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1.
J Pediatr Endocrinol Metab ; 36(5): 470-477, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37006164

RESUMO

OBJECTIVES: Children 10-20 years old in the US are currently obese, showing suboptimal hydration as 60% fail to meet the US Dietary Reference Intakes for water. Studies have shown a significant inverse association between hydration status and body composition in children, although most failed to use the Dual-X-Ray Absorptiometry Scan (DEXA), the gold standard for body composition. Limited studies used an objective marker to measure hydration, such as urine specific gravity (USG) from a 24-h urine collection. Therefore, this study aimed to examine the association between hydration status (measured from USG in a 24-h urine sample and assessed from three 24-h dietary recalls) and body fat % and lean mass (assessed from a DEXA scan) in children (10-13 years, n=34) and adolescents (18-20 years, n=34). METHODS: Body composition was measured using DEXA, total water intake (mL/d) was assessed from three 24-h dietary recalls and analyzed using the Nutrition Data System for Research (NDSR). Hydration status was objectively measured using USG via 24-h urine collection. RESULTS: Overall body fat % was 31.7 ± 7.31, total water intake was 1746 ± 762.0 mL/d, and USG score was 1.020 ± 0.011 uG. Linear regressions showed significance between total water intake and lean mass (B=12.2, p<0.05). Logistic regressions showed no significant association between body composition and USG and total water intake. CONCLUSIONS: Findings showed total water intake was significantly associated with lean mass. Future research should be conducted to explore other objective markers of hydration and with a larger sample.


Assuntos
Composição Corporal , Água Corporal , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Ingestão de Líquidos , Urinálise , Obesidade
2.
Pediatr Res ; 94(2): 796-802, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36750740

RESUMO

BACKGROUND: Children 10-20 years old in the US have suboptimal hydration status. Hydration is best assessed using an objective marker, such as urine specific gravity (USG) from a 24-h urine collection. There are limited studies associating hydration from an objective marker with intake assessed from 24-h recalls in children. The objective of the study was to evaluate which foods or beverages are significantly associated with an objective marker of hydration (USG) in a sample of children and adolescents. METHODS: Intake was assessed from three 24-h dietary recalls and analyzed using the Nutrition Data System for Research (NDSR). Hydration status was objectively measured using USG via 24-h urine collection. Associations were assessed with logistic regressions. RESULTS: A total of 68 children and adolescents were recruited (50% females). Average overall USG score was 1.020 ± 0.011 uG with 39.7% categorized as dehydrated. After adjusting for age and sex, fruit juice (1.009, 95% CI: 1.001, 1.018) and all beverages (1.001, 95% CI: 1.000, 1.002) were significantly associated with higher odds of being euhydrated. CONCLUSIONS: The main predictors of hydration were fruit juice and all beverages intake. Future research should be conducted to explore differences in dietary patterns in a larger, more generalizable sample. IMPACT: Findings showed that the main predictors of hydration were water and fruit juice intake in children and water intake in adolescents in southern Florida. This is the first study to examine which type of beverages and foods are associated with USG, an objective marker of hydration status, in US children and adolescents. Provides further insight into the use of objective markers to assess hydration status, while providing data to assist epidemiological studies that may have limited resources to examine beverages and foods that contribute to hydration.


Assuntos
Dieta , Ingestão de Líquidos , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Masculino , Bebidas , Água , Água Corporal
3.
J Cancer Res Clin Oncol ; 148(7): 1641-1682, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35441887

