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Infant cereals are typically the first foods introduced as complementary foods. Cereals used to elaborate complementary foods, such as wheat, maize and rice, are susceptible to mycotoxin contamination. Among mycotoxins, fumonisins have been epidemiologically associated, in humans, with oesophageal cancer, neural tube defects and stunting. Fumonisins have been found in maize and wheat grains in Argentina. In the present study, a survey was conducted to determine their occurrence in 82 wheat-based and multicereal-based infant cereal items collected from retail stores in Rio Cuarto, Argentina, using HPLC-MS. Of these samples, 84% showed FBs contamination with levels ranging from 0.05 to 992 µg/kg). Although FB1 was the most prevalent fumonisin, FB2 was found at higher levels. Most samples had levels below the limit of 200 µg/kg set for Argentinean cereal products for children. The outcome of this survey provides information on the naturally presence of fumonisin in infant cereal intended for children in Argentina, which can be helpful to consider relevant monitoring programmes.
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The aim of this study was to determine the impact of Kluyveromyces marxianus VM004 culture conditions on the cell wall (CW) structure and its influence on aflatoxin B1 binding. The yeast was inoculated into two types of culture media: yeast extract-peptone-dextrose (YPD) broth and dried distiller's grains with solubles (DDG). The CW was extracted from the biomass produced in these media. AFB1 (150ng/ml) adsorption tests using the biomass (1×107cells/ml) and the CW (0.001g) were performed at pH 2 and pH 8. Transmission electron microscopy (TEM) evaluated the CW thickness, and infrared spectroscopy (IR) determined the CW composition. Biomass production in YPD was higher than that in DDG. Cell diameter (µm) and CW thickness (µm) increased in the DDG medium. The CW percentage obtained in DDG was higher than that in YPD. The absorbance of carbohydrates by IR was higher in YPD. pH influenced AFB1 adsorption, which was lower at pH 8. The proportion of ß-glucan and chitin present in CW was higher in the YPD medium. The IR method allowed to study the CW carbohydrate variation under the influence of these carbon sources. In conclusion, the culture media composition influenced the ß-glucan and chitin composition and consequently, AFB1 adsorption.
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Maize (Zea mays L.) may be infected by Fusarium verticillioides and F. proliferatum, and consequently contaminated with fumonisins (FBs), as well as the co-products of bioethanol intended for animal feed. Laccase enzymes have a wide industrial application such as mycotoxin degradation. The aims were to isolate and identify fungal laccase-producing strains, to evaluate laccase production, to determine the enzymatic stability under fermentation conditions, and to analyse the effectiveness in vitro of enzymatic extracts (EEs) containing laccases in degrading FB1. Strains belonging to Funalia trogii, Phellinus tuberculosus, Pleurotus ostreatus, Pycnoporus sanguineus and Trametes gallica species showed laccase activity. Different isoforms of laccases were detected depending on the evaluated species. For the FB1 decontamination assays, four enzymatic activities (5, 10, 15 and 20 U/mL) were tested, in the absence and presence of vanillic acid (VA) and 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) as redox mediators (1 and 10 mM). Trametes gallica B4-IMICO-RC EE was the most effective strain in buffer, achieving a 60% of FB1 reduction. Laccases included in EEs remained stable at different alcoholic degrees in maize steep liquor (MSL), but no significant FB1 reduction was observed under the conditions evaluated using MSL. This study demonstrate that although laccases could be good candidates for the development of a strategy to reduce FB1, further studies are necessary to optimise this process in MSL.
