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INTRODUCTION: Food intake biomarkers are used to estimate dietary exposure; however, selecting a single biomarker to evaluate a specific dietary component is difficult due to the overlap of diverse compounds from different foods. Therefore, combining two or more biomarkers can increase the sensitivity and specificity of food intake estimates. OBJECTIVE: This study aimed to evaluate the ability of metabolite panels to distinguish between self-reported fruit consumers and non-consumers among participants in the Longitudinal Study of Adult Health. MATERIALS AND METHODS: A total of 93 healthy adults of both sexes were selected from the Longitudinal Study of Adult Health. A 24-h dietary recall was obtained using the computer-assisted 24-h food recall GloboDiet software, and 24-h urine samples were collected from each participant. Metabolites were identified in urine using liquid chromatography coupled with high-resolution mass spectrometry by comparing their exact mass and fragmentation patterns using free-access databases. Multivariate receiver operating characteristic curve (ROC) analysis and partial least squares discriminant analysis were used to verify the ability of the metabolite combination to classify daily and non-daily fruit consumers. Fruit intake was identified using a 24 h dietary recall (24 h-DR). RESULTS: Bananas, grapes, and oranges are included in the summary. The panel of biomarkers exhibited an area under the curve (AUC) > 0.6 (Orange AUC = 0.665; Grape AUC = 0.622; Bananas AUC = 0.602; All fruits AUC = 0.679; Citrus AUC = 0.693) and variable importance projection score > 1.0, and these were useful for assessing the sensitivity and predictability of food intake in our population. CONCLUSION: A panel of metabolites was able to classify self-reported fruit consumers with strong predictive power and high specificity and sensitivity values except for banana and total fruit intake.
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Biomarcadores , Frutas , Metabolômica , Humanos , Feminino , Masculino , Biomarcadores/urina , Frutas/metabolismo , Frutas/química , Metabolômica/métodos , Pessoa de Meia-Idade , Adulto , Estudos Longitudinais , Brasil , Dieta , Idoso , Cromatografia Líquida/métodosRESUMO
BACKGROUNDS AND AIMS: Childhood obesity is increasing substantially across the world. The World Obesity Federation (WOF) and World Health Organization (WHO) predicted that in 2030 > 1 billion people will be obese, and by 2035 over 4 billion will reach obesity worldwide. According to WHO, the world soon cannot afford the economic cost of obesity, and we need to act to stop obesity acceleration now. Data in the literature supports that the first 1000 days of life are essential in preventing obesity and related adversities. Therefore, using basic research, the present a study that focuses on the immediate effect of overnutrition and serotonin modulation during the lactation period. METHODS: Using a neonatal overfeeding model, male Wistar rats were divided into four groups based on nutrition or serotonin modulation by pharmacological treatment up to 22 days of life. Cellular and mitochondrial function markers, oxidative stress biomarkers and mRNA levels of hedonic and homeostatic genes were evaluated. RESULTS: Our data showed that overfeeding during lactation decrease NAD/NADH ratio, citrate synthase activity, and increase ROS production. Lipid and protein oxidation were increased in overfed animals, with a decrease in antioxidant defenses, we also observe a differential expression of mRNA levels of homeostatic and hedonic genes. On the contrary, serotonin modulation with selective serotonin reuptake inhibitors treatment reduces harmful effects caused by overnutrition. CONCLUSION: Early effects of overnutrition significantly affect the prefrontal cortex at molecular and cellular level, which could mediate obesity-related neurodegenerative dysfunction.
