Efficacy of nutrition therapy with food rich in methionine for treating nonalcoholic fatty liver / Eficacia de la terapia nutricional con alimentos ricos en metionina para el tratamiento de hígado graso no alcohólico

Non-Alcoholic Fatty Liver disease (NAFLD) can lead to Non Alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The treatment for NAFLD involves modification of caloric intake and physical activity. NAFLD has a pro-oxidant nature; therefore, it is logical to suppose that the antioxidant methionine can be used as a treatment for this disease. Aim. This study aimed to evaluate the effect of high-methionine dietary therapy on patients with NAFLD. Materials and methods. A randomized clinical study was conducted over three months. In this study, 121 NAFLD patients participated, and the age of the participants was ≥ 20 years (experimental group included 56 and control group 65), all of whom were randomized and matched by sex, recluted from the ISSSTE hospital in Xalapa, Mexico. The patients were instructed to consume food to cover the recommended methionine daily doses, and the daily amount consumed was calculated. Methionine effect was measured as NAFLD regression and quality of life improvement. Results. Nutritional therapy induced NAFLD regression and diminished central fat accumulation, blood pressure, and the fatty liver index. Some parameters, such as liver enzymes, did not changed. The quality of life of patients improved after treatment. Conclusions. In this study, we show a hepatoprotective effect induced only in three months of chances in the diet, thus, a longer diet may generate more relevant benefits in the resistant parameters of our study(AU)

La enfermedad del hígado graso no alcohólico (NAFLD) puede conducir a la esteatohepatitis no alcohólica (NASH), la cirrosis y el cáncer de hígado. El tratamiento para NAFLD es la modificación de la ingesta calórica y la actividad física. Debido a que NAFLD tiene una naturaleza pro-oxidante; es lógico suponer que el antioxidante metionina puede utilizarse en el tratamiento de esta enfermedad. Objetivo. el presente trabajo evaluó el papel de la terapia nutricional con alimentos ricos en metioninaen pacientes con NAFLD. Materiales y Métodos. Se realizó un ensayo clínico aleatorizado durante tres meses. Participaron en el estudio 121 pacientes con NAFLD con edad ≥ 20 años (56 en el grupo experimental y 65 en el control), todos aleatorizados y pareados por sexo, reclutados de la Clínica Hospital ISSTE en la ciudad de Xalapa, México, en el año 2015. Se instruyó a los pacientes en consumir los alimentos hasta completar la dosis diaria recomendada de metioninay se calculó la cantidad diaria consumida. Su efecto se midió como la regresión de NAFLD y la mejora de la calidad de vida. Resultados. La terapia nutricional retrocedió NAFLD; disminuyó la acumulación de grasa central, la presión arterial y el índice de hígado graso. Algunos parámetros, como las enzimas de la función hepática, no se modificaron con el tratamiento. Otro parámetro fue la mejora de la calidad de vida de los pacientes tratados. Conclusiones. En este trabajo mostramos un impacto hepatoprotector producido con tan solo tres meses de cambios en la dieta, por lo que una dieta más prolongada podría generar beneficios aún más significativos en los parámetros resistentes en nuestro protocolo(AU)

Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology / 中国中药杂志

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.

Clinical characteristics and genetic analysis of a child with Galactosemia due to compound heterozygous variants of GALT gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis of a child with Galactosemia.@*METHODS@#A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing.@*RESULTS@#Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR).@*CONCLUSION@#Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.

