However, the SeNPs obtained under different synthesis conditions, i.e. by using different stabilizers as well as reducing agents, exhibited different antimicrobial activity as well as cytotoxicity which are crucial for their applications. In this paper, the antimicrobial screening of the selected systems is presented, which was determined by the broth microdilution method, and inhibitory influence on the production of monomicrobial and dual-species biofilm was evaluated. The potential mechanism of action of different systems is proposed. Additionally, the cytotoxicity of SeNPs was examined on the MRC-5 cell line, in the same concentration interval as for antimicrobial testing. It was shown that formulation SeNPs-BSA expressed a significantly lower cytotoxic effect than the other two formulations.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Bioengineering and Biotechnology",
title = "Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure",
volume = "8",
doi = "10.3389/fbioe.2020.624621"
}

Filipović, N., Ušjak, D., Milenković, M., Zheng, K., Liverani, L., Boccaccini, A. R.,& Stevanović, M.. (2021). Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure. in Frontiers in Bioengineering and Biotechnology
Frontiers Media S.A.., 8.
https://doi.org/10.3389/fbioe.2020.624621

Filipović N, Ušjak D, Milenković M, Zheng K, Liverani L, Boccaccini AR, Stevanović M. Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure. in Frontiers in Bioengineering and Biotechnology. 2021;8.
doi:10.3389/fbioe.2020.624621 .

Filipović, Nenad, Ušjak, Dušan, Milenković, Marina, Zheng, Kai, Liverani, Liliana, Boccaccini, Aldo R., Stevanović, Magdalena, "Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure" in Frontiers in Bioengineering and Biotechnology, 8 (2021),
https://doi.org/10.3389/fbioe.2020.624621 . .

TY  - JOUR
AU  - Ušjak, Dušan
AU  - Dinić, Miroslav
AU  - Novović, Katarina
AU  - Ivković, Branka
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
AU  - Milenković, Marina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3752
AB  - An increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real-time PCR was used to evaluate mRNA expression of biofilm-associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin- and collagen-mediated adhesion, surface motility, and quorum-sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2′-hydroxy-2-methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.
PB  - Wiley-VCH Verlag
T2  - Chemistry and Biodiversity
T1  - Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,
Adhesion and Surface Motility of Acinetobacter baumannii by
Inhibiting ompA Gene Expression
VL  - 18
IS  - 1
DO  - 10.1002/cbdv.202000786
ER  - 

@article{
author = "Ušjak, Dušan and Dinić, Miroslav and Novović, Katarina and Ivković, Branka and Filipović, Nenad and Stevanović, Magdalena and Milenković, Marina",
year = "2021",
abstract = "An increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real-time PCR was used to evaluate mRNA expression of biofilm-associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin- and collagen-mediated adhesion, surface motility, and quorum-sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2′-hydroxy-2-methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.",
publisher = "Wiley-VCH Verlag",
journal = "Chemistry and Biodiversity",
title = "Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,
Adhesion and Surface Motility of Acinetobacter baumannii by
Inhibiting ompA Gene Expression",
volume = "18",
number = "1",
doi = "10.1002/cbdv.202000786"
}

Ušjak, D., Dinić, M., Novović, K., Ivković, B., Filipović, N., Stevanović, M.,& Milenković, M.. (2021). Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,
Adhesion and Surface Motility of Acinetobacter baumannii by
Inhibiting ompA Gene Expression. in Chemistry and Biodiversity
Wiley-VCH Verlag., 18(1).
https://doi.org/10.1002/cbdv.202000786

Ušjak D, Dinić M, Novović K, Ivković B, Filipović N, Stevanović M, Milenković M. Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,
Adhesion and Surface Motility of Acinetobacter baumannii by
Inhibiting ompA Gene Expression. in Chemistry and Biodiversity. 2021;18(1).
doi:10.1002/cbdv.202000786 .

Ušjak, Dušan, Dinić, Miroslav, Novović, Katarina, Ivković, Branka, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina, "Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,
Adhesion and Surface Motility of Acinetobacter baumannii by
Inhibiting ompA Gene Expression" in Chemistry and Biodiversity, 18, no. 1 (2021),
https://doi.org/10.1002/cbdv.202000786 . .

