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1.
Environ Microbiol ; 18(12): 4653-4661, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27059806

RESUMO

In this study, a random mutant library of Herbaspirillum seropedicae SmR1 was constructed by Tn5 insertion and a mutant incapable of utilizing naringenin as a carbon source was isolated. The Tn5 transposon was found to be inserted in the fdeE gene (Hsero_1007), which encodes a monooxygenase. Two other mutant strains in fdeC (Hsero_1005) and fdeG (Hsero_1009) genes coding for a dioxygenase and a putative cyclase, respectively, were obtained by site-directed mutagenesis and then characterized. Liquid Chromatography coupled to mass spectrometry (LC-MS)/MS analyses of culture supernatant from the fdeE mutant strain revealed that naringenin remained unaltered, suggesting that the FdeE protein is involved in the initial step of naringenin degradation. LC-MS/MS analyses of culture supernatants from the wild-type (SmR1) and FdeC deficient mutant suggested that in H. seropedicae SmR1 naringenin is first mono-oxygenated by the FdeE protein, to produce 5,7,8-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one, that is subsequently dioxygenated and cleaved at the A-ring by the FdeC dioxygenase, since the latter compound accumulated in the fdeC strain. After meta-cleavage of the A-ring, the subsequent metabolic steps generate oxaloacetic acid that is metabolized via the tricarboxylic acid cycle. This bacterium can also modify naringenin by attaching a glycosyl group to the B-ring or a methoxy group to the A-ring, leading to the generation of dead-end products.


Assuntos
Flavanonas/metabolismo , Herbaspirillum/metabolismo , Biodegradação Ambiental , Herbaspirillum/enzimologia , Herbaspirillum/genética , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Espectrometria de Massas em Tandem
2.
Curr Gene Ther ; 23(4): 245-260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37170970

RESUMO

Leukemia is a type of cancer that affects white blood cells. In this disease, immature blood cells undergo genetic mutations, leading to excessive replication and reduced cell death compared to healthy cells. In cancer, there may be the activation of oncogenes and the deactivation of tumor suppressor genes that control certain cellular functions. Despite the undeniable contribution to the patient's recovery, conventional cancer treatments may have some not-so-beneficial effects. In this case, gene therapy appears as an alternative to classical treatments. Gene therapy delivers genetic material to cells to replace or modify dysfunctional genes, a safe method for neoplasms. One of the types of nucleic acids explored in gene therapy is microRNA (miRNA), a group of endogenous, non-proteincoding, small single-stranded RNA molecules involved in the regulation of gene expression, cell division, differentiation, angiogenesis, migration, apoptosis, and carcinogenesis. This review aims to bring together the most recent advances found in the literature on cancer gene therapy based on microRNAs in the oncological context, focusing on leukemia.


Assuntos
Leucemia , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , MicroRNAs/metabolismo , Neoplasias/genética , Neoplasias/terapia , Neoplasias/patologia , Leucemia/genética , Leucemia/terapia , Terapia Genética/métodos , Modelos Teóricos , Regulação Neoplásica da Expressão Gênica
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