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1.
Sci Rep ; 11(1): 6768, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762648

RESUMO

The NR3C1 glucocorticoid receptor (GR) gene is a component of the stress response system, which can be regulated by epigenetic mechanisms. NR3C1 methylation has been associated with trauma and mental issues, including depression, post-traumatic stress, anxiety, and personality disorders. Previous studies have reported that stressful events are involved in NR3C1 gene methylation, suggesting that its regulation under environmental effects is complex. The present study aimed to analyze associations involving stressors such as socioeconomic status, health conditions, and lifestyle in relation to NR3C1 methylation in adults. This study included 386 individual users of the Brazilian Public Unified Health System (SUS), and evaluated socioeconomic and health conditions, body mass index, cortisol levels, and lifestyle. Data were correlated with NR3C1 methylation, determined using DNA pyrosequencing. The results showed that alcohol consumption, overweight, and high cortisol levels were related to NR3C1 demethylation, while depression was related to its methylation. Habits, lifestyle, and health status may influence NR3C1 gene regulation via methylation, revealing the complexity of environmental impacts on NR3C1 methylation.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Cortisona/sangue , Metilação de DNA , Depressão/genética , Sobrepeso/genética , Receptores de Glucocorticoides/genética , Adulto , Biomarcadores , Ilhas de CpG , Estudos Transversais , Depressão/metabolismo , Suscetibilidade a Doenças , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/metabolismo , Receptores de Glucocorticoides/metabolismo , Fatores Socioeconômicos , Adulto Jovem
2.
PLoS One ; 13(7): e0197699, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30063700

RESUMO

OBJECTIVE: To assess the association between indicators of psychosocial stress and central adiposity in adult users of the Unified Health System (SUS) from Southeast of Brazil. METHODS: This cross-sectional study was conducted with 384 adults (20 to 59 years old) from the city of Alegre, Southeastern Brazil. The simple random sample represented the population using the public health system of the municipality. The prevalence of obesity was based on the Body Mass Index, and central adiposity (dependent variable) was measured by waist circumference in centimeters. The independent variables were the following indicators of psychosocial stress: food and nutrition insecurity (yes/no), serum cortisol (µg/dL), symptoms suggestive of depression using the Beck Depression Inventory-II ≥ 17 (yes/no), and altered blood pressure ≥ 130/85 mmHg (yes/no). Univariate linear regression was performed between central adiposity and each stress indicator, and later the models were adjusted for socioeconomic, health, and lifestyle variables. All analyses were made separately by rural and urban location. RESULTS: The prevalence of weight excess, by the classification of the Body Mass Index ≥ 25.0 kg/m2, was 68.3% and, by waist circumference, 71.5% of individuals presented an increased risk for metabolic complications related to central adiposity. Mean waist circumference scores for the rural and urban population were 89.3 ± 12.7 cm and 92.9 ± 14.7 cm, respectively (p = 0.012). Indicators of stress that were associated with central adiposity were: cortisol in the rural population (ß = -0.60; 95% CI = -1.09;-0.11) and altered blood pressure in the urban population (ß = 6.66; 95% CI = 2.14;11.18). This occurred both in the raw analysis and in the models adjusted for confounding factors. CONCLUSION: Central adiposity was inversely associated with cortisol in the rural population and directly associated with higher arterial blood pressure in the urban population, suggesting a local influence on how individuals react to stress.


Assuntos
Depressão/epidemiologia , Abastecimento de Alimentos/estatística & dados numéricos , Hipertensão/epidemiologia , Obesidade Abdominal/epidemiologia , Estresse Psicológico/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Brasil/epidemiologia , Estudos Transversais , Depressão/sangue , Depressão/fisiopatologia , Feminino , Humanos , Hidrocortisona/sangue , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/fisiopatologia , Prevalência , Saúde Pública/estatística & dados numéricos , Fatores de Risco , População Rural , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , População Urbana , Circunferência da Cintura
3.
J Oral Pathol Med ; 47(6): 566-574, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29693741

RESUMO

BACKGROUND: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. MATERIALS AND METHODS: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed. RESULTS: Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035). CONCLUSION: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.


Assuntos
Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais/biossíntese , Anidrase Carbônica IX/biossíntese , Neoplasias Bucais/metabolismo , Inibidor 1 de Ativador de Plasminogênio/biossíntese , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Idoso , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Anidrase Carbônica IX/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Análise Multivariada , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
PLoS One ; 13(3): e0194884, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29590186

RESUMO

AIMS: Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. METHODS AND RESULTS: We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. CONCLUSION: JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.


Assuntos
Adrenomedulina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/secundário , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias Bucais/patologia , Neoplasias Orofaríngeas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Epigênese Genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/cirurgia , Prognóstico , Taxa de Sobrevida
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