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Aims: This study aimed to improve malnutrition in mice and elderlies with a new dairy/buriti oral dietary supplement. Background: Malnutrition is a prevalent problem in the elderly; therefore, oral dietary supplementation is an important strategy to reduce the incidence of this health problem. Objective: The present study evaluated the effects of a low-cost food supplement, made from by-products of the dairy and fruit industry in the Brazilian Cerrado (Buriti), on the nutritional status and the recovery of the metabolic profile of malnourished animals and elderly women. Methods: In the pre-clinical phase, Swiss mice were divided into six groups and subjected to malnutrition and renutrition. The clinical phase was carried out with 25 elderly women residing at a long-term institution, aged ≥ 65 years and with malnutrition or risk of malnutrition. Results: The analyzes showed improvements in anthropometric parameters and an increase in serum albumin levels, in addition to lipid profile improvement in the preclinical phase and an increase in the red blood cells and hemoglobin in the clinical phase. Conclusion: The supplement based on buriti was able to reverse malnutrition promoting improvements in anthropometric and biochemical parameters.

The urban demographic in most developing countries often depend on fossilized fuel generators to meet the electricity supply gap from the national grid. Due to health and environmental concerns with fossilized fuel, local renewable energy resources offer a tentative replacement but often involve high initial upfront costs for their deployment. This work addresses the initial cost barrier issue with renewable energy deployment by focusing on Nigeria as a case study. More specifically, this work proposes a Solar Nano grid concept as an alternative to fossilized generators. The proposed Solar Nano grid concept presents the flexibility to deploy PV systems based on budgetary constraints and the option of upgrading the system (adding newer units to existing ones) in the future. While adding new units to old ones gives rise to compatibility and aging issues in the PV systems, simulation studies show that it is possible to eliminate such concerns by applying a set of design protocols and principles in the proposed Solar Nano grid. An assembled lab-scale Solar Nano grid system validated the simulation findings. With the validated model, this work puts forth possible strategy for reducing the upfront cost of PV system deployment to about 10% of the initial value.

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.

Background Head and neck squamous cell carcinoma (HNSC) etiopathogenesis remains unclear, and the biological changes with the activation of heat shock proteins (HSPs) and prion protein (PRNP) promoted by hypoxia in HNSC are undetermined. Objective This study investigates hypoxia's effect in lymph node metastasis by PRNP expression changes and its main partners. Methods The study combined a theoretical/cell culture study with a case-control study. First, bioinformatics and cell culture were performed. A case-control study was performed in a second step by comparing HNSC patients with and without lymph node metastasis. Analyses The Cancer Genome Atlas (TCGA) data source validate the theory in the global population study. Results Bioinformatics analysis suggests that hypoxia-inducible factor-1α (HIF1A) is associated with HSPA4, HSP90AA1, and PRNP expression. TCGA data validate the hypothesis that higher HSP90AA1, HSPA4, and PRNP are related to metastases and low survival. Herein, the cell study demonstrated that muted PRNP did not respond to hypoxia. Conclusions Our results collectively provide the first evidence that PRNP promotes HNSC lymph node metastasis progression through the upregulation of HSPA4, HSP90AA1, and HIF1A. Our findings may provide a molecular basis for the promoting Role of PRNP in HNSC progression.

Background: Malnutrition induced by dietary restriction produces several metabolic changes that affect body weight, the digestive system, and annex organs, including the liver. Malnutrition generates an inflammatory state and increases oxidative stress. The liver is one of the body vital organs, becoming necessary to analyze the impact of food supplementation on the repair of possible changes that may occur in this organ due to malnutrition. Aims: To evaluate the effects of a low-cost supplementation derived from Buriti and dairy byproducts on liver recovery in malnourished mice, focusing on the expression of oxidative stressrelated genes, as well as biochemical and histological parameters. Methods: Swiss mice were divided into six groups and submitted to two treatment phases: food restriction, for malnutrition onset; and renutrition, with mice being fed with different diets. Results: Our results indicate that dietary supplementation was successful in recovering liver damage caused by malnutrition in animal models. The new supplement has been shown to recover liver damage with similar or superior results compared to the commercial reference supplement on the market. Conclusion: Our work presents a new composition of low cost food supplement based on buriti and dairy by-products, proven to be effective in the malnutrition treatment of malnutrition. The improvements were proven through the recovery of body weight, reduction of inflammation and oxidative stress.

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.

