Infant Bronchiolitis Endotypes and the Risk of Developing Childhood Asthma: Lessons From Cohort Studies

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a heterogeneous condition associated with a high risk of developing childhood asthma. Yet, the exact mechanisms underlying the bronchiolitis-asthma link remain uncertain. Birth cohort studies have reported this association at the population level, including only small groups of patients with a history of bronchiolitis, and have attempted to identify the underlying biological mechanisms. Although this evidence has provided valuable insights, there are still unanswered questions regarding severe bronchiolitis-asthma pathogenesis. Recently, a few bronchiolitis cohort studies have attempted to answer these questions by applying unbiased analytical approaches to biological data. These cohort studies have identified novel bronchiolitis subtypes (i.e., endotypes) at high risk for asthma development, representing essential and enlightening evidence. For example, one distinct severe respiratory syncytial virus (RSV) bronchiolitis endotype is characterized by the presence of Moraxella catarrhalis and Streptococcus pneumoniae, higher levels of type I/II IFN expression, and changes in carbohydrate metabolism in nasal airway samples, and is associated with a high risk for childhood asthma development. Although these findings hold significance for the design of future studies that focus on childhood asthma prevention, they require validation. However, this scoping review puts the above findings into clinical context and emphasizes the significance of future research in this area aiming to offer new bronchiolitis treatments and contribute to asthma prevention. (AU)

Early gut microbiological changes and metabolomic changes in patients with sepsis: a preliminary study / Cambios microbiológicos intestinales tempranos y cambios metabólicos en pacientes con sepsis: un estudio preliminar

The gut microbiota is closely related to the development of sepsis. The aim of this study was to explore changes in the gut microbiota and gut metabolism, as well as potential relationships between the gut microbiota and environmental factors in the early stages of sepsis. Fecal samples were collected from 10 septic patients on the first and third days following diagnosis in this study. The results showed that in the early stages of sepsis, the gut microbiota is dominated by microorganisms that are tightly associated with inflammation, such as Escherichia-Shigella, Enterococcus, Enterobacteriaceae, and Streptococcus. On sepsis day 3 compared to day 1, there was a significant decrease in Lactobacillus and Bacteroides and a significant increase in Enterobacteriaceae, Streptococcus, and Parabacteroides. Culturomica_massiliensis, Prevotella_7 spp., Prevotellaceae, and Pediococcus showed significant differences in abundance on sepsis day 1, but not on sepsis day 3. Additionally, 2-keto-isovaleric acid 1 and 4-hydroxy-6-methyl-2-pyrone metabolites significantly increased on sepsis day 3 compared to day 1. Prevotella_7 spp. was positively correlated with phosphate and negatively correlated with 2-keto-isovaleric acid 1 and 3-hydroxypropionic acid 1, while Prevotella_9 spp. was positively correlated with sequential organ failure assessment score, procalcitonin and intensive care unit stay time. In conclusion, the gut microbiota and metabolites are altered during sepsis, with some beneficial microorganisms decreasing and some pathogenic microorganisms increasing. Furthermore, Prevotellaceae members may play different roles in the intestinal tract, with Prevotella_7 spp. potentially possessing beneficial health properties and Prevotella_9 spp. potentially playing a promoting role in sepsis.(AU)

Progress of gut microbiome and its metabolomics in early screening of colorectal cancer

Gut microbes are widely considered to be closely associated with colorectal cancer (CRC) development. The microbiota is regarded as a potential identifier of CRC, as several studies have found great significant changes in CRC patients' microbiota and metabolic groups. Changes in microbiota, like Fusobacterium nucleatum and Bacteroides fragilis, also alter the metabolic activity of the host, promoting CRC development. In contrast, the metabolome is an intuitive discriminative biomarker as a small molecular bridge to distinguish CRC from healthy individuals due to the direct action of microbes on the host. More diagnostic microbial markers have been found, and the potential discriminatory power of microorganisms in CRC has been investigated through the combined use of biomic genomic metabolomics, bringing new ideas for screening fecal microbial markers. In this paper, we discuss the potential of microorganisms and their metabolites as biomarkers in CRC screening, hoping to provide thoughts and references for non-invasive screening of CRC (AU)

Despite similar clinical features metabolomics reveals distinct signatures in insulin resistant and progressively obese minipigs

