Stefania Olla
Researcher
Area of interest:
A computational chemist, with organic synthesis background and ability to plan, coordinate projects and resources. In depth expertise in supporting drug discovery optimization programs via the development and application of virtual screening technologies such as structure-based and ligand-based pharmacophore models, docking calculations. In depth knowledge in 3D QSAR, homology modelling, ADME-Tox and virtual screening cascade. Identification and selection of in silico druggable target resulting from genetic associations. Identification and selection of druggable targets and development of target-based and phenotypic assays. Expertise in autoimmune diseases including multiple sclerosis and central nervous system diseases. In silico approaches have been applied to identify and optimize kinase inhibitors as potential anticancer agents, antifungal agents, sirtuin modulators and protein-protein inhibitors. Excellent ability to work as a team, organization, flexibility, punctuality and responsibility.
Most significant publications:
2026
Gacem, Nadjet; Bezukladova, Svetlana; Windener, Farina; Karam, Tala; Ottoboni, Linda; Brambilla, Elena; Ruffini, Francesca; Soman, Karthik; Garcia-Diaz, Beatriz; Levy, Marion J F; Cui, Qiao-Ling; Formato, Alessia; Deboux, Cyrille; Chazot, Jeremy; Panic, Radmila; Albrecht, Stefanie; Yilmaz, Elif Nur; González, Raquel Guerrero; Eberini, Ivano; Olla, Stefania; Bresciani, Alberto; Goebels, Norbert; Zipp, Frauke; Agresti, Cristina; Antel, Jack; Evercooren, Anne Baron-Van; Kuhlmann, Tanja; Baranzini, Sergio E; Panina-Bordignon, Paola; Nait-Oumesmar, Brahim; Martino, Gianvito
In silico screening and preclinical validation identify bavisant as a therapeutic candidate for multiple sclerosis Journal Article
In: Sci. Transl. Med., 18 (833), pp. eads0633, 2026.
@article{Gacem2026-sl,
title = {In silico screening and preclinical validation identify bavisant
as a therapeutic candidate for multiple sclerosis},
author = {Nadjet Gacem and Svetlana Bezukladova and Farina Windener and Tala Karam and Linda Ottoboni and Elena Brambilla and Francesca Ruffini and Karthik Soman and Beatriz Garcia-Diaz and Marion J F Levy and Qiao-Ling Cui and Alessia Formato and Cyrille Deboux and Jeremy Chazot and Radmila Panic and Stefanie Albrecht and Elif Nur Yilmaz and Raquel Guerrero González and Ivano Eberini and Stefania Olla and Alberto Bresciani and Norbert Goebels and Frauke Zipp and Cristina Agresti and Jack Antel and Anne Baron-Van Evercooren and Tanja Kuhlmann and Sergio E Baranzini and Paola Panina-Bordignon and Brahim Nait-Oumesmar and Gianvito Martino},
year = {2026},
date = {2026-01-01},
journal = {Sci. Transl. Med.},
volume = {18},
number = {833},
pages = {eads0633},
abstract = {Current treatments for multiple sclerosis (MS) are insufficient
to delay the neurodegenerative process that is the main cause of
disability progression in patients with MS. Therapeutics aimed at
supporting myelin regeneration and neuroprotection are thus a
major unmet medical need for the progressive forms of MS. To
address this, we developed a strategy combining in silico
screening of more than 1500 repurposed compounds with a
validation pipeline of models, encompassing rodent and human in
vitro assays as well as mouse models of
demyelination/remyelination. From the initial library, 273 drugs
were prioritized in silico on the basis of the predicted effects
on myelination and neuroprotection, and among them, 160 were
potentially nontoxic. We identified 32 molecules that exerted a
promyelinating and a neuroprotective action on rodent and human
oligodendroglia and neurons. Our data identified classes of
compounds with potentially distinct mechanisms of action that may
foster remyelination and neuroprotection. The therapeutic
activity of one selected drug, the histamine receptor H3
antagonist bavisant, was further validated in mouse models of
demyelination and axonal injury reproducing some key pathological
features occurring in MS. Our in vivo studies demonstrated that
bavisant promoted remyelination and neuroprotection when
administered to LPC-treated, cuprizone-fed, or MOG-induced EAE
mice, as well as in a human oligodendroglia chimeric mouse model
of demyelination/remyelination. These findings provide
proof-of-concept validation for bavisant as a candidate for
neuroprotective clinical trials in MS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Current treatments for multiple sclerosis (MS) are insufficient
to delay the neurodegenerative process that is the main cause of
disability progression in patients with MS. Therapeutics aimed at
supporting myelin regeneration and neuroprotection are thus a
major unmet medical need for the progressive forms of MS. To
address this, we developed a strategy combining in silico
screening of more than 1500 repurposed compounds with a
validation pipeline of models, encompassing rodent and human in
vitro assays as well as mouse models of
demyelination/remyelination. From the initial library, 273 drugs
were prioritized in silico on the basis of the predicted effects
on myelination and neuroprotection, and among them, 160 were
potentially nontoxic. We identified 32 molecules that exerted a
promyelinating and a neuroprotective action on rodent and human
oligodendroglia and neurons. Our data identified classes of
compounds with potentially distinct mechanisms of action that may
foster remyelination and neuroprotection. The therapeutic
activity of one selected drug, the histamine receptor H3
antagonist bavisant, was further validated in mouse models of
demyelination and axonal injury reproducing some key pathological
features occurring in MS. Our in vivo studies demonstrated that
bavisant promoted remyelination and neuroprotection when
administered to LPC-treated, cuprizone-fed, or MOG-induced EAE
mice, as well as in a human oligodendroglia chimeric mouse model
of demyelination/remyelination. These findings provide
proof-of-concept validation for bavisant as a candidate for
neuroprotective clinical trials in MS.
