TY  - CONF
AU  - Bisenić, Aleksandar
AU  - Tomić, Sergej
AU  - Bekić, Marina
AU  - Pavlović, Luka
AU  - Dinić, Miroslav
AU  - Terzić- Vidojević, Amarela
AU  - Radojević, Dušan
AU  - Soković Bajić, Svetlana
AU  - Mitrović, Hristina
AU  - Jakovljević, Stefan
AU  - Stevanović, Dušan
AU  - Golić, Nataša
AU  - Đokić, Jelena
PY  - 2024
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2374
AB  - Alterations in gut microbiota and deregulation
of the gut immune system are recognized
as important events in autoimmune diseases.
The knowledge about the important role of anaerobic
gut bacteria that produce short-chain
fatty acids (SCFAs), in the regulation of intestinal
barrier and immune response made a way
for the development of microbiota-based interventions.
Our research aimed to isolate the
strains with the potential to produce SCFAs,
from healthy volunteer fecal material, and to
test their effects on IL-8 production in the culture
of intestinal epithelial cells (Caco2) as an in
vitro system imitating initial intestinal inflammation,
the effects on the expression of neuronal
activity-regulated genes of Caenorhabditis
elegans, and the effect on the development
of experimental autoimmune encephalomyelitis
(EAE), a mouse model of multiple  sclerosis.
Three isolated butyric acid (BA)-producing
strains, and three acetic acid (AA)-producing
strains diminished the production of IL-8 in Caco-
2 cells treated with IL-1β/TNF-α. Further, all
BA-producing strains stimulated the expression
of important neuro-related genes in C. elegans.
Based on the strongest effects in these
assays an isolate identified as Faecalimonas sp.
NGB245 strain was further tested in EAE model.
The oral treatment of EAE-induced mice with
this strain for 16h per day for 15 days resulted
in alleviated daily clinical scores, maximal
clinical scores, and the duration of the illness
in comparison to the effect of media used for
strain cultivation. These results point to the potential
of NGB245 to modify the gut-brain axis
opening the field for future development of microbiota-
based therapy for the diseases associated
with immune response dysfunctions.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health
T1  - SHORT-CHAIN FATTY ACID-PRODUCING FAECALIMONAS SP. NGB245 STRAIN REGULATES THE EXPRESSION OF NEURONAL ACTIVITY-REGULATED GENES AND ATTENUATES THE SYMPTOMS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
EP  - 116
SP  - 116
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2374
ER  - 

@conference{
author = "Bisenić, Aleksandar and Tomić, Sergej and Bekić, Marina and Pavlović, Luka and Dinić, Miroslav and Terzić- Vidojević, Amarela and Radojević, Dušan and Soković Bajić, Svetlana and Mitrović, Hristina and Jakovljević, Stefan and Stevanović, Dušan and Golić, Nataša and Đokić, Jelena",
year = "2024",
abstract = "Alterations in gut microbiota and deregulation
of the gut immune system are recognized
as important events in autoimmune diseases.
The knowledge about the important role of anaerobic
gut bacteria that produce short-chain
fatty acids (SCFAs), in the regulation of intestinal
barrier and immune response made a way
for the development of microbiota-based interventions.
Our research aimed to isolate the
strains with the potential to produce SCFAs,
from healthy volunteer fecal material, and to
test their effects on IL-8 production in the culture
of intestinal epithelial cells (Caco2) as an in
vitro system imitating initial intestinal inflammation,
the effects on the expression of neuronal
activity-regulated genes of Caenorhabditis
elegans, and the effect on the development
of experimental autoimmune encephalomyelitis
(EAE), a mouse model of multiple  sclerosis.
Three isolated butyric acid (BA)-producing
strains, and three acetic acid (AA)-producing
strains diminished the production of IL-8 in Caco-
2 cells treated with IL-1β/TNF-α. Further, all
BA-producing strains stimulated the expression
of important neuro-related genes in C. elegans.
Based on the strongest effects in these
assays an isolate identified as Faecalimonas sp.
NGB245 strain was further tested in EAE model.
The oral treatment of EAE-induced mice with
this strain for 16h per day for 15 days resulted
in alleviated daily clinical scores, maximal
clinical scores, and the duration of the illness
in comparison to the effect of media used for
strain cultivation. These results point to the potential
of NGB245 to modify the gut-brain axis
opening the field for future development of microbiota-
based therapy for the diseases associated
with immune response dysfunctions.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health",
title = "SHORT-CHAIN FATTY ACID-PRODUCING FAECALIMONAS SP. NGB245 STRAIN REGULATES THE EXPRESSION OF NEURONAL ACTIVITY-REGULATED GENES AND ATTENUATES THE SYMPTOMS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS",
pages = "116-116",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2374"
}

Bisenić, A., Tomić, S., Bekić, M., Pavlović, L., Dinić, M., Terzić- Vidojević, A., Radojević, D., Soković Bajić, S., Mitrović, H., Jakovljević, S., Stevanović, D., Golić, N.,& Đokić, J.. (2024). SHORT-CHAIN FATTY ACID-PRODUCING FAECALIMONAS SP. NGB245 STRAIN REGULATES THE EXPRESSION OF NEURONAL ACTIVITY-REGULATED GENES AND ATTENUATES THE SYMPTOMS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health
Serbian Society for Microbiology., 116-116.
https://hdl.handle.net/21.15107/rcub_imagine_2374

Bisenić A, Tomić S, Bekić M, Pavlović L, Dinić M, Terzić- Vidojević A, Radojević D, Soković Bajić S, Mitrović H, Jakovljević S, Stevanović D, Golić N, Đokić J. SHORT-CHAIN FATTY ACID-PRODUCING FAECALIMONAS SP. NGB245 STRAIN REGULATES THE EXPRESSION OF NEURONAL ACTIVITY-REGULATED GENES AND ATTENUATES THE SYMPTOMS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health. 2024;:116-116.
https://hdl.handle.net/21.15107/rcub_imagine_2374 .

Bisenić, Aleksandar, Tomić, Sergej, Bekić, Marina, Pavlović, Luka, Dinić, Miroslav, Terzić- Vidojević, Amarela, Radojević, Dušan, Soković Bajić, Svetlana, Mitrović, Hristina, Jakovljević, Stefan, Stevanović, Dušan, Golić, Nataša, Đokić, Jelena, "SHORT-CHAIN FATTY ACID-PRODUCING FAECALIMONAS SP. NGB245 STRAIN REGULATES THE EXPRESSION OF NEURONAL ACTIVITY-REGULATED GENES AND ATTENUATES THE SYMPTOMS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS" in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health (2024):116-116,
https://hdl.handle.net/21.15107/rcub_imagine_2374 .

TY  - CONF
AU  - Dinić, Miroslav
AU  - L. Burgess, Jamie
AU  - Lukić, Jovanka
AU  - Catanuto, Paola
AU  - Radojević, Dušan
AU  - Marjanović, Jelena
AU  - Verpile, Rebecca
AU  - R. Thaller, Seth
AU  - Gonzalez, Tammy
AU  - Golić, Nataša
AU  - Tomić- Canić, Marjana
AU  - Strahinić, Ivana
AU  - Pastar, Irena
PY  - 2024
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2378
AB  - Skin microbiome emerged as an important
factor which can balance tissue repair process
and wound healing. Recent evidence suggest
that intracellular bacterial localization could be
associated with the aberrant healing observed
in patients with chronic wounds, while therapeutics
targeting intracellular bacteria remain
limited. Probiotic lactobacilli and their bioactive
lysates (postbiotics) are well known for their role
in maintenance of gut epithelial homeostasis.
Hence, in this study we focused to understand
the mechanisms of cutaneous response to fourteen
postbiotics derived from different lactobacilli
to reduce intracellular Staphylococcus aureus
colonization and promote healing. Latilactobacillus
curvatus BGMK2-41 demonstrated the
most efficient capability to reduce intracellular infection by S. aureus in keratinocytes in vitro and
infection of human skin explants. Reduction of
bacterial number was followed by upregulation
of the expression of antimicrobial response
genes. Furthermore, BGMK2-41 postbiotic treatment
stimulates keratinocyte migration in vitro
and increases expression of anti-inflammatory
cytokine IL-10, promotes wound closure and
strengthens the epidermal barrier via upregulation
of tight junction proteins in a human ex vivo
wound model. Altogether, this study provided
evidence that postbiotics could stimulate fortification
of epithelial barrier to suppress dissemination
of intracellular pathogens which can be
used as a novel approach to treat dermatologic
and wound healing disorders associated with
persistent infections.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health
T1  - HOST-MICROBIOTA INTERPLAY REGULATES EPITHELIAL BARRIER FUNCTION AND WOUND HEALING
EP  - 133
SP  - 133
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2378
ER  - 

@conference{
author = "Dinić, Miroslav and L. Burgess, Jamie and Lukić, Jovanka and Catanuto, Paola and Radojević, Dušan and Marjanović, Jelena and Verpile, Rebecca and R. Thaller, Seth and Gonzalez, Tammy and Golić, Nataša and Tomić- Canić, Marjana and Strahinić, Ivana and Pastar, Irena",
year = "2024",
abstract = "Skin microbiome emerged as an important
factor which can balance tissue repair process
and wound healing. Recent evidence suggest
that intracellular bacterial localization could be
associated with the aberrant healing observed
in patients with chronic wounds, while therapeutics
targeting intracellular bacteria remain
limited. Probiotic lactobacilli and their bioactive
lysates (postbiotics) are well known for their role
in maintenance of gut epithelial homeostasis.
Hence, in this study we focused to understand
the mechanisms of cutaneous response to fourteen
postbiotics derived from different lactobacilli
to reduce intracellular Staphylococcus aureus
colonization and promote healing. Latilactobacillus
curvatus BGMK2-41 demonstrated the
most efficient capability to reduce intracellular infection by S. aureus in keratinocytes in vitro and
infection of human skin explants. Reduction of
bacterial number was followed by upregulation
of the expression of antimicrobial response
genes. Furthermore, BGMK2-41 postbiotic treatment
stimulates keratinocyte migration in vitro
and increases expression of anti-inflammatory
cytokine IL-10, promotes wound closure and
strengthens the epidermal barrier via upregulation
of tight junction proteins in a human ex vivo
wound model. Altogether, this study provided
evidence that postbiotics could stimulate fortification
of epithelial barrier to suppress dissemination
of intracellular pathogens which can be
used as a novel approach to treat dermatologic
and wound healing disorders associated with
persistent infections.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health",
title = "HOST-MICROBIOTA INTERPLAY REGULATES EPITHELIAL BARRIER FUNCTION AND WOUND HEALING",
pages = "133-133",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2378"
}

Dinić, M., L. Burgess, J., Lukić, J., Catanuto, P., Radojević, D., Marjanović, J., Verpile, R., R. Thaller, S., Gonzalez, T., Golić, N., Tomić- Canić, M., Strahinić, I.,& Pastar, I.. (2024). HOST-MICROBIOTA INTERPLAY REGULATES EPITHELIAL BARRIER FUNCTION AND WOUND HEALING. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health
Serbian Society for Microbiology., 133-133.
https://hdl.handle.net/21.15107/rcub_imagine_2378

Dinić M, L. Burgess J, Lukić J, Catanuto P, Radojević D, Marjanović J, Verpile R, R. Thaller S, Gonzalez T, Golić N, Tomić- Canić M, Strahinić I, Pastar I. HOST-MICROBIOTA INTERPLAY REGULATES EPITHELIAL BARRIER FUNCTION AND WOUND HEALING. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health. 2024;:133-133.
https://hdl.handle.net/21.15107/rcub_imagine_2378 .

Dinić, Miroslav, L. Burgess, Jamie, Lukić, Jovanka, Catanuto, Paola, Radojević, Dušan, Marjanović, Jelena, Verpile, Rebecca, R. Thaller, Seth, Gonzalez, Tammy, Golić, Nataša, Tomić- Canić, Marjana, Strahinić, Ivana, Pastar, Irena, "HOST-MICROBIOTA INTERPLAY REGULATES EPITHELIAL BARRIER FUNCTION AND WOUND HEALING" in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health (2024):133-133,
https://hdl.handle.net/21.15107/rcub_imagine_2378 .