Obesity is a major contributor to the silent and progressive development of type 2 diabetes (T2D) whose prevention could be improved if individuals at risk were identified earlier. Our aim is to identify early phenotypes that precede T2D in diet-induced obese minipigs. We fed four groups of minipigs (n = 5–10) either normal-fat or high-fat high-sugar diet during 2, 4, or 6 months. Morphometric features were recorded, and metabolomics and clinical parameters were assessed on fasting plasma samples. Multivariate statistical analysis on 46 morphometrical and clinical parameters allowed to differentiate 4 distinct phenotypes: NFC (control group) and three others (HF2M, HF4M, HF6M) corresponding to the different stages of the obesity progression. Compared to NFC, we observed a rapid progression of body weight and fat mass (4-, 7-, and tenfold) in obese phenotypes. Insulin resistance (IR; 2.5-fold increase of HOMA-IR) and mild dyslipidemia (1.2- and twofold increase in total cholesterol and HDL) were already present in the HF2M and remained stable in HF4M and HF6M. Plasma metabolome revealed subtle changes of 23 metabolites among the obese groups, including a progressive switch in energy metabolism from amino acids to lipids, and a transient increase in de novo lipogenesis and TCA-related metabolites in HF2M. Low anti-oxidative capacities and anti-inflammatory response metabolites were found in the HF4M, and a perturbed hexose metabolism was observed in HF6M. Overall, we show that IR and progressively obese minipigs reveal phenotype-specific metabolomic signatures for which some of the identified metabolites could be considered as potential biomarkers of early progression to TD2. (AU)

Characterization of the fecal microbiota in gastrointestinal cancer patients and healthy people

BackgroundThe incidence and mortality of gastrointestinal (GI) tumors are high in China. Some studies suggest that the gut microbiota is related to the occurrence and development of tumors. At present, there are no prospective studies based on the correlation between gastrointestinal tumors and gut microbiota in the Chinese population. The objective of this report is to characterize the fecal microbiota in healthy control participants and patients with esophageal cancer, gastric cancer, and colorectal cancer.MethodsPatients with locally advanced or metastatic esophageal, gastric, and colorectal cancer were enrolled, and healthy people were included as controls. 16S rRNA sequencing was used to analyze the characteristics of fecal microbiota. PICRUSt software was used for functional prediction.ResultsSignificant differences in the composition and abundance of fecal microbiota were identified between gastrointestinal cancer patients (n = 130) and healthy controls (n = 147). The abundance of Faecalibacterium prausnitzii, Clostridium clostridioforme and Bifidobacterium adolescent in tumor groups were all significantly lower than in the control group (P < 0.05). The levels of Blautia producta and R. faecis in the gastric (n = 46) and colorectal cancer (n = 44) groups were significantly lower than those in the control group (P < 0.05). The level of Butyricicoccus pullicaecorum in the esophageal cancer (n = 40) and gastric cancer groups was significantly lower than that in the control group (P < 0.05).

Calorie restriction changes lipidomic profiles and maintains mitochondrial function and redox balance during isoproterenol-induced cardiac hypertrophy

Typically, healthy cardiac tissue utilizes more fat than any other organ. Cardiac hypertrophy induces a metabolic shift leading to a preferential consumption of glucose over fatty acids to support the high energetic demand. Calorie restriction is a dietary procedure that induces health benefits and lifespan extension in many organisms. Given the beneficial effects of calorie restriction, we hypothesized that calorie restriction prevents cardiac hypertrophy, lipid content changes, mitochondrial and redox dysregulation. Strikingly, calorie restriction reversed isoproterenol-induced cardiac hypertrophy. Isolated mitochondria from hypertrophic hearts produced significantly higher levels of succinate-driven H2O2 production, which was blocked by calorie restriction. Cardiac hypertrophy lowered mitochondrial respiratory control ratios, and decreased superoxide dismutase and glutathione peroxidase levels. These effects were also prevented by calorie restriction. We performed lipidomic profiling to gain insights into how calorie restriction could interfere with the metabolic changes induced by cardiac hypertrophy. Calorie restriction protected against the consumption of several triglycerides (TGs) linked to unsaturated fatty acids. Also, this dietary procedure protected against the accumulation of TGs containing saturated fatty acids observed in hypertrophic samples. Cardiac hypertrophy induced an increase in ceramides, phosphoethanolamines, and acylcarnitines (12:0, 14:0, 16:0, and 18:0). These were all reversed by calorie restriction. Altogether, our data demonstrate that hypertrophy changes the cardiac lipidome, causes mitochondrial disturbances, and oxidative stress. These changes are prevented (at least partially) by calorie restriction intervention in vivo. This study uncovers the potential for calorie restriction to become a new therapeutic intervention against cardiac hypertrophy, and mechanisms in which it acts. (AU)

Biomarcadores sanguíneos en la enfermedad de Alzheimer / Blood biomarkers in Alzheimer's disease

