RESUMO
OBJECTIVE: Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells. METHODS: Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies. RESULTS: Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53. CONCLUSIONS: This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions.
RESUMO
INTRODUCTION: The effect of gestational age and fetal growth on the oxidant/antioxidant status of breast milk is poorly understood. OBJECTIVE: To evaluate the oxidative stress biomarkers in colostrum and mature milk according to gestational age and fetal growth. METHOD: A longitudinal study with mothers of premature and term infants, born in a tertiary referral hospital between 2014-2018. Inclusion criteria: postpartum women with a singleton pregnancy, who intended to exclusively breastfeed. Exclusion criteria: maternal diabetes, use of medication, drug addiction, congenital infection or malformation, mastitis, and failure to collect colostrum. Four groups were formed according to gestational age and birth weight (appropriate and small): Preterm small (n = 37), Preterm appropriate (n = 99), Full-term small (n = 65), and Full-term appropriate (control, n = 69). The colostrum samples were collected between 24-72 h and the mature milk was sampled in the 4th week of lactation for malondialdehyde (biomarker for lipid peroxidation) and Glutathione peroxidase, Catalase, and Superoxide dismutase measurements. The data were compared among groups using the Chi-square test or Fisher's exact test, one-way analysis of variance followed by Wald's Distribution test and repeated measures analysis of variance. RESULTS: We found a lower malondialdehyde level in colostrum in preterm groups and term small for gestational age, and the antioxidant enzymes Superoxide dismutase and Catalase activities were higher for preterm compared to term groups. The malondialdehyde levels differed in mature milk samples (Full-term small > Full-term appropriate > Preterm small > Preterm appropriate). The malondialdehyde levels increased during lactation in all groups except Preterm appropriate, and the levels of Catalase decreased in preterm groups. CONCLUSION: The oxidative status in breast milk is influenced by gestational age and fetal growth, which increased antioxidant defense for preterm infants and decreased oxidative stimuli for small for gestational age infants. These findings contribute to encouraging breastfeeding for newborns.
Assuntos
Colostro , Leite Humano , Recém-Nascido , Lactente , Gravidez , Feminino , Humanos , Idade Gestacional , Catalase , Antioxidantes , Estudos Longitudinais , Recém-Nascido Prematuro , Desenvolvimento Fetal , Superóxido DismutaseRESUMO
RESUMO Introdução: As crianças com síndrome de Down (SD) podem apresentar maior incidência de neofobia e de seletividade alimentar, sobrepeso e obesidade. A alimentação saudável e equilibrada é de suma importância para o crescimento adequado dessas crianças. Objetivo: Avaliar a adequação dos componentes da dieta e o estado nutricional de crianças e adolescentes com síndrome de Down em seguimento no ambulatório de pediatria genética do Hospital das Clínicas de Botucatu. Método: Estudo clínico descritivo transversal, com coleta de dados clínicos e avaliação nutricional, realizadopor meio de dados antropométricos e recordatório alimentar para avaliação da dieta. Análise estatística dos testes de Qui-quadrado e de Tukey. Resultados: Foram incluídos 35 crianças e dois adolescentes. Os diagnósticos nutricionais foram 2,7% de magreza, 81,1% de eutrofia, 8,1% de obesidade e 8,1% em risco ou sobrepeso. Houve excesso de ingestão de lipídeos naqueles com sobrepeso e obesidade, e a dieta deficiente em fibras foi prevalente a partir do primeiro ano de vida, bem como excesso de calorias e adequação de ferro e zinco. Entre os dois adolescentes, predominou a dieta com déficits em macro e micronutrientes, exceto em vitamina C e colesterol. Conclusões: A dieta com excesso de calorias, carboidratos e lipídios, como tambémcom déficit de fibras, aponta uma alimentação pouco balanceada entre crianças e adolescentes com SD, principalmente após o primeiro ano de vida, apesar do seu adequado estado nutricional.
RESUMEN Introducción: los niños consíndrome de Down (SD) pueden presentar mayor incidencia de neofobia yde selectividad alimentaria, sobrepeso y obesidad. La alimentación saludabley equilibradaes de gran importancia para el crecimiento adecuado de estos niños. Objetivo: la adecuación de los componentes de la dieta yel estado nutricional de niños y adolescentes con síndrome de Downasistidosen la clínica médica depediatría genética delHospital das Clínicas de Botucatu. Método: estudio clínico descriptivo transversal, con recolección de datos clínicos yevaluación nutricional, realizado medianteindicadores antropométricos y recordatorio alimentario para la evaluación de la dieta. Análisis estadísticode laspruebas de ji-cuadrado y de Tukey. Resultados: fueron incluidos 35niños ydos adolescentes. Los diagnósticos nutricionales fueron 2,7% de delgadez, 81,1% de eutrofia, 8,1% de obesidady8,1% en riesgo o sobrepeso. Hubo exceso de ingestión delípidosenaquellos con sobrepeso y obesidad, yla dieta deficiente en fibrasfueprevalentea partir del primer año de vida, así como exceso de calorías y adecuación de hierro y zinc. Entre los dos adolescentes, predominóla dieta con déficits en macro y micronutrientes, excepto en vitamina C y colesterol. Conclusiones: la dieta con exceso de calorías, carbohidratosylípidos, como tambiéncondéficit de fibras, señala una alimentación poco balanceada entre niños y adolescentes con SD, principalmente trasel primer año de vida, apesar de su adecuado estado nutricional.