Background Lychnophora ericoides Mart. (Asteraceae) is a Brazilian plant commonly used in folk medicine to treat pain and inflammation by topical administration. In recent years, this medicine has begun to be used orally. However, no study concerning its toxicity profile has been reported. Objective The study evaluates the potential toxicity of the ethanolic extract from leaves of the Lychnophora ericoides, through the methods of acute and sub-acute oral administration in mice. Method An acute toxicity study was performed according to the Organization for Economic Cooperation and Development protocol (OECD 423). A single extract dose of 50, 300, and 2000 mg/kg (n=3/group) was administered orally to female Swiss mice. For subacute toxicity, the protocol OECD 407 was followed. Doses of 50, 300, and 500 mg/kg (n=10/group) of the extract were administered daily to Swiss mice of both sexes for 28 days. Abnormal behavior, muscle strength, toxic symptoms, weight, and death were observed when assessing toxicity. Biochemical analysis, hematological analysis, macroscopic examination, and histopathological examination of several organs were conducted at the end of the treatment period. Results In acute and subacute toxicity, the extract did not produce mortality. The acute toxicity study revealed alterations in the behavioral test and histopathological changes in the liver, kidney, lung, and spleen. The subacute oral toxicity test showed changes in hematologic and biochemical parameters. Histopathological examination of liver, kidney, spleen, lung, and heart indicated degenerative characteristics with inflammatory infiltrates focus. Conclusion The study results suggest that oral use of Lychnophora ericoides leaves extract should be performed with caution in low doses in both single and repeated administrations.

Nowadays the adipose tissue is recognized as one of the most critical endocrine organs releasing many adipokines that regulate metabolism, inflammation and body homeostasis. There are several described adipokines, including the renin-angiotensin system (RAS) components that are especially activated in some diseases with increased production of angiotensin II and several pro-inflammatory hormones. On the other hand, RAS also expresses angiotensin-(1-7), which is now recognized as the main peptide on counteracting Ang II effects. New studies have shown that increased activation of ACE2/Ang-(1-7)/MasR arm can revert and prevent local and systemic dysfunctions improving lipid profile and insulin resistance by modulating insulin actions, and reducing inflammation. In this context, the present review shows the interaction and relevance of Ang-(1-7) effects on regulating adipokines, and as one adipokine itself, modulating body homeostasis, with emphasis on its anti-inflammatory properties, especially in the context of metabolic disorders with focus on obesity and type 2 diabetes mellitus pandemic.

Despite all the development of modern medicine, around 100 compounds derived from natural products were undergoing clinical trials only at the end of 2013. Among these natural substances in clinical trials, we found the resveratrol (RES), a pharmacological multi-target drug. RES analgesic properties have been demonstrated, although the bases of these mechanisms have not been fully elucidated. The aim of this study was to evaluate the involvement of opioid and cannabinoid systems in RES-induced peripheral antinociception. Paw withdrawal method was used and hyperalgesia was induced by carrageenan (200 μg/paw). All drugs were given by intraplantar injection in male Swiss mice (n = 5). RES (100 μg/paw) administered in the right hind paw induced local antinociception that was antagonized by naloxone, non-selective opioid receptor antagonist, and clocinnamox, μOR selective antagonist. Naltrindole and nor-binaltorfimine, selective antagonists for δOR and kOR, respectively, did not reverse RES-induced peripheral antinociception. CB1R antagonist AM251, but not CB2R antagonist AM630, antagonized RES-induced peripheral antinociception. Peripheral antinociception of RES intermediate-dose (50 μg/paw) was increased by: (i) bestatin, inhibitor of endogenous opioid degradation involved-enzymes; (ii) MAFP, inhibitor of anandamide amidase; (iii) JZL184, inhibitor of 2-arachidonoylglycerol degradation involved-enzyme; (iv) VDM11, endocannabinoid reuptake inhibitor. Acute and peripheral administration of RES failed to affect the amount of μOR, CB1R and CB2R. Experimental data suggest that RES induces peripheral antinociception through μOR and CB1R activation by endogenous opioid and endocannabinoid releasing.