TY  - CONF
AU  - Ušjak, Dušan
AU  - Dinić, Miroslav
AU  - Novović, Katarina
AU  - Ivković, Branka
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
AU  - Milenković, Marina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3758
AB  - Uvod: Acinetobacter baumannii je globalno rasprostranjen nozokomijalni patogen koji se odlikuje izuzetnom sposobnošću ekstremno brzog sticanja rezistencije na antibiotike, kao i adaptacije na preživljavanje u suvim uslovima bolničke sredine [1]. Zbog velike zastupljenosti rezistentnih sojeva protiv kojih ne postoji delotvorna terapija, Svetska zdravstvena organizacija (WHO, 2017) i Centri za kontrolu i prevenciju bolesti (CDC, 2019), označili su A. baumannii kao patogen od kritične važnosti za otkriće novih antimikrobnih agenasa ili novih terapijskih strategija [2]. Targetiranje virulencije je oblik alternativnog terapijskog pristupa koji pruža mogućnost prevencije teže kliničke slike kod inficiranih pacijenata posredstvom inhibicije ekspresije ključnih faktora virulencije, uz istovremenu redukovanu selekciju rezistentnih mutanata [3].
Rezultati i Diskusija: Od četiri različito supstituisana hidroksihalkona, sintetisanih u postupku bazno-katalizovane Claisen-Schmidt kondenzacije, selektiran je metkosi-supstituisani derivat kao najpotentniji inhibitor produkcije biofilma kod A. baumannii. Primenom Real-Time kvantitativne PCR metode sa reverznom transkriptazom ispitan je uticaj subinhibitornih koncentracija selektiranog jedinjenja (70, 35 i 10 μg/mL) na ekspresiju gena faktora virulencije povezanih sa produkcijom biofilma kod A. baumannii: ompA, bap i abaI. Pokazana je značajna dozno-zavisna nishodna ekspresija ompA gena, koji kodira OmpA protein spoljašnje membrane ćelijskog zida, koji učestvuje u brojnim virulentnim osobinama A. baumannii, kao što su adhezija, citotoksičnost, motilitet i rezistencija na imunski odgovor i antibiotike [4]. Takođe, zabeležena je značajna inhibicija ekspresije bap gena, koja je neophodna za adheziju na humane epitelne ćelije, i abaI gena, integralnog dela bakterijskog kvorum-sensing sistema, koji kodira sintazu autoinduktorskih molekula. Sposobnost antivirulentnog delovanja metoksi-supstituisanog derivata hidroksihalkona potvrđena je demonstracijom inhibicije fenotipske ekspresije faktora virulencije povezanih sa ekspresijom ompA, bap i abaI gena, kao što su adhezija za komponente ekstracelularnog matriksa (fibronektin i kolagen), površinski motilitet i produkcija autoinduktorskih molekula.
Zaključak: Metoksi-supstituisani hidroksihalkon ispoljava antivirulentno dejstvo protiv A. baumannii, pre svega posredstvom nishodne regulacije ompA gena, što se reflektuje u inhibiciji produkcije biofilma, sposobnosti adhezije i površinskog motiliteta ovog patogena.
AB  - Over the last two decades, Acinetobacter baumannii has emerged as one of the most troublesome pathogens, rapidly acquiring resistance to virtually all available antibiotics. This has urged researchers to seek alternative ways to fight this pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm activity of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. We used quantitative Real-Time PCR to evaluate mRNA expression of virulence-associated genes (ompA, bap, abaI) in extensively drug-resistant (XDR) A. baumannii wound isolate and A. baumannii ATCC 19606 strain, treated with selected compound. Also, we tested biofilm production, fibronectin- and collagen-mediated adhesion, surface motility and quorum-sensing activity of treated strains. The results revealed downregulation of the expression of all tested virulence genes together with the reduction of biofilm production, adhesion and motility. The most notable finding is significant reduction of ompA gene expression, whose encoded protein product is associated with numerous virulence traits of A. baumannii. Therefore, we conclude that selected methoxy-substituted hydroxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of the bacterial adhesins, most importantly OmpA, which is reflected in reduced biofilm formation, adhesion and surface motility.
C3  - FEMS Online Conference on Microbiology
T1  - Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression
UR  - https://hdl.handle.net/21.15107/rcub_farfar_3758
ER  - 

