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1.
Adv Exp Med Biol ; 1310: 509-531, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33834448

RESUMEN

Metabolomics is the systematic study of metabolite profiles of complex biological systems, and involves the systematic identification and quantification of metabolites. Metabolism is integrated with all biochemical reactions in biological systems; thus metabolite profiles provide collective information on biochemical processes induced by genetic or environmental perturbations. Transcriptomes or proteomes may not be functionally active and not always reflect phenotypic variations. The metabolome, however, consists of the biomolecules closest to the phenotype of living organisms, and is often called the molecular phenotype of biological systems. Thus, metabolome alterations can easily result in disease states, providing important clues to understand pathophysiological mechanisms contributing to various biomedical symptoms. The metabolome and metabolomics have been emphasized in translational research related to biomarker discovery, drug target discovery, drug responses, and disease mechanisms. This review describes the basic concepts, workflows, and applications of mass spectrometry-based metabolomics in translational research.


Asunto(s)
Metabolómica , Investigación en Medicina Traslacional , Espectrometría de Masas , Metaboloma , Fenotipo
2.
Adv Exp Med Biol ; 1280: 1-18, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791971

RESUMEN

Due to the great diversity of chemical and physical properties of metabolites as well as a wide range of concentrations of metabolites present in metabolomic samples, performing comprehensive and quantitative metabolome analysis is a major analytical challenge. Conventional approach of combining various techniques and methods with each detecting a fraction of the metabolome can lead to the increase in overall metabolomic coverage. However, this approach requires extensive investment in equipment and analytical expertise with still relatively low coverage and low sample throughput. Chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) offers an alternative means of increasing metabolomic coverage while maintaining high quantification precision and accuracy. This chapter describes the CIL LC-MS method and its key features for metabolomic analysis.


Asunto(s)
Metabolómica , Espectrometría de Masas en Tándem , Cromatografía Liquida , Marcaje Isotópico , Metaboloma
3.
Adv Exp Med Biol ; 1280: 97-113, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791977

RESUMEN

Most microbe-associated infectious diseases severely affect human health. However, clinical diagnosis of pathogenic diseases remains challenging due to the lack of specific and highly reliable methods. To better understand the diagnosis, pathogenesis, and treatment of these diseases, systems biology-driven metabolomics goes beyond the annotated phenotype and better targets the functions than conventional approaches. As a novel strategy for analysis of metabolomes in microbes, microbial metabolomics has been recently used to study many diseases, such as obesity, urinary tract infection (UTI), and hepatitis C. In this chapter, we attempt to introduce various microbial metabolomics methods to better interpret the microbial metabolism underlying a diversity of infectious diseases and inspire scientists to pay more attention to microbial metabolomics, enabling broadly and efficiently its translational applications to infectious diseases, from molecular diagnosis to therapeutic discovery.


Asunto(s)
Metabolómica , Infecciones Urinarias , Humanos , Metaboloma , Biología de Sistemas
4.
Cell Death Dis ; 12(3): 258, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33707411

RESUMEN

The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.


Asunto(s)
/sangre , Metaboloma , /metabolismo , Anticuerpos Monoclonales Humanizados/administración & dosificación , Biomarcadores/sangre , /tratamiento farmacológico , Femenino , Humanos , Masculino , Metabolómica , Pronóstico
5.
Nat Commun ; 12(1): 1618, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712622

RESUMEN

Cytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1ß, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/metabolismo , Citocinas/sangre , Metaboloma , Animales , Estudios de Casos y Controles , Estudios de Cohortes , Síndrome de Liberación de Citoquinas/terapia , Femenino , Estudios de Seguimiento , Humanos , Técnicas In Vitro , Mediadores de Inflamación/sangre , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Estudios Longitudinales , Macaca mulatta , Masculino , Redes y Vías Metabólicas , Pandemias
6.
Gut Microbes ; 13(1): 1-19, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33685349