Assessment of MTR Rs1805087 SNP as Possible Modifier ofSickle Cell Disease Severity in a Nigerian Population

BACKGROUND: Sickle cell disease is the commonest geneticdisorder in Nigeria, affecting 2­3% of an estimated population of 160million people. The role of genetic mutations in folate cycle genes,and the variable phenotypic expressions constituting disease severity,needs to be critically examined.OBJECTIVE: This study was carried out to establish the pattern ofmethionine synthase gene mutations (rs1805087 SNP), and its possibleassociation with disease severity in adults with sickle cell anaemia inLagos, Nigeria.METHODOLOGY: This is a cross-sectional study of seventy (70)subjects with sickle cell disease (HbSS) matched for age and genderwith known apparently healthy haemoglobin genotype AA (HbAA)subjects, as cases and controls respectively. Structured questionnaireswere used to obtain demographic, clinical and other phenotypic dataneeded to compute disease severity. Pattern of MTR A2756G genemutation and homocysteine assay (Hcy) were assessed by PolymeraseCh ain Reaction and Enzyme- linked Immun osorbent Assayrespectively. Full blood count analysis of participants was done usingthe KX-21 Automated Analyzer (Sysmex Corporation, Japan).RESULTS: The mutant genotypes MTR 2756 AG/GG were recordedin 46.4% (n =55) of subjects with disease severity score >7. Elevatedplasma homocysteine (HHcy) was significantly associated withdisease severity among HbSS subjects (OR=17.2, CI: 3.490-86.079;p=0.0001). Conversely, no significant association was observed withthe mutant genotypes MTR 2756 AG/GG and disease severity(p>0.05).CONCLUSION: While HHcy is significantly associated withphenotypic expression of HbSS, the MTR 2756 SNPs did not appearto independently influence homocysteine level or disease severity inHbSS subjects

Metabolomic changes of neonatal sepsis: an exploratory clinical study / 中国当代儿科杂志

OBJECTIVES@#To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission.@*METHODS@#A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points.@*RESULTS@#On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism.@*CONCLUSIONS@#The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma / 中华肿瘤杂志

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

Effect of chromium-methionine supplementation on meat quality of broilers reared under heat stress / [Efeito da suplementação de cromo-metionina na qualidade da carne de frangos de corte criados em estresse por calor]

Objetivou-se avaliar o efeito da suplementação de cromo-metionina em dietas para frangos de corte criados em estresse por calor, no período de 22 a 43 dias de idade, nos parâmetros de qualidade da carne. Foram utilizados 336 frangos de corte, machos, da linhagem Cobb 500, com 21 dias de idade, distribuídos em delineamento em blocos inteiramente ao acaso, com quatro blocos (cada câmara climática), seis tratamentos (0; 0,10; 0,20; 0,40; 0,80 e 1,20mgkg-1 de Cr na forma de Cr-metionina), oito repetições e sete aves por unidade experimental. Aos 43 dias de idade, duas aves por unidade experimental foram selecionadas e abatidas para avaliação da qualidade da carne de peito, por meio dos parâmetros de pH15min, pH24h, luminosidade (L*), teor de vermelho (a*), teor de amarelo (b*), croma (C*), ângulo hue (Hº), capacidade de retenção de água, perda de peso por cozimento e força de cisalhamento. Houve efeito quadrático (P=0,0070) na capacidade de retenção de água da carne de peito. A suplementação de CrMet não afetou (P>0,05) os demais parâmetros de qualidade da carne. Assim, recomenda-se a suplementação de 0,59mgkg-1 de CrMet para frangos de corte para melhoria da capacidade de retenção de água do peito.(AU)

Avaliação nutricional e metabólica de borregas alimentadas com níveis crescentes de aminoácidos protegidos / [Nutritional and metabolic evaluation of feeding lambs with growing levels of protein amino acids]