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Hipernutrição , Obesidade Infantil , Criança , Humanos , Ratos , Animais , Feminino , Masculino , Sobrepeso , Ratos Wistar , Serotonina , Hipernutrição/complicações , Hipernutrição/metabolismo , Ingestão de Alimentos , Córtex Pré-Frontal/metabolismo , RNA MensageiroRESUMO
BACKGROUND: The capacity of an individual to respond to changes in food intake so that postprandial metabolic perturbations are resolved, and metabolism returns to its pre-prandial state, is called phenotypic flexibility. This ability may be a more important indicator of current health status than metabolic markers in a fasting state. AIM: In this parallel randomized controlled trial study, an energy-restricted healthy diet and 2 dietary challenges were used to assess the effect of weight loss on phenotypic flexibility. METHODS: Seventy-two volunteers with overweight and obesity underwent a 12-wk dietary intervention. The participants were randomized to a weight loss group (WLG) with 20% less energy intake or a weight-maintenance group (WMG). At weeks 1 and 12, participants were assessed for body composition by MRI. Concurrently, markers of metabolism and insulin sensitivity were obtained from the analysis of plasma metabolome during 2 different dietary challenges-an oral glucose tolerance test (OGTT) and a mixed-meal tolerance test. RESULTS: Intended weight loss was achieved in the WLG (-5.6 kg, P < 0.0001) and induced a significant reduction in total and regional adipose tissue as well as ectopic fat in the liver. Amino acid-based markers of insulin action and resistance such as leucine and glutamate were reduced in the postprandial phase of the OGTT in the WLG by 11.5% and 28%, respectively, after body weight reduction. Weight loss correlated with the magnitude of changes in metabolic responses to dietary challenges. Large interindividual variation in metabolic responses to weight loss was observed. CONCLUSION: Application of dietary challenges increased sensitivity to detect metabolic response to weight loss intervention. Large interindividual variation was observed across a wide range of measurements allowing the identification of distinct responses to the weight loss intervention and mechanistic insight into the metabolic response to weight loss.
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Dieta , Sobrepeso , Redução de Peso , Sobrepeso/dietoterapia , Sobrepeso/metabolismo , Humanos , Masculino , Feminino , Adulto , Composição Corporal , Tecido Adiposo , Insulina/metabolismo , BiomarcadoresRESUMO
Metabolic-associated fatty liver disease (MAFLD) is a condition characterized by excessive accumulation of triglycerides in hepatocytes, currently considered the number one cause of chronic liver disease. MAFLD is strongly associated with obesity, type 2 diabetes, hyperlipidaemia, and hypertension. Emphasis has been placed on the use of green tea (GT), produced from the Camellia sinensis plant, rich in antioxidants as polyphenols and catechins, on obesity and MAFLD treatment/prevention. Studies carried out in rodent models housed at a standard temperature (ST, 22°C) are being questioned as ST is a determining factor on generating changes in the physiology of immune response, and energy metabolism. On the other hand, it seems that thermoneutrality (TN, 28°C) represents a closer parallel to human physiology. In this perspective, we investigated the effects of GT (500 mg/kg of body weight, over 12 weeks, 5 days/week) by comparing mice housed at ST or TN in a model of MAFLD of diet-induced obese males C57Bl/6 mice. We show that the liver phenotype at TN exhibits a more severe MAFLD while GT ameliorates this condition. In parallel, GT restores the expression of genes involved in the lipogenic pathway, regardless of temperature, with slight modifications in lipolysis/fatty acid oxidation. We observed an increase promoted by GT in PPARα and PPARγ proteins independently of housing temperature and a dual pattern of bile acid synthesis. Thus, animals' conditioning temperature is a key factor that can interfere in the results involving obesity and MAFLD, although GT has beneficial effects against MAFLD independently of the housing temperature of mice.
