TY  - JOUR
AU  - Mrkalić, Emina
AU  - Šmit, Biljana
AU  - Matić, Sanja
AU  - Jelić, Ratomir
AU  - Ćendić Serafinović, Marina
AU  - Gligorijević, Nevenka
AU  - Čavić, Milena
AU  - Aranđelović, Sandra
AU  - Grgurić-Šipka, Sanja
AU  - Soldatović, Tanja
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5880
AB  - The four novel complexes [{cis-PtCl(NH3)2(μ-4,4′ -bipyridyl)ZnCl(terpy)}](ClO4)2 (C1), [{trans-PtCl(NH3)2(μ-
4,4′ -bipyridyl)ZnCl(terpy)}](ClO4)2 (C2), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C3) and [{trans-
PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C4) (where terpy = 2,2′ :6′ ,2′ ′ -terpyridine) were synthesized and
characterized. Acid–base titrations and concentration dependent kinetic measurements for the reactions with
biologically relevant ligands such as guanosine-5′ -monophosphate (5′ -GMP), inosine-5′ -monophosphate (5′ -IMP)
and glutathione (GSH), were studied at pH 7.4 and 37 ◦C. The binding of the heterometallic bridged cis- or trans-
Pt(II)-Zn(II) complexes to calf thymus DNA (CT-DNA) was studied by UV absorption and fluorescence emission
spectroscopy and molecular docking. The results indicated that the complexes bind strongly to DNA, through
groove binding, hydrogen bonds, and hydrophobic or electrostatic interaction. The possible in vitro DNA protective
effect of cis- and trans-Pt-L-Zn complexes has shown that C3 had significant dose-dependent DNA-protective
effect and the same ability to inhibit peroxyl as well as hydroxyl radicals. Antiproliferative effect of the
complexes, mRNA expression of apoptosis and repair-related genes after treatment in cancer cells indicated that
newly synthesized C2 exhibited highly selective cytotoxicity toward colon carcinoma HCT116 cells. Only
treatment with trans analog C2 induced effect similar to the typical DNA damaging agent such as cisplatin,
characterized by p53 mediated cell response, cell cycle arrest and certain induction of apoptotic related genes.
Both cis- and trans-isomers C1 and C2 showed potency to elicit expression of PARP1 mRNA and in vitro DNA
binding.
PB  - Elsevier
T2  - J. Inorg. Biochem.
T1  - Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent
VL  - 240
DO  - https://doi.org/10.1016/j.jinorgbio.2022.112100
ER  - 

@article{
author = "Mrkalić, Emina and Šmit, Biljana and Matić, Sanja and Jelić, Ratomir and Ćendić Serafinović, Marina and Gligorijević, Nevenka and Čavić, Milena and Aranđelović, Sandra and Grgurić-Šipka, Sanja and Soldatović, Tanja",
year = "2023",
abstract = "The four novel complexes [{cis-PtCl(NH3)2(μ-4,4′ -bipyridyl)ZnCl(terpy)}](ClO4)2 (C1), [{trans-PtCl(NH3)2(μ-
4,4′ -bipyridyl)ZnCl(terpy)}](ClO4)2 (C2), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C3) and [{trans-
PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C4) (where terpy = 2,2′ :6′ ,2′ ′ -terpyridine) were synthesized and
characterized. Acid–base titrations and concentration dependent kinetic measurements for the reactions with
biologically relevant ligands such as guanosine-5′ -monophosphate (5′ -GMP), inosine-5′ -monophosphate (5′ -IMP)
and glutathione (GSH), were studied at pH 7.4 and 37 ◦C. The binding of the heterometallic bridged cis- or trans-
Pt(II)-Zn(II) complexes to calf thymus DNA (CT-DNA) was studied by UV absorption and fluorescence emission
spectroscopy and molecular docking. The results indicated that the complexes bind strongly to DNA, through
groove binding, hydrogen bonds, and hydrophobic or electrostatic interaction. The possible in vitro DNA protective
effect of cis- and trans-Pt-L-Zn complexes has shown that C3 had significant dose-dependent DNA-protective
effect and the same ability to inhibit peroxyl as well as hydroxyl radicals. Antiproliferative effect of the
complexes, mRNA expression of apoptosis and repair-related genes after treatment in cancer cells indicated that
newly synthesized C2 exhibited highly selective cytotoxicity toward colon carcinoma HCT116 cells. Only
treatment with trans analog C2 induced effect similar to the typical DNA damaging agent such as cisplatin,
characterized by p53 mediated cell response, cell cycle arrest and certain induction of apoptotic related genes.
Both cis- and trans-isomers C1 and C2 showed potency to elicit expression of PARP1 mRNA and in vitro DNA
binding.",
publisher = "Elsevier",
journal = "J. Inorg. Biochem.",
title = "Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent",
volume = "240",
doi = "https://doi.org/10.1016/j.jinorgbio.2022.112100"
}

Mrkalić, E., Šmit, B., Matić, S., Jelić, R., Ćendić Serafinović, M., Gligorijević, N., Čavić, M., Aranđelović, S., Grgurić-Šipka, S.,& Soldatović, T.. (2023). Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent. in J. Inorg. Biochem.
Elsevier., 240.
https://doi.org/https://doi.org/10.1016/j.jinorgbio.2022.112100

Mrkalić E, Šmit B, Matić S, Jelić R, Ćendić Serafinović M, Gligorijević N, Čavić M, Aranđelović S, Grgurić-Šipka S, Soldatović T. Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent. in J. Inorg. Biochem.. 2023;240.
doi:https://doi.org/10.1016/j.jinorgbio.2022.112100 .

Mrkalić, Emina, Šmit, Biljana, Matić, Sanja, Jelić, Ratomir, Ćendić Serafinović, Marina, Gligorijević, Nevenka, Čavić, Milena, Aranđelović, Sandra, Grgurić-Šipka, Sanja, Soldatović, Tanja, "Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent" in J. Inorg. Biochem., 240 (2023),
https://doi.org/https://doi.org/10.1016/j.jinorgbio.2022.112100 . .