Objetivou-se avaliar a inclusão de níveis de lisina e metionina protegidas na dieta sobre os parâmetros nutricionais e metabólicos energéticos e hepáticos de borregas em crescimento. Utilizaram-se cinco borregas ½ sangue Dorper x Santa Inês, com aproximadamente oito meses de idade e peso médio de 50 ± 2,3kg, distribuídas em esquema quadrado latino 5x5 (cinco tratamentos, cinco animais e cinco períodos). Os tratamentos consistiram na inclusão de diferentes níveis de lisina e metionina protegidas da degradação ruminal (MicroPEARLS LM®) na ração, sendo: 0g, 8g, 16g, 24g e 32g por dia. A dieta era composta por silagem de milho e concentrado na relação 30V:70C. Realizou-se um ensaio de digestibilidade para determinar consumo e digestibilidade da matéria seca (CMS/DGMS), balanço de nitrogênio e metabólitos sanguíneos. O CMS (kg/dia) em relação ao peso metabólico apresentou equação linear positiva, sendo maior no tratamento que ofertou 32g de aminoácidos por dia, assim como o nitrogênio ingerido e o balanço de nitrogênio, sendo positivo em todos os tratamentos. Não houve diferença (P>0,05) para a digestibilidade da MS e o metabolismo energético e hepático. Lisina e metionina protegidas da degradação ruminal podem ser incluídas na ração de borregas em crescimento até 32g/dia sem causar efeitos negativos na digestibilidade da MS e no metabolismo.(AU)

The objective was to evaluate the inclusion of protected lysine and methionine levels on the diet, over the nutritional parameters and energetic and hepatic metabolites of growing lambs. Five lambs ½ blood Dorper x Santa Inês, with approximately eight months of age and average weight of 50kg, were distributed in a 5x5 latin square scheme (five treatments and five replicates). The treatments consisted of the inclusion of different levels of lysine and methionine protected from ruminal degradation (MicroPEARLS LM®) in the diet, being: 0g, 8g, 16g, 24g and 32g. The diet was composed of corn silage and concentrated 30V:70C in the ratio. A digestibility assay was performed to determine dry matter intake and digestibility (DMI/DDMI), nitrogen balance and blood metabolites. The DMI (kg/day) in relation to the metabolic weight had a positive linear equation, being higher in treatment 32g, as well as the ingested nitrogen and nitrogen balance, being positive in all treatments. There was no difference (P>0.05) for the digestibility of DM, energetic and hepatic metabolism. Lysine and methionine protected from ruminal degradation can be included in the diet of growing lambs up to 32g without causing negative effects on DM digestibility and metabolism.(AU)

Níveis Séricos do BDNF na Proteção Cardiovascular e em Resposta ao Exercício / Serum Levels of BDNF in Cardiovascular Protection and in Response to Exercise

Resumo As doenças cardiovasculares (DCV) são atualmente a maior causa de morte no Brasil e no mundo. Em 2016 as DCV foram responsáveis por mais de 17 milhões de mortes, representando 31% de todas as mortes em nível global. Mecanismos moleculares e genéticos podem estar envolvidos na proteção cardiovascular e devem ser considerados nas novas abordagens terapêuticas. Nesse sentido, recentes estudos têm relatado que o Fator Neurotrófico Derivado do Encéfalo (Brain-Derived Neurotrophic Factor, BDNF) está reduzido em indivíduos predispostos a desenvolverem DCV, e que o treinamento físico aeróbio aumenta as quantidades de BDNF circulante. O BDNF é uma neurotrofina encontrada em altas concentrações no hipocampo e córtex cerebral, sendo considerada molécula-chave na manutenção da plasticidade sináptica e na sobrevivência das células neuronais. Além da plasticidade neuronal, BDNF também é importante na função vascular, promovendo angiogênese por meio da regulação por espécies reativas de oxigênio (ROS). Entretanto, uma variante do gene do BDNF em humanos, o polimorfismo Val66Met (substituição do aminoácido valina por uma metionina na posição 66 do códon), que ocorre em 20-30% da população caucasiana, pode afetar as concentrações de BDNF no plasma e sua atividade em todos os tecidos periféricos contendo receptores tirosina quinase B (TrkB), como o endotélio. De fato, recentemente observamos que o polimorfismo Val66Met prejudica a reatividade vascular e o BDNF circulante em resposta ao treinamento físico. Dessa forma, apresentaremos a seguir uma discussão sobre os níveis séricos de BDNF na proteção cardiovascular, a variante genética Val66Met na reatividade vascular e o efeito do exercício físico.

