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  1. Article ; Online: Perspectives From Systems Biology to Improve Knowledge of

    Horácio, Elvira Cynthia Alves / Hickson, Jéssica / Murta, Silvane Maria Fonseca / Ruiz, Jeronimo Conceição / Nahum, Laila Alves

    Frontiers in cellular and infection microbiology

    2021  Volume 11, Page(s) 653670

    Abstract: Neglected Tropical Diseases include a broad range of pathogens, hosts, and vectors, which represent evolving complex systems. Leishmaniasis, caused by ... ...

    Abstract Neglected Tropical Diseases include a broad range of pathogens, hosts, and vectors, which represent evolving complex systems. Leishmaniasis, caused by different
    MeSH term(s) Animals ; Drug Resistance ; Humans ; Leishmania ; Leishmaniasis ; Psychodidae ; Systems Biology
    Language English
    Publishing date 2021-04-30
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2021.653670
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment.

    Hickson, Jéssica / Athayde, Lucas Felipe Almeida / Miranda, Thainá Godinho / Junior, Policarpo Ademar Sales / Dos Santos, Anderson Coqueiro / da Cunha Galvão, Lúcia Maria / da Câmara, Antônia Cláudia Jácome / Bartholomeu, Daniella Castanheira / de Souza, Rita de Cássia Moreira / Murta, Silvane Maria Fonseca / Nahum, Laila Alves

    Parasites & vectors

    2022  Volume 15, Issue 1, Page(s) 194

    Abstract: Background: Components of the antioxidant defense system in Trypanosoma cruzi are potential targets for new drug development. Superoxide dismutases (SODs) constitute key components of antioxidant defense systems, removing excess superoxide anions by ... ...

    Abstract Background: Components of the antioxidant defense system in Trypanosoma cruzi are potential targets for new drug development. Superoxide dismutases (SODs) constitute key components of antioxidant defense systems, removing excess superoxide anions by converting them into oxygen and hydrogen peroxide. The main goal of the present study was to investigate the genes coding for iron superoxide dismutase (FeSOD) in T. cruzi strains from an evolutionary perspective.
    Methods: In this study, molecular biology methods and phylogenetic studies were combined with drug assays. The FeSOD-A and FeSOD-B genes of 35 T. cruzi strains, belonging to six discrete typing units (Tcl-TcVI), from different hosts and geographical regions were amplified by PCR and sequenced using the Sanger method. Evolutionary trees were reconstructed based on Bayesian inference and maximum likelihood methods. Drugs that potentially interacted with T. cruzi FeSODs were identified and tested against the parasites.
    Results: Our results suggest that T. cruzi FeSOD types are members of distinct families. Gene copies of FeSOD-A (n = 2), FeSOD-B (n = 4) and FeSOD-C (n = 4) were identified in the genome of the T. cruzi reference clone CL Brener. Phylogenetic inference supported the presence of two functional variants of each FeSOD type across the T. cruzi strains. Phylogenetic trees revealed a monophyletic group of FeSOD genes of T. cruzi TcIV strains in both distinct genes. Altogether, our results support the hypothesis that gene duplication followed by divergence shaped the evolution of T. cruzi FeSODs. Two drugs, mangafodipir and polaprezinc, that potentially interact with T. cruzi FeSODs were identified and tested in vitro against amastigotes and trypomastigotes: mangafodipir had a low trypanocidal effect and polaprezinc was inactive.
    Conclusions: Our study contributes to a better understanding of the molecular biodiversity of T. cruzi FeSODs. Herein we provide a successful approach to the study of gene/protein families as potential drug targets.
    MeSH term(s) Antioxidants ; Bayes Theorem ; Chagas Disease/parasitology ; Humans ; Phylogeny ; Superoxide Dismutase/genetics ; Superoxides ; Trypanosoma cruzi/genetics
    Chemical Substances Antioxidants ; Superoxides (11062-77-4) ; Superoxide Dismutase (EC 1.15.1.1)
    Language English
    Publishing date 2022-06-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2409480-8
    ISSN 1756-3305 ; 1756-3305
    ISSN (online) 1756-3305
    ISSN 1756-3305
    DOI 10.1186/s13071-022-05319-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment

    Hickson, Jéssica / Athayde, Lucas Felipe Almeida / Miranda, Thainá Godinho / Junior, Policarpo Ademar Sales / dos Santos, Anderson Coqueiro / da Cunha Galvão, Lúcia Maria / da Câmara, Antônia Cláudia Jácome / Bartholomeu, Daniella Castanheira / de Souza, Rita de Cássia Moreira / Murta, Silvane Maria Fonseca / Nahum, Laila Alves

    Parasites & vectors. 2022 Dec., v. 15, no. 1

    2022  

    Abstract: BACKGROUND: Components of the antioxidant defense system in Trypanosoma cruzi are potential targets for new drug development. Superoxide dismutases (SODs) constitute key components of antioxidant defense systems, removing excess superoxide anions by ... ...

    Abstract BACKGROUND: Components of the antioxidant defense system in Trypanosoma cruzi are potential targets for new drug development. Superoxide dismutases (SODs) constitute key components of antioxidant defense systems, removing excess superoxide anions by converting them into oxygen and hydrogen peroxide. The main goal of the present study was to investigate the genes coding for iron superoxide dismutase (FeSOD) in T. cruzi strains from an evolutionary perspective. METHODS: In this study, molecular biology methods and phylogenetic studies were combined with drug assays. The FeSOD-A and FeSOD-B genes of 35 T. cruzi strains, belonging to six discrete typing units (Tcl–TcVI), from different hosts and geographical regions were amplified by PCR and sequenced using the Sanger method. Evolutionary trees were reconstructed based on Bayesian inference and maximum likelihood methods. Drugs that potentially interacted with T. cruzi FeSODs were identified and tested against the parasites. RESULTS: Our results suggest that T. cruzi FeSOD types are members of distinct families. Gene copies of FeSOD-A (n = 2), FeSOD-B (n = 4) and FeSOD-C (n = 4) were identified in the genome of the T. cruzi reference clone CL Brener. Phylogenetic inference supported the presence of two functional variants of each FeSOD type across the T. cruzi strains. Phylogenetic trees revealed a monophyletic group of FeSOD genes of T. cruzi TcIV strains in both distinct genes. Altogether, our results support the hypothesis that gene duplication followed by divergence shaped the evolution of T. cruzi FeSODs. Two drugs, mangafodipir and polaprezinc, that potentially interact with T. cruzi FeSODs were identified and tested in vitro against amastigotes and trypomastigotes: mangafodipir had a low trypanocidal effect and polaprezinc was inactive. CONCLUSIONS: Our study contributes to a better understanding of the molecular biodiversity of T. cruzi FeSODs. Herein we provide a successful approach to the study of gene/protein families as potential drug targets.
    Keywords Bayesian theory ; Trypanosoma cruzi ; amastigotes ; antioxidant activity ; biodiversity ; drug development ; drug therapy ; drugs ; gene duplication ; genes ; hydrogen peroxide ; molecular biology ; monophyly ; oxygen ; statistical analysis ; superoxide dismutase ; trypomastigotes ; zinc carnosine
    Language English
    Dates of publication 2022-12
    Size p. 194.
    Publishing place BioMed Central
    Document type Article
    ZDB-ID 2409480-8
    ISSN 1756-3305
    ISSN 1756-3305
    DOI 10.1186/s13071-022-05319-2
    Database NAL-Catalogue (AGRICOLA)

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