RESUMO

PURPOSE: The mechanisms contributing to recurrence of glioblastoma (GBM), an aggressive neuroepithelial brain tumor, remain unknown. We have recently shown that nuclear respiratory factor 1 (NRF1) is an oncogenic transcription factor and its transcriptional activity is associated with the progression and prognosis of GBM. Herein, we extend our efforts to (1) identify influential NRF1-driven gene and microRNA (miRNA) expression for the aggressiveness of mesenchymal GBM; and (2) understand the molecular basis for its poor response to therapy. METHODS: Clinical data and RNA-Seq from four independent GBM cohorts were analyzed by Bayesian Network Inference with Java Objects (BANJO) and Markov chain Monte Carlo (MCMC)-based gene order to identify molecular drivers of mesenchymal GBM as well as prognostic indicators of poor response to radiation and chemotherapy. RESULTS: We are the first to report sex-specific NRF1 motif enriched gene signatures showing increased susceptibility to GBM. Risk estimates for GBM were increased by greater than 100-fold with the joint effect of NRF1-driven gene signatures-CDK4, DUSP6, MSH2, NRF1, and PARK7 in female GBM patients and CDK4, CASP2, H6PD, and NRF1 in male GBM patients. NRF1-driven causal Bayesian network genes were predictive of poor survival and resistance to chemoradiation in IDH1 wild-type mesenchymal GBM patients. NRF1-regulatable miRNAs were also associated with poor response to chemoradiation therapy in female IDH1 wild-type mesenchymal GBM. Stable overexpression of NRF1 reprogramed human astrocytes into neural stem cell-like cells expressing SOX2 and nestin. These cells differentiated into neurons and form tumorospheroids. CONCLUSIONS: In summary, our novel discovery shows that NRF1-driven causal genes and miRNAs involved in cancer cell stemness and mesenchymal features contribute to cancer aggressiveness and recurrence of aggressive therapy-resistant glioblastoma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , MicroRNAs , Fator 1 Nuclear Respiratório , Teorema de Bayes , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Feminino , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Fator 1 Nuclear Respiratório/genética , Prognóstico , Transcriptoma
4.
J Trace Elem Med Biol ; 62: 126636, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32957075

RESUMO

Autophagy is a conserved catabolic process that plays an important role in cellular homeostasis. The study of the interplay between autophagy and zinc has gained interest over the last years. Multiple studies have indicated that zinc stimulates autophagy and is critical for basal and induced autophagy in mammalian cells. Conversely, autophagy is induced by zinc starvation in yeast. There are no studies analyzing the role of zinc in either Microautophagy or Chaperone-Mediated-Autophagy. The mechanisms by which zinc modulates autophagy are still poorly understood. Studies examining loss of function of genes involved in cellular zinc homeostasis have provided novel insights into the role of zinc in autophagy. Autophagy may help cells adapt to changes in zinc availability in medium by controlling zinc mobilization, recycling, and secretion. Zinc is a key player in toxic and protective autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Zinco/farmacologia , Animais , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Metalotioneína/metabolismo , Mitofagia/efeitos dos fármacos
5.
Ecancermedicalscience ; 14: 1082, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863876

RESUMO

INTRODUCTION: Head and neck cancers (NHCs) are of multifaceted origins, and tobacco and alcohol are the primary risk factors. Currently, other factors associated with the genesis of these tumours are being considered, among these viral infections, especially human papillomavirus (HPV) infection. OBJECTIVE: The objective was to evaluate HPV infection, HPV-16 E6 load and its physical status in patients with squamous cell carcinoma in the head and neck and evaluate its effects in the survival of these patients. METHODOLOGY: A total of 80 fresh biopsies of HNC were evaluated. The genetic material was extracted using the commercial kit QIAGEN. The detection and classification of HPV were carried out using INNO-LiPA, whereas the quantification and analysis of integration of the viral genome into the host cell were carried out using real-time PCR. RESULTS: The average age of the patients included was 60.34 ± 14.48 years, with a predominance of the male gender. The most frequent HPV infection was genotype 16 (52.8%), with an average of 10 copies of the HPV-16 E6/ß-globin gene. Furthermore, an integration of the viral genome in the host cell was observed in 86% of cases with a statistically significant relationship between the location of the tumour and the viral load (p < 0.05). CONCLUSIONS: HPV-16 is the most common infection, and its physical status in the host cell is the determining factor in establishing response to treatment. However, more studies are needed to demonstrate the role of HPV infection in carcinogenesis.

