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Virtual reality-based exercise (exergames) improves cognition of the elderly but the neurophysiological effects are poorly understood. The hypothesis herein established is that an ultrafast neurophysiological adaptation occurs in prefrontal cortex of elderly after completion of a single exergames session. To reinforce the aforementioned hypothesis, individuals living in a Long-Term Care Home (LTCH) participated in the study and were randomly allocated into two groups (Virtual Reality Group, VRG, n = 5; and Active Control Group, ACG n = 5). VRG performed six exercises with exergames and ACG performed exercises with the same VRG movements but with no virtual reality. Assessment of frontal cortical activity at rest and during cognitive testing via electroencephalographic activity (EEG) was performed before and immediately after the intervention. Significant decrease in relative power of EEG (RPEEG) Beta brainwave (−29 ± 18%) in the left prefrontal cortex of VRG compared to ACG (4 ± 9%) (p = 0.007). A slight improvement on semantic fluency in VRG (ES=0.21) was noted. An ultrafast prefrontal cortical adaptation may occur as an effect of a single exergames session, causing a small improvement on cognition of institutionalized elderly.

Background: Obesity is a serious health problem that dysregulate Renin-Angiotensin System (RAS) and intestinal microbiota. Objective: The present study aimed to evaluate the Angiotensin-(1-7) [ANG-(1-7)] oral formulation effects on obese mice intestinal microbiota. Methods: Mice were divided into four groups: obese and non-obese treated with ANG-(1-7) and obese and non-obese without ANG-(1-7) during four weeks. Results: We observed a significant decrease in the fasting plasma glucose, total cholesterol, triglycerides, and Low-density lipoprotein levels and increased High-density lipoprotein in animals treated with ANG-(1-7). The histological analysis showed intestinal villi height reduction in mice treated with ANG-(1-7). Additionally, increased Bacteroidetes and decreased Firmicutes (increased Bacteroidetes/ Firmicutes ratio) and Enterobacter cloacae populations were observed in the High-Fat Diet + ANG-(1-7) group. Receptor toll-like 4 (TLR4) intestinal mRNA expression was reduced in the HFD+ANG-(1-7) group. Finally, the intestinal expression of the neutral amino acid transporter (B0AT1) was increased in animals treated with ANG-(1-7), indicating a possible mechanism associated with tryptophan uptake. Conclusion: The results of the present study suggest for the first time an interaction between oral ANG-(1-7) and intestinal microbiota modulation.

Objective The purpose of the present study was to investigate the effect of acupuncture on xerostomia in irradiated patients with head and neck squamous cell carcinoma (HNSCC). Study Design A preventive, 2-arm, parallel, single-blind trial was performed. Patients with HNSCC (N = 296) were checked for eligibility, and 107 patients were enrolled in the study. The study comprised 1 group that did not receive the intervention (n = 55) and the interventional group that received traditional and auricular acupuncture (n = 52). The primary outcome was the reduction of the patients’ xerostomia after treatment. In addition, the secondary outcome was the reduction of anxiety. Results The current acupuncture protocol reduced the xerostomia score and increased saliva volume and density without changing salivary pH. Additionally, acupuncture decreased the Beck Anxiety Inventory (BAI) score after radiation therapy. Conclusion Combining traditional and auricular acupuncture reduced xerostomia and increased saliva volume without changing the saliva's pH in irradiated patients with HNSCC. Additionally, the combination of traditional and auricular acupuncture reduced BAI scores.

Highlights • Conditioned Fear Stress (CFS) reduced the locomotor activity of the animals. • CFS showed no influence on the progression of neoplasia. • No association between HNSCC staging and BAI scores were observed. • There is no relationship between CFS and oral squamous cell carcinoma., Cancer patients present a higher risk of experiencing anxiety disorders (AD). However, it is not clear if AD might be associated with cancer development. Thus, our study aimed to evaluate if AD might be related to head and neck squamous cell carcinoma (HNSCC) development. The combination of an applied animal basic study and a retrospective diagnostic case and control study in patients was performed. As a result, we obtained that stress reduced the locomotor activity of the animals in the group stress and stress + 4NqO (p < 0.0001). The stress showed no influence on the progression of neoplasia in mice. In the same way, the case group did not present differences in anxiety scores in comparison to control. Moreover, no association between HNSCC staging and anxiety scores was observed. In conclusion, our in vivo findings in humans and animals have shown that there is no relationship between AD and oral squamous cell carcinoma.

INTRODUÇÃO: A caquexia associada ao câncer (CAC) é uma síndrome paraneoplásica que ocorre com indivíduos com câncer que é caracterizada pela diminuição gradual de tecidos muscular esquelética e de tecido adiposo, promovendo um quadro de consumação física do indivíduo. A ocorrência de CAC determina de forma significativa a uma pior qualidade de vida e de sobrevida de indivíduos com câncer. A CAC não pode ser revertida pelo amparo nutricional convencional. Tratamentos não-farmacológicos empregados para a CAC tem reportado a realização de atividade física para possibilitar adaptações neurais e de hipertrofia muscular em indivíduos com a síndrome. OBJETIVO: Verificar os efeitos da atividade física em ambiente enriquecido na histomorfometria da musculatura esquelética de camundongos C57BL/6 submetidos ao modelo tumoral murino de caquexia associada ao câncer (CAC) MÉTODOS: Foram utilizados 38 camundongos C57BL/6 fêmeas, distribuídos aleatoriamente nos grupos de estudo. Todos os animais foram submetidos ao modelo tumoral murino singênico de Melanoma Cutâneo (MTMSMC) com a inoculação subcutânea de células B16F10. Os grupos de estudo são animais do experimento diagnostico CRC (n = 12), animais sedentários (n = 11) e animais submetidos à prática de atividade física em ambiente enriquecido (n = 15). O seguimento do estudo ocorreu por um período de dez dias. Após esse momento, todos os animais foram sacrificados e amostras de tecido muscular esquelético do gastrocnêmio foram submetidas às análises histomorfométricas. RESULTADOS: Os resultados da análise inferencial do peso absoluto e relativo muscular esquelético não diferiram entre os grupos do estudo. Todas as comparações das variáveis apresentaram tamanho do efeito pequeno. A análise histomorfométrica muscular revelou que a área da fibra muscular não diferiu entre os grupos do estudo. Contudo, essa área muscular, apresentou tamanho do efeito pequeno. CONCLUSÃO: Os resultados apresentados mostraram que a realização de atividade física no ambiente enriquecido não influenciou na área da fibra do músculo do gastrocnêmio de camundongos C57BL/6 submetidos ao MTMSMC, associada à CAC.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Background: Older adults require special attention during cognitive-motor tasks since automatic postural control is reduced. AIM: To analyze the effect of physical exercise on dual-task processing of healthy older women performing standing balance. Method: Sixteen healthy older women were assessed in a quiet standing position with eyes open/closed (single-task, EO, and EC) and with a cognitive task (dual-task, DT) using a Wii Balance Board. All individuals performed training (aerobic, strength, and virtual reality exercises) at moderate effort. Center of pressure (CoP) anteroposterior and mediolateral displacement were analyzed over time pre- and post-training. The Wilcoxon test was used to compare pre- and post-training. Results: Greater variability in CoP was observed pre- compared to post-training. In the DT, there was a significance decrease in post-training variability compared to pre-training (p

Background Davilla elliptica A. St.-Hil, also known as “lixeirinha or sambaibinha” is a shrub belonging to the Dilleniaceae family that occurs naturally in the Brazilian savannah (Cerrado). Research studies have shown evidence of its gastroprotective effect, as well as its benefits as an anti-nociceptive, anti-inflammatory, and antioxidant. However, there are no studies testing the potential effects of D. elliptica on treating metabolic parameters and obesity. Purpose The aim of the present study was to investigate D. elliptica effects on hepatic steatosis induced by a high-fat/high-sugar diet. Methods Animal experimentation was performed using male Swiss mice divided into four groups: ST (standard control), HLHS (obese control), HLHS+EAF (ethyl-acetate fraction), and HLHS+PL (leaf powder). The groups were treated for four weeks with 0.26 mg/kg/body weight. Results The main findings of the present study showed that D. elliptica reduced hepatic lipid deposition, body weight, triglycerides, and total cholesterol levels. Gene expression analysis showed that GPX4 and PPARγ mRNA were significantly suppressed in HLHS + EAF mice livers. Conclusion The present study contributes to elucidating the D. elliptica metabolic role in decreasing GPX4 and PPARγ expression in the HLHS group.