to delay the neurodegenerative process that is the main cause of
disability progression in patients with MS. Therapeutics aimed at
supporting myelin regeneration and neuroprotection are thus a
major unmet medical need for the progressive forms of MS. To
address this, we developed a strategy combining in silico
screening of more than 1500 repurposed compounds with a
validation pipeline of models, encompassing rodent and human in
vitro assays as well as mouse models of
demyelination/remyelination. From the initial library, 273 drugs
were prioritized in silico on the basis of the predicted effects
on myelination and neuroprotection, and among them, 160 were
potentially nontoxic. We identified 32 molecules that exerted a
promyelinating and a neuroprotective action on rodent and human
oligodendroglia and neurons. Our data identified classes of
compounds with potentially distinct mechanisms of action that may
foster remyelination and neuroprotection. The therapeutic
activity of one selected drug, the histamine receptor H3
antagonist bavisant, was further validated in mouse models of
demyelination and axonal injury reproducing some key pathological
features occurring in MS. Our in vivo studies demonstrated that
bavisant promoted remyelination and neuroprotection when
administered to LPC-treated, cuprizone-fed, or MOG-induced EAE
mice, as well as in a human oligodendroglia chimeric mouse model
of demyelination/remyelination. These findings provide
proof-of-concept validation for bavisant as a candidate for
neuroprotective clinical trials in MS.
2025
Ölla, Stefania; Colombarolli, Stella Garcia; Siguri, Chiara; Murrau, Davide; Vitali, Alberto"
Phage display selection and in silico characterization of peptides as potential GroEL modulators Journal Article
In: Pharmaceutics, 18 (1), pp. 46, 2025.
@article{Olla2025-lv,
title = {Phage display selection and in silico characterization of
peptides as potential GroEL modulators},
author = {Stefania Ölla and Stella Garcia Colombarolli and Chiara Siguri and Davide Murrau and Alberto" Vitali},
year = {2025},
date = {2025-12-01},
journal = {Pharmaceutics},
volume = {18},
number = {1},
pages = {46},
publisher = {MDPI AG},
abstract = {Background/Objectives. Antibiotic resistance is an escalating
global health concern, highlighting the need for innovative
antibacterial strategies beyond traditional drugs. GroEL, a
highly conserved bacterial chaperonin essential for protein
folding and stress tolerance, represents a promising but
underexplored therapeutic target. This study aimed to identify
short peptides capable of binding GroEL monomers and potentially
altering their function, with the long-term goal of disrupting
bacterial survival mechanisms. Methods. A phage display
screening of a 12-mer peptide library was performed against
purified GroEL monomers, yielding five candidate peptides
(G1-G5). Their interactions with GroEL were analyzed through
molecular docking and molecular dynamics simulations using
three-dimensional GroEL structures (1MNF, 1XCK, 8S32). Stability
of binding and interaction profiles were assessed through
molecular dynamics-based analyses and MM/GBSA free energy
calculations. Results. Peptides G4 and G5 displayed the most
stable and energetically favorable interactions, with G4-8S32
showing the strongest binding (-116.68 kcal/mol). These peptides
localized near inter-subunit interfaces, suggesting potential
interference with GroEL oligomerization or allosteric
transitions, which are critical for its biological function.
Conclusions. Our findings demonstrate that short peptides can
stably bind GroEL and potentially modulate its activity.
Peptides G4 and G5 represent at our knowledge the first
promising scaffolds for developing a novel class of
peptide-based antibacterial agents targeting conserved
chaperonin systems. This work introduces a new avenue that
warrants further experimental validation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background/Objectives. Antibiotic resistance is an escalating
global health concern, highlighting the need for innovative
antibacterial strategies beyond traditional drugs. GroEL, a
highly conserved bacterial chaperonin essential for protein
folding and stress tolerance, represents a promising but
underexplored therapeutic target. This study aimed to identify
short peptides capable of binding GroEL monomers and potentially
altering their function, with the long-term goal of disrupting
bacterial survival mechanisms. Methods. A phage display
screening of a 12-mer peptide library was performed against
purified GroEL monomers, yielding five candidate peptides
(G1-G5). Their interactions with GroEL were analyzed through
molecular docking and molecular dynamics simulations using
three-dimensional GroEL structures (1MNF, 1XCK, 8S32). Stability
of binding and interaction profiles were assessed through
molecular dynamics-based analyses and MM/GBSA free energy
calculations. Results. Peptides G4 and G5 displayed the most
stable and energetically favorable interactions, with G4-8S32
showing the strongest binding (-116.68 kcal/mol). These peptides
localized near inter-subunit interfaces, suggesting potential
interference with GroEL oligomerization or allosteric
transitions, which are critical for its biological function.
Conclusions. Our findings demonstrate that short peptides can
stably bind GroEL and potentially modulate its activity.
Peptides G4 and G5 represent at our knowledge the first
promising scaffolds for developing a novel class of
peptide-based antibacterial agents targeting conserved
chaperonin systems. This work introduces a new avenue that
warrants further experimental validation.
global health concern, highlighting the need for innovative
antibacterial strategies beyond traditional drugs. GroEL, a
highly conserved bacterial chaperonin essential for protein
folding and stress tolerance, represents a promising but
underexplored therapeutic target. This study aimed to identify
short peptides capable of binding GroEL monomers and potentially
altering their function, with the long-term goal of disrupting
bacterial survival mechanisms. Methods. A phage display
screening of a 12-mer peptide library was performed against
purified GroEL monomers, yielding five candidate peptides
(G1-G5). Their interactions with GroEL were analyzed through
molecular docking and molecular dynamics simulations using
three-dimensional GroEL structures (1MNF, 1XCK, 8S32). Stability
of binding and interaction profiles were assessed through
molecular dynamics-based analyses and MM/GBSA free energy
calculations. Results. Peptides G4 and G5 displayed the most
stable and energetically favorable interactions, with G4-8S32
showing the strongest binding (-116.68 kcal/mol). These peptides
localized near inter-subunit interfaces, suggesting potential
interference with GroEL oligomerization or allosteric
transitions, which are critical for its biological function.
Conclusions. Our findings demonstrate that short peptides can
stably bind GroEL and potentially modulate its activity.