6.
J Cancer Res Clin Oncol ; 146(11): 2777-2815, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32705365

RESUMO

PURPOSE: Nuclear respiratory factor 1 (NRF1) drives estrogen-dependent breast tumorigenesis. Herein we examined the impact of NRF1 activity on the aggressiveness and disparate molecular signature of breast cancer in Black, White, Asian, and Hispanic women. METHODS: NRF1 activity by transcription factor target enrichment analysis and causal NRF1-target gene signatures by Bayesian Network Inference with Java Objects (BANJO) and Markov Chain Monte Carlo (MCMC)-based gene order were examined in The Cancer Genome Atlas (TCGA) breast cancer cohorts. RESULTS: We are the first to report increased NRF1 activity based on its differential effects on genome-wide transcription associated with luminal A and B, HER2+ and triple-negative (TN) molecular subtypes of breast cancer in women of different race/ethnicity. We observed disparate NRF1 motif-containing causal gene signatures unique to Black, White, Asian, and Hispanic women for luminal A breast cancer. Further gene order searches showed molecular heterogeneity of each subtype of breast cancer. Six different gene order sequences involving CDK1, HMMR, CCNB2, CCNB1, E2F1, CREB3L4, GTSE1, and LMNB1 with almost equal weight predicted the probability of luminal A breast cancer in whites. Three different gene order sequences consisting of CCNB1 and GTSE1, and CCNB1, LMNB1, CDK1 or CASP3 predicted almost 100% probability of luminal B breast cancer in whites; CCNB1 and LMNB1 or GTSE predicted 100% HER2+ breast cancer in whites. GTSE1 and TUBA1C combined together predicted 100% probability of developing TNBC in whites; NRF1, TUBA1B and BAX with EFNA4, and NRF1 and BTRC predicated 100% TNBC in blacks. High expressor NRF1 TN breast tumors showed unfavorable prognosis with a high risk of breast cancer death in white women. CONCLUSION: Our findings showed how sensitivity to high NRF1 transcriptional activity coupled with its target gene signatures contribute to racial differences in luminal A and TN breast cancer subtypes. This knowledge may be useful in personalized intervention to prevent and treat this clinically challenging problem.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Fator 1 Nuclear Respiratório/genética , Transcriptoma/genética , Adulto , Feminino , Humanos , Pessoa de Meia-Idade
7.
J Caffeine Adenosine Res ; 8(1): 10-17, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30023988

RESUMO

Background: Caffeine acts as an anorexic agent, increases energy expenditures, and decreases total body fat mass, and could be detrimental to people living with HIV (PLWH). The objective of this study was to explore the relationship between caffeine consumption, body composition measures (fat mass, body mass index [BMI], and lean body mass [LBM]), nutrient intakes, CD4 counts, and HIV viral load in PLWH. Methods: A convenience sample of 130 PLWH was recruited and followed for 3 months. Caffeine intake, body composition measures, and nutrient intakes were collected using Modified Caffeine Consumption Questionnaire, bioimpedance analyses, and 24-hour dietary recalls. Linear regressions were used to analyze the baseline data for relationships between these variables. Linear mixed models (LMMs) were used to determine the overtime changes. Results: In baseline, linear regression analysis, higher caffeine consumption was associated with lower fat mass (ß = -0.994, p = 0.042). However, BMI and LBM did not show any significant association with caffeine intake. LMM analysis showed that the association between caffeine intake and fat mass strengthened overtime (ß = -1.987, p = 0.035). Baseline linear regression analysis showed that higher caffeine intake was significantly associated with lower caloric intakes from fat (ß = -1.902, p = 0.044) and lower total caloric intake (ß = -1.643, p = 0.042). However, LMM analysis showed that these associations diminished and lost significance overtime. There were no associations between body composition measures, nutrient intakes, CD4 counts, and HIV viral load. Conclusions: Caffeine intake adversely affected dietary intakes of macronutrients and total fat mass. Therefore, caffeine, a known anorectic, should be regulated in PLWH.