Introducción: El diagnóstico precoz de la enfermedad de Alzheimer mediante la utilización de biomarcadores podría facilitar la instauración y monitorización de intervenciones terapéuticas tempranas con potencial capacidad para modificar significativamente el curso de la enfermedad.DesarrolloLos biomarcadores clásicos de líquido cefalorraquídeo y de neuroimagen estructural y funcional aprobados tienen una aplicación clínica limitada, dado su carácter invasivo o su elevado coste. La identificación de biomarcadores más accesibles y menos costosos, como los sanguíneos, facilitaría su aplicación en la práctica clínica. Se presenta una revisión bibliográfica de los principales biomarcadores bioquímicos sanguíneos con potencial utilidad para el diagnóstico de la enfermedad de Alzheimer.ConclusionesLos biomarcadores sanguíneos son coste y tiempo efectivos con respecto a los marcadores de líquido cefalorraquídeo. Sin embargo, la aplicabilidad inmediata de los biomarcadores bioquímicos sanguíneos en la práctica clínica es poco esperable. Las principales limitaciones estriban en la dificultad para la medición y estandarización de los umbrales entre los diferentes laboratorios y en los fallos de replicación de resultados. Entre todas las moléculas estudiadas, los biomarcadores de apoptosis y neurodegeneración, al igual que los paneles de biomarcadores obtenidos mediante aproximaciones ómicas —como la metabolómica de forma aislada o combinada— ofrecen los resultados más prometedores. (AU)

Introduction: The early diagnosis of Alzheimer's disease (AD) via the use of biomarkers could facilitate the implementation and monitoring of early therapeutic interventions with the potential capacity to significantly modify the course of the disease.DevelopmentClassic cerebrospinal fluid biomarkers and approved structural and functional neuroimaging have a limited clinical application given their invasive nature and/or high cost. The identification of more accessible and less costly biomarkers, such as blood biomarkers, would facilitate application in clinical practice. We present a literature review of the main blood biochemical biomarkers with potential use for diagnosing Alzheimer's disease.ConclusionsBlood biomarkers are cost and time effective with regard to cerebrospinal fluid biomarkers. However, the immediate applicability of blood biochemical biomarkers in clinical practice is not very likely. The main limitations come from the difficulties in measuring and standardising thresholds between different laboratories and in failures to replicate results. Among all the molecules studied, apoptosis and neurodegeneration biomarkers and the biomarker panels obtained through omics approaches, such as isolated or combined metabolomics, offer the most promising results. (AU)

Metabolómica de la nefropatía diabética: tras la huella de indicadores de desarrollo y progresión / Metabolomics of the diabetic nephropathy: behind the fingerprint of development and progression indicators

Los métodos de diagnóstico actuales son poco sensibles para detectar las etapas iniciales de la nefropatía diabética tipo 2. En este trabajo se hace una revisión de estudios de aproximación metabolómica para la identificación de biomarcadores de esta enfermedad con potencialidad para diferenciar entre etapas tempranas, evaluar y direccionar el tratamiento y coadyuvar a ralentizar el daño renal. Utilizando bases de datos públicas (Pubmed y Google Scholar) y privadas (Scopus y Web of Knowledge), se realizó una búsqueda sistemática de la información que se ha publicado de metabolómica de la nefropatía diabética en distintos bioespecímenes (orina, suero, plasma y sangre). Posteriormente, se utilizó el programa MetaboAnalyst 4.0 para evidenciar las vías metabólicas que están asociadas con estos metabolitos. Con los datos de la literatura se identificaron grupos de metabolitos potenciales para la monitorización de la nefropatía diabética. Destacan en la orina: el óxido-3-hidroxiisovalerato, TMAO, aconitato y citrato y derivados del hidroxipropionato; en el suero: el citrato, la creatinina, la arginina y sus derivados; y en el plasma: aminoácidos como histidina, metionina y arginina. Utilizando el programa MetaboAnalyst 4.0 se detectaron las rutas metabólicas que están relacionadas con estos metabolitos. La búsqueda de biomarcadores relacionados con la progresión de la nefropatía diabética junto con estrategias analíticas para su detección y cuantificación son el punto de partida para el diseño de nuevos métodos de análisis químico-clínico. La correlación con la disfunción de vías metabólicas podría ser utilizada para la evaluación integral del tratamiento y seguimiento clínico de este padecimiento

Current diagnostic methods are not very sensitive to detect the initial stages diabetic nephropathy of type 2. In this work, a review of metabolomic approximation studies for the identification of biomarkers of this disease with potential to differentiate between early stages, evaluate and direct treatment and help slow kidney damage. Using public (Pubmed and Google Scholar) and private (Scopus and Web of Knowledge) databases, a systematic search of the information published related to metabolomics of diabetic nephropathy in different biospecimens (urine, serum, plasma and blood) was made. Later, the MetaboAnalyst 4.0 software was used to identify the metabolic pathways associated with these metabolites. Groups of potential metabolites were identified for monitoring diabetic nephropathy with the available literature data. In the urine, oxide-3-hydroxyisovalerate, TMAO, aconite and citrate and hydroxypropionate derivatives are highlighted; meanwhile, in the serum: citrate, creatinine, arginine and its derivatives; and in the plasma: amino acids such as histidine, methionine and arginine has a potential contribution. Using MetaboAnalyst 4.0 the metabolic pathways related to these metabolites were related. The search for biomarkers to measure the progression of diabetic nephropathy, together with analytical strategies for their detection and quantification, are the starting point for designing new methods of clinical chemistry analysis. The association between the metabolic pathway dysfunction could be useful for the overall assessment of the treatment and clinical follow-up of this disease

