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  1. AU="Anderloni, Giulia"
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  1. Article ; Online: Asn25 Deamidation as an Allosteric Tool to Increase IFNβ-1a Biological Activity.

    Lipari, Elisa / Saporiti, Simona / Eberini, Ivano / Massimo, Luigia / Mazzarella, Enrico / Anderloni, Giulia / Rossi, Mara / D'Amici, Fabio / Pergola, Carlo / Palinsky, Wolf / D'Acunto, Cosimo Walter / Centola, Fabio

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

    2022  Volume 42, Issue 6, Page(s) 251–266

    Abstract: Interferon beta (IFNβ) is a well-known cytokine, belonging to the type I family, that exerts antiviral, immunomodulatory, and antiproliferative activity. It has been reported that the artificially deamidated form of recombinant IFNβ-1a at Asn25 position ... ...

    Abstract Interferon beta (IFNβ) is a well-known cytokine, belonging to the type I family, that exerts antiviral, immunomodulatory, and antiproliferative activity. It has been reported that the artificially deamidated form of recombinant IFNβ-1a at Asn25 position shows an increased biological activity. As a deepening of the previous study, the molecular mechanism underlying this biological effect was investigated in this work by combining experimental and computational techniques. Specifically, the binding to IFNAR1 and IFNAR2 receptors and the canonical pathway of artificially deamidated IFNβ-1a molecule were analyzed in comparison to the native form. As a result, a change in receptor affinity of deamidated IFNβ-1a with respect to the native form was observed, and to better explore this molecular interaction, molecular dynamics simulations were carried out. Results confirmed, as previously hypothesized, that the N25D mutation can locally change the interaction network of the mutated residue but also that this effect can be propagated throughout the molecule. In fact, many residues not involved in the interaction with IFNAR1 in the native form participate to the recognition in the deamidated molecule, enhancing the binding to IFNAR1 receptor and consequently an increase of signaling cascade activation. In particular, a higher STAT1 phosphorylation and interferon-stimulated gene expression was observed under deamidated IFNβ-1a cell treatment. In conclusion, this study increases the scientific knowledge of deamidated IFNβ-1a, deciphering its molecular mechanism, and opens new perspectives to novel therapeutic strategies.
    MeSH term(s) Antiviral Agents/metabolism ; Immunologic Factors ; Interferon beta-1a ; Interferon-beta/metabolism ; Interferons ; Signal Transduction
    Chemical Substances Antiviral Agents ; Immunologic Factors ; Interferon-beta (77238-31-4) ; Interferons (9008-11-1) ; Interferon beta-1a (XRO4566Q4R)
    Language English
    Publishing date 2022-05-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1226675-9
    ISSN 1557-7465 ; 1079-9907
    ISSN (online) 1557-7465
    ISSN 1079-9907
    DOI 10.1089/jir.2021.0209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Sphingosine 1-Phosphate Receptor 1 Is Required for MMP-2 Function in Bone Marrow Mesenchymal Stromal Cells: Implications for Cytoskeleton Assembly and Proliferation.

    Sassoli, Chiara / Pierucci, Federica / Tani, Alessia / Frati, Alessia / Chellini, Flaminia / Matteini, Francesca / Vestri, Ambra / Anderloni, Giulia / Nosi, Daniele / Zecchi-Orlandini, Sandra / Meacci, Elisabetta

    Stem cells international

    2018  Volume 2018, Page(s) 5034679

    Abstract: Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling ...