Abstract Cardiovascular disease (CVD) is currently the leading cause of death in Brazil and worldwide. In 2016, CVD accounted for more than 17 million deaths, representing 31% of all deaths globally. Molecular and genetic mechanisms may be involved in vascular protection and should be considered in new therapeutic approaches. In this sense, recent studies have reported that brain-derived neurotrophic factor (BDNF) is reduced in individuals predisposed to develop CVD, and that aerobic physical training increases the amounts of circulating BDNF. BDNF is a neurotrophin found at high concentrations in the hippocampus and cerebral cortex and is considered a key molecule for the maintenance of synaptic plasticity and survival of neuronal cells. In addition to neuronal plasticity, BDNF is also important in vascular function, promoting angiogenesis through the regulation of reactive oxygen species (ROS). However, a variant of the BDNF gene in humans, the Val66Met polymorphism (substitution of the amino acid valine for a methionine at position 66 of the codon), occurring in 20-30% of the Caucasian population, may affect plasma BDNF concentrations and its activity in all peripheral tissues containing tyrosine kinase B receptors (TrkB), such as the endothelium. Thus, we will present a discussion about the role of serum BDNF levels in cardiovascular protection, Val66Met genetic variant in vascular reactivity and the effect of physical exercise.

Estimación del balance de metionina y lisina metabolizable en vacas de leche en pastoreo / Estimation of the balance of metabolizable lysine and methionine for grazing dairy cows

RESUMEN Objetivos. El objetivo de este trabajo fue estimar en vacas en pastoreo, tanto la reproducibilidad como la precisión del balance de metionina (Met) y lisina (Lis), aminoácidos más limitantes en la producción de leche, cuando se comparan los valores predichos versus los valores observados. Materiales y métodos. Se usaron 12 vacas durante un periodo de 20 días. Control: animales pastoreando y suplementados con alimento balanceado; Met-Lis: igual al control y el suplemento se ajustó con Lis y Met protegida. Para los valores predichos para la suplementación de Met y Lis, se tuvo en cuenta el promedio del consumo de materia seca (CMS) del hato, basado en la oferta y el consumo de pasto y los valores de proteína microbiana. Los valores observados se determinaron con base en el CMS individual usando marcadores externos e internos, además, la producción individual de proteína microbiana. Se realizó una prueba de t pareada y un modelo de predicción para determinar la eficiencia fue determinado usando el error cuadrático medio de predicción (ECMP) y el coeficiente de concordancia (CCC). Resultados. Se encontraron diferencias significativas entre la suplementación y el balance de Met y Lis, entre los valores predichos y los valores observados para el CMS del forraje, la digestibilidad de la proteína microbiana, la producción de proteína microbiana, el suministro y el balance de Lis y Met. El CCC del balance de Lis y Met fue bajo (0.10), el ECMP fue alto, excepto para el CMS, que tuvo una concordancia moderada (0.63) y un bajo ECMP(4.42). Conclusiones. Estos resultados demuestran la falta de precisión de las herramientas que se usan para balancear las raciones individuales de vacas en pastoreo, ya que subestiman la suplementación y el balance de los aminoácidos.

ABSTRACT Objective. The aim of this study was to determine in grazing cows, the reproducibility and accuracy of the balance between predicted values, when compared with the observed values for the most limiting amino acids in milk protein synthesis, the methionine (Met) and Lysine (Lys). Materials and methods. Twelve lactating cows were used for a 20-day experimental period. Control: animals grazing and supplemented with balanced food; Met-Lys: same as control and supplemented with adjusted rumen protected Met and Lys. For Met and Lys supply predicted values, it was taking in account the average of the dry matter intake (DMI) of the herd, based in offer and foraging control and values of microbial protein data. Observed values were determined based in the individual DMI intake, using external and internal markers and the individual microbial protein production. A t-paired-sample test was performed and the efficiency of the model's prediction was determined using the mean square prediction error (MSPE) and the concordance coefficient (CCC). Results. Significant differences were found between the predicted and observed values for DMI forage, digestible microbial protein and microbial protein production, supply and the balance of Lys and Met. The CCC for Lys and Met balance were low (0.10), the MSPE was high except for the total DMI with a moderate concordance (0.63) and low MSPE (4.42). Conclusions. These results indicate a lack of precision of the tools, which underestimates the supply and balance of amino acids in individual grazing cows.