Influencia de la enfermedad pulmonar obstructiva crónica en los componentes orgánicos volátiles en pacientes con cáncer de pulmón no microcítico / Influence of Chronic Obstructive Pulmonary Disease on Volatile Organic Compounds in Patients with Non-small Cell Lung Cancer

INTRODUCCIÓN: La etiología del cáncer de pulmón es multifactorial. La exposición al humo del tabaco y el papel que desempeñan los compuestos carcinógenos presentes en él explicarían la frecuente asociación de cáncer de pulmón con enfermedad pulmonar obstructiva crónica (EPOC), enfermedad igualmente muy ligada al tabaquismo. En ambas entidades se desencadena una inflamación mantenida debida al incremento del estrés oxidativo (por ejemplo, peroxidación lipídica), que genera sustancias de bajo peso molecular llamadas compuestos orgánicos volátiles (VOC), que son excretadas durante la respiración. La metabolómica de los VOC ofrece una medida indirecta del grado de estrés oxidativo. OBJETIVO: El objetivo de este trabajo es determinar la influencia relativa de la EPOC en el perfil de los VOC en pacientes con cáncer de pulmón no microcítico (CPNM), estudiando previamente la posible variación de los VOC en función de la histología. PACIENTES Y MÉTODOS: Se analizó el aire exhalado de 107 pacientes de CPNM, clasificados en 2 grupos: CPNM con EPOC y CPNM sin EPOC. La muestra de aire exhalado se recogió mediante BioVOC®) y se traspasó a tubos de desorción para su posterior análisis por cromatografía de gases y espectrometría de masas. Los VOC analizados fueron aldehídos lineales y ácidos carboxílicos. RESULTADOS Y CONCLUSIONES: No se han encontrado diferencias estadísticamente significativas de los VOC con respecto a la histología. Los pacientes con CPNM con EPOC presentan 1,7 (1,1-2,7) veces más probabilidad de detección de ácido propanoico (IC 95%: 1,22-6,2) que los pacientes CPNM sin EPOC (p = 0,013)

INTRODUCTION: The etiology of lung cancer is multifactorial. Exposure to tobacco smoke and the role played by the carcinogenic compounds that it contains would explain the common association between lung cancer and chronic obstructive pulmonary disease (COPD), a disease which is very much linked to tobacco use. In both diseases, sustained inflammation is caused by increased oxidative stress (for example, lipid peroxidation). This generates low molecular weight substances called volatile organic compounds (VOC) that are excreted during breathing. VOC metabolomics provides an indirect measure of oxidative stress. OBJECTIVE: The aim of this study was to establish the relative influence of COPD on the VOC profile in patients with non-small cell lung cancer (NSCLC), by first studying the possible variation of VOC associated with lung cancer histology. PATIENTS AND METHODS: Exhaled air was tested in 107 NSCLC patients, who were divided into 2 groups: NSCLC with COPD and non-COPD with NSCLC. The exhaled air sample was obtained with the BIOVOC® sampler, and transferred to desorption tubes for later analysis by thermal desorption-gas chromatography-mass spectrometry. The VOC analysis showed lineal aldehydes and carboxylic acids. RESULTS AND CONCLUSIONS: No statistically significant differences were found in VOC associated with histology. NSCLC and COPD patients present a 1.7-fold (1.1-2.7) probability of detection of propionic acid (95% CI: 1.22- 6.2) than patients without COPD or NSCLC (P = 0.013)

Diferencias en los metabolismos de sudor según el estadio diagnóstico en cáncer de pulmón escamoso / Metabolite differences in sweat according to diagnostic stage in squamous-cell lung cancer

Objetivo: determinar si la metabolómica aplicada a una muestra de sudor permite diferenciar la concentración relativa de ciertos metabolitos en pacientes con cáncer de pulmón en estadio inicial (I - II) respecto a estadios avanzados (III - IV). Pacientes y métodos: fueron incluidos 21 pacientes diagnosticados de cáncer escamoso de pulmón en un hospital universitario. Para la inducción del sudor se utilizaron discos de Pilogel(R) y la recolección mediante dispositivo Macroduct(R) conservando la muestra a -80 ºC. Para el análisis metabolómico se utilizó un cromatógrafo de líquidos acoplado a un espectrómetro de masas de alta resolución (LC - QTOF) provisto de fuente de ionización por electroespray. Los datos se procesaron con el software MassHunter Workstation y se realizó análisis de cambio (FC, Fold Change Analysis) para detectar las diferencias de concentración relativa de metabolitos entre los diferentes estadios tumorales. Resultados: se estudiaron 21 muestras de sudor pertenecientes a 9 pacientes en estadio I - II y 12 en estadio III - IV. En una lista preferente de 16 compuestos que incluyeron diversos aminoácidos, azúcares, ácidos carboxílicos y ácidos grasos, no se observaron cambios significativos según la extensión tumoral. El análisis de cambio mostró que una trihexosa (FC: -2,175) fue el compuesto con diferencias significativas de concentración relativa en las muestras de sudor según los dos estadios tumoral comparados. Conclusión: en muestras de sudor de pacientes con carcinoma escamoso de pulmón la huella metabolómica se mantiene relativamente estable con escasas diferencias en la concentración relativa de metabolitos, únicamente se observó un cambio significativo en una trihexosa en estadios de cáncer de pulmón inicial y avanzado