    Abstract Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling and proliferation and secretion ability, is played by matrix metalloproteinase- (MMP-) 2. Therefore, the identification of paracrine/autocrine regulators of MMP-2 function may be of great relevance for improving BM-MSC therapeutic potential. We recently reported that BM-MSCs release the bioactive lipid sphingosine 1-phosphate (S1P) and, here, we demonstrated an impairment of MMP-2 expression/release when the S1P receptor subtype S1PR1 is blocked. Notably, active S1PR1/MMP-2 signalling is required for F-actin structure assembly (lamellipodia, microspikes, and stress fibers) and, in turn, cell proliferation. Moreover, in experimental conditions resembling the damaged/regenerating tissue microenvironment (hypoxia), S1P/S1PR1 system is also required for HIF-1
    Language English
    Publishing date 2018-03-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2573856-2
    ISSN 1687-9678 ; 1687-966X
    ISSN (online) 1687-9678
    ISSN 1687-966X
    DOI 10.1155/2018/5034679
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Protective Value of Maternal Group B Streptococcus Antibodies: Quantitative and Functional Analysis of Naturally Acquired Responses to Capsular Polysaccharides and Pilus Proteins in European Maternal Sera.

    Fabbrini, Monica / Rigat, Fabio / Rinaudo, C Daniela / Passalaqua, Irene / Khacheh, Sceida / Creti, Roberta / Baldassarri, Lucilla / Carboni, Filippo / Anderloni, Giulia / Rosini, Roberto / Maione, Domenico / Grandi, Guido / Telford, John L / Margarit, Immaculada

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2016  Volume 63, Issue 6, Page(s) 746–753

    Abstract: Background: Group B Streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. A vaccine targeting pregnant women could protect infants through placentally transferred antibodies. The association between GBS maternal antibody concentrations ...

    Abstract Background: Group B Streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. A vaccine targeting pregnant women could protect infants through placentally transferred antibodies. The association between GBS maternal antibody concentrations and the risk of neonatal infection has been investigated in US and African populations. Here we studied naturally acquired immunoglobulin G (IgG) responses to GBS capsular polysaccharides (CPS) and pilus proteins in European pregnant women.
    Methods: Maternal sera were prospectively collected in 8 EU countries from 473 GBS non-colonized and 984 colonized pregnant women who delivered healthy neonates and from 153 mothers of infants with GBS disease. GBS strains from these colonized women and infected infants were obtained in parallel and their capsular and pilus types were identified by serological and molecular methods. Maternal serum concentrations of IgG anti- Ia, -Ib, -III and -V polysaccharides and anti-BP-1, -AP1-2a and -BP-2b pilus proteins were determined by enzyme-linked immunosorbent assay. Antibody functional activity was quantified by Opsonophagocytic Killing Assay.
    Results: Antibody levels against CPS and pilus proteins were significantly higher in GBS colonized women delivering healthy babies than in mothers of neonates with GBS disease or non-colonized women. Moreover, maternal anti-capsular IgG concentrations showed a significant correlation with functional titers measured by Opsonophagocytic Killing Assay.
    Conclusions: Maternal anti-capsular IgG concentrations above 1 µg/mL mediated GBS killing in vitro and were predicted to respectively reduce by 81% (95% confidence interval, 40%-100%) and 78% (45%-100%) the risk of GBS Ia and III early-onset disease in Europe.
    MeSH term(s) Antibodies, Bacterial/blood ; Europe/epidemiology ; Female ; Fimbriae, Bacterial/immunology ; Humans ; Immunity, Maternally-Acquired ; Immunoglobulin G/blood ; Polysaccharides, Bacterial/immunology ; Pregnancy ; Prospective Studies ; Streptococcal Infections/epidemiology ; Streptococcal Infections/immunology ; Streptococcus agalactiae/immunology
    Chemical Substances Antibodies, Bacterial ; Immunoglobulin G ; Polysaccharides, Bacterial
    Language English
    Publishing date 2016-07-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciw377
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mesenchymal stromal cell secreted sphingosine 1-phosphate (S1P) exerts a stimulatory effect on skeletal myoblast proliferation.

    Sassoli, Chiara / Frati, Alessia / Tani, Alessia / Anderloni, Giulia / Pierucci, Federica / Matteini, Francesca / Chellini, Flaminia / Zecchi Orlandini, Sandra / Formigli, Lucia / Meacci, Elisabetta

    PloS one

    2014  Volume 9, Issue 9, Page(s) e108662

    Abstract: Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem ... ...