Utilidad de la 18f-colina pet/tc en hiperparatiroidismo primario persistente o recurrente: experiencia inicial / Usefulness of 18f-choline pet / tc in persistent or recurrent primary hyperparathyroidism: initial experience

El hiperparatiroidismo persistente/recurrente representa un desafío en la localización del tejido paratiroideo hiperfuncionante. En esta subpoblación, los métodos convencionales ofrecen un menor rédito diagnóstico. La 18F-colina PET/TC podría ser una buena alternativa dada su mejor resolución espacial, capacidad de detectar glándulas ectópicas y la conjunción de la imagen molecular y anatómica. Sin embargo, la evidencia en este subgrupo de pacientes es escasa. Objetivo: evaluar la utilidad de la 18F-colina PET/TC como método de localización en el hiperparatiroidismo persistente o recurrente. Materiales y métodos: se analizaron los pacientes con 18F-colina PET/TC para hiperparatiroidismo entre diciembre de 2015 y enero de 2018 en un centro terciario de alto volumen. Se analizaron el número de lesiones, su localización, tamaño y el Standard Uptake Value máximo (SUV max) en las imágenes tempranas y tardías. Se compararon los resultados con los métodos convencionales. Resultados: 7 de 15 pacientes habían sido operados previamente (persistentes/recurrentes). La 18F-colina PET/TC detectó 6/7 casos (83,33%), la ecografía cervical 1/4 (25%) y el SPECT de paratiroides y la resonancia nuclear magnética 2/5 (40%). El SUV max obtenido fue variable, en la mitad de los casos a los 10 minutos y en los restantes a la hora; el tamaño promedio de las lesiones fue 8,61 mm (6-12 mm). Conclusiones: la 18F-colina PET/TC muestra una alta tasa de detección en los pacientes con hiperparatiroidismo persistente/recurrente. La combinación del comportamiento biológico del PET con los hallazgos morfológicos aportados por la TC con contraste endovenoso le ofrecería ventajas sobre otros estudios que podrían posicionarlo como método de primera línea en esta subpoblación. (AU)

Persistent or recurrent hyperparathyroidism represents a challenge regarding the localization of the hyper-functioning parathyroid tissue. In this subpopulation of hyperpharathyroid patients, conventional methods have a low diagnostic yield. The 18F-choline PET /CT could be a good alternative given its better spatial resolution, ability to detect ectopic glands, and the conjunction of the molecular and anatomical image. However, the evidence in this subgroup of patients is limited. Objective: to evaluate the utility of 18F-choline PET/ CT as a localization method in persistent or recurrent hyperparathyroidism. Materials and methods: patients with 18F-choline PET / CT for hyperparathyroidism between December 2015 and January 2018 in a high-volume tertiary center were included. The number of lesions, and their location, size, and maximum Standard Uptake Value (SUV) in the early and late images were analyzed. The results were compared to conventional methods. Results: 7 of 15 patients had been previously operated (persistent/recurrent). 18F-choline PET / CT detected 6/7 cases (83,33%), cervical ultrasound 1/4 (25%) and parathyroid SPECT and magnetic resonance 2/5 (40%). The maximum SUV was variable, one half at 10 minutes and the other half at 60 minutes; the average size of the lesions was 8.61 mm (6-12 mm). Conclusions: 18F-Choline PET / CT shows a high detection rate in patients with persistent / recurrent hyperparathyroidism. The combination of the biological behavior of PET with the morphological findings provided by CT with intravenous contrast would offer advantages over other studies that could position it as a first line method in this subpopulation. (AU)