Previous studies have shown that the clove essential oil concentration of 200 mg/kg did not present toxicity and histopathological changes in the liver. Based on the evidence presented in this study, we decided to evaluate in vivo the ability of a previously developed fermented dairy beverage, tested only in vitro, in which the standard chemical preservative, potassium sorbate, was replaced by clove essential oil (2 μl/ml), to be a functional food. To this end, twenty-four male Swiss mice were divided into three groups and submitted insulin sensitivity (IST) and glucose tolerance (GTT) testing, evaluation of physiological and biochemical parameters, histopathological analysis and quantification of the expression of anti-inflammatory and pro-inflammatory cytokines in the liver, after administering daily of the fermented dairy beverage with or without clove essential oil by gavage during 30 days. The group that received the fermented dairy beverage with clove essential oil showed a lower glycemic level in GTT, a higher sensitivity to insulin and a higher glucose decay constant rate (Kitt), with relation to the other groups. In the evaluation of physiological parameters there were no signs of toxicity in the mice during the experimental period. The biochemical parameters, histopathological analysis and expression of anti-inflammatory (IL-10) and pro-inflammatory (IL1β, IL6 e TNFα) cytokines in the liver of the mice, was not significantly affected by the treatment. These results corroborated by bioinformatics analysis demonstrate that the fermented dairy beverage with clove essential oil it can function as a substitute for conventional chemical preservatives and reduce glycemic levels. Estudios previos han demostrado que la concentración de aceite esencial de clavo de 200 mg / kg no presenta toxicidad y cambios histopatológicos en el hígado. Con base en la evidencia encontrada en este estudio, decidimos evaluar in vivo la capacidad de una bebida láctea fermentada desarrollada previamente, probada solo in vitro, en la que el conservante químico estándar, sorbato de potasio, fue reemplazado por aceite esencial de clavo (2 μl / ml), para ser un alimento funcional. Con este fin, veinticuatro ratones suizos se dividieron en tres grupos y se sometieron a pruebas de sensibilidad a la insulina (ITS) y tolerancia a la glucosa (GTT), evaluación de parámetros fisiológicos y bioquímicos, análisis histopatológico y cuantificación de la expresión de antiinflamatorios y pro- citocinas -inflamatorias normativas, después de la administración después de la administración administración de bebida láctea fermentada con o sin aceite esencial de clavo por sonda durante 30 días. El grupo que bebió la leche italiana fermentado con aceite esencial de clavo presentó menor nivel de glucemia en el GTT, mayor sensibilidad a la insulina y mayor tasa constante de desintegración de glucosa (Kitt), en relación a los otros grupos. En la evaluación de los parámetros fisiológicos, no hubo evidencia de toxicidad en los ratones durante el período experimental. Parámetros bioquímicos, análisis histopatológico y expresión de citocinas antiinflamatorias (IL-10) y proinflamatorias (IL1β, IL6 y TNFα) en el hígado de ratones no afectados por el tratamiento. Estos resultados corroborados por análisis bioinformáticos demuestran que la bebida láctea fermentada con aceite esencial de clavo puede actuar como sustituto de los conservantes químicos convencionales y reducir los niveles glucémicos. Estudos anteriores demonstraram que o óleo essencial de cravo da índia na concentração de 200 mg/kg não apresentou toxicidade e alterações histopatológicas no fígado. Com base nas evidências apresentadas neste estudo, decidimos avaliar in vivo a capacidade de uma bebida láctea fermentada desenvolvida e testada anteriormente apenas in vitro, na qual o conservante químico padrão, sorbato de potássio, foi substituído por óleo essencial de cravo (2 μl / ml), para ser um alimento funcional. Para isso, vinte e quatro camundongos Swiss machos foram divididos em três grupos e submetidos a testes de sensibilidade à insulina (TSI) e tolerância à glicose (TTG), avaliação de parâmetros fisiológicos e bioquímicos, análise histopatológica e quantificação da expressão de antiinflamatórios e pró-citocinas inflamatórias no fígado, após administração diária da bebida láctea fermentada com ou sem óleo essencial de cravo da índia por gavagem durante 30 dias. O grupo que recebeu a bebida láctea fermentada com esse óleo essencial apresentou menor nível glicêmico no TTG, maior sensibilidade à insulina e maior taxa constante de decaimento da glicose (Kitt), em relação aos demais grupos. Na avaliação dos parâmetros fisiológicos não houve indícios de toxicidade nos camundongos durante o período experimental. Os parâmetros bioquímicos, a análise histopatológica e a expressão das citocinas antiinflamatórias (IL-10) e pró-inflamatórias (IL1β, IL6 e TNFα) no fígado dos camundongos não foram significativamente afetados pelo tratamento. Esses resultados corroborados por análises de bioinformática demonstram que a bebida láctea fermentada com óleo essencial de cravo da india pode funcionar como substituto dos conservantes químicos convencionais e reduzir os níveis glicêmicos.

Neutrophil extracellular traps (NETs) represent an innate organism defense mechanism characterized by neutrophil release of intracellular material to capture any aggressor agent. Elevated NETs release is associated with increased inflammatory response and related diseases, such as obesity. Chronic physical training is one of the main strategies to treat and prevent obesity. The relationship between physical training and NETs is still under study. The present review, followed by a bioinformatics analysis, demonstrates the meaningful connection between physical exercise, obesity, and NETs. The bioinformatics indicated TNF-α as a leading gene after the ontological analysis followed by positive-interleukin-6 regulation, chemokines, and inflammatory response regulation. The main results pointed to a relevant regulatory effect of physical training on NETs release, indicating physical exercise as a possible therapeutic target on modulating NETs and inflammation.

The present article reviews the effects of the textile in the wound healing process, as well as the availability of these products in the market. A brief description of applications is given based on the literature obtained from searching the scientific databases, besides the data obtained from secondary sources, like books and congress proceedings. The historical context of the textiles used in wounds, their general characteristics, particularities in the healing process, and incorporation of new technologies are discussed. It was evidenced that the textiles and associated technologies might influence directly or indirectly the stimulation of collagen, cell migration, angiogenesis, and reduction of pro-inflammatory factors and fibroblasts. However, the mechanisms by which the textiles act in the healing process are not well established in the literature. The interaction among textile engineering, biotechnology, medicine, and pharmacology is essential for the improvement and development of new products with better efficiency and accessibility.

