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  1. Article ; Online: In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model.

    Dos Santos, Reinaldo Sousa / Medina-Gali, Regla María / Babiloni-Chust, Ignacio / Marroqui, Laura / Nadal, Angel

    International journal of molecular sciences

    2022  Volume 23, Issue 9

    Abstract: There is a need to develop identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity. Here we used the human EndoC-βH1 β-cell line, the rat β-cell line INS-1E and dispersed mouse islet cells to assess the effects of ... ...

    Abstract There is a need to develop identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity. Here we used the human EndoC-βH1 β-cell line, the rat β-cell line INS-1E and dispersed mouse islet cells to assess the effects of endocrine disruptors on cell viability and glucose-stimulated insulin secretion (GSIS). We tested six chemicals at concentrations within human exposure (from 0.1 pM to 1 µM). Bisphenol-A (BPA) and tributyltin (TBT) were used as controls while four other chemicals, namely perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS) and dichlorodiphenyldichloroethylene (DDE), were used as "unknowns". Regarding cell viability, BPA and TBT increased cell death as previously observed. Their mode of action involved the activation of estrogen receptors and PPARγ, respectively. ROS production was a consistent key event in BPA-and TBT-treated cells. None of the other MDCs tested modified viability or ROS production. Concerning GSIS, TBT increased insulin secretion while BPA produced no effects. PFOA decreased GSIS, suggesting that this chemical could be a "new" diabetogenic agent. Our results indicate that the EndoC-βH1 cell line is a suitable human β-cell model for testing diabetogenic MDCs. Optimization of the test methods proposed here could be incorporated into a set of protocols for the identification of MDCs.
    MeSH term(s) Animals ; Benzhydryl Compounds/metabolism ; Benzhydryl Compounds/toxicity ; Endocrine Disruptors/metabolism ; Endocrine Disruptors/toxicity ; Glucose/metabolism ; Humans ; Insulin Secretion ; Insulin-Secreting Cells/metabolism ; Mice ; Rats ; Reactive Oxygen Species/metabolism
    Chemical Substances Benzhydryl Compounds ; Endocrine Disruptors ; Reactive Oxygen Species ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-05-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23095040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A combination of Polypodium leucotomos extract with vitamin A, vitamin C and selenium as an immune adjuvant against recurrent infections

    Visedo Colino, Alejandra / Hernández Rocamora, Flavia Tamara / Pardo Zapata, José / Gosálbez, Julio / Ortega-Villaizán Romo, María del Mar / Medina-Gali, Regla Maria / González Fernández, David / Pérez-Fernández, Alejandro

    Food and Agricultural Immunology. 2023 Dec. 31, v. 34, no. 1 p.2249261-

    2023  

    Abstract: Plant chemodiversity is a helpful tool for disease prevention and a basis for adjuvant treatments to conventional therapies. In this regard, the extract of Polypodium leucotomos rhizomes, PLE, has shown benefits fighting inflammation and recurrent ... ...

    Abstract Plant chemodiversity is a helpful tool for disease prevention and a basis for adjuvant treatments to conventional therapies. In this regard, the extract of Polypodium leucotomos rhizomes, PLE, has shown benefits fighting inflammation and recurrent infections but its molecular mechanism is poorly undersood. This work shows that Plesinox 3A, containing PLE, Vitamins A, C, and selenium, helps modulate the initial inflammatory response triggered by bacterial LPS through the upregulation of IL8 and IL10, together with downregulation of COX2, IL1B and TNF, in a more efficient manner than PLE alone. Additionally, this formulation enhances the antiviral response through the upregulation of MX1, IFNA1 and IFNG in different cell types. Finally, the addition of vitamins and selenium to PLE in Plesinox 3A greatly boosts the anti-bacterial properties of PLE alone. Overall, these findings support the combined use of PLE, vitamins, and selenium, in the form of Plesinox 3A as an immune booster to prevent recurrent infections, highlighting a gene set potentially involved in its beneficial effect, as well as showing its direct anti-bacterial properties, which are greater than those of PLE alone.
    Keywords Polypodium ; adjuvants ; ascorbic acid ; disease prevention ; genes ; inflammation ; interleukin-10 ; interleukin-8 ; selenium ; vitamin A ; Polypodium leucotomos extract ; molecular mechanism ; anti-inflammatory ; anti-viral ; anti-bacterial
    Language English
    Dates of publication 2023-1231
    Publishing place Taylor & Francis
    Document type Article ; Online
    ZDB-ID 1015019-5
    ISSN 1465-3443 ; 0954-0105
    ISSN (online) 1465-3443
    ISSN 0954-0105
    DOI 10.1080/09540105.2023.2249261
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Antiviral Activity of a Turbot (