Objective To provide a systematic review on the demographic and socioeconomic factors associated with edentulism among older persons. Background Edentulism (complete loss of the natural teeth) is one of the main problems affecting the oral health of the elderly individuals. Many unfavourable socioeconomic factors are considered important predictors of edentulism. Materials and methods This review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The search for published studies was conducted on PubMed, Web of Science, SciELO, Google and Google Scholar. Only observational epidemiological studies published in either English or Portuguese prior to June 2018 were included in our study. The bibliographic and methodological characteristics of the selected studies were evaluated. The Review Manager 5.3 software was used in the meta-analysis. Results We identified 343 articles, 24 of which met all the eligibility criteria and were included in the review. Unfavourable demographic and socioeconomic conditions were associated with the highest proportion of edentulous individuals. Age, level of education, and socioeconomic status were the main factors that were found to influence edentulism among elderly individuals. The meta-analysis results showed a lower risk of edentulism in men (OR = 0.93; 95% CI = 0.90-0.96) and no significant differences in the risk of developing edentulism among different races/ethnicities or skin colours (OR = 0.68; 95% CI = 0.45-1.01). Conclusion Better socioeconomic conditions and male sex were identified as protective factors against edentulism among older individuals. Thus, public policies aimed at helping the most vulnerable populations must be implemented.

Background: Spatial navigation is a prodromal dementia marker. Exercise used alongside virtual reality improves many cognitive functions, but effects on spatial navigation are still unclear.Objective: To investigate the effect of virtual reality-based physical exercise with 2D exergames on spatial navigation in institutionalized non-robust older persons.Method: A total of 14 older persons (aged ≧ 60) were randomly allocated to the exergame (EG) and active control (ACG) groups. EG performed exercises with 2D exergames, while the ACG used the same movements as the EG, but without the use of virtual reality. Spatial navigation was assessed through the Floor Maze Test, where the immediate maze time (IMT) and delayed maze time (DMT) were recorded.Results: Spatial navigation was enhanced in EG participants compared to ACG individuals. A significant (p = 0.01) IMT reduction between groups was observed, while DMT time without prior planning was significantly different at the significance threshold (p = 0.07).Conclusions: Virtual reality-based exercise improves the spatial navigation of institutionalized non-robust older persons. This study should be replicated to confirm the findings reported herein.Clinical Trial Registration: This study was registered in the Brazilian Registry of Clinical Trials (Protocol RBR-8dv3kg - https://ensaiosclinicos.gov.br/rg/RBR-8dv3kg).

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Scope: this study has a novel approach to investigate the effects of oral supplementation of kefir grains on metabolic improvement and the expression of the antioxidant enzymes Glutathione Peroxidase (GPx) and Catalase (CAT) of the liver in malnourished mice. Method and results: swiss mice were divided into four groups and subjected to two treatment phases: the food restriction phase of 20% in relation to the control group was maintained until animals reached a weight deficit of about 20% in relation to their original weight and the renutrition phase, the animals received diets every day for 30 days. Diets (chow powder plus kefir grains) were administered orally. Thereafter, during throughout the experiment measurements of body weight and energy consumption were obtained. After the end of treatment, fasting glucose tolerance tests were performed at night and insulin sensitivity with fed mice. Soon in then, the mice were euthanized by beheading in guillotine and the blood and liver were collected for evaluation of biochemical parameters, Histopathological assessments and Reverse transcriptase (RT-PCR). Conclusion: the present study demonstrated the kefir grains ability to modulate inflammation and hepatic oxidative-stress under malnourished-state.

Background: Obesity and non-alcoholic fatty liver disease (NAFLD) have been increasing at an alarming rate worldwide. Bifidobacterium longum (BL), a common member of the human gut microbiota, has important health benefits through several mechanisms. Objectives: We evaluated the BL supplementation effects on body metabolism and renin-angiotensin components hepatic expression in mice fed a high-fat diet. Methods: Thirty-two male mice were divided into four groups: standard diet + placebo (ST), standard diet + Bifidobacterium longum (ST + BL), high-fat diet + placebo (HFD) and high-fat diet + Bifidobacterium longum (HFD + BL). Following the obesity induction period, the ST + BL and HFD + BL groups were supplemented with Bifidobacterium longum for 4 weeks. Then, body, biochemical, histological and molecular parameters were evaluated. Results: HFD + BL mice had a significant decrease in adipose tissue mass and blood glucose levels, as well as a significant reduction in blood glucose during an intraperitoneal glucose tolerance test. The treatment also resulted in reduced levels of total cholesterol and hepatic fat accumulation. Moreover, we observed an increase in angiotensin converting enzyme 2 (ACE2) and Mas receptor (MASR) expression levels in BL-treated obese mice. Conclusions: These data demonstrate that BL may have the potential to prevent obesity and NAFLD by modulating the mRNA expression of renin-angiotensin system components.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Outra Agência The main goal of the present study was to evaluate the metabolic profile, inflammatory markers and the gene expression of the renin–angiotensin system (RAS) components in the visceral adipose tissue of eutrophic, obese and malnourished individuals and mice models of obesity and food restriction. Male Swiss mice were divided into eight groups and fed different levels of food restriction (20%, 40%, or 60%) using standard or high-fat diet. Metabolic profile and adipose tissues were assessed. The expression of AGT (Angiotensinogen), ACE (Angiotensin-converting enzyme), ACE2 (Angiotensin-converting enzyme 2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the mice epididymal adipose tissue and the human visceral adipose tissue was assessed. The main findings showed reduced body weight, improved metabolism, decreased adipose tissues weight and reduced adipocyte area in mice submitted to food restriction. Diminished expression of IL-6, TNF-α, AGT, AT1 and ACE was detected in the 20% and 40% food restriction animal groups, although they were increased in the 60% malnourished group. Increased expression of IL-6, TNF-α, AGT and ACE in obese and malnourished individuals was observed. Adipocytes size was increased in obese individuals and reduced in malnutrition. In conclusion, we found that food restriction of 20% and 40% improved the metabolic profile, ameliorated the inflammatory status and down-regulated the RAS in mice. Severe 60% food restriction (malnutrition), however, stimulated a proinflammatory state and increased AGT and ACE expression in the adipose tissue of mice. A similar profile was observed in the adipose tissue of obese and malnourished humans, supporting the critical role of inflammation and RAS as mediators of metabolic disorders.