TY  - JOUR
AU  - Nešić, Andrijana N.
AU  - Stojsavljević, Aleksandar
AU  - Jagodić, Jovana
AU  - Čavić, Milena
AU  - Stefanović, Aleksandra
AU  - Manojlović, Dragan D.
AU  - Gavrović-Jankulović, Marija
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5636
AB  - Background: Although essential trace elements (ETEs) play pivotal roles in life-supporting biochemical processes, their function in innate and adaptive immunity has not been fully elucidated, particularly during immunization. Furthermore, the association between anti-SARS-CoV-2 specific IgG antibodies and ETE levels with vaccine responsiveness has not been investigated. Methods: The present study explored the status of ETEs (Mn, Cu, Zn, and Se) in sera of healthy women before and after vaccination with the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in a follow-up period of six months. The main aim was to explore links between ETE levels and IgG antibodies produced against Spike glycoprotein's Receptor-Binding Domain (RBD). Results: A recombinant protein of SARS-CoV-2 comprising the receptor binding domain was successfully expressed in HEK-293 T cells. The purified protein was suitable for producing a sensitive antibody detection assay for human serum and monitored seropositivity, indicating a transient response with peak anti-SARS-CoV-2 IgG levels 2 months after vaccination. In parallel to increasing antibody titers, serum concentrations of Cu, Mn, and Se were not affected by vaccination, and concentrations remained relatively constant at the different sampling times during the 6-month observation period. Total serum Zn concentrations were slightly elevated when compared between the first and last sampling dates. Overall, no consistent effects of vaccination on any of the three trace elements analyzed in our study were observed. Conclusion: Vaccination of adult healthy female volunteers with an mRNA vaccine was not associated with consistent changes in serum trace element concentrations over a six-month observation period.
PB  - Elsevier
T2  - Journal of Trace Elements in Medicine and Biology
T1  - A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels
VL  - 74
SP  - 127079
DO  - 10.1016/j.jtemb.2022.127079
ER  - 

@article{
author = "Nešić, Andrijana N. and Stojsavljević, Aleksandar and Jagodić, Jovana and Čavić, Milena and Stefanović, Aleksandra and Manojlović, Dragan D. and Gavrović-Jankulović, Marija",
year = "2022",
abstract = "Background: Although essential trace elements (ETEs) play pivotal roles in life-supporting biochemical processes, their function in innate and adaptive immunity has not been fully elucidated, particularly during immunization. Furthermore, the association between anti-SARS-CoV-2 specific IgG antibodies and ETE levels with vaccine responsiveness has not been investigated. Methods: The present study explored the status of ETEs (Mn, Cu, Zn, and Se) in sera of healthy women before and after vaccination with the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in a follow-up period of six months. The main aim was to explore links between ETE levels and IgG antibodies produced against Spike glycoprotein's Receptor-Binding Domain (RBD). Results: A recombinant protein of SARS-CoV-2 comprising the receptor binding domain was successfully expressed in HEK-293 T cells. The purified protein was suitable for producing a sensitive antibody detection assay for human serum and monitored seropositivity, indicating a transient response with peak anti-SARS-CoV-2 IgG levels 2 months after vaccination. In parallel to increasing antibody titers, serum concentrations of Cu, Mn, and Se were not affected by vaccination, and concentrations remained relatively constant at the different sampling times during the 6-month observation period. Total serum Zn concentrations were slightly elevated when compared between the first and last sampling dates. Overall, no consistent effects of vaccination on any of the three trace elements analyzed in our study were observed. Conclusion: Vaccination of adult healthy female volunteers with an mRNA vaccine was not associated with consistent changes in serum trace element concentrations over a six-month observation period.",
publisher = "Elsevier",
journal = "Journal of Trace Elements in Medicine and Biology",
title = "A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels",
volume = "74",
pages = "127079",
doi = "10.1016/j.jtemb.2022.127079"
}

Nešić, A. N., Stojsavljević, A., Jagodić, J., Čavić, M., Stefanović, A., Manojlović, D. D.,& Gavrović-Jankulović, M.. (2022). A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels. in Journal of Trace Elements in Medicine and Biology
Elsevier., 74, 127079.
https://doi.org/10.1016/j.jtemb.2022.127079

Nešić AN, Stojsavljević A, Jagodić J, Čavić M, Stefanović A, Manojlović DD, Gavrović-Jankulović M. A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels. in Journal of Trace Elements in Medicine and Biology. 2022;74:127079.
doi:10.1016/j.jtemb.2022.127079 .

Nešić, Andrijana N., Stojsavljević, Aleksandar, Jagodić, Jovana, Čavić, Milena, Stefanović, Aleksandra, Manojlović, Dragan D., Gavrović-Jankulović, Marija, "A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels" in Journal of Trace Elements in Medicine and Biology, 74 (2022):127079,
https://doi.org/10.1016/j.jtemb.2022.127079 . .

TY  - DATA
AU  - Nešić, Andrijana N.
AU  - Stojsavljević, Aleksandar
AU  - Jagodić, Jovana
AU  - Čavić, Milena
AU  - Stefanović, Aleksandra
AU  - Manojlović, Dragan D.
AU  - Gavrović-Jankulović, Marija
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5658
AB  - Background: Although essential trace elements (ETEs) play pivotal roles in life-supporting biochemical processes, their function in innate and adaptive immunity has not been fully elucidated, particularly during immunization. Furthermore, the association between anti-SARS-CoV-2 specific IgG antibodies and ETE levels with vaccine responsiveness has not been investigated. Methods: The present study explored the status of ETEs (Mn, Cu, Zn, and Se) in sera of healthy women before and after vaccination with the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in a follow-up period of six months. The main aim was to explore links between ETE levels and IgG antibodies produced against Spike glycoprotein's Receptor-Binding Domain (RBD). Results: A recombinant protein of SARS-CoV-2 comprising the receptor binding domain was successfully expressed in HEK-293 T cells. The purified protein was suitable for producing a sensitive antibody detection assay for human serum and monitored seropositivity, indicating a transient response with peak anti-SARS-CoV-2 IgG levels 2 months after vaccination. In parallel to increasing antibody titers, serum concentrations of Cu, Mn, and Se were not affected by vaccination, and concentrations remained relatively constant at the different sampling times during the 6-month observation period. Total serum Zn concentrations were slightly elevated when compared between the first and last sampling dates. Overall, no consistent effects of vaccination on any of the three trace elements analyzed in our study were observed. Conclusion: Vaccination of adult healthy female volunteers with an mRNA vaccine was not associated with consistent changes in serum trace element concentrations over a six-month observation period.
PB  - Elsevier
T2  - Journal of Trace Elements in Medicine and Biology
T1  - Supplementary material for: Nešić, A., Stojsavljević, A., Jagodić, J., Čavić, M., Stefanović, A., Manojlović, D.,& Gavrović-Jankulović, M.. (2022). A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels. in Journal of Trace Elements in Medicine and Biology Elsevier., 74, 127079. https://doi.org/10.1016/j.jtemb.2022.127079
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5658
ER  - 