Feasibility and Stability of Liver Biopsy before Treatment for Preclinical Nonalcoholic Fatty Liver Studies

BACKGROUND: The heterogeneity of histological findings in preclinical diet-induced nonalcoholic fatty liver disease (NAFLD) animal models is highly challenging. Here, we aimed to evaluate the feasibility and stability of repeated liver biopsy in NAFLD animal models. METHODS: Heterogeneity of diet-induced NAFLD was evaluated at different time points in 52 high-fat diet (HFD), 35 methionine choline-deficiency diet (MCD), and 166 western diet (WD) induced NAFLD mice. Serial liver biopsies (left lateral, right medial, and left medial lobes) were performed monthly for up to 3 months. Mortality rates and changes in food intake, body weight, and liver enzymes were assessed. RESULTS: At 12 weeks, of the HFD animals, 14% and 30% did not develop steatosis and lobular inflammation, respectively; of the MCD animals, 7% did not develop lobular inflammation; and of the WD animals, 14% and 51% did not develop steatosis and lobular inflammation, respectively. The mortality rate of repeated liver biopsy was 1.62% (2/123 mice died). Repeated liver biopsy can be used to trace disease progression. Although body weight, food intake, and liver enzymes slightly changed after biopsy, all recovered within a week. Repeated liver biopsy did not affect the degrees of inflammation and steatosis of the other liver lobes. CONCLUSION: The diet-induced NAFLD models were quite heterogeneous. Our results suggest that the repeated liver biopsy before treatment was applicable and stable in this NAFLD animal study.

Four amino acids as serum biomarkers for anti-asthma effects in the ovalbumin-induced asthma mouse model treated with extract of Asparagus cochinchinensis / 한국실험동물학회지

The butanol extract of Asparagus cochinchinensis roots fermented with Weissella cibaria (BAW) effectively prevents inflammation and remodeling of airway in the ovalbumin (OVA)-induced asthma model. To characterize biomarkers that can predict the anti-asthmatic effects induced by BAW treatment, we measured the alteration of endogenous metabolites in the serum of OVA-induced asthma mice after administration of low concentration BAW (BAWLo, 250 mg/kg) and high concentration BAW (BAWHi, 500 mg/kg) using ¹H nuclear magnetic resonance (¹H-NMR) spectral data. The number of immune cells and serum concentration of IgE as well as thickness of the respiratory epithelium and infiltration of inflammatory cells in the airway significantly recovered in the OVA+BAW treated group as compared to the OVA+Vehicle treated group. In the metabolic profile analysis, the pattern recognition showed completely separate clustering of serum analysis parameters between the OVA+Vehicle and OVA+BAW treated groups. Of the total endogenous metabolites, 19 metabolites were upregulated or downregulated in the OVA+Vehicle treated group as compared to the Control treated group. However, only 4 amino acids (alanine, glycine, methionine and tryptophan) were significantly recovered after BAWLo and BAWHi treatment. This study provides the first results pertaining to metabolic changes in the asthma model mice treated with OVA+BAW. Additionally, these findings show that 4 metabolites can be used as one of biomarkers to predict the anti-asthmatic effects.

Comparison of the Plasma Metabolome Profiles Between the Internal Thoracic Artery and Ascending Aorta in Patients Undergoing Coronary Artery Bypass Graft Surgery Using Gas Chromatography Time-of-Flight Mass Spectrometry