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Diabetes Mellitus Tipo 2 , Chá , Masculino , Camundongos , Humanos , Animais , Camundongos Obesos , Temperatura , Habitação , Diabetes Mellitus Tipo 2/complicações , Obesidade/metabolismoRESUMO
BACKGROUND: Pregnancy and postpartum are periods of intense changes in women's metabolism. The knowledge of the metabolites and maternal factors underlying these changes is limited. OBJECTIVES: We aimed to investigate the maternal factors that could influence serum metabolome changes from late pregnancy to the first months of postpartum. METHODS: Sixty-eight healthy women from a Brazilian prospective cohort were included. Maternal blood and general characteristics were collected during pregnancy (28-35 wk) and postpartum (27-45 d). A targeted metabolomics approach was applied to quantify 132 serum metabolites, including amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines (LPC), diacyl phosphatidylcholines (PC), alkyl:acyl phosphatidylcholines (PC-O), sphingomyelins with (SM) and without hydroxylation [SM(OH)], and hexoses. Metabolome changes from pregnancy to postpartum were measured as log2 fold change (log2FC), and simple linear regressions were employed to evaluate associations between maternal variables and metabolite log2FC. Multiple comparison-adjusted P values of < 0.05 were considered significant. RESULTS: Of 132 metabolites quantified in serum, 90 changed from pregnancy to postpartum. Most metabolites belonging to PC and PC-O classes decreased, whereas most LPC, acylcarnitines, biogenic amines, and a few amino acids increased in postpartum. Maternal prepregnancy body mass index (ppBMI) showed positive associations with leucine and proline. A clear opposite change pattern was observed for most metabolites across ppBMI categories. Few phosphatidylcholines were decreased in women with normal ppBMI, while an increase was observed in women with obesity. Similarly, women with high postpartum levels of total cholesterol, LDL cholesterol, and non-HDL cholesterol showed increased sphingomyelins, whereas a decrease was observed for women with lower levels of those lipoproteins. CONCLUSIONS: The results revealed several maternal serum metabolomic changes from pregnancy to postpartum, and the maternal ppBMI and plasma lipoproteins were associated with these changes. We highlight the importance of the nutritional care of women prepregnancy to improve their metabolic risk profile.
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Metaboloma , Esfingomielinas , Humanos , Gravidez , Feminino , Índice de Massa Corporal , Estudos Prospectivos , Metabolômica/métodos , Período Pós-Parto , Lipoproteínas , Aminoácidos , Colesterol , Fosfatidilcolinas , Aminas BiogênicasRESUMO
Monoterpenes, volatile metabolites produced by plants, are involved in the taste and aroma perception of fruits and vegetables and have been used for centuries in gastronomy, as food preservatives and for therapeutic purposes. Biological activities such as antimicrobial, analgesic and anti-inflammatory are well-established for some of these molecules. More recently, the ability of monoterpenes to regulate energy metabolism, and exert antidiabetic, anti-obesity and gut microbiota modulation activities have been described. Despite their promising health effects, the lack of reliable quantification of monoterpenes in food, hindered the investigation of their role as dietary bioactive compounds in epidemiological studies. Moreover, only few studies have documented the biotransformation of these compounds and identified the monoterpene metabolites with biological activity. This review presents up-to-date knowledge about the occurrence of monoterpenes in food, their bioavailability and potential role in the modulation of intermediate metabolism and inflammation, focusing on novel findings of molecular mechanisms, underlining research gaps and new avenues to be explored.
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Monoterpenos , Plantas , Monoterpenos/farmacologia , Monoterpenos/metabolismo , Plantas/metabolismo , Frutas/metabolismo , Anti-Inflamatórios/farmacologiaRESUMO
Metabolic switching has been raised as an important phenomenon to be studied in relation to xenobiotic metabolites, since the dose of the exposure determines the formation of metabolites and their bioactivity. Limonene is a monoterpene mostly found in citrus fruits with health activity, and its phase II metabolites and activity are still not clear. The aim of this work was to evaluate the effects of D-limonene in the development of diet-induced obesity in mice and to investigate metabolites that could be generated in a study assessing different doses of supplementation. Animals were induced to obesity and supplemented with 0.1% or 0.8% D-limonene added to the feed. Limonene phase I and II metabolites were identified in liver and urine by LC-ESI-qToF-MS/MS. To the best of our knowledge, in this study three new phase I metabolites and ten different phase II metabolites were first attributed to D-limonene. Supplementation with 0.1% D-limonene was associated with lower weight gain and a trend to lower accumulation of adipose tissue deposits. The metabolites limonene-8,9-diol, perillic acid and perillic acid-8,9-diol should be explored in future research as anti-obesogenic agents as they were the metabolites most abundant in the urine of mice that received 0.1% D-limonene in their feed.