Objective: To determine whether applying metabolomics to a sweat sample allows different metabolite concentrations to be differentiated in patients with early-stage lung cancer (stages I-II) compared to advanced stages (III-IV). Patients and methods: 21 patients diagnosed with squamouscell lung cancer in a university hospital were included. Pilogel(R) discs were used to induce sweat, which was collected using the Macroduct(R) system, storing the samples at -80 ºC. For the metabolomic analysis, a liquid chromatograph was used, attached to a high-resolution mass spectrometer (LC - QTOF) supplied with electrospray ionization. The data was processed using the MassHunter Workstation software and a fold change analysis (FC) was done to detect differences in metabolite concentrations between different tumor stages. Results: 21 sweat samples from 9 stage I-II patients and 12 stage III-IV patients were studied. In a list of 16 compounds that included several amino acids, sugars, carboxylic acids and fatty acids, no significant changes were observed according to tumor extension. The change analysis showed that a trihexose (FC: -2.175) was the compound with significant concentration differences in sweat samples according to the two tumor stages compared. Conclusion: In sweat samples from patients with squamouscell lung cancer, metabolomic markers remain relatively stable with slight differences in metabolite concentrations, only observing a significant change in a trihexose between early and advanced stages of lung cancer

Papel de las ómicas en la nutrición de precisión: fortalezas y debilidades / The role of omics in precision nutrition: strengths and weaknesses

La medicina de precisión ha tomado un gran impulso en los últimos años. Aunque todavía no existe una definición única generalmente aceptada, se basa en considerar relevantes las características particulares de cada persona para adaptar mejor las medidas terapéuticas o preventivas de una manera más personalizada. De manera análoga, ha surgido el concepto de nutrición de precisión, en el que se pretende proporcionar las mejores recomendaciones dietéticas para prevenir o tratar una enfermedad de acuerdo con las características de la persona. Entre estas características cobran especial relevancia las basadas en las ómicas. Inicialmente, la genómica y, posteriormente, la epigenómica, la metabolómica, la proteómica y la transcriptómica están aportándonos nueva información sobre la distinta respuesta a la dieta basada en el genotipo, sobre nuevos biomarcadores precoces de enfermedad, sobre la ingesta o sobre efectos reguladores de la dieta. Pero la nutrición de precisión todavía puede extenderse mucho más incluyendo aspectos más holísticos que no estén centrados en la enfermedad, sino en el bienestar y otros indicadores de salud positiva. Para ello, a las mencionadas ómicas se han sumado otras ómicas que permiten un análisis más multidimensional. También la gastronomía tiene un papel relevante en la nutrición de precisión. Aunque todavía nos encontramos en una fase preliminar de estudio y de validación en nutrición de precisión, existe un gran potencial en este campo que es necesario desarrollar. En este contexto, revisaremos el papel de las ómicas en la nutrición de precisión, así como sus principales fortalezas y debilidades

Precision medicine has taken huge strides forward in recent years. Although there is still no generally accepted single definition, it basically considers the particular characteristics of each person as relevant in order to better adapt therapeutic or preventive measures in a more personalized fashion. Likewise, the concept of precision nutrition has gathered strength, in which the aim is to provide the best dietary recommendations to prevent or treat a disease in accordance with the characteristics of the individual in question. Of special importance among these characteristics are those based on omics. Initially genomics, and now epigenomics, metabolomics, proteomics and transcriptomics are providing us with new information on the different responses to the diet based on genotype, on new early biomarkers of disease, on dietary intake, or on the regulatory effects of diet. However, precision nutrition can go further still to include much more holistic aspects, not focusing on the disease, but on wellbeing and other indicators of positive health. Hence, other omics have been added to those mentioned above that provide us with a more multidimensional analysis. Gastronomy also plays an important role in precision nutrition. Although we are still at the preliminary validation stage of precision nutrition, this field presents huge potential for development. In this context, we shall review the role of omics in precision nutrition as well as their main strengths and weaknesses

A GC-MS untargeted metabolomics analysis in the plasma and liver of rats lacking dipeptidyl-peptidase type IV enzyme activity