Resumo Objetivo: investigar a prática autorreferida dos profissionais da atenção primária à saúde (APS) sobre aconselhamento em infecções sexualmente transmissíveis (ISTs) e HIV/aids em Montes Claros, MG, Brasil, 2015-2016. Métodos: estudo transversal, mediante aplicação de questionário a médicos e enfermeiros da APS; a prática desses profissionais foi classificada, segundo manuais do Ministério da Saúde, como adequada/inadequada; foram investigadas quatro unidades temáticas - realização do aconselhamento; medidas de prevenção; avaliação de comportamento de risco e vulnerabilidade; e testagem sorológica. Resultados: participaram 146 profissionais (41,1% médicos; 58,9% enfermeiros); apenas 25,7% referiram práticas adequadas; o domínio com maior proporção de prática autorreferida inadequada foi ‘avaliação de comportamento de risco e vulnerabilidade’ (69,9%); médicos referiram prática global com maior chance de ser adequada que enfermeiros (OR=3,48 - IC95% 1,57;7,70), especialmente na unidade temática ‘testagem sorológica’. Conclusão: as práticas autorreferidas de aconselhamento em ISTs e HIV/aids na APS mostraram-se inadequadas, indicando a necessidade de intensificar a sensibilização/capacitação dos profissionais. Resumen Objetivo: describir investigar la práctica auto-referida de los profesionales de la atención primaria de salud (APS) sobre aconsejar en enfermedades transmisibles sexualmente (ETS) y VIH/SIDA en Montes Claros, MG, Brasil, 2015-2016. Métodos: estudio transversal por cuestionario aplicado a médicos y enfermeros; la práctica fue clasificada según los manuales del Ministerio de Salud, en adecuada/inadecuada; se investigaron dominios - realización del asesoramiento; medidas de prevención; evaluación de comportamiento de riesgo y vulnerabilidad; pruebas serológicas. Resultados: participaron 146 profesionales (41,1% médicos; 58,9% enfermeros); sólo el 25,7% de los profesionales reportaron prácticas adecuadas; el dominio con mayor proporción de práctica auto-referida inadecuada fue la ‘evaluación del comportamiento de riesgo y vulnerabilidad (69,9%); los médicos tuvieron una práctica global con mayor probabilidad de ser adecuada que los enfermeros (OR=3,48 - IC95% 1,57;7,70), especialmente en la unidad temática ‘pruebas serológicas’. Conclusión: las prácticas de asesoramiento en ITS y VIH/SIDA en la APS se mostraron inadecuadas, revelando la necesidad de intensificar la sensibilización/capacitación de los profesionales. Abstract Objective: to investigate self-reported counseling practice of primary health care (PHC) professionals on sexually transmitted infections (STI) and HIV/AIDS in Montes Claros, MG, Brazil, 2015-2016. Methods: this was a cross-sectional study using a questionnaire answered by PHC physicians and nurses; their practice was classified as being adequate/inadequate based on the recommendations of Ministry of Health manuals; four thematic areas were investigated - counseling provision; prevention measures; risk behavior and vulnerability assessment; serological testing. Results: 146 professionals participated (41.1% physicians; 58.9% nurses); only 25.7% of professionals reported adequate practices; the area with the highest proportion of inadequate self-reported practice was ‘risk behavior and vulnerability assessment’ (69.9%); physicians overall practice was more likely to be appropriate than that of nurses (OR=3.48 - 95%CI 1.57;7.70), especially for ‘serological testing’. Conclusion: self-reported STI and HIV/AIDS counseling practices in PHC were found to be inadequate, revealing the need to intensify health professional awareness-raising/training.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Oral Mucositis (OM) is a common adverse effect of head and neck squamous cell carcinoma (HNSCC) treatment. The purpose of this study was to investigate the significance of early changes in tissue electrical parameters (TEPs) in predicting the development of OM in HNSCC patients receiving radiation therapy (RT). The current study combined two study designs. The first was a case-control study. The control group comprised of RT patients who did not receive head and neck RT, and patients with HNSCC who received RT comprised the case group. In the second part of the study, the case group was included in a parallel cohort. A total of 320 patients were assessed for eligibility, and 135 patients were enrolled. Double blinding was performed, and neither the patients nor the care providers knew the measured parameters. The primary outcome was the detection of between-group changes in local TEPs over the follow-up period. The secondary outcome was the appearance of OM grades II, III, or IV and the predictive value of local TEPs in determining the incidence of OM after RT. The variables, impedance module, resistance, reactance, phase angle, and capacitance, were analyzed by the receiver operator curves (ROC). The case and control groups did not differ in demographic and clinical characteristics. Radiation therapy increased the local impedance module, resistance, reactance, and phase angle and reduced the local tissue capacitance in both groups. Evaluation of TEPs in the first week of RT correlated with the development of OM lesions during cancer therapy. ROC analysis showed that local impedance module and resistance presented higher specificity than did other parameters in predicting OM. In conclusion, local tissue electrical parameters measured at the first RT week can be useful tools to predict oral mucositis.

Objective Malignant salivary gland tumors (MSGTs) present different phenotypic characteristics and various clinical outcomes, which proved to be a diagnostic challenge. Considering the heterogeneity of MSGT, this study aims to identify molecule related to the nature of MSGT. Methods For screening, proteomic analysis comparing MSGT with pleomorphic adenoma (PA) and salivary gland was performed. The MSGT-associated protein which presented in the higher number in the Gene Expression Omnibus (GEO) database was selected. To validate the data, immunohistochemistry (IHC) was performed in 14 patients with PA, 22 patients with MSGT, and 14 controls. Results 16 proteins were associated with MSGT. ANXA2 was the primary protein, according to GEO database analyses. ANXA2 was most expressed in the cell membrane. However, some ANXA2 staining was also observed in the cytoplasm and nucleus. ANXA2 was highly expressed in MSGT in comparison with control. Also, ANXA2 has a higher expression in adenocarcinoma not otherwise specified (ANOS) and myoepithelial carcinoma (MC) in comparison with PA. Conclusion In conclusion, this study demonstrated that MSGT presented higher levels of ANXA2 in comparison with normal salivary glands. Also, ANXA2 might be interesting as a molecular marker of ANOS and MS.

Background: visceral obesity has been considered a risk factor for metabolic and cardiovascular complications. In an attempt to reduce the visceral adipose tissue, omentectomy has been proposed to be performed along with bariatric surgery. Objective: the goal of this study was to evaluate whether omentectomy associated with sleeve gastrectomy (SG) is beneficial to the inflammatory and metabolic profile of rats fed a standard diet (STD) or high-fat diet (HFD). Setting: University hospital, Brazil. Methods: for this experiment, male Wistar rats were randomly divided into 6 groups as follows: sham surgery (STD+L or HFD+L), SG alone (STD+SG or HFD+SG), or SG with omentectomy (STD+SGO or HFD+SGO). Anthropometric data and metabolic profiles were evaluated, and the tissue expression of inflammatory markers in the visceral adipose tissue was measured. Results: in rats with diet-induced obesity treated with SG with or without omentectomy, there was a reduction in weight (HFD+SG: P

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of GA on oral squamous cell carcinoma. In a second step to confirm theoretical results, migration, invasion, proliferation, and gene expression (Col1A1, E-cadherin, HIF-1α, and caspase-3) were performed under normoxic and hypoxic conditions. Our study indicated that treatment with GA resulted in the inhibition of cell proliferation, migration, and invasion in neoplastic cells. Observation of the molecular mechanism showed that GA upregulates E-cadherin expression and downregulates Col1A1 and HIF-1α expression, suggesting that GA might be a potential anticancer compound. In conclusion, the present study demonstrated that GA significantly reduces cell proliferation, invasion, and migration by increasing E-cadherin and repressing Col1A1.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Objective: a healthy diet is essential for the prevention of metabolic syndrome. The present study evaluated the effect of resveratrol associated with high-polyunsaturated fat and high-protein diets on expression of adipogenic and lipogenic genes. Research methods & procedures: FVB/N mice were divided into 6 groups (n = 7 each) and fed with experimental diets for 60 days: standard (ST), high-fat diet (HFD), and high-protein diet (HPD), with and without resveratrol (RSV) (4 g/kg diet). The body weight, food intake, energy intake (kcal), and blood parameters (HDL-C, total cholesterol, glucose, and triglyceride levels) were assessed. Real-time PCR was performed to analyze the expression of adipogenesis and lipogenesis markers: PPARγ, SREBP-1c, ACC and FAS in samples from perigonadal adipose tissue. Results: in the HPD + RSV group, resveratrol decreased body weight, body adiposity, adipose tissue weight, adipocyte area, total cholesterol, ACC and FAS expression, and increased HDL-cholesterol in comparison to HPD. In the HPD group there was a decrease in adipocyte area, as well as PPARγ, SREBP-1c and ACC expression in comparison to ST. While in HFD + RSV, resveratrol decreased levels of total cholesterol in comparison to HFD. In the HFD group there was decrease in body weight, and PPARγ, SREBP-1c and ACC expression in comparison to ST. Conclusions: the obtained results show that resveratrol decreases lipogenesis markers and metabolic parameters in the setting of a high-protein diet. Moreover, resveratrol decreased total cholesterol in both diets. These results point to the increased potential of resveratrol use in prevention of metabolic syndrome, acting on different dietary compositions.

Background Skin cancer represents the most common worldwide malignancy. Angiogenesis is an important factor in tumor growth and metastasis. Given these facts, the purpose of the current study was to compare the levels of angiogenic proteins in the context of the most common malignant and premalignant skin lesions. Methods Immunohistochemistry of CD31, HIF1A, VEGFR1 and VEGFR2 was performed in basal cell carcinoma (BCC), actinic keratosis (AK) and squamous cell carcinoma of the skin (SCCS). Results SCCS presented with increased levels of HIF1A, VEGFR1 and VEGFR2 in comparison to AK. In addition, SCCS also demonstrated increased levels of HIF1A to BCCLR or BCCHR. BCC presented with more vessels than AK. However, no correlation was observed among CD31, HIF1A, VEGFR1 and VEGFR2. Conclusions SCCS presented with higher levels of HIF1A, VEGFR1 and VEGFR2, while BCC demonstrated an increased number of vessels in relation to AK. These data suggest that antiangiogenic therapy might be useful for skin cancer treatment.

