TY  - JOUR
AU  - Rasin, Puthiyavalappil
AU  - Basheer, Sabeel M.
AU  - Haribabu, Jebiti
AU  - Aneesrahman, K. N.
AU  - Manakkadan, Vipin
AU  - Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri
AU  - Bhuvanesh, Nattamai
AU  - Echeverria, Cesar
AU  - Santibanez, Juan F.
AU  - Sreekanth, Anandaram
PY  - 2024
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1463
AB  - A novel Coumarin-based 1,2-pyrazole, HCPyTSC is synthesised and characterized. The chemosensor has been shown to have efficient colourimetric and fluorescence sensing capabilities for the quick and selective detection of fluoride and copper ions. At 376 and 430 nm, the HCPyTSC exhibits selective sensing for Cu2+ and F− ions. By examining the natural bond orbital (NBO) analysis and the potential energy curve (PES) of the ground state for the function of the C–H bond, it has been determined from the theoretical study at hand that the deprotonation was taken from the ‘CH’ proton of the pyrazole ring. For F− and Cu2+, the HCPyTSC detection limits were 4.62 nM and 15.36 nM, respectively. Similarly, the binding constants (Kb) for F− and Cu2+ ions in acetonitrile medium were found to be 2.06 × 105 M−1 and 1.88 × 105 M−1. Chemosensor HCPyTSC with and without F− and Cu2+ ions have an emission and absorption response that can imitate a variety of logic gates, including the AND, XOR, and OR gates. Additionally, a paper-based sensor strip with the HCPyTSC was created for use in practical, flexible F− sensing applications. The paper-based sensor was more effective in detecting F− than other anions. The effectiveness of HCPyTSC for the selective detection of F− in living cells as well as its cell permeability were examined using live-cell imaging in T24 cells.
PB  - Elsevier
T2  - Heliyon
T1  - Host-guest interactions of coumarin-based 1,2-pyrazole using analytical and computational methods: Paper strip-based detection, live cell imaging, logic gates and keypad lock applications
IS  - 1
SP  - e24077
VL  - 10
DO  - 10.1016/j.heliyon.2024.e24077
ER  - 

@article{
author = "Rasin, Puthiyavalappil and Basheer, Sabeel M. and Haribabu, Jebiti and Aneesrahman, K. N. and Manakkadan, Vipin and Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri and Bhuvanesh, Nattamai and Echeverria, Cesar and Santibanez, Juan F. and Sreekanth, Anandaram",
year = "2024",
abstract = "A novel Coumarin-based 1,2-pyrazole, HCPyTSC is synthesised and characterized. The chemosensor has been shown to have efficient colourimetric and fluorescence sensing capabilities for the quick and selective detection of fluoride and copper ions. At 376 and 430 nm, the HCPyTSC exhibits selective sensing for Cu2+ and F− ions. By examining the natural bond orbital (NBO) analysis and the potential energy curve (PES) of the ground state for the function of the C–H bond, it has been determined from the theoretical study at hand that the deprotonation was taken from the ‘CH’ proton of the pyrazole ring. For F− and Cu2+, the HCPyTSC detection limits were 4.62 nM and 15.36 nM, respectively. Similarly, the binding constants (Kb) for F− and Cu2+ ions in acetonitrile medium were found to be 2.06 × 105 M−1 and 1.88 × 105 M−1. Chemosensor HCPyTSC with and without F− and Cu2+ ions have an emission and absorption response that can imitate a variety of logic gates, including the AND, XOR, and OR gates. Additionally, a paper-based sensor strip with the HCPyTSC was created for use in practical, flexible F− sensing applications. The paper-based sensor was more effective in detecting F− than other anions. The effectiveness of HCPyTSC for the selective detection of F− in living cells as well as its cell permeability were examined using live-cell imaging in T24 cells.",
publisher = "Elsevier",
journal = "Heliyon",
title = "Host-guest interactions of coumarin-based 1,2-pyrazole using analytical and computational methods: Paper strip-based detection, live cell imaging, logic gates and keypad lock applications",
number = "1",
pages = "e24077",
volume = "10",
doi = "10.1016/j.heliyon.2024.e24077"
}

Rasin, P., Basheer, S. M., Haribabu, J., Aneesrahman, K. N., Manakkadan, V., Vadakkedathu Palakkeezhillam, V. N., Bhuvanesh, N., Echeverria, C., Santibanez, J. F.,& Sreekanth, A.. (2024). Host-guest interactions of coumarin-based 1,2-pyrazole using analytical and computational methods: Paper strip-based detection, live cell imaging, logic gates and keypad lock applications. in Heliyon
Elsevier., 10(1), e24077.
https://doi.org/10.1016/j.heliyon.2024.e24077

Rasin P, Basheer SM, Haribabu J, Aneesrahman KN, Manakkadan V, Vadakkedathu Palakkeezhillam VN, Bhuvanesh N, Echeverria C, Santibanez JF, Sreekanth A. Host-guest interactions of coumarin-based 1,2-pyrazole using analytical and computational methods: Paper strip-based detection, live cell imaging, logic gates and keypad lock applications. in Heliyon. 2024;10(1):e24077.
doi:10.1016/j.heliyon.2024.e24077 .

Rasin, Puthiyavalappil, Basheer, Sabeel M., Haribabu, Jebiti, Aneesrahman, K. N., Manakkadan, Vipin, Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri, Bhuvanesh, Nattamai, Echeverria, Cesar, Santibanez, Juan F., Sreekanth, Anandaram, "Host-guest interactions of coumarin-based 1,2-pyrazole using analytical and computational methods: Paper strip-based detection, live cell imaging, logic gates and keypad lock applications" in Heliyon, 10, no. 1 (2024):e24077,
https://doi.org/10.1016/j.heliyon.2024.e24077 . .

TY  - JOUR
AU  - Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri
AU  - Haribabu, Jebiti
AU  - Suresh Kumar, Vaishnu
AU  - Manakkadan, Vipin
AU  - Rasin, Puthiyavalappil
AU  - Bhuvanesh, Nattamai
AU  - Echeverria, Cesar
AU  - Santibanez, Juan F.
AU  - Sreekanth, Anandaram
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1325
AB  - A couple of N-(4)-morpholine/pyrrolidine-substituted thiosemicarbazones (TSCs) of fluorene-2-carboxaldehyde (FM and FP), and their corresponding thiadiazoles (TDZs) (CFM and CFP), were synthesized and characterized (elemental analysis, ultraviolet–visible [UV–Visible], Fourier transform infrared [FT-IR], nuclear magnetic resonance [NMR; 1H & 13C], high-resolution mass spectrometry [HRMS], and single-crystal X-ray diffraction [SCXRD]) for the evaluation of their anticancer potential. The TDZs were obtained unexpectedly and are possibly formed via single-step metal (copper)-mediated oxidative cyclizations of the TSCs. The synthesized compounds are fairly stable in phosphate buffer at the biological pH of 7.4. The density functional theory [DFT] studies were performed to predict the optimized structures and physicochemical properties of these compounds. The compounds were further subjected to computational and experimental biomolecular investigations in order to evaluate their anticancer activity in detail. CFM had the most potent activity against human breast adenocarcinoma (MCF-7) and human urinary bladder (T24) cancer cells, with IC50 values of 12.00 and 24.80 μM, respectively. In contrast, CFM had negligible cytotoxicity (IC50 = 98.70 μM) against kidney epithelial cells extracted from an African green monkey (Vero) normal cells. This outcome was preferable to that of the widely used medicine Cisplatin. Molecular docking studies were performed with the breast cancer protein “cytochrome P450 1A1” (CYP1A1) and bovine serum albumin (BSA) to predict how effectively the compounds bind to the receptor. The ADMET findings suggest that these compounds have considerable drug-likeness and oral bioavailability. These insights may open the door for additional medical research into the bioactivities of TSCs and TDZs produced from bioactive carbonyl compounds.
PB  - Wiley-Blackwell
T2  - Applied Organometallic Chemistry
T1  - Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization
IS  - 8
SP  - e7174
VL  - 37
DO  - 10.1002/aoc.7174
ER  - 

@article{
author = "Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri and Haribabu, Jebiti and Suresh Kumar, Vaishnu and Manakkadan, Vipin and Rasin, Puthiyavalappil and Bhuvanesh, Nattamai and Echeverria, Cesar and Santibanez, Juan F. and Sreekanth, Anandaram",
year = "2023",
abstract = "A couple of N-(4)-morpholine/pyrrolidine-substituted thiosemicarbazones (TSCs) of fluorene-2-carboxaldehyde (FM and FP), and their corresponding thiadiazoles (TDZs) (CFM and CFP), were synthesized and characterized (elemental analysis, ultraviolet–visible [UV–Visible], Fourier transform infrared [FT-IR], nuclear magnetic resonance [NMR; 1H & 13C], high-resolution mass spectrometry [HRMS], and single-crystal X-ray diffraction [SCXRD]) for the evaluation of their anticancer potential. The TDZs were obtained unexpectedly and are possibly formed via single-step metal (copper)-mediated oxidative cyclizations of the TSCs. The synthesized compounds are fairly stable in phosphate buffer at the biological pH of 7.4. The density functional theory [DFT] studies were performed to predict the optimized structures and physicochemical properties of these compounds. The compounds were further subjected to computational and experimental biomolecular investigations in order to evaluate their anticancer activity in detail. CFM had the most potent activity against human breast adenocarcinoma (MCF-7) and human urinary bladder (T24) cancer cells, with IC50 values of 12.00 and 24.80 μM, respectively. In contrast, CFM had negligible cytotoxicity (IC50 = 98.70 μM) against kidney epithelial cells extracted from an African green monkey (Vero) normal cells. This outcome was preferable to that of the widely used medicine Cisplatin. Molecular docking studies were performed with the breast cancer protein “cytochrome P450 1A1” (CYP1A1) and bovine serum albumin (BSA) to predict how effectively the compounds bind to the receptor. The ADMET findings suggest that these compounds have considerable drug-likeness and oral bioavailability. These insights may open the door for additional medical research into the bioactivities of TSCs and TDZs produced from bioactive carbonyl compounds.",
publisher = "Wiley-Blackwell",
journal = "Applied Organometallic Chemistry",
title = "Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization",
number = "8",
pages = "e7174",
volume = "37",
doi = "10.1002/aoc.7174"
}

Vadakkedathu Palakkeezhillam, V. N., Haribabu, J., Suresh Kumar, V., Manakkadan, V., Rasin, P., Bhuvanesh, N., Echeverria, C., Santibanez, J. F.,& Sreekanth, A.. (2023). Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization. in Applied Organometallic Chemistry
Wiley-Blackwell., 37(8), e7174.
https://doi.org/10.1002/aoc.7174

Vadakkedathu Palakkeezhillam VN, Haribabu J, Suresh Kumar V, Manakkadan V, Rasin P, Bhuvanesh N, Echeverria C, Santibanez JF, Sreekanth A. Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization. in Applied Organometallic Chemistry. 2023;37(8):e7174.
doi:10.1002/aoc.7174 .

Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri, Haribabu, Jebiti, Suresh Kumar, Vaishnu, Manakkadan, Vipin, Rasin, Puthiyavalappil, Bhuvanesh, Nattamai, Echeverria, Cesar, Santibanez, Juan F., Sreekanth, Anandaram, "Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization" in Applied Organometallic Chemistry, 37, no. 8 (2023):e7174,
https://doi.org/10.1002/aoc.7174 . .

TY  - JOUR
AU  - Santibanez, Juan F.
AU  - Villar, Victor H.
AU  - Echeverria, Cesar
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1291
T2  - Pharmaceutics
T1  - Current and Future Cancer Chemoprevention Strategies
IS  - 5
SP  - 1543
VL  - 15
DO  - 10.3390/pharmaceutics15051543
ER  - 

@article{
author = "Santibanez, Juan F. and Villar, Victor H. and Echeverria, Cesar",
year = "2023",
journal = "Pharmaceutics",
title = "Current and Future Cancer Chemoprevention Strategies",
number = "5",
pages = "1543",
volume = "15",
doi = "10.3390/pharmaceutics15051543"
}

Santibanez, J. F., Villar, V. H.,& Echeverria, C.. (2023). Current and Future Cancer Chemoprevention Strategies. in Pharmaceutics, 15(5), 1543.
https://doi.org/10.3390/pharmaceutics15051543

Santibanez JF, Villar VH, Echeverria C. Current and Future Cancer Chemoprevention Strategies. in Pharmaceutics. 2023;15(5):1543.
doi:10.3390/pharmaceutics15051543 .

Santibanez, Juan F., Villar, Victor H., Echeverria, Cesar, "Current and Future Cancer Chemoprevention Strategies" in Pharmaceutics, 15, no. 5 (2023):1543,
https://doi.org/10.3390/pharmaceutics15051543 . .