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Fumonisinas , Lacase , Zea mays , Zea mays/microbiologia , Zea mays/química , Lacase/metabolismo , Fumonisinas/metabolismo , Etanol/metabolismo , Fusarium/enzimologia , Fusarium/metabolismo , Descontaminação/métodos , Fermentação , Fungos/enzimologia , BiocombustíveisRESUMO
Direct-to-Mass Spectrometry and ambient ionization techniques can be used for biochemical fingerprinting in a fast way. Data processing is typically accomplished with vendor-provided software tools. Here, a novel, open-source functionality, entitled Tidy-Direct-to-MS, was developed for data processing of direct-to-MS data sets. It allows for fast and user-friendly processing using different modules for optional sample position detection and separation, mass-to-charge ratio drift detection and correction, consensus spectra calculation, and bracketing across sample positions as well as feature abundance calculation. The tool also provides functionality for the automated comparison of different sets of parameters, thereby assisting the user in the complex task of finding an optimal combination to maximize the total number of detected features while also checking for the detection of user-provided reference features. In addition, Tidy-Direct-to-MS has the capability for data quality review and subsequent data analysis, thereby simplifying the workflow of untargeted ambient MS-based metabolomics studies. Tidy-Direct-to-MS is implemented in the Python programming language as part of the TidyMS library and can thus be easily extended. Capabilities of Tidy-Direct-to-MS are showcased in a data set acquired in a marine metabolomics study reported in MetaboLights (MTBLS1198) using a transmission mode Direct Analysis in Real Time-Mass Spectrometry (TM-DART-MS)-based method.
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Espectrometria de Massas , Metabolômica , Software , Metabolômica/métodos , Espectrometria de Massas/métodos , Linguagens de ProgramaçãoRESUMO
Resumen Objetivo: Explorar y discutir literatura científica teórica y práctica para comparar la diversificación y la especialización deportivas tempranas como un enfoque deportivo y educativo. Métodos: Se realizó una revisión sistemática siguiendo las pautas PRISMA, se incluyó un total de 61 estudios. Resultados: Entrenadores, padres e hijos consideran que la mejor forma de desarrollar el talento deportivo y alcanzar la élite en el deporte es participar en una sola disciplina y hacerlo lo antes posible para lograr la especialización y las máximas habilidades técnicas, físicas y psicológicas. Los caminos de especialización deportiva pueden conducir a una situación física, social y mental que comprometa su desarrollo integral. Conclusión: Se puede plantear, en primer lugar, la diversificación deportiva en edades tempranas y luego la especialización; una vez alcanzadas las bases de la fuerza, el acondicionamiento y el entrenamiento neuromuscular, así como una maduración psicomotora específica, para que su rendimiento deportivo y su salud no se vean comprometidos en el mediano o largo plazo. Es necesario considerar que pocos niños logran obtener un lugar en los deportes de élite, por lo que, para muchos de ellos, la educación en torno al deporte será la base para el ejercicio de su ciudadanía como personas activas.
Abstract Purpose: To explore and discuss theoretical and practical scientific literature to compare sports diversification and early sports specialization as a sport and educational approach. Methods: A systematic review was conducted following PRISMA guidelines, and 61 studies were included. Results: Coaches, parents, and children consider that the best way to develop sports talent and enter the elite in sports is to practice a single discipline as early as possible to achieve specialization and maximum technical skills and physical and psychological conditions. Sports specialization paths may lead to a physical, social, and mental state that compromises their integral development. Conclusion: Sports diversification should be considered first at an early age and, afterward, the specialization once the bases of strength, conditioning, neuromuscular training, and a specific psychomotor maturation have been achieved, so that sports performance and health are not compromised in the medium or long term. It is necessary to consider that few children enter elite sports, so for many of them, sports education will be the basis for exercising their citizenship as active people.
Resumo Objetivos: Explorar e discutir literatura científica teórica e prática para comparar a diversificação e especialização esportiva precoce como uma abordagem esportiva e educacional. Métodos: uma revisão sistemática foi realizada seguindo as diretrizes do PRISMA, um total de 61 estudos foram incluídos Resultados: Treinadores, pais e crianças acreditam que a melhor maneira de desenvolver talentos esportivos e ingressar na elite do esporte é participar de uma única disciplina e fazer o mais cedo possível para alcançar a especialização e o máximo de habilidades técnicas, físicas e psicológicas. Os caminhos da especialização esportiva podem levar a uma situação física, social e mental que comprometa seu desenvolvimento integral. Conclusão: Primeiro, a diversificação esportiva pode ser considerada em uma idade precoce e depois a especialização, uma vez que os princípios básicos de força, condicionamento e treinamento neuromuscular tenham sido alcançados, bem como a maturação psicomotora específica para que seu desempenho esportivo e saúde não sejam comprometidos a médio ou longo prazo. É necessário considerar que poucas crianças conseguem obter um lugar nos esportes de elite, de modo que, para muitas delas, a educação em torno do esporte será a base para o exercício de sua cidadania como pessoas ativas.
