RESUMO

The Brazil nut is an excellent source of selenium (Se), an essential micronutrient for human health. In this study, we hypothesized that Brazil nut intake modulates circulating microRNAs (miRNAs) in obese women and aimed to evaluate the effects of this nut intake on circulating miRNAs in women with obesity or metabolic syndrome (MetS). A randomized controlled clinical trial was conducted on 54 subjects recruited from the Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to 2 groups: a Brazil nut group (BN group, n = 29) and a control group (CO group, n = 25); both were monitored for 2 months. BN group members were instructed to consume 1 Brazil nut (approximately 1261 µg/Se) per day; CO group members were instructed not to consume any. Biochemical parameters related to Se status and 25 circulating miRNAs in plasma were evaluated in all patients both at baseline and after 2 months. Expression levels of 2 miRNAs (miR-454-3p and miR-584-5p) were significantly increased after Brazil nut intake. To investigate the effect of MetS on circulating miRNAs at baseline, we performed comparisons between women with MetS (n = 23) and women without MetS (others, n = 31). Circulating miR-375 levels were significantly lower (P = .012) in women with MetS. In conclusion, our findings suggested that a daily intake of 1 Brazil nut increased circulating miR-454-3p and miR-584-5p expression levels in obese women, and our network analysis indicated a link between Se intake, vitamin D metabolism, and calcium homeostasis.

Assuntos

Bertholletia/metabolismo , Dieta/métodos , MicroRNAs/sangue , Nozes/metabolismo , Obesidade/sangue , Adulto , Biomarcadores/sangue , Brasil , Feminino , Humanos , Obesidade/metabolismo

RESUMO

OBJECTIVE: Increased inflammatory response is an important factor in the pathophysiology of obesity. The mineral selenium (Se), of which one of the main food sources is the Brazil nut, has important antioxidant and anti-inflammatory functions through the action of selenoproteins. Thus, the evaluation of the influence of this micronutrient in this context is of great relevance. The aim of this study was to evaluate the effects of Brazil nut intake with high Se concentrations on inflammatory biomarkers and its relation to Se status in obese women. METHODS: A randomized controlled clinical trial was carried out with 55 women recruited at Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to either the Brazil nut group (BN) or the control group (CO) and followed up for 2 mo. The BN group consumed 1 unit/d of Brazil nuts (∼ 1261 µg/Se); the CO group did not receive any intervention. At baseline and after 2 mo, analysis of biochemical parameters related to Se status, oxidative stress, and inflammatory biomarkers were performed. RESULTS: At baseline, both groups did not present Se deficiency. In the BN group, a significant increase (P < 0.05) in all Se biomarkers and in gene expression of several proinflammatory parameters (interleukin-6, tumor necrosis factor-α, and Toll-like receptors 2 and 4) were observed after the intervention period. No changes were observed for the CO group. CONCLUSION: Although there were no changes in plasma inflammatory biomarkers levels, a significant increase in gene expression may be an indication of a proinflammatory stimulus in obesity, induced by the consumption of Brazil nuts with high Se levels.

Assuntos

Bertholletia , Dieta/efeitos adversos , Mediadores da Inflamação/sangue , Obesidade/sangue , Selênio/sangue , Adulto , Bertholletia/química , Biomarcadores/sangue , Dieta/métodos , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Inflamação , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Selênio/administração & dosagem , Adulto Jovem

RESUMO

MicroRNAs (miRNAs) are post-transcriptional gene expression regulators which expression is frequently altered in hepatocellular carcinoma (HCC). ß-ionone (ßI) is noted for its ability to inhibit persistent preneoplastic lesions (pPNLs) in liver rats. We evaluated the expression of miRNAs involved in carcinogenesis and possible targets modulated by ßI, in pPNLs and surrounding of microdissected tissues. Rats subjected to resistant hepatocyte model were treated during promotion stage with ßI (16 mg/100 g body weight) or corn oil (CO; 0.25 mL/100 g body weight; controls). Five animals receive no treatment (NT). In CO group, 38 and 29 miRNAs showed reduced expression relative to NT (P < 0.05) in pPNLs and surrounding, respectively. No miRNAs showed increased expression in surrounding of the CO compared to NT group; however, 30 miRNAs showed increased expression (P ≤ 0.05) in pPNLs of the CO group. There was no difference between ßI and CO groups (P > 0.05) in the expression of miRNAs in surrounding. In pPNLs ßI increased expression of miR-122 and miR-34a (P ≤ 0.05) and reduced of Igf2 (P ≤ 0.05), target of the latter, compared to CO. Additionally, ßI decreased the expression of miR-181c and its target Gdf2 (P ≤ 0.05). ßI reduced the expression of miR-181b and miR-708 (P ≤ 0.05) and increased the expression of their respective target mRNAs Timp3 and Mtss1 (P ≤ 0.05), relative to CO group. Modulation of miRNAs target genes by ßI was confirmed in vitro. ßI is a promising chemopreventive agent in the initial stages of hepatocarcinogenesis, as it modulates the expression of the miRNAs and target genes that can alter the metastatic phenotype of HCC. © 2016 Wiley Periodicals, Inc.

Assuntos

Anticarcinógenos/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/prevenção & controle , Fígado/efeitos dos fármacos , MicroRNAs/genética , Norisoprenoides/uso terapêutico , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/prevenção & controle , Ratos , Ratos Wistar

RESUMO

CD4+ type 1 T regulatory (Tr1) cells have a crucial role in inducing tolerance. Immune regulation by these cells is mainly mediated through the secretion of high amounts of IL-10. Several studies have suggested that this regulatory population may be involved in tumor-mediated immune-suppression. However, direct evidence of a role for Tr1 cells in human solid tumors is lacking. Using ex vivo isolated cells from individuals with hepatocellular carcinoma (HCC; n = 39) or liver metastases from colorectal cancer (LM-CRC; n = 60) we identify a CD4+FoxP3-IL-13-IL-10+ T cell population in tumors of individuals with primary or secondary liver cancer that is characterized as Tr1 cells by the expression of CD49b and the lymphocyte activation gene 3 (LAG-3) and strong suppression activity of T cell responses in an IL-10 dependent manner. Importantly, the presence of tumor-infiltrating Tr1 cells is correlated with tumor infiltration of plasmacytoid dendritic cells (pDCs). pDCs exposed to tumor-derived factors enhance IL-10 production by Tr1 cells through up-regulation of the inducible co-stimulatory ligand (ICOS-L). These findings suggest a role for pDCs and ICOS-L in promoting intra-tumoral immunosuppression by Tr1 cells in human liver cancer, which may foster tumor progression and which might interfere with attempts of immunotherapeutic intervention.