This study was achieved with the aim to find metabolic changes between Fischer rats with different dipeptidyl peptidase-type 4 (DPPIV) expression. The DPPIV is an enzyme expressed in several tissues and is critically involved in the regulation of meal-related insulin secretion in healthy individuals. The metabolic consequences of chronic DPPIV inhibition were analyzed in a surrogate animal model of genetic enzyme deficiency. Hyphenated gas chromatography–mass spectrometry (GC-MS) and multivariate data analysis techniques were used to study the metabolic aqueous fraction profile of 18 plasma and liver samples in two syngeneic rat strains differing in DPPIV activity (DPPIV+ vs. DPPIV-). The hyperglycemic response following oral glucose administration was attenuated in DPPIV- rats, as expected. Statistical significant differences between the two strains were observed among the low molecular weight polar metabolites analyzed from plasma and liver. These included a decrease in malic acid and glutamine and an increase in pyroglutamic acid, serine, and alanine in plasma of DPPIV- rats. In addition, palmitic acid, l-proline, and ribitol were decreased in the liver of DPPIV- strain. Such alterations were compatible with a normal phenotype. These results suggest that long-term exposure to DPPIV inhibitors looks compatible with an overall balanced metabolism

Fiebre sin foco en lactantes menores de 3 meses. ¿Qué hay de nuevo? / Fever without source in infants less than 3 months of age. What's new?

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A review on emerging frontiers of house dust mite and cockroach allergy research

Currently, mankind is afflicted with diversified health issues, allergies being a common, yet little understood malady. Allergies, the outcome of a baffled immune system encompasses myriad allergens and causes an array of health consequences, ranging from transient to recurrent and mild to fatal. Indoor allergy is a serious hypersensitivity in genetically-predisposed people, triggered by ingestion, inhalation or mere contact of allergens, of which mite and cockroaches are one of the most-represented constituents. Arduous to eliminate, these aeroallergens pose constant health challenges, mostly manifested as respiratory and dermatological inflammations, leading to further aggravations if unrestrained. Recent times have seen an unprecedented endeavour to understand the conformation of these allergens, their immune manipulative ploys and other underlying causes of pathogenesis, most importantly therapies. Yet a large section of vulnerable people is ignorant of these innocuous-looking immune irritants, prevailing around them, and continues to suffer. This review aims to expedite this field by a concise, informative account of seminal findings in the past few years, with particular emphasis on leading frontiers like genome-wide association studies (GWAS), epitope mapping, metabolomics etc. Drawbacks linked to current approaches and solutions to overcome them have been proposed

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Papel en la obesidad de la microbiota intestinal / Role of gut microbiota in obesity

La contribución de la microbiota intestinal al desarrollo de diversas enfermedades, incluyendo la obesidad, se está estudiando minuciosamente. Aunque los mecanismos no están completamente definidos, las perturbaciones en la composición de la microbiota intestinal parecen estar relacionados con el sobrepeso, revelando alteraciones en los niveles de Bacteriodetes y Firmicutes en comparación con individuos delgados. La modulación de la comunidad bacteriana intestinal orientada a favorecer el crecimiento de bacterias ‘saludables’ y reducir las dañinas podría ser una eficaz herramienta terapéutica contra la obesidad. El consumo de dietas con alto contenido en grasa y azúcares afecta notablemente a la composición de la microbiota, alterando su equilibrio hacia patrones asociados a obesidad, siendo un punto de partida para un tratamiento de precisión de esta enfermedad. La interacción entre componentes de la dieta y la microbiota intestinal podría ser, en parte, responsable de sus beneficios para la salud, por lo que la administración de compuestos bioactivos podría promover el crecimiento de bacterias beneficiosas en detrimento de otras patógenas o asociadas a la obesidad. El impacto sobre el metaboloma de las intervenciones dietéticas y la administración de polifenoles se podría identificar mediante metabolómica no dirigida de las heces, permitiendo estratificar los individuos en función de la intervención dietética con el fin de aplicar tratamientos personalizados. Esta revisión pretende proporcionar una instantánea de este sistema complejo que comprende microbiota intestinal, dieta, polifenoles, metabolismo del individuo y obesidad, y cuyo conocimiento se beneficia de tecnologías avanzadas como la secuenciación de última generación y la metabolómica no dirigida (AU)