Diet macronutrient heterogeneity hinders animal studies' data extrapolation from metabolic disorders to human diseases.The present study aimed to evaluate different fat-diet compositions' effect on inducing lipid/glucose metabolism alterations in mice.Swiss male mice were fed for 12 weeks with five different diets: Standard Diet (ST), American Institute of Nutrition 93 for growth (AIN93G) high-butter/high-sugar (HBHS), high-lard/high-sugar (HLHS), and high-oil/high-sugar diet (soybean oil) (HOHS). Several parameters, such as serum biochemistry, histology, and liver mRNA expression, were accessed.The main findings revealed that the HLHS diet dramatically altered liver metabolism inducing hepatic steatosis and increased total cholesterol, triglycerides, VLDL, increasing liver CCAAT/enhancer binding protein (CEBP-α), Acetyl-CoA carboxylase (ACC) and Catalase (CAT) mRNA expression. Moreover, the HLHS diet increased glucose intolerance and reduced insulin sensitivity.High-fat/high-sugar diets are efficient to induce obesity and metabolic syndrome-associated alterations, and diets enriched with lard and sugar showed more effective results.

Elevated peripheral expression of homocysteine (Hcy) is associated with an increased risk of coronary heart disease and stroke, diabetes, and cancer. It is also associated with cognitive impairment as it has been reported that high levels of Hcy cause cognitive dysfunction and memory deficit. Among several etiological factors that contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Hcy seems to directly contribute to the generation of neurotoxicity factors. This study aims to hypothesize the molecular mechanism by which exercise can reduce the risk of neurological complications promoted by hyperhomocysteinemia (HHcy), and discuss how exercise could reduce the risk of developing AD by using bioinformatics network models. According to the genes network, there are connections between proteins and amino acids associated with Hcy, exercise, and AD. Studies have evidenced that exercise may be one of several processes by which acid nitric availability can be maximized in the human body, which is particularly important in reducing cell loss and tau pathology and, thereby, leading to a reduced risk of complications associated with HHcy and AD.

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 Background: Diabetes mellitus (DM) is a public health problem, which requires enhanced self-care in order to avoid complications. However, cognitive impairment can reduce these abilities and may affect health literacy (HL) of patients in terms to understand and apply information. Therefore, this study evaluated the correlation between cognitive condition and HL related to medication adherence, physical activity and nutritional status among people living with DM. Methods: a cross-sectional study was carried out among elderly people (≥ 60 years old) with DM. The cognitive condition was evaluated using the Mini-Mental State Examination (MMSE) and the HL using the following questionnaires: Literacy Assessment for Diabetes (LAD-60), Nutritional Literacy among People with Diabetes (NLD), Health Literacy on the Practice of Physical Activities among Diabetics (HLPPA - D), and Health Literacy regarding Drug Adherence among Diabetics (HLDA-D). Sociodemographic and biochemical profile was also evaluated. Spearman correlation was used (p

Purpose Leptin, an important hormone controlling energy homeostasis, has been linked to the pathogenesis of oral squamous cell carcinoma (OSCC). Evidence indicates that head and neck cancer patients undergoing radiotherapy show decreased leptin levels after radiotherapy treatment. Thus, we investigated, through phenotypic and molecular analyses, whether leptin can compromise the therapeutic effect of ionizing radiation and neoplastic behavior of OSCC cells. Methods The human OSCC-derived cell lines SCC9 and SCC4 were treated with human recombinant leptin and exposed to 6 Gy of irradiation. We performed the in vitro assays of cell migration, death, proliferation, and colony-forming ability. The reactive oxygen species (ROS) levels and proteome analysis by mass spectrometry were also conducted. Results Leptin was able to increase cell proliferation, migration, and colony-forming ability, despite the suppressive effect induced by irradiation. Furthermore, the leptin promoted a significant reduction of ROS intracellular accumulation, and increased expression of the cancer-related proteins, as ACTC1, KRT6A, and EEF2 in irradiated OSCC cells. Conclusions Our findings suggest that leptin impairs responsivity of OSCC cells to the ionizing radiation, reducing the suppressive effects of irradiation on the neoplastic phenotype, and increasing protein expression critical to carcinogenesis.

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 Non-alcoholic fatty liver disease (NAFLD) is currently considered an important component of metabolic syndrome (MetS). The spectrum of NAFLD includes conditions that range from simple hepatic steatosis to non-alcoholic steatohepatitis. NAFLD is correlated with liver-related death and is predicted to be the most frequent indication for liver transplantation by 2030. Insulin resistance is directly correlated to the central mechanisms of hepatic steatosis in NAFLD patients, which is strongly correlated to the imbalance of the renin–angiotensin system, that is involved in lipid and glucose metabolism. Among the emerging treatment approaches for NAFLD is the anti-hypertensive agent telmisartan, which has positive effects on liver, lipid, and glucose metabolism, especially through its action on the renin–angiotensin system, by blocking the ACE/AngII/AT1 axis and increasing ACE2/Ang(1–7)/Mas axis activation. However, treatment with this drug is only recommended for patients with an established indication for anti-hypertensive therapy. Thus, there is an increased need for large randomized controlled trials with the aim of elucidating the effects of telmisartan on liver disease, especially NAFLD. From this perspective, the present review aims to provide a brief examination of the pathogenesis of NAFLD/NASH and the role of telmisartan on preventing liver disorders and thus to improve the discussion on potential therapies.