@conference{
author = "Ušjak, Dušan and Dinić, Miroslav and Novović, Katarina and Ivković, Branka and Filipović, Nenad and Stevanović, Magdalena and Milenković, Marina",
year = "2020",
abstract = "Uvod: Acinetobacter baumannii je globalno rasprostranjen nozokomijalni patogen koji se odlikuje izuzetnom sposobnošću ekstremno brzog sticanja rezistencije na antibiotike, kao i adaptacije na preživljavanje u suvim uslovima bolničke sredine [1]. Zbog velike zastupljenosti rezistentnih sojeva protiv kojih ne postoji delotvorna terapija, Svetska zdravstvena organizacija (WHO, 2017) i Centri za kontrolu i prevenciju bolesti (CDC, 2019), označili su A. baumannii kao patogen od kritične važnosti za otkriće novih antimikrobnih agenasa ili novih terapijskih strategija [2]. Targetiranje virulencije je oblik alternativnog terapijskog pristupa koji pruža mogućnost prevencije teže kliničke slike kod inficiranih pacijenata posredstvom inhibicije ekspresije ključnih faktora virulencije, uz istovremenu redukovanu selekciju rezistentnih mutanata [3].
Rezultati i Diskusija: Od četiri različito supstituisana hidroksihalkona, sintetisanih u postupku bazno-katalizovane Claisen-Schmidt kondenzacije, selektiran je metkosi-supstituisani derivat kao najpotentniji inhibitor produkcije biofilma kod A. baumannii. Primenom Real-Time kvantitativne PCR metode sa reverznom transkriptazom ispitan je uticaj subinhibitornih koncentracija selektiranog jedinjenja (70, 35 i 10 μg/mL) na ekspresiju gena faktora virulencije povezanih sa produkcijom biofilma kod A. baumannii: ompA, bap i abaI. Pokazana je značajna dozno-zavisna nishodna ekspresija ompA gena, koji kodira OmpA protein spoljašnje membrane ćelijskog zida, koji učestvuje u brojnim virulentnim osobinama A. baumannii, kao što su adhezija, citotoksičnost, motilitet i rezistencija na imunski odgovor i antibiotike [4]. Takođe, zabeležena je značajna inhibicija ekspresije bap gena, koja je neophodna za adheziju na humane epitelne ćelije, i abaI gena, integralnog dela bakterijskog kvorum-sensing sistema, koji kodira sintazu autoinduktorskih molekula. Sposobnost antivirulentnog delovanja metoksi-supstituisanog derivata hidroksihalkona potvrđena je demonstracijom inhibicije fenotipske ekspresije faktora virulencije povezanih sa ekspresijom ompA, bap i abaI gena, kao što su adhezija za komponente ekstracelularnog matriksa (fibronektin i kolagen), površinski motilitet i produkcija autoinduktorskih molekula.
Zaključak: Metoksi-supstituisani hidroksihalkon ispoljava antivirulentno dejstvo protiv A. baumannii, pre svega posredstvom nishodne regulacije ompA gena, što se reflektuje u inhibiciji produkcije biofilma, sposobnosti adhezije i površinskog motiliteta ovog patogena., Over the last two decades, Acinetobacter baumannii has emerged as one of the most troublesome pathogens, rapidly acquiring resistance to virtually all available antibiotics. This has urged researchers to seek alternative ways to fight this pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm activity of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. We used quantitative Real-Time PCR to evaluate mRNA expression of virulence-associated genes (ompA, bap, abaI) in extensively drug-resistant (XDR) A. baumannii wound isolate and A. baumannii ATCC 19606 strain, treated with selected compound. Also, we tested biofilm production, fibronectin- and collagen-mediated adhesion, surface motility and quorum-sensing activity of treated strains. The results revealed downregulation of the expression of all tested virulence genes together with the reduction of biofilm production, adhesion and motility. The most notable finding is significant reduction of ompA gene expression, whose encoded protein product is associated with numerous virulence traits of A. baumannii. Therefore, we conclude that selected methoxy-substituted hydroxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of the bacterial adhesins, most importantly OmpA, which is reflected in reduced biofilm formation, adhesion and surface motility.",
journal = "FEMS Online Conference on Microbiology",
title = "Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression",
url = "https://hdl.handle.net/21.15107/rcub_farfar_3758"
}

Ušjak, D., Dinić, M., Novović, K., Ivković, B., Filipović, N., Stevanović, M.,& Milenković, M.. (2020). Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression. in FEMS Online Conference on Microbiology.
https://hdl.handle.net/21.15107/rcub_farfar_3758

Ušjak D, Dinić M, Novović K, Ivković B, Filipović N, Stevanović M, Milenković M. Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression. in FEMS Online Conference on Microbiology. 2020;.
https://hdl.handle.net/21.15107/rcub_farfar_3758 .