RESUMEN

The current pandemic of coronavirus disease (COVID) 2019 constitutes a global public health issue. Regarding the emerging importance of the gut-lung axis in viral respiratory infections, analysis of the gut microbiota's composition and functional activity during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be instrumental in understanding and controling COVID 19. We used a nonhuman primate model (the macaque), that recapitulates mild COVID-19 symptoms, to analyze the effects of a SARS-CoV-2 infection on dynamic changes of the gut microbiota. 16S rRNA gene profiling and analysis of ß diversity indicated significant changes in the composition of the gut microbiota with a peak at 10-13 days post-infection (dpi). Analysis of bacterial abundance correlation networks confirmed disruption of the bacterial community at 10-13 dpi. Some alterations in microbiota persisted after the resolution of the infection until day 26. Some changes in the relative bacterial taxon abundance associated with infectious parameters. Interestingly, the relative abundance of Acinetobacter (Proteobacteria) and some genera of the Ruminococcaceae family (Firmicutes) was positively correlated with the presence of SARS-CoV-2 in the upper respiratory tract. Targeted quantitative metabolomics indicated a drop in short-chain fatty acids (SCFAs) and changes in several bile acids and tryptophan metabolites in infected animals. The relative abundance of several taxa known to be SCFA producers (mostly from the Ruminococcaceae family) was negatively correlated with systemic inflammatory markers while the opposite correlation was seen with several members of the genus Streptococcus. Collectively, SARS-CoV-2 infection in a nonhuman primate is associated with changes in the gut microbiota's composition and functional activity.


Asunto(s)
/microbiología , Microbioma Gastrointestinal , Macaca/microbiología , Macaca/virología , Animales , Bacterias/clasificación , Modelos Animales de Enfermedad , Heces , Femenino , Metaboloma , ARN Ribosómico 16S/genética
7.
Ter Arkh ; 93(1): 49-58, 2021 Jan 10.
Artículo en Ruso | MEDLINE | ID: mdl-33720626

RESUMEN

AIM: To determine the prevalence of refractory hypertension (RfH) in patients with and without type 2 diabetes mellitus (DM), as well as to evaluate whether diabetic patients with RfH significant differ from those with uncontrolled resistant hypertension (RH) in clinical phenotype, metabolic profile and endothelial function. MATERIALS AND METHODS: The study included 193 patients with RH: RH 74 patients with diabetes and 119 patients without DM. Uncontrolled RH and RfH were defined by the presence of uncontrolled blood pressure BP (140 and/or 90 mm Hg) despite the use of 3 but 5 antihypertensive drugs (for RH) and 5 antihypertensive drugs, including a mineralocorticoid receptor antagonist (for RfH). Clinical examination, lab tests were performed. Flow-mediated dilation (FMD) and vasoreactivity of middle cerebral artery (MCA) using both breath-holding and hyperventilation test were measured by high-resolution ultrasound. RESULTS: The prevalence of refractory hypertension in patients with and without DM was similar (30% vs 28%, respectively). No differences in BP levels, data of echocardiography and clinical phenotype were found between the diabetic groups, but value of HOMA index, plasma resistin level and postprandial glycaemia were higher in patients with RfH. FMD and MCA reactivity to the breath-holding test were worse in patients with RfH, and they had a more pronounced vasoconstrictor response of MCA to the hyperventilation test compared to patients with RH. CONCLUSION: The prevalence of RfH is the same in patients with and without diabetes. Diabetic patients with refractory hypertension have a more unfavorable metabolic profile and greater impairment of endothelial function than patients with uncontrolled resistant hypertension.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipertensión , Antihipertensivos/farmacología , Presión Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Metaboloma
8.
Anal Chim Acta ; 1152: 338267, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33648648