TY  - JOUR
AU  - Prado, Yolanda
AU  - Echeverría, Cesar
AU  - Feijóo, Carmen G.
AU  - Riedel, Claudia A.
AU  - Cabello-Verrugio, Claudio
AU  - Santibanez, Juan F.
AU  - Simon, Felipe
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1296
AB  - Sepsis syndrome develops through enhanced secretion of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS). Sepsis syndrome is characterized by vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality, among others. Endotoxemia-derived sepsis is an important cause of sepsis syndrome. During endotoxemia, circulating endotoxin interacts with endothelial cells (ECs), inducing detrimental effects on endothelium function. The endotoxin induces the conversion of ECs into fibroblasts, which are characterized by a massive change in the endothelial gene-expression pattern. This downregulates the endothelial markers and upregulates fibrotic proteins, mesenchymal transcription factors, and extracellular matrix proteins, producing endothelial fibrosis. Sepsis progression is modulated by the consumption of specific nutrients, including ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoids. However, the underlying mechanism is poorly described. The notion that gene expression is modulated during inflammatory conditions by nutrient consumption has been reported. However, it is not known whether nutrient consumption modulates the fibrotic endothelial gene-expression pattern during sepsis as a mechanism to decrease vascular hyperpermeability, hypotension, MODS, and mortality. Therefore, the aim of this study was to investigate the impact of the consumption of dietary ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoid supplements on the modulation of fibrotic endothelial gene-expression patterns during sepsis and to determine the effects on sepsis outcomes. Our results indicate that the consumption of supplements based on ω-3 fatty acids and polyphenolic antioxidant flavonoids was effective for improving endotoxemia outcomes through prophylactic ingestion and therapeutic usage. Thus, our findings indicated that specific nutrient consumption improves sepsis outcomes and should be considered in treatment.
PB  - MDPI
T2  - Antioxidants
T1  - Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats
IS  - 3
SP  - 659
VL  - 12
DO  - 10.3390/antiox12030659
ER  - 

@article{
author = "Prado, Yolanda and Echeverría, Cesar and Feijóo, Carmen G. and Riedel, Claudia A. and Cabello-Verrugio, Claudio and Santibanez, Juan F. and Simon, Felipe",
year = "2023",
abstract = "Sepsis syndrome develops through enhanced secretion of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS). Sepsis syndrome is characterized by vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality, among others. Endotoxemia-derived sepsis is an important cause of sepsis syndrome. During endotoxemia, circulating endotoxin interacts with endothelial cells (ECs), inducing detrimental effects on endothelium function. The endotoxin induces the conversion of ECs into fibroblasts, which are characterized by a massive change in the endothelial gene-expression pattern. This downregulates the endothelial markers and upregulates fibrotic proteins, mesenchymal transcription factors, and extracellular matrix proteins, producing endothelial fibrosis. Sepsis progression is modulated by the consumption of specific nutrients, including ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoids. However, the underlying mechanism is poorly described. The notion that gene expression is modulated during inflammatory conditions by nutrient consumption has been reported. However, it is not known whether nutrient consumption modulates the fibrotic endothelial gene-expression pattern during sepsis as a mechanism to decrease vascular hyperpermeability, hypotension, MODS, and mortality. Therefore, the aim of this study was to investigate the impact of the consumption of dietary ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoid supplements on the modulation of fibrotic endothelial gene-expression patterns during sepsis and to determine the effects on sepsis outcomes. Our results indicate that the consumption of supplements based on ω-3 fatty acids and polyphenolic antioxidant flavonoids was effective for improving endotoxemia outcomes through prophylactic ingestion and therapeutic usage. Thus, our findings indicated that specific nutrient consumption improves sepsis outcomes and should be considered in treatment.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats",
number = "3",
pages = "659",
volume = "12",
doi = "10.3390/antiox12030659"
}

Prado, Y., Echeverría, C., Feijóo, C. G., Riedel, C. A., Cabello-Verrugio, C., Santibanez, J. F.,& Simon, F.. (2023). Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats. in Antioxidants
MDPI., 12(3), 659.
https://doi.org/10.3390/antiox12030659

Prado Y, Echeverría C, Feijóo CG, Riedel CA, Cabello-Verrugio C, Santibanez JF, Simon F. Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats. in Antioxidants. 2023;12(3):659.
doi:10.3390/antiox12030659 .

Prado, Yolanda, Echeverría, Cesar, Feijóo, Carmen G., Riedel, Claudia A., Cabello-Verrugio, Claudio, Santibanez, Juan F., Simon, Felipe, "Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats" in Antioxidants, 12, no. 3 (2023):659,
https://doi.org/10.3390/antiox12030659 . .

TY  - JOUR
AU  - Mojsilović, Slavko
AU  - Mojsilović, Sonja
AU  - Bjelica, Sunčica
AU  - Santibanez, Juan F.
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1180
AB  - Transforming growth factor-beta1 (TGF-beta 1) plays a crucial role in tumor progression. It can inhibit early cancer stages but promotes tumor growth and development at the late stages of tumorigenesis. TGF-beta 1 has a potent immunosuppressive function within the tumor microenvironment that largely contributes to tumor cells' immune escape and reduction in cancer immunotherapy responses. Likewise, myeloid-derived suppressor cells (MDSCs) have been postulated as leading tumor promoters and a hallmark of cancer immune evasion mechanisms. This review attempts to analyze the prominent roles of both TGF-beta 1 and MDSCs and their interplay in cancer immunity. Furthermore, therapies against either TGF-beta 1 or MDSCs, and their potential synergistic combination with immunotherapies are discussed. Simultaneous TGF-beta 1 and MDSCs inhibition suggest a potential improvement in immunotherapy or subverted tumor immune resistance.
PB  - Wiley
T2  - Developmental Dinamics
T1  - Transforming growth factor-beta1 and myeloid-derived suppressor cells: A cancerous partnership
EP  - 124
IS  - 1
SP  - 105
DO  - 10.1002/dvdy.339
ER  - 

@article{
author = "Mojsilović, Slavko and Mojsilović, Sonja and Bjelica, Sunčica and Santibanez, Juan F.",
year = "2022",
abstract = "Transforming growth factor-beta1 (TGF-beta 1) plays a crucial role in tumor progression. It can inhibit early cancer stages but promotes tumor growth and development at the late stages of tumorigenesis. TGF-beta 1 has a potent immunosuppressive function within the tumor microenvironment that largely contributes to tumor cells' immune escape and reduction in cancer immunotherapy responses. Likewise, myeloid-derived suppressor cells (MDSCs) have been postulated as leading tumor promoters and a hallmark of cancer immune evasion mechanisms. This review attempts to analyze the prominent roles of both TGF-beta 1 and MDSCs and their interplay in cancer immunity. Furthermore, therapies against either TGF-beta 1 or MDSCs, and their potential synergistic combination with immunotherapies are discussed. Simultaneous TGF-beta 1 and MDSCs inhibition suggest a potential improvement in immunotherapy or subverted tumor immune resistance.",
publisher = "Wiley",
journal = "Developmental Dinamics",
title = "Transforming growth factor-beta1 and myeloid-derived suppressor cells: A cancerous partnership",
pages = "124-105",
number = "1",
doi = "10.1002/dvdy.339"
}

Mojsilović, S., Mojsilović, S., Bjelica, S.,& Santibanez, J. F.. (2022). Transforming growth factor-beta1 and myeloid-derived suppressor cells: A cancerous partnership. in Developmental Dinamics
Wiley.(1), 105-124.
https://doi.org/10.1002/dvdy.339

Mojsilović S, Mojsilović S, Bjelica S, Santibanez JF. Transforming growth factor-beta1 and myeloid-derived suppressor cells: A cancerous partnership. in Developmental Dinamics. 2022;(1):105-124.
doi:10.1002/dvdy.339 .

Mojsilović, Slavko, Mojsilović, Sonja, Bjelica, Sunčica, Santibanez, Juan F., "Transforming growth factor-beta1 and myeloid-derived suppressor cells: A cancerous partnership" in Developmental Dinamics, no. 1 (2022):105-124,
https://doi.org/10.1002/dvdy.339 . .

TY  - JOUR
AU  - Đikić, Dragoslava
AU  - Bogdanović, Andrija
AU  - Marković, Dragana
AU  - Mitrović-Ajtić, Olivera
AU  - Subotički, Tijana
AU  - Diklić, Miloš
AU  - Vukotić, Milica
AU  - Dragojević, Teodora
AU  - Živković, Emilija
AU  - Santibanez, Juan F.
AU  - Čokić, Vladan
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1202
AB  - Chronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the pro-liferation-related AKT/mTOR signaling pathway and the relationship with inflammatory factors in chronic myelogenous leukemia (CML). The activity of the antioxidant enzymes superoxide dis-mutase, glutathione peroxidase, and catalase is reduced in erythrocytes while levels of the oxidative stress markers malondialdehyde and protein carbonyl are elevated in the plasma of patients with CML. In addition, nitrogen species (nitrotyrosine, iNOS, eNOS) and inflammation markers (IL-6, NFkB, and S100 protein) were increased in granulocytes of CML while anti-inflammatory levels of IL-10 were decreased in plasma. CML granulocytes exhibited greater resistance to cytotoxic H2O2 activity compared to healthy subjects. Moreover, phosphorylation of the apoptotic p53 protein was reduced while the activity of the AKT/mTOR signaling pathway was increased, which was further enhanced by oxidative stress (H2O2) in granulocytes and erythroleukemic K562 cells. IL-6 caused oxidative stress and DNA damage that was mitigated using antioxidant or inhibition of inflammatory NFkB transcription factor in K562 cells. We demonstrated the presence of oxidative and ni-trosative stress in CML, with the former mediated by AKT/mTOR signaling and stimulated by in-flammation.
PB  - MDPI
T2  - Biomolecules
T1  - Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia
IS  - 2
SP  - 247
VL  - 12
DO  - 10.3390/biom12020247
ER  - 

@article{
author = "Đikić, Dragoslava and Bogdanović, Andrija and Marković, Dragana and Mitrović-Ajtić, Olivera and Subotički, Tijana and Diklić, Miloš and Vukotić, Milica and Dragojević, Teodora and Živković, Emilija and Santibanez, Juan F. and Čokić, Vladan",
year = "2022",
abstract = "Chronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the pro-liferation-related AKT/mTOR signaling pathway and the relationship with inflammatory factors in chronic myelogenous leukemia (CML). The activity of the antioxidant enzymes superoxide dis-mutase, glutathione peroxidase, and catalase is reduced in erythrocytes while levels of the oxidative stress markers malondialdehyde and protein carbonyl are elevated in the plasma of patients with CML. In addition, nitrogen species (nitrotyrosine, iNOS, eNOS) and inflammation markers (IL-6, NFkB, and S100 protein) were increased in granulocytes of CML while anti-inflammatory levels of IL-10 were decreased in plasma. CML granulocytes exhibited greater resistance to cytotoxic H2O2 activity compared to healthy subjects. Moreover, phosphorylation of the apoptotic p53 protein was reduced while the activity of the AKT/mTOR signaling pathway was increased, which was further enhanced by oxidative stress (H2O2) in granulocytes and erythroleukemic K562 cells. IL-6 caused oxidative stress and DNA damage that was mitigated using antioxidant or inhibition of inflammatory NFkB transcription factor in K562 cells. We demonstrated the presence of oxidative and ni-trosative stress in CML, with the former mediated by AKT/mTOR signaling and stimulated by in-flammation.",
publisher = "MDPI",
journal = "Biomolecules",
title = "Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia",
number = "2",
pages = "247",
volume = "12",
doi = "10.3390/biom12020247"
}

Đikić, D., Bogdanović, A., Marković, D., Mitrović-Ajtić, O., Subotički, T., Diklić, M., Vukotić, M., Dragojević, T., Živković, E., Santibanez, J. F.,& Čokić, V.. (2022). Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia. in Biomolecules
MDPI., 12(2), 247.
https://doi.org/10.3390/biom12020247

Đikić D, Bogdanović A, Marković D, Mitrović-Ajtić O, Subotički T, Diklić M, Vukotić M, Dragojević T, Živković E, Santibanez JF, Čokić V. Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia. in Biomolecules. 2022;12(2):247.
doi:10.3390/biom12020247 .

Đikić, Dragoslava, Bogdanović, Andrija, Marković, Dragana, Mitrović-Ajtić, Olivera, Subotički, Tijana, Diklić, Miloš, Vukotić, Milica, Dragojević, Teodora, Živković, Emilija, Santibanez, Juan F., Čokić, Vladan, "Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia" in Biomolecules, 12, no. 2 (2022):247,
https://doi.org/10.3390/biom12020247 . .