Renin-Angiotensin System (RAS) is an important peptide cascade involved in physiological processes. RAS homeostasis disruption produces several cardiovascular and metabolic disorders, such as arterial hypertension, atherosclerosis, acute myocardial infarct, obesity, diabetes, metabolic syndrome and increases gastrointestinal tract (GIT) cell proliferation. Angiotensin (Ang)-(1-7) peptide is the main RAS counter-regulatory axis effector. It is formed from ACE2 enzyme and acts mainly through Mas receptor (MasR). In this context, the aim of the present study was to evaluate alterations in small intestine morphology and intestinal microbiota composition in MasR knockout C57BL/6 mice. We analyzed glucose tolerance; insulin sensitivity and blood collected for biochemical parameters as well as small intestine tissues samples for immunohistochemistry. mRNA and bacteria gDNA expression evaluation. mRNA expression was evaluated by qRT-PCR for TLR4, PI3K and AKT. The main results showed that Mas-R-knockout mice presented lower body weight. MasR-knockout mice also presented increased fasted blood glucose and total cholesterol with reduced HDL, lower glucose tolerance and impaired insulin sensitivity. Increased intestinal mucosa length, increased intestinal villi, reduced Lieberkühn crypt depth. The increased expression of cell proliferation markers Ki-67 and Cyclin D1 and increased TLR4, PI3K and AKT expressions were observed with augmented Bacteroidetes and decreased amount of Firmicutes. That results suggests that MasR deletion generated changes in intestinal microbiota, possibly due to a lower neutral amino acids absorption followed by a compensatory increase in intestinal villi length associated with disbiosis and LPS overproduction that ultimately lead to proliferation and cell inflammation.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Diabetes is a metabolic condition associated with hyperglycemia manifested by the elevation of blood glucose levels occurring when the pancreas decreases or stops the production of insulin, in case of insulin resistance or both. The current literature supports that insulin resistance may be responsible for the memory decline associated with diabetes. Glucose transporters (GLUTs) are a family of proteins involved in glucose transport across biological membranes. GLUT-1 and GLUT-3 are involved in glucose delivery to the brain. Evidence suggests that both transporters are downregulated in chronic peripheral hyperglycemia. Here we show the mechanisms of glucose transport and its influence on cognitive function, including a hypothesis of how peripheral hyperglycemia related genes network interactions may lead to glucose transporters downregulation and its possible consequences.

Introduction Gallic acid (GA) is a natural endogenous polyphenol found in a variety of fruits, vegetables and wines, with beneficial effects on the energetic homeostasis. Aim The present study aimed to investigate oral gallic acid effects on liver steatosis and hepatic lipogenesis markers in obese mice evaluating new possible molecular related mechanisms. Methods Twenty-four Swiss male mice were divided into four groups and fed for 60 days with standard diet (ST), standard diet plus gallic acid (ST + GA), high-fat diet (HFD), and high-fat diet plus gallic acid (HFD + GA). We evaluated the relationship between body weight, food intake and serum levels of total cholesterol, triglycerides, insulin, aspartate and alanine transaminases. Liver histology was analyzed by hematoxylin and eosin staining. These results were accompanied by bioinformatics analyses. The acetyl-CoA carboxylase (ACC), sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was assessed by quantitative real-time reverse transcriptase PCR (qRT-PCR). Results The main findings of the present study showed that GA reduced liver steatosis, body weight and plasma insulin levels. Analyzes of hepatic steatosis related genes expression showed that ACC and FAS mRNA were significantly suppressed in liver of HFD + GA mice. These data was corroborated by bioinformatics analysis. Conclusion These data suggest an important clinical application of GA in the prevention and treatment of liver diseases.

The objective of this study was to evaluate the effects of a vertical ladder device for resistance exercises with or without electrical shock stimulus on muscle strength, body composition, limb volume, muscle fibres and plasma lactate and glycemia of female mice. This device is represented by a vertical ladder with electrostimulation. It was analysed in groups of C57BL/6 mice practicing spontaneous physical activity in enriched environment, practicing resisted climbing exercises, practicing resistance exercises with the utility model in question and controls. The acute effects of blood lactate and dark light-box behaviour, and the short-term chronic effects of muscle strength, limb volume, body composition, muscle fibre area, and central and light-dark quantification were verified. According to the findings, the vertical electrostimulation ladder model presented acute effects on lactate levels, similar to other experimental models of resistance exercise and physical activity. The behaviour in the light-dark box test showed no difference between the groups. Regarding the short-term chronic response, the best results were obtained in the impact-stimulated resistive exercise in the limb traction muscle variables, greater brown adipose tissue weight, greater quadriceps femoral muscle structure, limb and greater weight number of nuclei in the skeletal striated muscle fibres. The use of the prototype showed similarities in the acute and chronic adaptations expected in resistance training. However, new study proposals should be encouraged, as the data presented here are the first notes on the use of this utility model. We would like to thank the Foundation for Research Support of the Minas Gerais State (FAPEMIG; grant numbers: PPM-00029-17 and DEG-00010-16); National Council for Scientific and Technological Development (CNPq, grant number: 150038/2017-8 and 430759/2016-9); and the Coordination of Improvement of Higher Education Personnel (CAPES) for the support to carry out this study. AMB De-Paula is research productivity fellow of the CNPq.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Diabetic cardiomyopathy (DC) describes diabetes-associated changes in the structure and function of myocardium that are not directly linked to other factors such as hypertension. Currently there are some models of DC; however, they take a large time period to mimic key features. In the present study, we investigated the effects of a short-term high-fat/high salt diet (HFHS) treatment on myocardial function and structure, and vascular reactivity in C57BL/6 male mice. After 14 weeks HFHS induced hypertension (MAP = 144.95 ± 16.13 vs 92.90 ± 18.95 mm Hg), low glucose tolerance (AUC = 1049.01 ± 74.79 vs 710.50 ± 52.57 a.u.), decreased insulin sensitivity (AUC = 429.83 ± 35.22 vs 313.67 ± 19.55 a.u.) and increased adiposity (epididymal fat weight 0.96 ± 0.10 vs 0.59 ± 0.06 OW/BW × 102), aspects present in metabolic syndrome. Cardiac evaluation showed diastolic dysfunction (E/A ratio = 1.20 vs 1.90 u.a.) and cardiomyocyte hypertrophy (cardiomyocyte area = 502.82 ± 31.46 vs 385.58 ± 22.11 μm2). Lastly, vascular reactivity was impaired with higher contractile response (136.10 ± 3.49 vs 120.37 ± 5.43%) and lower response to endothelium-dependent vasorelaxation (74.01 ± 4.35 vs 104.84 ± 3.57%). In addition, the diet was able to induce an inward coronary remodeling (vascular total area: SCNS 6185 ± 800.6 vs HFHS 4085 ± 213.7 μm2). Therefore, we conclude that HFHS short-term treatment was able to induce metabolic syndrome-like state, cardiomyopathy and vascular injury working as an important tool to study cardiometabolic diseases.