RESUMEN

Although SARS-CoV-2 can invade the intestine, though its effect on digestion and absorption is not fully understood. In the present study, 56 COVID-19 patients and 47 age- and sex-matched healthy subjects were divided into a discovery cohort and a validation cohort. Blood, faeces and clinical information were collected from the patients in the hospital and at discharge. The faecal metabolome was analysed using gas chromatography-mass spectrometry, and Spearman's correlation analyses of clinical features, the serum metabolome, and the faecal micro- and mycobiota were conducted. The results showed that, the faeces of COVID-19 patients were enriched with important nutrients that should be metabolized or absorbed, such as sucrose and 2-palmitoyl-glycerol; diet-related components that cannot be synthesized by humans, such as 1,5-anhydroglucitol and D-pinitol; and harmful metabolites, such as oxalate, were also detected. In contrast, purine metabolites such as deoxyinosine and hypoxanthine, low-water-soluble long-chain fatty alcohols/acids such as behenic acid, compounds rarely occurring in nature such as D-allose and D-arabinose, and microbe-related compounds such as 2,4-di-tert-butylphenol were depleted in the faeces of COVID-19 patients. Moreover, these metabolites significantly correlated with altered serum metabolites such as oxalate and gut microbesincluding Ruminococcaceae, Actinomyces, Sphingomonas and Aspergillus. Although levels of several faecal metabolites, such as sucrose, 1,5-anhydroglucitol and D-pinitol, of discharged patients were not different from those of healthy controls (HCs), those of oxalate and 2-palmitoyl-glycerol did differ. Therefore, alterations in the faecal metabolome of COVID-19 patients may reflect malnutrition and intestinal inflammation and warrant greater attention. The results of present study provide new insights into the pathogenesis and treatment of COVID-19.


Asunto(s)
/fisiopatología , Disbiosis/diagnóstico , Heces/química , Microbioma Gastrointestinal/fisiología , Metaboloma/fisiología , Adulto , Bacterias/metabolismo , Estudios de Cohortes , Disbiosis/fisiopatología , Heces/microbiología , Femenino , Hongos/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad
9.
Methods Mol Biol ; 2265: 461-474, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33704734

RESUMEN

Gut microbiota influence and modulate host immune responses. In preclinical cancer models, mice lacking gut microbiota have a markedly diminished response to immune checkpoint inhibitor therapy. Further, in melanoma patients, specific commensal gut microbiota have been associated with a positive clinical response to immunotherapy. In order to study the gut microbiome and metabolome, we have developed methods for fecal sample collection and processing, microbiome and metabolome profiling, and bioinformatic analysis. This protocol will be a useful tool for interrogating the taxonomic composition and functional output of a melanoma patient's gut microbiome.


Asunto(s)
Heces/microbiología , Microbioma Gastrointestinal , Melanoma , Metaboloma , Metabolómica , Animales , Humanos , Melanoma/metabolismo , Melanoma/microbiología , Ratones
10.
Methods Mol Biol ; 2292: 203-212, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33651364

RESUMEN

The pathogenesis of cancer involves multiple molecular alterations at the level of genome, epigenome, and stromal environment, resulting in several deregulated signal transduction pathways. Metabolites are not only end products of gene and protein expression but also a consequence of the mutual relationship between the genome and the internal environment. Considering that metabolites serve as a comprehensive chemical fingerprint of cell metabolism, metabolomics is emerging as the method able to discover metabolite biomarkers that can be developed for early cancer detection, prognosis, and response to treatment. Urine represents a noninvasive source, available and rich in metabolites, useful for cancer diagnosis, prognosis, and treatment monitoring. In this chapter, we reported the main published evidences on urinary metabolic biomarkers in the studied cancers related to hepatopancreatic and urinary tract with the aim at discussing their promising role in clinical practice.


Asunto(s)
Redes y Vías Metabólicas , Neoplasias/metabolismo , Neoplasias/orina , Animales , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/orina , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/orina , Metaboloma , Metabolómica/métodos , Neoplasias/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/orina , Pronóstico , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/orina
11.
Chem Biol Interact ; 338: 109401, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33556367