8.
Biometals ; 31(2): 217-232, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29392448

RESUMO

Autophagy is a conserved mechanism that plays a housekeeping role by eliminating protein aggregates and damaged organelles. Recent studies have demonstrated that acute ethanol intoxication induces hepatic autophagy in mice. The effect of dietary zinc intake on hepatic autophagic flux during ethanol intoxication has not been evaluated using animal models. Herein, we investigated whether zinc deficiency and excess can affect autophagic flux in the liver in mice and in human hepatoma cells acutely exposed to ethanol. A mouse model of binge ethanol feeding was utilized to analyze the effect of low, adequate, and high zinc intake on hepatic autophagic flux during ethanol intoxication. Autophagic flux was inferred by analyzing LC3II/LC3I ratio, protein levels of p62/SQSTM1, Beclin1 and Atg7, and phosphorylation of 4EBP1. In addition, the degradation of the fusion protein LC3-GFP and the formation of autophagosomes and autolysosomes were evaluated in cells. Ethanol treatment stimulated autophagy in mice and cells. High zinc intake resulted in enhanced autophagy in mice exposed to ethanol. Conversely, zinc deficiency was consistently associated with impaired ethanol-induced autophagy in mice and cells. Zinc-deficient mice exhibited a high degree of ethanol-driven steatosis. Furthermore, zinc depletion increased apoptosis in cells exposed to ethanol. The results of this study suggest that adequate zinc intake is necessary for proper stimulation of autophagy by ethanol. Poor zinc status is commonly found among alcoholics and could likely contribute to faulty autophagy.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Autofagia/efeitos dos fármacos , Suplementos Nutricionais , Zinco/metabolismo , Animais , Apoptose/efeitos dos fármacos , Etanol/toxicidade , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lisossomos/efeitos dos fármacos , Camundongos , Zinco/administração & dosagem , Zinco/deficiência
9.
J Assoc Nurses AIDS Care ; 28(6): 897-906, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28830705

RESUMO

We explored the relationship between caffeine consumption, insomnia, and HIV disease progression (CD4+ T cell counts and HIV viral loads). Caffeine intake and insomnia levels were measured using the Modified Caffeine Consumption Questionnaire and the Pittsburgh Insomnia Rating Scale (PIRS) in 130 clinically stable participants who were living with HIV, taking antiretroviral therapy, and recruited from the Miami Adult Studies on HIV cohort. Linear regressions showed that caffeine consumption was significantly and adversely associated with distress score, quality-of-life score, and global PIRS score. Linear regression analyses also showed that global PIRS score was significantly associated with lower CD4+ T cell counts and higher HIV viral loads. Caffeine could have precipitated insomnia in susceptible people living with HIV, which could be detrimental to their disease progression states.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Cafeína/administração & dosagem , Infecções por HIV/complicações , Infecções por HIV/virologia , Distúrbios do Início e da Manutenção do Sono/complicações , Carga Viral/efeitos dos fármacos , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Cafeína/farmacologia , Estudos Transversais , Progressão da Doença , Feminino , Florida , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
10.
Ecancermedicalscience ; 11: 740, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28626490

RESUMO

Sarcomas are infrequent and heterogeneous tumours. They represent 1-2% of all malignant neoplasms in adults and between 4% and 10% of head and neck cancers. METHODS: The research was retrospective, descriptive, and cross-sectional. RESULTS: A study population of 62 patients with a mean age of 44 years was obtained; the most frequent location was the soft tissues of the neck (25.3%) and the mean tumour size was 7.1 cm; the most frequent diagnosis was undifferentiated pleomorphic sarcoma (25.5%) and the majority were stage III (41.4%). The lowest survival rates were associated with T2a and T2b tumours (p = 0.014), the presence of lymph node metastasis (p = 0.001), advanced stages (p = 0.003), and invasion of bone, blood vessels and/or nerves (p = 0.008). CONCLUSIONS: Late diagnosis is the main factor associated with decreased survival in patients with head and neck sarcomas.

11.
Viral Immunol ; 30(4): 271-277, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28409659

RESUMO

Although there are many studies on adverse health effects of substance use and HIV disease progression, similar studies about caffeine consumption are few. In this study, we investigated the effects of caffeine on immunological and virological markers of HIV disease progression. A convenience sample of 130 clinically stable people living with HIV/AIDS on antiretroviral therapy (65 consuming ≤250 mg/day and 65 consuming >250 mg/day of caffeine) were recruited from the Miami Adult Studies on HIV (MASH) cohort. This study included a baseline and 3-month follow-up visit. Demographics, body composition measures, substance use, Modified Caffeine Consumption Questionnaire (MCCQ), and CD4 count and HIV viral load were obtained for all participants. Multivariable linear regression and Linear Mixed Models (LMMs) were used to understand the effect of caffeine consumption on CD4 count and HIV viral load. The mean age of the cohort was 47.9 ± 6.4 years, 60.8% were men and 75.4% were African Americans. All participants were on ART during both the visits. Mean caffeine intake at baseline was 337.6 ± 305.0 mg/day and did not change significantly at the 3-month follow-up visit. Multivariable linear regressions after adjustment for covariates showed significant association between caffeine consumption and higher CD4 count (ß = 1.532, p = 0.049) and lower HIV viral load (ß = -1.067, p = 0.048). LMM after adjustment for covariates showed that the relationship between caffeine and CD4 count (ß = 1.720, p = 0.042) and HIV viral load (ß = -1.389, p = 0.033) continued over time in a dose-response manner. Higher caffeine consumption was associated with higher CD4 cell counts and lower HIV viral loads indicating beneficial effects on HIV disease progression. Further studies examining biochemical effects of caffeine on CD4 cell counts and viral replication need to be done in the future.