TY  - JOUR
AU  - Vukotić, Milica
AU  - Kapor, Sunčica
AU  - Dragojević, Teodora
AU  - Đikić, Dragoslava
AU  - Mitrović-Ajtić, Olivera
AU  - Diklić, Miloš
AU  - Subotički, Tijana
AU  - Živković, Emilija
AU  - Beleslin-Čokić, Bojana
AU  - Vojvodić, Aleksandar
AU  - Santibanez, Juan F.
AU  - Gotić, Mirjana
AU  - Čokić, Vladan
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1226
AB  - Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been identified as a major cellular source of fibrosis, the exact molecular mechanism and signaling pathways involved have not been identified thus far. Here, we show that BM-MSCs contribute to fibrosis in myeloproliferative neoplasms (MPNs) by differentiating into αSMA-positive myofibroblasts. These cells display a dysregulated extracellular matrix with increased FN1 production and secretion of profibrotic MMP9 compared to healthy donor cells. Fibrogenic TGFβ and inflammatory JAK2/STAT3 and NFκB signaling pathway activity is increased in BM-MSCs of MPN patients. Moreover, coculture with mononuclear cells from MPN patients was sufficient to induce fibrosis in healthy BM-MSCs. Inhibition of JAK1/2, SMAD3 or NFκB significantly reduced the fibrotic phenotype of MPN BM-MSCs and was able to prevent the development of fibrosis induced by coculture of healthy BM-MSCs and MPN mononuclear cells with overly active JAK/STAT signaling, underlining their involvement in fibrosis. Combined treatment with JAK1/2 and SMAD3 inhibitors showed synergistic and the most favorable effects on αSMA and FN1 expression in BM-MSCs. These results support the combined inhibition of TGFβ and inflammatory signaling to extenuate fibrosis in MPN.
PB  - Korean Society of Medical Biochemistry and Molecular Biology [Associate Organisation]
PB  - Springer Nature [Commercial Publisher]
T2  - Experimental & Molecular Medicine
T1  - Inhibition of proinflammatory signaling impairs fibrosis of bone marrow mesenchymal stromal cells in myeloproliferative neoplasms
EP  - 284
IS  - 3
SP  - 273
VL  - 54
DO  - 10.1038/s12276-022-00742-y
ER  - 

@article{
author = "Vukotić, Milica and Kapor, Sunčica and Dragojević, Teodora and Đikić, Dragoslava and Mitrović-Ajtić, Olivera and Diklić, Miloš and Subotički, Tijana and Živković, Emilija and Beleslin-Čokić, Bojana and Vojvodić, Aleksandar and Santibanez, Juan F. and Gotić, Mirjana and Čokić, Vladan",
year = "2022",
abstract = "Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been identified as a major cellular source of fibrosis, the exact molecular mechanism and signaling pathways involved have not been identified thus far. Here, we show that BM-MSCs contribute to fibrosis in myeloproliferative neoplasms (MPNs) by differentiating into αSMA-positive myofibroblasts. These cells display a dysregulated extracellular matrix with increased FN1 production and secretion of profibrotic MMP9 compared to healthy donor cells. Fibrogenic TGFβ and inflammatory JAK2/STAT3 and NFκB signaling pathway activity is increased in BM-MSCs of MPN patients. Moreover, coculture with mononuclear cells from MPN patients was sufficient to induce fibrosis in healthy BM-MSCs. Inhibition of JAK1/2, SMAD3 or NFκB significantly reduced the fibrotic phenotype of MPN BM-MSCs and was able to prevent the development of fibrosis induced by coculture of healthy BM-MSCs and MPN mononuclear cells with overly active JAK/STAT signaling, underlining their involvement in fibrosis. Combined treatment with JAK1/2 and SMAD3 inhibitors showed synergistic and the most favorable effects on αSMA and FN1 expression in BM-MSCs. These results support the combined inhibition of TGFβ and inflammatory signaling to extenuate fibrosis in MPN.",
publisher = "Korean Society of Medical Biochemistry and Molecular Biology [Associate Organisation], Springer Nature [Commercial Publisher]",
journal = "Experimental & Molecular Medicine",
title = "Inhibition of proinflammatory signaling impairs fibrosis of bone marrow mesenchymal stromal cells in myeloproliferative neoplasms",
pages = "284-273",
number = "3",
volume = "54",
doi = "10.1038/s12276-022-00742-y"
}

Vukotić, M., Kapor, S., Dragojević, T., Đikić, D., Mitrović-Ajtić, O., Diklić, M., Subotički, T., Živković, E., Beleslin-Čokić, B., Vojvodić, A., Santibanez, J. F., Gotić, M.,& Čokić, V.. (2022). Inhibition of proinflammatory signaling impairs fibrosis of bone marrow mesenchymal stromal cells in myeloproliferative neoplasms. in Experimental & Molecular Medicine
Korean Society of Medical Biochemistry and Molecular Biology [Associate Organisation]., 54(3), 273-284.
https://doi.org/10.1038/s12276-022-00742-y

Vukotić M, Kapor S, Dragojević T, Đikić D, Mitrović-Ajtić O, Diklić M, Subotički T, Živković E, Beleslin-Čokić B, Vojvodić A, Santibanez JF, Gotić M, Čokić V. Inhibition of proinflammatory signaling impairs fibrosis of bone marrow mesenchymal stromal cells in myeloproliferative neoplasms. in Experimental & Molecular Medicine. 2022;54(3):273-284.
doi:10.1038/s12276-022-00742-y .

Vukotić, Milica, Kapor, Sunčica, Dragojević, Teodora, Đikić, Dragoslava, Mitrović-Ajtić, Olivera, Diklić, Miloš, Subotički, Tijana, Živković, Emilija, Beleslin-Čokić, Bojana, Vojvodić, Aleksandar, Santibanez, Juan F., Gotić, Mirjana, Čokić, Vladan, "Inhibition of proinflammatory signaling impairs fibrosis of bone marrow mesenchymal stromal cells in myeloproliferative neoplasms" in Experimental & Molecular Medicine, 54, no. 3 (2022):273-284,
https://doi.org/10.1038/s12276-022-00742-y . .

TY  - JOUR
AU  - Ružić, Dušan
AU  - Đoković, Nemanja
AU  - Srdić-Rajić, Tatjana
AU  - Echeverria, Cesar
AU  - Nikolić, Katarina
AU  - Santibanez, Juan F.
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1212
AB  - The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies.
T2  - Pharmaceutics
T1  - Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention
IS  - 1
SP  - 209
VL  - 14
DO  - 10.3390/pharmaceutics14010209
ER  - 

@article{
author = "Ružić, Dušan and Đoković, Nemanja and Srdić-Rajić, Tatjana and Echeverria, Cesar and Nikolić, Katarina and Santibanez, Juan F.",
year = "2022",
abstract = "The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies.",
journal = "Pharmaceutics",
title = "Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention",
number = "1",
pages = "209",
volume = "14",
doi = "10.3390/pharmaceutics14010209"
}

Ružić, D., Đoković, N., Srdić-Rajić, T., Echeverria, C., Nikolić, K.,& Santibanez, J. F.. (2022). Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention. in Pharmaceutics, 14(1), 209.
https://doi.org/10.3390/pharmaceutics14010209

Ružić D, Đoković N, Srdić-Rajić T, Echeverria C, Nikolić K, Santibanez JF. Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention. in Pharmaceutics. 2022;14(1):209.
doi:10.3390/pharmaceutics14010209 .

Ružić, Dušan, Đoković, Nemanja, Srdić-Rajić, Tatjana, Echeverria, Cesar, Nikolić, Katarina, Santibanez, Juan F., "Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention" in Pharmaceutics, 14, no. 1 (2022):209,
https://doi.org/10.3390/pharmaceutics14010209 . .

TY  - JOUR
AU  - Echeverría, César
AU  - Martin, Aldo
AU  - Simon, Felipe
AU  - Salas, Cristian O.
AU  - Nazal, Mariajesus
AU  - Varela, Diego
AU  - Pérez-Castro, Ramón A.
AU  - Santibanez, Juan F.
AU  - Valdés-Valdés, Ricardo O.
AU  - Forero-Doria, Oscar
AU  - Echeverría, Javier
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1261
AB  - Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species.  Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models.  Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo.  Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth.  Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.
PB  - Frontiers Media S.A
T2  - Frontiers in Pharmacology
T1  - In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma
IS  - 9
SP  - 1003264
VL  - 13
DO  - 10.3389/fphar.2022.1003264
ER  - 

@article{
author = "Echeverría, César and Martin, Aldo and Simon, Felipe and Salas, Cristian O. and Nazal, Mariajesus and Varela, Diego and Pérez-Castro, Ramón A. and Santibanez, Juan F. and Valdés-Valdés, Ricardo O. and Forero-Doria, Oscar and Echeverría, Javier",
year = "2022",
abstract = "Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species.  Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models.  Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo.  Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth.  Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.",
publisher = "Frontiers Media S.A",
journal = "Frontiers in Pharmacology",
title = "In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma",
number = "9",
pages = "1003264",
volume = "13",
doi = "10.3389/fphar.2022.1003264"
}

Echeverría, C., Martin, A., Simon, F., Salas, C. O., Nazal, M., Varela, D., Pérez-Castro, R. A., Santibanez, J. F., Valdés-Valdés, R. O., Forero-Doria, O.,& Echeverría, J.. (2022). In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma. in Frontiers in Pharmacology
Frontiers Media S.A., 13(9), 1003264.
https://doi.org/10.3389/fphar.2022.1003264

Echeverría C, Martin A, Simon F, Salas CO, Nazal M, Varela D, Pérez-Castro RA, Santibanez JF, Valdés-Valdés RO, Forero-Doria O, Echeverría J. In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma. in Frontiers in Pharmacology. 2022;13(9):1003264.
doi:10.3389/fphar.2022.1003264 .

Echeverría, César, Martin, Aldo, Simon, Felipe, Salas, Cristian O., Nazal, Mariajesus, Varela, Diego, Pérez-Castro, Ramón A., Santibanez, Juan F., Valdés-Valdés, Ricardo O., Forero-Doria, Oscar, Echeverría, Javier, "In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma" in Frontiers in Pharmacology, 13, no. 9 (2022):1003264,
https://doi.org/10.3389/fphar.2022.1003264 . .

TY  - JOUR
AU  - Ružić, Dušan
AU  - Ellinger, Bernhard
AU  - Đoković, Nemanja
AU  - Santibanez, Juan F.
AU  - Gul, Sheraz
AU  - Beljkaš, Milan
AU  - Đurić, Ana
AU  - Ganesan, Arasu
AU  - Pavić, Aleksandar
AU  - Srdić-Rajić, Tatjana
AU  - Petković, Miloš
AU  - Nikolić, Katarina
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1271
AB  - Abstract  Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations.
PB  - Multidisciplinary Digital Publishing Institute (MDPI)
T2  - Pharmaceutics
T1  - Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation
IS  - 12
SP  - 2600
VL  - 14
DO  - 10.3390/pharmaceutics14122600
ER  - 

@article{
author = "Ružić, Dušan and Ellinger, Bernhard and Đoković, Nemanja and Santibanez, Juan F. and Gul, Sheraz and Beljkaš, Milan and Đurić, Ana and Ganesan, Arasu and Pavić, Aleksandar and Srdić-Rajić, Tatjana and Petković, Miloš and Nikolić, Katarina",
year = "2022",
abstract = "Abstract  Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations.",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
journal = "Pharmaceutics",
title = "Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation",
number = "12",
pages = "2600",
volume = "14",
doi = "10.3390/pharmaceutics14122600"
}

Ružić, D., Ellinger, B., Đoković, N., Santibanez, J. F., Gul, S., Beljkaš, M., Đurić, A., Ganesan, A., Pavić, A., Srdić-Rajić, T., Petković, M.,& Nikolić, K.. (2022). Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation. in Pharmaceutics
Multidisciplinary Digital Publishing Institute (MDPI)., 14(12), 2600.
https://doi.org/10.3390/pharmaceutics14122600

Ružić D, Ellinger B, Đoković N, Santibanez JF, Gul S, Beljkaš M, Đurić A, Ganesan A, Pavić A, Srdić-Rajić T, Petković M, Nikolić K. Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation. in Pharmaceutics. 2022;14(12):2600.
doi:10.3390/pharmaceutics14122600 .

Ružić, Dušan, Ellinger, Bernhard, Đoković, Nemanja, Santibanez, Juan F., Gul, Sheraz, Beljkaš, Milan, Đurić, Ana, Ganesan, Arasu, Pavić, Aleksandar, Srdić-Rajić, Tatjana, Petković, Miloš, Nikolić, Katarina, "Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation" in Pharmaceutics, 14, no. 12 (2022):2600,
https://doi.org/10.3390/pharmaceutics14122600 . .

TY  - JOUR
AU  - Mojsilović, Sonja
AU  - Mojsilović, Slavko
AU  - Villar, Victor H.
AU  - Santibanez, Juan F.
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1167
AB  - Besides transformed cells, the tumors are composed of various cell types that contribute to undesirable tumor progression. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in the tumor microenvironment (TME). Within the TME, TAMs exhibit high plasticity and undergo specific functional metabolic alterations according to the availability of tumor tissue oxygen and nutrients, thus further contributing to tumorigenesis and cancer progression. Here, we review the main functional TAM metabolic patterns influenced by TME, including glycolysis, amino acid, and fatty acid metabolism. Moreover, this review discusses antitumor immunotherapies that affect TAM functionality by inducing cell repolarizing and metabolic profiles towards an antitumoral phenotype. Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.
PB  - Hindawi
T2  - Analytical Cellular Pathology
T1  - The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?
SP  - e5523055
VL  - 2021
DO  - 10.1155/2021/5523055
ER  - 

@article{
author = "Mojsilović, Sonja and Mojsilović, Slavko and Villar, Victor H. and Santibanez, Juan F.",
year = "2021",
abstract = "Besides transformed cells, the tumors are composed of various cell types that contribute to undesirable tumor progression. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in the tumor microenvironment (TME). Within the TME, TAMs exhibit high plasticity and undergo specific functional metabolic alterations according to the availability of tumor tissue oxygen and nutrients, thus further contributing to tumorigenesis and cancer progression. Here, we review the main functional TAM metabolic patterns influenced by TME, including glycolysis, amino acid, and fatty acid metabolism. Moreover, this review discusses antitumor immunotherapies that affect TAM functionality by inducing cell repolarizing and metabolic profiles towards an antitumoral phenotype. Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.",
publisher = "Hindawi",
journal = "Analytical Cellular Pathology",
title = "The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?",
pages = "e5523055",
volume = "2021",
doi = "10.1155/2021/5523055"
}

Mojsilović, S., Mojsilović, S., Villar, V. H.,& Santibanez, J. F.. (2021). The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?. in Analytical Cellular Pathology
Hindawi., 2021, e5523055.
https://doi.org/10.1155/2021/5523055

Mojsilović S, Mojsilović S, Villar VH, Santibanez JF. The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?. in Analytical Cellular Pathology. 2021;2021:e5523055.
doi:10.1155/2021/5523055 .

Mojsilović, Sonja, Mojsilović, Slavko, Villar, Victor H., Santibanez, Juan F., "The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?" in Analytical Cellular Pathology, 2021 (2021):e5523055,
https://doi.org/10.1155/2021/5523055 . .