Peptides G4 and G5 represent at our knowledge the first
promising scaffolds for developing a novel class of
peptide-based antibacterial agents targeting conserved
chaperonin systems. This work introduces a new avenue that
warrants further experimental validation.
Ölla, Stefania; Idda, Maria Laura; Deiana, Manila; Lodde, Valeria; Delogu, Giuseppe; Caria, Antonio Cristian; Floris, Matteo; Cucca, Francesco"
Substituted 2-pyrrolinone compounds as inhibitors of B-cell activating factor (BAFF) for autoimmune diseases treatment Journal Article
In: Life Sci., 380 (123938), pp. 123938, 2025.
@article{Olla2025-or,
title = {Substituted 2-pyrrolinone compounds as inhibitors of B-cell
activating factor (BAFF) for autoimmune diseases treatment},
author = {Stefania Ölla and Maria Laura Idda and Manila Deiana and Valeria Lodde and Giuseppe Delogu and Antonio Cristian Caria and Matteo Floris and Francesco" Cucca},
year = {2025},
date = {2025-11-01},
journal = {Life Sci.},
volume = {380},
number = {123938},
pages = {123938},
publisher = {Elsevier BV},
abstract = {B-cell activating factor (BAFF) is a cytokine that plays a
critical role in the proliferation and differentiation of B
cells. We have previously demonstrated that its inherited
overexpression is associated with increased circulating B cell
and immunoglobulin levels, correlating with increased risk of
multiple sclerosis and systemic lupus erythematosus. These
findings suggest that enhanced BAFF expression may be involved
in the causal biology of these disorders, thus supporting the
rationale for therapeutic inhibition of this cytokine. However,
to date, no small-molecule modulator capable of inhibiting BAFF
is available. We therefore employed a virtual screening approach
to analyze a library of 275,561 small molecules, followed by in
vitro validation of 218 selected compounds with potential to
disrupt the interaction between BAFF and its receptor BAFFR. Our
results identified two promising small molecules, C45 and C145,
belonging to the substituted 2-pyrrolinone family, which
effectively inhibited BAFF activity. These compounds warrant
further investigation as potential therapeutic agents for
BAFF-driven autoimmune diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
B-cell activating factor (BAFF) is a cytokine that plays a
critical role in the proliferation and differentiation of B
cells. We have previously demonstrated that its inherited
overexpression is associated with increased circulating B cell
and immunoglobulin levels, correlating with increased risk of
multiple sclerosis and systemic lupus erythematosus. These
findings suggest that enhanced BAFF expression may be involved
in the causal biology of these disorders, thus supporting the
rationale for therapeutic inhibition of this cytokine. However,
to date, no small-molecule modulator capable of inhibiting BAFF
is available. We therefore employed a virtual screening approach
to analyze a library of 275,561 small molecules, followed by in
vitro validation of 218 selected compounds with potential to
disrupt the interaction between BAFF and its receptor BAFFR. Our
results identified two promising small molecules, C45 and C145,
belonging to the substituted 2-pyrrolinone family, which
effectively inhibited BAFF activity. These compounds warrant
further investigation as potential therapeutic agents for
BAFF-driven autoimmune diseases.
critical role in the proliferation and differentiation of B
cells. We have previously demonstrated that its inherited
overexpression is associated with increased circulating B cell
and immunoglobulin levels, correlating with increased risk of
multiple sclerosis and systemic lupus erythematosus. These
findings suggest that enhanced BAFF expression may be involved
in the causal biology of these disorders, thus supporting the
rationale for therapeutic inhibition of this cytokine. However,
to date, no small-molecule modulator capable of inhibiting BAFF
is available. We therefore employed a virtual screening approach
to analyze a library of 275,561 small molecules, followed by in
vitro validation of 218 selected compounds with potential to
disrupt the interaction between BAFF and its receptor BAFFR. Our
results identified two promising small molecules, C45 and C145,
belonging to the substituted 2-pyrrolinone family, which
effectively inhibited BAFF activity. These compounds warrant
further investigation as potential therapeutic agents for
BAFF-driven autoimmune diseases.
Cacciola, Anna; DÁngelo, Valeria; Gaetano, Federica De; Fais, Antonella; German`o, Maria Paola; Masala, Valentina; Olla, Stefania; Pistar`a, Venerando; Stancanelli, Rosanna; Tuberoso, Carlo Ignazio Giovanni; Ventura, Cinzia Anna
The Anti-Angiogenic Effect of Cynara cardunculus L. subsp. cardunculus Waste Product Journal Article
In: Foods, 14 (15), pp. 2656, 2025.
@article{Cacciola2025-ix,
title = {The Anti-Angiogenic Effect of Cynara cardunculus L. subsp.
cardunculus Waste Product},
author = {Anna Cacciola and Valeria DÁngelo and Federica De Gaetano and Antonella Fais and Maria Paola German`o and Valentina Masala and Stefania Olla and Venerando Pistar`a and Rosanna Stancanelli and Carlo Ignazio Giovanni Tuberoso and Cinzia Anna Ventura},
year = {2025},
date = {2025-07-01},
journal = {Foods},
volume = {14},
number = {15},
pages = {2656},
publisher = {MDPI AG},
abstract = {Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L.
var. sylvestris (Lam.) Fiori), the wild cardoon, is known for
its culinary applications and potential health benefits. Due to
this, and given the growing interest in circular economies,
deepening our under-standing of the effects of wild cardoon leaf
waste on angiogenesis and collagenase activity represents a
valuable opportunity to valorise agricultural byproducts as
health-promoting ingredients. In this study, the waste product
of wild cardoon leaves was extracted to examine its chemical
composition and biological activities. Analytical techniques
identified several bioactive compounds, including flavonoids,
hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids,
and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos
and the chick chorioallantoic membrane demonstrated
dose-dependent antiangiogenic effects, particularly enhanced by
the complexation with hydroxypropyl-$beta$-cyclodextrin
(HP-$beta$-CD). Considering the link between angiogenesis and
collagenase, the potential effects of the extract on collagenase
activity was investigated. The extract alone inhibited
collagenase with an IC50 value comparable to that of the
standard inhibitor while its complexed form exhibited a 4.5-fold
greater inhibitory activity. A molecular docking study examined
the interaction between the main compounds and collagenase. In
conclusion, wild cardoon leaves can represent a valuable source
of bioactive compounds. This study demonstrated that the
complexation of the extract with cyclodextrin determines an
increase in its biological activity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L.
