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1.
Gut Microbes ; 13(1): 1-9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33550892

RESUMO

Microbiota-derived molecules called short-chain fatty acids (SCFAs) play a key role in the maintenance of the intestinal barrier and regulation of immune response during infectious conditions. Recent reports indicate that SARS-CoV-2 infection changes microbiota and SCFAs production. However, the relevance of this effect is unknown. In this study, we used human intestinal biopsies and intestinal epithelial cells to investigate the impact of SCFAs in the infection by SARS-CoV-2. SCFAs did not change the entry or replication of SARS-CoV-2 in intestinal cells. These metabolites had no effect on intestinal cells' permeability and presented only minor effects on the production of anti-viral and inflammatory mediators. Together our findings indicate that the changes in microbiota composition of patients with COVID-19 and, particularly, of SCFAs do not interfere with the SARS-CoV-2 infection in the intestine.


Assuntos
COVID-19/virologia , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Mucosa Intestinal/virologia , Adulto , Idoso , Células CACO-2 , Colo/virologia , Células Epiteliais/virologia , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Carga Viral , Internalização do Vírus , Adulto Jovem
2.
Sci Rep ; 11(1): 1432, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446839

RESUMO

Single-chain variable fragments (scFvs) are small-sized artificial constructs composed of the immunoglobulin heavy and light chain variable regions connected by a peptide linker. We have previously described an anti-fibroblast growth factor 2 (FGF2) immunoglobulin G (IgG) monoclonal antibody (mAb), named 3F12E7, with notable antitumor potential revealed by preclinical assays. FGF2 is a known angiogenesis-associated molecule implicated in tumor progression. In this report, we describe a recombinant scFv format for the 3F12E7 mAb. The results demonstrate that the generated 3F12E7 scFv, although prone to aggregation, comprises an active anti-FGF2 product that contains monomers and small oligomers. Functionally, the 3F12E7 scFv preparations specifically recognize FGF2 and inhibit tumor growth similar to the corresponding full-length IgG counterpart in an experimental model. In silico molecular analysis provided insights into the aggregation propensity and the antigen-recognition by scFv units. Antigen-binding determinants were predicted outside the most aggregation-prone hotspots. Overall, our experimental and prediction dataset describes an scFv scaffold for the 3F12E7 mAb and also provides insights to further engineer non-aggregated anti-FGF2 scFv-based tools for therapeutic and research purposes.


Assuntos
Inibidores da Angiogênese/química , Antineoplásicos Imunológicos/química , Fator 2 de Crescimento de Fibroblastos/química , Proteínas de Neoplasias/química , Anticorpos de Cadeia Única , Humanos , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética
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