    Abstract Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration.
    MeSH term(s) Animals ; Bone Marrow Cells ; Cell Proliferation/drug effects ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Lysophospholipids/metabolism ; Lysophospholipids/pharmacology ; Mesenchymal Stem Cells/metabolism ; Mice ; Myoblasts, Skeletal/metabolism ; Paracrine Communication/drug effects ; Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors ; Regeneration/drug effects ; Signal Transduction ; Sphingosine/analogs & derivatives ; Sphingosine/metabolism ; Sphingosine/pharmacology ; Vascular Endothelial Growth Factor A/metabolism ; Wound Healing/drug effects
    Chemical Substances Culture Media, Conditioned ; Lysophospholipids ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse ; sphingosine 1-phosphate (26993-30-6) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; sphingosine kinase (EC 2.7.1.-) ; Sphingosine (NGZ37HRE42)
    Language English
    Publishing date 2014-09-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0108662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Expression of factor H binding protein in meningococcal strains can vary at least 15-fold and is genetically determined.

    Biagini, Massimiliano / Spinsanti, Marco / De Angelis, Gabriella / Tomei, Sara / Ferlenghi, Ilaria / Scarselli, Maria / Rigat, Fabio / Messuti, Nicola / Biolchi, Alessia / Muzzi, Alessandro / Anderloni, Giulia / Brunelli, Brunella / Cartocci, Elena / Buricchi, Francesca / Tani, Chiara / Stella, Maria / Moschioni, Monica / Del Tordello, Elena / Colaprico, Annalisa /
    Savino, Silvana / Giuliani, Marzia M / Delany, Isabel / Pizza, Mariagrazia / Costantino, Paolo / Norais, Nathalie / Rappuoli, Rino / Masignani, Vega

    Proceedings of the National Academy of Sciences of the United States of America

    2016  Volume 113, Issue 10, Page(s) 2714–2719

    Abstract: Factor H binding protein (fHbp) is a lipoprotein of Neisseria meningitidis important for the survival of the bacterium in human blood and a component of two recently licensed vaccines against serogroup B meningococcus (MenB). Based on 866 different amino ...

    Abstract Factor H binding protein (fHbp) is a lipoprotein of Neisseria meningitidis important for the survival of the bacterium in human blood and a component of two recently licensed vaccines against serogroup B meningococcus (MenB). Based on 866 different amino acid sequences this protein is divided into three variants or two families. Quantification of the protein is done by immunoassays such as ELISA or FACS that are susceptible to the sequence variation and expression level of the protein. Here, selected reaction monitoring mass spectrometry was used for the absolute quantification of fHbp in a large panel of strains representative of the population diversity of MenB. The analysis revealed that the level of fHbp expression can vary at least 15-fold and that variant 1 strains express significantly more protein than variant 2 or variant 3 strains. The susceptibility to complement-mediated killing correlated with the amount of protein expressed by the different meningococcal strains and this could be predicted from the nucleotide sequence of the promoter region. Finally, the absolute quantification allowed the calculation of the number of fHbp molecules per cell and to propose a mechanistic model of the engagement of C1q, the recognition component of the complement cascade.
    MeSH term(s) Amino Acid Sequence ; Antigens, Bacterial/genetics ; Antigens, Bacterial/immunology ; Antigens, Bacterial/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/immunology ; Bacterial Proteins/metabolism ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Genetic Variation ; Humans ; Mass Spectrometry/methods ; Meningitis, Meningococcal/immunology ; Meningitis, Meningococcal/microbiology ; Meningococcal Vaccines/immunology ; Neisseria meningitidis, Serogroup B/classification ; Neisseria meningitidis, Serogroup B/genetics ; Neisseria meningitidis, Serogroup B/metabolism ; Phylogeny ; Species Specificity
    Chemical Substances Antigens, Bacterial ; Bacterial Proteins ; Meningococcal Vaccines ; factor H-binding protein, Neisseria meningitidis
    Language English
    Publishing date 2016-03-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1521142113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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