var. sylvestris (Lam.) Fiori), the wild cardoon, is known for
its culinary applications and potential health benefits. Due to
this, and given the growing interest in circular economies,
deepening our under-standing of the effects of wild cardoon leaf
waste on angiogenesis and collagenase activity represents a
valuable opportunity to valorise agricultural byproducts as
health-promoting ingredients. In this study, the waste product
of wild cardoon leaves was extracted to examine its chemical
composition and biological activities. Analytical techniques
identified several bioactive compounds, including flavonoids,
hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids,
and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos
and the chick chorioallantoic membrane demonstrated
dose-dependent antiangiogenic effects, particularly enhanced by
the complexation with hydroxypropyl-$beta$-cyclodextrin
(HP-$beta$-CD). Considering the link between angiogenesis and
collagenase, the potential effects of the extract on collagenase
activity was investigated. The extract alone inhibited
collagenase with an IC50 value comparable to that of the
standard inhibitor while its complexed form exhibited a 4.5-fold
greater inhibitory activity. A molecular docking study examined
the interaction between the main compounds and collagenase. In
conclusion, wild cardoon leaves can represent a valuable source
of bioactive compounds. This study demonstrated that the
complexation of the extract with cyclodextrin determines an
increase in its biological activity.
var. sylvestris (Lam.) Fiori), the wild cardoon, is known for
its culinary applications and potential health benefits. Due to
this, and given the growing interest in circular economies,
deepening our under-standing of the effects of wild cardoon leaf
waste on angiogenesis and collagenase activity represents a
valuable opportunity to valorise agricultural byproducts as
health-promoting ingredients. In this study, the waste product
of wild cardoon leaves was extracted to examine its chemical
composition and biological activities. Analytical techniques
identified several bioactive compounds, including flavonoids,
hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids,
and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos
and the chick chorioallantoic membrane demonstrated
dose-dependent antiangiogenic effects, particularly enhanced by
the complexation with hydroxypropyl-$beta$-cyclodextrin
(HP-$beta$-CD). Considering the link between angiogenesis and
collagenase, the potential effects of the extract on collagenase
activity was investigated. The extract alone inhibited
collagenase with an IC50 value comparable to that of the
standard inhibitor while its complexed form exhibited a 4.5-fold
greater inhibitory activity. A molecular docking study examined
the interaction between the main compounds and collagenase. In
conclusion, wild cardoon leaves can represent a valuable source
of bioactive compounds. This study demonstrated that the
complexation of the extract with cyclodextrin determines an
increase in its biological activity.
Simbula, Michela; Manchinu, Maria Francesca; Olla, Stefania; Congiu, Michela; Vaccargiu, Simona; Caria, Cristian Antonio; Poddie, Daniela; Ristaldi, Maria Serafina
Drugs repurposing of molecules modulating human delta globin gene expression via a model of transgenic foetal liver cells: Implications for beta-hemoglobinopathy therapeutics Journal Article
In: Biomolecules, 15 (4), pp. 565, 2025.
@article{Simbula2025-nd,
title = {Drugs repurposing of molecules modulating human delta globin
gene expression via a model of transgenic foetal liver cells:
Implications for beta-hemoglobinopathy therapeutics},
author = {Michela Simbula and Maria Francesca Manchinu and Stefania Olla and Michela Congiu and Simona Vaccargiu and Cristian Antonio Caria and Daniela Poddie and Maria Serafina Ristaldi},
year = {2025},
date = {2025-04-01},
journal = {Biomolecules},
volume = {15},
number = {4},
pages = {565},
publisher = {MDPI AG},
abstract = {Beta-hemoglobinopathies such as beta-thalassemia and sickle cell
disease are severe genetic blood disorders affecting the beta
globin chain of haemoglobin A ($alpha$2$beta$2). Activation of
delta globin, the non-alpha globin of HbA2 ($alpha$2$delta$2),
could represent a possible approach to improve the clinical
severity of these pathologies. Notably, the therapeutic
potential of delta globin has been demonstrated in previous
studies using a mouse model of beta-thalassemia and sickle cell
disease. The present study evaluated delta globin gene
activation by small molecules in erythroid cells isolated from
transgenic murine foetal liver. A screening of 119 molecules,
selected for their potential in drug repurposing, was performed
without prior selection based on specific pathways of interest.
Three candidates-Nexturastat, Stattic and Palbociclib-were found
to have high efficacy on delta globin expression. Palbociclib
also proved effective in increasing gamma globin expression. All
of these compounds have pharmacokinetic profiles that are
beneficial for clinical application, providing potential inducer
agents of HbA2 that could have therapeutic effects in the
treatment of beta-hemoglobinopathies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Beta-hemoglobinopathies such as beta-thalassemia and sickle cell
disease are severe genetic blood disorders affecting the beta
globin chain of haemoglobin A ($alpha$2$beta$2). Activation of
delta globin, the non-alpha globin of HbA2 ($alpha$2$delta$2),
could represent a possible approach to improve the clinical
severity of these pathologies. Notably, the therapeutic
potential of delta globin has been demonstrated in previous
studies using a mouse model of beta-thalassemia and sickle cell
disease. The present study evaluated delta globin gene
activation by small molecules in erythroid cells isolated from
transgenic murine foetal liver. A screening of 119 molecules,
selected for their potential in drug repurposing, was performed
without prior selection based on specific pathways of interest.
