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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.

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.

Background:: The microbiome is now known for its important role in whole-body homeostasis. A dysbiosis of the normal microbiota is correlated with metabolic disorders. In this sense, the search for compounds able to modulate the microbiome is needed. Resveratrol, a natural compound found in grapes seems to be a promising candidate. Objective:: In this study, our motivation was to evaluate the effects of the association between Resveratrol and Lactococcus lactis, a probiotic, on the composition of the gastrointestinal microbiota and body weight of mice. Methods:: Twenty female mice were divided into 4 groups: (1) standard diet, (2) standard diet plus Lactococcus lactis, (3) standard diet plus resveratrol, and (4) standard diet plus Lactococcus lactis and resveratrol. At the end of the treatment period, samples of blood, mucus, stomach, and small and large intestines were collected for analysis. Total levels of Immunoglobulin A and Immunoglobulin E, Lac+ and Lac- bacteria and Lactobacillus were measured. Results:: The main results indicate that the association between resveratrol and probiotics was able to decrease mice body weight, as compared to the other groups, in addition to decrease the number of Lac- bacteria and increasing the number of Lac+ bacteria. The levels of secretory IgA were also decreased, compared to the animals treated with only probiotics or resveratrol. Conclusion:: We observed potential synergism between Resveratrol and Lactococcus lactis mainly in modulating the stomach and intestinal microbiota.

Acosmium dasycarpum (Vog.) Yakovlev, is a Brazilian medicinal plant, belonging to the Fabaceae family known as "Unha D'anta", exclusively found in the Cerrado (Brazilian Savanna) region, and has already shown tranquilizing, hypotensive, antineoplastic and antiseptic activities reported by traditional medicine and scientific evidences. Considering that overweight and obesity are an increasing worldwide health problem, the present study aimed to investigate the anti-obesity effect of bark powder and the dichloromethane extract of A. dasycarpum compared to the most abundant bioactive component (lupeol) using an obese mice model induced by a high-fat diet (HFD). The extracts derived from root bark of A. dasycarpum were characterized (phytochemical screening and GC–MS analysis) and their biological effects tested. After obesity inducement, Swiss male mice were treated with bark root powder or dichloromethane extract or lupeol (all treatments with 10 mg/1000 g/body weight dose) during 14 days. Oral glucose tolerance, insulin sensitivity, lipid profile, histology, ultrasound imaging and adipogenic genes expression were evaluated. The main results showed that A. dasycarpum root bark powder and dichloromethane extract reduced body weight and adiposity as evidenced by histology and ultrasound imaging. We also verified an improved glycemic and lipid profiles by reducing triglycerides, LDL and increasing HDL. The A. dasycarpum treatment suppressed the expression of CCAAT/enhancer-binding protein (C/EBPα), fatty acid translocase (FAT), and stearoyl coenzyme A desaturase-1 (SCD-1) adipogenic genes when compared to the obese control group. In conclusion, A. dasycarpum root bark showed a potential to be an accessible adjuvant treatment for obesity.

Background and Aim: Broiler meat is susceptible to lipid oxidation due to its high content of unsaturated fatty acids, especially when stored for a long time. Concerning with that problem, we can add natural compounds to the animal feed, as the plant essential oils, which have antioxidant, antimicrobial, and antifungal activities. The objective of this study was to evaluate the antioxidant activity, fatty acid profile, and chemical composition of the meat of broilers fed with diets containing different essential oil, including lemongrass (Cymbopogon flexuosus) and pedestrian tea (Lippia aff. rotundifolia). Materials and Methods: The experimental design used was a 4×4 factorial scheme (storage time×diets), and each treatment was repeated thrice. The treatments were applied as negative control (without antimicrobial); positive control (ration supplemented with 10 ppm of enramycin and 42 ppm of salinomycin), lemongrass (ration with 120 mg of essential oil of lemongrass for each kilogram of live weight of the animals), and pedestrian tea (ration with 120 mg of essential oil of pedestrian tea for each kilogram of live weight of the animals). Storage was performed after slaughter and evaluated monthly for 4 months. Results: The inclusion of lemongrass oil and pedestrian tea in the broiler diet did not change the ether extract content of the meat sample obtained from thigh and drumstick. The storage time promotes an increase in the moisture loss of the meat from the 2nd month in all treatments. There was an interaction between the additive and storage time for moisture loss. In the 2nd month of storage, the meat from broilers fed the antibiotic-containing feed had a lower moisture loss than those from broilers in the other treatment groups. The fatty acid profile did not differ statistically between the different treatment groups. The inclusion of additives in the food dropped the lipid oxidation at the 2nd month of storage. From the 3rd month, however, only the essential oils showed antioxidant effect. Conclusion: Antioxidant activity was positive for treatments that included essential oils. The lemongrass oil and pedestrian tea can be used as antioxidant additives in broiler diets to improve the oxidative stability of thigh-drumstick meat during storage. The results of the study suggest a good prospective for further research with profitability of usage essentials oils examined, for their economical application as feed components in broiler nutrition.