Ušjak, Dušan, Dinić, Miroslav, Novović, Katarina, Ivković, Branka, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina, "Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression" in FEMS Online Conference on Microbiology (2020),
https://hdl.handle.net/21.15107/rcub_farfar_3758 .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinovic, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipić, Metka
AU  - Zegura, Bojana
AU  - Tomic, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3328
AB  - Poly (e-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1-4 mu m with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants.
PB  - Elsevier Science BV, Amsterdam
T2  - Materials Science & Engineering C: Materials for Biological Applications
T1  - Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles
VL  - 96
SP  - 776
EP  - 789
DO  - 10.1016/j.msec.2018.11.073
ER  - 

@article{
author = "Filipović, Nenad and Veselinovic, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipić, Metka and Zegura, Bojana and Tomic, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (e-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1-4 mu m with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Materials Science & Engineering C: Materials for Biological Applications",
title = "Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles",
volume = "96",
pages = "776-789",
doi = "10.1016/j.msec.2018.11.073"
}

Filipović, N., Veselinovic, L., Ražić, S., Jeremić, S., Filipić, M., Zegura, B., Tomic, S., Čolić, M.,& Stevanović, M.. (2019). Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science & Engineering C: Materials for Biological Applications
Elsevier Science BV, Amsterdam., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073

Filipović N, Veselinovic L, Ražić S, Jeremić S, Filipić M, Zegura B, Tomic S, Čolić M, Stevanović M. Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science & Engineering C: Materials for Biological Applications. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073 .

Filipović, Nenad, Veselinovic, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipić, Metka, Zegura, Bojana, Tomic, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science & Engineering C: Materials for Biological Applications, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 . .

TY  - JOUR
AU  - Dinić, Miroslav
AU  - Pecikoza, Uroš
AU  - Đokić, Jelena
AU  - Stepanović-Petrović, Radica
AU  - Milenković, Marina
AU  - Stevanović, Magdalena
AU  - Filipović, Nenad
AU  - Begović, Jelena
AU  - Golić, Nataša
AU  - Lukić, Jovanka
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3152
AB  - The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS) produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11) to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR) and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia) and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1 beta and iNOS mRNAs in rat's paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1 beta, TNF-alpha and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Pharmacology
T1  - Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats
VL  - 9
DO  - 10.3389/fphar.2018.00001
ER  - 

@article{
author = "Dinić, Miroslav and Pecikoza, Uroš and Đokić, Jelena and Stepanović-Petrović, Radica and Milenković, Marina and Stevanović, Magdalena and Filipović, Nenad and Begović, Jelena and Golić, Nataša and Lukić, Jovanka",
year = "2018",
abstract = "The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS) produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11) to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR) and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia) and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1 beta and iNOS mRNAs in rat's paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1 beta, TNF-alpha and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Pharmacology",
title = "Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats",
volume = "9",
doi = "10.3389/fphar.2018.00001"
}

Dinić, M., Pecikoza, U., Đokić, J., Stepanović-Petrović, R., Milenković, M., Stevanović, M., Filipović, N., Begović, J., Golić, N.,& Lukić, J.. (2018). Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats. in Frontiers in Pharmacology
Frontiers Media Sa, Lausanne., 9.
https://doi.org/10.3389/fphar.2018.00001

Dinić M, Pecikoza U, Đokić J, Stepanović-Petrović R, Milenković M, Stevanović M, Filipović N, Begović J, Golić N, Lukić J. Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats. in Frontiers in Pharmacology. 2018;9.
doi:10.3389/fphar.2018.00001 .

Dinić, Miroslav, Pecikoza, Uroš, Đokić, Jelena, Stepanović-Petrović, Radica, Milenković, Marina, Stevanović, Magdalena, Filipović, Nenad, Begović, Jelena, Golić, Nataša, Lukić, Jovanka, "Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats" in Frontiers in Pharmacology, 9 (2018),
https://doi.org/10.3389/fphar.2018.00001 . .