Three candidates-Nexturastat, Stattic and Palbociclib-were found
to have high efficacy on delta globin expression. Palbociclib
also proved effective in increasing gamma globin expression. All
of these compounds have pharmacokinetic profiles that are
beneficial for clinical application, providing potential inducer
agents of HbA2 that could have therapeutic effects in the
treatment of beta-hemoglobinopathies.
disease are severe genetic blood disorders affecting the beta
globin chain of haemoglobin A ($alpha$2$beta$2). Activation of
delta globin, the non-alpha globin of HbA2 ($alpha$2$delta$2),
could represent a possible approach to improve the clinical
severity of these pathologies. Notably, the therapeutic
potential of delta globin has been demonstrated in previous
studies using a mouse model of beta-thalassemia and sickle cell
disease. The present study evaluated delta globin gene
activation by small molecules in erythroid cells isolated from
transgenic murine foetal liver. A screening of 119 molecules,
selected for their potential in drug repurposing, was performed
without prior selection based on specific pathways of interest.
Three candidates-Nexturastat, Stattic and Palbociclib-were found
to have high efficacy on delta globin expression. Palbociclib
also proved effective in increasing gamma globin expression. All
of these compounds have pharmacokinetic profiles that are
beneficial for clinical application, providing potential inducer
agents of HbA2 that could have therapeutic effects in the
treatment of beta-hemoglobinopathies.
2024
Floris, Sonia; Pintus, Francesca; Fais, Antonella; Era, Benedetta; Raho, Nicola; Siguri, Chiara; Orr`u, Germano; Fais, Sara; Tuberoso, Carlo Ignazio Giovanni; Olla, Stefania; Petrillo, Amalia Di
Biological potential of Asphodelus microcarpus extracts: $A$-glucosidase and antibiofilm activities in vitro Journal Article
In: Molecules, 29 (21), pp. 5063, 2024.
@article{Floris2024-lf,
title = {Biological potential of Asphodelus microcarpus extracts:
$A$-glucosidase and antibiofilm activities in vitro},
author = {Sonia Floris and Francesca Pintus and Antonella Fais and Benedetta Era and Nicola Raho and Chiara Siguri and Germano Orr`u and Sara Fais and Carlo Ignazio Giovanni Tuberoso and Stefania Olla and Amalia Di Petrillo},
year = {2024},
date = {2024-10-01},
journal = {Molecules},
volume = {29},
number = {21},
pages = {5063},
publisher = {MDPI AG},
abstract = {Type 2 diabetes (T2D), characterized by insulin resistance and
$beta$-cell dysfunction, requires continuous advancements in
management strategies, particularly in controlling postprandial
hyperglycemia to prevent complications. Current antidiabetics,
which have $alpha$-amylase and $alpha$-glucosidase inhibitory
activities, have side effects, prompting the search for better
alternatives. In addition, diabetes patients are particularly
vulnerable to yeast infections because an unusual sugar
concentration promotes the growth of Candida spp. in areas like
the mouth and genitalia. Asphodelus microcarpus contains
bioactive flavonoids with potential enzyme inhibitory
properties. This study investigates $alpha$-amylase and
$alpha$-glucosidase inhibitory activities and antioxidant and
antimycotic capacity of ethanolic extracts from different parts
of A. microcarpus. Results show that extracts significantly
inhibit $alpha$-glucosidase, with the IC50 value being up to 25
times higher than for acarbose, while exerting low
$alpha$-amylase activity. The extracts also demonstrated strong
antioxidant properties and low cytotoxicity. The presence of
phenolic compounds is likely responsible for the observed
biological activities. Molecular docking analysis of 11 selected
compounds identified emodin and luteolin as significant
inhibitors of $alpha$-glucosidase. Additionally, the extracts
demonstrated significant antibiofilm action against an MDR
strain of Candida albicans. These findings suggest that A.
microcarpus is a promising source of natural compounds for T2D
management.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Type 2 diabetes (T2D), characterized by insulin resistance and
$beta$-cell dysfunction, requires continuous advancements in
management strategies, particularly in controlling postprandial
hyperglycemia to prevent complications. Current antidiabetics,
which have $alpha$-amylase and $alpha$-glucosidase inhibitory
activities, have side effects, prompting the search for better
alternatives. In addition, diabetes patients are particularly
vulnerable to yeast infections because an unusual sugar
concentration promotes the growth of Candida spp. in areas like
the mouth and genitalia. Asphodelus microcarpus contains
bioactive flavonoids with potential enzyme inhibitory
properties. This study investigates $alpha$-amylase and
$alpha$-glucosidase inhibitory activities and antioxidant and
antimycotic capacity of ethanolic extracts from different parts
of A. microcarpus. Results show that extracts significantly
inhibit $alpha$-glucosidase, with the IC50 value being up to 25
times higher than for acarbose, while exerting low
$alpha$-amylase activity. The extracts also demonstrated strong
antioxidant properties and low cytotoxicity. The presence of
phenolic compounds is likely responsible for the observed
biological activities. Molecular docking analysis of 11 selected
compounds identified emodin and luteolin as significant
inhibitors of $alpha$-glucosidase. Additionally, the extracts
demonstrated significant antibiofilm action against an MDR
strain of Candida albicans. These findings suggest that A.
microcarpus is a promising source of natural compounds for T2D
management.
$beta$-cell dysfunction, requires continuous advancements in
management strategies, particularly in controlling postprandial
hyperglycemia to prevent complications. Current antidiabetics,
which have $alpha$-amylase and $alpha$-glucosidase inhibitory
activities, have side effects, prompting the search for better
alternatives. In addition, diabetes patients are particularly
vulnerable to yeast infections because an unusual sugar
concentration promotes the growth of Candida spp. in areas like
the mouth and genitalia. Asphodelus microcarpus contains
bioactive flavonoids with potential enzyme inhibitory
properties. This study investigates $alpha$-amylase and
$alpha$-glucosidase inhibitory activities and antioxidant and
antimycotic capacity of ethanolic extracts from different parts
of A. microcarpus. Results show that extracts significantly
inhibit $alpha$-glucosidase, with the IC50 value being up to 25
times higher than for acarbose, while exerting low
$alpha$-amylase activity. The extracts also demonstrated strong
antioxidant properties and low cytotoxicity. The presence of
phenolic compounds is likely responsible for the observed
biological activities. Molecular docking analysis of 11 selected
compounds identified emodin and luteolin as significant
inhibitors of $alpha$-glucosidase. Additionally, the extracts
demonstrated significant antibiofilm action against an MDR
strain of Candida albicans. These findings suggest that A.
microcarpus is a promising source of natural compounds for T2D
management.