TY  - JOUR
AU  - Krstić, Jelena
AU  - Mojsilović, Slavko
AU  - Mojsilović, Sonja
AU  - Santibanez, Juan F.
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1220
AB  - Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury. The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response. Interleukin (IL)-17A, produced in the early phase of inflammation, influences the fate of osteoprogenitors. Due to their inherent capacity to differentiate into osteoblasts, mesenchymal stem/stromal cells (MSCs) contribute to bone healing and regeneration. This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs. The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described. To this end, divergent information exists about the capacity of IL-17A to regulate MSCs’ osteogenic fate, depending on the tissue context and target cell type, along with contradictory findings in the same cell types. Therefore, we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17, which may help in the understanding of IL-17A function in bone repair and regeneration.
PB  - Baishideng Publishing Group
T2  - World Journal of Stem Cells
T1  - Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation
EP  - 1713
IS  - 11
SP  - 1696
VL  - 13
DO  - 10.4252/wjsc.v13.i11.1696
ER  - 

@article{
author = "Krstić, Jelena and Mojsilović, Slavko and Mojsilović, Sonja and Santibanez, Juan F.",
year = "2021",
abstract = "Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury. The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response. Interleukin (IL)-17A, produced in the early phase of inflammation, influences the fate of osteoprogenitors. Due to their inherent capacity to differentiate into osteoblasts, mesenchymal stem/stromal cells (MSCs) contribute to bone healing and regeneration. This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs. The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described. To this end, divergent information exists about the capacity of IL-17A to regulate MSCs’ osteogenic fate, depending on the tissue context and target cell type, along with contradictory findings in the same cell types. Therefore, we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17, which may help in the understanding of IL-17A function in bone repair and regeneration.",
publisher = "Baishideng Publishing Group",
journal = "World Journal of Stem Cells",
title = "Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation",
pages = "1713-1696",
number = "11",
volume = "13",
doi = "10.4252/wjsc.v13.i11.1696"
}

Krstić, J., Mojsilović, S., Mojsilović, S.,& Santibanez, J. F.. (2021). Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation. in World Journal of Stem Cells
Baishideng Publishing Group., 13(11), 1696-1713.
https://doi.org/10.4252/wjsc.v13.i11.1696

Krstić J, Mojsilović S, Mojsilović S, Santibanez JF. Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation. in World Journal of Stem Cells. 2021;13(11):1696-1713.
doi:10.4252/wjsc.v13.i11.1696 .

Krstić, Jelena, Mojsilović, Slavko, Mojsilović, Sonja, Santibanez, Juan F., "Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation" in World Journal of Stem Cells, 13, no. 11 (2021):1696-1713,
https://doi.org/10.4252/wjsc.v13.i11.1696 . .

TY  - JOUR
AU  - Subotički, Tijana
AU  - Mitrović-Ajtić, Olivera
AU  - Živković, Emilija
AU  - Diklić, Miloš
AU  - Đikić, Dragoslava
AU  - Tošić, Milica
AU  - Beleslin-Čokić, Bojana
AU  - Dragojević, Teodora
AU  - Gotić, Mirjana
AU  - Santibanez, Juan F.
AU  - Čokić, Vladan
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1136
AB  - Background: Chronic inflammation has been recognized in neoplastic disorders, including myeloproliferative neoplasm (MPN), as an important regulator of angiogenesis. Aims: We investigated the influence of vascular endothelial growth factor (VEGF) and pro-inflammatory interleukin-6 (IL-6) on the expression of angiogenic factors, as well as inflammation-related signaling in mononuclear cells (MNC) of patients with MPN and JAK2V617F positive human erythroleukemic (HEL) cells. Results: We found that IL-6 did not change the expression of angiogenic factors in the MNC of patients with MPN and HEL cells. However, IL-6 and the JAK1/2 inhibitor Ruxolitinib significantly increased angiogenic factors—endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor-1 alpha (HIF-1α)—in patients with polycythemia vera (PV). Furthermore, VEGF significantly increased the expression of HIF-1α and eNOS genes, the latter inversely regulated by PI3K and mTOR signaling in the MNC of primary myelofibrosis (PMF). VEGF and inhibitors of inflammatory JAK1/2, PI3K, and mTOR signaling reduced the eNOS protein expression in HEL cells. VEGF also decreased the expression of eNOS and HIF-1α proteins in the MNC of PMF. In contrast, VEGF increased eNOS and HIF-1α protein expression in the MNC of patients with PV, which was mediated by the inflammatory signaling. VEGF increased the level of IL-6 immunopositive MNC of MPN. In summary, VEGF conversely regulated gene and protein expression of angiogenic factors in the MNC of PMF, while VEGF increased angiogenic factor expression in PV mediated by the inflammation-related signaling. Conclusion: The angiogenic VEGF induction of IL-6 supports chronic inflammation that, through positive feedback, further promotes angiogenesis with concomitant JAK1/2 inhibition.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - VEGF Regulation of Angiogenic Factors via Inflammatory Signaling in Myeloproliferative Neoplasms
IS  - 13
SP  - 6671
VL  - 22
DO  - 10.3390/ijms22136671
ER  - 

@article{
author = "Subotički, Tijana and Mitrović-Ajtić, Olivera and Živković, Emilija and Diklić, Miloš and Đikić, Dragoslava and Tošić, Milica and Beleslin-Čokić, Bojana and Dragojević, Teodora and Gotić, Mirjana and Santibanez, Juan F. and Čokić, Vladan",
year = "2021",
abstract = "Background: Chronic inflammation has been recognized in neoplastic disorders, including myeloproliferative neoplasm (MPN), as an important regulator of angiogenesis. Aims: We investigated the influence of vascular endothelial growth factor (VEGF) and pro-inflammatory interleukin-6 (IL-6) on the expression of angiogenic factors, as well as inflammation-related signaling in mononuclear cells (MNC) of patients with MPN and JAK2V617F positive human erythroleukemic (HEL) cells. Results: We found that IL-6 did not change the expression of angiogenic factors in the MNC of patients with MPN and HEL cells. However, IL-6 and the JAK1/2 inhibitor Ruxolitinib significantly increased angiogenic factors—endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor-1 alpha (HIF-1α)—in patients with polycythemia vera (PV). Furthermore, VEGF significantly increased the expression of HIF-1α and eNOS genes, the latter inversely regulated by PI3K and mTOR signaling in the MNC of primary myelofibrosis (PMF). VEGF and inhibitors of inflammatory JAK1/2, PI3K, and mTOR signaling reduced the eNOS protein expression in HEL cells. VEGF also decreased the expression of eNOS and HIF-1α proteins in the MNC of PMF. In contrast, VEGF increased eNOS and HIF-1α protein expression in the MNC of patients with PV, which was mediated by the inflammatory signaling. VEGF increased the level of IL-6 immunopositive MNC of MPN. In summary, VEGF conversely regulated gene and protein expression of angiogenic factors in the MNC of PMF, while VEGF increased angiogenic factor expression in PV mediated by the inflammation-related signaling. Conclusion: The angiogenic VEGF induction of IL-6 supports chronic inflammation that, through positive feedback, further promotes angiogenesis with concomitant JAK1/2 inhibition.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "VEGF Regulation of Angiogenic Factors via Inflammatory Signaling in Myeloproliferative Neoplasms",
number = "13",
pages = "6671",
volume = "22",
doi = "10.3390/ijms22136671"
}

Subotički, T., Mitrović-Ajtić, O., Živković, E., Diklić, M., Đikić, D., Tošić, M., Beleslin-Čokić, B., Dragojević, T., Gotić, M., Santibanez, J. F.,& Čokić, V.. (2021). VEGF Regulation of Angiogenic Factors via Inflammatory Signaling in Myeloproliferative Neoplasms. in International Journal of Molecular Sciences
MDPI., 22(13), 6671.
https://doi.org/10.3390/ijms22136671

Subotički T, Mitrović-Ajtić O, Živković E, Diklić M, Đikić D, Tošić M, Beleslin-Čokić B, Dragojević T, Gotić M, Santibanez JF, Čokić V. VEGF Regulation of Angiogenic Factors via Inflammatory Signaling in Myeloproliferative Neoplasms. in International Journal of Molecular Sciences. 2021;22(13):6671.
doi:10.3390/ijms22136671 .

Subotički, Tijana, Mitrović-Ajtić, Olivera, Živković, Emilija, Diklić, Miloš, Đikić, Dragoslava, Tošić, Milica, Beleslin-Čokić, Bojana, Dragojević, Teodora, Gotić, Mirjana, Santibanez, Juan F., Čokić, Vladan, "VEGF Regulation of Angiogenic Factors via Inflammatory Signaling in Myeloproliferative Neoplasms" in International Journal of Molecular Sciences, 22, no. 13 (2021):6671,
https://doi.org/10.3390/ijms22136671 . .

TY  - JOUR
AU  - Subotički, Tijana
AU  - Mitrović-Ajtić, Olivera 
AU  - Đikić, Dragoslava
AU  - Santibanez, Juan F.
AU  - Tošić, Milica
AU  - Čokić, Vladan
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1151
AB  - Hydroxyurea (HU) causes nitric oxide (NO) bioactivation, acting as both a NO donor and a stimulator of NO synthase (NOS). To examine whether HU effects are NO mediated by chemical degradation or enzymatic induction, we studied human and mouse erythroid cells during proliferation, apoptosis, and differentiation. The HU and NO donor demonstrated persisted versus temporary inhibition of erythroid cell growth during differentiation, as observed by γ-and β-globin gene expression. HU decreased the percentage of erythroleukemic K562 cells in the G2/M phase that was reversed by N-nitro l-arginine methyl ester hydrochloride (L-NAME). Besides activation of endothelial NOS, HU significantly increased apoptosis of K562 cells, again demonstrating NOS dependence. Administration of HU to mice significantly inhibited colony-forming unit-erythroid (CFU-E), mediated by NOS. Moreover, burst-forming-units-erythroid (BFU-E) and CFU-E ex vivo growth was inhibited by the administration of nitrate or nitrite to mice. Chronic in vivo NOS inhibition with L-NAME protected the bone marrow cellularity despite HU treatment of mice. NO metabolites and HU reduced the frequency of NOS-positive cells from CFU-E and BFU-E colonies that was reverted by NOS inhibition. HU regulation of the G2/M phase, apoptosis, differentiation, cellularity, and NOS immunoreactive cells was NOS dependent. Inhalation of NO therapy as well as strategies to increase endogenous NO production could replace or enhance HU activity.
PB  - Multidisciplinary Digital Publishing Institute (MDPI)
T2  - Genes
T1  - Nitric Oxide Synthase Dependency in Hydroxyurea Inhibition of Erythroid Progenitor Growth
IS  - 8
SP  - 1145
VL  - 12
DO  - 10.3390/genes12081145
ER  - 

@article{
author = "Subotički, Tijana and Mitrović-Ajtić, Olivera  and Đikić, Dragoslava and Santibanez, Juan F. and Tošić, Milica and Čokić, Vladan",
year = "2021",
abstract = "Hydroxyurea (HU) causes nitric oxide (NO) bioactivation, acting as both a NO donor and a stimulator of NO synthase (NOS). To examine whether HU effects are NO mediated by chemical degradation or enzymatic induction, we studied human and mouse erythroid cells during proliferation, apoptosis, and differentiation. The HU and NO donor demonstrated persisted versus temporary inhibition of erythroid cell growth during differentiation, as observed by γ-and β-globin gene expression. HU decreased the percentage of erythroleukemic K562 cells in the G2/M phase that was reversed by N-nitro l-arginine methyl ester hydrochloride (L-NAME). Besides activation of endothelial NOS, HU significantly increased apoptosis of K562 cells, again demonstrating NOS dependence. Administration of HU to mice significantly inhibited colony-forming unit-erythroid (CFU-E), mediated by NOS. Moreover, burst-forming-units-erythroid (BFU-E) and CFU-E ex vivo growth was inhibited by the administration of nitrate or nitrite to mice. Chronic in vivo NOS inhibition with L-NAME protected the bone marrow cellularity despite HU treatment of mice. NO metabolites and HU reduced the frequency of NOS-positive cells from CFU-E and BFU-E colonies that was reverted by NOS inhibition. HU regulation of the G2/M phase, apoptosis, differentiation, cellularity, and NOS immunoreactive cells was NOS dependent. Inhalation of NO therapy as well as strategies to increase endogenous NO production could replace or enhance HU activity.",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
journal = "Genes",
title = "Nitric Oxide Synthase Dependency in Hydroxyurea Inhibition of Erythroid Progenitor Growth",
number = "8",
pages = "1145",
volume = "12",
doi = "10.3390/genes12081145"
}

Subotički, T., Mitrović-Ajtić, O., Đikić, D., Santibanez, J. F., Tošić, M.,& Čokić, V.. (2021). Nitric Oxide Synthase Dependency in Hydroxyurea Inhibition of Erythroid Progenitor Growth. in Genes
Multidisciplinary Digital Publishing Institute (MDPI)., 12(8), 1145.
https://doi.org/10.3390/genes12081145

Subotički T, Mitrović-Ajtić O, Đikić D, Santibanez JF, Tošić M, Čokić V. Nitric Oxide Synthase Dependency in Hydroxyurea Inhibition of Erythroid Progenitor Growth. in Genes. 2021;12(8):1145.
doi:10.3390/genes12081145 .

Subotički, Tijana, Mitrović-Ajtić, Olivera , Đikić, Dragoslava, Santibanez, Juan F., Tošić, Milica, Čokić, Vladan, "Nitric Oxide Synthase Dependency in Hydroxyurea Inhibition of Erythroid Progenitor Growth" in Genes, 12, no. 8 (2021):1145,
https://doi.org/10.3390/genes12081145 . .

