An industrialized diet as a determinant of methylation in the 1F region of the NR3C1 gene promoter.

Background: Dietary composition can modify gene expression, favoring the development of chronic diseases via epigenetic mechanisms. Objective: Our study aimed to investigate the relationship between dietary patterns and NR3C1 gene methylation in users of the Brazilian Public Unified Health System (SUS). Methods: We recruited 250 adult volunteers and evaluated their socioeconomic status, psychosocial characteristics, lifestyle, and anthropometrics. Peripheral blood was collected and evaluated for cortisol levels, glycemia, lipid profile, and insulin resistance; methylation of CpGs 40-47 of the 1F region of the NR3C1 gene was also measured. Factors associated with degree of methylation were evaluated using generalized linear models (p < 0.05). Lifestyle variables and health variables were included as confounding factors. Results: The findings of our cross-sectional study indicated an association between NR3C1 DNA methylation and intake of processed foods. We also observed relevant associations of average NR3C1 DNA across the segment analyzed, methylation in component 1 (40-43), and methylation in component 2 (44-47) with a pattern of consumption of industrialized products in relation to BMI, serum cortisol levels, and lipid profile. These results may indicate a relationship between methylation and metabolic changes related to the stress response. Conclusion: These findings suggest an association of methylation and metabolic alterations with stress response. In addition, the present study highlights the significant role of diet quality as a stress-inducing factor that influences NR3C1 methylation. This relationship is further linked to changes in psychosocial factors, lifestyle choices, and cardiometabolic variables, including glucose levels, insulin resistance, and hyperlipidemia.

Lifestyle and NR3C1 exon 1F gene methylation is associated with changes in glucose levels and insulin resistance.

AIMS: the present study aimed to investigate how glucose and insulin levels may be associated with changes in NR3C1 gene methylation levels in adults. MAIN METHODS: 375 volunteers users of the Brazilian Public Unified Health System (SUS) were recruited to assess socioeconomic status, lifestyle, anthropometric data, blood glucose and serum cortisol levels, insulin resistance, and NR3C1 gene methylation assessment. Factors associated with glucose levels and insulin resistance were investigated using multivariate analysis GLzM at 5% significance (p<0.05). KEY FINDINGS: our results verified that glucose levels and insulin resistance were directly related to NR3C1 gene methylation and age, while not being overweight and obese and no tobacco consumption were indirectly related to glucose levels and insulin resistance. SIGNIFICANCE: habits and lifestyle may influence NR3C1 gene regulation, revealing the complexity of environmental impacts on NR3C1 methylation. Furthermore, associated risk factors must be taken into account in epigenetic studies as they directly interfere with blood glucose levels and insulin resistance.

Juçara (Euterpe edulis Mart.) Supplementation Reduces Aberrant Crypt Foci and Increases SOD1 Expression in the Colorectal Mucosa of Carcinogenesis-Induced Rats.

Antioxidants present in food can act as a protective factor against the development of colorectal cancer (CRC) by reducing the development of aberrant crypt foci (ACF). This study aimed to analyze the effects of supplementation with juçara fruit pulp on the number of ACF and the SOD1 expression in an experimental model of CRC. Colorectal carcinogenesis was induced with 1,2-dimethylhydrazine (DMH) in 16 young female rats (Rattus norvegicus) given a diet supplemented with either juçara fruit pulp (DMH+/juçara+) or control (DMH+/juçara-). Five animals were used as a negative control (DMH-/juçara-). The (DMH+/juçara+) group received 14 days of supplementation (100 ml/animal/day) at 2-day intervals for 1 month. The number of ACF, area of positive staining for SOD1, and SOD1 expression score were evaluated. The (DMH+/juçara+) group presented a lower number of ACF, ACF > 3 crypts, and greater SOD1 expression in the colorectal mucosa. Based on the reduction in the number of lesions and possible positive impact on antioxidant enzymes, juçara fruit pulp appears to support the prevention of CRC, opening new possibilities for its use in dietary supplementation, as well as in the development of products and medications for the prevention and treatment of CRC.

A view of the maternal inheritance of Espírito Santo populations: The contrast between the admixed and Pomeranian descent groups.

In addition to its valuable utility in forensic investigations, mitochondrial DNA (mtDNA) analysis is a reliable tool to uncover the origins of admixed populations, such as Brazilians. The state of Espírito Santo (ES), similar to other coastal Brazilian states, has a population shaped by 3 main ancestral roots: Amerindian, African and European. Among the latter, the Pomeranian descendants stand out due to the preservation of the traditional aspects of their culture, especially the Pomeranian language. Despite the genetic data already available, there is no mtDNA database that adequately reflects the diversity, the geographic distribution, and the origins of the maternal lineages from ES. To increase the knowledge of maternal ancestry and to investigate the population's genetic stratification, a total of 291 samples were collected in the 4 macroregions (Metropolitan, South, Central and North) of ES and in the Pomeranian communities. Complete control region data were produced for the general (N=214) and Pomeranian (N=77) groups. Regarding the general population, the high values of haplotype diversity (H=99.9%) and pairwise differences (MNPD=16.9) found are in agreement with those reported for other populations in the southeast region of the country. Regarding maternal inheritance, the ES populations stood out due to the predominance of European haplogroups (49.5%), although the North macroregion had a higher African ancestry (47.1%). Among the Pomeranians, the lowest MNPD value (11.2) and the high percentage of shared haplotypes (15%) were indicative of founder events. The FST analysis showed that the Pomeranians (98.7% of European lineages) are genetically isolated from the other admixed populations in Brazil. This study demonstrated that the ES state contains singularities regarding the intrapopulational and interpopulational diversity of mtDNA. Even after 5 centuries of interethnic admixture, the present-day population of Espírito Santo harbors genetic marks that trace back to the historical aspects of its formation.