Caballero-Oteyza, Andrés; Crisponi, Laura; Peng, Xiao P; Wang, Hongying; Mrovecova, Pavla; Olla, Stefania; Siguri, Chiara; Marnissi, Farida; Jouhadi, Zineb; Aksentijevich, Ivona; Grimbacher, Bodo; Proietti, Michele
OTULIN-related conditions: Report of a new case and review of the literature using GenIA Journal Article
In: Clin. Immunol., 265 (110292), pp. 110292, 2024.
@article{Caballero-Oteyza2024-rg,
title = {OTULIN-related conditions: Report of a new case and review of
the literature using GenIA},
author = {Andrés Caballero-Oteyza and Laura Crisponi and Xiao P Peng and Hongying Wang and Pavla Mrovecova and Stefania Olla and Chiara Siguri and Farida Marnissi and Zineb Jouhadi and Ivona Aksentijevich and Bodo Grimbacher and Michele Proietti},
year = {2024},
date = {2024-08-01},
journal = {Clin. Immunol.},
volume = {265},
number = {110292},
pages = {110292},
publisher = {Elsevier BV},
abstract = {ÖTULIN encodes an eponymous linear deubiquitinase (DUB)
essential for controlling inflammation as a negative regulator
of the canonical NF-$kappa$B signaling pathway via the
regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF)
mutations in OTULIN cause an autosomal recessive condition named
Otulin-Related Autoinflammatory Syndrome (ORAS), also known as
Otulipenia or AutoInflammation, Panniculitis, and Dermatosis
Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN
Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has
been linked to an incompletely penetrant, dominantly inherited
susceptibility to invasive Staphylococcal infections. At the
same time, a recent novel ORAS-like inflammatory syndrome was
described in association with a heterozygous missense mutation
that appears to exert dominant negative (DN) effects. In this
manuscript, we report the identification of a novel homozygous
missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan
infant with an ORAS phenotype and provide experimental evidence
for its pathogenicity. We go on to systematically review the
literature for OTULIN-associated conditions by using the GenIA
database (www.geniadb.net) to collect, extract and harmonize all
clinical, laboratory and functional data for published patients
and variants. Our comprehensive synthesis of genotypic,
phenotypic, and mechanistic data enables a more in-depth view of
the diverse mechanisms and pathways by which the OTULIN
pathogenic variants may lead to human immune disease. This
review may help variant classification activities and inform
future variant evaluation, as well as the development of
diagnostic and management guidelines. It also identifies current
knowledge gaps and raises additional questions warranting future
investigation."},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
ÖTULIN encodes an eponymous linear deubiquitinase (DUB)
essential for controlling inflammation as a negative regulator
of the canonical NF-$kappa$B signaling pathway via the
regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF)
mutations in OTULIN cause an autosomal recessive condition named
Otulin-Related Autoinflammatory Syndrome (ORAS), also known as
Otulipenia or AutoInflammation, Panniculitis, and Dermatosis
Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN
Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has
been linked to an incompletely penetrant, dominantly inherited
susceptibility to invasive Staphylococcal infections. At the
same time, a recent novel ORAS-like inflammatory syndrome was
described in association with a heterozygous missense mutation
that appears to exert dominant negative (DN) effects. In this
manuscript, we report the identification of a novel homozygous
missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan
infant with an ORAS phenotype and provide experimental evidence
for its pathogenicity. We go on to systematically review the
literature for OTULIN-associated conditions by using the GenIA
database (www.geniadb.net) to collect, extract and harmonize all
clinical, laboratory and functional data for published patients
and variants. Our comprehensive synthesis of genotypic,
phenotypic, and mechanistic data enables a more in-depth view of
the diverse mechanisms and pathways by which the OTULIN
pathogenic variants may lead to human immune disease. This
review may help variant classification activities and inform
future variant evaluation, as well as the development of
diagnostic and management guidelines. It also identifies current
knowledge gaps and raises additional questions warranting future
investigation."
essential for controlling inflammation as a negative regulator
of the canonical NF-$kappa$B signaling pathway via the
regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF)
mutations in OTULIN cause an autosomal recessive condition named
Otulin-Related Autoinflammatory Syndrome (ORAS), also known as
Otulipenia or AutoInflammation, Panniculitis, and Dermatosis
Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN
Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has
been linked to an incompletely penetrant, dominantly inherited
susceptibility to invasive Staphylococcal infections. At the
same time, a recent novel ORAS-like inflammatory syndrome was
described in association with a heterozygous missense mutation
that appears to exert dominant negative (DN) effects. In this
manuscript, we report the identification of a novel homozygous
missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan
infant with an ORAS phenotype and provide experimental evidence
for its pathogenicity. We go on to systematically review the
literature for OTULIN-associated conditions by using the GenIA
database (www.geniadb.net) to collect, extract and harmonize all
clinical, laboratory and functional data for published patients
and variants. Our comprehensive synthesis of genotypic,
phenotypic, and mechanistic data enables a more in-depth view of
the diverse mechanisms and pathways by which the OTULIN
pathogenic variants may lead to human immune disease. This
review may help variant classification activities and inform
future variant evaluation, as well as the development of
diagnostic and management guidelines. It also identifies current
knowledge gaps and raises additional questions warranting future
investigation."
Petrillo, Amalia Di; Siguri, Chiara; Delogu, Giovanna L; Fais, Antonella; Era, Benedetta; Floris, Sonia; Pintus, Francesca; Kumar, Amit; Fantini, Massimo Claudio; Olla, Stefania
Exploring Asphodelus microcarpus as a source of xanthine oxidase inhibitors: Insights from in silico and in vitro studies Journal Article
In: Chem. Biol. Interact., 397 (111087), pp. 111087, 2024.