Assuntos
Cafeína , Infecções por HIV/patologia , Adulto , Contagem de Linfócito CD4 , Progressão da Doença , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Carga Viral
12.
J. oral res. (Impresa) ; 6(4): 86-91, Apr. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-907721

RESUMO

Introduction: Infection caused by potentially oncogenic viruses, such as HPV and EBV, favors the role of certain oncoproteins that can induce dysplasias and malignant lesions. Objective: To evaluate the prevalence of HPV and EBV and their relation with the expression of p53 and PCNA in patients with oral carcinoma. Methodology: Twenty-seven oral squamous cell carcinomas (OSCC) were evaluated; DNA extraction was conducted using the QIAamp DNA mini kit; viral detection was obtained using the INNO-LiPA kit for HPV, and nested PCR was used for EBV. The evaluation of molecular markers was performed through immunohistochemical staining. Results: The mean age of the patients was 60.55 +/- 13.94 years, and 52 percent of these were female. Of the patients, 59 percent were tobacco users and 63 percent were alcohol consumers. HPV was detected in 70 percent of the patients with the predominance of genotype 16 (60 percent). As for EBV infection, it was observed in 59 percent of cases. p53 and PCNA immunopositivity corresponded to 44 percent and 59 percent, respectively. The tongue was the anatomical location with highest positivity for both viruses as well as for the expression of molecular markers. The 48 percent of the cases presented infection by both viruses. Conclusion: HPV and EBV infection together with the expression of p53 and PCNA were more frequently observed in advanced stages of the disease, suggesting a more relevant role in the progression than in tumor genesis.


Assuntos
Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Carcinoma de Células Escamosas/virologia , /isolamento & purificação , Neoplasias Bucais/virologia , Papillomaviridae/isolamento & purificação , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , /fisiologia , /genética , Imuno-Histoquímica , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Prevalência , Antígeno Nuclear de Célula em Proliferação , Papillomaviridae/genética
13.
J Diabetes Res ; 2015: 921274, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25977930

RESUMO

The aim of this study was to assess the differences in correlation of PPARGC1A polymorphisms with type 2 diabetes (T2D) risk in adults of African origins: African Americans and Haitian Americans. The case-control study consisted of >30 years old, self-identified Haitian Americans (n = 110 cases and n = 116 controls) and African Americans (n = 124 cases and n = 122 controls) living in South Florida with and without T2D. Adjusted logistic regression indicated that both SNP rs7656250 (OR = 0.22, P = 0.005) and rs4235308 (OR = 0.42, P = 0.026) showed protective association with T2D in Haitian Americans. In African Americans, however, rs4235308 showed significant risk association with T2D (OR = 2.53, P = 0.028). After stratification with sex, in Haitian Americans, both rs4235308 (OR = 0.38, P = 0.026) and rs7656250 (OR = 0.23, P = 0.006) showed protective association with T2D in females whereas in African American males rs7656250 had statistically significant protective effect on T2D (OR = 0.37, P = 0.043). The trends observed for genetic association of PPARGC1A SNPs, rs4235308, and rs7656250 for T2D between Haitian Americans and African Americans point out differences in Black race and warrant replicative study with larger sample size.


Assuntos
População Negra/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adulto , Idoso , População Negra/etnologia , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/etnologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fatores Sexuais
14.
Ecancermedicalscience ; 8: 475, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25374623

RESUMO

INTRODUCTION: Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). METHODS: We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. RESULTS: The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. CONCLUSIONS: This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression.