RESUMEN

The tyrosine kinase inhibitor sorafenib (SOR) is being used increasingly in combination with other anticancer agents like paclitaxel, but this increases the potential for drug toxicity. SOR inhibits several human CYPs, including CYP2C8, which is a major enzyme in the elimination of oncology drugs like paclitaxel and imatinib. It has been reported that CYP2C8 inhibition by SOR in human liver microsomes is potentiated by NADPH-dependent biotransformation. This implicates a SOR metabolite in enhanced inhibition, although the identity of that metabolite is presently unclear. The present study evaluated the capacity of the major N-oxide metabolite of SOR (SNO) to inhibit CYP2C8-dependent paclitaxel 6α-hydroxylation. The IC50 of SNO against CYP2C8 activity was found to be 3.7-fold lower than that for the parent drug (14 µM versus 51 µM). In molecular docking studies, both SOR and SNO interacted with active site residues in CYP2C8, but four additional major hydrogen and halogen bonding interactions were identified between SNO and amino acids in the B-B' loop region and helixes F' and I that comprise the catalytic region of the enzyme. In contrast, the binding of both SOR and SNO to active site residues in the closely related human CYP2C9 enzyme was similar, as were the IC50s determined against CYP2C9-mediated losartan oxidation. These findings suggest that the active metabolite SNO could impair the elimination of coadministered drugs that are substrates for CYP2C8, and mediate toxic adverse events, perhaps in those individuals in whom SNO is formed extensively.


Asunto(s)
Inhibidores del Citocromo P-450 CYP2C8/farmacología , Citocromo P-450 CYP2C8/química , Citocromo P-450 CYP2C8/metabolismo , Metaboloma , Simulación del Acoplamiento Molecular , Óxidos/farmacología , Sorafenib/metabolismo , Sorafenib/farmacología , Adulto , Biotransformación/efectos de los fármacos , Dominio Catalítico , Humanos , Losartán/farmacología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Persona de Mediana Edad , Oxidación-Reducción , Especificidad por Sustrato/efectos de los fármacos
12.
Nat Commun ; 12(1): 1335, 2021 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-33637740

RESUMEN

Understanding a complex microbial ecosystem such as the human gut microbiome requires information about both microbial species and the metabolites they produce and secrete. These metabolites are exchanged via a large network of cross-feeding interactions, and are crucial for predicting the functional state of the microbiome. However, till date, we only have information for a part of this network, limited by experimental throughput. Here, we propose an ecology-based computational method, GutCP, using which we predict hundreds of new experimentally untested cross-feeding interactions in the human gut microbiome. GutCP utilizes a mechanistic model of the gut microbiome with the explicit exchange of metabolites and their effects on the growth of microbial species. To build GutCP, we combine metagenomic and metabolomic measurements from the gut microbiome with optimization techniques from machine learning. Close to 65% of the cross-feeding interactions predicted by GutCP are supported by evidence from genome annotations, which we provide for experimental testing. Our method has the potential to greatly improve existing models of the human gut microbiome, as well as our ability to predict the metabolic profile of the gut.


Asunto(s)
Ecología , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiología , Intestinos/microbiología , Algoritmos , Biología Computacional/métodos , Humanos , Aprendizaje Automático , Metaboloma , Metabolómica , Metagenómica , Modelos Biológicos
13.
J Chromatogr A ; 1640: 461942, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33588274

RESUMEN

Recent years have seen the field of extracellular vesicle (EV) studies burgeoning. This is mainly because EV constituents including nucleic acid, proteins, lipids, and metabolites are promising sources towards disease biomarker discovery. However, EV study remains challenging due to the complexity of biofluids as well as technical limitations during sample preparation. Here, we proposed a simple method combing ultrafiltration (UF) and phospholipid affinity to collect high purity EVs from 30 mL of urine sample for their metabolomic profiling. Ultracentrifugation (UC) for EV isolation was applied as a reference method. Western blot (WB) analysis, nanoparticles tracking analysis (NTA) and electron microscopy (EM) were used to assess EV protein markers and to characterize vesicle size and morphology. The results revealed that more than 1010 EV particles could be isolated from a 30 mL urine sample by the proposed method, and the resulting EVs carry specific protein markers and had a typical "cup shape" morphology. This suggests that our method is suitable for EV isolation and can provide sufficient EV quantity to ensure downstream analysis. Further untargeted metabolomic profiling of isolated EVs by UHPLC-QTOF-MS detected 433 metabolites by our methods and 432 metabolites by UC with a MS/MS similarity score greater than 0.7. We then applied the lipid metabolites-targeted method using UHPLC-QTrap-MS with the MRM mode, which successfully detected 467 compounds from urine EVs. This indicates that UF integrating phospholipid affinity is a reliable method for metabolic analysis of urinary EVs, which holds the potential for EV clinical application towards biomarker investigation from their metabolites.