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.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Objective: the increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. Subjects and methods: the present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. Results: the prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). Conclusions: we were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

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: because the impact of conditioned fear stress on apical bone resorption is unknown, the aim of the current studywas to use a rat model to evaluate the impact of conditioned fear stress on the bone resorption of inflammatory apical periodontitis lesions. Methods: twenty-five animals were divided into two groups. They underwent a surgical procedure in the first left lower molar tooth to expose the dental pulp and induce inflammatory apical periodontitis lesions through the retention of contamination (bacterial infection) during a 56-day period. The animals in the case group were stressed daily by using electrical stimuli (1.10 mA), whereas the animals in the control group were absent from the stressful stimuli (shocks). The open field test was performed to validate the stress methodology. The jaws were removed and collected for histological and radiographic analyses. Results: stressed animals presented increased levels of bone loss and inflammatory cells in the root apex in comparison with the control group (P = 0.0001). However, no radiographic differences were observed between the groups (P > 0.05). Conclusions: our results demonstrated that conditioned fear stress could modify a periapical lesion by increasing the size of bone loss there. Conditioned fear stress also increased the total number of inflammatory cells compared with the control group. Studies evaluating the impact of conditioned fear stress on human periapical inflammatory lesions should be encouraged.

Currently, angiotensin-(1-7) [Ang-(1-7)] is recognized as the main peptide on counteracting the angiotensin II (Ang II) effects in the renin-angiotensin system (RAS), with crucial metabolic relevance. While Ang II is increased in endocrine disorders such as obesity, diabetes, and dyslipidemia, important studies showed that augmented activation of angiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas axis is able to revert hormonal dysregulation improving insulin resistance, lipid metabolism and modulating insulin actions. The present chapter recapitulates new data indicating that the Ang-(1-7) is one of the most promising hormones on regulating endocrine diseases.

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

// Talita Antunes Guimaraes 1 , Lucyana Conceicao Farias 1 , Eliane Sobrinho Santos 1, 5 , Carlos Alberto de Carvalho Fraga 6, 7 , Lissur Azevedo Orsini 2 , Leandro de Freitas Teles 1 , John David Feltenberger 3 , Sabrina Ferreira de Jesus 1 , Marcela Goncalves de Souza 1 , Sergio Henrique Sousa Santos 4 , Alfredo Mauricio Batista de Paula 1 , Ricardo Santiago Gomez 2, * Andre Luiz Sena Guimaraes 1, * 1 Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil 2 Department of Clinical, Surgery and Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil 3 Texas Tech University Health Science Center, Lubbock, TX, USA 4 Institute of Agricultural Sciences, Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil 5 Instituto Federal de Educacao, Ciencia e Tecnologia do Norte de Minas Gerais (IFNMG), Aracuai, Minas Gerais, Brazil 6 Faculdades Integradas Pitagoras, Montes Claros, Minas Gerais, Brazil 7 Faculdades Unidas do Norte de Minas, Montes Claros, Minas Gerais, Brazil * These authors contributed equally to this work Correspondence to: Andre Luiz Sena Guimaraes, email: andreluizguimaraes@gmail.com Ricardo Santiago Gomez, email: rsgomez.ufmg@gmail.com Keywords: proliferation, oral cancer, metformin, PDH, LDH-A Received: March 21, 2016 Accepted: July 09, 2016 Published: July 26, 2016 ABSTRACT Background: Metformin is a biguanide, belonging to the oral hypoglycemic agents and is a widely used in the treatment of type 2 diabetes. Evidence indicate that Metformin inhibits cell proliferation in several human cancers and inhibits the Warburg phenomenon in tumor cells. Results: Low PDH levels were observed in OSCC, and Metformin promotes an increase in PDH levels in hypoxic conditions. Metformin also reduced HIF-1α mRNA and protein levels. Metformin demonstrated antiproliferative effects, inhibited migration, increased the number of apoptotic cells and increased the transcription of caspase 3. Objective: The present study aims to explore the effects of Metformin in hypoxic conditions. Specifically, we focused on pyruvate dehydrogenase (PDH), (hypoxia-inducible factor 1α) HIF-1α levels and the oral squamous cell carcinoma (OSCC) cell phenotype. Additionally, we also investigated a theoretical consequence of Metformin treatment. Methods: PDH levels in patients with OSCC and oral dysplasia were evaluated. Metformin was administered in vitro to test the effect of Metformin under hypoxic conditions. The results were complemented by Bioinformatics analyses. Conclusions: In conclusion, our current findings show that Metformin reduces HIF-1α gene expression and increases PDH expression. Metformin inhibits cell proliferation and migration in the OSCC cell line model. Additionally, Metformin enhances the number of apoptotic cells and caspase 3 levels. Interestingly enough, Metformin did not increase the mutant p53 levels under hypoxic conditions.