    Falco, Alberto / Medina-Gali, Regla María / Poveda, José Antonio / Bello-Perez, Melissa / Novoa, Beatriz / Encinar, José Antonio

    Marine drugs

    2019  Volume 17, Issue 2

    Abstract: Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot ( ...

    Abstract Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (
    MeSH term(s) Amino Acid Sequence ; Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Cell Line ; Cyprinidae ; Fish Diseases/drug therapy ; Fish Diseases/virology ; Flatfishes ; Hydrogen-Ion Concentration ; Peptide Fragments/chemistry ; Peptide Fragments/pharmacology ; Phospholipids/chemistry ; Phospholipids/pharmacology ; Proteolipids/chemistry ; Proteolipids/pharmacology ; Rhabdoviridae/drug effects ; Rhabdoviridae/physiology ; Viremia/drug therapy ; Viremia/virology ; Virus Internalization/drug effects ; Virus Replication/drug effects
    Chemical Substances Antiviral Agents ; NK-lysin ; Peptide Fragments ; Phospholipids ; Proteolipids
    Language English
    Publishing date 2019-02-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2175190-0
    ISSN 1660-3397 ; 1660-3397
    ISSN (online) 1660-3397
    ISSN 1660-3397
    DOI 10.3390/md17020087
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Rag1 immunodeficiency-induced early aging and senescence in zebrafish are dependent on chronic inflammation and oxidative stress.

    Novoa, Beatriz / Pereiro, Patricia / López-Muñoz, Azucena / Varela, Mónica / Forn-Cuní, Gabriel / Anchelin, Monique / Dios, Sonia / Romero, Alejandro / Martinez-López, Alicia / Medina-Gali, Regla María / Collado, Manuel / Coll, Julio / Estepa, Amparo / Cayuela, María Luisa / Mulero, Victoriano / Figueras, Antonio

    Aging cell

    2019  Volume 18, Issue 5, Page(s) e13020

    Abstract: In mammals, recombination activating gene 1 (RAG1) plays a crucial role in adaptive immunity, generating a vast range of immunoglobulins. ... ...

    Abstract In mammals, recombination activating gene 1 (RAG1) plays a crucial role in adaptive immunity, generating a vast range of immunoglobulins. Rag1
    MeSH term(s) Aging/immunology ; Animals ; Cellular Senescence/immunology ; Chronic Disease ; Homeodomain Proteins/immunology ; Inflammation/immunology ; Oxidative Stress/immunology ; Zebrafish/immunology
    Chemical Substances Homeodomain Proteins ; RAG-1 protein (128559-51-3)
    Language English
    Publishing date 2019-07-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.13020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: pH-dependent solution structure and activity of a reduced form of the host-defense peptide myticin C (Myt C) from the mussel Mytilus galloprovincialis.

    Martinez-Lopez, Alicia / Encinar, Jose Antonio / Medina-Gali, Regla Maria / Balseiro, Pablo / Garcia-Valtanen, Pablo / Figueras, Antonio / Novoa, Beatriz / Estepa, Amparo

    Marine drugs

    2013  Volume 11, Issue 7, Page(s) 2328–2346

    Abstract: Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish ... ...