@article{Di_Petrillo2024-ac,
title = {Exploring Asphodelus microcarpus as a source of xanthine oxidase
inhibitors: Insights from in silico and in vitro studies},
author = {Amalia Di Petrillo and Chiara Siguri and Giovanna L Delogu and Antonella Fais and Benedetta Era and Sonia Floris and Francesca Pintus and Amit Kumar and Massimo Claudio Fantini and Stefania Olla},
year = {2024},
date = {2024-07-01},
journal = {Chem. Biol. Interact.},
volume = {397},
number = {111087},
pages = {111087},
publisher = {Elsevier BV},
abstract = {Xanthine oxidase (XO) plays a critical role in purine
catabolism, catalyzing the conversion of hypoxanthine to
xanthine and xanthine to uric acid, contributing to superoxide
anion production. This process is implicated in various human
diseases, particularly gout. Traditional XO inhibitors, such as
allopurinol and febuxostat, while effective, may present side
effects. Our study focuses on Asphodelus microcarpus, a plant
renowned for traditional anti-inflammatory uses. Recent
investigations into its phenolic-rich flowers, notably abundant
in luteolin derivatives, reveal its potential as a natural
source of XO inhibitors. In the present research, XO inhibition
by an ethanolic flowers extract from A. microcarpus is reported.
In silico docking studies have highlighted luteolin derivatives
as potential XO inhibitors, and molecular dynamics support that
luteolin 7-O-glucoside has the highest binding stability
compared to other compounds and controls. In vitro studies
confirm that luteolin 7-O-glucoside inhibits XO more effectively
than the standard inhibitor allopurinol, with an IC50 value of
4.8 $mu$g/mL compared to 11.5 $mu$g/mL, respectively. These
findings underscore the potential therapeutic significance of A.
microcarpus in managing conditions related to XO activity. The
research contributes valuable insights into the health-promoting
properties of A. microcarpus and its potential application in
natural medicine, presenting a promising avenue for further
exploration in disease management.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Xanthine oxidase (XO) plays a critical role in purine
catabolism, catalyzing the conversion of hypoxanthine to
xanthine and xanthine to uric acid, contributing to superoxide
anion production. This process is implicated in various human
diseases, particularly gout. Traditional XO inhibitors, such as
allopurinol and febuxostat, while effective, may present side
effects. Our study focuses on Asphodelus microcarpus, a plant
renowned for traditional anti-inflammatory uses. Recent
investigations into its phenolic-rich flowers, notably abundant
in luteolin derivatives, reveal its potential as a natural
source of XO inhibitors. In the present research, XO inhibition
by an ethanolic flowers extract from A. microcarpus is reported.
In silico docking studies have highlighted luteolin derivatives
as potential XO inhibitors, and molecular dynamics support that
luteolin 7-O-glucoside has the highest binding stability
compared to other compounds and controls. In vitro studies
confirm that luteolin 7-O-glucoside inhibits XO more effectively
than the standard inhibitor allopurinol, with an IC50 value of
4.8 $mu$g/mL compared to 11.5 $mu$g/mL, respectively. These
findings underscore the potential therapeutic significance of A.
microcarpus in managing conditions related to XO activity. The
research contributes valuable insights into the health-promoting
properties of A. microcarpus and its potential application in
natural medicine, presenting a promising avenue for further
exploration in disease management.
catabolism, catalyzing the conversion of hypoxanthine to
xanthine and xanthine to uric acid, contributing to superoxide
anion production. This process is implicated in various human
diseases, particularly gout. Traditional XO inhibitors, such as
allopurinol and febuxostat, while effective, may present side
effects. Our study focuses on Asphodelus microcarpus, a plant
renowned for traditional anti-inflammatory uses. Recent
investigations into its phenolic-rich flowers, notably abundant
in luteolin derivatives, reveal its potential as a natural
source of XO inhibitors. In the present research, XO inhibition
by an ethanolic flowers extract from A. microcarpus is reported.
In silico docking studies have highlighted luteolin derivatives
as potential XO inhibitors, and molecular dynamics support that
luteolin 7-O-glucoside has the highest binding stability
compared to other compounds and controls. In vitro studies
confirm that luteolin 7-O-glucoside inhibits XO more effectively
than the standard inhibitor allopurinol, with an IC50 value of
4.8 $mu$g/mL compared to 11.5 $mu$g/mL, respectively. These
findings underscore the potential therapeutic significance of A.
microcarpus in managing conditions related to XO activity. The
research contributes valuable insights into the health-promoting
properties of A. microcarpus and its potential application in
natural medicine, presenting a promising avenue for further
exploration in disease management.
Serra, Rita; Rallo, Vincenzo; Steri, Maristella; Olla, Stefania; Piras, Maria Grazia; Marongiu, Michele; Gorospe, Myriam; Schlessinger, David; Pinna, Antonio; Fiorillo, Edoardo; Cucca, Francesco; Angius, Andrea
Ä large-scale screening identified in USH2A gene the P3272L founder pathogenic variant explaining familial Usher syndrome in Sardinia, Italy" Journal Article
In: BMC Ophthalmol., 24 (1), pp. 306, 2024.
@article{Serra2024-ps,
title = {Ä large-scale screening identified in USH2A gene the P3272L
founder pathogenic variant explaining familial Usher syndrome in
Sardinia, Italy"},
author = {Rita Serra and Vincenzo Rallo and Maristella Steri and Stefania Olla and Maria Grazia Piras and Michele Marongiu and Myriam Gorospe and David Schlessinger and Antonio Pinna and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},
year = {2024},
date = {2024-07-01},
journal = {BMC Ophthalmol.},
volume = {24},
number = {1},
pages = {306},
publisher = {Springer Science and Business Media LLC},
abstract = {BACKGROUND: Usher syndrome (USH) encompasses a group of
disorders characterized by congenital sensorineural hearing loss
(SNHL) and retinitis pigmentosa (RP). We described the clinical
findings, natural history, and molecular analyses of USH
patients identified during a large-scale screening to identify
quantitative traits related to ocular disorders in the SardiNIA
project cohort. METHODS: We identified 3 USH-affected families
out of a cohort of 6,148 healthy subjects. 9 subjects presented
a pathological phenotype, with SNHL and RP. All patients and
their family members underwent a complete ophthalmic examination
including best-corrected visual acuity, slit-lamp biomicroscopy,
fundoscopy, fundus autofluorescence, spectral-domain optical
coherence tomography, and electrophysiological testing.
