Taurine supplementation regulates Iκ-Bα protein expression in adipose tissue and serum IL-4 and TNF-α concentrations in MSG obesity.

PURPOSE: Obesity is usually associated with low-grade inflammation, which impairs insulin action. The amino acid, taurine (TAU), regulates glucose homeostasis and lipid metabolism and presents anti-inflammatory actions. Here, we evaluated whether inflammatory markers are altered in the serum and retroperitoneal adipose tissue of monosodium glutamate (MSG) obese rats, supplemented or not with TAU. METHODS: Male Wistar rats received subcutaneous injections of MSG (4 mg/kg body weight/day, MSG group) or hypertonic saline (CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5 % TAU in their drinking water (CTAU and MTAU). RESULTS: At 120 days of age, MSG rats were obese and hyperinsulinemic. TAU supplementation reduced fat deposition without affecting insulinemia in MTAU rats. MSG rats presented increased pIκ-Bα/Iκ-Bα protein expression in the retroperitoneal adipose tissue. TAU supplementation decreased the ratio of pIκ-Bα/Iκ-Bα protein, possibly contributing to the increased Iκ-Bα content in MTAU adipose tissue. Furthermore, MSG obesity or supplementation did not alter TNF-α, IL-1ß or IL-6 content in adipose tissue. In contrast, MSG rats presented lower serum TNF-α, IL-4 and IL-10 concentrations, and these alterations were prevented by TAU treatment. CONCLUSION: MSG obesity in rats was not associated with alterations in pro-inflammatory markers in retroperitoneal fat stores; however, reductions in the serum concentrations of anti-inflammatory cytokines and of TNF-α were observed. TAU treatment decreased adiposity, and this effect was associated with the normalization of circulating TNF-α and IL-4 concentrations in MTAU rats.

A sportomics soccer investigation unveils an exercise-induced shift in tyrosine metabolism leading to hawkinsinuria.

Tyrosine metabolism has an intense role in the synthesis of neurotransmitters. Our study used an untargeted, sportomics-based analysis of urine samples to investigate changes in metabolism during a soccer match in 30 male junior professional soccer players. Samples were collected before and after the match and analyzed using liquid chromatography and mass spectrometry. Results showed significant changes in tyrosine metabolism. Exercise caused a downregulation of the homogentisate metabolites 4-maleylacetoacetate and succinylacetone to 20% (p = 4.69E-5) and 16% (p = 4.25E-14), respectively. 4-Hydroxyphenylpyruvate, a homogentisate precursor, was found to be upregulated by 26% (p = 7.20E-3). The concentration of hawkinsin and its metabolite 4-hydroxycyclohexyl acetate increased ~six-fold (p = 1.49E-6 and p = 9.81E-6, respectively). Different DOPA metabolism pathways were also affected by exercise. DOPA and dopaquinone increased four-to six-fold (p = 5.62E-14 and p = 4.98E-13, respectively). 3-Methoxytyrosine, indole-5,6-quinone, and melanin were downregulated from 1 to 25%, as were dopamine and tyramine (decreasing to up to 5% or 80%; p= 5.62E-14 and p = 2.47E-2, respectively). Blood TCO2 decreased as well as urinary glutathione and glutamate (40% and 10% respectively) associated with a two-fold increase in pyroglutamate. Our study found unexpected similarities between exercise-induced changes in metabolism and the inherited disorder Hawkinsinuria, suggesting a possible transient condition called exercise-induced hawkinsinuria (EIh). Additionally, our research suggests changes in DOPA pathways may be involved. Our findings suggest that soccer exercise could be used as a model to search for potential countermeasures in Hawkinsinuria and other tyrosine metabolism disorders.

USE OF METABOLOMICS TO THE DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE.