TY  - JOUR
AU  - Kapor, Sunčica
AU  - Vukotić, Milica
AU  - Subotički, Tijana
AU  - Đikić, Dragoslava
AU  - Mitrović-Ajtić, Olivera
AU  - Radojković, Milica
AU  - Čokić, Vladan
AU  - Santibanez, Juan F.
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1172
AB  - Hydroxyurea (HU) is an antineoplastic agent that functions as an antimetabolite compound by inhibiting the ribonucleotide reductase. HU acts mainly as a cytostatic drug that through DNA replication stress may trigger a premature senescence-like cell phenotype, though its influence on bone marrow-derived mesenchymal stem/stromal cell (BMMSC) functions has not elucidated yet. Our results indicate that HU inhibits the growth of human BMMSC alongside senescence-like changes in both morphology and replicative potential, provokes cell cycle arrest at the S phase without affecting cellular viability and induces the expression of senescence-associated β-galactosidase and p16INK4. Moreover, HU-induced senescent BMMSC, although they did not change MSC markers expression, exhibited reduced capacity osteogenic and adipogenic differentiation. Conversely, HU treatment increased immunoregulatory functions of BMMSC compared with untreated cells and determined by T-cell proliferation. Interestingly, HU did not influence the capacity of BMMSC to induce monocytic myeloid-derived suppressor cells. Thus, these results suggest that HU improves the BMMSC functions on the T-cell inhibition and preserves their interaction with myeloid cell compartment. Mechanistically, BMMSC under HU treatment displayed a downregulation of mTOR and p38 MAPK signaling that may explain the reduced cell differentiation and increased immunomodulation activities. Together, the results obtained in this investigation suggest that HU by inducing senescence-like phenotype of BMMSC influences their cellular differentiation and immunoregulatory functions.
PB  - MDPI
T2  - Journal of Personalized Medicine
T1  - Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro
IS  - 11
SP  - 1048
VL  - 11
DO  - 10.3390/jpm11111048
ER  - 

@article{
author = "Kapor, Sunčica and Vukotić, Milica and Subotički, Tijana and Đikić, Dragoslava and Mitrović-Ajtić, Olivera and Radojković, Milica and Čokić, Vladan and Santibanez, Juan F.",
year = "2021",
abstract = "Hydroxyurea (HU) is an antineoplastic agent that functions as an antimetabolite compound by inhibiting the ribonucleotide reductase. HU acts mainly as a cytostatic drug that through DNA replication stress may trigger a premature senescence-like cell phenotype, though its influence on bone marrow-derived mesenchymal stem/stromal cell (BMMSC) functions has not elucidated yet. Our results indicate that HU inhibits the growth of human BMMSC alongside senescence-like changes in both morphology and replicative potential, provokes cell cycle arrest at the S phase without affecting cellular viability and induces the expression of senescence-associated β-galactosidase and p16INK4. Moreover, HU-induced senescent BMMSC, although they did not change MSC markers expression, exhibited reduced capacity osteogenic and adipogenic differentiation. Conversely, HU treatment increased immunoregulatory functions of BMMSC compared with untreated cells and determined by T-cell proliferation. Interestingly, HU did not influence the capacity of BMMSC to induce monocytic myeloid-derived suppressor cells. Thus, these results suggest that HU improves the BMMSC functions on the T-cell inhibition and preserves their interaction with myeloid cell compartment. Mechanistically, BMMSC under HU treatment displayed a downregulation of mTOR and p38 MAPK signaling that may explain the reduced cell differentiation and increased immunomodulation activities. Together, the results obtained in this investigation suggest that HU by inducing senescence-like phenotype of BMMSC influences their cellular differentiation and immunoregulatory functions.",
publisher = "MDPI",
journal = "Journal of Personalized Medicine",
title = "Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro",
number = "11",
pages = "1048",
volume = "11",
doi = "10.3390/jpm11111048"
}

Kapor, S., Vukotić, M., Subotički, T., Đikić, D., Mitrović-Ajtić, O., Radojković, M., Čokić, V.,& Santibanez, J. F.. (2021). Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro. in Journal of Personalized Medicine
MDPI., 11(11), 1048.
https://doi.org/10.3390/jpm11111048

Kapor S, Vukotić M, Subotički T, Đikić D, Mitrović-Ajtić O, Radojković M, Čokić V, Santibanez JF. Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro. in Journal of Personalized Medicine. 2021;11(11):1048.
doi:10.3390/jpm11111048 .

Kapor, Sunčica, Vukotić, Milica, Subotički, Tijana, Đikić, Dragoslava, Mitrović-Ajtić, Olivera, Radojković, Milica, Čokić, Vladan, Santibanez, Juan F., "Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro" in Journal of Personalized Medicine, 11, no. 11 (2021):1048,
https://doi.org/10.3390/jpm11111048 . .

TY  - JOUR
AU  - Subotički, Tijana
AU  - Mitrović-Ajtić, Olivera
AU  - Đikić, Dragoslava
AU  - Kovačić, Marijana
AU  - Santibanez, Juan F.
AU  - Tošić, Milica
AU  - Čokić, Vladan
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1196
AB  - In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degradation products) effects on erythroid colony growth and NOS/NO levels in mice using NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Hydroxyurea and nitrite/nitrate decreased the bone marrow cellularity that was blocked by PTIO only for the NO metabolites. Hydroxyurea inhibition of colony-forming unit-erythroid (CFU-E) formation and reticulocytes was reversed by PTIO. Moreover, hydroxyurea, through a negative feedback mechanism, reduced inducible NOS (iNOS) expressing cells in CFU-E, also prevented by PTIO. Nitrate inhibition of burst-forming units-erythroid (BFU-E) colony growth was blocked by PTIO, but not in mature CFU-E. The presented results reveal that NO release and/or production mediates the hydroxyurea inhibition of mature erythroid colony growth and the frequency of iNOS immunoreactive CFU-E.
PB  - MDPI
T2  - Biomolecules
T1  - Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
IS  - 11
SP  - 1562
VL  - 11
DO  - 10.3390/biom11111562
ER  - 

@article{
author = "Subotički, Tijana and Mitrović-Ajtić, Olivera and Đikić, Dragoslava and Kovačić, Marijana and Santibanez, Juan F. and Tošić, Milica and Čokić, Vladan",
year = "2021",
abstract = "In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degradation products) effects on erythroid colony growth and NOS/NO levels in mice using NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Hydroxyurea and nitrite/nitrate decreased the bone marrow cellularity that was blocked by PTIO only for the NO metabolites. Hydroxyurea inhibition of colony-forming unit-erythroid (CFU-E) formation and reticulocytes was reversed by PTIO. Moreover, hydroxyurea, through a negative feedback mechanism, reduced inducible NOS (iNOS) expressing cells in CFU-E, also prevented by PTIO. Nitrate inhibition of burst-forming units-erythroid (BFU-E) colony growth was blocked by PTIO, but not in mature CFU-E. The presented results reveal that NO release and/or production mediates the hydroxyurea inhibition of mature erythroid colony growth and the frequency of iNOS immunoreactive CFU-E.",
publisher = "MDPI",
journal = "Biomolecules",
title = "Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth",
number = "11",
pages = "1562",
volume = "11",
doi = "10.3390/biom11111562"
}

Subotički, T., Mitrović-Ajtić, O., Đikić, D., Kovačić, M., Santibanez, J. F., Tošić, M.,& Čokić, V.. (2021). Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth. in Biomolecules
MDPI., 11(11), 1562.
https://doi.org/10.3390/biom11111562

Subotički T, Mitrović-Ajtić O, Đikić D, Kovačić M, Santibanez JF, Tošić M, Čokić V. Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth. in Biomolecules. 2021;11(11):1562.
doi:10.3390/biom11111562 .

Subotički, Tijana, Mitrović-Ajtić, Olivera, Đikić, Dragoslava, Kovačić, Marijana, Santibanez, Juan F., Tošić, Milica, Čokić, Vladan, "Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth" in Biomolecules, 11, no. 11 (2021):1562,
https://doi.org/10.3390/biom11111562 . .

TY  - JOUR
AU  - Ćupić-Miladinović, Dejana
AU  - Prevendar-Crnić, Andreja
AU  - Peković, Sanja
AU  - Dacić, Sanja
AU  - Ivanović, Saša
AU  - Santibanez, Juan F.
AU  - Ćupić, Vitomir
AU  - Borozan, Nevena
AU  - Antonijević-Miljaković, Evica
AU  - Borozan, Sunčica
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1073
AB  - Chlorpyrifos is a extensively used organophosphate pesticide (OP). In this study, we closely looked into neurotoxicity of CPF and effect of vitamin B1, by checking the levels of cholinesterases, determining the activity of parameters of oxidative stress, inflammation and also level of apoptotic regulator. The study was performed on a total of 80 male Japanese quails (Coturnix japonica), (two control and 6 experimental groups, n = 10). Three group of quails were given by gavage chlorpyrifos (CPF) for 7 consecutive days at doses of 1.50 mg/kg b.w., 3.00 mg/kg b.w., and 6.00 mg/kg b.w. Another three groups were treated with 10 mg/kg b.w. of vitamin B1 i.m. 30 min after CPF application (in above mentioned doses). Our study have proved that all doses of CPF significantly inhibited cholinesterases in brain, while vitamin B1 reactivated them. CPF has led to an increase in the concentration of malondialdehyde (MDA), and activity of catalase (CAT), superoxide dismutase (SOD), glutathione5-transferase (GST), while tiamin changed the activity of antioxidant enzymes: CAT, SOD, GST. CPF stimulated apoptosis by decreasing B-cell lymphoma (Bcl-2) in brain, while application of vitamin B1 caused an increase of this parameter. CPF amplified inflammatory effect by elevating levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Thiamine proved its anti-inflammatory property by decreasing the expression of iNOS and interleukin-1(IL-1) and interleukin-6(IL-6). This study is highly pertinent because there is little defense currently available to humans and animals to prevent toxic effects of pesticides.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T1  - Recovery of brain cholinesterases and effect on parameters of oxidative stress and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration
SP  - 109312
VL  - 333
DO  - 10.1016/j.cbi.2020.109312
ER  - 

@article{
author = "Ćupić-Miladinović, Dejana and Prevendar-Crnić, Andreja and Peković, Sanja and Dacić, Sanja and Ivanović, Saša and Santibanez, Juan F. and Ćupić, Vitomir and Borozan, Nevena and Antonijević-Miljaković, Evica and Borozan, Sunčica",
year = "2021",
abstract = "Chlorpyrifos is a extensively used organophosphate pesticide (OP). In this study, we closely looked into neurotoxicity of CPF and effect of vitamin B1, by checking the levels of cholinesterases, determining the activity of parameters of oxidative stress, inflammation and also level of apoptotic regulator. The study was performed on a total of 80 male Japanese quails (Coturnix japonica), (two control and 6 experimental groups, n = 10). Three group of quails were given by gavage chlorpyrifos (CPF) for 7 consecutive days at doses of 1.50 mg/kg b.w., 3.00 mg/kg b.w., and 6.00 mg/kg b.w. Another three groups were treated with 10 mg/kg b.w. of vitamin B1 i.m. 30 min after CPF application (in above mentioned doses). Our study have proved that all doses of CPF significantly inhibited cholinesterases in brain, while vitamin B1 reactivated them. CPF has led to an increase in the concentration of malondialdehyde (MDA), and activity of catalase (CAT), superoxide dismutase (SOD), glutathione5-transferase (GST), while tiamin changed the activity of antioxidant enzymes: CAT, SOD, GST. CPF stimulated apoptosis by decreasing B-cell lymphoma (Bcl-2) in brain, while application of vitamin B1 caused an increase of this parameter. CPF amplified inflammatory effect by elevating levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Thiamine proved its anti-inflammatory property by decreasing the expression of iNOS and interleukin-1(IL-1) and interleukin-6(IL-6). This study is highly pertinent because there is little defense currently available to humans and animals to prevent toxic effects of pesticides.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions",
title = "Recovery of brain cholinesterases and effect on parameters of oxidative stress and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration",
pages = "109312",
volume = "333",
doi = "10.1016/j.cbi.2020.109312"
}

Ćupić-Miladinović, D., Prevendar-Crnić, A., Peković, S., Dacić, S., Ivanović, S., Santibanez, J. F., Ćupić, V., Borozan, N., Antonijević-Miljaković, E.,& Borozan, S.. (2021). Recovery of brain cholinesterases and effect on parameters of oxidative stress and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration. in Chemico-Biological Interactions
Elsevier., 333, 109312.
https://doi.org/10.1016/j.cbi.2020.109312

Ćupić-Miladinović D, Prevendar-Crnić A, Peković S, Dacić S, Ivanović S, Santibanez JF, Ćupić V, Borozan N, Antonijević-Miljaković E, Borozan S. Recovery of brain cholinesterases and effect on parameters of oxidative stress and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration. in Chemico-Biological Interactions. 2021;333:109312.
doi:10.1016/j.cbi.2020.109312 .

Ćupić-Miladinović, Dejana, Prevendar-Crnić, Andreja, Peković, Sanja, Dacić, Sanja, Ivanović, Saša, Santibanez, Juan F., Ćupić, Vitomir, Borozan, Nevena, Antonijević-Miljaković, Evica, Borozan, Sunčica, "Recovery of brain cholinesterases and effect on parameters of oxidative stress and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration" in Chemico-Biological Interactions, 333 (2021):109312,
https://doi.org/10.1016/j.cbi.2020.109312 . .