TY  - CONF
AU  - Golić, Nataša
AU  - Terzić Vidojević, Amarela
AU  - Tolinački, Maja
AU  - Dinić, Miroslav
AU  - Đokić, Jelena
AU  - Todorović Vukotić, Nevena
AU  - Lukić, Jovanka
AU  - Živković, Milica
AU  - Nastasijević, Branislav
AU  - Soković, Svetlana
AU  - Brdarić, Emilija
AU  - Radojević, Dušan
PY  - 2024
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2372
AB  - There has been an epidemic of various non-communicable
degenerative and autoimmune diseases,
strongly associated with the modern
lifestyle. Among them, neurodegenerative and
psychiatric disorders represent a huge burden on
society. Recently, all these diseases have been associated
with the gut microbiota dysbiosis. Gut
microbiota-host interaction research has been
greatly improved due to development of molecular
high-throughput techniques based on
various ‘omics’ techniques coupled with bioinformatics
and data science developments. However,
the mechanisms of the host–microbiota crosstalk
are still poorly understood. The NextGenBiotics
project proposes an innovative integrative
multi-omics research strategy for deciphering
the mechanism behind the cross-talk among
microbiota and gut-brain-axis. The 118 novel
NGPs candidates belonging to Dorea sp., Blautia
sp., Bacteroides sp., Roseburia sp., Sellimonas
sp., Faecalicatena sp., Phascolarctobacterium faecium,
and Faecalimonas sp. were cultivated. The
25 NGPs with confirmed safe status and potential
probiotic potential were screened in C. elegans
model for their effects on behavioural and neuronal
activity. The most prominent candidates
with ability to upregulate expression of genes
involved in neurotransmiting are further tested
in EAE (an animal model for MS) and CUMS depression
model. The specific microbiota-derived
metabolites have been identified as potential
neuro- and psycho-biotics. The NextGenBiotics is
highly ambitious project, dedicated to pioneering
work in the field of multi-omics studies related
to the cultivation of novel anaerobic NGPs
and the studying of their effect on MGBA. This
concept enabled studying bidirectional communication
between gut microbiota and brain
on the functional level that will significantly
contribute to the growing body data related to
MGBA. The results obtained during NextGenBiotics
determined the genes/metabolites and the
associated mechanisms involved in health-promoting
effects of NGPs in MGBA beyond stateof-
the-art, broadening the scientific knowledge
and opening up the possible novel therapeutic
approaches in prevention and therapy of neurodegenerative
and psychiatric diseases.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health
T1  - THE USE OF INTEGRATIVE MULTI-OMICS APPROACH IN CULTIVATION AND CHARACTERIZATION OF GUT BACTERIA RELATED TO MICROBIOTA-GUT-BRAIN AXIS AS A SOURCE FOR NEXT GENERATION PROBIOTICS
EP  - 106
SP  - 106
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2372
ER  - 

@conference{
author = "Golić, Nataša and Terzić Vidojević, Amarela and Tolinački, Maja and Dinić, Miroslav and Đokić, Jelena and Todorović Vukotić, Nevena and Lukić, Jovanka and Živković, Milica and Nastasijević, Branislav and Soković, Svetlana and Brdarić, Emilija and Radojević, Dušan",
year = "2024",
abstract = "There has been an epidemic of various non-communicable
degenerative and autoimmune diseases,
strongly associated with the modern
lifestyle. Among them, neurodegenerative and
psychiatric disorders represent a huge burden on
society. Recently, all these diseases have been associated
with the gut microbiota dysbiosis. Gut
microbiota-host interaction research has been
greatly improved due to development of molecular
high-throughput techniques based on
various ‘omics’ techniques coupled with bioinformatics
and data science developments. However,
the mechanisms of the host–microbiota crosstalk
are still poorly understood. The NextGenBiotics
project proposes an innovative integrative
multi-omics research strategy for deciphering
the mechanism behind the cross-talk among
microbiota and gut-brain-axis. The 118 novel
NGPs candidates belonging to Dorea sp., Blautia
sp., Bacteroides sp., Roseburia sp., Sellimonas
sp., Faecalicatena sp., Phascolarctobacterium faecium,
and Faecalimonas sp. were cultivated. The
25 NGPs with confirmed safe status and potential
probiotic potential were screened in C. elegans
model for their effects on behavioural and neuronal
activity. The most prominent candidates
with ability to upregulate expression of genes
involved in neurotransmiting are further tested
in EAE (an animal model for MS) and CUMS depression
model. The specific microbiota-derived
metabolites have been identified as potential
neuro- and psycho-biotics. The NextGenBiotics is
highly ambitious project, dedicated to pioneering
work in the field of multi-omics studies related
to the cultivation of novel anaerobic NGPs
and the studying of their effect on MGBA. This
concept enabled studying bidirectional communication
between gut microbiota and brain
on the functional level that will significantly
contribute to the growing body data related to
MGBA. The results obtained during NextGenBiotics
determined the genes/metabolites and the
associated mechanisms involved in health-promoting
effects of NGPs in MGBA beyond stateof-
the-art, broadening the scientific knowledge
and opening up the possible novel therapeutic
approaches in prevention and therapy of neurodegenerative
and psychiatric diseases.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health",
title = "THE USE OF INTEGRATIVE MULTI-OMICS APPROACH IN CULTIVATION AND CHARACTERIZATION OF GUT BACTERIA RELATED TO MICROBIOTA-GUT-BRAIN AXIS AS A SOURCE FOR NEXT GENERATION PROBIOTICS",
pages = "106-106",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2372"
}

Golić, N., Terzić Vidojević, A., Tolinački, M., Dinić, M., Đokić, J., Todorović Vukotić, N., Lukić, J., Živković, M., Nastasijević, B., Soković, S., Brdarić, E.,& Radojević, D.. (2024). THE USE OF INTEGRATIVE MULTI-OMICS APPROACH IN CULTIVATION AND CHARACTERIZATION OF GUT BACTERIA RELATED TO MICROBIOTA-GUT-BRAIN AXIS AS A SOURCE FOR NEXT GENERATION PROBIOTICS. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health
Serbian Society for Microbiology., 106-106.
https://hdl.handle.net/21.15107/rcub_imagine_2372

Golić N, Terzić Vidojević A, Tolinački M, Dinić M, Đokić J, Todorović Vukotić N, Lukić J, Živković M, Nastasijević B, Soković S, Brdarić E, Radojević D. THE USE OF INTEGRATIVE MULTI-OMICS APPROACH IN CULTIVATION AND CHARACTERIZATION OF GUT BACTERIA RELATED TO MICROBIOTA-GUT-BRAIN AXIS AS A SOURCE FOR NEXT GENERATION PROBIOTICS. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health. 2024;:106-106.
https://hdl.handle.net/21.15107/rcub_imagine_2372 .

Golić, Nataša, Terzić Vidojević, Amarela, Tolinački, Maja, Dinić, Miroslav, Đokić, Jelena, Todorović Vukotić, Nevena, Lukić, Jovanka, Živković, Milica, Nastasijević, Branislav, Soković, Svetlana, Brdarić, Emilija, Radojević, Dušan, "THE USE OF INTEGRATIVE MULTI-OMICS APPROACH IN CULTIVATION AND CHARACTERIZATION OF GUT BACTERIA RELATED TO MICROBIOTA-GUT-BRAIN AXIS AS A SOURCE FOR NEXT GENERATION PROBIOTICS" in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health (2024):106-106,
https://hdl.handle.net/21.15107/rcub_imagine_2372 .

TY  - CONF
AU  - Mitrović, Hristina
AU  - Brdarić, Emilija
AU  - Bisenić, Aleksandar
AU  - Jakovljević, Stefan
AU  - Dinić, Miroslav
AU  - Đokić, Jelena
AU  - Terzić-Vidojević, Amarela
AU  - Tolinački, Maja
AU  - Radojević, Dušan
AU  - Golić, Nataša
AU  - Soković Bajić, Svetlana
PY  - 2024
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2389
AB  - Psychobiotics are live bacterial strains impacting the central nervous system, producing
neuroactive substances like GABA. GABA from
microbiota influences neural signals, affecting
neurological parameters, sleep, appetite, mood,
and cognition, traversing the intestinal barrier to bind to receptors on enteric neurons and
the vagus nerve. Lactobacillus and Bifidobacterium species can synthesize GABA from dietary
glutamate, with Lactobacillus rhamnosus shown
to reduce anxiety and depressive behavior, elevating hippocampal GABA. Limited knowledge
exists about anaerobic GABA producers, warranting further research for a comprehensive
understanding. Material for isolation comprised
fecal samples from healthy donors, with isolation conducted in an anaerobic chamber within
a maximum of 1 hour after sampling. Isolated
bacteria were identified through sequencing
the 16S rRNA gene. For bacterial cultivation, different types of media were used. PYG medium
contains hematine and vitamin K, essential supplements for the cultivation of anaerobic bacteria. All media included 0.1% L-cysteine, playing a
role in oxygen reduction, and 0.5% glutamate, a
precursor for GABA production. After identification, the presence of GABA in 8 tested bacterial
species was determined using the TLC method.
Quantification of GABA was performed using the
HPLC method. Furthermore, the positive effects
observed in Caco2 cells with induced inflammation, after treatment with certain anaerobic postbiotics producing GABA, indicate the potential
anti-inflammatory effects of these postbiotics.
The study implies anti-inflammatory effects of
anaerobic GABA producers, offering insights into the complex interplay among gut microbiota,
immune function, and mental health. Recognizing inflammation’s role in depressive symptoms,
targeting anaerobic bacteria involved in GABA
synthesis could modulate neurotransmitters and
inflammatory responses, presenting a comprehensive approach to mental well-being. Advancing research in this area contributes to a holistic
understanding of anaerobic bacteria, GABA production, gut microbiota, and mental health. This
offers avenues for novel therapeutic approaches
and enhances overall quality of life.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health
T1  - FROM GUT TO LAB: UNLOCKING ANTI-INFLAMMATORY POTENTIAL WITH GABA-PRODUCING BACTERIA
EP  - 111
SP  - 111
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2389
ER  - 

@conference{
author = "Mitrović, Hristina and Brdarić, Emilija and Bisenić, Aleksandar and Jakovljević, Stefan and Dinić, Miroslav and Đokić, Jelena and Terzić-Vidojević, Amarela and Tolinački, Maja and Radojević, Dušan and Golić, Nataša and Soković Bajić, Svetlana",
year = "2024",
abstract = "Psychobiotics are live bacterial strains impacting the central nervous system, producing
neuroactive substances like GABA. GABA from
microbiota influences neural signals, affecting
neurological parameters, sleep, appetite, mood,
and cognition, traversing the intestinal barrier to bind to receptors on enteric neurons and
the vagus nerve. Lactobacillus and Bifidobacterium species can synthesize GABA from dietary
glutamate, with Lactobacillus rhamnosus shown
to reduce anxiety and depressive behavior, elevating hippocampal GABA. Limited knowledge
exists about anaerobic GABA producers, warranting further research for a comprehensive
understanding. Material for isolation comprised
fecal samples from healthy donors, with isolation conducted in an anaerobic chamber within
a maximum of 1 hour after sampling. Isolated
bacteria were identified through sequencing
the 16S rRNA gene. For bacterial cultivation, different types of media were used. PYG medium
contains hematine and vitamin K, essential supplements for the cultivation of anaerobic bacteria. All media included 0.1% L-cysteine, playing a
role in oxygen reduction, and 0.5% glutamate, a
precursor for GABA production. After identification, the presence of GABA in 8 tested bacterial
species was determined using the TLC method.
Quantification of GABA was performed using the
HPLC method. Furthermore, the positive effects
observed in Caco2 cells with induced inflammation, after treatment with certain anaerobic postbiotics producing GABA, indicate the potential
anti-inflammatory effects of these postbiotics.
The study implies anti-inflammatory effects of
anaerobic GABA producers, offering insights into the complex interplay among gut microbiota,
immune function, and mental health. Recognizing inflammation’s role in depressive symptoms,
targeting anaerobic bacteria involved in GABA
synthesis could modulate neurotransmitters and
inflammatory responses, presenting a comprehensive approach to mental well-being. Advancing research in this area contributes to a holistic
understanding of anaerobic bacteria, GABA production, gut microbiota, and mental health. This
offers avenues for novel therapeutic approaches
and enhances overall quality of life.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health",
title = "FROM GUT TO LAB: UNLOCKING ANTI-INFLAMMATORY POTENTIAL WITH GABA-PRODUCING BACTERIA",
pages = "111-111",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2389"
}

Mitrović, H., Brdarić, E., Bisenić, A., Jakovljević, S., Dinić, M., Đokić, J., Terzić-Vidojević, A., Tolinački, M., Radojević, D., Golić, N.,& Soković Bajić, S.. (2024). FROM GUT TO LAB: UNLOCKING ANTI-INFLAMMATORY POTENTIAL WITH GABA-PRODUCING BACTERIA. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health
Serbian Society for Microbiology., 111-111.
https://hdl.handle.net/21.15107/rcub_imagine_2389

Mitrović H, Brdarić E, Bisenić A, Jakovljević S, Dinić M, Đokić J, Terzić-Vidojević A, Tolinački M, Radojević D, Golić N, Soković Bajić S. FROM GUT TO LAB: UNLOCKING ANTI-INFLAMMATORY POTENTIAL WITH GABA-PRODUCING BACTERIA. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health. 2024;:111-111.
https://hdl.handle.net/21.15107/rcub_imagine_2389 .

Mitrović, Hristina, Brdarić, Emilija, Bisenić, Aleksandar, Jakovljević, Stefan, Dinić, Miroslav, Đokić, Jelena, Terzić-Vidojević, Amarela, Tolinački, Maja, Radojević, Dušan, Golić, Nataša, Soković Bajić, Svetlana, "FROM GUT TO LAB: UNLOCKING ANTI-INFLAMMATORY POTENTIAL WITH GABA-PRODUCING BACTERIA" in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health (2024):111-111,
https://hdl.handle.net/21.15107/rcub_imagine_2389 .