BACKGROUND: Crohn's disease and ulcerative colitis are the primary inflammatory bowel diseases (IBD), and its pathogenesis is related to genetic and environmental factors. Currently, the diagnosis of IBD results in a multidisciplinary approach with significant disadvantages, such as its invasive nature, time spent, and the fact that 10% of patients remain without diagnostic classification. However, new methodologies of analysis have emerged that allowed the expansion of knowledge about IBD, as the metabolomics, the study of metabolites. The presence and prevalence of such metabolites may prove to be useful as biomarkers in the diagnosis of IBD. OBJECTIVE: Analyze fecal samples for metabolic analysis in the diagnosis of inflammatory bowel diseases (IBD), providing differentiation between Crohn's disease and ulcerative colitis. METHODS: This is an observational study with 21 patients diagnosed with IBD (ulcerative colitis 11 and Crohn's disease 10) and 15 healthy controls, all with the consent and clarification. The fecal extracts of all patients are submitted to a high-resolution Nuclear Magnetic Resonance Hydrogen (1H-NMR) spectroscopy combined with multivariate and univariate pattern recognition techniques. Through the metabolomics of fecal extracts, gives us a characterization of employing a noninvasive approach. RESULTS: We identify some metabolites, such as lactate, succinate, alanine, and tyrosine, in the Crohn's disease fecal samples, and leucine, alanine, and tyrosine in the ulcerative colitis fecal samples. All the amino acids presented positive covariance for disease correlation. CONCLUSION: The results showed different metabolic profiles between IBD patients and healthy volunteers based on 1H-NMR analysis of fecal extracts. Moreover, the approach discriminated patients with Crohn's disease and ulcerative colitis. The metabolomics analysis is promising as a novel diagnostic technique for further IBD recognition and surveillance. New studies are necessary to validate these findings.

Production, purification, characterization and application of a new halotolerant and thermostable endoglucanase of Botrytis ricini URM 5627.

A halotolerant endoglucanase with a molecular mass of 39 kDa was obtained from the solid fermentation of sugarcane bagasse by the fungus Botrytis ricini URM 5627 and isolated using only two purification processes: fractionation with ammonium sulphate and size-exclusion chromatography resulting in an activity of 1289.83 U/mL. After the isolation, biochemical characterizations were performed, giving a temperature of 50 °C and optimum pH of 5. The enzyme was stable at 39-60 °C for 60 min and at a pH of 4-6. The enzymatic activity increased in the presence of Na+, Mn2+, Mg2+ and Zn2+ and decreased in the presence of Ca2+, Cu2+, and Fe2+. The endoglucanase revealed a halotolerant profile since its activity increased proportionally to an increase in NaCl concentration. The maximum activity was reached at 2 M NaCl with a 75% increase in activity. The enzyme had a Km of 0.1299 ±â€¯0.0096 mg/mL and a Vmax of 0.097 ±â€¯0.00121 mol/min/mL. During application in saccharification tests, the enzyme was able to hydrolyse sugarcane bagasse, rice husk, and wheat bran, with the highest production of reducers/fermentable sugars within 24 h of saccharification for wheat bran (137.21 mg/g). Therefore, these properties combined make this isolated enzyme a potential candidate for biotechnological and industrial applications.

Improvement in the expression of hepatic genes involved in fatty acid metabolism in obese rats supplemented with taurine.