@misc{
author = "Nešić, Andrijana N. and Stojsavljević, Aleksandar and Jagodić, Jovana and Čavić, Milena and Stefanović, Aleksandra and Manojlović, Dragan D. and Gavrović-Jankulović, Marija",
year = "2022",
abstract = "Background: Although essential trace elements (ETEs) play pivotal roles in life-supporting biochemical processes, their function in innate and adaptive immunity has not been fully elucidated, particularly during immunization. Furthermore, the association between anti-SARS-CoV-2 specific IgG antibodies and ETE levels with vaccine responsiveness has not been investigated. Methods: The present study explored the status of ETEs (Mn, Cu, Zn, and Se) in sera of healthy women before and after vaccination with the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in a follow-up period of six months. The main aim was to explore links between ETE levels and IgG antibodies produced against Spike glycoprotein's Receptor-Binding Domain (RBD). Results: A recombinant protein of SARS-CoV-2 comprising the receptor binding domain was successfully expressed in HEK-293 T cells. The purified protein was suitable for producing a sensitive antibody detection assay for human serum and monitored seropositivity, indicating a transient response with peak anti-SARS-CoV-2 IgG levels 2 months after vaccination. In parallel to increasing antibody titers, serum concentrations of Cu, Mn, and Se were not affected by vaccination, and concentrations remained relatively constant at the different sampling times during the 6-month observation period. Total serum Zn concentrations were slightly elevated when compared between the first and last sampling dates. Overall, no consistent effects of vaccination on any of the three trace elements analyzed in our study were observed. Conclusion: Vaccination of adult healthy female volunteers with an mRNA vaccine was not associated with consistent changes in serum trace element concentrations over a six-month observation period.",
publisher = "Elsevier",
journal = "Journal of Trace Elements in Medicine and Biology",
title = "Supplementary material for: Nešić, A., Stojsavljević, A., Jagodić, J., Čavić, M., Stefanović, A., Manojlović, D.,& Gavrović-Jankulović, M.. (2022). A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels. in Journal of Trace Elements in Medicine and Biology Elsevier., 74, 127079. https://doi.org/10.1016/j.jtemb.2022.127079",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5658"
}

Nešić, A. N., Stojsavljević, A., Jagodić, J., Čavić, M., Stefanović, A., Manojlović, D. D.,& Gavrović-Jankulović, M.. (2022). Supplementary material for: Nešić, A., Stojsavljević, A., Jagodić, J., Čavić, M., Stefanović, A., Manojlović, D.,& Gavrović-Jankulović, M.. (2022). A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels. in Journal of Trace Elements in Medicine and Biology Elsevier., 74, 127079. https://doi.org/10.1016/j.jtemb.2022.127079. in Journal of Trace Elements in Medicine and Biology
Elsevier..
https://hdl.handle.net/21.15107/rcub_cherry_5658

Nešić AN, Stojsavljević A, Jagodić J, Čavić M, Stefanović A, Manojlović DD, Gavrović-Jankulović M. Supplementary material for: Nešić, A., Stojsavljević, A., Jagodić, J., Čavić, M., Stefanović, A., Manojlović, D.,& Gavrović-Jankulović, M.. (2022). A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels. in Journal of Trace Elements in Medicine and Biology Elsevier., 74, 127079. https://doi.org/10.1016/j.jtemb.2022.127079. in Journal of Trace Elements in Medicine and Biology. 2022;.
https://hdl.handle.net/21.15107/rcub_cherry_5658 .

Nešić, Andrijana N., Stojsavljević, Aleksandar, Jagodić, Jovana, Čavić, Milena, Stefanović, Aleksandra, Manojlović, Dragan D., Gavrović-Jankulović, Marija, "Supplementary material for: Nešić, A., Stojsavljević, A., Jagodić, J., Čavić, M., Stefanović, A., Manojlović, D.,& Gavrović-Jankulović, M.. (2022). A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels. in Journal of Trace Elements in Medicine and Biology Elsevier., 74, 127079. https://doi.org/10.1016/j.jtemb.2022.127079" in Journal of Trace Elements in Medicine and Biology (2022),
https://hdl.handle.net/21.15107/rcub_cherry_5658 .

TY  - JOUR
AU  - Nešić, Andrijana N.
AU  - Čavić, Milena
AU  - Popović, Milica M.
AU  - Gavrović-Jankulović, Marija
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4549
AB  - Actinidin (Act d 1), a highly abundant cysteine protease from kiwifruit, is one of the major contributors to the development of kiwifruit allergy. Many studies have focused on the optimization of Act d 1 purification and its role in the development of food allergies. Testing on cell culture monolayers is a common step in the elucidation of food allergen sensitization. In the case of cysteine proteases, an additional activation step with l-cysteine is required before the testing. Hence, we aimed to evaluate whether l-cysteine already present in commonly used cell culture media would suffice for Act d 1 activation. Successfully activated Act d 1 (98.1% of proteolytic activity, as compared to l-cysteine activated Act d 1) was further tested in two commonly used 2D model systems (Caco-2 and HEK293 cells) to evaluate its role on the mRNA expression of cytokines involved in the innate immunity (IL-1β, IL-6, TNFα, TSLP). Furthermore, the contribution of Act d 1 in the promotion of inflammation through regulation of inducible nitric oxide synthase (iNOS) mRNA expression was also examined. These results demonstrate that activation of cysteine proteases can be achieved without previous enzyme incubation in l-cysteine -containing solution. Act d 1 incubated in cell culture medium was able to modulate gene expression of pro-inflammatory cytokines when tested on two model systems of the epithelial barrier. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.
PB  - Springer Nature
T2  - Molecular Biology Reports
T1  - A new approach for activation of the kiwifruit cysteine protease for usage in in-vitro testing
VL  - 48
IS  - 5
SP  - 4065
EP  - 4072
DO  - 10.1007/s11033-021-06416-8
ER  - 