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Maize (Zea mays L.) is an important crop in Argentina. Aspergillus section Flavi can infect this crop at the pre-harvest stage, and the harvested grains can be contaminated with aflatoxins (AFs). During the production of bioethanol from maize, AF levels can increase up to three times in the final co-products, known as, dry and wet distiller's grain with solubles (DDGS and WDGS), intended for animal feed. Fungal enzymes like laccases can be a useful tool for reducing AF contamination in the co-products obtained from this process. The aim of the present study was to evaluate the ability of laccase enzymes included in enzymatic extracts (EE) produced by different species in the Basidiomycota phylum to reduce AF (AFB1 and AFB2) accumulation under the conditions of in vitro assays. Four laccase activities (5, 10, 15, and 20 U/mL) exerted by nine isolates were evaluated in the absence and presence of vanillic acid (VA), serving as a laccase redox mediator for the degradation of total AFs. The enzymatic stability in maize steep liquor (MSL) was confirmed after a 60 h incubation period. The most effective EE in terms of reducing AF content in the buffer was selected for an additional assay carried out under the same conditions using maize steep liquor obtained after the saccharification stage during the bioethanol production process. The highest degradation percentages were observed at 20 U/mL of laccase enzymatic activity and 1 mM of VA, corresponding to 26% for AFB1 and 26.6% for AFB2. The present study provides valuable data for the development of an efficient tool based on fungal laccases for preventing AF accumulation in the co-products of bioethanol produced from maize used for animal feed.
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Aflatoxinas , Basidiomycota , Animais , Zea mays , Descontaminação , Lacase , Ácido VanílicoRESUMO
Glutathione (GSH) is one of the main antioxidant molecules present in cells. It harbors a thiol group responsible for sustaining cellular redox homeostasis. This moiety can react with cellular electrophiles such as formaldehyde yielding the compound S-hydroxymethyl-GSH (HSMGSH). HSMGSH is the substrate of the enzyme alcohol dehydrogenase 5 (ADH5) and thus a key intermediate in formaldehyde metabolism. In this work, we describe a method for the chemical synthesis of HSMGSH and a pipeline to identify this compound in complex cell extracts by means of ultra-high-performance liquid chromatography coupled to high-resolution spectrometry (UHPLC-HRMS). This method also allows determining GSH and oxidized disulfide (GSSG) in the same samples, thus providing broad information about formaldehyde-GSH metabolism.
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Antioxidantes , Glutationa , Humanos , Dissulfeto de Glutationa/química , Cromatografia Líquida de Alta Pressão/métodos , Glutationa/metabolismo , Antioxidantes/metabolismo , Compostos de Sulfidrila , OxirreduçãoRESUMO
BACKGROUND: Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown. RESULTS: Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features. CONCLUSIONS: These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Adenosil-Homocisteinase , Plasticidade Celular , CarcinogêneseRESUMO
INTRODUCTION: There is still no community consensus regarding strategies for data quality review in liquid chromatography mass spectrometry (LC-MS)-based untargeted metabolomics. Assessing the analytical robustness of data, which is relevant for inter-laboratory comparisons and reproducibility, remains a challenge despite the wide variety of tools available for data processing. OBJECTIVES: The aim of this study was to provide a model to describe the sources of variation in LC-MS-based untargeted metabolomics measurements, to use it to build a comprehensive curation pipeline, and to provide quality assessment tools for data quality review. METHODS: Human serum samples (n=392) were analyzed by ultraperformance liquid chromatography coupled to high-resolution mass spectrometry (UPLC-HRMS) using an untargeted metabolomics approach. The pipeline and tools used to process this dataset were implemented as part of the open source, publicly available TidyMS Python-based package. RESULTS: The model was applied to understand data curation practices used by the metabolomics community. Sources of variation, which are often overlooked in untargeted metabolomic studies, were identified in the analysis. New tools were used to characterize certain types of variations. CONCLUSION: The developed pipeline allowed confirming data robustness by comparing the experimental results with expected values predicted by the model. New quality control practices were introduced to assess the analytical quality of data.