15.
Biometals ; 27(6): 1087-96, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25012760

RESUMO

Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the role of zinc in the regulation of autophagy, the role of autophagy in zinc metabolism, and the potential role of autophagy as a mediator of the protective effects of zinc. Data from in vitro studies consistently support the notion that zinc is critical for early and late autophagy. Studies have shown inhibition of early and late autophagy in cells cultured in medium treated with zinc chelators. Conversely, excess zinc added to the medium has shown to potentiate the stimulation of autophagy by tamoxifen, H2O2, ethanol and dopamine. The potential role of autophagy in zinc homeostasis has just begun to be investigated. Increasing evidence indicates that autophagy dysregulation causes significant changes in cellular zinc homeostasis. Autophagy may mediate the protective effect of zinc against lipid accumulation, apoptosis and inflammation by promoting degradation of lipid droplets, inflammasomes, p62/SQSTM1 and damaged mitochondria. Studies with humans and animal models are necessary to determine whether autophagy is influenced by zinc intake.


Assuntos
Autofagia/fisiologia , Zinco/fisiologia , Animais , Apoptose , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteínas de Transporte/metabolismo , Endossomos/metabolismo , Etanol/farmacologia , Regulação da Expressão Gênica , Homeostase , Humanos , Inflamassomos/metabolismo , Inflamação/metabolismo , Metabolismo dos Lipídeos , Lisossomos/metabolismo , Mamíferos/fisiologia , Zinco/farmacologia
16.
Int Neurourol J ; 18(2): 50-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24987556

RESUMO

In this article we introduce modern statistical machine learning and bioinformatics approaches that have been used in learning statistical relationships from big data in medicine and behavioral science that typically include clinical, genomic (and proteomic) and environmental variables. Every year, data collected from biomedical and behavioral science is getting larger and more complicated. Thus, in medicine, we also need to be aware of this trend and understand the statistical tools that are available to analyze these datasets. Many statistical analyses that are aimed to analyze such big datasets have been introduced recently. However, given many different types of clinical, genomic, and environmental data, it is rather uncommon to see statistical methods that combine knowledge resulting from those different data types. To this extent, we will introduce big data in terms of clinical data, single nucleotide polymorphism and gene expression studies and their interactions with environment. In this article, we will introduce the concept of well-known regression analyses such as linear and logistic regressions that has been widely used in clinical data analyses and modern statistical models such as Bayesian networks that has been introduced to analyze more complicated data. Also we will discuss how to represent the interaction among clinical, genomic, and environmental data in using modern statistical models. We conclude this article with a promising modern statistical method called Bayesian networks that is suitable in analyzing big data sets that consists with different type of large data from clinical, genomic, and environmental data. Such statistical model form big data will provide us with more comprehensive understanding of human physiology and disease.

17.
Rev. venez. oncol ; 25(1): 2-9, ene.-mar. 2013. tab
Artigo em Espanhol | LILACS | ID: lil-718960

RESUMO

Evaluación molecular de márgenes de resección en pacientes con carcinoma de células escamosas de cavidad oral sometidos a cirugía. 16 pacientes con carcinoma escamoso de cavidad oral, en cualquiera de sus localizaciones, sin tratamientos previos, intervenidos quirúrgicamente en el 2011. La pieza operatoria fue procesada por anatomía patológica a través del método tradicional, realizándose cortes adicionales que incluían: tumor y 0,5 cm de margen no tumoral. Se realizó hematoxilina-eosina y complementó con inmunomarcaje para p53, PCNA, Ki-67, factor de crecimiento epidérmico y receptor de crecimiento endotelial vascular. De los 16 pacientes en estudio la mayoría eran del género masculino, la edad promedio fue cercana a los 60 años, la mayoría eran pacientes consumidores de tabaco y alcohol. La lengua fue la localización más frecuente y los tumores se encontraban en un estadio avanzado (estadio III y IV). Estudio molecular: todos los marcadores evaluados se encontraban positivos en los márgenes de resección en el 93,75% de los pacientes. Los marcadores de proliferación celular como el PCNA y Ki-67 así como el p-53 se encontraban positivos entre 1,5 cm a 2 cm del tumor con un marcaje intenso. Por el contrario, el factor de crecimiento epidérmico el receptor de crecimiento endotelial vascular se encontraban positivos hasta 1,5 cm pero con menor intensidad. En el cáncer oral podemos observar con frecuencia cambios moleculares en el tejido aparentemente sano que rodea el tumor hasta por lo menos 15 mm.