Molecular mechanisms of lip squamous cell carcinoma (LSCC) and actinic cheilitis (AC) are unclear. We aimed at assessing loss of heterozygosity (LOH) and TP53 and BRAF V600E mutations in these lesions. Formalin-fixed paraffin-embedded (FFPE) samples of 17 LSCC and 16 AC were included, with additional 5 fresh LSCC genotyped for TP53 mutations. LOH was assessed by six polymorphic markers located at 9p22, 9q22, and 17p13 and correlated with cell proliferation (Ki-67) and P53 immunostaining. Direct sequencing of TP53 exons 2–11 (fresh samples), and exons 5–9 (FFPE samples) was carried out. BRAF V600E mutation was genotyped in eight LSCC. LOH occurred in at least one marker in 15/17 LSCC and in 9/16 AC. The marker exhibiting the highest frequency of allelic loss (FAL) in LSCC was D9S157 (8/12 informative cases) and D9S287 in AC (4/11 informative cases). Cell proliferation was not correlated with LOH or with the FAL and no correlation between P53 IHC and 17p LOH was observed. We found TP53 missense mutations in both lesions and nonsense in LSCC, including CC>TT transition, which is a marker of UV damage. BRAF V600E mutation was not detected. LOH and TP53 mutations detected in LSCC and AC may be associated with tumorigenesis, whereas BRAF V600E mutation does not seem to significantly contribute to LSCC pathogenesis.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Oral squamous cell carcinoma (OSCC) is the most frequent oral malignant neoplasia. As consequence of OSCC treatment, oral mucositis (OM) is one of the most common adverse effects of OSCC treatment. Currently, there is no consensus for OM treatment. The purpose of the current study was to test the combination of red and infrared low-level laser therapy (LLLT) for OM treatment. Primary culture of human fibroblast was performed to identify LLLT dose. After laboratory tests, a two-arm parallel, single-blind, controlled study was conducted. The two arms were group 1, both 660- and 808-nm wavelengths (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2), and group 2, only 660-nm wavelength (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2). Both treatments were performed twice a week. Group 1 presented a reduction of mucositis grade in comparison to group 2. Group 1 also presented reduction of analgesics prescription. But no significant differences between groups 1 and 2 were observed according to the pain scale. In conclusion, the current study demonstrated that a combination of red and infrared at a higher dose (300 J/cm2) reduced both oral mucositis grade and analgesics prescription. The effects of the combination of RT and LLLT are unclear and need more studies.

Background: the renin-angiotensin system (RAS) is a critical contributing factor to obesity and related diseases. Several studies have shown the relationship of obesity with cyclooxygenase-2. Objectives: based on these facts, we aimed to investigate the celecoxib oral administration (a selective anti-inflammatory inhibitor of cyclooxygenase-2 (ICOX-2)) effects, in mice fed a high-fat diet by assessing the renin-angiotensin system and inflammatory markers expression. Methods: FVB/N male mice were divided into 3 groups and fed with experimental diets, standard, high-fat diet and high-fat diet plus ICOX-2 at a dose of 100mg/kg/body weight. Body weight, food intake, blood parameters and RAS/inflammatory markers expression were assessed. Results: the main findings showed that diet-induced obese mice treated with COX-2 inhibitor showed significantly improved glucose and insulin homeostasis, presented decreased body weight gain and the biochemical analyses revealed reduced triglyceride levels and higher serum HDL-c levels as compared to HFD and ST. These results were accompanied by a downregulation of AGT, ACE, TNF-α and IL-6 expression in the group receiving treatment. Conclusion: taken together, these results indicate that ICOX-2 may exhibit therapeutic potential for obesity via the renin-angiotensin system and inflammation.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Objectives: to analyze the mRNA expression of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the liver and white adipose tissue samples of individuals with class III obesity (body mass index ≥40.0 kg/m2) with non-alcoholic fatty liver disease (NAFLD). Methods: this cross-sectional study included patients with class III obesity exhibiting early or late morphological presentation of NAFLD (non-alcoholic hepatic steatosis [NAFL], n = 8 and non-alcoholic steatohepatitis [NASH], n = 13, respectively). All patients underwent bariatric surgery and peripheral blood, liver, and visceral white adipose tissue (WAT) samples were collected. Socio-demographic, anthropometric, clinical, plasma biochemical, and nutritional characteristics of each study subject were assessed and compared between patients presenting with NAFL and NASH. IL-6 and TNF-α mRNA expression in the liver and WAT samples were measured by using quantitative real time-polymerase chain reaction (qRT-PCR). Results: individuals with class III obesity and NASH showed higher body mass index (BMI) and higher IL-6 and TNF-α mRNA expression in the WAT compared to that of patients with NAFL (p = 0.01, for all associations). Conclusions: individuals with class III obesity with higher morphological severity of NAFLD exhibited higher BMI and higher IL-6 and TNF-α expression in the WAT. Future prospective studies are warranted to determine how BMI, IL-6, and TNF-α affect the progression of NAFLD in individuals with class III obesity.

Background Lipogenesis is a process that involves the fatty acids synthesis. Resveratrol and enalapril have been studied for their beneficial physiological properties on the glucose and lipid metabolism. Objectives The aim of the present study was to evaluate the oral administration of resveratrol and enalapril effects on glucose and lipid metabolism, evaluating the white pad lipogenesis genes expression in mice. Methods Swiss male mice were divided into four groups and treated for eight weeks as follows: Standard diet ad libitum (G1); Standard diet + Resveratrol (G2); Standard diet + Enalapril (G3); Standard diet + Resveratrol + Enalapril (G4), where resveratrol was administered with the food and enalapril with the water. Body weight, lipid profile, adiposity, glycemic parameters and epididymal adipocytes area were assessed. The expression levels of FAS, ACC, PPARγ and SREBP-1c were assessed by RT-PCR. Results The main findings showed an improvement in the insulin sensitivity and glucose tolerance in the group G2 as compared to G1. Similar results were found for the fasting glucose levels. Decreased triglycerides were observed in the animals treated with resveratrol and enalapril, along with decreased weight of the epididymal adipose tissue in the animals of the G2 group. A mild reduction in the group G4 as compared to the group G1 was observed. Decreased mRNA expression of FAS, ACC and PPARγ in the G4 group when compared to the G1 group were observed. Conclusion In conclusion the resveratrol and enalapril association improved the glucose and lipid profiles by modulating the expression of some lipogenesis genes, which are critical regulators of metabolic homeostasis.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Background: the complex pathophysiology of obesity includes low-grade chronic inflammation of white adipose tissue, an increase in plasma levels of pro-inflammatory cytokines as well as genetic factors, which have all emerged as important risk factors. Objective: evaluate the association between the TNFα-308G/A variant and sociodemographic, clinical and behavioral variables in an urban population using overall and central obesity as the measured outcome. Methods: a cross-sectional population-based study was conducted. Anthropometric measures and genotyping were assessed in 808 individuals. The associations were tested using the hierarchical theoretical model and multiple logistic regressions. Results: thirty-one percent of subjects were overweight while 19.4% were obese. No association was observed between genotype frequencies of TNFα-308G/A and either obesity or other variables of adiposity, including waist circumference, waist to height ratio, conicity index, and fat mass. However, age, gender, physical inactivity, and other comorbidities were associated with measures of excess adiposity in the hierarchical model. The phase angle of AA genotype was lower than GA and GG genotypes (p < 0.05). Conclusion: the rs1800629 SNP of the TNFA gene was not associated with the adiposity indicators evaluated in this based population study. However, AA genotype is more likely to have low cellular membrane integrity.

Background Recent studies have shown a relationship between adiposity traits and a low-grade inflammation of adipose tissue resulting from chronic activation of the innate immune system as interleukin-1 beta (IL-1β). However, this association remains controversial. Besides, the Quilombola communities that have presumed different genetic background and it could change the obesity vulnerability. Objective To estimate the association between IL-1β and adiposity traits like obesity or abdominal obesity in Quilombola communities. A cross-sectional population-based study was conducted the northern region of Minas Gerais with the representative sample of 756 individuals aged ≥ 18 years. The swab oral was used for DNA extraction and the IL-1β rs1143634 polymorphism was evaluated by RFLP-PCR. The interviewed and measures were done using specific protocols. It was estimated to outcomes: the overweight (body mass index ≥ 25 kg/m2), abdominal obesity (waist circumference ≥ 88 cm for women and ≥ 102 cm for men), and the high conicity index (≥ 1.18 cm or women e ≥ 1.25 cm for men). Poisson regression multivariate models were constructed considering genotype and the outcomes, adjusted for socioeconomic and lifestyle variables. Results The distribution of IL-1β for the TT genotype was (11.9%), CT (25.1%) and CC (63.0%). The women TT carriers showed a higher regular soft drink consumption (p = 0.048). The height was lower in man TT carriers (p = 0.041) and lower weight (p = 0.025). The CT genotype showed higher BMI (p = 0.037). The CT and TT carriers showed less prevalence ratio to abdominal obesity even adjusted to socioeconomic and lifestyle variables, there no associations between genotype and overweight or high conicity index. Conclusions In conclusion, after socioeconomic and lifestyle adjustment T variant of rs1143634 is a protection factor for central obesity in Quilombola communities.

