RESUMO
l-asparaginases play a crucial role in the treatment of acute lymphoblastic leukemia (ALL), a type of cancer that mostly affects children and teenagers. However, it is common for these molecules to cause adverse reactions during treatment. These downsides ignite the search for novel asparaginases to mitigate these problems. Thus, this work aimed to produce and characterize a recombinant asparaginase from Phaseolus vulgaris (Asp-P). In this study, Asp-P was expressed in Escherichia coli with high yields and optimum activity at 40 °C, pH 9.0. The enzyme Km and Vmax values were 7.05 mM and 1027 U/mg, respectively. Asp-P is specific for l-asparagine, showing no activity against l-glutamine and other amino acids. The enzyme showed a higher cytotoxic effect against Raji than K562 cell lines, but only at high concentrations. In silico analysis indicated that Asp-P has lower immunogenicity than a commercial enzyme. Asp-P induced biofilm formation by Candida sp. due to sublethal dose, showing an underexplored potential of asparaginases. The absence of glutaminase activity, lower immunogenicity and optimal activity similar to physiological temperature conditions are characteristics that indicate Asp-P as a potential new commercial enzyme in the treatment of ALL and its underexplored application in the treatment of other diseases.
Assuntos
Asparaginase , Phaseolus , Proteínas Recombinantes , Asparaginase/química , Asparaginase/farmacologia , Asparaginase/genética , Asparaginase/imunologia , Phaseolus/química , Humanos , Cinética , Proteínas Recombinantes/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Leucemia/tratamento farmacológico , Células K562 , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Concentração de Íons de Hidrogênio , TemperaturaRESUMO
Surfactants are applied in several industrial processes when the modification of interface activity and the stability of colloidal systems are required. Lipopeptides are a class of microbial biosurfactants produced by species of the Bacillus genus. The present study aimed at assembling and analyzing the genome of a new Bacillus vallismortis strain, TIM68, that was shown to produce surfactant lipopeptides. The draft genome was also screened for common virulence factors and antibiotics resistance genes to investigate the strain biosafety. Comparative genomics analyses, i.e., synteny, average nucleotide identity (ANI), and pangenome, were also carried out using strain TIM68 and publicly available B. vallismortis complete and partial genomes. Three peptide synthetase operons were found in TIM68 genome, and they were surfactin A, mojavensin, and a novel plipastatin-like lipopeptide named vallisin. No virulence factors that render pathogenicity to the strain have been identified, but a region of prophage, that may contain unknown pathogenic factors, has been predicted. The pangenome of the species was characterized as closed, with 57% of genes integrating the core genome. The results obtained here on the genetic potential of TIM68 strain should contribute to its exploration in biotechnological applications.
Assuntos
Bacillus , Lipopeptídeos , Lipopeptídeos/farmacologia , Tensoativos/farmacologia , Tensoativos/química , Bacillus/genética , GenômicaRESUMO
Chronic kidney disease (CKD) is a serious public health problem and its prevalence is growing in many countries, often related to issues resulting from the lifestyle in growing economies and the population's life expectancy. Nutritional therapy is a beneficial but still neglected strategy for preventing CKD and delaying disease progression. The aim of this study was to assess the association of dietary patterns with CKD development and progression. Observational studies conducted in adult humans and the correlation between the adopted dietary pattern and prevalent and incident cases of CKD were assessed. A significant association was observed between unhealthy dietary patterns and an increased risk of developing or worsening CKD, as well as an adverse effect. Whereas healthy eating patterns characterized by the consumption of fruit, vegetables and dietary fibre showed nephroprotective outcomes.