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Food intake triggers extensive changes in the blood metabolome. The kinetics of these changes depend on meal composition and on intrinsic, health-related characteristics of each individual, making the assessment of changes in the postprandial metabolome an opportunity to assess someone's metabolic status. To enable the usage of dietary challenges as diagnostic tools, profound knowledge about changes that occur in the postprandial period in healthy individuals is needed. In this study, we characterize the time-resolved changes in plasma levels of 634 metabolites in response to an oral glucose tolerance test (OGTT), an oral lipid tolerance test (OLTT), and a mixed meal (SLD) in healthy young males (n = 15). Metabolite levels for samples taken at different time points (20 per individual) during the challenges were available from targeted (132 metabolites) and non-targeted (502 metabolites) metabolomics. Almost half of the profiled metabolites (n = 308) showed a significant change in at least one challenge, thereof 111 metabolites responded exclusively to one particular challenge. Examples include azelate, which is linked to ω-oxidation and increased only in OLTT, and a fibrinogen cleavage peptide that has been linked to a higher risk of cardiovascular events in diabetes patients and increased only in OGTT, making its postprandial dynamics a potential target for risk management. A pool of 89 metabolites changed their plasma levels during all three challenges and represents the core postprandial response to food intake regardless of macronutrient composition. We used fuzzy c-means clustering to group these metabolites into eight clusters based on commonalities of their dynamic response patterns, with each cluster following one of four primary response patterns: (i) "decrease-increase" (valley-like) with fatty acids and acylcarnitines indicating the suppression of lipolysis, (ii) "increase-decrease" (mountain-like) including a cluster of conjugated bile acids and the glucose/insulin cluster, (iii) "steady decrease" with metabolites reflecting a carryover from meals prior to the study, and (iv) "mixed" decreasing after the glucose challenge and increasing otherwise. Despite the small number of subjects, the diversity of the challenges and the wealth of metabolomic data make this study an important step toward the characterization of postprandial responses and the identification of markers of metabolic processes regulated by food intake.
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In recent years, bile acids (BA) have received great interest due to their pleiotropic biological activity and the presence of plasma membrane-bound and nuclear receptors. Moreover, BA in blood have been identified by metabolite screening approaches as biomarkers that are associated with various diseases and even with a human longevity phenotype. With the growing interest in the microbiota contribution to the health-disease trajectory, BA that undergo deconjugation and other modifications by bacteria in the large intestine have become a prime target as a microbiome diversity modifier. We here profiled BA by a quantitative and a semiquantitative approach in 15 healthy and phenotypically very similar young individuals for over a 36-h fasting period, an oral glucose tolerance test (OGTT), and an oral lipid tolerance test (OLTT). We demonstrate a remarkable heterogeneity of the responses and describe the different dynamics of the plasma changes that likely originate from different routes by which BA enters the peripheral blood, and that may represent a direct secretion from the liver into the blood and a route that reaches the blood as a spill-over after passing from the gallbladder through the intestine and the portal system. We discuss the finding that an individual transport process involved in the passage of BA could be a critical determinant in the kinetics of plasma appearance and the overall phenotypic variability found.