Resumo: Objetivou-se investigar a validade da autopercepção da presença da cárie dentária e fatores associados, mediante estudo com 795 adultos (35-44 anos). A variável dependente foi autopercepção da presença da cárie dentária, as independentes reunidas em blocos. Três modelos logísticos foram conduzidos: (1) todos os adultos; (2) adultos com lesões de cárie normativa; e (3) adultos sem tais lesões. A autopercepção da presença da cárie dentária apresentou sensibilidade de 77,7%, especificidade de 58%, acurácia de 65%, valor preditivo positivo de 52% e valor preditivo negativo de 81%. No Modelo 1, a autopercepção da presença da cárie dentária foi associada ao tempo de uso dos serviços odontológicos, acesso à informação, uso de fio dental, lesões normativas, percepção da necessidade de tratamento, dor, insatisfação com a saúde bucal e geral. No Modelo 2, a autopercepção da presença da cárie dentária foi associada ao tempo de uso dos serviços odontológicos, percepção da necessidade de tratamento e insatisfação com a saúde bucal e geral. No Modelo 3, autopercepção da presença da cárie dentária foi associada ao tempo de uso dos serviços odontológicos, acesso à informação, percepção da necessidade de tratamento, insatisfação com a saúde bucal e uso de fio dental. A autopercepção da presença da cárie dentária mostrou utilidade limitada como método de diagnóstico. Abstract: This study aimed to analyze the validity of self-perceived dental caries and associated factors in a sample of 795 adults (35-44 years). The dependent variable was self-perceived dental caries, and the independent variables were combined in blocks. Three logistic models were performed: (1) all adults; (2) adults with a formal diagnosis of caries; and (3) adults without such caries. Self-perceived dental caries showed 77.7% sensitivity, 58% specificity, 65% accuracy, 52% positive predictive value, and 81% negative predictive value. In Model 1, self-perceived dental caries was associated with time of use of dental services, access to information, flossing, formal diagnosis of caries, self-perceived need for treatment, toothache, and dissatisfaction with oral health and general health. In Model 2, self-perceived dental caries was associated with time of use of dental services, self-perceived need for treatment, and dissatisfaction with oral health and general health. In Model 3, self-perceived dental caries was associated with time of use of dental services, access to information, flossing, self-perceived need for treatment, and dissatisfaction with oral health. Self-perceived dental caries showed limited utility as a diagnostic method. Resumen: Se tuvo como objetivo investigar la validez de la autopercepción de la presencia de la caries dental y factores asociados, mediante un estudio con 795 adultos (35-44 años). La variable dependiente fue autopercepción de la presencia de la caries dental, las independientes se reunieron en bloques. Se realizaron tres modelos logísticos: (1) todos los adultos; (2) adultos con lesiones de caries conforme a la norma; y (3) adultos sin tales lesiones. La autopercepción de la presencia de la caries dental presentó sensibilidad de un 77,7%, especificidad de un 58%, precisión de un 65%, valor predictivo positivo de un 52% y valor predictivo negativo de un 81%. En el Modelo 1, la autopercepción de la presencia de la caries dental se asoció al tiempo de uso de los servicios odontológicos, acceso a la información, uso de hilo dental, lesiones conforme a la norma, percepción de la necesidad de tratamiento, dolor, insatisfacción con la salud bucal y general. En el Modelo 2, la autopercepción de la presencia de la caries dental se asoció al tiempo de uso de los servicios odontológicos, percepción de la necesidad de tratamiento e insatisfacción con la salud bucal y general. En el Modelo 3, la autopercepción de la presencia de la caries dental se asoció al tiempo de uso de los servicios odontológicos, acceso a la información, percepción de la necesidad de tratamiento, insatisfacción con la salud bucal y uso de hilo dental. La autopercepción de la presencia de la caries dental mostró utilidad limitada como método de diagnóstico.

Background Kaposi's sarcoma (KS) persists today as a highly prevalent vascular cancer, often found in HIV patients. Studies have shown that angiopoietin 2 (Ang2), a pro-angiogenic protein, is involved in the pathogenesis of this tumor. However, expression of this protein has not been investigated in oral KS lesions. Thus, we aimed to investigate the expression of Ang2 in samples of oral KS Methods Immunohistochemistry was used to evaluate Ang2 expression in 14 oral KS cases, with degrees of expression being analyzed in a semi-quantitative manner. In addition, clinical information such as age, gender, race, tumor location, size, color and appearance, as well as HIV status, was collected and included in the analysis Results All patients were white males, mostly HIV-positive, with a mean age of 40 years. Clinically, the lesions were dark red/blue/purple masses, ranging from 1-2.5 cm in diameter, found in various locations such as the tongue, palate, and gingiva. Expression of Ang2 was noted in 72% (10/14) of the samples. Of these, 10% showed weak expression, 60% moderate and 30% strong expression Conclusions Our results indicate that Ang2 is expressed in oral KS and, consistent with results from previous studies, show that Ang2 may contribute to the pathogenesis of this lesion. This article is protected by copyright. All rights reserved.

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P < .05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC.

The presence of cervical metastasis is responsible for high morbidity and mortality rates in individuals with head and neck squamous cell carcinoma (HNSCC). S100A4, a pleiotropic EF-hand calcium-binding protein, is expressed in various normal and cancer cell types. During cancer progression, molecular disturbances in S100A4 can modulate the activity and expression of pre-metastatic and metastatic genes. In this study, we investigated the association between S100A4 methylation status and protein expression as well as the expression of the S100A4 related-proteins annexin A2 (ANXA2), matrix metallopeptidase-9, and endoglin, for metastasis and other clinicopathological parameters in HNSCC. Formalin-fixed, paraffin-embedded blocks of metastatic and non-metastatic HNSCC and matched cervical lymph node (LN) samples (metastatic LN = mLN, non-metastatic = nmLN, and control LN (lymphadenitis) = cLN) were submitted for methylation specific-polymerase chain reaction and immunohistochemistry. Our results showed that S100A4 methylation status failed to demonstrate association with cervical metastasis and other clinicopathological factors related to HNSCC. HNSCC samples from patients that presented with metastatic disease showed high S100A4 and endoglin expression (p

Aims The aim of the presente study was to examine the effects of oral gallic acid (GA) administration on the brown adipose tissue of obese mice fed with high-fat diet. New mechanisms and interactions pathways in thermogenesis were accessed through bioinformatics analyses. Main methods Swiss male mice were divided into four groups and fed during 60 days with: standard diet, standard diet combined with gallic acid, high-fat diet and high-fat diet combined with gallic acid. Body weight, food intake, and blood parameters (glucose tolerance test, total-cholesterol, high-density low-c, triglyceride and glucose levels) were evaluated. Brown and subcutaneous white adipose tissue histological analysis were performed. SIRT1 and PGC1−α mRNA expression in the brown adipose tissue were assessed. Key findings Our main findings showed that the gallic acid improved glucose tolerance and metabolic parameters. These results were accompanied by bioinformatics analyses that evidenced SIRT1 as main target in the thermogenesis process, confirmed as increased SIRT1 mRNA expression was evidenced in the brown adipose tissue. Significance Together, the data suggest that the gallic acid effect in brown adipose tissue may improve body metabolism, glucose homeostasis and increase thermogenesis.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Liraglutide, an important pharmacological agent used to improve glycemic status and weight control, has emerged as a therapeutic strategy for hepatic steatosis treatment. Objective: The aim of the present study was to analyze the influence of liraglutide in hepatic steatosis and evaluate the potential target genes involved in the liraglutide action in the hepatic steatosis through a bioin-formatics study. Methods & procedures: We performed an animal study with male mice divided into three groups: standard, high-fat diet and the third group were fed a high-fat diet and treated with liraglutide at a dose of 0.6 mg/kg body weight. Blood parameters (glucose tolerance and insulin sensitivity tests, total cholesterol, high-density lipo-protein-C, triglycerides and glucose levels) were evaluated. mRNA analysis for ACC and FAS were performed.Gene databases, and bioinformatics algorithms were used to generate molecular targets for liraglutide and he-patic steatosis based on in silico investigation. Interactions networks between protein coding were accessed. Results: The present study showed that liraglutide decreased glucose levels, total cholesterol and triglycerides in obese animals as compared to the high-fat-fed obese mice. AKT and RPS6KB1 genes presented higher disease-related connectivity. Interaction Network exhibited a power law behavior in correlation: 0.896; R2: 0.796. Ontological analysis demonstrated different mechanisms associated such as regulation of signaling process. Conclusion: The present study reveals relevant information regarding the liraglutide effects in hepatic steatosis. The liraglutide improved hyperglycemia and attenuated hepatic steatosis in mice fed a high-fat diet.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior The present study aimed to evaluate the effects of resveratrol on FNDC5 and thermogenesis markers expression in the adipose tissue of mice and humans. Thirty-two male mice were randomly divided into four groups (n = 8) and fed with: Standard Diet; Standard Diet + Resveratrol (400 mg/kg); High-fat Diet; High-fat Diet + Resveratrol for eight weeks. Twenty male and female volunteers, aged 30–55 years, BMI ≥ 30 kg/m² were divided into two groups and treated for four weeks with 500 mg trans-resveratrol or placebo, adipose tissue biopsies were taken. Analysis of body weight, food intake, glycemic and lipid profiles, mRNA expression from tissues and primary culture of adipocytes were performed. The main results show that resveratrol improves the glycaemic and lipid profiles along with an increase in the levels of UCP1, PRDM16, PGC1α, and SIRT1. The increase in FNDC5 expression was observed in the mouse and human subcutaneous adipose tissue. The SIRT1 antagonist in adipocyte primary culture resulted in decreased FNDC5 expression. Our data suggest that improved metabolism produced by oral administration of resveratrol is, at least in part, associated with increased thermogenesis followed by high expression of UCP1, PRDM16, PGC1α and that increased FNDC5 expression in the subcutaneous adipose tissue from mice and human might be modulated by SIRT1.