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Curadoria de Dados , Metabolômica , Humanos , Cromatografia Líquida , Reprodutibilidade dos Testes , Espectrometria de Massas em TandemRESUMO
The ultimate goal of surgical treatment in cancer is to remove the tumor mass for restoring a healthy state. A 16-lipid panel that discriminated healthy controls from clear cell renal cell carcinoma (ccRCC) patients in a prior study was evaluated in the present work in paired-serum samples collected from patients (n = 41) before and after nephrectomy. Changes in the lipid and metabolite fingerprints from ccRCC patients were investigated and compared with fingerprints from healthy individuals obtained by means of ultra-performance liquid chromatography-high-resolution mass spectrometry. The lipid panel differentiated phenotypes associated with metabolic restoration after surgery, representing a serum signature of phenoreversion to a healthy metabolic state. In particular, PC 16:0/0:0, PC 18:2/18:2, and linoleic acid allowed discriminating serum samples from ccRCC patients with poor prognosis from those with an improved outcome during the follow-up period. Ratios of PC 16:0/0:0 and PC 18:2/18:2 with linoleic acid levels may contribute as prognostic tools to support decision-making during the patient follow-up care. The preliminary character of these results should be validated with larger cohorts, including subjects with different ethnicities, life style, and diets. MetaboLights study references: MTBLS1839, MTBLS3838, and MTBLS4629.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/cirurgia , Ácido Linoleico , Prognóstico , Biomarcadores TumoraisRESUMO
Formaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking, likely contributing to the onset of the human DNA repair condition Fanconi Anaemia. Mutations in the genes coding for FA detoxifying enzymes underlie a human inherited bone marrow failure syndrome (IBMFS), even in the presence of functional DNA repair, raising the question of whether FA causes relevant cellular damage beyond genotoxicity. Here, we report that FA triggers cellular redox imbalance in human cells and in Caenorhabditis elegans. Mechanistically, FA reacts with the redox-active thiol group of glutathione (GSH), altering the GSH:GSSG ratio and causing oxidative stress. FA cytotoxicity is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), which metabolizes FA-GSH products, lastly yielding reduced GSH. Furthermore, we show that GSH synthesis protects human cells from FA, indicating an active role of GSH in preventing FA toxicity. These findings might be relevant for patients carrying mutations in FA-detoxification systems and could suggest therapeutic benefits from thiol-rich antioxidants like N-acetyl-L-cysteine.
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Aldeído Oxirredutases/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Anemia de Fanconi/metabolismo , Formaldeído/toxicidade , Glutationa/metabolismo , Aldeído Oxirredutases/genética , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Dano ao DNA , Modelos Animais de Doenças , Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Formaldeído/metabolismo , Técnicas de Inativação de Genes , Células HCT116 , Humanos , Oxirredução , Estresse OxidativoRESUMO
Resumen El propósito de esta investigación fue examinar el enlace entre los hábitos de actividad física de los niños centroamericanos, su nivel de autoestima, edad y país de origen. Este fue un estudio correlacional de muestras probabilísticas aleatorias por conglomerados, que evaluó 5291 estudiantes matriculados en cuarto, quinto y sexto grado, de los cuales el 52.3 % corresponde a niñas y el 47.7 % a niños, pertenecientes a 74 escuelas en Guatemala, Honduras, El Salvador, Costa Rica, Nicaragua y Panamá, con una edad media de 10.90 ± 1.13. En todas las naciones, se utilizó el cuestionario LAWSEQ para medir el nivel de autoestima y se aplicó el de actividad física para la niñez (PAQ-C). Un análisis de regresión logística binaria fue ejecutado para estimar si las variables independientes podrían predecir el nivel de autoestima de los infantes. Los resultados mostraron que el 47 % de los estudiantes se percibió con un bajo nivel de actividad física y, con respecto a la autoestima, quienes poseen de 9 a 10 años tuvieron porcentajes más bajos, con 51.6 % y 47.7 %, respectivamente. En cuanto al país de origen, los niños de Costa Rica y Guatemala tienen un mejor nivel de autoestima que aquellos habitantes de El Salvador, Nicaragua, Honduras y Panamá. Además, se determinó que la edad, el nivel de actividad física y el país de origen predecían el 58 % del nivel de autoestima infantil centroamericana. Esto demuestra la importancia de promover la actividad física en dicho sector poblacional, para contribuir al desarrollo de su autoestima.