TY  - JOUR
AU  - Čolić, Miodrag
AU  - Miljuš, Nataša
AU  - Đokić, Jelena
AU  - Bekić, Marina
AU  - Krivokuća, Aleksandra
AU  - Tomić, Sergej
AU  - Radojević, Dušan
AU  - Radanović, Marina
AU  - Eraković, Mile
AU  - Ismaili, Bashkim
AU  - Škrbić, Ranko
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/20/15407
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2167
AB  - Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low—10; high—40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6, MCP-1, GRO-α, RANTES, IP-10, HIF-1α, SDF-1, and HGF but increased the expression of IL-8, TLR3, TGF-β, TGF-β/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES, MMP3, and BMP2 but inhibited TLR2 and GRO-α gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4, HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs. PoPEx also potentiated most genes’ expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions
IS  - 20
SP  - 15407
VL  - 24
DO  - 10.3390/ijms242015407
ER  - 

@article{
author = "Čolić, Miodrag and Miljuš, Nataša and Đokić, Jelena and Bekić, Marina and Krivokuća, Aleksandra and Tomić, Sergej and Radojević, Dušan and Radanović, Marina and Eraković, Mile and Ismaili, Bashkim and Škrbić, Ranko",
year = "2023",
abstract = "Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low—10; high—40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6, MCP-1, GRO-α, RANTES, IP-10, HIF-1α, SDF-1, and HGF but increased the expression of IL-8, TLR3, TGF-β, TGF-β/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES, MMP3, and BMP2 but inhibited TLR2 and GRO-α gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4, HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs. PoPEx also potentiated most genes’ expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions",
number = "20",
pages = "15407",
volume = "24",
doi = "10.3390/ijms242015407"
}

Čolić, M., Miljuš, N., Đokić, J., Bekić, M., Krivokuća, A., Tomić, S., Radojević, D., Radanović, M., Eraković, M., Ismaili, B.,& Škrbić, R.. (2023). Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions. in International Journal of Molecular Sciences, 24(20), 15407.
https://doi.org/10.3390/ijms242015407

Čolić M, Miljuš N, Đokić J, Bekić M, Krivokuća A, Tomić S, Radojević D, Radanović M, Eraković M, Ismaili B, Škrbić R. Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions. in International Journal of Molecular Sciences. 2023;24(20):15407.
doi:10.3390/ijms242015407 .

Čolić, Miodrag, Miljuš, Nataša, Đokić, Jelena, Bekić, Marina, Krivokuća, Aleksandra, Tomić, Sergej, Radojević, Dušan, Radanović, Marina, Eraković, Mile, Ismaili, Bashkim, Škrbić, Ranko, "Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions" in International Journal of Molecular Sciences, 24, no. 20 (2023):15407,
https://doi.org/10.3390/ijms242015407 . .

TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Ilić, Nataša
AU  - Đokić, Jelena
AU  - Stojanović, Dušica
AU  - Vasilev, Saša
AU  - Gruden-Movsesijan, Alisa
AU  - Tomić, Sergej
PY  - 2023
UR  - https://www.microbiota-site.com/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2188
AB  - ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, 
in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes 
suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte 
glycoprotein 
(MOG)-induced experimental autoimmune encephalomyelitis 
(EAE). Additionally, we 
investigated how the changes of gut microbiota associate with EAE and the effects of therapy.
Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 
mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 
post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to 
decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment.
Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory 
cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE 
induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut 
microbiota diversity and preserved the richness of species with immunomodulatory properties.
Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 
together with gut microbiota modification is very promising therapeutic strategy for MS.
C3  - 10th ISM World Congress on Targeting Microbiota
T1  - NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION
EP  - 77
SP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2188
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Ilić, Nataša and Đokić, Jelena and Stojanović, Dušica and Vasilev, Saša and Gruden-Movsesijan, Alisa and Tomić, Sergej",
year = "2023",
abstract = "ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, 
in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes 
suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte 
glycoprotein 
(MOG)-induced experimental autoimmune encephalomyelitis 
(EAE). Additionally, we 
investigated how the changes of gut microbiota associate with EAE and the effects of therapy.
Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 
mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 
post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to 
decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment.
Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory 
cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE 
induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut 
microbiota diversity and preserved the richness of species with immunomodulatory properties.
Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 
together with gut microbiota modification is very promising therapeutic strategy for MS.",
journal = "10th ISM World Congress on Targeting Microbiota",
title = "NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION",
pages = "77-77",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2188"
}

Radojević, D., Bekić, M., Ilić, N., Đokić, J., Stojanović, D., Vasilev, S., Gruden-Movsesijan, A.,& Tomić, S.. (2023). NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION. in 10th ISM World Congress on Targeting Microbiota, 77-77.
https://hdl.handle.net/21.15107/rcub_imagine_2188

Radojević D, Bekić M, Ilić N, Đokić J, Stojanović D, Vasilev S, Gruden-Movsesijan A, Tomić S. NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION. in 10th ISM World Congress on Targeting Microbiota. 2023;:77-77.
https://hdl.handle.net/21.15107/rcub_imagine_2188 .

Radojević, Dušan, Bekić, Marina, Ilić, Nataša, Đokić, Jelena, Stojanović, Dušica, Vasilev, Saša, Gruden-Movsesijan, Alisa, Tomić, Sergej, "NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION" in 10th ISM World Congress on Targeting Microbiota (2023):77-77,
https://hdl.handle.net/21.15107/rcub_imagine_2188 .

TY  - CONF
AU  - Dinić, Miroslav
AU  - Jakovljević, Stefan
AU  - Radojević, Dušan
AU  - Brdarić, Emilija
AU  - Bajić, Svetlana
AU  - Đokić, Jelena
AU  - Golić, Nataša
PY  - 2023
UR  - https://www.microbiota-site.com/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2189
AB  - Introduction: New theories of ageing recognized gut microbiota as one of twelve hallmarks of ageing (1). 
Recent data conducted on Caenorhabditis elegans imply a potential role of Lactobacillus species and other 
commensal bacteria 
in regulation of ageing highlighting TFEB/HLH-30-dependent autophagy, p38 
MAPK/PMK-1 signalling and mitochondrial function as activated longevity-associated mechanisms (2,3). 
Here, we explore the potential of bacterial polysaccharides 
loosely attached to bacterial cell wall 
(exopolysaccharides), considering it is still unknown which bacterial molecules could activate longevity 
signalling pathways.
Materials & Methods: Caenorhabditis elegans was used as ageing model. Evaluation of worm’s lifespan 
and locomotion rate were performed by feeding worms with six exopolysaccharide-producing lactobacilli. 
Worms fed with two selected strains were subjected to RNAseq analysis. Identified upregulated genes were 
confirmed by qPCR and expression of their mammalian orthologs checked in human HepG2 cell.
Results: Two strains of lactobacilli showed the most pronounced effect on worms’ lifespan. RNAseq analysis 
identified core gene signature associate with exopolysaccharide-induced longevity. The expression of 
identified fmo-2, gsto-1, nlp-29, and clec-47 genes were confirmed by qPCR, while upregulation of FMO-5 
was confirmed in HepG2 cells.
Conclusion: Overall, our results imply that bacteria-derived exopolysaccharides could stimulate longevity-
promoting flavin-containing monooxygenase 2 to regulate lifespan in Caenorhabditis elegans
C3  - 10th ISM World Congress on Targeting Microbiota
T1  - EXOPOLYSACCHARIDE-PRODUCING GUT BACTERIA MODULATE HOST AGEING
EP  - 65
SP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2189
ER  - 

@conference{
author = "Dinić, Miroslav and Jakovljević, Stefan and Radojević, Dušan and Brdarić, Emilija and Bajić, Svetlana and Đokić, Jelena and Golić, Nataša",
year = "2023",
abstract = "Introduction: New theories of ageing recognized gut microbiota as one of twelve hallmarks of ageing (1). 
Recent data conducted on Caenorhabditis elegans imply a potential role of Lactobacillus species and other 
commensal bacteria 
in regulation of ageing highlighting TFEB/HLH-30-dependent autophagy, p38 
MAPK/PMK-1 signalling and mitochondrial function as activated longevity-associated mechanisms (2,3). 
Here, we explore the potential of bacterial polysaccharides 
loosely attached to bacterial cell wall 
(exopolysaccharides), considering it is still unknown which bacterial molecules could activate longevity 
signalling pathways.
Materials & Methods: Caenorhabditis elegans was used as ageing model. Evaluation of worm’s lifespan 
and locomotion rate were performed by feeding worms with six exopolysaccharide-producing lactobacilli. 
Worms fed with two selected strains were subjected to RNAseq analysis. Identified upregulated genes were 
confirmed by qPCR and expression of their mammalian orthologs checked in human HepG2 cell.
Results: Two strains of lactobacilli showed the most pronounced effect on worms’ lifespan. RNAseq analysis 
identified core gene signature associate with exopolysaccharide-induced longevity. The expression of 
identified fmo-2, gsto-1, nlp-29, and clec-47 genes were confirmed by qPCR, while upregulation of FMO-5 
was confirmed in HepG2 cells.
Conclusion: Overall, our results imply that bacteria-derived exopolysaccharides could stimulate longevity-
promoting flavin-containing monooxygenase 2 to regulate lifespan in Caenorhabditis elegans",
journal = "10th ISM World Congress on Targeting Microbiota",
title = "EXOPOLYSACCHARIDE-PRODUCING GUT BACTERIA MODULATE HOST AGEING",
pages = "65-65",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2189"
}

Dinić, M., Jakovljević, S., Radojević, D., Brdarić, E., Bajić, S., Đokić, J.,& Golić, N.. (2023). EXOPOLYSACCHARIDE-PRODUCING GUT BACTERIA MODULATE HOST AGEING. in 10th ISM World Congress on Targeting Microbiota, 65-65.
https://hdl.handle.net/21.15107/rcub_imagine_2189

Dinić M, Jakovljević S, Radojević D, Brdarić E, Bajić S, Đokić J, Golić N. EXOPOLYSACCHARIDE-PRODUCING GUT BACTERIA MODULATE HOST AGEING. in 10th ISM World Congress on Targeting Microbiota. 2023;:65-65.
https://hdl.handle.net/21.15107/rcub_imagine_2189 .

Dinić, Miroslav, Jakovljević, Stefan, Radojević, Dušan, Brdarić, Emilija, Bajić, Svetlana, Đokić, Jelena, Golić, Nataša, "EXOPOLYSACCHARIDE-PRODUCING GUT BACTERIA MODULATE HOST AGEING" in 10th ISM World Congress on Targeting Microbiota (2023):65-65,
https://hdl.handle.net/21.15107/rcub_imagine_2189 .

TY  - JOUR
AU  - Popović, Nikola
AU  - Stevanović, Dušan
AU  - Radojević, Dušan
AU  - Veljović, Katarina
AU  - Đokić, Jelena
AU  - Golić, Nataša
AU  - Terzić-Vidojević, Amarela
PY  - 2023
UR  - https://www.mdpi.com/2076-2607/11/12/2844
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2209
AB  - This study aimed to explore the probiogenomic characteristics of artisanal bacteriocin-producing Enterococcus faecium BGZLM1-5 and its potential application in reducing Listeria monocytogenes in a milk model. The BGZLM1-5 strain was isolated from raw cow’s milk from households in the Zlatar Mountain region. The whole genome sequencing approach and bioinformatics analyses reveal that the strain BGZLM1-5 is non-pathogenic to humans. Bacteriocin-containing supernatant was thermally stable and antimicrobial activity retained 75% of the initial activity compared with that of the control after treatment at 90 °C for 30 min. Antimicrobial activity maintained relative stability at pH 3–11 and retained 62.5% of the initial activity compared with that of the control after treatment at pH 1, 2, and 12. The highest activity of the partially purified bacteriocin was obtained after precipitation at 40% saturation with ammonium sulfate and further purification by mixing with chloroform. Applying 3% and 5% (v/v) of the bacteriocin-containing supernatant and 0.5% (v/v) of the partially purified bacteriocin decreased the viable number of L. monocytogenes ATCC19111 after three days of milk storage by 23.5%, 63.5%, and 58.9%, respectively.
T2  - Microorganisms
T1  - Insight into the Postbiotic Potential of the Autochthonous Bacteriocin-Producing Enterococcus faecium BGZLM1-5 in the Reduction in the Abundance of Listeria monocytogenes ATCC19111 in a Milk Model
IS  - 12
SP  - 2844
VL  - 11
DO  - 10.3390/microorganisms11122844
ER  - 

@article{
author = "Popović, Nikola and Stevanović, Dušan and Radojević, Dušan and Veljović, Katarina and Đokić, Jelena and Golić, Nataša and Terzić-Vidojević, Amarela",
year = "2023",
abstract = "This study aimed to explore the probiogenomic characteristics of artisanal bacteriocin-producing Enterococcus faecium BGZLM1-5 and its potential application in reducing Listeria monocytogenes in a milk model. The BGZLM1-5 strain was isolated from raw cow’s milk from households in the Zlatar Mountain region. The whole genome sequencing approach and bioinformatics analyses reveal that the strain BGZLM1-5 is non-pathogenic to humans. Bacteriocin-containing supernatant was thermally stable and antimicrobial activity retained 75% of the initial activity compared with that of the control after treatment at 90 °C for 30 min. Antimicrobial activity maintained relative stability at pH 3–11 and retained 62.5% of the initial activity compared with that of the control after treatment at pH 1, 2, and 12. The highest activity of the partially purified bacteriocin was obtained after precipitation at 40% saturation with ammonium sulfate and further purification by mixing with chloroform. Applying 3% and 5% (v/v) of the bacteriocin-containing supernatant and 0.5% (v/v) of the partially purified bacteriocin decreased the viable number of L. monocytogenes ATCC19111 after three days of milk storage by 23.5%, 63.5%, and 58.9%, respectively.",
journal = "Microorganisms",
title = "Insight into the Postbiotic Potential of the Autochthonous Bacteriocin-Producing Enterococcus faecium BGZLM1-5 in the Reduction in the Abundance of Listeria monocytogenes ATCC19111 in a Milk Model",
number = "12",
pages = "2844",
volume = "11",
doi = "10.3390/microorganisms11122844"
}

Popović, N., Stevanović, D., Radojević, D., Veljović, K., Đokić, J., Golić, N.,& Terzić-Vidojević, A.. (2023). Insight into the Postbiotic Potential of the Autochthonous Bacteriocin-Producing Enterococcus faecium BGZLM1-5 in the Reduction in the Abundance of Listeria monocytogenes ATCC19111 in a Milk Model. in Microorganisms, 11(12), 2844.
https://doi.org/10.3390/microorganisms11122844

Popović N, Stevanović D, Radojević D, Veljović K, Đokić J, Golić N, Terzić-Vidojević A. Insight into the Postbiotic Potential of the Autochthonous Bacteriocin-Producing Enterococcus faecium BGZLM1-5 in the Reduction in the Abundance of Listeria monocytogenes ATCC19111 in a Milk Model. in Microorganisms. 2023;11(12):2844.
doi:10.3390/microorganisms11122844 .

