Modulation of all-trans retinoic acid-induced MiRNA expression in neoplastic cell lines: a systematic review.

BACKGROUND: Cancer is a genetic and epigenetic disease that involves inactivation of tumor suppressor genes and activation of proto-oncogenes. All-trans retinoic acid (ATRA) is an isomer of retinoic acid involved in the onset of differentiation and apoptosis of a number of normal and cancer cells, functioning as an anti-cancer agent in several neoplasms. Ectopic changes in the expression of certain microRNAs (miRNAs) occur in response to ATRA, leading to phenotypic alterations in neoplastic cell lines. Moreover, the modulation of miRNA patterns upon ATRA-treatment may represent an effective chemopreventive and anti-cancer therapy strategy. The present systematic review was performed to provide an overview of the modulation of ATRA-induced miRNA expression in different types of neoplastic cells and identify the efficacy of intervention factors (i.e., concentration and duration of treatment) and how they influence expression profiles of oncogenesis-targeting miRNAs. METHODS: A systematic search was conducted according to the PRISMA statement via the US National Library of Medicine MEDLINE/PubMed bibliographic search engine. RESULTS: The search identified 31 experimental studies involving human cell lines from nine different cancer types (neuroblastoma, acute myeloid leukemia, breast cancer, lung cancer, pancreatic cancer, glioma, glioblastoma, embryonal carcinoma, and colorectal cancer) treated with ATRA at concentrations ranging from 10- 3 µmol/L to 102 µmol mol/L for 24 h to 21 days. CONCLUSION: The concentrations used and the duration of treatment of cancer cells with ATRA varied widely. The presence of ATRA in the culture medium of cancer cells was able to modulate the expression of more than 300 miRNAs, and inhibit invasive behavior and deregulated growth of cancer cells, resulting in total tumor remission in some cases. ATRA may thus be broadly effective for neoplasm treatment and prevention, although these studies may not accurately represent in vivo conditions. Additional studies are required to elucidate ATRA-induced miRNA modulation during neoplasm treatment.

Positive effects of zinc supplementation on growth, GH, IGF1, and IGFBP3 in eutrophic children.

Zinc is an essential micronutrient for growth and development. Its deficiency causes growth retardation in children and adolescents. The present study analyzes the effect of zinc on growth hormone (GH) secretion, insulin-like growth factor 1 (IGF1), and insulin-like growth factor-binding protein 3 (IGFBP3) in normal children before puberty. Thirty normal children were studied, 15 boys and 15 girls, aged 6-9 years. They were orally supplemented with 5 mg Zn/day for 3 months and 0.06537 mg Zn/kg body weight was injected before and after oral supplementation. Dietary intake and anthropometric measurements were assessed at baseline and end of study. Plasma GH levels increased during intravenous zinc administration and IGF1 and IGFBP3 increased after oral zinc supplementation. There was a positive correlation between the areas under the curves of GH and zinc after oral supplementation. Zinc supplementation was possibly effective in improving the body zinc status of the children, secretory levels of IGF1 and IGFBP3, GH potentialization, and height.

Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing.

The genetics underlying non-syndromic familial non-medullary thyroid carcinoma (FNMTC) is still poorly understood. To identify susceptibility genes for FNMTC, we performed whole-exome sequencing (WES) in a Brazilian family affected by papillary thyroid carcinoma (PTC) in three consecutive generations. WES was performed in four affected and two unaffected family members. Manual inspection in over 100 previously reported susceptibility genes for FNMTC showed that no variants in known genes co-segregated with disease phenotype in this family. Novel candidate genes were investigated using PhenoDB and filtered using Genome Aggregation (gnomAD) and Online Archive of Brazilian Mutations (ABraOM) population databases. The missense variant p.Ile657Met in the NID1 gene was the only variant that co-segregated with the disease, while absent in unaffected family members and controls. The allele frequency for this variant was <0.0001 in the gnomAD and ABbraOM databases. In silico analysis predicted the variant to be deleterious or likely damaging to the protein function. Somatic mutations in NID1 gene were found in nearly 500 cases of different cancer subtypes in the intOGen platform. Immunohistochemistry analysis showed NID1 expression in PTC cells, while it was absent in normal thyroid tissue. Our findings were corroborated using data from the TCGA cohort. Moreover, higher expression of NID1 was associated with higher likelihood of relapse after treatment and N1b disease in PTCs from the TCGA cohort. Although replication studies are needed to better understand the role of this variant in the FNMTC susceptibility, the NID1 variant (c.1971T>G) identified in this study fulfills several criteria that suggest it as a new FNMTC predisposing gene.