Objetivou-se testar a associação entre perdas dentárias por cárie (PDC) e variáveis relativas ao acesso a informações em saúde bucal. Foram analisados dados de 780 adultos (35-44 anos) participantes de um estudo epidemiológico. A variável dependente foi o total de PDC e as independentes foram reunidas em blocos de variáveis: demográficas e socioeconômicas; utilização dos serviços odontológicos; acesso a informações em saúde bucal (informações sobre como evitar problemas bucais, sobre higiene bucal e sobre dieta) e; comportamentais. Conduziu-se regressão linear múltipla hierarquizada. O número médio de PDC foi de 7,03 (EP= 0,31) e 83% dos adultos haviam perdido algum dente por cárie. As PDC foram maiores entre os mais velhos, os com menor escolaridade, as mulheres, os que raramente ou nunca receberam informações sobre higiene bucal, os que escovavam os dentes uma vez ou menos ao dia e entre os que não usavam fio dental. Adultos que raramente/nunca receberam informações dos serviços odontológicos sobre higiene bucal perderam 2,15 dentes a mais por cárie que aqueles que sempre/frequentemente receberam tais informações (p = 0,000). Assim, sugere-se que a garantia do acesso à informação deva ser incentivada a fim de contribuir com maior equidade em saúde bucal. This study sought to establish the association between tooth loss due to dental caries and variables related to access to information on oral health in adults aged 35-44 years (n = 780) who participated in a large epidemiological study. The dependent variable was total tooth loss due to caries. The independent variables were grouped into blocks: demographic and socio-economic characteristics, use of dental service, access to oral health information (about how to prevent oral problems; oral hygiene; and diet), and behaviors. The analysis was conducted using hierarchical multiple linear regression. The mean number of lost teeth due to caries was 7.03. High numbers of lost teeth were higher among females and older adults; low levels of education; adults who rarely/never received oral hygiene information; those who brushed their teeth once a day or less; and those adults who did not use dental floss (p < 0.05). Adults who rarely/never received oral hygiene information from dental services lost 2.15 more teeth due to caries than those who always/often received such information (p = 0,000). Thus, it is suggested that access to information should be encouraged to contribute to greater equity in oral health.

Oral cancer is a world health problem, and one of the highest incidence rates of oral cancer worldwide occurs in Brazil. STAG2 is part of the cohesin complex which is responsible for sister chromatid cohesion. STAG2 loss of expression was reported in a range of tumors, and STAG2 loss was found to cause chromosomal instability and aneuploidy in cancer cells. On the basis of these findings, we investigated STAG2 expression in oral cancer and potentially malignant lesions. We investigated STAG2 immunoexpression in oral cancer, lip cancer, oral leukoplakia, and actinic cheilitis, including complete clinical information. Normal oral mucosa samples were included as normal controls. STAG2 protein was highly expressed in all samples. We further tested STAG2 expression in gastric adenocarcinomas and glioblastomas, as these tumor types were previously shown to lose STAG2 expression. We found homogenous expression of STAG2 by these tumor cells. Our results suggest that STAG2 loss of expression is not a common event in oral carcinogenesis.

Oral Mucinous Adenocarcinoma is a rare malignant neoplasm characterized by large amounts of extracellular epithelial mucin-containing small cordlike and nestlike clusters of epithelium. The purpose of the current study was to describe a rare case of primary mucinous adenocarcinoma in the minor salivary gland and its immunohistochemical features. A 64-year-old man was referred for evaluation of a swelling located in the left side of the mandible. A fine needle aspiration cytology revealed atypical neoplastic cells with increased and hyperchromatic nuclei. An incisional biopsy showed lakes of mucin loculated by fibrotic stroma. In the mucin pools, tumor cells could be observed floating both individually and in small clumps, either solid or clustering around microlumin. Necrotic areas were not noticed. Considering all these features, the final diagnosis was mucinous adenocarcinoma. The patient was directed to the oncology department for treatment and has remained disease free with no sign of cervical lymph nodes during the 27 months follow-up period. An immunohistochemical panel was performed and the tumor presented positive staining for Ki-67, MCM2, 34β12, AE1AE3, CK 18, Glut 1, EMA, E-Caderin, CK 19, CD 138 and CK 7.

OBJECTIVE: This study aimed to investigate the expression of the MSH2 DNA repair protein in head and neck squamous cell carcinoma (HNSCC) in order to analyze its association with clinicopathologic factors and overall survival of patients. MATERIAL AND METHODS: Clinical data and primary lesions of HNSSC were collected from 55 patients who underwent surgical resection with postoperative radiotherapy in Montes Claros, state of Minas Gerais, Brazil, between 2000 and 2008. Immunohistochemical reactions were performed to analyze MSH2 protein expression. RESULTS: Bivariate analysis showed no significant correlation or association between MSH2 expression and clinicopathologic parameters by Mann-Whitney and Kruskal-Wallis tests. Patients with locoregional metastatic disease (OR=4.949, p