Popović, Nikola, Stevanović, Dušan, Radojević, Dušan, Veljović, Katarina, Đokić, Jelena, Golić, Nataša, Terzić-Vidojević, Amarela, "Insight into the Postbiotic Potential of the Autochthonous Bacteriocin-Producing Enterococcus faecium BGZLM1-5 in the Reduction in the Abundance of Listeria monocytogenes ATCC19111 in a Milk Model" in Microorganisms, 11, no. 12 (2023):2844,
https://doi.org/10.3390/microorganisms11122844 . .

TY  - JOUR
AU  - Radojević, Dušan
AU  - Bajić, Svetlana Soković
AU  - Dinić, Miroslav
AU  - Bisenić, Aleksandar
AU  - Đokić, Jelena
AU  - Golić, Nataša
PY  - 2023
UR  - https://aseestant.ceon.rs/index.php/arhfarm/article/view/46986
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2294
AB  - The microbiome-gut-brain axis (MGBA) represents a close two-way relationship between the gut and the central nervous system (CNS) mediated by the immune system, the enteric nervous system (ENS), the vagus nerve, and the gut microbiome. Gut microbes, including bacteria, fungi, and viruses, can communicate with the CNS and modulate the physiology of the brain in health and disease, which marks them as an important MGBA factor. It is becoming increasingly evident that gut microbiome dysbiosis is implicated in the onset and severity of different neurodegenerative and psychiatric diseases including multiple sclerosis (MS). MS is a chronic disease of the CNS associated with different genetic and environmental risk factors. Neuroinflammation and demyelination in the brain and the spinal cord are hallmark features of MS. The accumulating evidence shows that the MGBA, although a relatively new concept, has an important role in MS. Therefore, the purpose of this article is to review recent research on the gut-brain connection in MS, and to highlight MS-associated gut microbiota constituents and the role of bacterial metabolites in MS.
AB  - Mikrobiom-crevo-mozak osovina (MGBA) predstavlja blisku dvosmernu vezu između creva i centralnog nervnog sistema (CNS) posredovanu imunskim sistemom, enteričnim nervnim sistemom   (ENS),   nervom   vagusom   i   mikrobiomom   creva.   Posredstvom   metabolita   koje   produkuju, mikroorganizmi creva, uključujući bakterije, gljive i viruse, komuniciraju sa CNS-om i tako utiču na funkcije mozga, zbog čega je mikrobiota creva prepoznata kao veoma važan faktor održavanja homeostaze MGBA. Takođe, veliki broj podataka ukazao je na povezanost disbioze mikrobioma creva i nastanka i težine simptoma različitih neurodegenerativnih i psihijatrijskih bolesti, uključujući multiplu sklerozu (MS), autoimunsku bolest nervnog sistema. MS je hronična bolest  CNS-a  povezana  sa  više  genetskih  faktora, kao i sa različitim sredinskim faktorima i životnim  navikama.  Najvažnija  obeležja  MS  su  neuroinflamacija  i  demijelinizacija  u  mozgu  i  kičmenoj moždini, a veliki broj istraživanja je ukazao i na specifične mikrobijalne markere ove bolesti. Cilj ovog rada je da pruži pregled najvažnijih podataka o povezanosti promena u sastavu i funkciji mikrobiote creva i patoloških promena karakterističnih za MS.
PB  - Centre for Evaluation in Education and Science
T2  - Archives of Pharmacy
T1  - The Microbiome-Gut-Brain Axis in Multiple Sclerosis
T1  - Mikrobiom-crevo-mozak osovina kod multiple skleroze
EP  - 462
IS  - Notebook 6
SP  - 441
VL  - 73
DO  - 10.5937/arhfarm73-46986
ER  - 

@article{
author = "Radojević, Dušan and Bajić, Svetlana Soković and Dinić, Miroslav and Bisenić, Aleksandar and Đokić, Jelena and Golić, Nataša",
year = "2023",
abstract = "The microbiome-gut-brain axis (MGBA) represents a close two-way relationship between the gut and the central nervous system (CNS) mediated by the immune system, the enteric nervous system (ENS), the vagus nerve, and the gut microbiome. Gut microbes, including bacteria, fungi, and viruses, can communicate with the CNS and modulate the physiology of the brain in health and disease, which marks them as an important MGBA factor. It is becoming increasingly evident that gut microbiome dysbiosis is implicated in the onset and severity of different neurodegenerative and psychiatric diseases including multiple sclerosis (MS). MS is a chronic disease of the CNS associated with different genetic and environmental risk factors. Neuroinflammation and demyelination in the brain and the spinal cord are hallmark features of MS. The accumulating evidence shows that the MGBA, although a relatively new concept, has an important role in MS. Therefore, the purpose of this article is to review recent research on the gut-brain connection in MS, and to highlight MS-associated gut microbiota constituents and the role of bacterial metabolites in MS., Mikrobiom-crevo-mozak osovina (MGBA) predstavlja blisku dvosmernu vezu između creva i centralnog nervnog sistema (CNS) posredovanu imunskim sistemom, enteričnim nervnim sistemom   (ENS),   nervom   vagusom   i   mikrobiomom   creva.   Posredstvom   metabolita   koje   produkuju, mikroorganizmi creva, uključujući bakterije, gljive i viruse, komuniciraju sa CNS-om i tako utiču na funkcije mozga, zbog čega je mikrobiota creva prepoznata kao veoma važan faktor održavanja homeostaze MGBA. Takođe, veliki broj podataka ukazao je na povezanost disbioze mikrobioma creva i nastanka i težine simptoma različitih neurodegenerativnih i psihijatrijskih bolesti, uključujući multiplu sklerozu (MS), autoimunsku bolest nervnog sistema. MS je hronična bolest  CNS-a  povezana  sa  više  genetskih  faktora, kao i sa različitim sredinskim faktorima i životnim  navikama.  Najvažnija  obeležja  MS  su  neuroinflamacija  i  demijelinizacija  u  mozgu  i  kičmenoj moždini, a veliki broj istraživanja je ukazao i na specifične mikrobijalne markere ove bolesti. Cilj ovog rada je da pruži pregled najvažnijih podataka o povezanosti promena u sastavu i funkciji mikrobiote creva i patoloških promena karakterističnih za MS.",
publisher = "Centre for Evaluation in Education and Science",
journal = "Archives of Pharmacy",
title = "The Microbiome-Gut-Brain Axis in Multiple Sclerosis, Mikrobiom-crevo-mozak osovina kod multiple skleroze",
pages = "462-441",
number = "Notebook 6",
volume = "73",
doi = "10.5937/arhfarm73-46986"
}

Radojević, D., Bajić, S. S., Dinić, M., Bisenić, A., Đokić, J.,& Golić, N.. (2023). The Microbiome-Gut-Brain Axis in Multiple Sclerosis. in Archives of Pharmacy
Centre for Evaluation in Education and Science., 73(Notebook 6), 441-462.
https://doi.org/10.5937/arhfarm73-46986

Radojević D, Bajić SS, Dinić M, Bisenić A, Đokić J, Golić N. The Microbiome-Gut-Brain Axis in Multiple Sclerosis. in Archives of Pharmacy. 2023;73(Notebook 6):441-462.
doi:10.5937/arhfarm73-46986 .

Radojević, Dušan, Bajić, Svetlana Soković, Dinić, Miroslav, Bisenić, Aleksandar, Đokić, Jelena, Golić, Nataša, "The Microbiome-Gut-Brain Axis in Multiple Sclerosis" in Archives of Pharmacy, 73, no. Notebook 6 (2023):441-462,
https://doi.org/10.5937/arhfarm73-46986 . .

TY  - THES
AU  - Radojević, Dušan
PY  - 2023
UR  - https://uvidok.rcub.bg.ac.rs/bitstream/handle/123456789/5241/Referat.pdf
UR  - https://eteze.bg.ac.rs/application/showtheses?thesesId=9215
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:30638/bdef:Content/download
UR  - https://plus.cobiss.net/cobiss/sr/sr/bib/121604617
UR  - https://nardus.mpn.gov.rs/handle/123456789/21542
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2116
AB  - Transfer mijeloidnih ćelija imunogenih ili supresivnih svojstava, ima velikipotencijal u lečenju malignih tumora ali i autoimunskih bolesti. Međutim, nije do krajaispitana veza funkcijskog potencijala mijeloidnih ćelija i sastava mikrobiote creva, kaojednog od ključnih regulatora imunskog sistema. U ovoj tezi je po prvi put ispitivana vezaizmeđu sastava mikrobiote creva i funkcijskog potencijala mijeloidnih ćelija, i to humanihdendritskih ćelija (DC) i supresorskih ćelija mijeloidnog porekla (MDSC) in vitro, kao ipotencijal MDSC pacova da suprimiraju autoimunski proces u modelu eksperimentalnogautoimunskog encefalomijelitisa (EAE). Rezultati su pokazali da DC dobijene od zdravihdonora koji su imali veći diverzitet mikrobiote creva i veću zastupljenost bakterija kojeproizvode masne kiseline kratkog lanca (SCFA) poseduju slabiji imunogeni potencijal uodnosu na DC poreklom iz donora koji su imali manji diverzitet mikrobiote i većuzastupljenost rodova Bifidobacterium i Collinsella. U modelu humanih MDSC je pokazanoda poliamini mikrobiote potenciraju imunosupresivna svojstva MDSC posredstvomintestinalnih epitelnih ćelija. Takođe, transfer MDSC aktiviranih prostaglandinom E2(MDSC-PGE2) u ţivotinje sa indukovanim EAE, ublaţava simptome EAE nakon migracijeu limfni sistem creva. Fenomen ublaţavanja simptoma EAE nakon transfera MDSC-PGE2je bio povezan sa smanjenom infiltracijom proinflamatornih i povećanom infiltracijomregulatornih ćelija u CNS i slezinu, očuvanjem integriteta intestinalne barijere, diverzitetamikrobiote creva i povećanjem zastupljenosti bakterija koje ispoljavaju imunoregulatorneosobine, poliamina i SCFA u fecesu. Ovi rezultati ukazuju na blisku povezanost mikro-biote creva i imunogenosti/supresivnosti mijeloidnih ćelija, što moţe biti iskorišćeno urazvoju novih efikasnijih terapija za maligne tumore i autoimunske bolesti.
AB  - The transfer of myeloid cells with immunogenic or suppressive properties holdsgreat potential for the treatment of malignant tumors or autoimmune diseases,respectively. However, the relationship between the functional potential of myeloid cellsand the composition of the gut microbiota, one of the most important regulators of theimmune system, has not yet been elucidated. In this thesis, we investigated for the firsttime the relationship between the gut microbiota composition and the functional potentialof myeloid cells, in human dendritic cell (DC) and myeloid derived suppressor cells(MDSC) differentiated in vitro, and the potential of rat MDSCs to suppress theautoimmune response in experimental autoimmune encephalomyelitis (EAE) model invivo. The results showed that DCs from healthy donors with higher gut microbiotadiversity and higher abundance of short-chain fatty acid (SCFA)-producing bacteria havelower immunogenic potential, in contrast to DCs from donors with lower gut microbiotadiversity and higher abundance of Bifidobacterium and Collinsella genera. In the humanMDSC model, polyamines produced by the microbiota were shown to enhance theimmunosuppressive properties of MDSCs by intestinal epithelial cells. Also, transfer ofanimal MDSCs activated with prostaglandin E2 (MDSC-PGE2) into animals with inducedEAE alleviates EAE symptoms after migration to the intestinal lymphatic system. Thephenomenon of alleviation of EAE symptoms after MDSC-PGE2 transfer was associatedwith decreased infiltration of pro-inflammatory and increased infiltration of regulatorycells in the CNS and spleen, maintenance of intestinal barrier integrity, diversity of theintestinal microbiota, and an increase in the abundance of immunoregulatory bacteria,polyamines, and SCFA in the feces. These results suggest a strong association between thegut microbiota and the immunogenicity/suppressiveness of myeloid cells that can beexploited in the development of new, more effective therapies for malignancies andautoimmune diseases.
PB  - Универзитет у Београду, Биолошки факултет
T2  - Универзитет у Београду
T1  - Uticaj sastava mikrobiote creva na imunomodulatorna svojstva i imunoterapijski potencijal dendritskih ćelija i supresorskih ćelija mijeloidnog porekla
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2116
ER  - 