BACKGROUND: The left internal thoracic artery (LITA) has been used as the first conduit of choice in coronary artery bypass grafting (CABG) because of excellent long-term patency and outcomes. However, no studies have examined substances other than nitric oxide that could be beneficial for the bypass conduit, native coronary artery or ischemic myocardium. This study was conducted to evaluate differences in metabolic profiles between the LITA and ascending aorta using gas chromatography-time of flight-mass spectrometry (GC-TOF-MS). METHODS: Twenty patients who underwent CABG using the LITA were prospectively enrolled. Plasma samples were collected simultaneously from the LITA and ascending aorta. GC-TOF-MS based untargeted metabolomic analyses were performed and a 2-step volcano plot analysis was used to identify distinguishable markers from two plasma metabolome profiles. Semi-quantitative and quantitative analyses were performed using GC-TOF-MS and enzyme-linked immunosorbent assay, respectively, after selecting target metabolites based on the metabolite set enrichment analysis. RESULTS: Initial volcano plot analysis demonstrated 5 possible markers among 851 peaks detected. The final analysis demonstrated that the L-cysteine peak was significantly higher in the LITA than in the ascending aorta (fold change = 1.86). The concentrations of intermediate metabolites such as L-cysteine, L-methionine and L-cystine in the ‘cysteine and methionine metabolism pathway' were significantly higher in the LITA than in the ascending aorta (2.0-, 1.4- and 1.2-fold, respectively). Quantitative analysis showed that the concentration of hydrogen sulfide (H2S) was significantly higher in the LITA. CONCLUSION: The plasma metabolome profiles of the LITA and ascending aorta were different, particularly higher plasma concentrations of L-cysteine and H2S in the LITA.

Combination of Magnetic Resonance Spectroscopy and ¹¹C-Methionine Positron Emission Tomography for the Accurate Diagnosis of Non-Enhancing Supratentorial Glioma

OBJECTIVE: To evaluate whether the combination of magnetic resonance spectroscopy (MRS) and 11C-methionine positron emission tomography (11C-MET PET) could increase accurate diagnostic sensitivity for non-enhancing supratentorial gliomas. MATERIALS AND METHODS: Between February 2012 and December 2017, 109 patients with non-enhanced supratentorial lesions on contrast-enhanced MRI were enrolled. Each patient underwent MRS and 11C-MET PET before treatment. A lesion was considered to be a glioma when either the MRS or 11C-MET PET results reached the diagnostic threshold. The radiological diagnosis was compared with the pathological diagnosis or medical diagnostic criteria. RESULTS: The sensitivity and specificity were 60.0% and 50.0% for MRS and 75.8% and 50.0% for 11C-MET PET, respectively. Upon combining the two modalities, the sensitivity and specificity of the imaging-based diagnosis prior to surgery reached 89.5% and 42.9%, respectively. Statistically significant differences in the sensitivities were observed between the combined and individual approaches (MRS alone, 89.5% vs. 60.0%, p < 0.001; 11C-MET PET alone, 89.5% vs. 75.8%, p = 0.001). However, no significant differences in specificity were observed between the combined and individual modalities. CONCLUSION: The combination of MRS and 11C-MET PET findings significantly increases accurate diagnostic sensitivity for non-enhancing supratentorial gliomas without significantly lowering the specificity. This finding suggests the potential of the combined MRS and 11C-MET PET approach in clinical applications.

Rumen-protected methionine in cattle: influences on reproduction, immune response, and productive performance / Metionina protegida da degradação ruminal em bovinos: influências na reprodução, resposta imune e desempenho produtivo

Nowadays, information and knowledge generated about the main ingredients used in cattle diets have enabled greater assertiveness in their formulation. Among the ingredients, amino acids stand out as a promising tool, capable of reducing total crude protein (CP) levels and adjusting optimal metabolizable protein concentrations in diets. Nutritional programs allow diets due to amino acid requirements, providing the opportunity to increase the efficiency of the use of dietary nitrogen, increasing the scarce protein concentrates, maintaining or even boosting performance. This review aimed to present the influences of methionine, in its formulation protected from ruminal degradation, according to reproductive parameters, immune response, and productive performance in cattle. Reproduction-related benefits are linked to the early days of embryonic implantation in the uterine environment, which initially secretes through the histotroph produced by endometrial glands, the nutrients needed to develop the conceptus until implantation, and vascular communication with the mother. Given the immune response, the main results are related to the benefits of innate immunity, with marked increase in phagocytic capacity of neutrophils and monocytes, as well as an important antioxidant effect mediated by methionine products, such as glutathione. When evaluating the influences on productivity, the most evident correlation is the increase in protein in the milk of cows supplemented with methionine. Over the past decade, studies investigating the potential benefits of this strategic supplementation in beef cattle were intensified, expanding the opportunities for the development of new experimental projects.(AU)

