Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?

BACKGROUND: Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock. METHODS: Blood samples were collected from 24 patients with septic shock at ICU admission and after 7 days of treatment. Twelve healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, and their miRNA and mRNA content was evaluated by qRT-PCR array. RESULTS: As compared with healthy volunteers, exosomes from patients with sepsis had significant changes in 65 exosomal miRNAs. Twenty-eight miRNAs were differentially expressed, both at enrollment and after 7 days, with similar kinetics (18 miRNAs upregulated and 10 downregulated). At enrollment, 35 differentially expressed miRNAs clustered patients with sepsis according to survival. The pathways enriched by the miRNAs of patients with sepsis compared with control subjects were related mostly to inflammatory response. The comparison of miRNAs from patients with sepsis according to hospital survival demonstrated pathways related mostly to cell cycle regulation. At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-fold; PRDX3, 2.6-fold; SOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-fold; SELS, 16-fold; GLRX2, 3.4-fold). The expression of myeloperoxidase mRNA remained elevated after 7 days (65-fold). CONCLUSIONS: Exosomes from patients with septic shock convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response, oxidative stress, and cell cycle regulation. Exosomes may represent a novel mechanism for intercellular communication during sepsis.

Vitamin A deficiency and associated factors in children in urban areas.

OBJECTIVE: To estimate the prevalence of vitamin A deficiency and its associated factors in children. METHODS: A cross-sectional population-based study, involving 1,211 children of both sexes, aged between six and 59 months old, was carried out in the urban zone of 9 cities in the state of Paraiba, Northeastern Brazil. Vitamin A status was assessed by serum retinol levels (high performance liquid chromatography - HPLC) and subclinical infection was assessed by C-reactive protein concentrations. Socioeconomic, demographic and sanitation conditions, as well as vitamin A supplement intake, were also evaluated. Children with serum retinol concentrations RESULTS: The prevalence of vitamin A deficiency was 21.8% (95%CI 19.6;24.2), showing an association with subclinical infection and lack of indoor plumbing. The prevalence of vitamin A deficiency was 21.8% (95%CI 19.6;24.2). After adjustment, vitamin A deficiency was found to be linked with subclinical infection and lack of indoor plumbing. Vitamin A deficiency was four times higher (CI95% 1.49;10.16) in children with subclinical infection whose homes were without indoor plumbing, compared to children who were not infected and with indoor plumbing in their homes. CONCLUSIONS: Despite activities aimed at the prevention and control of vitamin A deficiency, hypovitaminosis A, remains a public health concern among children under five.

Deficiencia de vitamina A e fatores associados em criancas de areas urbanas / Vitamin A deficiency and associated factors in children in urban areas

OBJETIVO: Analisar a prevalência da deficiência de vitamina A em crianças e os fatores associados. MÉTODOS: Estudo de corte transversal de base populacional realizado com 1.211 crianças de seis a 59 meses de idade, de ambos os sexos, procedentes da área urbana de nove cidades do estado da Paraíba, Brasil. O estado nutricional de vitamina A foi avaliado pelas concentrações séricas de retinol e presença de infecção subclínica avaliada pelas concentrações de proteína C-reativa. Foram investigadas as condições socioeconômicas, demográficas, de saneamento, além da suplementação prévia com vitamina A. Foram consideradas com deficiência de vitamina A as crianças com concentrações de retinol sérico < 0,70 µmol/L. Níveis séricos de vitamina A < 0,70 µmol/L com prevalência ≥ 20% foram considerados como grave problema de saúde pública. Análises uni e multivaridas foram conduzidas para testar associações estatísticas (p < 0,05). RESULTADOS: A prevalência de deficiência de vitamina A foi de 21,8% (IC95% 19,6;24,2), mostrando associação com a presença de infecção subclínica e ausência de água no domicílio. A prevalência de deficiência de vitamina A foi de 21,8% (IC95% 19,6;24,2). Após ajuste para confundimento, a deficiência de vitamina A mostrou-se associada com a presença de infecção subclínica e com a ausência de água no domicílio. A ocorrência da deficiência de vitamina A foi quatro vezes maior (IC95% 1,49;10,16) em crianças com infecção subclínica e sem água no domicilio, comparativamente às crianças ...

OBJECTIVE To estimate the prevalence of vitamin A deficiency and its associated factors in children. METHODS A cross-sectional population-based study, involving 1,211 children of both sexes, aged between six and 59 months old, was carried out in the urban zone of 9 cities in the state of Paraiba, Northeastern Brazil. Vitamin A status was assessed by serum retinol levels (high performance liquid chromatography – HPLC) and subclinical infection was assessed by C-reactive protein concentrations. Socioeconomic, demographic and sanitation conditions, as well as vitamin A supplement intake, were also evaluated. Children with serum retinol concentrations RESULTS The prevalence of vitamin A deficiency was 21.8% (95%CI 19.6;24.2), showing an association with subclinical infection and lack of indoor plumbing. The prevalence of vitamin A deficiency was 21.8% (95%CI 19.6;24.2). After adjustment, vitamin A deficiency was found to be linked with subclinical infection and lack of indoor plumbing. Vitamin A deficiency was four times higher (CI95% 1.49;10.16) in children with subclinical infection whose homes were without indoor plumbing, compared to children who were not infected and with indoor plumbing in their homes. CONCLUSIONS Despite activities aimed at the prevention and control of vitamin A deficiency, hypovitaminosis A, remains a public health concern among children under five. .