PAI-1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma.

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.

FGFR4 profile as a prognostic marker in squamous cell carcinoma of the mouth and oropharynx.

BACKGROUND: Fibroblast growth factor receptor 4 (FGFR4) is a member of a receptor tyrosine kinase family of enzymes involved in cell cycle control and proliferation. A common single nucleotide polymorphism (SNP) Gly388Arg variant has been associated with increased tumor cell motility and progression of breast cancer, head and neck cancer and soft tissue sarcomas. The present study evaluated the prognostic significance of FGFR4 in oral and oropharynx carcinomas, finding an association of FGFR4 expression and Gly388Arg genotype with tumor onset and prognosis. PATIENTS AND METHODS: DNA from peripheral blood of 122 patients with oral and oropharyngeal squamous cell carcinomas was used to determine FGFR4 genotype by PCR-RFLP. Protein expression was assessed by immunohistochemistry (IHC) on paraffin-embedded tissue microarrays. RESULTS: Presence of allele Arg388 was associated with lymphatic embolization and with disease related premature death. In addition, FGFR4 low expression was related with lymph node positivity and premature relapse of disease, as well as disease related death. CONCLUSION: Our results propose FGFR4 profile, measured by the Gly388Arg genotype and expression, as a novel marker of prognosis in squamous cell carcinoma of the mouth and oropharynx.

HIF1-alpha expression predicts survival of patients with squamous cell carcinoma of the oral cavity.

BACKGROUND: Oral squamous cell carcinoma is an important cause of death and morbidity wordwide and effective prognostic markers are still to be discovered. HIF1α protein is associated with hypoxia response and neovascularization, essential conditions for solid tumors survival. The relationship between HIF1α expression, tumor progression and treatment response in head and neck cancer is still poorly understood. PATIENTS AND METHODS: In this study, we investigated HIF1α expression by immunohistochemistry in tissue microarrays and its relationship with clinical findings, histopathological results and survival of 66 patients with squamous cell carcinoma of the lower mouth. RESULTS: Our results demonstrated that high HIF1α expression is associated with local disease-free survival, independently from the choice of treatment. Furthermore, high expression of HIF1α in patients treated with postoperative radiotherapy was associated with survival, therefore being a novel prognostic marker in squamous cell carcinoma of the mouth. Additionally, our results showed that MVD was associated with HIF1α expression and local disease relapse. CONCLUSION: These findings suggest that HIF1α expression can be used as a prognostic marker and predictor of postoperative radiotherapy response, helping the oncologist choose the best treatment for each patient.

Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous cell carcinoma.

Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene with several potential functions, including cell differentiation, cell cycle regulation and response to hormones, nickel and stress. The purpose of this study was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal squamous cell carcinomas searching for its role in the clinical course of these tumors. We investigated immunohistochemical expression of NDRG1 protein in 412 tissue microarray cores of tumor samples from 103 patients with oral and oropharyngeal squamous cell carcinomas and in 110 paraffin-embedded surgical margin sections. The results showed NDRG1 up-regulation in 101/103 (98.1 %) tumor samples, but no expression in any normal tissue sample. Western blot assays confirmed the immunohistochemical findings, suggesting that lower levels of NDRG1 are associated with a high mortality rate. NDRG1 overexpression was related to long-term specific survival (HR = 0.38; p = 0.009), whereas the presence of lymph-node metastasis showed the opposite association with survival (HR = 2.45; p = 0.013). Our findings reinforce the idea that NDRG1 plays a metastasis suppressor role in oral and oropharyngeal squamous cell carcinomas and may be a useful marker for these tumors.

Microbial leakage through the implant-abutment interface of Morse taper implants in vitro.

OBJECTIVES: The aim of this study was to determine and compare the frequency of bacterial leakage of Streptococcus sanguinis biotype II along the implant-abutment interface between two systems of morse taper dental implants. Different methods of activation of the taper abutments were used: tapped-in (Bicon) and screwed-in (Ankylos). MATERIALS AND METHODS: Twenty sterile assemblies were used and attached, 10 Bicon and 10 Ankylos implants, according to manufacturers' specifications. They were then totally immersed within 20 test tubes containing a sterile nutrient solution brain-heart infusion (BHI). The internal part of the 20 implants was previously inoculated with 0.1 microl of S. sanguinis II (ATCC 10557) and then connected to the respective abutments. The assemblies were incubated under anaerobic conditions for 14 days in an autoclave at 37 degrees C. They were monitored daily for solution cloudiness resultant from microbial leakage on the interface of the assemblies. For statistical analysis, the Fisher test was applied and significance was assigned at the 5% level. RESULTS: There was solution cloudiness, indicating the finding of bacterial growth inside two Bicon assemblies and two Ankylos assemblies 48 h after incubation. Microbial leakage was further substantiated by testing the suspension for the presence of Streptococcus sp. None of the sterility controls were contaminated. The frequency of bacterial leakage along the implant-abutment interface, with the two different morse taper implant systems, was 20% of the assemblies of each system. There were no statistical differences between them. CONCLUSION: Irrespective of which of the two morse taper implant connection systems of activation was analyzed, tapped-in (Bicon) or screwed-in (Ankylos), this in vitro experiment showed bacterial leakage along the implant-abutment interface.