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.

We have previously demonstrated the presence of Angiotensin (Ang)-(1-7) in rat ovary homogenates and its stimulatory effect on estradiol and progesterone production. The present study was undertaken to identify the cellular localization of Ang-(1-7) and its receptor Mas in the rat ovary in the different phases of the estrous cycle. Ang-(1-7) and Mas were localized by immunohistochemistry and Mas mRNA expression was assessed by RT-PCR. Immunostaining for both Ang-(1-7) and Mas was found in all phases of the estrous cycle, particularly in the thecal and interstitial cells, as well as in regressing corpora lutea. However, granulosa cells were positive only in antral and preovulatory follicles at proestrus and estrus phases. This pattern contrasted with the distribution of the octapeptide Ang II, which was abundant in granulosa but not in theca cells. In addition, the expression of Mas mRNA was demonstrated in all estrous cycle phases. Angiotensin-converting enzyme activity did not vary between estrous cycle phases, whereas prolyl endopeptidase activity was significantly higher in diestrus and neutral endopeptidase activity was significantly higher in metestrus. These data provide the first evidence that new RAS components are dynamically expressed in the ovary across the rat estrous cycle. Further functional studies should clarify the role of Ang-(1-7) signaling through Mas receptor in the regulation of ovarian physiology.

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.

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.

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.

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.

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.

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.

Background: Brazilian flora is rich in plants with medicinal properties, which though popular, has contributed to the development of a range of phytotherapic products that use plants to treat and cure diseases. However, studies that use Brazilian plants in the treatment of metabolic disorders are still scarce in the literature. Objective: The aim of this study was to analyze the effect of hepatotoxicity Lafoensia pacari on the metabolism of mice with obesity induced by a high-fat diet and to verify the phytochemical difference between the Lafoensia pacari bark of the trunk, leaves, and branches. Methods: The plant material was collected from April to May in the municipality of Bonito de Minas, MG, Brazil. Qualitative tests for the presence of secondary metabolite classes were performed for leaves, branches and bark of the trunk. Through histological analysis, we evaluated hepatocytes and cell lesions in the liver. Results: The comparative phytochemical analysis of the plant did not reveal alterations between the different plant parts. The phytochemical test showed that is preferable to use the leaves to make the extract to be applied, aiming to reduce the plant aggression. After treatment, greater changes were observed in the animals that received the high-fat diet and the hydroethanolic extract; the levels of AST, ALT, albumin and creatinine that were increased, thus demonstrating a possible toxicity. There were no significant differences in body weight. In the histological analysis, the animals without plant treatment displayed decreased liver weight and reduction in the inflammatory infiltrate. Conclusion: We conclude that Lafoensia pacari should be better evaluated for oral consumption and may cause liver damage.

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.