BACKGROUND: The histopathology and immune responses of the healing process of leishmaniasis are still poorly studied. OBJECTIVES: This study aimed to examine the histopathological and immunological aspects of lesions of patients with cutaneous leishmaniasis before and after different therapeutic methods. METHODS: We studied 23 individuals grouped according to the treatments: Glucantime, Glucantime + Leishvacin and Glucantime + Leishvacin associated with Bacillus Calmette-Guerin. For analysis of the histopathological changes present in the dermis and epidermis, histological sections were stained with hematoxylin and eosin. The samples were immunostained before and after treatment to analyze the expression of interferon (IFN)-γ, interleukin (IL) 12, IL-10 and IL-4. RESULTS: Before treatment the presence of intense infiltrates of mononuclear cells was noticed and after treatment, even with a diagnosis of clinical cure, the subjects still showed a moderate inflammatory process. In the immunohistochemical analyses, we noticed a difference between the cytokines, with increased expression of cytokines IFN-γ and IL-12 compared to IL 10 and IL-4, both before and after treatment and, comparatively, the difference in this expression was more intense before treatment. However, the cytokine expression analyzed by treatment group showed no statistically significant difference. CONCLUSION: We conclude that a clinical cure does not always coincide with the histopathological one, and that before treatment there is a predominance of Th1 cytokines. In terms of treatment type, there was no difference in the progression of healing for all the three types of treatment, indicating their clinical equivalence. FUNDAMENTOS: A histopatologia e as respostas imunológicas do processo de cura da leishmaniose são ainda pouco estudadas. OBJETIVOS: Este estudo teve como objetivo avaliar os aspectos histopatológicos e imunológicos das lesões de pacientes com leishmaniose tegumentar, antes e após diferentes métodos terapêuticos. MÉTODOS: Foram estudados 23 indivíduos agrupados de acordo com os tratamentos: Glucantime, Glucantime + Leishvacin e Glucantime + Leishvacin associado com Bacilo Calmette-Guerin. Para a análise das alterações histopatológicas presentes na derme e epiderme, cortes histológicos foram corados com hematoxilina e eosina. Para avaliar a expressão de interferon (IFN)-γ, interleucina (IL) 12, IL-10 e IL-4 foi utilizada a técnica de imuno-histoquímica antes e após o tratamento. RESULTADOS: Antes do tratamento houve um intenso infiltrado de células mononucleares, após o tratamento, mesmo com um diagnóstico de cura clínica, apresentou-se ainda um moderado processo inflamatório. Na análise imuno-histoquímica, notamos uma diferença entre as citocinas, com expressão aumentada de citocinas IFN-γ e IL-12 em comparação com IL-10 e IL-4 tanto antes quanto depois do tratamento, e comparativamente, a diferença nesta expressão mostrou-se mais intensa antes do tratamento. No entanto, a expressão das citocinas analisadas por grupo de tratamento não mostraram diferenças estatisticamente significativas. CONCLUSÃO: Concluímos que uma cura clínica nem sempre coincide com a cura histopatológica, e que antes do tratamento há uma predominância de citocinas Th1. Para os tratamentos, não houve diferença na progressão da cura para todos os três tipos de tratamento, indicando a equivalência clínica dos tratamentos.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Background: sleeve gastrectomy (SG) has been used as a multipurpose surgical procedure for the treatment of obesity. Objectives: the present study aimed to assess the effects of SG on the metabolic and inflammatory profile and renin-angiotensin system (RAS) expression in the white adipose tissue of male rats with obesity induced by a high-fat diet. Methods: male Wistar rats were treated with a standard diet or high-fat diet and submitted to SG or sham surgery. The glycemic and lipid profiles and gene expression of inflammatory markers and RAS components in adipose tissue were evaluated. Results: SG led to weight loss, decreased adiposity (p < 0.01) and a reduction in plasma glucose (p < 0.05), C-peptide (p < 0.05), insulin (p < 0.001) and total cholesterol (p < 0.05) levels. In addition, SG led to a decrease in the expression of tumor necrosis factor-alpha (TNF-α) (p < 0.01), interleukin- 6 (IL-6) (p < 0.001), angiotensinogen (AGT) (p < 0.001) and angiotensin converting enzyme (ACE) (p < 0.05) and increased the expression of angiotensin converting enzyme 2 (ACE2) (p < 0.05) in white adipose tissue. No statistically significant differences were observed for AT1 (p = 0.10) and Mas (p = 0.22) receptors. Conclusion: this study showed that SG leads to weight loss and improves metabolic parameters. Changes in the expression of RAS components and of inflammatory molecules in adipose tissue seem to play a role the before beneficial effects of the SG.

Aim: The present study aimed to analyze the expression of IL6, UCP1 and SIRT1 in adipose tissue (WAT and BAT) in association to clinical, metabolic and anthropometric parameters in obese humans. Methods: WAT and BAT samples from obese patients (n=27) were collected. IL6, UCP1 and SIRT1 markers were measured by qRT-PCR. The association between IL6, UCP1 and SIRT1 mRNA expression and anthropometric and clinical parameters were evaluated, using appropriate statistical tests. Results: Our results demonstrated that high levels of IL6 are associated with altered glucose levels in the WAT (p=0.01). In contrast, high levels of IL6 in the BAT were associated with decreased % fat (p=0.01) and fat weight (p=0.02) and increased mVO2 (p=0.02) and VO2 (p=0.02). For UCP1, a higher expression in the BAT was observed when compared to the WAT (p=0.0001). This gene expression was associated with lower values of BMI (p=0.03), % fat (P=0.02) and fat weight (P=0.02) and increased mVO2 (p=0.041) and VO2 (p=0.001). In the WAT, decreased levels of SIRT1 were associated with increased fat weight (p=0.02); in the BAT, associations were found for % fat (p=0.018) and mVO2 (p=0.03). Conclusion: These results reveal different characteristics in the biological actions between WAT and BAT in obese humans. Increased levels of IL6, UCP1 and SIRT1 in the BAT were associated with metabolic parameters improvements.

The aim of this study is to assess whether C1772T and G1790A hypoxia-inducible factor-1 (HIF-1)α polymorphisms are associated with risk of oral lichen planus (OLP). Restriction fragment length polymorphism analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 32 OLP and 88 individuals without OLP. The frequency of the CC, TT, GA, and AA genotypes was higher in patients with OLP. Notably, individuals carrying the C and A, and T and A haplotypes showed a significant association OLP risk. Our study demonstrated that the C1772T and G1790A polymorphisms of HIF-1α gene increased the risk of OLP. C1772T and G1790A polymorphisms of HIF-1α gene had differing patterns of allelic imbalance in the normal samples and subsequent chronic lesions. Further studies are necessary to elucidate the HIF-1α pathway in OLP, which would facilitate the development of novel therapeutic strategies for the prevention and treatment of OLP. These results, in conjunction with previous studies, suggest that HIF-1α may play important roles in the chronicity of oral mucosa lesions of OLP patients. Taken together, we suggest that HIF-1α polymorphisms enhance its target genes, thereby altering the microenvironment and supporting sequential release of inflammatory mediators or cellular events in OLP. It appears unlikely that inhibition of a single proinflammatory mediator will prove useful in clinical practice, but several ways to reprogram mediators engaged in a wide array of roles simultaneously are encouraging.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais Outra Agência Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Lipogenesis is the process by which fatty acids are synthesized. In metabolic syndrome, an insulin resistant state along with high plasma levels of free fatty acids (FFA) and hyperglycemia may contribute to the lipogenic process. The aim of the present study was to investigate the effects of oral administration of metformin on the expression of lipogenic genes and glycemic profile in mice fed with low-carbohydrate high-fat diet by evaluating their metabolic profile. SWISS male mice were divided into 4 groups (N = 7) that were fed with standard (ST), standard plus metformin (ST + MET), low-carbohydrate high-fat diet (LCHFD) and low-carbohydrate high-fat diet plus metformin (LCHFD + MET) (100 mg kg−1 diet) diets respectively. Food intake, body weight and blood parameters, such as glucose tolerance, insulin sensitivity, glucose, HDL-c, total cholesterol, triglycerides, ASL and ALT levels were assessed. Histological analyses were performed on hematoxylin and eosin-stained epididymal adipose tissue histological specimens. The expression levels of peroxisome proliferator-activated receptor (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), were assessed by RT-PCR. This study showed that metformin decreased adipocyte area, body weight and food consumption in obese animals when compared to the standard group. Furthermore, the expression of lipogenic markers in adipose tissue were diminished in obese animals treated with metformin. This data showed that oral administration of metformin improved glucose and lipid metabolic parameters in white adipose tissue by reducing the expression of lipogenesis markers, suggesting an important clinical application of MET in treating obesity-related diseases in metabolic syndrome.

This study aimed to evaluate the association between several different aspects of disease in head and neck squamous cell carcinoma (HNSCC): morphological grading, Ki67 proliferation index (PI), invasive front, adjacent non-malignant mucosa (ANMM), recurrence and overall survival of the patients. Sixty-four fully reviewed and followed-up patients with primary HNSCC were matched according to recurrence of the lesion and placed in one of two groups of 32 cases. Chi-square and Fisher's exact tests were used to analyze the clinicopathological parameters between both groups of patients. Association between Ki67 PI and clinicopathological parameters was also analyzed through chi-square and Fisher's exact tests with the binary logistic regression model used as a multivariate analysis. In addition, survival analysis was also performed. Our results showed that high-risk dysplasia in ANMM and high Ki67 PI in ANMM of HNSCC exhibited a higher risk of tumor recurrence. Survival analysis showed that T3/T4 tumor sizes and high Ki67 PI were significantly associated with an increase in the risk of death in multivariate analysis. Our results revealed that high-risk dysplasia and high Ki67 PI of the ANMM are parameters which are indicative of tumor recurrence. Furthermore, T3/T4 tumor sizes and high Ki67 PI in the invasive front appear to be important prognostic tools for HNSCC.