Abstract This research aimed to examine the relationships between the levels of self-esteem of Central American schoolchildren and their physical activity habits, ages, and countries of origin. This was a correlational study of random cluster probabilistic samples, which evaluated 5,291 students enrolled in fourth, fifth, and sixth grades, 52.3% of whom were girls and 47.7% boys, from 74 schools in Guatemala, Honduras, El Salvador, Costa Rica, Nicaragua, and Panama, with an average age of 10.90 ± 1.13 years. Lawrence's Self-Esteem Questionnaire (LAWSEQ) was used to measure levels of self-esteem, and the physical activity questionnaire for boys and girls (PAQ-C) was applied in all the countries. A binary logistic regression analysis was conducted to estimate the statistical probability that the independent variables (age, level of activity, and country of origin) could predict the level of self-esteem. The results of this investigation showed that 47% of the children under study perceive themselves to have a low level of physical activity and that children from 9 to 10 years had lower percentages of self-esteem with 51.6% and 47.7%, respectively. In terms of country of origin, children from Costa Rica and Guatemala have a better level of self-esteem than those living in El Salvador, Nicaragua, Honduras, and Panama. In addition, it was determined that age, level of physical activity, and country of origin predicted 58% of the level of self-esteem of Central American children. This situation shows the importance of promoting physical activity in childhood to contribute to the development of self-esteem.
Resumo O objetivo desta pesquisa foi examinar a ligação entre os hábitos de atividade física de crianças da América Central, seu nível de autoestima, idade e país de origem. Este foi um estudo correlacional de amostras probabilísticas aleatórias por conglomerados, que avaliou 5.291 estudantes matriculados na quarta, quinta e sexta séries do ensino fundamental, dos quais 52,3% correspondem a meninas e 47,7% a meninos, pertencentes a 74 escolas na Guatemala, Honduras, El Salvador, Costa Rica, Nicarágua e Panamá, com média de idade de 10,90 ± 1,13. Nesses países, o questionário LAWSEQ foi utilizado para medir o nível de autoestima e o questionário de atividade física para a infância (PAQ-C) foi aplicado. Uma análise de regressão logística binária foi realizada para estimar se as variáveis independentes poderiam predizer o nível de autoestima das crianças. Os resultados mostraram que 47% dos estudantes se perceberam com baixo nível de atividade física e, no que se refere à autoestima, aqueles com 9 a 10 anos apresentaram percentuais menores, com 51,6% e 47,7%, respectivamente. Quanto ao país de origem, as crianças da Costa Rica e da Guatemala apresentam um nível de autoestima superior as de El Salvador, Nicarágua, Honduras e Panamá. Além disso, determinou-se que a idade, o nível de atividade física e o país de origem previam os 58% do nível de autoestima da criança centro-americana. Isso mostra a importância da promoção da atividade física nesse setor populacional, de forma a contribuir para o desenvolvimento de sua autoestima.