TY  - JOUR
AU  - Santibanez, Juan F.
AU  - Obradović, Hristina
AU  - Krstić, Jelena
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1159
AB  - Bone morphogenetic protein (BMP)2 strongly affects the differentiation program of myoblast cells by inhibiting myogenesis and inducing osteogenic differentiation. In turn, extracellular matrix (ECM) proteinases, such as urokinase-type plasminogen activator (uPA), can influence the fate of muscle stem cells by participating in ECM reorganization. Although both BMP2 and uPA have antagonistic roles in muscles cells differentiation, no connection between them has been elucidated so far. This study aims to determine whether BMP2 regulates uPA expression in the myogenic C2C12 cell line and its impact on muscle cell fate differentiation. Our results showed that BMP2 did not modify C2C12 cell proliferation in a growth medium or myogenic differentiation medium. Although BMP2 inhibited myogenesis and induced osteogenesis, these effects were achieved with different doses of BMP2. Low concentrations of BMP2 blocked myogenesis, while a higher concentration was needed to induce osteogenesis. Reduced uPA expression was noticed alongside myogenic inhibition at low concentrations of BMP2. BMP2 activated p38 MAPK signaling to inhibit uPA activity. Furthermore, ectopic human uPA expression reduced BMP2′s ability to inhibit the myogenic differentiation of C2C12 cells. In conclusion, BMP2 inhibits uPA expression through p38 MAPK and in vitro myogenesis at non-osteogenic concentrations, while uPA ectopic expression prevents BMP2 from inhibiting myogenesis in C2C12 cells.
PB  - Elsevier
T2  - Acta Histochemica
T1  - BMP2 downregulates urokinase-type plasminogen activator via p38 MAPK: Implications in C2C12 cells myogenic differentiation
IS  - 6
SP  - 151774
VL  - 123
DO  - 10.1016/j.acthis.2021.151774
ER  - 

@article{
author = "Santibanez, Juan F. and Obradović, Hristina and Krstić, Jelena",
year = "2021",
abstract = "Bone morphogenetic protein (BMP)2 strongly affects the differentiation program of myoblast cells by inhibiting myogenesis and inducing osteogenic differentiation. In turn, extracellular matrix (ECM) proteinases, such as urokinase-type plasminogen activator (uPA), can influence the fate of muscle stem cells by participating in ECM reorganization. Although both BMP2 and uPA have antagonistic roles in muscles cells differentiation, no connection between them has been elucidated so far. This study aims to determine whether BMP2 regulates uPA expression in the myogenic C2C12 cell line and its impact on muscle cell fate differentiation. Our results showed that BMP2 did not modify C2C12 cell proliferation in a growth medium or myogenic differentiation medium. Although BMP2 inhibited myogenesis and induced osteogenesis, these effects were achieved with different doses of BMP2. Low concentrations of BMP2 blocked myogenesis, while a higher concentration was needed to induce osteogenesis. Reduced uPA expression was noticed alongside myogenic inhibition at low concentrations of BMP2. BMP2 activated p38 MAPK signaling to inhibit uPA activity. Furthermore, ectopic human uPA expression reduced BMP2′s ability to inhibit the myogenic differentiation of C2C12 cells. In conclusion, BMP2 inhibits uPA expression through p38 MAPK and in vitro myogenesis at non-osteogenic concentrations, while uPA ectopic expression prevents BMP2 from inhibiting myogenesis in C2C12 cells.",
publisher = "Elsevier",
journal = "Acta Histochemica",
title = "BMP2 downregulates urokinase-type plasminogen activator via p38 MAPK: Implications in C2C12 cells myogenic differentiation",
number = "6",
pages = "151774",
volume = "123",
doi = "10.1016/j.acthis.2021.151774"
}

Santibanez, J. F., Obradović, H.,& Krstić, J.. (2021). BMP2 downregulates urokinase-type plasminogen activator via p38 MAPK: Implications in C2C12 cells myogenic differentiation. in Acta Histochemica
Elsevier., 123(6), 151774.
https://doi.org/10.1016/j.acthis.2021.151774

Santibanez JF, Obradović H, Krstić J. BMP2 downregulates urokinase-type plasminogen activator via p38 MAPK: Implications in C2C12 cells myogenic differentiation. in Acta Histochemica. 2021;123(6):151774.
doi:10.1016/j.acthis.2021.151774 .

Santibanez, Juan F., Obradović, Hristina, Krstić, Jelena, "BMP2 downregulates urokinase-type plasminogen activator via p38 MAPK: Implications in C2C12 cells myogenic differentiation" in Acta Histochemica, 123, no. 6 (2021):151774,
https://doi.org/10.1016/j.acthis.2021.151774 . .

TY  - JOUR
AU  - Kapor, Sunčica
AU  - Santibanez, Juan F.
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1163
AB  - Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone marrow. Myeloid-derived suppressor cells (MDSCs) and mesenchymal stromal cells (MSCs) display immunoregulatory properties by controlling the innate and adaptive immune systems that may induce a tolerant and supportive microenvironment for neoplasm development. This review analyzes the main features of MDSCs and MSCs in myeloid malignancies. The number of MDSCs is elevated in myeloid malignancies exhibiting high immunosuppressive capacities, whereas MSCs, in addition to their immunosuppression contribution, regulate myeloid leukemia cell proliferation, apoptosis, and chemotherapy resistance. Moreover, MSCs may promote MDSC expansion, which may mutually contribute to the creation of an immuno-tolerant neoplasm microenvironment. Understanding the implication of MDSCs and MSCs in myeloid malignancies may favor their potential use in immunotherapeutic strategies.
PB  - MDPI
T2  - Journal of Clinical Medicine
T1  - Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies
IS  - 13
SP  - 2788
VL  - 10
DO  - 10.3390/jcm10132788
ER  - 

@article{
author = "Kapor, Sunčica and Santibanez, Juan F.",
year = "2021",
abstract = "Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone marrow. Myeloid-derived suppressor cells (MDSCs) and mesenchymal stromal cells (MSCs) display immunoregulatory properties by controlling the innate and adaptive immune systems that may induce a tolerant and supportive microenvironment for neoplasm development. This review analyzes the main features of MDSCs and MSCs in myeloid malignancies. The number of MDSCs is elevated in myeloid malignancies exhibiting high immunosuppressive capacities, whereas MSCs, in addition to their immunosuppression contribution, regulate myeloid leukemia cell proliferation, apoptosis, and chemotherapy resistance. Moreover, MSCs may promote MDSC expansion, which may mutually contribute to the creation of an immuno-tolerant neoplasm microenvironment. Understanding the implication of MDSCs and MSCs in myeloid malignancies may favor their potential use in immunotherapeutic strategies.",
publisher = "MDPI",
journal = "Journal of Clinical Medicine",
title = "Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies",
number = "13",
pages = "2788",
volume = "10",
doi = "10.3390/jcm10132788"
}

Kapor, S.,& Santibanez, J. F.. (2021). Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies. in Journal of Clinical Medicine
MDPI., 10(13), 2788.
https://doi.org/10.3390/jcm10132788

Kapor S, Santibanez JF. Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies. in Journal of Clinical Medicine. 2021;10(13):2788.
doi:10.3390/jcm10132788 .

Kapor, Sunčica, Santibanez, Juan F., "Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies" in Journal of Clinical Medicine, 10, no. 13 (2021):2788,
https://doi.org/10.3390/jcm10132788 . .

TY  - JOUR
AU  - Kapor, Sunčica
AU  - Čokić, Vladan
AU  - Santibanez, Juan F.
PY  - 2021
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1174
AB  - Hydroxyurea (HU) is a water-soluble antiproliferative agent used for decades in neoplastic and nonneoplastic conditions. HU is considered an essential medicine because of its cytoreduction functions. HU is an antimetabolite that inhibits ribonucleotide reductase, which causes a depletion of the deoxyribonucleotide pool and dramatically reduces cell proliferation. The proliferation arrest, depending on drug concentration and exposure, may promote a cellular senescence phenotype associated with cancer cell therapy resistance and inflammation, influencing neighboring cell functions, immunosuppression, and potential cancer relapse. HU can induce cellular senescence in both healthy and transformed cells in vitro, in part, because of increased reactive oxygen species (ROS). Here, we analyze the main molecular mechanisms involved in cytotoxic/genotoxic HU function, the potential to increase intracellular ROS levels, and the principal features of cellular senescence induction. Understanding the mechanisms involved in HU's ability to induce cellular senescence may help to improve current chemotherapy strategies and control undesirable treatment effects in cancer patients and other diseases.
PB  - Hindawi
T2  - Oxidative Medicine and Cellular Longevity
T1  - Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?
SP  - e7753857
VL  - 2021
DO  - 10.1155/2021/7753857
ER  - 

@article{
author = "Kapor, Sunčica and Čokić, Vladan and Santibanez, Juan F.",
year = "2021",
abstract = "Hydroxyurea (HU) is a water-soluble antiproliferative agent used for decades in neoplastic and nonneoplastic conditions. HU is considered an essential medicine because of its cytoreduction functions. HU is an antimetabolite that inhibits ribonucleotide reductase, which causes a depletion of the deoxyribonucleotide pool and dramatically reduces cell proliferation. The proliferation arrest, depending on drug concentration and exposure, may promote a cellular senescence phenotype associated with cancer cell therapy resistance and inflammation, influencing neighboring cell functions, immunosuppression, and potential cancer relapse. HU can induce cellular senescence in both healthy and transformed cells in vitro, in part, because of increased reactive oxygen species (ROS). Here, we analyze the main molecular mechanisms involved in cytotoxic/genotoxic HU function, the potential to increase intracellular ROS levels, and the principal features of cellular senescence induction. Understanding the mechanisms involved in HU's ability to induce cellular senescence may help to improve current chemotherapy strategies and control undesirable treatment effects in cancer patients and other diseases.",
publisher = "Hindawi",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?",
pages = "e7753857",
volume = "2021",
doi = "10.1155/2021/7753857"
}

Kapor, S., Čokić, V.,& Santibanez, J. F.. (2021). Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?. in Oxidative Medicine and Cellular Longevity
Hindawi., 2021, e7753857.
https://doi.org/10.1155/2021/7753857

Kapor S, Čokić V, Santibanez JF. Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?. in Oxidative Medicine and Cellular Longevity. 2021;2021:e7753857.
doi:10.1155/2021/7753857 .

Kapor, Sunčica, Čokić, Vladan, Santibanez, Juan F., "Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?" in Oxidative Medicine and Cellular Longevity, 2021 (2021):e7753857,
https://doi.org/10.1155/2021/7753857 . .

TY  - JOUR
AU  - Maslovarić, Irina
AU  - Ilić, Vesna
AU  - Stančić, Ana
AU  - Santibanez, Juan F.
AU  - Trivanović, Drenka
AU  - Drvenica, Ivana
AU  - Krstić, Jelena
AU  - Mojsilović, Slavko
AU  - Okić Đorđević, Ivana
AU  - Bugarski, Diana
PY  - 2020
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1003
AB  - Introduction. Blood products, i.e. platelet rich plasma (PRP), leukocyte-poor plasma (PRP) and platelet poor plasma (PPP), have previously been used to improve muscle regeneration. In this study, six months' frozen-stored PPP of individuals who practiced different types of physical exercise was analysed; it could steer mouse C2C12 myoblast cells towards proliferation, migration and myogenic differentiation, and it could affect the morphology/shape of myotubes. Materials and Methods. PPP of male Olympic weightlifters, football players and professional folk dancers, aged 15-19, was collected 12 h post-training and stored for 6 months at -20°C. C2C12 cell proliferation was assessed by MTT test, motility by scratch assay, myogenic differentiation by myotube formation and gelatinase activity by gel-zymography. Results and Conclusions. PPP induced proliferation and migration of C2C12 cells. Proliferative capacity was as follows: weightlifters  gt  dancers  gt  football players; mean migratory capacity was: weightlifters = dancers  gt  football players. PPP induced formation of myotubes; significant inter-individual variations were detected: PPP from weightlifters induced formation of round myotubes, and PPP from football players and dancers induced formation of elongated myotubes. The mean myotube area was as follows: football players  gt  dancers  gt  weightlifters. PPP gelatinolytic activity was observed; it was negatively correlated with C2C12 myoblast proliferation. These results provide general but distinct evidence that PPP of individuals practicing certain types of exercise can specifically modify myoblast morphology/function. This is significant for explaining physiological responses and adaptations to exercise. In conclusion, longterm, frozen-stored PPP preserves its potential to modify myoblast morphology and function.
AB  - Uvod. Krvna plazma obogaćena leukocitima, plazma sa niskim sadržajem leukocita i plazma sa niskim sadržajem trombocita (platelet poor plasma; PPP) su produkti krvi koji se koriste za stimulaciju regeneracije mišića. U ovom radu smo ispitivali da li zamrzavana PPP osoba koje se bave različitim tipovima fizičke aktivnosti, usmerava C2C12 myoblaste u pravcu povećane proliferacije, migracije i miogene diferencijacije, i da li utiče na morfologiju/izgled miotuba. Materijal i metode. PPP osoba muškog pola starih 15-19 godina je izolovana iz krvi dizača tegova, fudbalera i profesionalnih igrača folklora, 12 sati nakon treninga. Uzorci PPP su čuvani šest meseci na -20ºC. Uticaj PPP na proliferaciju C2C12 ćelija je analiziran MTT testom, na migraciju "scratch" testom, a uticaj na miogenu diferencijaciju je analiziran na osnovu sposobnosti PPP da indukuju formiranje miotuba. Želatinolitička aktivnost PPP je analizirana gel-zimografijom. Rezultati i zaključak. Uzorci PPP su indukovali proliferaciju i migraciju C2C12 ćelija, a kapacitet da stimulišu proliferaciju je bio: dizači tegova  gt  igrači  gt  fudbaleri. Kapacitet PPP da utiču na migraciju C2C12 ćelija je bio: dizači tegova = igrači  gt  fudbaleri. Svi uzorci PPP su indukovali formiranje miotuba, ali su zapažene značajne interindividualne varijacije. PPP dizača tegova su indukovali formiranje okruglih miotuba, dok su miotube formirane u prisustvu PPP igrača i fudbalera bile izdužene. Površina miotuba se, zavisno od tipa fizičke aktivnosti, menjala po sledećem rasporedu: fudbaleri  gt  igrači  gt  dizači tegova. Želatinolitička aktivnost PPP je nagativno korelirala sa proliferacijom C2C12 ćelija. Rezultati ove studije pokazuju da PPP osoba koje se bave određenim tipom fizičke aktivnosti mogu da na specifičan način modulišu morfologiju/funciju mioblasta. Ovaj rezultat je od značaja za objašnjnje fiziološkog odgovora i adaptacije na vežbanje. On pokazuje i da PPP nakon dugotrajnog zamrzavanja imaju očuvanu spospbnost modifikovanja morfologije i funkcije mioblasta.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Veterinarski glasnik
T1  - Platelet-poor plasma of athletes is a potent inducer of Myogenic differentiation of C2C12 myoblasts
T1  - Platelet-poor plazma sportista kao potencijalni induktor miogene diferencijacije C2C12 mioblasta
EP  - 33
IS  - 1
SP  - 18
VL  - 74
DO  - 10.2298/VETGL190414019M
ER  - 