@phdthesis{
author = "Radojević, Dušan",
year = "2023",
abstract = "Transfer mijeloidnih ćelija imunogenih ili supresivnih svojstava, ima velikipotencijal u lečenju malignih tumora ali i autoimunskih bolesti. Međutim, nije do krajaispitana veza funkcijskog potencijala mijeloidnih ćelija i sastava mikrobiote creva, kaojednog od ključnih regulatora imunskog sistema. U ovoj tezi je po prvi put ispitivana vezaizmeđu sastava mikrobiote creva i funkcijskog potencijala mijeloidnih ćelija, i to humanihdendritskih ćelija (DC) i supresorskih ćelija mijeloidnog porekla (MDSC) in vitro, kao ipotencijal MDSC pacova da suprimiraju autoimunski proces u modelu eksperimentalnogautoimunskog encefalomijelitisa (EAE). Rezultati su pokazali da DC dobijene od zdravihdonora koji su imali veći diverzitet mikrobiote creva i veću zastupljenost bakterija kojeproizvode masne kiseline kratkog lanca (SCFA) poseduju slabiji imunogeni potencijal uodnosu na DC poreklom iz donora koji su imali manji diverzitet mikrobiote i većuzastupljenost rodova Bifidobacterium i Collinsella. U modelu humanih MDSC je pokazanoda poliamini mikrobiote potenciraju imunosupresivna svojstva MDSC posredstvomintestinalnih epitelnih ćelija. Takođe, transfer MDSC aktiviranih prostaglandinom E2(MDSC-PGE2) u ţivotinje sa indukovanim EAE, ublaţava simptome EAE nakon migracijeu limfni sistem creva. Fenomen ublaţavanja simptoma EAE nakon transfera MDSC-PGE2je bio povezan sa smanjenom infiltracijom proinflamatornih i povećanom infiltracijomregulatornih ćelija u CNS i slezinu, očuvanjem integriteta intestinalne barijere, diverzitetamikrobiote creva i povećanjem zastupljenosti bakterija koje ispoljavaju imunoregulatorneosobine, poliamina i SCFA u fecesu. Ovi rezultati ukazuju na blisku povezanost mikro-biote creva i imunogenosti/supresivnosti mijeloidnih ćelija, što moţe biti iskorišćeno urazvoju novih efikasnijih terapija za maligne tumore i autoimunske bolesti., The transfer of myeloid cells with immunogenic or suppressive properties holdsgreat potential for the treatment of malignant tumors or autoimmune diseases,respectively. However, the relationship between the functional potential of myeloid cellsand the composition of the gut microbiota, one of the most important regulators of theimmune system, has not yet been elucidated. In this thesis, we investigated for the firsttime the relationship between the gut microbiota composition and the functional potentialof myeloid cells, in human dendritic cell (DC) and myeloid derived suppressor cells(MDSC) differentiated in vitro, and the potential of rat MDSCs to suppress theautoimmune response in experimental autoimmune encephalomyelitis (EAE) model invivo. The results showed that DCs from healthy donors with higher gut microbiotadiversity and higher abundance of short-chain fatty acid (SCFA)-producing bacteria havelower immunogenic potential, in contrast to DCs from donors with lower gut microbiotadiversity and higher abundance of Bifidobacterium and Collinsella genera. In the humanMDSC model, polyamines produced by the microbiota were shown to enhance theimmunosuppressive properties of MDSCs by intestinal epithelial cells. Also, transfer ofanimal MDSCs activated with prostaglandin E2 (MDSC-PGE2) into animals with inducedEAE alleviates EAE symptoms after migration to the intestinal lymphatic system. Thephenomenon of alleviation of EAE symptoms after MDSC-PGE2 transfer was associatedwith decreased infiltration of pro-inflammatory and increased infiltration of regulatorycells in the CNS and spleen, maintenance of intestinal barrier integrity, diversity of theintestinal microbiota, and an increase in the abundance of immunoregulatory bacteria,polyamines, and SCFA in the feces. These results suggest a strong association between thegut microbiota and the immunogenicity/suppressiveness of myeloid cells that can beexploited in the development of new, more effective therapies for malignancies andautoimmune diseases.",
publisher = "Универзитет у Београду, Биолошки факултет",
journal = "Универзитет у Београду",
title = "Uticaj sastava mikrobiote creva na imunomodulatorna svojstva i imunoterapijski potencijal dendritskih ćelija i supresorskih ćelija mijeloidnog porekla",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2116"
}

Radojević, D.. (2023). Uticaj sastava mikrobiote creva na imunomodulatorna svojstva i imunoterapijski potencijal dendritskih ćelija i supresorskih ćelija mijeloidnog porekla. in Универзитет у Београду
Универзитет у Београду, Биолошки факултет..
https://hdl.handle.net/21.15107/rcub_imagine_2116

Radojević D. Uticaj sastava mikrobiote creva na imunomodulatorna svojstva i imunoterapijski potencijal dendritskih ćelija i supresorskih ćelija mijeloidnog porekla. in Универзитет у Београду. 2023;.
https://hdl.handle.net/21.15107/rcub_imagine_2116 .

Radojević, Dušan, "Uticaj sastava mikrobiote creva na imunomodulatorna svojstva i imunoterapijski potencijal dendritskih ćelija i supresorskih ćelija mijeloidnog porekla" in Универзитет у Београду (2023),
https://hdl.handle.net/21.15107/rcub_imagine_2116 .

TY  - JOUR
AU  - Dinić, Miroslav
AU  - Jakovljević, Stefan
AU  - Popović, Nikola
AU  - Radojević, Dušan
AU  - Veljović, Katarina
AU  - Golić, Nataša
AU  - Terzić-Vidojević, Amarela
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2091
AB  - Yogurt represent one of the oldest fermented foods containing viable lactic acid bacteria and many bioactive compounds that could exhibit beneficial effects on human health and train our immune system to better respond to invading pathogens. Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus are commonly used for yogurt preparation under controlled temperature and environmental conditions. In this study, we investigated probiotic features of S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21 strains isolated from artisanal sour milk and yogurt by using Caenorhabditis elegans as an in vivo model system. Further, we evaluated content of total fat, saturated fatty acids, proteins, and lactose, as well as vitamins and AA of yogurt prepared from above-mentioned starter cultures during 21 d of storage at 4°C to get insights of final product stability. We showed that S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21 strains applied in combination upregulated the expression of autophagy-related genes in C. elegans. Beside autophagy, we observed activation of TIR-1-dependent transcription of lysozyme-like antimicrobial genes involved in the immune defense of C. elegans. Upregulation of these genes strongly correlates with an increase in the longevity of the worms fed with yogurt culture bacteria. Further, we showed that yogurt prepared with S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21, as a final product, is rich with vitamin B2 and dominant AA known by their prolongevity properties. Taken together, our study pointed to the beneficial features of the tested starter cultures and yogurt and highlighted their potential to be used as a fermented food with added-value properties.
PB  - Elsevier
PB  - American Dairy Science Association
T2  - Journal of Dairy Science
T2  - Journal of Dairy ScienceJournal of Dairy Science
T1  - Stability and bioactive compounds assessment of yogurt containing novel natural starter cultures with the ability to promote longevity in Caenorhabditis elegans
EP  - 7460
IS  - 11
SP  - 7447
VL  - 106
DO  - 10.3168/jds.2023-23342
ER  - 

@article{
author = "Dinić, Miroslav and Jakovljević, Stefan and Popović, Nikola and Radojević, Dušan and Veljović, Katarina and Golić, Nataša and Terzić-Vidojević, Amarela",
year = "2023",
abstract = "Yogurt represent one of the oldest fermented foods containing viable lactic acid bacteria and many bioactive compounds that could exhibit beneficial effects on human health and train our immune system to better respond to invading pathogens. Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus are commonly used for yogurt preparation under controlled temperature and environmental conditions. In this study, we investigated probiotic features of S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21 strains isolated from artisanal sour milk and yogurt by using Caenorhabditis elegans as an in vivo model system. Further, we evaluated content of total fat, saturated fatty acids, proteins, and lactose, as well as vitamins and AA of yogurt prepared from above-mentioned starter cultures during 21 d of storage at 4°C to get insights of final product stability. We showed that S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21 strains applied in combination upregulated the expression of autophagy-related genes in C. elegans. Beside autophagy, we observed activation of TIR-1-dependent transcription of lysozyme-like antimicrobial genes involved in the immune defense of C. elegans. Upregulation of these genes strongly correlates with an increase in the longevity of the worms fed with yogurt culture bacteria. Further, we showed that yogurt prepared with S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21, as a final product, is rich with vitamin B2 and dominant AA known by their prolongevity properties. Taken together, our study pointed to the beneficial features of the tested starter cultures and yogurt and highlighted their potential to be used as a fermented food with added-value properties.",
publisher = "Elsevier, American Dairy Science Association",
journal = "Journal of Dairy Science, Journal of Dairy ScienceJournal of Dairy Science",
title = "Stability and bioactive compounds assessment of yogurt containing novel natural starter cultures with the ability to promote longevity in Caenorhabditis elegans",
pages = "7460-7447",
number = "11",
volume = "106",
doi = "10.3168/jds.2023-23342"
}

Dinić, M., Jakovljević, S., Popović, N., Radojević, D., Veljović, K., Golić, N.,& Terzić-Vidojević, A.. (2023). Stability and bioactive compounds assessment of yogurt containing novel natural starter cultures with the ability to promote longevity in Caenorhabditis elegans. in Journal of Dairy Science
Elsevier., 106(11), 7447-7460.
https://doi.org/10.3168/jds.2023-23342

Dinić M, Jakovljević S, Popović N, Radojević D, Veljović K, Golić N, Terzić-Vidojević A. Stability and bioactive compounds assessment of yogurt containing novel natural starter cultures with the ability to promote longevity in Caenorhabditis elegans. in Journal of Dairy Science. 2023;106(11):7447-7460.
doi:10.3168/jds.2023-23342 .

Dinić, Miroslav, Jakovljević, Stefan, Popović, Nikola, Radojević, Dušan, Veljović, Katarina, Golić, Nataša, Terzić-Vidojević, Amarela, "Stability and bioactive compounds assessment of yogurt containing novel natural starter cultures with the ability to promote longevity in Caenorhabditis elegans" in Journal of Dairy Science, 106, no. 11 (2023):7447-7460,
https://doi.org/10.3168/jds.2023-23342 . .

TY  - CONF
AU  - Bekić, Marina
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Vučević, Dragana
AU  - Vasilev, Saša
AU  - Tomić, Sergej
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2042
AB  - Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease
development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS
pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong
immunosuppressive functions which can be exploited in the treatment of autoimmune diseases.
Considering the limited data on MDSCs application in MS therapy and their poorly studied effects
on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated
according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG)
E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with
MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota
features in control and MDSC-treated animals by using a shotgun metagenomics approach. In
mice, PGE2-activated MDSC significantly inhibited the onset and clinical course of EAE. This effect
correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2,
as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is
also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2
and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in
the control EAE group, while in both MDSC treatments the increase in relative abundances of
Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties,
was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the
increase in pathways involved in the production of potentially immunoregulatory metabolites
in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the
efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in
order to improve MDSC-based EAE therapy.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation
EP  - 97
SP  - 97
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2042
ER  - 

@conference{
author = "Bekić, Marina and Đokić, Jelena and Radojević, Dušan and Vučević, Dragana and Vasilev, Saša and Tomić, Sergej",
year = "2023",
abstract = "Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease
development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS
pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong
immunosuppressive functions which can be exploited in the treatment of autoimmune diseases.
Considering the limited data on MDSCs application in MS therapy and their poorly studied effects
on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated
according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG)
E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with
MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota
features in control and MDSC-treated animals by using a shotgun metagenomics approach. In
mice, PGE2-activated MDSC significantly inhibited the onset and clinical course of EAE. This effect
correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2,
as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is
also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2
and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in
the control EAE group, while in both MDSC treatments the increase in relative abundances of
Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties,
was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the
increase in pathways involved in the production of potentially immunoregulatory metabolites
in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the
efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in
order to improve MDSC-based EAE therapy.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation",
pages = "97-97",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2042"
}

Bekić, M., Đokić, J., Radojević, D., Vučević, D., Vasilev, S.,& Tomić, S.. (2023). Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 97-97.
https://hdl.handle.net/21.15107/rcub_imagine_2042

Bekić M, Đokić J, Radojević D, Vučević D, Vasilev S, Tomić S. Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation. in 4th Belgrade Bioinformatics Conference. 2023;4:97-97.
https://hdl.handle.net/21.15107/rcub_imagine_2042 .

Bekić, Marina, Đokić, Jelena, Radojević, Dušan, Vučević, Dragana, Vasilev, Saša, Tomić, Sergej, "Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation" in 4th Belgrade Bioinformatics Conference, 4 (2023):97-97,
https://hdl.handle.net/21.15107/rcub_imagine_2042 .