The contribution of the gut microbiota to the development of many diseases, including obesity, is being thoroughly explored. Although mechanisms are not fully understood, perturbations on gut microbiota composition seem to be related to overweight. Indeed, subjects with excessive body weight, show impairment in intestinal levels of Bacteriodetes and Firmicutes as compared to lean individuals. Therefore, modulation of gut bacterial community with approaches that could enhance the growth of ‘healthy’ bacteria and reduce harmful bacteria might be an effective therapeutic tool against obesity. Bi-directional interactions between natural compounds and the gut microbiota taking place at intestinal level, has been hypothesized to be partly responsible for the health beneficial outcomes. The consumption of high-fat high-sucrose diets strongly impacts gut microbiota composition impairing the bacterial balance towards an obesity-associated gut microbial pattern, which may be the basis for a precision management of obesity. Remarkably, the administration of bioactive compounds could counteract the disturbance of gut microbiota related to diet-induced obesity, promoting the growth of some beneficial bacteria while reducing some pathogenic and obesity- associated microbes. Biological outcomes exerted by dietary interventions and polyphenol administration on global host metabolome might be distinguished through a faecal non-targeted metabolomic analysis, where individuals might be also stratified in different groups based on the dietary intervention for personalized treatments . Therefore, this overview aimed to provide a snapshot of this complex system consisting of gut microbiota, diet and polyphenols, host metabolism and obesity taking advantage of advanced technologies namely next-generation sequencing and untargeted metabolomics (AU)

Técnicas invasivas y no invasivas en el diagnóstico de embriones humanos / Invasive and non-invasive techniques in human embryos diagnostic

Las técnicas de reproducción asistida se han desarrollado con el objetivo de aumentar las tasas de implantación y reducir el número de embriones transferidos. El conocimiento sobre la morfología embrionaria y el desarrollo de la tecnología molecular aplicada al diagnóstico preimplantacional, han supuesto un gran avance en el rendimiento de los ciclos, mejorando los resultados clínicos y disminuyendo la tasa de aborto. El objetivo de esta revisión es describir el estado actual de las técnicas de diagnóstico embrionario. Técnicas como el time-lapse aplicada a la morfocinética nos permiten estudiar de manera continua el desarrollo embrionario, aportando un enfoque más dinámico. Tecnología molecular como la metabolómica dirigida o la proteómica, muestran nuevos elementos de evaluación sobre las primeras etapas del desarrollo hasta blastocisto. Estudios sobre el secretoma embrionario en medios de cultivo in-vitro intentan predecir patrones de desarrollo en los embriones. La búsqueda de estrategias de diagnóstico y biomarcadores asociados a calidad embrionaria, aneuploidías y potencial implantatorio son nuevos retos a los que se enfrenta la tecnología en medicina reproductiva

The assisted reproduction techniques have been developed with the aim of increasing implantation rates and reducing the number of embryos transferred. Knowledge about embryonic morphology and the development of molecular technology applied to preimplantation diagnosis has resulted in great progress in terms of cycle performance, improving clinical outcomes and reducing the rate of abortion. The aim of this review is to describe embryonic diagnostic techniques. Currently, techniques like time-lapse applied to morphokinetics allow us to continuously study embryonic development providing a more dynamic approach. Molecular techniques such as directed metabolomics or proteomics show new elements of evaluation since the early stages of development to blastocyst. Studies on the metabolism of embryos cultured in-vitro are providing data that improve embryo selection. The development of diagnostic strategies and biomarkers associated with embryonic quality, aneuploidy and implantatory potential are new challenges for the future in reproductive medicine technology

Metabolómica de la lágrima / Human tear metabolome

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Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders / Concentraciones circulantes de PCSK9 en población con diabetes tipo 2 y alteraciones metabólicas asociadas

Background: PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis. Methods: There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients. Results: The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%;p < 0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C). Conclusions: PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism

Introducción: PCSK9 es una molécula clave en la regulación del metabolismo lipídico. Estudios previos sugieren que la expresión y función de PCSK9 entorno a la regulación del receptor LDL puede alterarse en la diabetes. El objetivo del estudio fue determinar los niveles circulantes de PCSK9 en pacientes con diabetes tipo 2 (DM) y otras enfermedades metabólicas y su relación con las lipoproteínas estudiadas mediante resonancia magnética nuclear (RMN) y la homeostasis de la glucosa. Métodos: Se estudiaron un total de 457 pacientes, afectos de DM y otras alteraciones metabólicas (síndrome metabólico [SMet], obesidad y dislipidemia aterogénica [DA] y otros). Se realizó anamnesis, antropometría, exploración física y estudio vascular de carótidas y adiposidad abdominal. Se realizó bioquímica incluyendo PCSK9 circulante (tras 6 semanas de lavado en pacientes con hipolipemiantes). Se estudió mediante RMN el perfil de lipoproteínas. Se determinaron las variantes genéticas rs505151 y rs11591147 del gen PCSK9. Resultados: Los niveles circulantes de PCSK9 están aumentados en pacientes con DM y SMet (14 y 13%; p<0.005, respectivamente). Los niveles circulantes de PCSK9 se correlacionaron de forma positiva con el perfil lipídico aterogénico y parámetros de resistencia insulínica. Los niveles circulantes de PCSK9 también se asociaron positivamente a DA, definida mediante el número y el tamaño de lipoproteínas analizado mediante RMN. Los portadores de la variante genética rs11591147 mostraron niveles inferiores de PCSK9 plasmática y cLDL. Conclusiones: Los niveles circulantes de PCSK9 están aumentados en pacientes con DM y SMet junto con parámetros de DA y metabolismo de la glucosa, más allá del cLDL