@article{
author = "Nešić, Andrijana N. and Čavić, Milena and Popović, Milica M. and Gavrović-Jankulović, Marija",
year = "2021",
abstract = "Actinidin (Act d 1), a highly abundant cysteine protease from kiwifruit, is one of the major contributors to the development of kiwifruit allergy. Many studies have focused on the optimization of Act d 1 purification and its role in the development of food allergies. Testing on cell culture monolayers is a common step in the elucidation of food allergen sensitization. In the case of cysteine proteases, an additional activation step with l-cysteine is required before the testing. Hence, we aimed to evaluate whether l-cysteine already present in commonly used cell culture media would suffice for Act d 1 activation. Successfully activated Act d 1 (98.1% of proteolytic activity, as compared to l-cysteine activated Act d 1) was further tested in two commonly used 2D model systems (Caco-2 and HEK293 cells) to evaluate its role on the mRNA expression of cytokines involved in the innate immunity (IL-1β, IL-6, TNFα, TSLP). Furthermore, the contribution of Act d 1 in the promotion of inflammation through regulation of inducible nitric oxide synthase (iNOS) mRNA expression was also examined. These results demonstrate that activation of cysteine proteases can be achieved without previous enzyme incubation in l-cysteine -containing solution. Act d 1 incubated in cell culture medium was able to modulate gene expression of pro-inflammatory cytokines when tested on two model systems of the epithelial barrier. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.",
publisher = "Springer Nature",
journal = "Molecular Biology Reports",
title = "A new approach for activation of the kiwifruit cysteine protease for usage in in-vitro testing",
volume = "48",
number = "5",
pages = "4065-4072",
doi = "10.1007/s11033-021-06416-8"
}

Nešić, A. N., Čavić, M., Popović, M. M.,& Gavrović-Jankulović, M.. (2021). A new approach for activation of the kiwifruit cysteine protease for usage in in-vitro testing. in Molecular Biology Reports
Springer Nature., 48(5), 4065-4072.
https://doi.org/10.1007/s11033-021-06416-8

Nešić AN, Čavić M, Popović MM, Gavrović-Jankulović M. A new approach for activation of the kiwifruit cysteine protease for usage in in-vitro testing. in Molecular Biology Reports. 2021;48(5):4065-4072.
doi:10.1007/s11033-021-06416-8 .

Nešić, Andrijana N., Čavić, Milena, Popović, Milica M., Gavrović-Jankulović, Marija, "A new approach for activation of the kiwifruit cysteine protease for usage in in-vitro testing" in Molecular Biology Reports, 48, no. 5 (2021):4065-4072,
https://doi.org/10.1007/s11033-021-06416-8 . .

TY  - JOUR
AU  - Nešić, Andrijana N.
AU  - Čavić, Milena
AU  - Popović, Milica M.
AU  - Zlatanova, Milena
AU  - Pieters, Raymond
AU  - Smit, Joost
AU  - Gavrović-Jankulović, Marija
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3799
AB  - Impairment of the intestinal barrier is one of the key events in the initiation of the sensitization process in food allergy. The aim of this study was to explore the effects of kiwifruit allergen Act d 1 on intestinal permeability and tight junction protein (TJP) gene expression in vivo and to explore its potential to activate the NF-ĸB signaling pathway and to regulate expression of epithelial pro-allergenic cytokines. Influences of Act d 1 on TJP gene expression and pro-allergenic cytokines in the mouse intestine was analyzed by qPCR upon allergen administration by oral gavage. The effect on the in vivo intestinal permeability was assessed in ELISA by measuring the translocation of β-lactoglobulin (BLG) into circulation. The capacity of Act d 1 to activate the NF-ĸB pathway was tested in HEK293 cells by fluorescent microscopy and flow cytometry. Administration of Actinidin (Act d 1) increased intestinal permeability to the BLG. This was accompanied by changes in gene expression of TJP mRNA and pro-allergenic cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) compared to the control. Act d 1 reduced TEER of the HEK293 monolayer, was positive in an NF-ĸB-reporter HEK293 cell assay, and induced secretion of TSLP. These findings shed more light on the molecular events in the sensitization process of kiwifruit but possibly also of other protease food allergens.
PB  - MDPI
T2  - Biomolecules
T1  - The kiwifruit allergen act d 1 activates NF-κB signaling and affects mRNA expression of TJ proteins and innate pro-allergenic cytokines
VL  - 9
IS  - 12
SP  - 816
DO  - 10.3390/biom9120816
ER  - 

@article{
author = "Nešić, Andrijana N. and Čavić, Milena and Popović, Milica M. and Zlatanova, Milena and Pieters, Raymond and Smit, Joost and Gavrović-Jankulović, Marija",
year = "2019",
abstract = "Impairment of the intestinal barrier is one of the key events in the initiation of the sensitization process in food allergy. The aim of this study was to explore the effects of kiwifruit allergen Act d 1 on intestinal permeability and tight junction protein (TJP) gene expression in vivo and to explore its potential to activate the NF-ĸB signaling pathway and to regulate expression of epithelial pro-allergenic cytokines. Influences of Act d 1 on TJP gene expression and pro-allergenic cytokines in the mouse intestine was analyzed by qPCR upon allergen administration by oral gavage. The effect on the in vivo intestinal permeability was assessed in ELISA by measuring the translocation of β-lactoglobulin (BLG) into circulation. The capacity of Act d 1 to activate the NF-ĸB pathway was tested in HEK293 cells by fluorescent microscopy and flow cytometry. Administration of Actinidin (Act d 1) increased intestinal permeability to the BLG. This was accompanied by changes in gene expression of TJP mRNA and pro-allergenic cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) compared to the control. Act d 1 reduced TEER of the HEK293 monolayer, was positive in an NF-ĸB-reporter HEK293 cell assay, and induced secretion of TSLP. These findings shed more light on the molecular events in the sensitization process of kiwifruit but possibly also of other protease food allergens.",
publisher = "MDPI",
journal = "Biomolecules",
title = "The kiwifruit allergen act d 1 activates NF-κB signaling and affects mRNA expression of TJ proteins and innate pro-allergenic cytokines",
volume = "9",
number = "12",
pages = "816",
doi = "10.3390/biom9120816"
}

Nešić, A. N., Čavić, M., Popović, M. M., Zlatanova, M., Pieters, R., Smit, J.,& Gavrović-Jankulović, M.. (2019). The kiwifruit allergen act d 1 activates NF-κB signaling and affects mRNA expression of TJ proteins and innate pro-allergenic cytokines. in Biomolecules
MDPI., 9(12), 816.
https://doi.org/10.3390/biom9120816

Nešić AN, Čavić M, Popović MM, Zlatanova M, Pieters R, Smit J, Gavrović-Jankulović M. The kiwifruit allergen act d 1 activates NF-κB signaling and affects mRNA expression of TJ proteins and innate pro-allergenic cytokines. in Biomolecules. 2019;9(12):816.
doi:10.3390/biom9120816 .

Nešić, Andrijana N., Čavić, Milena, Popović, Milica M., Zlatanova, Milena, Pieters, Raymond, Smit, Joost, Gavrović-Jankulović, Marija, "The kiwifruit allergen act d 1 activates NF-κB signaling and affects mRNA expression of TJ proteins and innate pro-allergenic cytokines" in Biomolecules, 9, no. 12 (2019):816,
https://doi.org/10.3390/biom9120816 . .