The molecular evaluation of resection margins in patients with squamous cell carcinoma of oral cavity who underwent surgery. Field of cancerization concept. We included 16 patients with oral cavity squamous cell carcinoma in any of their locations,without pre treatment, surgically treated in our hospital in the 2011 year. The surgical specimen was processed by the pathology department of our institution, through the traditional method, additional sectioned including the tumor and at least 0.5 cm margin non tumorigenic. Study was performed hematoxylin eosin and was supplemented with immunostaining for p53, PCNA, Ki-67, epidermal growth factor receptor and vascular endothelial growth factor receptor. The most important features of the 16 patients studied were: The majorities were male, the average age was around 60 years old; most of them were tobacco and alcohol consumers. The tongue was the most frequent location and most of the tumors were in an advanced stage (stage III y IV). In molecular evaluation all the markers were positive in the resection margins in 93.75% of all patients. The cell proliferation markers suchas PCNA and Ki-67 and the p-53 were positive 1.5 cm to2 cm tumor with intense staining. Conversely, epidermal receptor grow factors and vascular endothelial grow factor receptor were positive up to 1.5 cm but with less intensity. In oral cancer can often observe molecular changes in the apparently healthy tissue surrounding the tumor to at least 15 mm.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , /uso terapêutico , Antígeno Nuclear de Célula em Proliferação/uso terapêutico , Boca/lesões , Carcinoma de Células Escamosas/diagnóstico , Genes erbB-1 , Neoplasias de Cabeça e Pescoço/diagnóstico , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Odontologia , Oncologia
18.
J Nutr Biochem ; 24(6): 1028-33, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23026491

RESUMO

Promoter analysis of the family of suppressors of cytokine signaling (SOCS) revealed that the human SOCS3 gene contains four binding sites for the metal regulatory transcription factor 1 (MTF-1) located within 1600 bp relative to the transcription start site. A series of experiments were carried out with human hepatoma cells (HepG2) and C57BL/6 mice to examine the effect of zinc on the regulation of SOCS3. In addition, we tested the role of MTF-1 in the regulation of SOCS3 expression using EMSA, chromatin immunoprecipitation assay and siRNA. Lastly, the role of the zinc transporter SLC39A14 on the basal expression of SOCS3 was evaluated. Results indicate that SOCS3 expression is regulated by zinc through an MTF-1-dependent mechanism. In addition, results from siRNA experiments suggest that SLC39A14 is required for basal expression of SOCS3. Further studies are needed to determine whether zinc status affects SOCS3 function.


Assuntos
Fígado/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Zinco/metabolismo , Animais , Proteínas de Transporte/metabolismo , Imunoprecipitação da Cromatina , Proteínas de Ligação a DNA/metabolismo , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica
19.
Am J Physiol Cell Physiol ; 301(4): C862-71, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21653899