ABSTRACT Introduction: Children with Down syndrome (DS) may have a prevalence of neophobia and food selectivity, overweight, and obesity. A healthy and balanced diet is of utmost importance for the proper growth of these children. Objective: To evaluate the adequacy of diet components and the nutritional status of children and adolescents with Down syndrome followed up at the outpatient care of genetic pediatrics, Hospital das Clínicas de Botucatu. Method: A cross-sectional descriptive clinical study, with a collection of clinical data and nutritional assessment, using anthropometric data and dietary records to evaluate the diet. Statistical analysis of the Chi-square and Tukey tests were performed. Results: A total of 35 children and two adolescents were included. Nutritional diagnoses were 2.7% lean, 81.1% eutrophic, 8.1% obese, and 8.1% at risk or overweight. There was an excess of lipid intake in overweight and obese children, and a fiber-deficient diet was prevalent since the first year of age, as well as extra calories and adequate iron and zinc intake. Among the two adolescents, a diet with deficits in macro and micronutrients, except for vitamin C and cholesterol, stood out. Conclusions: A diet with an excess of calories, carbohydrates, and lipids, as well as a fiber-deficient diet, indicates an unbalanced diet among children and adolescents with DS, especially after one year of age, despite their adequate nutritional status.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Avaliação Nutricional , Criança , Adolescente , Síndrome de Down , Dieta , Pediatria , Magreza , Zinco , Carboidratos , Micronutrientes , Sobrepeso , Eutrofização , Alimentos , Transtorno Alimentar Restritivo Evitativo , Seletividade Alimentar , Genética , Ferro , Lipídeos , ObesidadeRESUMO
INTRODUCTION: Preeclampsia (PE) is a systemic inflammatory disease, and its effect on human milk immune components is poorly understood. OBJECTIVE: To investigate whether PE affects human milk cytokine levels. METHODS: This was a prospective observational study involving mothers diagnosed with PE and with singleton pregnancy with no fetal malformation. The following cases were excluded: diabetes, chorioamnionitis, use of illicit drugs and alcohol, mastitis and congenital infection. In total, 228 mothers were studied and divided into two groups matched by gestational age: PE (n = 114) and normotensive (control, n = 114). Colostrum was collected from 24-72 hours postpartum, and mature milk was collected at the end of the first month. Cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12, and TNF-α) were measured using flow cytometry. A generalized linear model with a gamma distribution was used to analyze the differences between groups versus time interaction. RESULTS: The mean gestational age was 36 weeks. Increased IL-1 and IL-6 levels and reduced IL-12 levels in the colostrum were detected in PE, while in the mature milk, the IL-6 and IL-8 levels were lower than those of the control group. CONCLUSIONS: PE is associated with increased levels of inflammatory cytokines in colostrum and decreased levels in mature milk.
Assuntos
Colostro/imunologia , Leite Humano/imunologia , Pré-Eclâmpsia/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Interleucina-6/análise , Interleucina-8/análise , Gravidez , Estudos Prospectivos , Fator de Necrose Tumoral alfa/análise , Adulto JovemRESUMO
RESUMO Objetivo: Avaliar se o conteúdo de gordura e o valor energético estimado no colostro diferem em função da idade gestacional e do crescimento fetal. Métodos: Estudo transversal com mães de recém-nascidos pré-termo e a termo nascidos em centro terciário em 2015-2016. Critério de inclusão: gestação única, sem diabetes, corioamnionite e mastite, sem uso de drogas ilícitas e álcool, ausência de malformação ou infecção congênita fetal. Foram constituídos quatro grupos conforme idade gestacional e crescimento fetal: pré-termo pequeno para a idade gestacional (n=33); pré-termo adequado (n=60); a termo pequeno (n=59) e a termo adequado para a idade gestacional (controle, n=73). O colostro foi coletado por extração manual entre 24 e 72 h pós-parto. Foram analisadas variáveis gestacionais e de nascimento. Os desfechos foram o conteúdo de gordura no colostro, pelo método do crematócrito, e o valor energético estimado. Na comparação entre grupos foram utilizados os testes do qui-quadrado ou Exato de Fisher, ANOVA e regressão linear multivariada. Resultados: A idade gestacional média foi de 34 semanas nos neonatos pré-termo e 39 semanas nos a termo. O crematócrito não diferiu entre os grupos, com valores médios de 3,3 a 4,0%; e o valor energético estimado foi de 52 a 56 kcal/dL. Crematócrito ≥4% foi mais frequente no grupo a termo pequeno para idade gestacional. Apenas no grupo de recém-nascidos pré-termo pequenos para a idade gestacional houve correlação entre crematócrito e índice de massa corpórea materno. Conclusões: O conteúdo de gordura e o valor energético estimado do colostro não diferiram em função da idade gestacional e do crescimento fetal.