TY  - JOUR
AU  - Nešić, Andrijana N.
AU  - Stam, Annemarie
AU  - Čavić, Milena
AU  - Ten Klooster, Jean Paul
AU  - Pieters, Raymond
AU  - Smit, Joost
AU  - Gavrović-Jankulović, Marija
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3485
AB  - In this study, two intestinal models were employed to assess the modulatory potential of a major kiwifruit allergen on the innate immunity of epithelial cells. Effects of Act d 1 were analyzed in terms of gene expression and structural changes of tight junction (TJ) proteins, as well as up-regulation of pro-inflammatory cytokines in Caco-2 cells and, for the first time, in mouse-derived intestinal 2-dimensional (2D) organoids.

Biologically active Act d 1 induced up-regulation of TJ genes for CLDN-2, CLDN-3, CLDN-4, ZO-1, and on the protein level induced release of pro-inflammatory cytokines IL-1β, TNFα and IL-33 in both employed model systems. In 2D-organoids, active Act d 1 impaired the TJ protein networks of E-cadherin, claudin-3, and ZO-1.

2D-organoids generated from mouse intestine are a promising new model system for the assessment of allergen-induced intestinal cell responses and a useful tool for mitigation of risks associated with novel food proteins.
T2  - Journal of Functional Foods
T1  - Activation of epithelial cells by the major kiwifruit allergen Act d 1 in human and mouse-derived intestinal model
VL  - 62
DO  - 10.1016/j.jff.2019.103556
ER  - 

@article{
author = "Nešić, Andrijana N. and Stam, Annemarie and Čavić, Milena and Ten Klooster, Jean Paul and Pieters, Raymond and Smit, Joost and Gavrović-Jankulović, Marija",
year = "2019",
abstract = "In this study, two intestinal models were employed to assess the modulatory potential of a major kiwifruit allergen on the innate immunity of epithelial cells. Effects of Act d 1 were analyzed in terms of gene expression and structural changes of tight junction (TJ) proteins, as well as up-regulation of pro-inflammatory cytokines in Caco-2 cells and, for the first time, in mouse-derived intestinal 2-dimensional (2D) organoids.

Biologically active Act d 1 induced up-regulation of TJ genes for CLDN-2, CLDN-3, CLDN-4, ZO-1, and on the protein level induced release of pro-inflammatory cytokines IL-1β, TNFα and IL-33 in both employed model systems. In 2D-organoids, active Act d 1 impaired the TJ protein networks of E-cadherin, claudin-3, and ZO-1.

2D-organoids generated from mouse intestine are a promising new model system for the assessment of allergen-induced intestinal cell responses and a useful tool for mitigation of risks associated with novel food proteins.",
journal = "Journal of Functional Foods",
title = "Activation of epithelial cells by the major kiwifruit allergen Act d 1 in human and mouse-derived intestinal model",
volume = "62",
doi = "10.1016/j.jff.2019.103556"
}

Nešić, A. N., Stam, A., Čavić, M., Ten Klooster, J. P., Pieters, R., Smit, J.,& Gavrović-Jankulović, M.. (2019). Activation of epithelial cells by the major kiwifruit allergen Act d 1 in human and mouse-derived intestinal model. in Journal of Functional Foods, 62.
https://doi.org/10.1016/j.jff.2019.103556

Nešić AN, Stam A, Čavić M, Ten Klooster JP, Pieters R, Smit J, Gavrović-Jankulović M. Activation of epithelial cells by the major kiwifruit allergen Act d 1 in human and mouse-derived intestinal model. in Journal of Functional Foods. 2019;62.
doi:10.1016/j.jff.2019.103556 .

Nešić, Andrijana N., Stam, Annemarie, Čavić, Milena, Ten Klooster, Jean Paul, Pieters, Raymond, Smit, Joost, Gavrović-Jankulović, Marija, "Activation of epithelial cells by the major kiwifruit allergen Act d 1 in human and mouse-derived intestinal model" in Journal of Functional Foods, 62 (2019),
https://doi.org/10.1016/j.jff.2019.103556 . .

TY  - JOUR
AU  - Nikolić, Jasna
AU  - Nešić, Andrijana N.
AU  - Čavić, Milena
AU  - Đorđević, Neda O.
AU  - Anđelković, Uroš
AU  - Atanasković-Marković, Marina
AU  - Drakulić, Branko J.
AU  - Gavrović-Jankulović, Marija
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2384
AB  - Background: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity. (C) 2016 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Biochimica et Biophysica Acta: General Subjects
T1  - Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells
VL  - 1861
IS  - 2
SP  - 126
EP  - 134
DO  - 10.1016/j.bbagen.2016.11.021
ER  - 

@article{
author = "Nikolić, Jasna and Nešić, Andrijana N. and Čavić, Milena and Đorđević, Neda O. and Anđelković, Uroš and Atanasković-Marković, Marina and Drakulić, Branko J. and Gavrović-Jankulović, Marija",
year = "2017",
abstract = "Background: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity. (C) 2016 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Biochimica et Biophysica Acta: General Subjects",
title = "Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells",
volume = "1861",
number = "2",
pages = "126-134",
doi = "10.1016/j.bbagen.2016.11.021"
}

Nikolić, J., Nešić, A. N., Čavić, M., Đorđević, N. O., Anđelković, U., Atanasković-Marković, M., Drakulić, B. J.,& Gavrović-Jankulović, M.. (2017). Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells. in Biochimica et Biophysica Acta: General Subjects
Elsevier Science Bv, Amsterdam., 1861(2), 126-134.
https://doi.org/10.1016/j.bbagen.2016.11.021

Nikolić J, Nešić AN, Čavić M, Đorđević NO, Anđelković U, Atanasković-Marković M, Drakulić BJ, Gavrović-Jankulović M. Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells. in Biochimica et Biophysica Acta: General Subjects. 2017;1861(2):126-134.
doi:10.1016/j.bbagen.2016.11.021 .

Nikolić, Jasna, Nešić, Andrijana N., Čavić, Milena, Đorđević, Neda O., Anđelković, Uroš, Atanasković-Marković, Marina, Drakulić, Branko J., Gavrović-Jankulović, Marija, "Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells" in Biochimica et Biophysica Acta: General Subjects, 1861, no. 2 (2017):126-134,
https://doi.org/10.1016/j.bbagen.2016.11.021 . .