TY  - CONF
AU  - Dinić, Miroslav
AU  - Jakovljević, Stefan
AU  - Radojević, Dušan
AU  - Brdarić, Emilija
AU  - Soković Bajić, Svetlana
AU  - Đokić, Jelena
AU  - Golić, Nataša
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2146
AB  - Introduction: Microbial community established in the gut has been recognized as an important factor
which influence host aging. Bacteria from the gut co-evolved with the host resulting in mutually beneficial interactions essential for host’s wellbeing. This complex crosstalk reflects mainly through the interaction between bacterial macromolecules (e.g., exopolysaccharides) and the host receptors leading
to the activation of various cellular pathways. Here, we explore the potential of different lactobacilli,
commonly used as probiotics, to activate longevity signalling in Caenorhabditis elegans.
Methods: Evaluation of C. elegans lifespan and aging parameters (locomotion rate and pharyngeal
pumping) were performed by feeding N2 wild-type worms with different Lactobacillus species. Worms
fed with selected strains were subjected to RNAseq analysis, qPCR and Western blot to evaluate activation of autophagy, immunity, antioxidative response and mitochondrial function. Activation of autophagy was confirmed in DA2123 GFP-labelled LGG-1 transgenic strain and JIN1375 hlh-30 (tm1978)
mutant, while immunity activation was evaluated by using KU25 pmk-1 (km25) mutant and through
nematode killing assays.
Results: Selected strains of lactobacilli promoted health and lifespan of worms through activation of
TFEB/HLH-30 dependent autophagy and p38 MAPK/PMK-1 dependent immune response which provided resistance of worms exposed to pathogens. Moreover, RNAseq analysis identified core gene signature associate with exopolysaccharide-induced longevity highlighting involvement of fmo-2, gsto-1,
nlp-29, and clec-47 genes in increased lifespan of the worms.
Conclusion: Analyzed lactobacilli showed potential to promote healthy aging and could be further investigated in order to better understand application of lactobacilli as pro-longevity probiotics.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - The role of the gut bacteria during host aging
EP  - 108
SP  - 108
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2146
ER  - 

@conference{
author = "Dinić, Miroslav and Jakovljević, Stefan and Radojević, Dušan and Brdarić, Emilija and Soković Bajić, Svetlana and Đokić, Jelena and Golić, Nataša",
year = "2023",
abstract = "Introduction: Microbial community established in the gut has been recognized as an important factor
which influence host aging. Bacteria from the gut co-evolved with the host resulting in mutually beneficial interactions essential for host’s wellbeing. This complex crosstalk reflects mainly through the interaction between bacterial macromolecules (e.g., exopolysaccharides) and the host receptors leading
to the activation of various cellular pathways. Here, we explore the potential of different lactobacilli,
commonly used as probiotics, to activate longevity signalling in Caenorhabditis elegans.
Methods: Evaluation of C. elegans lifespan and aging parameters (locomotion rate and pharyngeal
pumping) were performed by feeding N2 wild-type worms with different Lactobacillus species. Worms
fed with selected strains were subjected to RNAseq analysis, qPCR and Western blot to evaluate activation of autophagy, immunity, antioxidative response and mitochondrial function. Activation of autophagy was confirmed in DA2123 GFP-labelled LGG-1 transgenic strain and JIN1375 hlh-30 (tm1978)
mutant, while immunity activation was evaluated by using KU25 pmk-1 (km25) mutant and through
nematode killing assays.
Results: Selected strains of lactobacilli promoted health and lifespan of worms through activation of
TFEB/HLH-30 dependent autophagy and p38 MAPK/PMK-1 dependent immune response which provided resistance of worms exposed to pathogens. Moreover, RNAseq analysis identified core gene signature associate with exopolysaccharide-induced longevity highlighting involvement of fmo-2, gsto-1,
nlp-29, and clec-47 genes in increased lifespan of the worms.
Conclusion: Analyzed lactobacilli showed potential to promote healthy aging and could be further investigated in order to better understand application of lactobacilli as pro-longevity probiotics.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "The role of the gut bacteria during host aging",
pages = "108-108",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2146"
}

Dinić, M., Jakovljević, S., Radojević, D., Brdarić, E., Soković Bajić, S., Đokić, J.,& Golić, N.. (2023). The role of the gut bacteria during host aging. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 108-108.
https://hdl.handle.net/21.15107/rcub_imagine_2146

Dinić M, Jakovljević S, Radojević D, Brdarić E, Soković Bajić S, Đokić J, Golić N. The role of the gut bacteria during host aging. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:108-108.
https://hdl.handle.net/21.15107/rcub_imagine_2146 .

Dinić, Miroslav, Jakovljević, Stefan, Radojević, Dušan, Brdarić, Emilija, Soković Bajić, Svetlana, Đokić, Jelena, Golić, Nataša, "The role of the gut bacteria during host aging" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):108-108,
https://hdl.handle.net/21.15107/rcub_imagine_2146 .

TY  - JOUR
AU  - Dinić, Miroslav
AU  - Popović, Nikola
AU  - Radojević, Dušan
AU  - Đokić, Jelena
PY  - 2023
UR  - https://aseestant.ceon.rs/index.php/arhfarm/article/view/46614
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2297
AB  - Probiotic lactobacilli exhibit the potential to promote health benefits for the host. Thanks to its numerous beneficial effects on human health, Limosilactobacillus fermentum stood out as an excellent candidate for the development of commercial probiotic preparations aiming to prevent community-acquired infections. In this study, several in vitro tests, including biofilm formation assay, assessment of antibiotic susceptibility, survival in simulated gastrointestinal tract conditions and attachment to intestinal Caco-2 cells, were used to estimate the safety and probiotic potential of L. fermentum BGHV110 strain. Additionally, Caenorhabditis elegans was used as an in vivo model system for the evaluation of L. fermentum BGHV110 influence on the host’s innate immune response. The results revealed that L. fermentum BGHV110 strain showed an excellent capability to survive harsh conditions of the gut, to attach to intestinal Caco-2 cells and to stimulate conserved p38 MAPK immunity pathway and expression of the clc-1 claudin-like gene and antimicrobial peptides in C. elegans in order to enhance the immune response against pathogens. Finally, L. fermentum BGHV110 showed no virulence traits and susceptibility to tested antibiotics, confirming its safety status which enables it to be applied as a future probiotic.
PB  - Centre for Evaluation in Education and Science
T2  - Archives of Pharmacy
T1  - Probiotic characterization of Limosilactobacillus fermentum BGHV110 strain and its influence on innate immune response in Caenorhabditis elegans
T1  - Probiotička karakterizacija soja Limosilactobacillus fermentum BGHV110 i njegov uticaj na urođeni imunski odgovor kod Caenorhabditis elegans
EP  - 585
IS  - Notebook 6
SP  - 571
VL  - 73
DO  - 10.5937/arhfarm73-46614
ER  - 

@article{
author = "Dinić, Miroslav and Popović, Nikola and Radojević, Dušan and Đokić, Jelena",
year = "2023",
abstract = "Probiotic lactobacilli exhibit the potential to promote health benefits for the host. Thanks to its numerous beneficial effects on human health, Limosilactobacillus fermentum stood out as an excellent candidate for the development of commercial probiotic preparations aiming to prevent community-acquired infections. In this study, several in vitro tests, including biofilm formation assay, assessment of antibiotic susceptibility, survival in simulated gastrointestinal tract conditions and attachment to intestinal Caco-2 cells, were used to estimate the safety and probiotic potential of L. fermentum BGHV110 strain. Additionally, Caenorhabditis elegans was used as an in vivo model system for the evaluation of L. fermentum BGHV110 influence on the host’s innate immune response. The results revealed that L. fermentum BGHV110 strain showed an excellent capability to survive harsh conditions of the gut, to attach to intestinal Caco-2 cells and to stimulate conserved p38 MAPK immunity pathway and expression of the clc-1 claudin-like gene and antimicrobial peptides in C. elegans in order to enhance the immune response against pathogens. Finally, L. fermentum BGHV110 showed no virulence traits and susceptibility to tested antibiotics, confirming its safety status which enables it to be applied as a future probiotic.",
publisher = "Centre for Evaluation in Education and Science",
journal = "Archives of Pharmacy",
title = "Probiotic characterization of Limosilactobacillus fermentum BGHV110 strain and its influence on innate immune response in Caenorhabditis elegans, Probiotička karakterizacija soja Limosilactobacillus fermentum BGHV110 i njegov uticaj na urođeni imunski odgovor kod Caenorhabditis elegans",
pages = "585-571",
number = "Notebook 6",
volume = "73",
doi = "10.5937/arhfarm73-46614"
}

Dinić, M., Popović, N., Radojević, D.,& Đokić, J.. (2023). Probiotic characterization of Limosilactobacillus fermentum BGHV110 strain and its influence on innate immune response in Caenorhabditis elegans. in Archives of Pharmacy
Centre for Evaluation in Education and Science., 73(Notebook 6), 571-585.
https://doi.org/10.5937/arhfarm73-46614

Dinić M, Popović N, Radojević D, Đokić J. Probiotic characterization of Limosilactobacillus fermentum BGHV110 strain and its influence on innate immune response in Caenorhabditis elegans. in Archives of Pharmacy. 2023;73(Notebook 6):571-585.
doi:10.5937/arhfarm73-46614 .

Dinić, Miroslav, Popović, Nikola, Radojević, Dušan, Đokić, Jelena, "Probiotic characterization of Limosilactobacillus fermentum BGHV110 strain and its influence on innate immune response in Caenorhabditis elegans" in Archives of Pharmacy, 73, no. Notebook 6 (2023):571-585,
https://doi.org/10.5937/arhfarm73-46614 . .

TY  - JOUR
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Dinić, Miroslav
AU  - Bisenić, Aleksandar
AU  - Golić, Nataša
AU  - Vucević, Dragana
AU  - Đokić, Jelena
AU  - Tomić, Sergej
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1540
AB  - Over-activated myeloid cells and disturbance in gut microbiota composition are critical factors contributing to the pathogenesis of Multiple Sclerosis (MS). Myeloid-derived suppressor cells (MDSCs) emerged as promising regulators of chronic inflammatory diseases, including autoimmune diseases. However, it remained unclear whether MDSCs display any therapeutic potential in MS, and how this therapy modulates gut microbiota composition. Here, we assessed the potential of in vitro generated bone marrow-derived MDSCs to ameliorate experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats and investigated how their application associates with the changes in gut microbiota composition. MDSCs differentiated with prostaglandin (PG)E2 (MDSC-PGE2) and control MDSCs (differentiated without PGE2) displayed strong immunosuppressive properties in vitro, but only MDSC-PGE2 significantly ameliorated EAE symptoms. This effect correlated with a reduced infiltration of Th17 and IFN-gamma-producing NK cells, and an increased proportion of regulatory T cells in the CNS and spleen. Importantly, both MDSCs and MDSC-PGE2 prevented EAE-induced reduction of gut microbiota diversity, but only MDSC-PGE2 prevented the extensive alterations in gut microbiota composition following their early migration into Payer's patches and mesenteric lymph nodes. This phenomenon was related to the significant enrichment of gut microbial taxa with potential immunoregulatory properties, as well as higher levels of butyrate, propionate, and putrescine in feces. This study provides new insights into the host-microbiota interactions in EAE, suggesting that activated MDSCs could be potentially used as an efficient therapy for acute phases of MS. Considering a significant association between the efficacy of MDSC-PGE2 and gut microbiota composition, our findings also provide a rationale for further exploring the specific microbial metabolites in MS therapy.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Gut Microbes
T1  - Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis
IS  - 1
VL  - 14
DO  - 10.1080/19490976.2022.2127455
ER  - 

@article{
author = "Radojević, Dušan and Bekić, Marina and Gruden-Movsesijan, Alisa and Ilić, Nataša and Dinić, Miroslav and Bisenić, Aleksandar and Golić, Nataša and Vucević, Dragana and Đokić, Jelena and Tomić, Sergej",
year = "2022",
abstract = "Over-activated myeloid cells and disturbance in gut microbiota composition are critical factors contributing to the pathogenesis of Multiple Sclerosis (MS). Myeloid-derived suppressor cells (MDSCs) emerged as promising regulators of chronic inflammatory diseases, including autoimmune diseases. However, it remained unclear whether MDSCs display any therapeutic potential in MS, and how this therapy modulates gut microbiota composition. Here, we assessed the potential of in vitro generated bone marrow-derived MDSCs to ameliorate experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats and investigated how their application associates with the changes in gut microbiota composition. MDSCs differentiated with prostaglandin (PG)E2 (MDSC-PGE2) and control MDSCs (differentiated without PGE2) displayed strong immunosuppressive properties in vitro, but only MDSC-PGE2 significantly ameliorated EAE symptoms. This effect correlated with a reduced infiltration of Th17 and IFN-gamma-producing NK cells, and an increased proportion of regulatory T cells in the CNS and spleen. Importantly, both MDSCs and MDSC-PGE2 prevented EAE-induced reduction of gut microbiota diversity, but only MDSC-PGE2 prevented the extensive alterations in gut microbiota composition following their early migration into Payer's patches and mesenteric lymph nodes. This phenomenon was related to the significant enrichment of gut microbial taxa with potential immunoregulatory properties, as well as higher levels of butyrate, propionate, and putrescine in feces. This study provides new insights into the host-microbiota interactions in EAE, suggesting that activated MDSCs could be potentially used as an efficient therapy for acute phases of MS. Considering a significant association between the efficacy of MDSC-PGE2 and gut microbiota composition, our findings also provide a rationale for further exploring the specific microbial metabolites in MS therapy.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Gut Microbes",
title = "Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis",
number = "1",
volume = "14",
doi = "10.1080/19490976.2022.2127455"
}

Radojević, D., Bekić, M., Gruden-Movsesijan, A., Ilić, N., Dinić, M., Bisenić, A., Golić, N., Vucević, D., Đokić, J.,& Tomić, S.. (2022). Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis. in Gut Microbes
Taylor & Francis Inc, Philadelphia., 14(1).
https://doi.org/10.1080/19490976.2022.2127455

Radojević D, Bekić M, Gruden-Movsesijan A, Ilić N, Dinić M, Bisenić A, Golić N, Vucević D, Đokić J, Tomić S. Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis. in Gut Microbes. 2022;14(1).
doi:10.1080/19490976.2022.2127455 .

Radojević, Dušan, Bekić, Marina, Gruden-Movsesijan, Alisa, Ilić, Nataša, Dinić, Miroslav, Bisenić, Aleksandar, Golić, Nataša, Vucević, Dragana, Đokić, Jelena, Tomić, Sergej, "Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis" in Gut Microbes, 14, no. 1 (2022),
https://doi.org/10.1080/19490976.2022.2127455 . .