TY  - JOUR
AU  - Stevanović, Magdalena
AU  - Filipović, Nenad
AU  - Đurđević, Jelena
AU  - Lukić, Miodrag
AU  - Milenković, Marina
AU  - Boccaccini, Aldo
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2427
AB  - In the bone tissue engineering field, there is a growing interest in the application of bioactive glass scaffolds (45S5Bioglass (R)) due to their bone bonding ability, osteoconductivity and osteoinductivity. However, such scaffolds still lack some of the required functionalities to enable the successful formation of new bone, e.g. effective antibacterial properties. A large number of studies suggest that selenium (Se) has significant role in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Selenium nanoparticles (SeNp) have also been reported to possess antibacterial as well as antiviral activities. In this investigation, uniform, stable, amorphous SeNp have been synthesized and additionally immobilized within spherical PLGA particles (PLGA/SeNp). These particles were used to coat bioactive glass-based scaffolds synthesized by the foam replica method. Samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy. (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). SeNp, 45S5Bioglass (R)/SeNp and 45S5Bioglass (R)/PLGA/SeNp showed a considerable antibacterial activity against Gram positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, one of the main causative agents of orthopedic infections. The functionalized Se-coated bioactive glass scaffolds represent a new family of bioactive, antibacterial scaffolds for bone tissue engineering applications.
PB  - Elsevier Science BV, Amsterdam
T2  - Colloids and Surfaces B: Biointerfaces
T1  - 45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity
VL  - 132
SP  - 208
EP  - 215
DO  - 10.1016/j.colsurfb.2015.05.024
ER  - 

@article{
author = "Stevanović, Magdalena and Filipović, Nenad and Đurđević, Jelena and Lukić, Miodrag and Milenković, Marina and Boccaccini, Aldo",
year = "2015",
abstract = "In the bone tissue engineering field, there is a growing interest in the application of bioactive glass scaffolds (45S5Bioglass (R)) due to their bone bonding ability, osteoconductivity and osteoinductivity. However, such scaffolds still lack some of the required functionalities to enable the successful formation of new bone, e.g. effective antibacterial properties. A large number of studies suggest that selenium (Se) has significant role in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Selenium nanoparticles (SeNp) have also been reported to possess antibacterial as well as antiviral activities. In this investigation, uniform, stable, amorphous SeNp have been synthesized and additionally immobilized within spherical PLGA particles (PLGA/SeNp). These particles were used to coat bioactive glass-based scaffolds synthesized by the foam replica method. Samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy. (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). SeNp, 45S5Bioglass (R)/SeNp and 45S5Bioglass (R)/PLGA/SeNp showed a considerable antibacterial activity against Gram positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, one of the main causative agents of orthopedic infections. The functionalized Se-coated bioactive glass scaffolds represent a new family of bioactive, antibacterial scaffolds for bone tissue engineering applications.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Colloids and Surfaces B: Biointerfaces",
title = "45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity",
volume = "132",
pages = "208-215",
doi = "10.1016/j.colsurfb.2015.05.024"
}

Stevanović, M., Filipović, N., Đurđević, J., Lukić, M., Milenković, M.,& Boccaccini, A.. (2015). 45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity. in Colloids and Surfaces B: Biointerfaces
Elsevier Science BV, Amsterdam., 132, 208-215.
https://doi.org/10.1016/j.colsurfb.2015.05.024

Stevanović M, Filipović N, Đurđević J, Lukić M, Milenković M, Boccaccini A. 45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity. in Colloids and Surfaces B: Biointerfaces. 2015;132:208-215.
doi:10.1016/j.colsurfb.2015.05.024 .

Stevanović, Magdalena, Filipović, Nenad, Đurđević, Jelena, Lukić, Miodrag, Milenković, Marina, Boccaccini, Aldo, "45S5Bioglass (R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity" in Colloids and Surfaces B: Biointerfaces, 132 (2015):208-215,
https://doi.org/10.1016/j.colsurfb.2015.05.024 . .