TY  - JOUR
AU  - Nikolić, Jasna
AU  - Nešić, Andrijana N.
AU  - Čavić, Milena
AU  - Đorđević, Neda O.
AU  - Anđelković, Uroš
AU  - Atanasković-Marković, Marina
AU  - Drakulić, Branko J.
AU  - Gavrović-Jankulović, Marija
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2384
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2954
AB  - ackground: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity. (C) 2016 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Biochimica et Biophysica Acta: General Subjects
T1  - Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells
VL  - 1861
IS  - 2
SP  - 126
EP  - 134
DO  - 10.1016/j.bbagen.2016.11.021
ER  - 

@article{
author = "Nikolić, Jasna and Nešić, Andrijana N. and Čavić, Milena and Đorđević, Neda O. and Anđelković, Uroš and Atanasković-Marković, Marina and Drakulić, Branko J. and Gavrović-Jankulović, Marija",
year = "2017",
abstract = "ackground: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity. (C) 2016 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Biochimica et Biophysica Acta: General Subjects",
title = "Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells",
volume = "1861",
number = "2",
pages = "126-134",
doi = "10.1016/j.bbagen.2016.11.021"
}

Nikolić, J., Nešić, A. N., Čavić, M., Đorđević, N. O., Anđelković, U., Atanasković-Marković, M., Drakulić, B. J.,& Gavrović-Jankulović, M.. (2017). Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells. in Biochimica et Biophysica Acta: General Subjects
Elsevier Science Bv, Amsterdam., 1861(2), 126-134.
https://doi.org/10.1016/j.bbagen.2016.11.021

Nikolić J, Nešić AN, Čavić M, Đorđević NO, Anđelković U, Atanasković-Marković M, Drakulić BJ, Gavrović-Jankulović M. Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells. in Biochimica et Biophysica Acta: General Subjects. 2017;1861(2):126-134.
doi:10.1016/j.bbagen.2016.11.021 .

Nikolić, Jasna, Nešić, Andrijana N., Čavić, Milena, Đorđević, Neda O., Anđelković, Uroš, Atanasković-Marković, Marina, Drakulić, Branko J., Gavrović-Jankulović, Marija, "Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells" in Biochimica et Biophysica Acta: General Subjects, 1861, no. 2 (2017):126-134,
https://doi.org/10.1016/j.bbagen.2016.11.021 . .

TY  - JOUR
AU  - Grozdanović, Milica M.
AU  - Čavić, Milena
AU  - Nešić, Andrijana N.
AU  - Anđelković, Uroš
AU  - Akbari, Peyman
AU  - Smit, Joost
AU  - Gavrović-Jankulović, Marija
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2039
AB  - Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Biochimica et Biophysica Acta: General Subjects
T1  - Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions
VL  - 1860
IS  - 3
SP  - 516
EP  - 526
DO  - 10.1016/j.bbagen.2015.12.005
ER  - 

@article{
author = "Grozdanović, Milica M. and Čavić, Milena and Nešić, Andrijana N. and Anđelković, Uroš and Akbari, Peyman and Smit, Joost and Gavrović-Jankulović, Marija",
year = "2016",
abstract = "Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Biochimica et Biophysica Acta: General Subjects",
title = "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions",
volume = "1860",
number = "3",
pages = "516-526",
doi = "10.1016/j.bbagen.2015.12.005"
}

Grozdanović, M. M., Čavić, M., Nešić, A. N., Anđelković, U., Akbari, P., Smit, J.,& Gavrović-Jankulović, M.. (2016). Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects
Elsevier Science Bv, Amsterdam., 1860(3), 516-526.
https://doi.org/10.1016/j.bbagen.2015.12.005

Grozdanović MM, Čavić M, Nešić AN, Anđelković U, Akbari P, Smit J, Gavrović-Jankulović M. Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects. 2016;1860(3):516-526.
doi:10.1016/j.bbagen.2015.12.005 .

Grozdanović, Milica M., Čavić, Milena, Nešić, Andrijana N., Anđelković, Uroš, Akbari, Peyman, Smit, Joost, Gavrović-Jankulović, Marija, "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions" in Biochimica et Biophysica Acta: General Subjects, 1860, no. 3 (2016):516-526,
https://doi.org/10.1016/j.bbagen.2015.12.005 . .

TY  - JOUR
AU  - Grozdanović, Milica M.
AU  - Čavić, Milena
AU  - Nešić, Andrijana N.
AU  - Anđelković, Uroš
AU  - Akbari, Peyman
AU  - Smit, Joost
AU  - Gavrović-Jankulović, Marija
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3559
AB  - Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Biochimica et Biophysica Acta: General Subjects
T1  - Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions
VL  - 1860
IS  - 3
SP  - 516
EP  - 526
DO  - 10.1016/j.bbagen.2015.12.005
ER  - 

@article{
author = "Grozdanović, Milica M. and Čavić, Milena and Nešić, Andrijana N. and Anđelković, Uroš and Akbari, Peyman and Smit, Joost and Gavrović-Jankulović, Marija",
year = "2016",
abstract = "Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Biochimica et Biophysica Acta: General Subjects",
title = "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions",
volume = "1860",
number = "3",
pages = "516-526",
doi = "10.1016/j.bbagen.2015.12.005"
}

Grozdanović, M. M., Čavić, M., Nešić, A. N., Anđelković, U., Akbari, P., Smit, J.,& Gavrović-Jankulović, M.. (2016). Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects
Elsevier Science Bv, Amsterdam., 1860(3), 516-526.
https://doi.org/10.1016/j.bbagen.2015.12.005

Grozdanović MM, Čavić M, Nešić AN, Anđelković U, Akbari P, Smit J, Gavrović-Jankulović M. Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects. 2016;1860(3):516-526.
doi:10.1016/j.bbagen.2015.12.005 .

Grozdanović, Milica M., Čavić, Milena, Nešić, Andrijana N., Anđelković, Uroš, Akbari, Peyman, Smit, Joost, Gavrović-Jankulović, Marija, "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions" in Biochimica et Biophysica Acta: General Subjects, 1860, no. 3 (2016):516-526,
https://doi.org/10.1016/j.bbagen.2015.12.005 . .