TY  - JOUR
AU  - Čolić, Miodrag
AU  - Bekić, Marina
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Savikin, Katarina
AU  - Miljus, Nataša
AU  - Marković, Milan
AU  - Skrbić, Ranko
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1605
AB  - Pomegranate peel extract (PoPEx) has been shown to have antioxidant and anti-inflammatory properties, but its effect on the adaptive immune system has not been sufficiently investigated. In this study, the treatment of human peripheral blood mononuclear cells (PBMC) with PoPEx (range 6.25-400 mu g/mL) resulted in cytotoxicity at concentrations of 100 mu g/mL and higher, due to the induction of apoptosis and oxidative stress, whereas autophagy was reduced. At non-cytotoxic concentrations, the opposite effect on these processes was observed simultaneously with the inhibition of PHA-induced PBMC proliferation and a significant decrease in the expression of CD4. PoPEx differently modulated the expression of activation markers (CD69, CD25, ICOS) and PD1 (inhibitory marker), depending on the dose and T-cell subsets. PoPEx (starting from 12.5 mu g/mL) suppressed the production of Th1 (IFN-gamma), Th17 (IL-17A, IL-17F, and IL-22), Th9 (IL-9), and proinflammatory cytokines (TNF-alpha and IL-6) in culture supernatants. Lower concentrations upregulated Th2 (IL-5 and IL-13) and Treg (IL-10) responses as well as CD4+CD25hiFoxp3+ cell frequency. Higher concentrations of PoPEx increased the frequency of IL-10- and TGF-beta-producing T-cells (much higher in the CD4+ subset). In conclusion, our study suggested for the first time complex immunoregulatory effects of PoPEx on T cells, which could assist in the suppression of chronic inflammatory and autoimmune diseases.
PB  - MDPI, Basel
T2  - Pharmaceutics
T1  - Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture
IS  - 6
VL  - 14
DO  - 10.3390/pharmaceutics14061140
ER  - 

@article{
author = "Čolić, Miodrag and Bekić, Marina and Tomić, Sergej and Đokić, Jelena and Radojević, Dušan and Savikin, Katarina and Miljus, Nataša and Marković, Milan and Skrbić, Ranko",
year = "2022",
abstract = "Pomegranate peel extract (PoPEx) has been shown to have antioxidant and anti-inflammatory properties, but its effect on the adaptive immune system has not been sufficiently investigated. In this study, the treatment of human peripheral blood mononuclear cells (PBMC) with PoPEx (range 6.25-400 mu g/mL) resulted in cytotoxicity at concentrations of 100 mu g/mL and higher, due to the induction of apoptosis and oxidative stress, whereas autophagy was reduced. At non-cytotoxic concentrations, the opposite effect on these processes was observed simultaneously with the inhibition of PHA-induced PBMC proliferation and a significant decrease in the expression of CD4. PoPEx differently modulated the expression of activation markers (CD69, CD25, ICOS) and PD1 (inhibitory marker), depending on the dose and T-cell subsets. PoPEx (starting from 12.5 mu g/mL) suppressed the production of Th1 (IFN-gamma), Th17 (IL-17A, IL-17F, and IL-22), Th9 (IL-9), and proinflammatory cytokines (TNF-alpha and IL-6) in culture supernatants. Lower concentrations upregulated Th2 (IL-5 and IL-13) and Treg (IL-10) responses as well as CD4+CD25hiFoxp3+ cell frequency. Higher concentrations of PoPEx increased the frequency of IL-10- and TGF-beta-producing T-cells (much higher in the CD4+ subset). In conclusion, our study suggested for the first time complex immunoregulatory effects of PoPEx on T cells, which could assist in the suppression of chronic inflammatory and autoimmune diseases.",
publisher = "MDPI, Basel",
journal = "Pharmaceutics",
title = "Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture",
number = "6",
volume = "14",
doi = "10.3390/pharmaceutics14061140"
}

Čolić, M., Bekić, M., Tomić, S., Đokić, J., Radojević, D., Savikin, K., Miljus, N., Marković, M.,& Skrbić, R.. (2022). Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture. in Pharmaceutics
MDPI, Basel., 14(6).
https://doi.org/10.3390/pharmaceutics14061140

Čolić M, Bekić M, Tomić S, Đokić J, Radojević D, Savikin K, Miljus N, Marković M, Skrbić R. Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture. in Pharmaceutics. 2022;14(6).
doi:10.3390/pharmaceutics14061140 .

Čolić, Miodrag, Bekić, Marina, Tomić, Sergej, Đokić, Jelena, Radojević, Dušan, Savikin, Katarina, Miljus, Nataša, Marković, Milan, Skrbić, Ranko, "Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture" in Pharmaceutics, 14, no. 6 (2022),
https://doi.org/10.3390/pharmaceutics14061140 . .

TY  - JOUR
AU  - Tertel, Tobias
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Stevanović, Dejan
AU  - Ilić, Nataša
AU  - Giebel, Bernd
AU  - Kosanović, Maja
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1517
AB  - COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13(+) and CD82(+) EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC(+) EVs than sera of the healthy donors and more CD24(+) EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.
PB  - Hoboken : Wiley
T2  - Journal of Extracellular Vesicles
T1  - Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients
IS  - 8
VL  - 11
DO  - 10.1002/jev2.12257
ER  - 

@article{
author = "Tertel, Tobias and Tomić, Sergej and Đokić, Jelena and Radojević, Dušan and Stevanović, Dejan and Ilić, Nataša and Giebel, Bernd and Kosanović, Maja",
year = "2022",
abstract = "COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13(+) and CD82(+) EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC(+) EVs than sera of the healthy donors and more CD24(+) EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.",
publisher = "Hoboken : Wiley",
journal = "Journal of Extracellular Vesicles",
title = "Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients",
number = "8",
volume = "11",
doi = "10.1002/jev2.12257"
}

Tertel, T., Tomić, S., Đokić, J., Radojević, D., Stevanović, D., Ilić, N., Giebel, B.,& Kosanović, M.. (2022). Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients. in Journal of Extracellular Vesicles
Hoboken : Wiley., 11(8).
https://doi.org/10.1002/jev2.12257

Tertel T, Tomić S, Đokić J, Radojević D, Stevanović D, Ilić N, Giebel B, Kosanović M. Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients. in Journal of Extracellular Vesicles. 2022;11(8).
doi:10.1002/jev2.12257 .

Tertel, Tobias, Tomić, Sergej, Đokić, Jelena, Radojević, Dušan, Stevanović, Dejan, Ilić, Nataša, Giebel, Bernd, Kosanović, Maja, "Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients" in Journal of Extracellular Vesicles, 11, no. 8 (2022),
https://doi.org/10.1002/jev2.12257 . .

TY  - JOUR
AU  - Bekić, Marina
AU  - Radanović, Marina
AU  - Đokić, Jelena
AU  - Tomić, Sergej
AU  - Eraković, Mile
AU  - Radojević, Dušan
AU  - Duka, Milos
AU  - Marković, Dejan
AU  - Marković, Milan
AU  - Ismaili, Bashkim
AU  - Bokonjić, Dejan
AU  - Čolić, Miodrag
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1558
AB  - Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-alpha, RANTES, TLR-2, HIF-1 alpha, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-alpha were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-beta, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis
IS  - 7
VL  - 23
DO  - 10.3390/ijms23073510
ER  - 

@article{
author = "Bekić, Marina and Radanović, Marina and Đokić, Jelena and Tomić, Sergej and Eraković, Mile and Radojević, Dušan and Duka, Milos and Marković, Dejan and Marković, Milan and Ismaili, Bashkim and Bokonjić, Dejan and Čolić, Miodrag",
year = "2022",
abstract = "Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-alpha, RANTES, TLR-2, HIF-1 alpha, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-alpha were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-beta, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis",
number = "7",
volume = "23",
doi = "10.3390/ijms23073510"
}

Bekić, M., Radanović, M., Đokić, J., Tomić, S., Eraković, M., Radojević, D., Duka, M., Marković, D., Marković, M., Ismaili, B., Bokonjić, D.,& Čolić, M.. (2022). Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis. in International Journal of Molecular Sciences
MDPI, Basel., 23(7).
https://doi.org/10.3390/ijms23073510

Bekić M, Radanović M, Đokić J, Tomić S, Eraković M, Radojević D, Duka M, Marković D, Marković M, Ismaili B, Bokonjić D, Čolić M. Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis. in International Journal of Molecular Sciences. 2022;23(7).
doi:10.3390/ijms23073510 .

Bekić, Marina, Radanović, Marina, Đokić, Jelena, Tomić, Sergej, Eraković, Mile, Radojević, Dušan, Duka, Milos, Marković, Dejan, Marković, Milan, Ismaili, Bashkim, Bokonjić, Dejan, Čolić, Miodrag, "Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis" in International Journal of Molecular Sciences, 23, no. 7 (2022),
https://doi.org/10.3390/ijms23073510 . .

TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Vasilev, Saša
AU  - Dinić, Miroslav
AU  - Golić, Nataša
AU  - Vučević, Dragana
AU  - Čolić, Miodrag
AU  - Tomić, Sergej
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1875
AB  - The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.
PB  - Novi Sad : Faculty of Sciences, Department of Biology and Ecology
C3  - Biologia Serbica
T1  - Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition
IS  - 1 (Special Edition)
SP  - 98
VL  - 43
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1875
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Gruden-Movsesijan, Alisa and Ilić, Nataša and Vasilev, Saša and Dinić, Miroslav and Golić, Nataša and Vučević, Dragana and Čolić, Miodrag and Tomić, Sergej and Đokić, Jelena",
year = "2021",
abstract = "The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.",
publisher = "Novi Sad : Faculty of Sciences, Department of Biology and Ecology",
journal = "Biologia Serbica",
title = "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition",
number = "1 (Special Edition)",
pages = "98",
volume = "43",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1875"
}

Radojević, D., Bekić, M., Gruden-Movsesijan, A., Ilić, N., Vasilev, S., Dinić, M., Golić, N., Vučević, D., Čolić, M., Tomić, S.,& Đokić, J.. (2021). Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica
Novi Sad : Faculty of Sciences, Department of Biology and Ecology., 43(1 (Special Edition)), 98.
https://hdl.handle.net/21.15107/rcub_imagine_1875

Radojević D, Bekić M, Gruden-Movsesijan A, Ilić N, Vasilev S, Dinić M, Golić N, Vučević D, Čolić M, Tomić S, Đokić J. Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica. 2021;43(1 (Special Edition)):98.
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

Radojević, Dušan, Bekić, Marina, Gruden-Movsesijan, Alisa, Ilić, Nataša, Vasilev, Saša, Dinić, Miroslav, Golić, Nataša, Vučević, Dragana, Čolić, Miodrag, Tomić, Sergej, Đokić, Jelena, "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition" in Biologia Serbica, 43, no. 1 (Special Edition) (2021):98,
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

TY  - JOUR
AU  - Radojević, Dušan
AU  - Tomić, Sergej
AU  - Mihajlović, Dusan
AU  - Tolinački, Maja
AU  - Pavlović, Bojan
AU  - Vucević, Dragana
AU  - Bojić, Svetlana
AU  - Golić, Nataša
AU  - Čolić, Miodrag
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1475
AB  - Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher alpha-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-alpha, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-alpha, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Gut Microbes
T1  - Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro
IS  - 1
VL  - 13
DO  - 10.1080/19490976.2021.1921927
ER  - 

@article{
author = "Radojević, Dušan and Tomić, Sergej and Mihajlović, Dusan and Tolinački, Maja and Pavlović, Bojan and Vucević, Dragana and Bojić, Svetlana and Golić, Nataša and Čolić, Miodrag and Đokić, Jelena",
year = "2021",
abstract = "Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher alpha-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-alpha, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-alpha, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Gut Microbes",
title = "Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro",
number = "1",
volume = "13",
doi = "10.1080/19490976.2021.1921927"
}

Radojević, D., Tomić, S., Mihajlović, D., Tolinački, M., Pavlović, B., Vucević, D., Bojić, S., Golić, N., Čolić, M.,& Đokić, J.. (2021). Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro. in Gut Microbes
Taylor & Francis Inc, Philadelphia., 13(1).
https://doi.org/10.1080/19490976.2021.1921927

Radojević D, Tomić S, Mihajlović D, Tolinački M, Pavlović B, Vucević D, Bojić S, Golić N, Čolić M, Đokić J. Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro. in Gut Microbes. 2021;13(1).
doi:10.1080/19490976.2021.1921927 .

Radojević, Dušan, Tomić, Sergej, Mihajlović, Dusan, Tolinački, Maja, Pavlović, Bojan, Vucević, Dragana, Bojić, Svetlana, Golić, Nataša, Čolić, Miodrag, Đokić, Jelena, "Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro" in Gut Microbes, 13, no. 1 (2021),
https://doi.org/10.1080/19490976.2021.1921927 . .