The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms. Nuclear sirtuins (SIRT 1, 2, 6 and 7) in particular may play an important role in the regulation of inflammatory responses. In the present review, we assessed the roles of nuclear sirtuins in inflammatory reactions: SIRT1 has been shown to suppress NF-κb activity, the master regulator of cellular inflammatory response, decrease COX-2 and iNOS production, and increase antioxidant gene expression that suppressed inflammation. SIRT2 activity included the deacetylation of p65 subunit of NF-κβ and RIP-1, while SIRT6 has been shown to interact with p65/RelA bound to the NF-κβ promoter region and repress transcriptional activity. Furthermore, recent studies have shown that the absence of SIRT7 produced an increase in inflammation, illustrating that SIRT7 also functioned to decrease inflammation. Given their significant roles in the regulation of chronic inflammation, nuclear sirtuins represent potential therapeutic targets in the control of chronic inflammatory diseases.

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.

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 Whey is a by-product of the dairy industry of great importance due to its high nutritional value, and can be used for the manufacture of fermented dairy drinks which, combined with fruit, increase the nutritional value and add characteristic flavors. Therefore, a fermented dairy beverage with caja-mango pulp (Spondias dulcis) was elaborated and its nutritional information as well as the physicalchemical stability were evaluated during storage. The results showed that the nutritional information met the requirements stipulated by the Brazilian legislation. The physical-chemical stability of the dairy fermented drink in terms of pH, acidity, syneresis and sedimentation was influenced by the storage time, possibly associated with uncontrolled factors in this study, such as the initial and final dairy culture concentration of the processed product, protein biodegradation during storage and low solids contents. It is concluded that the elaborated drink constitutesa food source of several nutrients, and may complement the daily diet of children, adolescents and adults, supplying nutritional deficiencies. Key words: whey, dairy industry, nutritional value, Spondias dulcis. O soro lácteo é um subproduto da indústria de laticínios de grande importância devido ao seu alto valor nutritivo, podendo ser utilizado para fabricação de bebida láctea fermentada que, associada a frutas, aumenta o valor nutricional e agrega sabores característicos. A partir disso, foi elaborada uma bebida láctea fermentada adicionada de polpa de cajá-manga (Spondias dulcis), sendo avaliada sua informação nutricional bem como a estabilidade físico-química, durante o armazenamento. Os resultados mostram que a informação nutricional atendeu os requisitos estipulados pela legislação brasileira. A estabilidade físico-química da bebida, quanto aos parâmetros analisados de pH, acidez, sinerese e sedimentação, sofreu influência pelo o tempo de armazenamento, possivelmente, associados a fatores não controlados neste estudo como a concentração de cultura láctea iniciadora e final do produto elaborado, a biodegradação de proteínas durante a estocagem e baixos teores de sólidos. Conclui-se que a bebida elaborada constitui um alimento fonte de diversos nutrientes, e poderá complementar a alimentação diária de crianças, adolescentes e adultos, suprindo as carências nutricionais.

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.

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 generation of large volumes of waste by industrial processes has become an object of study because of the necessity to characterize the composition of residues in order to suggest appropriate treatments and to minimize adverse environmental impacts. We performed analyses of total fixed and volatile solids, moisture, and chemical oxygen demand (COD). We found high organic matter content. We also measured physicochemical characteristics, including corrosivity, reactivity, and toxicity. Sewage sludge showed levels of chloride and sodium above the maximum allowed limits. These data suggest the potential for anaerobic digestion as a treatment option for sewage sludge and for its use as a biofertilizer.

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.

This study aimed at investigating the effect of fermented dairy beverage with clove essential oil (CEO) on the levels of reactive oxygen species (ROS) through endogenous enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). For this, bioinformatic analysis was performed using the Genecards and String platforms. Headspace was used to analyze and confirm the compounds at low concentrations. Antioxidant activity was analyzed using the DPPH free radical sequestration method. For analysis of antioxidant activity, twenty-four male Swiss mice were divided into three groups and submitted histopathological analysis, analysis of CAT, SOD,GPx transcripts, and CAT and SOD enzyme activity in visceral adipose tissue were evaluated.The leader genes found were PIK3CD, PIK3CB, AKT1, and PIK3CA, as they had the highest WNL values. The beverage containing CEO showed higher antioxidant activity, with free radical scavenging capacity above 80%. In the in vivo analyses, it was possible to verify a reduction in the average adipocyte area size (μm2) between the groups that received fermented dairy beverage. Although functional studies have shown that the antioxidant enzymes, CAT and SOD, showed similar concentrations in visceral adipose tissue of the three groups, the expression levels of GPx1, CAT, and SOD were higher in group 2. Surprisingly, the group 3, that received the fermented dairy beverage with CEO had the lowest SOD concentration (p

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.