TY  - JOUR
AU  - Čavić, Milena
AU  - Grozdanović, Milica M.
AU  - Bajić, Aleksandar
AU  - Jankovic, Radmila
AU  - Andjus, Pavle R.
AU  - Gavrović-Jankulović, Marija
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1866
AB  - Actinidin, a kiwifruit cysteine protease, is a marker allergen for genuine sensitization to this food allergen source. Inhalatory cysteine proteases have the capacity for disruption of tight junctions (TJs) enhancing the permeability of the bronchial epithelium. No such properties have been reported for allergenic food proteases so far. The aim was to determine the effect of actinidin on the integrity of T84 monolayers by evaluating its action on the TJ protein occludin. Immunoblot and immunofluorescence were employed for the detection of occludin protein alterations. Gene expression was evaluated by RT-PCR. Breach of occludin network was assessed by measuring transepithelial resistance, blue dextran leakage and passage of allergens from the apical to basolateral compartment. Actinidin exerted direct proteolytic cleavage of occludin; no alteration of occludin gene expression was detected. There was a reduction of occludin staining upon actinidin treatment as a consequence of its degradation and dispersion within the membrane. There was an increase in permeability of the T84 monolayer resulting in reduced transepithelial resistance, blue dextran leakage and passage of allergens actinidin and thaumatin-like protein from the apical to basolateral compartment. Opening of TJs by actinidin may increase intestinal permeability and contribute to the process of sensitization in kiwifruit allergy. (C) 2014 Elsevier Ltd. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Food and Chemical Toxicology
T1  - The effect of kiwifruit (Actinidia deliciosa) cysteine protease actinidin on the occludin tight junction network in T84 intestinal epithelial cells
VL  - 72
SP  - 61
EP  - 68
DO  - 10.1016/j.fct.2014.07.012
ER  - 

@article{
author = "Čavić, Milena and Grozdanović, Milica M. and Bajić, Aleksandar and Jankovic, Radmila and Andjus, Pavle R. and Gavrović-Jankulović, Marija",
year = "2014",
abstract = "Actinidin, a kiwifruit cysteine protease, is a marker allergen for genuine sensitization to this food allergen source. Inhalatory cysteine proteases have the capacity for disruption of tight junctions (TJs) enhancing the permeability of the bronchial epithelium. No such properties have been reported for allergenic food proteases so far. The aim was to determine the effect of actinidin on the integrity of T84 monolayers by evaluating its action on the TJ protein occludin. Immunoblot and immunofluorescence were employed for the detection of occludin protein alterations. Gene expression was evaluated by RT-PCR. Breach of occludin network was assessed by measuring transepithelial resistance, blue dextran leakage and passage of allergens from the apical to basolateral compartment. Actinidin exerted direct proteolytic cleavage of occludin; no alteration of occludin gene expression was detected. There was a reduction of occludin staining upon actinidin treatment as a consequence of its degradation and dispersion within the membrane. There was an increase in permeability of the T84 monolayer resulting in reduced transepithelial resistance, blue dextran leakage and passage of allergens actinidin and thaumatin-like protein from the apical to basolateral compartment. Opening of TJs by actinidin may increase intestinal permeability and contribute to the process of sensitization in kiwifruit allergy. (C) 2014 Elsevier Ltd. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Food and Chemical Toxicology",
title = "The effect of kiwifruit (Actinidia deliciosa) cysteine protease actinidin on the occludin tight junction network in T84 intestinal epithelial cells",
volume = "72",
pages = "61-68",
doi = "10.1016/j.fct.2014.07.012"
}

Čavić, M., Grozdanović, M. M., Bajić, A., Jankovic, R., Andjus, P. R.,& Gavrović-Jankulović, M.. (2014). The effect of kiwifruit (Actinidia deliciosa) cysteine protease actinidin on the occludin tight junction network in T84 intestinal epithelial cells. in Food and Chemical Toxicology
Pergamon-Elsevier Science Ltd, Oxford., 72, 61-68.
https://doi.org/10.1016/j.fct.2014.07.012

Čavić M, Grozdanović MM, Bajić A, Jankovic R, Andjus PR, Gavrović-Jankulović M. The effect of kiwifruit (Actinidia deliciosa) cysteine protease actinidin on the occludin tight junction network in T84 intestinal epithelial cells. in Food and Chemical Toxicology. 2014;72:61-68.
doi:10.1016/j.fct.2014.07.012 .

Čavić, Milena, Grozdanović, Milica M., Bajić, Aleksandar, Jankovic, Radmila, Andjus, Pavle R., Gavrović-Jankulović, Marija, "The effect of kiwifruit (Actinidia deliciosa) cysteine protease actinidin on the occludin tight junction network in T84 intestinal epithelial cells" in Food and Chemical Toxicology, 72 (2014):61-68,
https://doi.org/10.1016/j.fct.2014.07.012 . .

TY  - JOUR
AU  - Čavić, Milena
AU  - Grozdanović, Milica
AU  - Bajić, Aleksandar
AU  - Srdić-Rajić, Tatjana
AU  - Andjus, Pavle R.
AU  - Gavrović-Jankulović, Marija
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1284
AB  - Actinidin belongs to the papain-like family of cysteine proteases and is a major kiwifruit allergen. In this study, the effect of actinidin on cellular morphology and adhesion of T84 intestinal cells was investigated. Both rounding and detachment of T84 cells were observed upon actinidin treatment. The morphological changes and cell desquamation was protease-dependent, as well as time- and concentration-dependent. Changes of intercellular adhesion and adhesion of epithelial cells to collagen upon actinidin treatment could be responsible for the cell rounding and give rise to discontinuous breaches in the epithelial monolayer observed in this study. Actinidin's action on cell morphology, adhesion and monolayer integrity were not due to compromised viability of T84 epithelial cells, as confirmed by MTT assay and flow cytometric analysis of the cell cycle. Damage to the epithelial monolayer of the intestine induced by actinidin should be further evaluated as an important factor in the development of kiwifruit allergy and other intestinal disorders.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Phytochemistry
T1  - Actinidin, a protease from kiwifruit, induces changes in morphology and adhesion of T84 intestinal epithelial cells
VL  - 77
SP  - 46
EP  - 52
DO  - 10.1016/j.phytochem.2011.12.014
ER  - 

@article{
author = "Čavić, Milena and Grozdanović, Milica and Bajić, Aleksandar and Srdić-Rajić, Tatjana and Andjus, Pavle R. and Gavrović-Jankulović, Marija",
year = "2012",
abstract = "Actinidin belongs to the papain-like family of cysteine proteases and is a major kiwifruit allergen. In this study, the effect of actinidin on cellular morphology and adhesion of T84 intestinal cells was investigated. Both rounding and detachment of T84 cells were observed upon actinidin treatment. The morphological changes and cell desquamation was protease-dependent, as well as time- and concentration-dependent. Changes of intercellular adhesion and adhesion of epithelial cells to collagen upon actinidin treatment could be responsible for the cell rounding and give rise to discontinuous breaches in the epithelial monolayer observed in this study. Actinidin's action on cell morphology, adhesion and monolayer integrity were not due to compromised viability of T84 epithelial cells, as confirmed by MTT assay and flow cytometric analysis of the cell cycle. Damage to the epithelial monolayer of the intestine induced by actinidin should be further evaluated as an important factor in the development of kiwifruit allergy and other intestinal disorders.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Phytochemistry",
title = "Actinidin, a protease from kiwifruit, induces changes in morphology and adhesion of T84 intestinal epithelial cells",
volume = "77",
pages = "46-52",
doi = "10.1016/j.phytochem.2011.12.014"
}