Serum zinc reference intervals and its relationship with dietary, functional, and biochemical indicators in 6- to 9-year-old healthy children.

BACKGROUND: Zinc is an important cause of morbidity, particularly among young children. The dietary, functional, and biochemical indicators should be used to assess zinc status and to indicate the need for zinc interventions. OBJECTIVE: The purpose of this study was to determine the zinc status and reference intervals for serum zinc concentration considering dietary, functional, and biochemical indicators in apparently healthy children in the Northeast Region of Brazil. DESIGN: The cross-sectional study included 131 healthy children: 72 girls and 59 boys, aged between 6 and 9 years. Anthropometric assessment was made by body mass index (BMI) and age; dietary assessment by prospective 3-day food register, and an evaluation of total proteins was performed. Zinc in the serum samples was analyzed in triplicate in the same assay flame, using atomic absorption spectrophotometry. RESULTS: With respect to dietary assessment, only the intake of fiber and calcium was below the recommendations by age and gender. All subjects were eutrophic according to BMI and age classification. Zinc intake correlated with energy (p=0.0019), protein (p=0.0054), fat (p<0.0001), carbohydrate (p=0.0305), fiber (p=0.0465), calcium (p=0.0006), and iron (p=0.0003) intakes. Serum zinc correlated with protein intake (p=0.0145) and serum albumin (p=0.0141), globulin (p=0.0041), and albumin/globulin ratio (p=0.0043). Biochemical parameters were all within the normal reference range. Reference intervals for basal serum zinc concentration were 0.70-1.14 µg/mL in boys, 0.73-1.17 µg/mL in girls, and 0.72-1.15 µg/mL in the total population. CONCLUSIONS: This study presents pediatric reference intervals for serum zinc concentration, considering dietary, functional, and biochemical indicators, which are useful to establish the zinc status in specific groups. In this regard, there are few studies in the literature conducted under these conditions, which make it an innovative methodology.

Bioelectrical impedance vector analysis for evaluating zinc supplementation in prepubertal and healthy children.

BACKGROUND: The prevalence of abnormal nutritional status has increased in children and adolescents. Nutritional assessment is important for monitoring the health and nutritional status. Bioelectrical impedance vector analysis (BIVA) combines changes in tissue hydration and structure and body composition that can be assessed. OBJECTIVES: The objective of this study was to use BIVA to evaluate nutritional status in 60 prepubertal children, aged between 8 and 9 years, supplemented with zinc, to detect possible changes in body composition. DESIGN: We performed a randomized, controlled, triple-blind study. The children were divided into the control group (CG; sorbitol 10%, n=29) or the experimental group (EG; 10 mg Zn/day, n=31), and the duration of the experiment was 3 months. Anthropometric assessments were performed for all of the children. RESULTS: The body mass index-for-age increased after oral zinc supplementation in the EG (p=0.005). BIVA indicated that the CG demonstrated a tendency for dehydration and decreased soft tissue and the EG demonstrated a tendency for increased soft tissue, primarily the fat-free mass. After analyses of BIVA ellipses, we observed that this method could detect improvements in body composition in healthy children supplemented with zinc. CONCLUSIONS: These results suggest that BIVA could be an auxiliary method for studying a small population undergoing zinc intervention.

Oral zinc supplementation may improve cognitive function in schoolchildren.

Zinc is an important micronutrient for humans, and zinc deficiency among schoolchildren is deleterious to growth and development, immune competence, and cognitive function. However, the effect of zinc supplementation on cognitive function remains poorly understood. The purpose of our study was to evaluate the effect of oral zinc supplementation (5 mg Zn/day for 3 months) on the Full Scale Intelligence Quotient (FSIQ), Verbal Intelligence Quotient (VIQ), and Performance Intelligence Quotient (PIQ) using a Wechsler Intelligence Scale for Children (WISC-III). We studied 36 schoolchildren aged 6 to 9 years (7.8 ± 1.1) using a nonprobability sampling method. The baseline serum zinc concentrations increased significantly after zinc supplementation (p < 0.0001), with no difference between sexes. Tests were administered under basal conditions before and after zinc supplementation, and there was no difference in FSIQ according to gender or age. The results demonstrated that zinc improved the VIQ only in the Information Subtest (p = 0.009), although the supplementation effects were more significant in relation to the PIQ, as these scores improved for the Picture Completion, Picture Arrangement, Block Design, and Object Assembly Subtests (p = 0.0001, for all subtests). In conclusion, zinc supplementation improved specific cognitive abilities, thereby positively influencing the academic performance of schoolchildren, even those without marginal zinc deficiency.

Influence of basal energy expenditure and body composition on bone mineral density in postmenopausal women.