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.

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.

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.

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.

The purpose of the current study was to use immune-inspired algorithm ClonALG whose performance is increased by using the Kohonen neural network training algorithm (Immune/Neural approach), to characterize the nature of salivary gland neoplasms (SGNs). The leader gene approach in order to identify biomarkers for SGNs. Extensive data were obtained for each of the 35 types of neoplasms. The gene leaders for each type of SGN were identified in a table and then divided according to the two different methods: K-means clustering and Immune/Neural approach. Genes related to SGNs were identified using PubMed, OMIM and Genecards databases. A bioinformatics algorithm was then applied, and the STRING database was employed to build networks of protein–protein interactions for each nature of an SGNs. The weighted number of links (WNL) and total interactions score (TIS) values were then obtained. Finally, the genes were clustered, and the gene leaders were identified using the K-means clustering method and the Immune/Neural approach.

Made available in DSpace on 2022-04-29T08:45:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-15 White adipose tissue (WAT) dysfunction and obesity are a consequence of a low-grade inflammation state. These WAT irregularities could result from abnormal metabolic renin-angiotensin system (RAS) control. Recently, tributyltin (TBT) has been found to play a critical role in these metabolic irregularities. However, TBT actions on the WAT-RAS functions are not currently well understood. In this study, we assessed whether TBT exposure resulted in metabolic syndrome (MetS) development and other metabolic complications as a result of abnormal modulation of WAT-RAS pathways. TBT (100 ng/kg/day) was administered to adult female Wistar rats, and their WAT morphophysiology and adipokine profiles were assessed. We further assessed the expression of Angiotensin-II receptor proteins (AT1R and AT2R) and proteins involved in downstream pathways mediating inflammation and adipogenesis modulation. TBT-exposed rats exhibited increases in body weight and adiposity. TBT rats present dyslipidemia and insulin resistance, suggesting MetS development. TBT promoted WAT inflammatory infiltration, AT1R protein overexpression and reduced Angiotensin-(1–7) expression. These TBT WAT abnormalities are reflected by NFκB activation, with higher adipokine levels (leptin, TNF-α and IL-6) and overexpression of AKT, ERK, P38, FAS and PPARγ protein. In vitro, TBT exposure stimulates lipid accumulation, reduces AT2R protein expression, and increases leptin, AKT and ERK protein expression in 3T3L1 cells. These findings suggest that TBT exposure participates in MetS development via the improper function of WAT-RAS metabolic control. Department of Morphology Healthy Sciences Center Federal University of Espírito Santo Department. of Food Science Faculty of Pharmacy Federal University of Minas Gerais Department of Pharmacology Biological Sciences Institute Federal University of Minas Gerais Department of Internal Medicine Botucatu School of Medicine University of São Paulo State Dept. of Basic Nursing Nursing School Federal University of Minas Gerais Health Science Graduate Program UNIMONTES Institute of Agricultural Sciences Food Engineering College Federal University of Minas Gerais Laboratório de Endocrinologia e Toxicologia Celular Programa de Pós-Graduação em Ciências Fisiológicas/CCS Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468, Prédio do básico I, sala 5

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 FAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro For many years lactate was seen as a metabolite from glucose metabolism. However, since the last century researchers have shown that this molecule has an important role on liver, muscle, and brain metabolism. Lactate traffics along whole body mediating many biological processes depending on specific situations. For example, glucose is the main substrate used during exercise but lactate released by striated skeletal muscle is used by own muscle as secondary fuel. On the other hand, neuronal firing in the brain is almost totally lactate-dependent. In addition, lactate has an important role on BDNF-mediated neuroplasticity. As this molecule has a pleiotropic role in the body, it was called as “lactormone” in 2009. Here we show basic concepts on peripheral and central metabolism and discuss neurobiological pathways of lactate, including an alternative hypothesis on lactate released during exercise.