Obesity is a chronic multifactorial disease and is currently a public health problem. Maternal obesity during pregnancy is more dangerous as it impairs the health of the mother and future generations. Obesity leads to several metabolic disorders. Since white adipose tissue is an endocrine tissue, obesity often leads to disordered secretion of inflammatory, glycemic, lipid and renin-angiotensin system (RAS) components. The RAS represents a link between obesity and its metabolic consequences. Therefore, our goal was to evaluate the possible changes caused by a high-fat diet in RAS-related receptor expression in the uterus and placenta of pregnant mice and determine the underlying effects of these changes in the fetuses' body composition. Breeding groups were formed after obesity induction by high-fat (HF) diet. Dams and fetuses were euthanized on the 19th day of the gestational period. The HF diet effectively induced obesity, glucose intolerance and insulin resistance in mice. Fetuses born from HF dams showed increased body weight and adiposity. Both results were accompanied by increased AT1R expression in placenta and uterus together with increased angiotensin-converting enzyme expression in the uterus and a decreased expression of MAS1 in placenta of HF dams. These results suggest a link between RAS, maternal obesity induced by HF diet and the fetuses' body adiposity. This new path now can be more thoroughly explored.

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 Aims: the aim of the present study was to evaluate the oral resveratrol effects associated with diet and physical training changes on anthropometric and biochemical parameters. Main methods: 25 individuals aged from 30 to 60 years old; with Body Mass Index (BMI) ≥ 30 kg/m2 were included in the study. Following the primary evaluation (anthropometric and clinical), the patients were randomly divided into 2 groups: (1) Placebo: Physical activity program + Diet + Placebo; (2) Resveratrol: Physical activity program + Diet + Resveratrol (RVS) (250 mg/day) for three months. Anthropometric and biochemical parameters were evaluated at baseline and after the treatment period. Key findings: the main findings showed that the resveratrol supplementation improved total cholesterol (TC), High-density Lipoprotein cholesterol (HDL-c), Very-low density Lipoprotein cholesterol (VLDL-c), urea, creatinine and albumin serum levels. Significance: these findings indicate that this polyphenol may be an option to potentiate the beneficial effects induced by dietary and physical activity programs in the Metabolic Syndrome (MetS) treatment.

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 We have read with interest the recent review by Zbinden-Foncea et al. suggesting that high levels of cardiorespiratory fitness induced by prior exercise training may confer some innate immune protection against coronavirus disease (COVID-19) by attenuating the “cytokine storm syndrome” by modulating angiotensin-converting enzyme 2 (ACE2) effects. However, it is important to highlight that the benefic effects of physical exercise also involves the angiotensin-(1-7)/MAS1 proto-oncogene, GPCR receptor (MAS receptor; Mas) axis activation.

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.

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 Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.

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.

The global rise in obesity rates is alarming since this condition is associated with chronic low-grade inflammation and secondary comorbidities as glucose intolerance, cardiovascular disease and liver damage. Therefore, a lot of dietary approaches are proposed to prevent and to treat obesity and its associated disorders. Virgin coconut oil (VCO) is well known as a functional food due to its significant amounts of medium-chain triglycerides. This study aimed to evaluate the effect of VCO on adiposity, metabolic and inflammatory dysfunctions induced by a high-refined carbohydrate-containing (HC) diet in mice. Male BALB/c mice were divided into two groups and fed with control (C) or HC diet to induce obesity for eight weeks. At the 9th week mice fed with HC diet were randomly regrouped into four groups, and were kept this way until the 12th week, as following: (i) HC diet alone or HC diet supplemented with three different VCO doses (ii) 1000 mg/kg, (iii) 3000 mg/kg and (iv) 9000 mg/kg. Regardless of the concentration used, VCO supplementation promoted lower adiposity and also improvement in glucose tolerance, lower serum glucose and lipid levels and decreased hepatic steatosis. Moreover, VCO intake induced a lower inflammatory response due to decreased number of leukocytes and TNF-α and IL-6 concentrations in adipose tissue, as well as reduced counts of total leukocytes, mononuclear and polymorphonuclear circulating cells. Our data showed that VCO can be considered as an interesting potential dietary approach to attenuate obesity and its metabolic and inflammatory alterations.