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Humanos , Masculino , Feminino , Criança , Educação Física e Treinamento/estatística & dados numéricos , Autoimagem , Autoavaliação (Psicologia) , América CentralAssuntos
Fumonisinas , Fungicidas Industriais , Fusarium , Triticum , Fungicidas Industriais/farmacologiaRESUMO
Fumonisin occurrence was reported in wheat grains and F. proliferatum has been suggested to be the main contributor to its presence in wheat. Thus, a survey was performed in order to study the impact of four commercial fungicides used in Argentina for controlling Fusarium head blight disease (epoxiconazole+metconazole, tebuconazole, pyraclostrobin+epoxiconazole, and prothioconazole) on growth and fumonisin production of two F. proliferatum strains in relation to water activity (aW; 0.99, 0.97, 0.95) and temperature (15°C and 25°C). Most fungicides reduced growth rates when compared to the control (reduction increased as fungicide concentration increased), and reduced fumonisin production when they were used at high doses; however, most fungicides enhanced fumonisin production at sublethal doses, with the exception of prothioconazole. Thus, fungicides used for FHB management could enhance fumonisin production by F. proliferatum strains present in wheat grains.
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Fumonisinas , Fungicidas Industriais , Fusarium , Fungicidas Industriais/farmacologia , TriticumRESUMO
A discovery-based lipid profiling study of serum samples from a cohort that included patients with clear cell renal cell carcinoma (ccRCC) stages I, II, III, and IV (n = 112) and controls (n = 52) was performed using ultraperformance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry and machine learning techniques. Multivariate models based on support vector machines and the LASSO variable selection method yielded two discriminant lipid panels for ccRCC detection and early diagnosis. A 16-lipid panel allowed discriminating ccRCC patients from controls with 95.7% accuracy in a training set under cross-validation and 77.1% accuracy in an independent test set. A second model trained to discriminate early (I and II) from late (III and IV) stage ccRCC yielded a panel of 26 compounds that classified stage I patients from an independent test set with 82.1% accuracy. Thirteen species, including cholic acid, undecylenic acid, lauric acid, LPC(16:0/0:0), and PC(18:2/18:2), identified with level 1 exhibited significantly lower levels in samples from ccRCC patients compared to controls. Moreover, 3α-hydroxy-5α-androstan-17-one 3-sulfate, cis-5-dodecenoic acid, arachidonic acid, cis-13-docosenoic acid, PI(16:0/18:1), PC(16:0/18:2), and PC(O-16:0/20:4) contributed to discriminate early from late ccRCC stage patients. The results are auspicious for early ccRCC diagnosis after validation of the panels in larger and different cohorts.
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Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais , Carcinoma de Células Renais/diagnóstico , Diagnóstico Precoce , Humanos , Neoplasias Renais/diagnóstico , Lipidômica , Aprendizado de Máquina , Espectrometria de MassasRESUMO
Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with 50-80% patients exhibiting mutations in the von Hippel-Lindau (VHL) gene. RSUME (RWD domain (termed after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases)-containing protein small ubiquitin-related modifier (SUMO) enhancer) acts as a negative regulator of VHL function in normoxia. A discovery-based metabolomics approach was developed by means of ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (MS) for fingerprinting the endometabolome of a human ccRCC cell line 786-O and three other transformed cell systems (n = 102) with different expressions of RSUME and VHL. Cross-validated orthogonal projection to latent structures discriminant analysis models were built on positive, negative, and a combination of positive- and negative-ion mode MS data sets. Discriminant feature panels selected by an iterative multivariate classification allowed differentiating cells with different expressions of RSUME and VHL. Fifteen identified discriminant metabolites with level 1, including glutathione, butyrylcarnitine, and acetylcarnitine, contributed to understand the role of RSUME in ccRCC. Altered pathways associated with the RSUME expression were validated by biological and bioinformatics analyses. Combined results showed that in the absence of VHL, RSUME is involved in the downregulation of the antioxidant defense system, whereas in the presence of VHL, it acts in rerouting energy-related pathways, negatively modulating the lipid utilization, and positively modulating the fatty acid synthesis, which may promote deposition in droplets.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Humanos , Neoplasias Renais/genética , Espectrometria de Massas , Fatores de Transcrição , Proteína Supressora de Tumor Von Hippel-Lindau/genéticaRESUMO
Preprocessing data in a reproducible and robust way is one of the current challenges in untargeted metabolomics workflows. Data curation in liquid chromatography-mass spectrometry (LC-MS) involves the removal of biologically non-relevant features (retention time, m/z pairs) to retain only high-quality data for subsequent analysis and interpretation. The present work introduces TidyMS, a package for the Python programming language for preprocessing LC-MS data for quality control (QC) procedures in untargeted metabolomics workflows. It is a versatile strategy that can be customized or fit for purpose according to the specific metabolomics application. It allows performing quality control procedures to ensure accuracy and reliability in LC-MS measurements, and it allows preprocessing metabolomics data to obtain cleaned matrices for subsequent statistical analysis. The capabilities of the package are shown with pipelines for an LC-MS system suitability check, system conditioning, signal drift evaluation, and data curation. These applications were implemented to preprocess data corresponding to a new suite of candidate plasma reference materials developed by the National Institute of Standards and Technology (NIST; hypertriglyceridemic, diabetic, and African-American plasma pools) to be used in untargeted metabolomics studies in addition to NIST SRM 1950 Metabolites in Frozen Human Plasma. The package offers a rapid and reproducible workflow that can be used in an automated or semi-automated fashion, and it is an open and free tool available to all users.