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Insulin secretion following ingestion of a carbohydrate load affects a multitude of metabolic pathways that simultaneously change direction and quantity of interorgan fluxes of sugars, lipids and amino acids. In the present study, we aimed at identifying markers associated with differential responses to an OGTT a population of healthy adults. By use of three metabolite profiling platforms, we assessed these postprandial responses of a total of 202 metabolites in plasma of 72 healthy volunteers undergoing comprehensive phenotyping and of which half enrolled into a weight-loss program over a three-month period. A standard oral glucose tolerance test (OGTT) served as dietary challenge test to identify changes in postprandial metabolite profiles. Despite classified as healthy according to WHO criteria, two discrete clusters (A and B) were identified based on the postprandial glucose profiles with a balanced distribution of volunteers based on gender and other measures. Cluster A individuals displayed 26% higher postprandial glucose levels, delayed glucose clearance and increased fasting plasma concentrations of more than 20 known biomarkers of insulin resistance and diabetes previously identified in large cohort studies. The volunteers identified by canonical postprandial responses that form cluster A may be called pre-pre-diabetics and defined as "at risk" for development of insulin resistance. Moreover, postprandial changes in selected fatty acids and complex lipids, bile acids, amino acids, acylcarnitines and sugars like mannose revealed marked differences in the responses seen in cluster A and cluster B individuals that sustained over the entire challenge test period of 240 min. Almost all metabolites, including glucose and insulin, returned to baseline values at the end of the test (at 240 min), except a variety of amino acids and here those that have been linked to diabetes development. Analysis of the corresponding metabolite profile in a fasting blood sample may therefore allow for early identification of these subjects at risk for insulin resistance without the need to undergo an OGTT.
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BACKGROUND: Advances in technology have led to the identification of a greater number of metabolites related to diet. Although fruit intake biomarkers have been reported in some studies, these findings require further replication, considering the relevance of fruits for diet quality and health. OBJECTIVES: The aim of this study was to explore the associations of a set of potential urinary biomarkers of diet, assessed using a targeted metabolomics approach, with self-reported fruit intake data in participants of a computer-assisted 24-h dietary recall (GloboDiet software) validation study. METHODS: A total of 93 individuals aged 43-72 y, 54% female, participated in this study. The subjects were a subsample of the Longitudinal Study of Adult Health (ELSA-Brasil). A 24-h dietary recall was obtained with the aid of GloboDiet software matching a 24-h urine sample from each participant. Candidate biomarkers were selected in a literature search and identified in urine by LC coupled to high-resolution MS. Spearman correlation analyses were performed between fruit intake and each biomarker. RESULTS: Spearman correlation analysis showed that total fruits intake was significantly correlated with citric acid (ρ = 0.213, P = 0.041), ferulic acid sulfate I (ρ = 0.240, P = 0.020), hesperetin glucuronide/homoeriodictyol glucuronide (ρ = 0.303, P = 0.003), hydroxyhippuric acid (ρ = 0.239, P = 0.021), homovanillic alcohol sulfate (ρ = 0.339, P = 0.001), methylgallic acid sulfate (ρ = 0.268, P = 0.009), naringenin glucuronide (NG; ρ = 0.278, P = 0.007), proline betaine (PB; ρ = 0.305, P = 0.003), syringic acid sulfate (ρ = 0.210, P = 0.044), and sinapic acid sulfate (ρ = 0.412, P < 0.001). Among them, 3 have been described in literature as promising biomarkers for intake of total fruit, oranges, and citrus fruit: NG, hesperetin glucuronide, and PB. CONCLUSIONS: Associations of total fruits intake with urinary measurements indicate the potential usefulness of dietary biomarkers in the Brazilian population as a complement to self-reported dietary assessments.
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Frutas , Glucuronídeos , Biomarcadores/urina , Brasil , Estudos Transversais , Dieta , Feminino , Humanos , Estudos Longitudinais , Masculino , Metabolômica , SulfatosRESUMO
We investigate the effect of the banana green peels extract (BPE) as a preventive treatment against NAFLD in high-fat diet fed mice. Mice received daily doses of 100 or 250 mg/kg of BPE for 12 weeks along with the high-fat diet. BPE reduced weight gain (p < .0001), adipose tissue hypertrophy (p < .0001), and improved glucose homeostasis (p < .0001). Plasma levels of glucose-dependent insulinotropic polypeptide, triglycerides, total cholesterol, LDL-cholesterol, non-esterified fatty acids, aspartate and alanine transaminase, leptin, and resistin were decreased in BPE treated mice (p < .05). BPE effects on lipid metabolism were associated with decreased gene expression of lipogenic enzymes and increased expression of enzymes related to fatty acid and cholesterol degradation (p < .05). Plasma and liver bile acid (BA) profiles were modulated by BPE, with positive correlations between specific BA and UCP-1, CPT-1 and PGC-1ß expression in brown adipose tissue (p < .05). BPE reduced hepatic steatosis and inflammation, possibly due to reduced p65 NF-κB nuclear translocation (p < .05) and modulation of oxidative stress (p < .05). These data indicate that BPE is a source of phytochemical compounds with promising effects toward the prevention of metabolic disorders associated with obesity.