    Abstract Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this "antibiotic-resistance era".
    MeSH term(s) Animals ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Antimicrobial Cationic Peptides/chemistry ; Antimicrobial Cationic Peptides/pharmacology ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Bivalvia/chemistry ; Blood Proteins/chemistry ; Blood Proteins/pharmacology ; Cells, Cultured ; Escherichia coli/drug effects ; Fishes ; Hydrogen-Ion Concentration ; Mytilus/chemistry ; Peptides/chemistry ; Peptides/pharmacology ; Protein Isoforms/chemistry ; Protein Isoforms/pharmacology ; Protein Structure, Secondary ; Rhabdoviridae/drug effects ; Solutions/chemistry ; Structure-Activity Relationship
    Chemical Substances Anti-Infective Agents ; Antimicrobial Cationic Peptides ; Antiviral Agents ; Blood Proteins ; Peptides ; Protein Isoforms ; Solutions ; myticin ; polypeptide C
    Language English
    Publishing date 2013-07-04
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2175190-0
    ISSN 1660-3397 ; 1660-3397
    ISSN (online) 1660-3397
    ISSN 1660-3397
    DOI 10.3390/md11072328
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Increasing versatility of the DNA vaccines through modification of the subcellular location of plasmid-encoded antigen expression in the in vivo transfected cells.

    Martinez-Lopez, Alicia / García-Valtanen, Pablo / Ortega-Villaizan, María Del Mar / Chico, Verónica / Medina-Gali, Regla María / Perez, Luis / Coll, Julio / Estepa, Amparo

    PloS one

    2013  Volume 8, Issue 10, Page(s) e77426

    Abstract: The route of administration of DNA vaccines can play a key role in the magnitude and quality of the immune response triggered after their administration. DNA vaccines containing the gene of the membrane-anchored glycoprotein (gpG) of the fish ... ...

    Abstract The route of administration of DNA vaccines can play a key role in the magnitude and quality of the immune response triggered after their administration. DNA vaccines containing the gene of the membrane-anchored glycoprotein (gpG) of the fish rhabdoviruses infectious haematopoietic necrosis virus (IHNV) or viral haematopoietic septicaemia virus (VHSV), perhaps the most effective DNA vaccines generated so far, confer maximum protection when injected intramuscularly in contrast to their low efficacy when injected intraperitoneally. In this work, taking as a model the DNA vaccine against VHSV, we focused on developing a more versatile DNA vaccine capable of inducing protective immunity regardless of the administration route used. For that, we designed two alternative constructs to gpG₁₋₅₀₇ (the wild type membrane-anchored gpG of VHSV) encoding either a soluble (gpG₁₋₄₆₂) or a secreted soluble (gpG(LmPle20-462)) form of the VHSV-gpG. In vivo immunisation/challenge assays showed that only gpG(LmPle20-462) (the secreted soluble form) conferred protective immunity against VHSV lethal challenge via both intramuscular and intraperitoneal injection, being this the first description of a fish viral DNA vaccine that confers protection when administered intraperitoneally. Moreover, this new DNA vaccine construct also conferred protection when administered in the presence of an oil adjuvant suggesting that DNA vaccines against rhabdoviruses could be included in the formulation of current multicomponent-intaperitoneally injectable fish vaccines formulated with an oil adjuvant. On the other hand, a strong recruitment of membrane immunoglobulin expressing B cells, mainly membrane IgT, as well as t-bet expressing T cells, at early times post-immunisation, was specifically observed in the fish immunised with the secreted soluble form of the VHSV-gpG protein; this may indicate that the subcellular location of plasmid-encoded antigen expression in the in vivo transfected cells could be an important factor in determining the ways in which DNA vaccines prime the immune response.
    MeSH term(s) Animals ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antigens, Viral/administration & dosage ; Antigens, Viral/genetics ; Antigens, Viral/immunology ; Cell Line ; Fish Diseases/blood ; Fish Diseases/immunology ; Fish Diseases/prevention & control ; Gene Expression ; Hemorrhagic Septicemia, Viral/genetics ; Hemorrhagic Septicemia, Viral/immunology ; Immunization ; Oncorhynchus/blood ; Oncorhynchus/immunology ; Oncorhynchus/virology ; Vaccines, DNA/administration & dosage ; Vaccines, DNA/genetics ; Vaccines, DNA/immunology ; Viral Structural Proteins/administration & dosage ; Viral Structural Proteins/genetics ; Viral Structural Proteins/immunology ; Viral Vaccines/administration & dosage ; Viral Vaccines/genetics ; Viral Vaccines/immunology
    Chemical Substances Antibodies, Viral ; Antigens, Viral ; Vaccines, DNA ; Viral Structural Proteins ; Viral Vaccines
    Language English
    Publishing date 2013-10-09
    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.0077426
    Database MEDical Literature Analysis and Retrieval System OnLINE

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