@article{
author = "Maslovarić, Irina and Ilić, Vesna and Stančić, Ana and Santibanez, Juan F. and Trivanović, Drenka and Drvenica, Ivana and Krstić, Jelena and Mojsilović, Slavko and Okić Đorđević, Ivana and Bugarski, Diana",
year = "2020",
abstract = "Introduction. Blood products, i.e. platelet rich plasma (PRP), leukocyte-poor plasma (PRP) and platelet poor plasma (PPP), have previously been used to improve muscle regeneration. In this study, six months' frozen-stored PPP of individuals who practiced different types of physical exercise was analysed; it could steer mouse C2C12 myoblast cells towards proliferation, migration and myogenic differentiation, and it could affect the morphology/shape of myotubes. Materials and Methods. PPP of male Olympic weightlifters, football players and professional folk dancers, aged 15-19, was collected 12 h post-training and stored for 6 months at -20°C. C2C12 cell proliferation was assessed by MTT test, motility by scratch assay, myogenic differentiation by myotube formation and gelatinase activity by gel-zymography. Results and Conclusions. PPP induced proliferation and migration of C2C12 cells. Proliferative capacity was as follows: weightlifters  gt  dancers  gt  football players; mean migratory capacity was: weightlifters = dancers  gt  football players. PPP induced formation of myotubes; significant inter-individual variations were detected: PPP from weightlifters induced formation of round myotubes, and PPP from football players and dancers induced formation of elongated myotubes. The mean myotube area was as follows: football players  gt  dancers  gt  weightlifters. PPP gelatinolytic activity was observed; it was negatively correlated with C2C12 myoblast proliferation. These results provide general but distinct evidence that PPP of individuals practicing certain types of exercise can specifically modify myoblast morphology/function. This is significant for explaining physiological responses and adaptations to exercise. In conclusion, longterm, frozen-stored PPP preserves its potential to modify myoblast morphology and function., Uvod. Krvna plazma obogaćena leukocitima, plazma sa niskim sadržajem leukocita i plazma sa niskim sadržajem trombocita (platelet poor plasma; PPP) su produkti krvi koji se koriste za stimulaciju regeneracije mišića. U ovom radu smo ispitivali da li zamrzavana PPP osoba koje se bave različitim tipovima fizičke aktivnosti, usmerava C2C12 myoblaste u pravcu povećane proliferacije, migracije i miogene diferencijacije, i da li utiče na morfologiju/izgled miotuba. Materijal i metode. PPP osoba muškog pola starih 15-19 godina je izolovana iz krvi dizača tegova, fudbalera i profesionalnih igrača folklora, 12 sati nakon treninga. Uzorci PPP su čuvani šest meseci na -20ºC. Uticaj PPP na proliferaciju C2C12 ćelija je analiziran MTT testom, na migraciju "scratch" testom, a uticaj na miogenu diferencijaciju je analiziran na osnovu sposobnosti PPP da indukuju formiranje miotuba. Želatinolitička aktivnost PPP je analizirana gel-zimografijom. Rezultati i zaključak. Uzorci PPP su indukovali proliferaciju i migraciju C2C12 ćelija, a kapacitet da stimulišu proliferaciju je bio: dizači tegova  gt  igrači  gt  fudbaleri. Kapacitet PPP da utiču na migraciju C2C12 ćelija je bio: dizači tegova = igrači  gt  fudbaleri. Svi uzorci PPP su indukovali formiranje miotuba, ali su zapažene značajne interindividualne varijacije. PPP dizača tegova su indukovali formiranje okruglih miotuba, dok su miotube formirane u prisustvu PPP igrača i fudbalera bile izdužene. Površina miotuba se, zavisno od tipa fizičke aktivnosti, menjala po sledećem rasporedu: fudbaleri  gt  igrači  gt  dizači tegova. Želatinolitička aktivnost PPP je nagativno korelirala sa proliferacijom C2C12 ćelija. Rezultati ove studije pokazuju da PPP osoba koje se bave određenim tipom fizičke aktivnosti mogu da na specifičan način modulišu morfologiju/funciju mioblasta. Ovaj rezultat je od značaja za objašnjnje fiziološkog odgovora i adaptacije na vežbanje. On pokazuje i da PPP nakon dugotrajnog zamrzavanja imaju očuvanu spospbnost modifikovanja morfologije i funkcije mioblasta.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Veterinarski glasnik",
title = "Platelet-poor plasma of athletes is a potent inducer of Myogenic differentiation of C2C12 myoblasts, Platelet-poor plazma sportista kao potencijalni induktor miogene diferencijacije C2C12 mioblasta",
pages = "33-18",
number = "1",
volume = "74",
doi = "10.2298/VETGL190414019M"
}

Maslovarić, I., Ilić, V., Stančić, A., Santibanez, J. F., Trivanović, D., Drvenica, I., Krstić, J., Mojsilović, S., Okić Đorđević, I.,& Bugarski, D.. (2020). Platelet-poor plasma of athletes is a potent inducer of Myogenic differentiation of C2C12 myoblasts. in Veterinarski glasnik
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 74(1), 18-33.
https://doi.org/10.2298/VETGL190414019M

Maslovarić I, Ilić V, Stančić A, Santibanez JF, Trivanović D, Drvenica I, Krstić J, Mojsilović S, Okić Đorđević I, Bugarski D. Platelet-poor plasma of athletes is a potent inducer of Myogenic differentiation of C2C12 myoblasts. in Veterinarski glasnik. 2020;74(1):18-33.
doi:10.2298/VETGL190414019M .

Maslovarić, Irina, Ilić, Vesna, Stančić, Ana, Santibanez, Juan F., Trivanović, Drenka, Drvenica, Ivana, Krstić, Jelena, Mojsilović, Slavko, Okić Đorđević, Ivana, Bugarski, Diana, "Platelet-poor plasma of athletes is a potent inducer of Myogenic differentiation of C2C12 myoblasts" in Veterinarski glasnik, 74, no. 1 (2020):18-33,
https://doi.org/10.2298/VETGL190414019M . .

TY  - JOUR
AU  - Mojsilović, Sonja
AU  - Tošić, Milica
AU  - Mojsilović, Slavko
AU  - Živanović, Marija
AU  - Bjelica, Sunčica
AU  - Srdić-Rajić, Tatjana
AU  - Santibanez, Juan F.
PY  - 2020
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1067
AB  - Purpose: Transforming growth factor-beta (TGF-beta) induces alternative macrophage activation that favors tumor progression and immunosuppression. Meanwhile, paclitaxel (PTx) induces macrophage (M phi) polarization towards antitumor phenotype. TGF-beta also increases tumor stroma macrophage recruitment by mechanisms that include cell motility enhancement and extracellular matrix degradation. In this study, we aimed to determine whether PTx regulates macrophage migration and urokinase-type plasminogen activator (uPA) expression induced by TGF-beta. Methods: We used mouse macrophage RAW 264.7 cells treated with PTx and TGF-beta combinations. Proliferation was analyzed by MTT and cell cycle assays. Immunofluorescence was performed to determine tubulin cytoskeleton and Smad3 nuclear localization. Western blot and transcriptional luciferase reporters were used to measure signal transduction activation. Migration was determined by wound healing assay. uPA activity was determined by zymography assay. Results: PTx decreased RAW 264.7 cell proliferation by inducing G2/M cell cycle arrest and profoundly modified the tubulin cytoskeleton. Also, PTx inhibited TGF-beta-induced Smad3 activation. Furthermore, PTx decreased cell migration and uPA expression stimulated by TGF-beta. Remarkably, p38 MAPK mediated PTx inhibition of uPA activity induced by TGF-beta but it was not implicated on cell migration inhibition. Conclusions: PTx inhibits TGF-beta induction of mouse M phi migration and uPA expression, suggesting that PTx, as TGF-beta targeting therapy, may enhance MT anticancer action within tumors.
PB  - Balkan Union of Oncology (B.U.ON.)
T2  - Journal of BUON
T1  - Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration
EP  - 1265
IS  - 2
SP  - 1257
VL  - 25
UR  - https://hdl.handle.net/21.15107/rcub_rimi_1067
ER  - 

@article{
author = "Mojsilović, Sonja and Tošić, Milica and Mojsilović, Slavko and Živanović, Marija and Bjelica, Sunčica and Srdić-Rajić, Tatjana and Santibanez, Juan F.",
year = "2020",
abstract = "Purpose: Transforming growth factor-beta (TGF-beta) induces alternative macrophage activation that favors tumor progression and immunosuppression. Meanwhile, paclitaxel (PTx) induces macrophage (M phi) polarization towards antitumor phenotype. TGF-beta also increases tumor stroma macrophage recruitment by mechanisms that include cell motility enhancement and extracellular matrix degradation. In this study, we aimed to determine whether PTx regulates macrophage migration and urokinase-type plasminogen activator (uPA) expression induced by TGF-beta. Methods: We used mouse macrophage RAW 264.7 cells treated with PTx and TGF-beta combinations. Proliferation was analyzed by MTT and cell cycle assays. Immunofluorescence was performed to determine tubulin cytoskeleton and Smad3 nuclear localization. Western blot and transcriptional luciferase reporters were used to measure signal transduction activation. Migration was determined by wound healing assay. uPA activity was determined by zymography assay. Results: PTx decreased RAW 264.7 cell proliferation by inducing G2/M cell cycle arrest and profoundly modified the tubulin cytoskeleton. Also, PTx inhibited TGF-beta-induced Smad3 activation. Furthermore, PTx decreased cell migration and uPA expression stimulated by TGF-beta. Remarkably, p38 MAPK mediated PTx inhibition of uPA activity induced by TGF-beta but it was not implicated on cell migration inhibition. Conclusions: PTx inhibits TGF-beta induction of mouse M phi migration and uPA expression, suggesting that PTx, as TGF-beta targeting therapy, may enhance MT anticancer action within tumors.",
publisher = "Balkan Union of Oncology (B.U.ON.)",
journal = "Journal of BUON",
title = "Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration",
pages = "1265-1257",
number = "2",
volume = "25",
url = "https://hdl.handle.net/21.15107/rcub_rimi_1067"
}

Mojsilović, S., Tošić, M., Mojsilović, S., Živanović, M., Bjelica, S., Srdić-Rajić, T.,& Santibanez, J. F.. (2020). Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration. in Journal of BUON
Balkan Union of Oncology (B.U.ON.)., 25(2), 1257-1265.
https://hdl.handle.net/21.15107/rcub_rimi_1067

Mojsilović S, Tošić M, Mojsilović S, Živanović M, Bjelica S, Srdić-Rajić T, Santibanez JF. Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration. in Journal of BUON. 2020;25(2):1257-1265.
https://hdl.handle.net/21.15107/rcub_rimi_1067 .

Mojsilović, Sonja, Tošić, Milica, Mojsilović, Slavko, Živanović, Marija, Bjelica, Sunčica, Srdić-Rajić, Tatjana, Santibanez, Juan F., "Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration" in Journal of BUON, 25, no. 2 (2020):1257-1265,
https://hdl.handle.net/21.15107/rcub_rimi_1067 .