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Musa , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Metabolismo dos Lipídeos , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologiaRESUMO
We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.
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COVID-19/epidemiologia , Brasil/epidemiologia , COVID-19/transmissão , Cidades/epidemiologia , Humanos , Modelos Estatísticos , Pandemias , SARS-CoV-2/isolamento & purificação , Fatores de TempoRESUMO
OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.
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Humanos , Masculino , Criança , Adolescente , COVID-19/complicações , Qualidade de Vida , Estudos Prospectivos , Centros de Atenção Terciária , Teste para COVID-19 , SARS-CoV-2 , América LatinaRESUMO
We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.
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BACKGROUND/AIMS: Skeletal mass loss is reported in several catabolic conditions and it has been associated with a reduced intracellular L-glutamine content. We investigated the association of intracellular L-glutamine concentration with the protein content in skeletal muscle cells. METHODS: We cultivated C2C12 myotubes in the absence or presence of 2 (reference condition), 8 or 16 mM L-glutamine for 48 hours, and the variations in the contents of amino acids and proteins measured. We used an inhibitor of L-glutamine synthesis (L-methionine sulfoximine - MSO) to promote a further reduction in intracellular L-glutamine levels. Amino acids contents in cells and media were measured using LC-MS/MS. We measured changes in phosphorylated Akt, RP-S6, and 4E-BP1contents in the absence or presence of insulin by western blotting. RESULTS: Reduced intracellular L-glutamine concentration was associated with decreased protein content and increased protein breakdown. Low intracellular glutamine levels were also associated with decreased p-Akt contents in the presence of insulin. A further decrease in intracellular L-glutamine caused by glutamine synthetase inhibitor reduced protein content and levels of amino acids generated from glutamine metabolism and increased bAib still further. Cells exposed to high medium glutamine levels did not have any change in protein content but exhibited increased contents of the amino acids derived from L-glutamine metabolism. CONCLUSION: Intracellular L-glutamine levels per se play a role in the control of protein content in skeletal muscle myotubes.
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Proteínas de Transporte/metabolismo , Glutamina/metabolismo , Insulina/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína S6 Ribossômica/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas de Transporte/análise , Proteínas de Ciclo Celular , Linhagem Celular , Cromatografia Líquida , Fatores de Iniciação em Eucariotos , Glutamina/análise , Insulina/análise , Camundongos , Fibras Musculares Esqueléticas/química , Fosfoproteínas/análise , Fosforilação , Proteínas Proto-Oncogênicas c-akt/análise , Proteína S6 Ribossômica/análise , Espectrometria de Massas em TandemRESUMO
Supplementation of cholate to a high fat diet can protect mice from diet-induced, increased body mass gain. It has been hypothesized that uncoupling protein 1 dependent, non-shivering thermogenesis in brown adipocytes provides the mechanism of increased energy expenditure to counteract excessive energy intake. We scrutinized this conjecture in wildtype mice and mice genetically devoid of a functional uncoupling protein 1 gene (C57BL/6J) as well as mice of the 129S6/SvEvTac strain that, in comparison, display an extraordinary capacity to recruit ectopic brown adipocytes. Protection from diet-induced, increased body mass gain by cholate supplementation was absent in 129S6/SvEvTac mice, a consequence of much lower bile acid absorption and spillover in this strain. Conversely, Ucp1-KO mice did not differ from C57BL/6J wildtype controls in any parameter assessed. Daily energy expenditure and resting metabolic rate of C57BL/6J mice remained unaffected by cholate supplementation. We conclude that protection of mice from diet-induced, increased body mass gain by cholate supplementation depends on the specific genetic background of C57BL/6J mice, does not involve increased energy expenditure and is independent of uncoupling protein 1 dependent non-shivering thermogenesis.