TY  - JOUR
AU  - Stevanović, Magdalena
AU  - Bracko, Ines
AU  - Milenković, Marina
AU  - Filipović, Nenad
AU  - Nunić, Jana
AU  - Filipić, Metka
AU  - Uskoković, Dragan P.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2184
AB  - A water-soluble antioxidant (ascorbic acid, vitamin C) was encapsulated together with poly(L-glutamic acid)-capped silver nanoparticles (AgNpPGA) within a poly(lactide-co-glycolide) (PLGA) polymeric matrix and their synergistic effects were studied. The PLGA/AgNpPGA/ascorbic acid particles synthesized by a physicochemical method with solvent/non-solvent systems are spherical, have a mean diameter of 775 nm and a narrow size distribution with a polydispersity index of 0.158. The encapsulation efficiency of AgNpPGA/ascorbic acid within PLGA was determined to be >90%. The entire amount of encapsulated ascorbic acid was released in 68 days, and the entire amount of AgNpPGAs was released in 87 days of degradation. The influence of PLGA/AgNpPGA/ascorbic acid on cell viability, generation of reactive oxygen species (ROS) in HepG2 cells, as well as antimicrobial activity against seven different pathogens was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGA/ascorbic acid particles. We measured the kinetics of ROS formation in HepG2 cells by a DCFH-DA assay, and found that PLGA/AgNpPGA/ascorbic acid caused a significant decrease in DCF fluorescence intensity, which was 2-fold lower than that in control cells after a 5 h exposure. This indicates that the PLGA/AgNpPGA/ascorbic acid microspheres either act as scavengers of intracellular ROS and/or reduce their formation. Also, the results of antimicrobial activity of PLGA/AgNpPGA/ascorbic acid obtained by the broth microdilution method showed superior and extended activity of these particles. The samples were characterized using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, zeta potential and particle size analysis. This paper presents a new approach to the treatment of infection that at the same time offers a very pronounced antioxidant effect.
PB  - Elsevier Sci Ltd, Oxford
T2  - Acta Biomaterialia
T1  - Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity
VL  - 10
IS  - 1
SP  - 151
EP  - 162
DO  - 10.1016/j.actbio.2013.08.030
ER  - 

@article{
author = "Stevanović, Magdalena and Bracko, Ines and Milenković, Marina and Filipović, Nenad and Nunić, Jana and Filipić, Metka and Uskoković, Dragan P.",
year = "2014",
abstract = "A water-soluble antioxidant (ascorbic acid, vitamin C) was encapsulated together with poly(L-glutamic acid)-capped silver nanoparticles (AgNpPGA) within a poly(lactide-co-glycolide) (PLGA) polymeric matrix and their synergistic effects were studied. The PLGA/AgNpPGA/ascorbic acid particles synthesized by a physicochemical method with solvent/non-solvent systems are spherical, have a mean diameter of 775 nm and a narrow size distribution with a polydispersity index of 0.158. The encapsulation efficiency of AgNpPGA/ascorbic acid within PLGA was determined to be >90%. The entire amount of encapsulated ascorbic acid was released in 68 days, and the entire amount of AgNpPGAs was released in 87 days of degradation. The influence of PLGA/AgNpPGA/ascorbic acid on cell viability, generation of reactive oxygen species (ROS) in HepG2 cells, as well as antimicrobial activity against seven different pathogens was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGA/ascorbic acid particles. We measured the kinetics of ROS formation in HepG2 cells by a DCFH-DA assay, and found that PLGA/AgNpPGA/ascorbic acid caused a significant decrease in DCF fluorescence intensity, which was 2-fold lower than that in control cells after a 5 h exposure. This indicates that the PLGA/AgNpPGA/ascorbic acid microspheres either act as scavengers of intracellular ROS and/or reduce their formation. Also, the results of antimicrobial activity of PLGA/AgNpPGA/ascorbic acid obtained by the broth microdilution method showed superior and extended activity of these particles. The samples were characterized using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, zeta potential and particle size analysis. This paper presents a new approach to the treatment of infection that at the same time offers a very pronounced antioxidant effect.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Acta Biomaterialia",
title = "Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity",
volume = "10",
number = "1",
pages = "151-162",
doi = "10.1016/j.actbio.2013.08.030"
}

Stevanović, M., Bracko, I., Milenković, M., Filipović, N., Nunić, J., Filipić, M.,& Uskoković, D. P.. (2014). Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity. in Acta Biomaterialia
Elsevier Sci Ltd, Oxford., 10(1), 151-162.
https://doi.org/10.1016/j.actbio.2013.08.030

Stevanović M, Bracko I, Milenković M, Filipović N, Nunić J, Filipić M, Uskoković DP. Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity. in Acta Biomaterialia. 2014;10(1):151-162.
doi:10.1016/j.actbio.2013.08.030 .

Stevanović, Magdalena, Bracko, Ines, Milenković, Marina, Filipović, Nenad, Nunić, Jana, Filipić, Metka, Uskoković, Dragan P., "Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity" in Acta Biomaterialia, 10, no. 1 (2014):151-162,
https://doi.org/10.1016/j.actbio.2013.08.030 . .