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: hypertension is a clinical condition of multifactorial etiology that imposes serious harm to the health of elderly individuals. Despite the fact that cardiovascular disorders influence the development of hypertension in this age group, several other genetic and environmental factors have been described in the literature, including the polymorphic variant of the angiotensin-converting enzyme (ACE) gene and the distribution of body fat. Objective: to assess the prevalence of hypertension among elderly individuals and its possible correlation with the I/D polymorphic variant of the ACE gene and other associated risk factors. Methods: population-based study using a hierarchical model and including 387 elderly individuals residing in the urban area of Ibiaí (Minas Gerais, Brazil). Results: on statistical analysis, the polymorphic variant of the ACE gene was not associated with hypertension (p = 0.316). On the other hand, there was a significant association between hypertension and the variables female sex, absence of a partner, consumption of more than one portion of salt per day, and changes in body mass index and waist-to-hip ratio. Conclusion: although the polymorphic variant of the ACE gene showed no influence on the prevalence of hypertension in elderly individuals, some variables such as individual, socioeconomic, metabolic, and behavioral habits were associated with this condition. Fundamento: a hipertensão arterial sistêmica (HAS) é uma condição clínica de etiologia multifatorial e de sério agravo à saúde do idoso. Apesar das alterações cardiovasculares influenciarem o desenvolvimento da HAS nesta faixa etária, vários outros fatores genéticos e ambientais têm sido descritos na literatura, incluindo a variante polimórfica do gene da enzima conversora da angiotensina (ECA) e a distribuição da gordura corporal. Objetivo: avaliar a prevalência da HAS entre idosos e sua possível correlação com a variante polimórfica I/D do gene da ECA e outros fatores de risco associados. Métodos: estudo de base populacional com 387 idosos residentes na zona urbana de Ibiaí (MG, Brasil) utilizando, para tal, um modelo hierarquizado. Resultados: à análise estatística, a variante polimórfica do gene da ECA não se mostrou associada à HAS (p = 0,316). Por outro lado, mostraram associação significativa com a HAS os fatores: sexo feminino, ausência de companheiro, consumo de mais de uma porção de sal ao dia e alterações nos índices de massa corporal e na relação cintura-quadril. Conclusão: apesar da variante polimórfica da ECA não ter mostrado influência sobre a prevalência de HAS em idosos, algumas variáveis individuais, socioeconômicas, metabólicas e de hábitos comportamentais mostraram associação com esta condição.

With the present PPL Special Issue on the “Renin-angiotensin system: Role in chronic diseases”, we have attempted to cover some of the chronic diseases associated with key components of RAS, and to address the most important aspects of its functional output. Furthermore, we aimed to include new tendencies and advances, some of them still controversial, but always contemplating what we consider as hot-points for research progress, drug developments and new treatments in a near future. The articles of the Special Issue bring several chronic diseases related to different organs and with various systemic effects.

The renin-angiotensin system (RAS) is now recognized as an important modulator of body metabolic processes. The discovery of angiotensin-converting enzyme 2 (ACE2) has renewed interest in the potential therapeutic role of RAS modulation. Recent studies have pointed out the importance of the local balance between ACE/Ang-II/AT1 and ACE2/Ang-(1-7)/Mas arms to avoid liver metabolic diseases. Furthermore, non-alcoholic fatty liver disease is an increasing health problem that includes a spectrum of hepatic steatosis, steatohepatitis and fibrosis. Some new studies revealed that RAS imbalance appears to promote hepatic fibrogenesis; while the activation of ACE2/Ang-(1-7)/Mas counter-regulatory axis is able to prevent liver injuries. In this context, the aim of the present review is to discuss the importance of RAS in the development and prevention of liver disease. AT1 receptor activation by Ang II induces hepatic stellate cell contraction and proliferation, causes oxidative stress, endothelial dysfunction, cell growth and inflammation. In addition, both AT1 blocker administration and ACE inhibitors lead to a reduction in inflammation and improvement of hepatic fibrosis. Conversely, Ang-(1-7) infusion reduces fibrosis and proliferation mainly by suppression of hepatic stellate cell activation; Mas receptor antagonism aggravates liver fibrosis and severe liver steatosis. In conclusion, the use of ACE/Ang II/AT1 axis inhibitors associated with ACE2/Ang(1-7)/Mas axis activation is a promising new strategy serving as a novel therapeutic regimen to prevent and treat chronic liver diseases as well as acute liver injury.

Low angiotensin-(1-7) (Ang-(1-7)) concentration is observed in some cardiovascular diseases and exercise training seems to restore its concentration in the heart. Recently, a novel formulation of an orally active Ang-(1-7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronically administered in experimental models of cardiovascular diseases. The present study examined whether chronic administration of HPB-CD/Ang-(1-7) produces beneficial cardiovascular effects in spontaneously hypertensive rats (SHR), as well as to compare the results obtained with those produced by exercise training. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1-7) (corresponding to 30μgkg(-1)day(-1) of Ang-(1-7)) by gavage, concomitantly or not to exercise training (treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis in the heart were performed. Chronic HPB-CD/Ang-(1-7) decreased arterial blood pressure (BP) and heart rate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure, restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index in SHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heart and vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability. Overall results were similar to those obtained with exercise training. These results show that chronic treatment with the HPB-CD/Ang-(1-7) inclusion compound produced beneficial effects in SHR resembling the ones produced by exercise training. This observation reinforces the potential cardiovascular therapeutic effect of this novel peptide formulation.

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.