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Ácidos e Sais Biliares/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos , Animais , Metabolismo Basal , Ácidos e Sais Biliares/farmacologia , Ácido Cólico/farmacologia , Ácido Cólico/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Especificidade da EspécieRESUMO
BACKGROUND: A number of computational tools for metabolism prediction have been developed over the last 20 years to predict the structures of small molecules undergoing biological transformation or environmental degradation. These tools were largely developed to facilitate absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies, although there is now a growing interest in using such tools to facilitate metabolomics and exposomics studies. However, their use and widespread adoption is still hampered by several factors, including their limited scope, breath of coverage, availability, and performance. RESULTS: To address these limitations, we have developed BioTransformer, a freely available software package for accurate, rapid, and comprehensive in silico metabolism prediction and compound identification. BioTransformer combines a machine learning approach with a knowledge-based approach to predict small molecule metabolism in human tissues (e.g. liver tissue), the human gut as well as the environment (soil and water microbiota), via its metabolism prediction tool. A comprehensive evaluation of BioTransformer showed that it was able to outperform two state-of-the-art commercially available tools (Meteor Nexus and ADMET Predictor), with precision and recall values up to 7 times better than those obtained for Meteor Nexus or ADMET Predictor on the same sets of pharmaceuticals, pesticides, phytochemicals or endobiotics under similar or identical constraints. Furthermore BioTransformer was able to reproduce 100% of the transformations and metabolites predicted by the EAWAG pathway prediction system. Using mass spectrometry data obtained from a rat experimental study with epicatechin supplementation, BioTransformer was also able to correctly identify 39 previously reported epicatechin metabolites via its metabolism identification tool, and suggest 28 potential metabolites, 17 of which matched nine monoisotopic masses for which no evidence of a previous report could be found. CONCLUSION: BioTransformer can be used as an open access command-line tool, or a software library. It is freely available at https://bitbucket.org/djoumbou/biotransformerjar/ . Moreover, it is also freely available as an open access RESTful application at www.biotransformer.ca , which allows users to manually or programmatically submit queries, and retrieve metabolism predictions or compound identification data.
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Roux-en-Y gastric bypass (RYGB) is an effective method to achieve sustained weight loss, but the mechanisms responsible for RYGB effects have not yet been fully characterized. In this study, we profiled the concentrations of 143 lipid metabolites in dry blood spots (DBS) of RYGB patients. DBS from obese patients (BMI range 35â»44 kg/m²) were collected 7 days before, 15 and 90 days after the surgery. LC-MS/MS was used to quantify acylcarnitines, phosphatidylcholines, sphingomyelins and bile acids. RYGB caused a rapid increase in acylcarnitine levels that proved to be only transient, contrasting with the sustained decrease in phosphatidylcholines and increase of sphingomyelins and bile acids. A PLS-DA analysis revealed a 3-component model (R² = 0.9, Q² = 0.74) with key metabolites responsible for the overall metabolite differences. These included the BCAA-derived acylcarnitines and sphingomyelins with 16 and 18 carbons. We found important correlations between the levels of BCAA-derived acylcarnitines and specific sphingomyelins with plasma cholesterol and triacylglycerol concentrations. Along with the marked weight loss and clinical improvements, RYGB induced specific alterations in plasma acylcarnitines, bile acid and phospholipid levels. This calls for more studies on RYGB effects aiming to elucidate the metabolic adaptations that follow this procedure.