Asunto(s)
Vesículas Extracelulares/metabolismo , Metabolómica/métodos , Fosfolípidos/aislamiento & purificación , Fosfolípidos/metabolismo , Ultrafiltración/métodos , Orina/química , Vesículas Extracelulares/ultraestructura , Humanos , Metaboloma , Espectrometría de Masas en Tándem , Titanio/química
14.
Animal ; 15(2): 100095, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33573980

RESUMEN

Optimal management of gilt reproduction requires oestrus synchronization. Hormonal treatments are used for this purpose, but there is a growing demand for non-hormonal alternatives, especially in organic farms. The boar effect is an important alternative opportunity to induce and synchronize oestrus without hormones. Before puberty, gilts exhibit a 'waiting period' during which boar exposure could induce and synchronize the first ovulation. We searched for salivary biomarkers of this period of boar effect receptivity to improve detection of the gilts to stimulate with the perspective of enhancing the efficacy of the boar effect. Saliva samples were collected from 30 Large-White×Landrace crossbred gilts between 140 and 175 days of age. Gilts were exposed twice a day to a boar and subjected to oestrus detection from 150 to 175 days of age. Among the 30 gilts, 10 were detected in oestrus 4 to 7 days after the first introduction of the boar and were considered receptive to the boar effect, 14 were detected in oestrus more than 8 days after first boar contact, and six did not show oestrus and were considered non-receptive. Saliva samples from six receptive and six non-receptive gilts were analyzed for steroidome and for metabolome using gas chromatography coupled to tandem mass spectrometry and 1H nuclear magnetic resonance spectroscopy, respectively. Four saliva samples per gilt were analyzed: 25 days and 11 days before boar introduction, the day of boar introduction, 3 days later for receptive gilts or 7 days later for non-receptive gilts. Twenty-nine steroids and 31 metabolites were detected in gilt saliva. Salivary concentrations of six steroids and three metabolites were significantly different between receptive and non-receptive gilts: progesterone and glycolate 25 days before boar introduction, 3α5ß20α- and 3ß5α20ß-hexahydroprogesterone, dehydroepiandrosterone, androstenediol, succinate, and butyrate 11 days before boar introduction, and 3ß5α-tetrahydroprogesterone on the day of boar introduction. Thus, nine potential salivary biomarkers of boar effect receptivity were identified in our experimental conditions. Further studies with higher numbers of gilts and salivary sampling points are necessary to ascertain their reliability.


Asunto(s)
Saliva , Maduración Sexual , Animales , Biomarcadores , Femenino , Cromatografía de Gases y Espectrometría de Masas/veterinaria , Masculino , Metaboloma , Reproducibilidad de los Resultados , Porcinos
15.
BMC Bioinformatics ; 22(1): 67, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33579202

RESUMEN

BACKGROUND: The search for statistically significant relationships between molecular markers and outcomes is challenging when dealing with high-dimensional, noisy and collinear multivariate omics data, such as metabolomic profiles. Permutation procedures allow for the estimation of adjusted significance levels without assuming independence among metabolomic variables. Nevertheless, the complex non-normal structure of metabolic profiles and outcomes may bias the permutation results leading to overly conservative threshold estimates i.e. lower than those from a Bonferroni or Sidak correction. METHODS: Within a univariate permutation procedure we employ parametric simulation methods based on the multivariate (log-)Normal distribution to obtain adjusted significance levels which are consistent across different outcomes while effectively controlling the type I error rate. Next, we derive an alternative closed-form expression for the estimation of the number of non-redundant metabolic variates based on the spectral decomposition of their correlation matrix. The performance of the method is tested for different model parametrizations and across a wide range of correlation levels of the variates using synthetic and real data sets. RESULTS: Both the permutation-based formulation and the more practical closed form expression are found to give an effective indication of the number of independent metabolic effects exhibited by the system, while guaranteeing that the derived adjusted threshold is stable across outcome measures with diverse properties.