Čavić, M., Grozdanović, M., Bajić, A., Srdić-Rajić, T., Andjus, P. R.,& Gavrović-Jankulović, M.. (2012). Actinidin, a protease from kiwifruit, induces changes in morphology and adhesion of T84 intestinal epithelial cells. in Phytochemistry
Pergamon-Elsevier Science Ltd, Oxford., 77, 46-52.
https://doi.org/10.1016/j.phytochem.2011.12.014

Čavić M, Grozdanović M, Bajić A, Srdić-Rajić T, Andjus PR, Gavrović-Jankulović M. Actinidin, a protease from kiwifruit, induces changes in morphology and adhesion of T84 intestinal epithelial cells. in Phytochemistry. 2012;77:46-52.
doi:10.1016/j.phytochem.2011.12.014 .

Čavić, Milena, Grozdanović, Milica, Bajić, Aleksandar, Srdić-Rajić, Tatjana, Andjus, Pavle R., Gavrović-Jankulović, Marija, "Actinidin, a protease from kiwifruit, induces changes in morphology and adhesion of T84 intestinal epithelial cells" in Phytochemistry, 77 (2012):46-52,
https://doi.org/10.1016/j.phytochem.2011.12.014 . .

TY  - CONF
AU  - Gavrović-Jankulović, Marija
AU  - Čavić, Milena
AU  - Grozdanović, M.
AU  - Cavic, D.
AU  - Jankovic, R.
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1526
PB  - Wiley-Blackwell, Hoboken
C3  - FEBS Journal / Federation of European of Biochemical Societies
T1  - The effect of kiwifruit cysteine protease actinidin on the epithelial integrity and the expression of proinflammatory cytokines in T84 human colonic cells
VL  - 279
SP  - 304
EP  - 304
UR  - https://hdl.handle.net/21.15107/rcub_cherry_1526
ER  - 

@conference{
author = "Gavrović-Jankulović, Marija and Čavić, Milena and Grozdanović, M. and Cavic, D. and Jankovic, R.",
year = "2012",
publisher = "Wiley-Blackwell, Hoboken",
journal = "FEBS Journal / Federation of European of Biochemical Societies",
title = "The effect of kiwifruit cysteine protease actinidin on the epithelial integrity and the expression of proinflammatory cytokines in T84 human colonic cells",
volume = "279",
pages = "304-304",
url = "https://hdl.handle.net/21.15107/rcub_cherry_1526"
}

Gavrović-Jankulović, M., Čavić, M., Grozdanović, M., Cavic, D.,& Jankovic, R.. (2012). The effect of kiwifruit cysteine protease actinidin on the epithelial integrity and the expression of proinflammatory cytokines in T84 human colonic cells. in FEBS Journal / Federation of European of Biochemical Societies
Wiley-Blackwell, Hoboken., 279, 304-304.
https://hdl.handle.net/21.15107/rcub_cherry_1526

Gavrović-Jankulović M, Čavić M, Grozdanović M, Cavic D, Jankovic R. The effect of kiwifruit cysteine protease actinidin on the epithelial integrity and the expression of proinflammatory cytokines in T84 human colonic cells. in FEBS Journal / Federation of European of Biochemical Societies. 2012;279:304-304.
https://hdl.handle.net/21.15107/rcub_cherry_1526 .

Gavrović-Jankulović, Marija, Čavić, Milena, Grozdanović, M., Cavic, D., Jankovic, R., "The effect of kiwifruit cysteine protease actinidin on the epithelial integrity and the expression of proinflammatory cytokines in T84 human colonic cells" in FEBS Journal / Federation of European of Biochemical Societies, 279 (2012):304-304,
https://hdl.handle.net/21.15107/rcub_cherry_1526 .

TY  - CONF
AU  - Čavić, Milena
AU  - Bajić, A.
AU  - Grozdanović, M.
AU  - Cavic, D.
AU  - Jakovljević, Ksenija
AU  - Andjus, P.
AU  - Gavrović-Jankulović, Marija
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1543
PB  - Wiley-Blackwell, Hoboken
C3  - Allergy
T1  - Kiwifruit allergen actinidin disrupts the epithelial monolayer integrity of human intestinal T84 cells
VL  - 67
SP  - 602
EP  - 603
UR  - https://hdl.handle.net/21.15107/rcub_cherry_1543
ER  - 

@conference{
author = "Čavić, Milena and Bajić, A. and Grozdanović, M. and Cavic, D. and Jakovljević, Ksenija and Andjus, P. and Gavrović-Jankulović, Marija",
year = "2012",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Allergy",
title = "Kiwifruit allergen actinidin disrupts the epithelial monolayer integrity of human intestinal T84 cells",
volume = "67",
pages = "602-603",
url = "https://hdl.handle.net/21.15107/rcub_cherry_1543"
}

Čavić, M., Bajić, A., Grozdanović, M., Cavic, D., Jakovljević, K., Andjus, P.,& Gavrović-Jankulović, M.. (2012). Kiwifruit allergen actinidin disrupts the epithelial monolayer integrity of human intestinal T84 cells. in Allergy
Wiley-Blackwell, Hoboken., 67, 602-603.
https://hdl.handle.net/21.15107/rcub_cherry_1543

Čavić M, Bajić A, Grozdanović M, Cavic D, Jakovljević K, Andjus P, Gavrović-Jankulović M. Kiwifruit allergen actinidin disrupts the epithelial monolayer integrity of human intestinal T84 cells. in Allergy. 2012;67:602-603.
https://hdl.handle.net/21.15107/rcub_cherry_1543 .

Čavić, Milena, Bajić, A., Grozdanović, M., Cavic, D., Jakovljević, Ksenija, Andjus, P., Gavrović-Jankulović, Marija, "Kiwifruit allergen actinidin disrupts the epithelial monolayer integrity of human intestinal T84 cells" in Allergy, 67 (2012):602-603,
https://hdl.handle.net/21.15107/rcub_cherry_1543 .