Background and Objective Recent evidence suggests that the use of fluoxetine could reduce periodontal disease severity. However, the effect of fluoxetine on periodontal disease has not been tested in the context of conditioned fear stress (CFS). We hypothesized that inhibition of chronic stress by fluoxetine might decrease the levels of bone loss in periodontal disease. The aim of the present study was to analyze the effect of fluoxetine on bone loss in chronic periodontitis. Material and Methods Fourteen Wistar rats were submitted to ligature-induced periodontal disease and divided into four groups (A–D). Groups A (n = 3) and B (n = 4) were not stressed, while Groups C (n = 3) and D (n = 4) were submitted to a CFS paradigm for 38 d. Daily fluoxetine (20 mg/kg) was administered to Groups B and D from day 20 to day 39, at which point the rats were submitted to an open field test and killed on day 40. Mandibles were removed for histological and immunohistochemical analyses. Results Stress was associated with a higher level of bone loss in Group C compared with Group A. Additionally, no differences in bone loss were observed among Groups A, B and D. Conclusion We showed that stress is associated with the progression of bone loss in a CFS model in rats and that fluoxetine treatment reduces the bone loss.

Aims: We hypothesized that a high-carbohydrate diet affects the cardiac performance by interfering in the metabolic steps involved in energy transfer in this organ. To verify this, we investigated the myocardial utilization of different substrates and contractile function in rats fed a high-carbohydrate diet, under normal flow and ischemia. Methods and Results: Male Wistar rats were fed over 9 days with standard (39.5% carbohydrate, 8% fiber) or high-carbohydrate diet (58% carbohydrate) and, afterwards, their cardiac function was examined using isolated heart preparations. The high-carbohydrate diet decreased the activity of the lipoprotein lipase, utilization of fatty acids, expression of the gene of peroxisome proliferator-activated receptor α and its target enzymes. In addition, decreased GLUT4 mass, glucose uptake, glycogen content and glycolytic intermediates were also observed. High-carbohydrate hearts displayed weaker activation of the glycolytic pathway during ischemia, according to minor production of lactate, in relation to control hearts. The functional impairment caused by high-carbohydrate diet shown by the decrease in the ventricular systolic strength, +d T/d t and −d T/d t was, at least in part, due to the low availability of adenosine triphosphate (ATP). Conclusion: Our data suggest that a high-carbohydrate diet can damage myocardial contractile function by decreasing the cardiac utilization of glucose and fatty acids and, consequently, the ATP pool.

In the present study we investigated the effects of physical training on plasma and cardiac angiotensin(1-7) [Ang(1-7)] levels. In addition, possible changes in expression of the Ang(1-7) Mas receptor in the heart were also evaluated. Normotensive Wistar rats and spontaneously hypertensive rats (SHR) were subjected to an 8 week period of 5% overload swimming training. Blood pressure was determined by a tail-cuff system. Heart and left ventricle weights and cardiomyocyte diameter were analysed to evaluate cardiac hypertrophy. Radioimmunoassay was used to measure angiotensin levels. Expression of Mas was determined by semi-quantitative polymerase chain reaction, immunofluorescence and Western blotting. Physical training induced cardiac hypertrophy in Wistar rats and SHR. A significant decrease of plasma angiotensin II (Ang II) levels in both strains was also observed. Strikingly, trained SHR, but not trained Wistar rats, showed a twofold increase in left ventricular Ang(1-7) levels. No significant changes were observed in plasma Ang(1-7) and left ventricular Ang II concentrations in either strain. Furthermore, Mas mRNA and protein expression in left ventricle were substantially increased in trained SHR. The physical training protocol used did not change blood pressure in either strain. These results suggest that the beneficial effects induced by swimming training in hypertensive rats might include an augmentation of Ang(1-7) and its receptor in the heart.

Cardiovascular diseases can be considered the most important cause of death in diabetic population and diabetes can in turn increase the risk of cardiovascular events. Inflammation process is currently recognized as responsible for the development and maintenance of diverse chronic diseases, including diabetes and atherosclerosis. Considering that adipose tissue is an important source of adipokines, which may present anti and proinflammatory effects, the aim of this review is to explore the role of the main adipokines in the pathophysiology of diabetes and atherosclerosis, highlighting the therapeutic options that could arise from the manipulation of these signaling pathways both in humans and in translational models.

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 Recent studies show that skipping breakfast is associated with an increased risk of obesity, diabetes and cardiovascular diseases. In this context, this study evaluated 400 patients from the Brazilian health service who had their nutritional status defined based on the body mass index and were classified as physically active or insufficient active. The energy intake and macronutrients was also assessed by a 24-hour dietary recall where the association of overweight/obesity with the investigated variables was evaluated using chi-square, Student's t test and multivariate analysis (p < 0.05). The main results showed that more than half of the studied population have the habit of omitting breakfast (55.8%), and among those, 81.2% were overweight/obese (p < 0.0001). Almost three-fourths of these individuals consumed no more than 4 meals a day (73.0%), and regarding this meal frequency/day, 78.8% of the individuals who reported having 4 meals or less a day were overweight/obese compared with 57.8% who reported as having 5-6 meals/day (p < 0.0001). The individuals who reported to omit breakfast had a higher chance of being overweight compared with those who had this habit (OR 2.20; 95% CI 1.40-3.60) and the chance of the physically insufficient active individuals to be overweight/obese was 2.9 times higher when compared to the active individuals (p < 0.0001). Our findings suggest that regular breakfast consumption may decrease overweight and obesity risk.