BACKGROUND: The aim of this study was to investigate the influence of body mass index, body weight, lean mass, fat mass, and basal energy expenditure on bone mineral density in postmenopausal women. METHODS: This was a cross-sectional, descriptive study of a sample of 50 women, with minimum time since menopause between 1 and 10 years. Bone mineral density was assessed at the lumbar spine (L2-L4), femoral neck, Ward's triangle, and trochanter using dual-energy X-ray absorptiometry. Body mass index, lean mass, fat mass, and basal energy expenditure were measured by bioimpedance. RESULTS: The mean age of the women was 51.49 ± 3.86 years and time since menopause was 3.50 ± 2.59 years. Significant negative correlations were found between chronological age and lumbar spine, femoral neck, Ward's triangle, and trochanteric bone mineral density. In regard to time since menopause, we also observed significant negative correlations with bone mineral density at the lumbar spine and Ward's triangle. The following significant positive correlations were recorded: body mass index with bone mineral density at the femoral neck and trochanter; fat mass with bone mineral density at the femoral neck and trochanter; lean mass with bone mineral density at the lumbar spine, femoral neck, and trochanter; and basal energy expenditure with bone mineral density at all sites assessed. On the other hand, the multiple linear regression model showed that: 20.2% of bone mineral density variability at the lumbar spine is related to lean mass and time since menopause; 22.3% of bone mineral density variability at the femoral neck is related to body weight and age; 18.9% of bone mineral density variability at Ward's triangle is related to age and basal energy expenditure; and 39% of bone mineral density variability at the trochanter is related to body mass index, age, and menarche. CONCLUSION: Changes in bone mineral density, specific for each skeletal site, are influenced by age, time since menopause, body weight, body mass index, lean mass, and basal energy expenditure. Lean mass and basal energy expenditure positively influenced bone mineral density at the lumbar spine and Ward's triangle, with a predominance of trabecular bone.

Protocolo diferenciado para terapia nutricional na esclerose lateral amiotrófica / Special protocol to nutritional therapy in amyotrophic lateral sclerosis

OBJETIVO: Discutir a terapia nutricional na Esclerose Lateral Amiotrófica (ELA), compartilhando um protocolo elaborado e utilizado em ambulatório especializado. MATERIAL E MÉTODOS: A fundamentação teórica desse artigo foi baseada na literatura científica publicada nas bases de dados PubMed e ISI Web of Science, utilizando os descritores "amyrotrophic lateral sclerosis" and "nutrition". RESULTADOS E DISCUSSÃO: Em síntese, a ELA é uma doença neurodegenerativa rara, com prognóstico desfavorável e tratamento paliativo. A desnutrição é bastante frequente nessa doença e aumenta o risco de morte dos pacientes. Assim, a terapia nutricional é imprescindível e deve estar integrada a uma assistência multidisciplinar. O monitoramento nutricional é recomendado pelo menos a cada três meses, incluindo avaliação nutricional e prescrição de dieta hipercalórica e hiperproteica, com adequada quantidade hídrica e de fibras. Em adição, os micronutrientes, sobretudo os antioxidantes, devem atingir a Ingestão Diária Recomendada. Modificações na consistência da dieta para tratar a disfagia são indicadas e a nutrição enteral deve ser desmistificada entre os pacientes e cuidadores. Esses pacientes são candidatos potenciais para uso da nutrição enteral, a qual deve ser indicada em casos de disfagia significativa ou prejuízo da função respiratória associada com baixa ingestão alimentar, índice de massa corporal menor que 18,5 ou 22,0 kg/m2 (para adultos e idosos, respectivamente) e/ou perda de peso acima de 10%. CONCLUSÃO: Sugere-se a padronização da terapia nutricional na ELA e a instituição de protocolo diferenciado na prática clínica. Com isso, a desnutrição pode ser evitada ou minimizada, contribuindo para melhor qualidade de vida e sobrevida desses pacientes

OBJECTIVE: To discuss the nutritional therapy in Amyotrophic Lateral Sclerosis (ALS), sharing a protocol performed and used by a specialized ambulatory care service. MATERIAL AND METHODS: The theoretical foundation of this paper was based on the literature published in both PubMed and ISI Web of Science, using "amyrotrophic lateral sclerosis" and "nutrition" as keywords. RESULTS AND DISCUSSION: In brief, ALS is a rare neurodegenerative disease with poor prognosis and palliative treatment. Malnutrition is very common in these patients and increases the risk of death among them. Nutritional therapy is essential and must be integrated into a multidisciplinary care. Nutritional monitoring is recommended at least once every three months. Nutritional assessment, high-calorie and highprotein diet with an adequate amount of water and fiber are recommended. In addition, micronutrients, especially antioxidants, must reach the Recommended Dietary Allowances. A diet texture modification for dysphagia is indicated and enteral nutrition should be demystified to patients and care givers during the follow-up care. ALS patients are potential candidates to use enteral nutrition, which should be indicated in cases of significant dysphagia or impaired respiratory function associated with low food intake, body mass index less than 18.5 or 22.0 kg/m² (for adults or elderlies, respectively), and/or body weight loss above 10%. CONCLUSION: We suggest the standardization of nutritional therapy in ALS and the establishment of a distinct protocol in clinical practice. Thus, malnutrition can be avoided or minimized, contributing to a better quality of life and survival of these patients