AIMS: Fat deposition in the liver, which leads to nonalcoholic fatty liver disease is associated with obesity. Taurine (Tau) regulates lipid metabolism, representing a possible nutraceutical agent against obesity and its comorbidities. Here, we investigated whether Tau supplementation prevents hepatic lipid accumulation by regulation of the main hepatic genes involved in de novo lipogenesis and ß-oxidation. MAIN METHODS: Male rats received subcutaneous injections of monosodium glutamate (MSG; 4 mg/kg body weight/day) or saline (control group, CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5% Tau in drinking water (CTau and MTau). KEY FINDINGS: MSG-treated rats were normoglycemic, hypertriglyceridemic and insulin resistant (IR). MSG rats also exhibited massive obesity and higher hepatic triglyceride (TG) content. This effect was associated with enhanced gene expression of fatty acid synthase (FASN), but reduced carbohydrate response element-binding protein (ChREBP), microsomal TG transfer protein (MTP) and carnitine palmitoyltransferase (CPT)-1a mRNAs in MSG livers. Tau supplementation decreased whole body fat accumulation and serum TG levels, without altering IR. Tau also normalized hepatic TG content by enhancing ChREBP, MTP, peroxisome proliferator-activated receptor (PPAR)-α, ACO (acyl-CoA oxidase) and CPT-1a gene expressions. SIGNIFICANCE: Therefore, increased hepatic TG deposition in MSG-obese rats is associated with an enhanced FASN, and reduced MTP and CPT-1a genes. Tau supplementation prevented obesity and hepatic TG deposition by upregulating MTP mRNA, ameliorating hepatic lipid efflux, and consequently enhancing PPAR-α which increases lipid oxidation through ACO and CPT-1a gene expressions.

Uso da metabolômica no diagnóstico de doenças inflamatórias intestinais / Use of metabolomics to the diagnosis of inflammatory bowel disease

ABSTRACT BACKGROUND: Crohn's disease and ulcerative colitis are the primary inflammatory bowel diseases (IBD), and its pathogenesis is related to genetic and environmental factors. Currently, the diagnosis of IBD results in a multidisciplinary approach with significant disadvantages, such as its invasive nature, time spent, and the fact that 10% of patients remain without diagnostic classification. However, new methodologies of analysis have emerged that allowed the expansion of knowledge about IBD, as the metabolomics, the study of metabolites. The presence and prevalence of such metabolites may prove to be useful as biomarkers in the diagnosis of IBD. OBJECTIVE: Analyze fecal samples for metabolic analysis in the diagnosis of inflammatory bowel diseases (IBD), providing differentiation between Crohn's disease and ulcerative colitis. METHODS: This is an observational study with 21 patients diagnosed with IBD (ulcerative colitis 11 and Crohn's disease 10) and 15 healthy controls, all with the consent and clarification. The fecal extracts of all patients are submitted to a high-resolution Nuclear Magnetic Resonance Hydrogen (1H-NMR) spectroscopy combined with multivariate and univariate pattern recognition techniques. Through the metabolomics of fecal extracts, gives us a characterization of employing a noninvasive approach. RESULTS: We identify some metabolites, such as lactate, succinate, alanine, and tyrosine, in the Crohn's disease fecal samples, and leucine, alanine, and tyrosine in the ulcerative colitis fecal samples. All the amino acids presented positive covariance for disease correlation. CONCLUSION: The results showed different metabolic profiles between IBD patients and healthy volunteers based on 1H-NMR analysis of fecal extracts. Moreover, the approach discriminated patients with Crohn's disease and ulcerative colitis. The metabolomics analysis is promising as a novel diagnostic technique for further IBD recognition and surveillance. New studies are necessary to validate these findings.