Perfiles metabolómicos de sujetos sanos y con cáncer de pulmón. Influencia de la carga tabáquica / The metabolomics of healthy subjects and those with lung cancer: the influence of smoking

INTRODUCCIÓN: la aplicación de técnicas metabolómicas presenta un gran potencial para la búsqueda de posibles biomarcadores de diagnóstico precoz en numerosas enfermedades. El empleo de procedimientos metabolómicos basados en espectrometría de masas permite estudiar las modificaciones metabólicas subyacentes al cáncer de pulmón (CP) y la influencia de la carga tabáquica (CT), medida en paquetes-año, en los correspondientes perfiles metabólicos. METODOLOGÍA: se estudió el suero de 9 controles sanos (no fumadores), 6 enfermos de CP con carga tabáquica moderada (CT 70). Se analizaron los metabolitos mediante técnicas de espectrometría de masas de alta resolución (DI-ESI-QTOFMS). Los perfiles metabólicos obtenidos se sometieron a análisis estadístico multivariante (PCA, PLS-DA). RESULTADOS: los tres grupos de estudio mostraron perfiles metabólicos claramente diferentes, lo que permitió identificar algunos posibles biomarcadores. Los niveles de glutatión se encontraron disminuidos en muestras de suero de pacientes con CP, mientras que se incrementó el contenido de distintos fosfolípidos de membrana (PL). La mayoría de estas anormalidades metabólicas se acentuó en pacientes con una CT elevada. CONCLUSIONES: el análisis metabolómico en muestras de suero permitió diferenciar claramente entre sujetos sanos y pacientes con CP. Así mismo, se identificaron posibles biomarcadores para el diagnóstico del CP (relacionados con rutas previamente conocidas en el proceso del cáncer). Además, estas alteraciones se vieron influenciadas por la carga tabáquica, confirmando la importancia del tabaquismo como factor de riesgo primario en el desarrollo del CP

By using high resolution metabolomics, we obtained the metabolomic profiles for patients who smoked and had lung cancer (LC) and a healthy, non-smoker control (HC) group; we assessed the influence of smoking on said profiles. The results show a clear discrimination between the metabolomic profiles of both groups studied; the metabolites causing said difference could be determined. Moreover, differences were encountered between the metabolomic profiles of heavy smokers with lung cancer compared to moderate smokers. INTRODUCTION: theapplicationof metabolomic techniques offers extensive potential to search for possible biomarkers in the early detection of several diseases. Using metabolomic procedures based on mass spectrometry allow us to study underlying metabolic changes in lung cancer and the influence of smoking, measured as packets/year, in the corresponding metabolic profiles. METHOD: the serum from 9 healthy control subjects (nonsmokers) was studied, as well as that of 6 patients with lung cancer who were moderate smokers (CT 70). The metabolites were analyzed using high resolution mass spectrometer techniques (DI-ESI-QTOF-MS). The metabolic profiles obtained were subject to multivariate statistical analysis (PCA, PLS-DA). RESULTS: the three groups studied showed clearly differentiated metabolic profiles, which facilitated the identification of certain biomarkers. Glutathione levels were found to be decreased in the sample from patients with lung cancer, while the content of various membrane phospholipids increased. Most of these metabolic abnormalities were heightened in patients who were heavy smokers. CONCLUSIONS: the metabolomics analysis in serum samples clearly differentiated healthy subjects from patients with lung cancer. Also, possible biomarkers were identified to diagnose lung cancer (linked to previously known routes in the cancer process. Moreover, these alterations were influenced by the amount smoked, thus confirming the importance of smoking as a primary risk factor in developing lung cáncer

Direct infussion Electrospray Mass Spectrometry as a new non-invasive tool for serum metabolomics in induced-stress subjects

Background and Objectives: Nanotechnology is becoming a tool for the study of changes in the metabolome of patients in different states of disease. Analytical techniques such as Electrospray Mass Spectrometry, allow to find biomarkers by determination of metabolites. Nowadays, there is not an objective analytical approach for diagnosis of stress. Thus, the objectives of this pilot work are: Describing the development of a fast, direct and non-invasive analytical protocol, applied for the first time, to study the metabolomic profile of patient´s different states through a disease. Testing the protocol in a pilot sample with non-stressed and stress-induced subjects. Methods: High resolution direct infusion electrospray mass spectrometry has been used to analyse the metabolome of blood samples (0.3 ml) from six subjects. Results: Data prove a clear discrimination between non-stressed and stressed states in the metabolome. Data showed different predominant metabolites in both states. Results allow objective characterization of the state of the patient. Conclusions: Although this is a pilot study, the method was successful in discriminating different metabolites in non-stressed and stress-induced subjects (AU)

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