Atualmente, as informações e o conhecimento gerado sobre os principais ingredientes utilizados em dietas para bovinos possibilitaram maior assertividade em suas formulações. Dentre esses ingredientes, os aminoácidos se destacam como uma ferramenta promissora, capaz de levar à redução nos níveis totais de proteína bruta e ajustar as concentrações ideais de proteína metabolizável nas dietas. Programas nutricionais permitem formular dietas por exigências de aminoácidos, oportunizando o aumento na eficiência de utilização do nitrogênio dietético, reduzindo dispêndios com concentrados ricos em proteína, com a manutenção, ou ainda, incremento de desempenho. Esta revisão buscou apresentar as influências da metionina, em sua formulação protegida da degradação ruminal, frente a parâmetros reprodutivos, resposta imune e desempenho produtivo em bovinos. Os benefícios relacionados à reprodução se mostram ligados aos primeiros dias de implantação embrionária no ambiente uterino, que inicialmente secreta, através do histotrofo produzido por glândulas endometriais, os nutrientes necessários para o desenvolvimento do concepto até a implantação e comunicação vascular com a mãe. Dada a resposta imune, os principais resultados estão relacionados aos benefícios da imunidade inata, com aumento acentuado da capacidade fagocitária de neutrófilos e monócitos, assim como um importante efeito antioxidante mediado por produtos originários da metionina, como a glutationa. Por fim, quando avaliadas as influências em produtividade, a correlação mais evidente é o incremento em proteína no leite de vacas suplementadas com metionina. Na última década, os estudos que investigam os potenciais benefícios dessa suplementação estratégica em bovinos de corte foram intensificados, abrindo um caminho de oportunidades para o desenvolvimento de novos projetos experimentais.(AU)

Investigation of the association of idiopathic male infertility with polymorphisms in the methionine synthase (MTR) gene / 대한생식의학회지

OBJECTIVE: Spermatogenesis is a complex process that is regulated by a number of genes, some of which are involved in folate-dependent 1-carbon metabolism. Methionine synthase (encoded by MTR) is a key enzyme participating in this pathway. This study aimed to investigate the relationship of the MTR 2756A > G polymorphism with idiopathic male fertility in the Iranian population. METHODS: The participants of this study included 100 men with idiopathic infertility and 100 healthy men as the control group. Genotyping of MTR 2756A > G was performed using the polymerase chain reaction and restriction fragment length polymorphism technique. The obtained data were analyzed using SPSS ver. 20.0 with a level of confidence of p G single-nucleotide polymorphism is not a predisposing factor for idiopathic infertility in men.

Methionine Adenosyltransferase 1: A Proteomic Surrogate Marker of Early Hepatocellular Carcinoma in Cirrhotic Patients

BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.

Links between Serine Biosynthesis Pathway and Epigenetics in Cancer Metabolism

Cancer metabolism is considered as one of major cancer hallmarks. It is important to understand cancer-specific metabolic changes and its impact on cancer biology to identify therapeutic potentials. Among cancer-specific metabolic changes, a role of serine metabolism has been discovered in various cancer types. Upregulation of serine synthesis pathway (SSP) supports cell proliferation and metastasis. The change of serine metabolism is, in part, mediated by epigenetic modifiers, such as Euchromatic histone-lysine N-methyltransferase 2 and Lysine Demethylase 4C. On the other hand, SSP also influences epigenetic landscape such as methylation status of nucleic acids and histone proteins via affecting S-adenosyl methionine production. In the review, we highlight recent evidences on interactions between SSP and epigenetic regulation in cancer. It may provide an insight on roles and regulation of SSP in cancer metabolism and the potential of serine metabolism for cancer therapy.