RESUMO CONTEXTO: A doença de Crohn e retocolite ulcerativa são as principais doenças inflamatórias intestinais (DII), e sua patogênese está relacionada a fatores genéticos e ambientais. Atualmente, o diagnóstico de DII resulta em uma abordagem multidisciplinar e apresenta desvantagens significativas, como sua natureza invasiva, tempo gasto e o fato de 10% dos pacientes permanecerem sem classificação diagnóstica. No entanto, surgiram novas metodologias de análise que permitiram ampliar o conhecimento sobre a DII, como a metabolômica, o estudo dos metabólitos. A presença e a prevalência desses metabólitos podem ser úteis como biomarcadores no diagnóstico da DII. OBJETIVO: Avaliar as amostras fecais por análise metabolômica no diagnóstico de DII, diferenciando os perfis metabólicos entre doença de Crohn e retocolite ulcerativa. MÉTODOS: Estudo observacional com 36 indivíduos (doença de Crohn 11, retocolite ulcerativa 10 e 15 controles saudáveis), todos com consentimento esclarecido. Os extratos fecais de todos os pacientes são submetidos a uma espectroscopia de alta resolução por ressonância magnética nuclear de hidrogênio (1H-RMN) combinada com técnicas de reconhecimento de padrões multivariados e univariados. Por meio da metabolômica utilizando extratos fecais, foi possível obter uma caracterização adequada das doenças inflamatórias intestinais através de uma abordagem não invasiva. RESULTADOS: Foi possível identificar os seguintes metabólitos nos pacientes com doen­ça de Crohn: lactato, succinato, alanina e tirosina e, no grupo retocolite ulcerativa encontrou-se leucina, alanina e tirosina. Todos os aminoácidos apresentaram covariância positiva para a doença. CONCLUSÃO: Os resultados demonstraram diferentes perfis metabólicos entre pacientes com DII e voluntários saudáveis, com base na análise por 1H-RMN dos extratos fecais. Além disso, pacientes com doença de Crohn e retocolite ulcerativa também podem ser discriminados usando essa abordagem. A análise metabolômica é promissora como uma nova técnica não invasiva de diagnóstico para melhor reconhecimento das DII. Novos estudos são necessários para validar esses achados.

Methanol extract from mycelium of endophytic fungus Rhizoctonia sp. induces antinociceptive and anti-inflammatory activities in mice.

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100 mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8 h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10 mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10 mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.

A dehydrorotenoid produced by callus tissue culture and wild plant roots of Boerhaavia coccinea

Calli cultures were established from leaves and stem of B. coccinea plantlet produced in vitro and analysed for isoflavonoid content. The quantification of 6,9,11-trihydroxy-6a,12a-dehydrorotenoid isolated from the roots of Boerhaavia coccinea P. Miller collected from its natural environment, and the same metabolite produced in callus tissue culture of the same plant are described in this paper. The rotinary quantitative HPLC analysis indicated that callus culture produced the same isoflavonoid compound found in the roots of intact wild growing plant. The amount of the secondary metabolite produced in vitro was 955.35 µg/g of dry cell weight, 2.5 times more than the highest amount concentration produced by the wild growing plant in its natural environment.

Cultura de calos foram estabelecidos de folhas e galhos finos de plântula de B. coccinea produzida in vitro e analisada para isoflavonóide. A quantificação do 6,9,11-triidroxi-6a,12a-desidro-rotenóide isolado das raízes de B. coccinea P Miller, coletada em seu habitat natural, e do mesmo rotenóide produzido na cultura de células estão descritos neste artigo. A análise rotineira em CLAE mostrou que a cultura de calos produziu o mesmo isoflavonóide encontrado nas raízes da planta do campo. A quantidade do metabólito secundário produzido in vitro foi de 955.35 µg/g de massa seca de callus, atingindo uma concentração de 2,5 vezes maior do que a quantidade do metabólito produzido pela planta em seu meio ambiente natural.

Efeito da adubação com boro e esterco bovino sobre a produtividade da figueira e as propriedades químicas do solo / Effect of boron and cattle manure fertilization on yield productivity fig tree and on soil properties

O objetivo deste trabalho foi verificar o efeito da adubação da cultura da figueira com boro e esterco bovino sobre a produtividade de figos verdes e as propriedades químicas do solo. Os tratamentos foram cinco doses de ácido bórico (0, 20, 40, 60 e 100g planta-1) combinadas com dois níveis de adubação de esterco (sem esterco e 10kg de esterco/planta). O delineamento experimental foi o de blocos casualizados em esquema de parcelas subdivididas e quatro repetições. A adubação com ácido bórico não afetou a produtividade de figos, enquanto que o esterco bovino aumentou-a. Os teores de fósforo e potássio no solo aumentaram significativamente e o teor de alumínio diminuiu significativamente em função da adubação com esterco bovino. O teor de B no solo, extraído pelo método da água quente, aumentou linearmente em função das doses de ácido bórico.