ABSTRACT Objective: To determine whether fat content and energy value change in colostrum according to gestational age and fetal growth. Methods: Cross-sectional study with mothers of preterm and term infants born in a tertiary center in 2015-2016. Inclusion criteria: single pregnancy, absence of diabetes, chorioamnionitis and mastitis, no use of illicit drugs or alcohol, without fetal congenital malformation or infection. Four groups were formed according to gestational age and fetal growth: preterm infants small for gestational age (PT-SGA; n=33) and appropriate for gestational age (PT-AGA; n=60), term infants small for gestational age (T-SGA; n=59) and appropriate for gestational age (T-AGA; control, n=73). Colostrum was collected between 24-72 hours postpartum. Gestational and birth variables were analyzed. Outcome variables were: fat content in colostrum (evaluated by crematocrit method) and estimated energy value. Chi-square or Fisher exact tests, ANOVA, and multivariable linear regression were used for comparison among groups. Results: Mean gestational age was 34 weeks in preterm infants and 39 weeks in term neonates. Crematocrit did not differ between groups, with mean values varying between 3.3 and 4.0%; estimated energy value was 52 to 56 kcal/dL. Crematocrit ≥4% was more frequent in the T-SGA group. Only in the PT-SGA group there was a correlation between crematocrit and body mass index of the mother. Conclusions: The fat content and energy value of colostrum did not change according to gestational age or fetal growth.
Assuntos
Humanos , Feminino , Recém-Nascido , Adulto , Adulto Jovem , Idade Gestacional , Colostro/química , Desenvolvimento Fetal/fisiologia , Lipídeos/análise , Estudos TransversaisRESUMO
OBJECTIVE: To determine whether fat content and energy value change in colostrum according to gestational age and fetal growth. METHODS: Cross-sectional study with mothers of preterm and term infants born in a tertiary center in 2015-2016. Inclusion criteria: single pregnancy, absence of diabetes, chorioamnionitis and mastitis, no use of illicit drugs or alcohol, without fetal congenital malformation or infection. Four groups were formed according to gestational age and fetal growth: preterm infants small for gestational age (PT-SGA; n=33) and appropriate for gestational age (PT-AGA; n=60), term infants small for gestational age (T-SGA; n=59) and appropriate for gestational age (T-AGA; control, n=73). Colostrum was collected between 24-72 hours postpartum. Gestational and birth variables were analyzed. Outcome variables were: fat content in colostrum (evaluated by crematocrit method) and estimated energy value. Chi-square or Fisher exact tests, ANOVA, and multivariable linear regression were used for comparison among groups. RESULTS: Mean gestational age was 34 weeks in preterm infants and 39 weeks in term neonates. Crematocrit did not differ between groups, with mean values varying between 3.3 and 4.0%; estimated energy value was 52 to 56 kcal/dL. Crematocrit ≥4% was more frequent in the T-SGA group. Only in the PT-SGA group there was a correlation between crematocrit and body mass index of the mother. CONCLUSIONS: The fat content and energy value of colostrum did not change according to gestational age or fetal growth.
OBJETIVO: Avaliar se o conteúdo de gordura e o valor energético estimado no colostro diferem em função da idade gestacional e do crescimento fetal. MÉTODOS: Estudo transversal com mães de recém-nascidos pré-termo e a termo nascidos em centro terciário em 2015-2016. Critério de inclusão: gestação única, sem diabetes, corioamnionite e mastite, sem uso de drogas ilícitas e álcool, ausência de malformação ou infecção congênita fetal. Foram constituídos quatro grupos conforme idade gestacional e crescimento fetal: pré-termo pequeno para a idade gestacional (n=33); pré-termo adequado (n=60); a termo pequeno (n=59) e a termo adequado para a idade gestacional (controle, n=73). O colostro foi coletado por extração manual entre 24 e 72 h pós-parto. Foram analisadas variáveis gestacionais e de nascimento. Os desfechos foram o conteúdo de gordura no colostro, pelo método do crematócrito, e o valor energético estimado. Na comparação entre grupos foram utilizados os testes do qui-quadrado ou Exato de Fisher, ANOVA e regressão linear multivariada. RESULTADOS: A idade gestacional média foi de 34 semanas nos neonatos pré-termo e 39 semanas nos a termo. O crematócrito não diferiu entre os grupos, com valores médios de 3,3 a 4,0%; e o valor energético estimado foi de 52 a 56 kcal/dL. Crematócrito ≥4% foi mais frequente no grupo a termo pequeno para idade gestacional. Apenas no grupo de recém-nascidos pré-termo pequenos para a idade gestacional houve correlação entre crematócrito e índice de massa corpórea materno. CONCLUSÕES: O conteúdo de gordura e o valor energético estimado do colostro não diferiram em função da idade gestacional e do crescimento fetal.