Comparação de três programas computacionais utilizados na avaliação de recordatórios alimentares 24 horas / Comparison of three softwares used for evaluating of 24-hour food recall / Comparación de tres programas de ordenador usados en la evaluación de recordatorios 24 h

A avaliação do consumo alimentar tem um papel importante na área de Nutrição e Saúde. Para tanto, são necessários métodos apropriados para estimar a ingestão de alimentos e nutrientes. O mercado da informática vem desenvolvendo diversos programas computacionais especializados em nutrição clínica. No entanto, a escolha do programa mais adequado tem sido uma decisão difícil em função das características operacionais disponíveis em cada um. Este estudo objetivou comparar três programas computacionais (Dietwin® profissional, Dietpro® 5i e Avanutri® revolution) utilizados na análise química nutricional de dez Recordatórios Alimentares de 24 horas oriundos de pacientes com Esclerose Lateral Amiotrófica, atendidos no Hospital Universitário da UFRN. Não houve diferença estatística entre os programas computacionais, com relação à energia, macronutrientes e micronutrientes. Todavia, foram detectadas divergências entre as gramaturas estipuladas para medidas caseiras de alguns alimentos. Além disso, observou-se quantificação equivocada do teor de ferro e cobre em dois alimentos. Conclui-se que é preciso ter cautela na escolha de um programa computacional especializado em nutrição clínica, pois poderá superestimar ou subestimar valores de energia ou nutrientes numa dieta prescrita ou consumida. Em adição, cuidado especial deve ser dado à origem das informações que alimentam o banco de dados desses programas, devendo ser as mais fidedignas possíveis.

Food intake assessment has an important role in nutrition research and health. For this purpose, right methods are needed to estimate appropriate intake of food and nutrients. The informatics market has developed several specialized computer programs in clinical nutrition . However, choosing the most appropriate program has been a difficult decision due all of operational features available in each one. This study aimed to compare three computer programs (Dietwin ® professional DietPro ® 5i and Avanutri Revolution ®) used in chemical analysis of ten 24-hour food recall from ten Amyotrophic Lateral Sclerosis patients, attending in by specific Multidisciplinary Team at Federal University of Rio Grande do Norte. There was no statistical difference between the three computer programs related to energy, macronutrients and micronutrients. Despite this, some differences were detected like measure portion food sizes. Moreover, there was wrong quantification of iron and copper content in two foods. We conclude that care should be taken to choose a computer program in clinical nutrition, because it can overestimate or underestimate values of calories and nutrients in a specific diet. In addition, it is necessary to be especially careful in the information sources that will feed the database of these programs. They should be as reliable as possible.

La evaluación de la ingesta alimentaria tiene un papel importante en la investigación en nutrición y salud. Para evaluar la ingesta de alimentos de un individuo se requieren métodos adecuados para la estimación de la ingesta de alimentos y nutrientes. El mercado de la informática ha desarrollado varios programas informáticos especializados en nutrición clínica. Sin embargo, elegir el programa más apropiado ha sido una decisión difícil a la luz de las características disponibles operativo. Este estudio tuvo por objetivo comparar los tres programas de ordenador (Dietwin ® profesional DietPro ® 5i y Avanutri Revolución ®) utilizados en el análisis químico de de recordatorios 24 h de pacientes con Esclerosis Amiotrófica Lateral. No hubo diferencia estadística entre los programas de ordenador, con respecto a la energía, macronutrientes y micronutrientes. Sin embargo, se detectaron diferencias entre los pesos fijados para tamaños de las porciones de algunos alimentos. Además, el contenido de hierro y el cobre se equivocaron en dos alimentos. El estudio demostró que se debe tener cuidado al elegir el mejor programa en la nutrición clínica, ya que puede sobreestimar o subestimar los valores de las calorías y nutrientes de una dieta prescrita o consumido. Además, la atención especial se debe dar a la fuente de la información introducida en la base de datos de estos programas debe ser lo más fiable posible.