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RESUMEN Introducción. Los programas de rehabilitación cardiovascular (PRC) representan una estrategia médico-sanitaria multidisciplinaria eficaz en la prevención y control de los problemas cardiovasculares. Objetivos. Evaluar el impacto de un PRC realizado en el espacio de trabajo, en la reducción del riesgo cardiovascular absoluto en los trabajadores de INCOR. Métodos. Estudio experimental. Se incluyó a 41 trabajadores con diferentes niveles de riesgo cardiovascular, evaluados previa y posteriormente a su participación en el PRC sobre su capacidad funcional, sus factores de riesgo cardiovascular y niveles de estrés. El programa de intervención en el trabajo consistió en 36 sesiones de actividad física controlada, consejería nutricional, consejería psicológica y evaluación de laboratorio. Resultados. Se redujo el riesgo cardiovascular global al nivel bajo en el 100% medido mediante el índice de Framingham y en la medición con el score ASCVD 2013, se eliminó el nivel de riesgo alto y el nivel intermedio se redujo de 17,5% a 10%. La capacidad funcional mejoró, incrementándose la clase funcional I de 19,5% a 90%. Los niveles de VLDL, LDL, colesterol total y triglicéridos se redujeron significativamente en la post-intervención, mientras que para el HDL, la proporción de trabajadores con valores no recomendables se incrementó al final de la intervención. Se encontró disminución significativa del nivel de estrés. Conclusiones. Un PRC puede ser implementado en el mismo ámbito laboral y mostrar su comprobada eficacia para reducir el riesgo cardiovascular y el estrés.
ABSTRACT Introduction. The cardiovascular rehabilitation programs (CRP) represent an effective multidisciplinary medical-health strategy in prevention and control of cardiovascular problems. Objective. To assess the impact of a CRP carried out in the workplace, in reducing absolute cardiovascular risk in INCOR workers. Methods. An experimental study. 41 workers with different levels of cardiovascular risk were included and were evaluated before and after their participation in the CRP on their functional capacity, cardiovascular risk factors and stress levels. The work intervention program consisted of 36 sessions of controlled physical activity, nutritional counseling, psychological counseling and laboratory evaluation. Results. The intervention get a reduction of the overall cardiovascular risk to the low level in all workers (100%), measured by the Framingham index and when it was measured with the ASCVD 2013 score, the high-risk level was eliminated and the intermediate level was reduced from 17,5% to 10%. The functional capacity shows an improvement, with an increase of cardiovascular risk level I from 19,5% to 90%. Blood lipids levels as VLDL, LDL, total cholesterol and triglycerides were significantly reduced in the post-intervention. Contrarily, in the HDL levels, the proportion of workers with non-recommended values increased to the end of the intervention. Finally, the CRP showed effectiveness in reducing workers' stress. Conclusion. A CRP could to be implemented on workplace and it shows effectiveness in reducing cardiovascular risk and stress.