Audiological evaluation was performed with a clinical
audiometer. Genotyping was performed using several arrays
integrated with whole genome sequence data providing
approximately 22 million markers equally distributed for each
subject analyzed. Molecular diagnostics focused on analysis of
the following candidate genes: MYO7A, USH1C, CDH23, PCDH15,
USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A
single missense causal variant in USH2A gene was identified in
homozygous status in all patients and in heterozygous status in
unaffected parents. The presence of multiple homozygous patients
with the same phenotypic severity of the syndromic form suggests
that the Sardinian USH phenotype is the result of a founder
effect on a specific pathogenic variant related haplotype. The
frequency of heterozygotes in general Sardinian population is
1.89. Additionally, to provide new insights into the structure
of usherin and the pathological mechanisms caused by small
pathogenic in-frame variants, like p.Pro3272Leu, molecular
dynamics simulations of native and mutant protein-protein and
protein-ligand complexes were performed that predicted a
destabilization of the protein with a decrease in the free
energy change. CONCLUSIONS: Our results suggest that our
approach is effective for the genetic diagnosis of USH. Based on
the heterozygous frequency, targeted screening of this variant
in the general population and in families at risk or with
familial USH can be suggested. This can lead to more accurate
molecular diagnosis, better genetic counseling, and improved
molecular epidemiology data that are critical for future
intervention plans. TRIAL REGISTRATION: We did not perform any
health-related interventions for the participants.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Usher syndrome (USH) encompasses a group of
disorders characterized by congenital sensorineural hearing loss
(SNHL) and retinitis pigmentosa (RP). We described the clinical
findings, natural history, and molecular analyses of USH
patients identified during a large-scale screening to identify
quantitative traits related to ocular disorders in the SardiNIA
project cohort. METHODS: We identified 3 USH-affected families
out of a cohort of 6,148 healthy subjects. 9 subjects presented
a pathological phenotype, with SNHL and RP. All patients and
their family members underwent a complete ophthalmic examination
including best-corrected visual acuity, slit-lamp biomicroscopy,
fundoscopy, fundus autofluorescence, spectral-domain optical
coherence tomography, and electrophysiological testing.
Audiological evaluation was performed with a clinical
audiometer. Genotyping was performed using several arrays
integrated with whole genome sequence data providing
approximately 22 million markers equally distributed for each
subject analyzed. Molecular diagnostics focused on analysis of
the following candidate genes: MYO7A, USH1C, CDH23, PCDH15,
USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A
single missense causal variant in USH2A gene was identified in
homozygous status in all patients and in heterozygous status in
unaffected parents. The presence of multiple homozygous patients
with the same phenotypic severity of the syndromic form suggests
that the Sardinian USH phenotype is the result of a founder
effect on a specific pathogenic variant related haplotype. The
frequency of heterozygotes in general Sardinian population is
1.89. Additionally, to provide new insights into the structure
of usherin and the pathological mechanisms caused by small
pathogenic in-frame variants, like p.Pro3272Leu, molecular
dynamics simulations of native and mutant protein-protein and
protein-ligand complexes were performed that predicted a
destabilization of the protein with a decrease in the free
energy change. CONCLUSIONS: Our results suggest that our
approach is effective for the genetic diagnosis of USH. Based on
the heterozygous frequency, targeted screening of this variant
in the general population and in families at risk or with
familial USH can be suggested. This can lead to more accurate
molecular diagnosis, better genetic counseling, and improved
molecular epidemiology data that are critical for future
intervention plans. TRIAL REGISTRATION: We did not perform any
health-related interventions for the participants.
disorders characterized by congenital sensorineural hearing loss
(SNHL) and retinitis pigmentosa (RP). We described the clinical
findings, natural history, and molecular analyses of USH
patients identified during a large-scale screening to identify
quantitative traits related to ocular disorders in the SardiNIA
project cohort. METHODS: We identified 3 USH-affected families
out of a cohort of 6,148 healthy subjects. 9 subjects presented
a pathological phenotype, with SNHL and RP. All patients and
their family members underwent a complete ophthalmic examination
including best-corrected visual acuity, slit-lamp biomicroscopy,
fundoscopy, fundus autofluorescence, spectral-domain optical
coherence tomography, and electrophysiological testing.
Audiological evaluation was performed with a clinical
audiometer. Genotyping was performed using several arrays
integrated with whole genome sequence data providing
approximately 22 million markers equally distributed for each
subject analyzed. Molecular diagnostics focused on analysis of
the following candidate genes: MYO7A, USH1C, CDH23, PCDH15,
USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A
single missense causal variant in USH2A gene was identified in
homozygous status in all patients and in heterozygous status in
unaffected parents. The presence of multiple homozygous patients
with the same phenotypic severity of the syndromic form suggests
that the Sardinian USH phenotype is the result of a founder
effect on a specific pathogenic variant related haplotype. The
frequency of heterozygotes in general Sardinian population is
1.89. Additionally, to provide new insights into the structure
of usherin and the pathological mechanisms caused by small
pathogenic in-frame variants, like p.Pro3272Leu, molecular
dynamics simulations of native and mutant protein-protein and
protein-ligand complexes were performed that predicted a
destabilization of the protein with a decrease in the free
energy change. CONCLUSIONS: Our results suggest that our
approach is effective for the genetic diagnosis of USH. Based on
the heterozygous frequency, targeted screening of this variant
in the general population and in families at risk or with
familial USH can be suggested. This can lead to more accurate
molecular diagnosis, better genetic counseling, and improved
molecular epidemiology data that are critical for future
intervention plans. TRIAL REGISTRATION: We did not perform any
health-related interventions for the participants.
- Monserrato
070 6754591