TY  - JOUR
AU  - Diklić, Miloš
AU  - Mitrović-Ajtić, Olivera
AU  - Subotički, Tijana
AU  - Đikić, Dragoslava
AU  - Kovačić, Marijana
AU  - Bjelica, Sunčica
AU  - Beleslin-Čokić, Bojana
AU  - Tošić, Milica
AU  - Leković, Danijela
AU  - Gotić, Mirjana
AU  - Santibanez, Juan F.
AU  - Čokić, Vladan
PY  - 2020
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1024
AB  - This study has been performed to determine the mechanism of activation of the myeloid related S100A proteins by inflammatory cytokines in myeloproliferative neoplasm (MPN). Besides microarray analysis of MPN-derived CD34(+) cells, we analysed the pro-inflammatory IL6 and anti-inflammatory IL10 dependence of NF-kappa B, PI3K-AKT, and JAK-STAT signalling during induction of S100A proteins in mononuclear cells of MPN, by immunoblotting and flow cytometry. We observed the reduced gene expression linked to NF-kappa B and inflammation signalling in MPN-derived CD34(+) cells. Both IL6 and IL10 reduced S100A8 and 100A9 protein levels mediated via NF-kappa B and PI3K signalling, respectively, in mononuclear cells of essential thrombocythemia (ET). We also determined the increased percentage of S100A8 and S100A9 positive granulocytes in ET and primary myelofibrosis, upgraded by the JAK2V617F mutant allele burden. S100A8/9 heterodimer induced JAK1/2-dependent mitotic arrest of the ET-derived granulocytes. Significance of the study We demonstrated that inflammation reduced the myeloid related S100A8/9 proteins by negative feedback mechanism in ET. S100A8/9 can be a diagnostic marker of inflammation in MPN, supported by the concomitant NF-kappa B and JAK1/2 signalling inhibition in regulation of myeloproliferation and therapy of MPN.
PB  - Wiley, Hoboken
T2  - Cell Biochemistry & Function
T1  - IL6 inhibition of inflammatory S100A8/9 proteins is NF-kappa B mediated in essential thrombocythemia
EP  - 372
IS  - 4
SP  - 362
VL  - 38
DO  - 10.1002/cbf.3482
ER  - 

@article{
author = "Diklić, Miloš and Mitrović-Ajtić, Olivera and Subotički, Tijana and Đikić, Dragoslava and Kovačić, Marijana and Bjelica, Sunčica and Beleslin-Čokić, Bojana and Tošić, Milica and Leković, Danijela and Gotić, Mirjana and Santibanez, Juan F. and Čokić, Vladan",
year = "2020",
abstract = "This study has been performed to determine the mechanism of activation of the myeloid related S100A proteins by inflammatory cytokines in myeloproliferative neoplasm (MPN). Besides microarray analysis of MPN-derived CD34(+) cells, we analysed the pro-inflammatory IL6 and anti-inflammatory IL10 dependence of NF-kappa B, PI3K-AKT, and JAK-STAT signalling during induction of S100A proteins in mononuclear cells of MPN, by immunoblotting and flow cytometry. We observed the reduced gene expression linked to NF-kappa B and inflammation signalling in MPN-derived CD34(+) cells. Both IL6 and IL10 reduced S100A8 and 100A9 protein levels mediated via NF-kappa B and PI3K signalling, respectively, in mononuclear cells of essential thrombocythemia (ET). We also determined the increased percentage of S100A8 and S100A9 positive granulocytes in ET and primary myelofibrosis, upgraded by the JAK2V617F mutant allele burden. S100A8/9 heterodimer induced JAK1/2-dependent mitotic arrest of the ET-derived granulocytes. Significance of the study We demonstrated that inflammation reduced the myeloid related S100A8/9 proteins by negative feedback mechanism in ET. S100A8/9 can be a diagnostic marker of inflammation in MPN, supported by the concomitant NF-kappa B and JAK1/2 signalling inhibition in regulation of myeloproliferation and therapy of MPN.",
publisher = "Wiley, Hoboken",
journal = "Cell Biochemistry & Function",
title = "IL6 inhibition of inflammatory S100A8/9 proteins is NF-kappa B mediated in essential thrombocythemia",
pages = "372-362",
number = "4",
volume = "38",
doi = "10.1002/cbf.3482"
}

Diklić, M., Mitrović-Ajtić, O., Subotički, T., Đikić, D., Kovačić, M., Bjelica, S., Beleslin-Čokić, B., Tošić, M., Leković, D., Gotić, M., Santibanez, J. F.,& Čokić, V.. (2020). IL6 inhibition of inflammatory S100A8/9 proteins is NF-kappa B mediated in essential thrombocythemia. in Cell Biochemistry & Function
Wiley, Hoboken., 38(4), 362-372.
https://doi.org/10.1002/cbf.3482

Diklić M, Mitrović-Ajtić O, Subotički T, Đikić D, Kovačić M, Bjelica S, Beleslin-Čokić B, Tošić M, Leković D, Gotić M, Santibanez JF, Čokić V. IL6 inhibition of inflammatory S100A8/9 proteins is NF-kappa B mediated in essential thrombocythemia. in Cell Biochemistry & Function. 2020;38(4):362-372.
doi:10.1002/cbf.3482 .

Diklić, Miloš, Mitrović-Ajtić, Olivera, Subotički, Tijana, Đikić, Dragoslava, Kovačić, Marijana, Bjelica, Sunčica, Beleslin-Čokić, Bojana, Tošić, Milica, Leković, Danijela, Gotić, Mirjana, Santibanez, Juan F., Čokić, Vladan, "IL6 inhibition of inflammatory S100A8/9 proteins is NF-kappa B mediated in essential thrombocythemia" in Cell Biochemistry & Function, 38, no. 4 (2020):362-372,
https://doi.org/10.1002/cbf.3482 . .

TY  - JOUR
AU  - Echeverria, Cesar
AU  - Eltit, Felipe
AU  - Santibanez, Juan F.
AU  - Gatica, Sebastian
AU  - Cabello-Verrugio, Claudio
AU  - Simon, Felipe
PY  - 2020
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1034
AB  - In recent years, the vascular endothelium has gained attention as a key player in the initiation and development of pregnancy disorders. Endothelium acts as an endocrine organ that preserves the homeostatic balance by responding to changes in metabolic status. However, in metabolic disorders, endothelial cells adopt a dysfunctional function, losing their normal responsiveness. During pregnancy, several metabolic changes occur, in which endothelial function decisively participates. Similarly, when pregnancy metabolic disorders occur, endothelial dysfunction plays a key role in pathogenesis. This review outlines the main findings regarding endothelial dysfunction in three main metabolic pathological conditions observed during pregnancy: gestational diabetes, hypertensive disorders, and obesity and hyperlipidemia. Organ, histological and cellular characteristics were thoroughly described. Also, we focused in discussing the underlying molecular mechanisms involved in the cellular signaling pathways that mediate responses in these pathological conditions.
PB  - Elsevier, Amsterdam
T2  - Biochimica et Biophysica Acta-Molecular Basis of Disease
T1  - Endothelial dysfunction in pregnancy metabolic disorders
IS  - 2
SP  - 165414
VL  - 1866
DO  - 10.1016/j.bbadis.2019.02.009
ER  - 

@article{
author = "Echeverria, Cesar and Eltit, Felipe and Santibanez, Juan F. and Gatica, Sebastian and Cabello-Verrugio, Claudio and Simon, Felipe",
year = "2020",
abstract = "In recent years, the vascular endothelium has gained attention as a key player in the initiation and development of pregnancy disorders. Endothelium acts as an endocrine organ that preserves the homeostatic balance by responding to changes in metabolic status. However, in metabolic disorders, endothelial cells adopt a dysfunctional function, losing their normal responsiveness. During pregnancy, several metabolic changes occur, in which endothelial function decisively participates. Similarly, when pregnancy metabolic disorders occur, endothelial dysfunction plays a key role in pathogenesis. This review outlines the main findings regarding endothelial dysfunction in three main metabolic pathological conditions observed during pregnancy: gestational diabetes, hypertensive disorders, and obesity and hyperlipidemia. Organ, histological and cellular characteristics were thoroughly described. Also, we focused in discussing the underlying molecular mechanisms involved in the cellular signaling pathways that mediate responses in these pathological conditions.",
publisher = "Elsevier, Amsterdam",
journal = "Biochimica et Biophysica Acta-Molecular Basis of Disease",
title = "Endothelial dysfunction in pregnancy metabolic disorders",
number = "2",
pages = "165414",
volume = "1866",
doi = "10.1016/j.bbadis.2019.02.009"
}

Echeverria, C., Eltit, F., Santibanez, J. F., Gatica, S., Cabello-Verrugio, C.,& Simon, F.. (2020). Endothelial dysfunction in pregnancy metabolic disorders. in Biochimica et Biophysica Acta-Molecular Basis of Disease
Elsevier, Amsterdam., 1866(2), 165414.
https://doi.org/10.1016/j.bbadis.2019.02.009

Echeverria C, Eltit F, Santibanez JF, Gatica S, Cabello-Verrugio C, Simon F. Endothelial dysfunction in pregnancy metabolic disorders. in Biochimica et Biophysica Acta-Molecular Basis of Disease. 2020;1866(2):165414.
doi:10.1016/j.bbadis.2019.02.009 .

Echeverria, Cesar, Eltit, Felipe, Santibanez, Juan F., Gatica, Sebastian, Cabello-Verrugio, Claudio, Simon, Felipe, "Endothelial dysfunction in pregnancy metabolic disorders" in Biochimica et Biophysica Acta-Molecular Basis of Disease, 1866, no. 2 (2020):165414,
https://doi.org/10.1016/j.bbadis.2019.02.009 . .

TY  - JOUR
AU  - Benjumeda-Wijnhoven, Isabel M.
AU  - Vallejos, Raul
AU  - Santibanez, Juan F.
AU  - Millán, Carola S.
AU  - Vivanco, Juan F.
PY  - 2020
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/992
AB  - The combination of biomaterials and stem cells for clinical applications constitute a great challenge in bone tissue engineering. Hence, cellular networks derived from cells-biomaterials crosstalk have a profound influence on cell behaviour and communication, preceding proliferation and differentiation. The purpose of this study was to investigate in vitro cellular networks derived from human gingival mesenchymal stem cells (hGMSCs) and calcium phosphate (CaP) bioceramic interaction. Biological performance of CaP bioceramic and hGMSCs interaction was evaluated through cell adhesion and distribution, cellular proliferation, and potential osteogenic differentiation, at three different times: 5 h, 1 week and 4 weeks. Results confirmed that hGMSCs met the required MSCs criteria while displaying osteogenic differentiaton capacities. We found a significant increase of cellular numbers and proliferation levels. Also, protein and mRNA OPN expression were upregulated in cells cultured with CaP bioceramic by day 21, suggesting an osteoinductible effect of the CaP bioceramic on hGMSCs. Remarkably, CaP bioceramic aggregations were obtained through hGMSCs bridges, suggesting the in vitro potential of macrostructures formation. We conclude that hGMSCs and CaP bioceramics with micro and macropores support hGMSC adhesion, proliferation and osteogenic differentiation. Our results suggest that investigations focused on the interface cells-biomaterials are essential for bone tissue regenerative therapies.
PB  - Nature Research, Berlin
T2  - Scientific Reports
T1  - Analysis of cell-biomaterial interaction through cellular bridge formation in the interface between hGMSCs and CaP bioceramics
IS  - 1
SP  - 16493
VL  - 10
DO  - 10.1038/s41598-020-73428-y
ER  - 

@article{
author = "Benjumeda-Wijnhoven, Isabel M. and Vallejos, Raul and Santibanez, Juan F. and Millán, Carola S. and Vivanco, Juan F.",
year = "2020",
abstract = "The combination of biomaterials and stem cells for clinical applications constitute a great challenge in bone tissue engineering. Hence, cellular networks derived from cells-biomaterials crosstalk have a profound influence on cell behaviour and communication, preceding proliferation and differentiation. The purpose of this study was to investigate in vitro cellular networks derived from human gingival mesenchymal stem cells (hGMSCs) and calcium phosphate (CaP) bioceramic interaction. Biological performance of CaP bioceramic and hGMSCs interaction was evaluated through cell adhesion and distribution, cellular proliferation, and potential osteogenic differentiation, at three different times: 5 h, 1 week and 4 weeks. Results confirmed that hGMSCs met the required MSCs criteria while displaying osteogenic differentiaton capacities. We found a significant increase of cellular numbers and proliferation levels. Also, protein and mRNA OPN expression were upregulated in cells cultured with CaP bioceramic by day 21, suggesting an osteoinductible effect of the CaP bioceramic on hGMSCs. Remarkably, CaP bioceramic aggregations were obtained through hGMSCs bridges, suggesting the in vitro potential of macrostructures formation. We conclude that hGMSCs and CaP bioceramics with micro and macropores support hGMSC adhesion, proliferation and osteogenic differentiation. Our results suggest that investigations focused on the interface cells-biomaterials are essential for bone tissue regenerative therapies.",
publisher = "Nature Research, Berlin",
journal = "Scientific Reports",
title = "Analysis of cell-biomaterial interaction through cellular bridge formation in the interface between hGMSCs and CaP bioceramics",
number = "1",
pages = "16493",
volume = "10",
doi = "10.1038/s41598-020-73428-y"
}

Benjumeda-Wijnhoven, I. M., Vallejos, R., Santibanez, J. F., Millán, C. S.,& Vivanco, J. F.. (2020). Analysis of cell-biomaterial interaction through cellular bridge formation in the interface between hGMSCs and CaP bioceramics. in Scientific Reports
Nature Research, Berlin., 10(1), 16493.
https://doi.org/10.1038/s41598-020-73428-y

Benjumeda-Wijnhoven IM, Vallejos R, Santibanez JF, Millán CS, Vivanco JF. Analysis of cell-biomaterial interaction through cellular bridge formation in the interface between hGMSCs and CaP bioceramics. in Scientific Reports. 2020;10(1):16493.
doi:10.1038/s41598-020-73428-y .

Benjumeda-Wijnhoven, Isabel M., Vallejos, Raul, Santibanez, Juan F., Millán, Carola S., Vivanco, Juan F., "Analysis of cell-biomaterial interaction through cellular bridge formation in the interface between hGMSCs and CaP bioceramics" in Scientific Reports, 10, no. 1 (2020):16493,
https://doi.org/10.1038/s41598-020-73428-y . .