RESUMO

Recent studies have shown that overexpression of the transmembrane protein Zrt- and Irt-like protein 14 (Zip14) stimulates the cellular uptake of zinc and nontransferrin-bound iron (NTBI). Here, we directly tested the hypothesis that Zip14 transports free zinc, iron, and other metal ions by using the Xenopus laevis oocyte heterologous expression system, and use of this approach also allowed us to characterize the functional properties of Zip14. Expression of mouse Zip14 in RNA-injected oocytes stimulated the uptake of (55)Fe in the presence of l-ascorbate but not nitrilotriacetic acid, indicating that Zip14 is an iron transporter specific for ferrous ion (Fe(2+)) over ferric ion (Fe(3+)). Zip14-mediated (55)Fe(2+) uptake was saturable (K(0.5) ≈ 2 µM), temperature-dependent (apparent activation energy, E(a) = 15 kcal/mol), pH-sensitive, Ca(2+)-dependent, and inhibited by Co(2+), Mn(2+), and Zn(2+). HCO(3)(-) stimulated (55)Fe(2+) transport. These properties are in close agreement with those of NTBI uptake in the perfused rat liver and in isolated hepatocytes reported in the literature. Zip14 also mediated the uptake of (109)Cd(2+), (54)Mn(2+), and (65)Zn(2+) but not (64)Cu (I or II). (65)Zn(2+) uptake also was saturable (K(0.5) ≈ 2 µM) but, notably, the metal-ion inhibition profile and Ca(2+) dependence of Zn(2+) transport differed from those of Fe(2+) transport, and we propose a model to account for these observations. Our data reveal that Zip14 is a complex, broad-scope metal-ion transporter. Whereas zinc appears to be a preferred substrate under normal conditions, we found that Zip14 is capable of mediating cellular uptake of NTBI characteristic of iron-overload conditions.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Ferro/metabolismo , Zinco/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica , Humanos , Camundongos , Oócitos , Isoformas de Proteínas , Ratos , Xenopus
20.
Rev. Inst. Nac. Hig ; 41(1): 31-37, jun. 2010. graf, tab
Artigo em Espanhol | LILACS, LIVECS | ID: lil-631771

RESUMO

El consumo de alimentos ricos en fibra dietética (FD) soluble e insoluble, afecta favorablemente el perfil de lípidos séricos al reducir las concentraciones de colesterol total, colesterol- LDL y triglicéridos (TG). El objetivo de este trabajo, fue comparar el efecto del consumo de dietas con avena (Avena sa tiva) y con caraotas negras (Phaseolus vulgaris ) sobre el perfil lipídico de ratas. Quince ratas machos, cepa Sprague Dawley, fueron alimentadas ad libitum por 18 días, con tres tipos de dietas: un con trol, una conteniendo caraotas negras (15% p/p) y otra con avena (15% p/p). La concentración del colesterol total sérico disminuyo 50,56% en el grupo alimentado con avena y 40,52% en el alimentado con caraotas. Así mismo, se observó una disminución de colesterol-LDL de 49,21% en el grupo alimentado con avena y un 42,93% en el grupo alimentado con caraotas. Hubo una reducción de 52,47% del colesterol-HDL en el grupo alimentado con avena y 31,29% para el grupo alimentado con caraotas; esta reducción no es beneficiosa. La concentración de TG séricos fue significativamente menor, un 50,20% para el grupo alimentado con avena y de 51,8% para el grupo alimentado con caraota. La disminución de los lípidos séricos debido a la dieta, con avena o con caraotas, mostró diferencias significativas respecto al control, pero, no entre ellas. La consideración de estos resultados en el caso de la salud humana es bien importante, particularmente en la disminución de la prevalencia de enfermedades cardiovasculares. El efecto de FD sobre los niveles de colesterol-HDL, son hasta los momentos, contradictorios.


The consumption of foods rich in soluble and insoluble dietary fiber (DF) favorably affects the serum lipid profile by lowering total cholesterol, LDL-cholesterol and triglycerides (TG). The objective of this work was to compare the effect of consumption of diets with oats (Avena sativa) and black beans (Pha seo lus vulgaris) on the lipid profile of rats. Fifteen male rats, Spra gue Dawley strain were fed ad libitum for 18 days, with three different diets: a control, one containing black beans (15% w / w) and another with oats (15% w / w). The serum total cholesterol concentration decreased 50.56% in the group fed with oats and 40.52% in the group fed with beans. Also a de crease of LDL-cholesterol 49.21% in the group fed with oats and 42.93% in the group fed with beans was observed. There was 52.47% reduction of HDLcho lesterol in the group fed with oats and 31.29% for the group fed with beans, this is not a be neficial reduction. The serum TG concentration was significantly lower, 50.20% for the group fed with oats and 51.8% for the group fed with beans. The decrease of these lipids due to diet containing oats or beans, was significantly different from control but not between them. Consideration of these results for human health is very important, particularly in reducing the prevalence of cardiovascular disease. The FD effect on HDL-cholesterol levels, are until now contradictory.


Assuntos
Humanos , Masculino , Feminino , Ratos , Triglicerídeos/análise , Fibras na Dieta/metabolismo , Colesterol/classificação , Avena/metabolismo , Saúde Pública , Phaseolus/classificação
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