TY  - JOUR
AU  - Dinić, Miroslav
AU  - Jakovljević, Stefan
AU  - Đokić, Jelena
AU  - Popović, Nikola
AU  - Radojević, Dušan
AU  - Strahinić, Ivana
AU  - Golić, Nataša
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1473
AB  - The host-microbiota cross-talk represents an important factor contributing to innate immune response and host resistance during infection. It has been shown that probiotic lactobacilli exhibit the ability to modulate innate immunity and enhance pathogen elimination. Here we showed that heat-inactivated probiotic strain Lactobacillus curvatus BGMK2-41 stimulates immune response and resistance of the Caenorhabditis elegans against Staphylococcus aureus and Pseudomonas aeruginosa. By employing qRT-PCR and western blot analysis we showed that heat-inactivated BGMK2-41 activated PMK-1/p38 MAPK immunity pathway which prolongs the survival of C. elegans exposed to pathogenic bacteria in nematode killing assays. The C. elegans pmk-1 mutant was used to demonstrate a mechanistic basis for the antimicrobial potential of BGMK2-41, showing that BGMK2-41 upregulated PMK-1/p38 MAPK dependent transcription of C-type lectins, lysozymes and tight junction protein CLC-1. Overall, this study suggests that PMK-1/p38 MAPK-dependent immune regulation by BGMK2-41 is essential for probiotic-mediated C. elegans protection against gram-positive and gram-negative bacteria and could be further explored for development of probiotics with the potential to increase resistance of the host towards pathogens.
PB  - Nature Portfolio, Berlin
T2  - Scientific Reports
T1  - Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria
IS  - 1
VL  - 11
DO  - 10.1038/s41598-021-00698-5
ER  - 

@article{
author = "Dinić, Miroslav and Jakovljević, Stefan and Đokić, Jelena and Popović, Nikola and Radojević, Dušan and Strahinić, Ivana and Golić, Nataša",
year = "2021",
abstract = "The host-microbiota cross-talk represents an important factor contributing to innate immune response and host resistance during infection. It has been shown that probiotic lactobacilli exhibit the ability to modulate innate immunity and enhance pathogen elimination. Here we showed that heat-inactivated probiotic strain Lactobacillus curvatus BGMK2-41 stimulates immune response and resistance of the Caenorhabditis elegans against Staphylococcus aureus and Pseudomonas aeruginosa. By employing qRT-PCR and western blot analysis we showed that heat-inactivated BGMK2-41 activated PMK-1/p38 MAPK immunity pathway which prolongs the survival of C. elegans exposed to pathogenic bacteria in nematode killing assays. The C. elegans pmk-1 mutant was used to demonstrate a mechanistic basis for the antimicrobial potential of BGMK2-41, showing that BGMK2-41 upregulated PMK-1/p38 MAPK dependent transcription of C-type lectins, lysozymes and tight junction protein CLC-1. Overall, this study suggests that PMK-1/p38 MAPK-dependent immune regulation by BGMK2-41 is essential for probiotic-mediated C. elegans protection against gram-positive and gram-negative bacteria and could be further explored for development of probiotics with the potential to increase resistance of the host towards pathogens.",
publisher = "Nature Portfolio, Berlin",
journal = "Scientific Reports",
title = "Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria",
number = "1",
volume = "11",
doi = "10.1038/s41598-021-00698-5"
}

Dinić, M., Jakovljević, S., Đokić, J., Popović, N., Radojević, D., Strahinić, I.,& Golić, N.. (2021). Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria. in Scientific Reports
Nature Portfolio, Berlin., 11(1).
https://doi.org/10.1038/s41598-021-00698-5

Dinić M, Jakovljević S, Đokić J, Popović N, Radojević D, Strahinić I, Golić N. Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria. in Scientific Reports. 2021;11(1).
doi:10.1038/s41598-021-00698-5 .

Dinić, Miroslav, Jakovljević, Stefan, Đokić, Jelena, Popović, Nikola, Radojević, Dušan, Strahinić, Ivana, Golić, Nataša, "Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria" in Scientific Reports, 11, no. 1 (2021),
https://doi.org/10.1038/s41598-021-00698-5 . .

TY  - JOUR
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Stevanović, Dejan
AU  - Ilić, Nataša
AU  - Gruden-Movsesijan, Alisa
AU  - Dinić, Miroslav
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Mitrović, Nebojša
AU  - Tomasević, Ratko
AU  - Mikić, Dragan
AU  - Stojanović, Dragos
AU  - Čolić, Miodrag
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1446
AB  - Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed similar to 140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with similar to 30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-gamma production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients
VL  - 12
DO  - 10.3389/fimmu.2021.614599
ER  - 

@article{
author = "Tomić, Sergej and Đokić, Jelena and Stevanović, Dejan and Ilić, Nataša and Gruden-Movsesijan, Alisa and Dinić, Miroslav and Radojević, Dušan and Bekić, Marina and Mitrović, Nebojša and Tomasević, Ratko and Mikić, Dragan and Stojanović, Dragos and Čolić, Miodrag",
year = "2021",
abstract = "Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed similar to 140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with similar to 30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-gamma production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients",
volume = "12",
doi = "10.3389/fimmu.2021.614599"
}

Tomić, S., Đokić, J., Stevanović, D., Ilić, N., Gruden-Movsesijan, A., Dinić, M., Radojević, D., Bekić, M., Mitrović, N., Tomasević, R., Mikić, D., Stojanović, D.,& Čolić, M.. (2021). Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients. in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 12.
https://doi.org/10.3389/fimmu.2021.614599

Tomić S, Đokić J, Stevanović D, Ilić N, Gruden-Movsesijan A, Dinić M, Radojević D, Bekić M, Mitrović N, Tomasević R, Mikić D, Stojanović D, Čolić M. Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients. in Frontiers in Immunology. 2021;12.
doi:10.3389/fimmu.2021.614599 .

Tomić, Sergej, Đokić, Jelena, Stevanović, Dejan, Ilić, Nataša, Gruden-Movsesijan, Alisa, Dinić, Miroslav, Radojević, Dušan, Bekić, Marina, Mitrović, Nebojša, Tomasević, Ratko, Mikić, Dragan, Stojanović, Dragos, Čolić, Miodrag, "Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients" in Frontiers in Immunology, 12 (2021),
https://doi.org/10.3389/fimmu.2021.614599 . .

TY  - JOUR
AU  - Dinić, Miroslav
AU  - Herholz, Marija
AU  - Kacarević, Uros
AU  - Radojević, Dušan
AU  - Novović, Katarina
AU  - Đokić, Jelena
AU  - Trifunović, Aleksandra
AU  - Golić, Nataša
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1431
AB  - Gut homeostasis is maintained by the close interaction between commensal intestinal microbiota and the host, affecting the most complex physiological processes, such as aging. Some commensal bacteria with the potential to promote healthy aging arise as attractive candidates for the development of pro-longevity probiotics. Here, we showed that heat-inactivated human commensal Lactobacillus fermentum BGHV110 (BGHV110) extends the lifespan of Caenorhabditis elegans and improves age-related physiological features, including locomotor function and lipid metabolism. Mechanistically, we found that BGHV110 promotes HLH30/TFEB-dependent autophagy to delay aging, as longevity assurance was completely abolished in the mutant lacking HLH-30, a major autophagy regulator in C. elegans. Moreover, we observed that BGHV110 partially decreased the content of lipid droplets in an HLH-30-dependent manner and, at the same time, slightly increased mitochondrial activity. In summary, this study demonstrates that specific factors from commensal bacteria can be used to exploit HLH-30/TFEB-mediated autophagy in order to promote longevity and fitness of the host.
PB  - Impact Journals LLC
T2  - Aging
T1  - Host-commensal interaction promotes health and lifespan in Caenorhabditis elegans through the activation of HLH-30/TFEB-mediated autophagy
EP  - 8054
IS  - 6
SP  - 8040
VL  - 13
DO  - 10.18632/aging.202885
ER  - 

@article{
author = "Dinić, Miroslav and Herholz, Marija and Kacarević, Uros and Radojević, Dušan and Novović, Katarina and Đokić, Jelena and Trifunović, Aleksandra and Golić, Nataša",
year = "2021",
abstract = "Gut homeostasis is maintained by the close interaction between commensal intestinal microbiota and the host, affecting the most complex physiological processes, such as aging. Some commensal bacteria with the potential to promote healthy aging arise as attractive candidates for the development of pro-longevity probiotics. Here, we showed that heat-inactivated human commensal Lactobacillus fermentum BGHV110 (BGHV110) extends the lifespan of Caenorhabditis elegans and improves age-related physiological features, including locomotor function and lipid metabolism. Mechanistically, we found that BGHV110 promotes HLH30/TFEB-dependent autophagy to delay aging, as longevity assurance was completely abolished in the mutant lacking HLH-30, a major autophagy regulator in C. elegans. Moreover, we observed that BGHV110 partially decreased the content of lipid droplets in an HLH-30-dependent manner and, at the same time, slightly increased mitochondrial activity. In summary, this study demonstrates that specific factors from commensal bacteria can be used to exploit HLH-30/TFEB-mediated autophagy in order to promote longevity and fitness of the host.",
publisher = "Impact Journals LLC",
journal = "Aging",
title = "Host-commensal interaction promotes health and lifespan in Caenorhabditis elegans through the activation of HLH-30/TFEB-mediated autophagy",
pages = "8054-8040",
number = "6",
volume = "13",
doi = "10.18632/aging.202885"
}

Dinić, M., Herholz, M., Kacarević, U., Radojević, D., Novović, K., Đokić, J., Trifunović, A.,& Golić, N.. (2021). Host-commensal interaction promotes health and lifespan in Caenorhabditis elegans through the activation of HLH-30/TFEB-mediated autophagy. in Aging
Impact Journals LLC., 13(6), 8040-8054.
https://doi.org/10.18632/aging.202885

Dinić M, Herholz M, Kacarević U, Radojević D, Novović K, Đokić J, Trifunović A, Golić N. Host-commensal interaction promotes health and lifespan in Caenorhabditis elegans through the activation of HLH-30/TFEB-mediated autophagy. in Aging. 2021;13(6):8040-8054.
doi:10.18632/aging.202885 .

Dinić, Miroslav, Herholz, Marija, Kacarević, Uros, Radojević, Dušan, Novović, Katarina, Đokić, Jelena, Trifunović, Aleksandra, Golić, Nataša, "Host-commensal interaction promotes health and lifespan in Caenorhabditis elegans through the activation of HLH-30/TFEB-mediated autophagy" in Aging, 13, no. 6 (2021):8040-8054,
https://doi.org/10.18632/aging.202885 . .

TY  - CONF
AU  - Kosanović, Maja
AU  - Tertel, Tobias
AU  - Đokić, Jelena
AU  - Ilić, Nataša
AU  - Radojević, Dušan
AU  - Stevanović, Dejan
AU  - Movsesijan, Alisa Gruden
AU  - Giebel, Bernd
AU  - Tomić, Sergej
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1434
PB  - Wiley, Hoboken
C3  - European Journal of Immunology
T1  - Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity
EP  - 352
SP  - 352
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1434
ER  - 

@conference{
author = "Kosanović, Maja and Tertel, Tobias and Đokić, Jelena and Ilić, Nataša and Radojević, Dušan and Stevanović, Dejan and Movsesijan, Alisa Gruden and Giebel, Bernd and Tomić, Sergej",
year = "2021",
publisher = "Wiley, Hoboken",
journal = "European Journal of Immunology",
title = "Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity",
pages = "352-352",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1434"
}

Kosanović, M., Tertel, T., Đokić, J., Ilić, N., Radojević, D., Stevanović, D., Movsesijan, A. G., Giebel, B.,& Tomić, S.. (2021). Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity. in European Journal of Immunology
Wiley, Hoboken., 51, 352-352.
https://hdl.handle.net/21.15107/rcub_imagine_1434

Kosanović M, Tertel T, Đokić J, Ilić N, Radojević D, Stevanović D, Movsesijan AG, Giebel B, Tomić S. Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity. in European Journal of Immunology. 2021;51:352-352.
https://hdl.handle.net/21.15107/rcub_imagine_1434 .

Kosanović, Maja, Tertel, Tobias, Đokić, Jelena, Ilić, Nataša, Radojević, Dušan, Stevanović, Dejan, Movsesijan, Alisa Gruden, Giebel, Bernd, Tomić, Sergej, "Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity" in European Journal of Immunology, 51 (2021):352-352,
https://hdl.handle.net/21.15107/rcub_imagine_1434 .

TY  - CONF
AU  - Bekić, Marina
AU  - Dinić, Miroslav
AU  - Radojević, Dušan
AU  - Ilić, Nataša
AU  - Vucević, Dragana
AU  - Vasilev, Sasa
AU  - Đokić, Jelena
AU  - Tomić, Sergej
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1436
PB  - Wiley, Hoboken
C3  - European Journal of Immunology
T1  - Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro
EP  - 179
SP  - 179
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1436
ER  - 

@conference{
author = "Bekić, Marina and Dinić, Miroslav and Radojević, Dušan and Ilić, Nataša and Vucević, Dragana and Vasilev, Sasa and Đokić, Jelena and Tomić, Sergej",
year = "2021",
publisher = "Wiley, Hoboken",
journal = "European Journal of Immunology",
title = "Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro",
pages = "179-179",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1436"
}

Bekić, M., Dinić, M., Radojević, D., Ilić, N., Vucević, D., Vasilev, S., Đokić, J.,& Tomić, S.. (2021). Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro. in European Journal of Immunology
Wiley, Hoboken., 51, 179-179.
https://hdl.handle.net/21.15107/rcub_imagine_1436

Bekić M, Dinić M, Radojević D, Ilić N, Vucević D, Vasilev S, Đokić J, Tomić S. Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro. in European Journal of Immunology. 2021;51:179-179.
https://hdl.handle.net/21.15107/rcub_imagine_1436 .

Bekić, Marina, Dinić, Miroslav, Radojević, Dušan, Ilić, Nataša, Vucević, Dragana, Vasilev, Sasa, Đokić, Jelena, Tomić, Sergej, "Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro" in European Journal of Immunology, 51 (2021):179-179,
https://hdl.handle.net/21.15107/rcub_imagine_1436 .