Asunto(s)
Metaboloma , Metabolómica , Modelos Biológicos , Marcadores Genéticos/genética , Metabolómica/métodos , Distribuciones Estadísticas
16.
Plant Physiol Biochem ; 160: 315-328, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33545609

RESUMEN

Soil salinity is among the crucial factors that impact on crop productivity, including oat (Avena sativa L.). Herein, we used two distinct oat cultivars with varied salt tolerance levels to unravel adaptive responses to salt stress by metabolomic and transcriptomic characterization. Metabolomic profiling revealed 201 metabolites, including saccharides, amino acids, organic acids, and secondary metabolites. The levels of most saccharides and amino acids were elevated in Baiyan 2 (BY2) as well as in Baiyan 5 (BY5) exposed to salt stress. In the tolerant cultivar BY2 exposed to 150 mM NaCl, concentrations of most of the metabolites increased significantly, with sucrose increased by 38.34-fold, Sophorose increased by 314.15-fold and Isomaltose 2 increased by 25.76-fold. In the sensitive cultivar BY5, the concentrations of most metabolites increased after the plant was exposed to 150 mM NaCl but decreased after the plant was exposed to 300 mM NaCl. Transcriptomic analysis revealed that gene expressions in BY5 were significantly affected under exposure to 300 mM NaCl (34040 genes up-regulated and 14757 genes down-regulated). Assessment of metabolic pathways as well as KEGG enrichment revealed that salt stress interferes with the biosynthesis of two oat cultivars, including capacity expenditure and sugar metabolism. Most of the BY2 genes enhanced energy consumption (for example, glycolysis) and biosynthesis (for instance, starch and sugar metabolism) under salt stress. In contrast, genes in BY5 were found to be down-regulated, leading to the inhibition of energy consumption and biosynthesis, which may also be attributed to salt sensitivity in BY5. In addition, the modified Na+/K+ transporter genes expression is associated with the predominant ionic responses in BY2, which leads low concentration of Na+ and high K+ when exposed to high salt situations. These findings suggest that the varied defensive capacities of these two oat cultivars in response to salt stress are due to their variations in energy-expenditure strategy, synthesis of energy substances and ion transport in roots. Our present study offers a crucial reference for oat cultivation under saline soil.


Asunto(s)
Avena , Metaboloma , Tolerancia a la Sal , Transcriptoma , Avena/genética , Avena/fisiología , Regulación de la Expresión Génica de las Plantas , Salinidad
17.
Sci Data ; 8(1): 52, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33563993

RESUMEN

In plants, secondary metabolite profiles provide a unique opportunity to explore seasonal variation and responses to the environment. These include both abiotic and biotic factors. In field experiments, such stress factors occur in combination. This variation alters the plant metabolic profiles in yet uninvestigated ways. This data set contains trait and mass spectrometry data of thirteen grassland species collected at four time points in the growing season in 2017. We collected above-ground vegetative material of seven grass and six herb species that were grown in plant communities with different levels of diversity in the Jena Experiment. For each sample, we recorded visible traits and acquired shoot metabolic profiles on a UPLC-ESI-Qq-TOF-MS. We performed the raw data pre-processing in Galaxy-W4M and prepared the data for statistical analysis in R by applying missing data imputation, batch correction, and validity checks on the features. This comprehensive data set provides the opportunity to investigate environmental dynamics across diverse neighbourhoods that are reflected in the metabolomic profile.


Asunto(s)
Pradera , Metaboloma , Plantas/metabolismo , Estaciones del Año , Biodiversidad , Cromatografía Liquida , Alemania , Espectrometría de Masas , Plantas/clasificación
18.
J Vis Exp ; (167)2021 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-33522510

RESUMEN

Follicle development from the primordial to antral stage is a dynamic process within the ovarian cortex, which includes endocrine and paracrine factors from somatic cells and cumulus cell-oocyte communication. Little is known about the ovarian microenvironment and how the cytokines and steroids produced in the surrounding milieu affect follicle progression or arrest. In vitro culture of ovarian cortex enables follicles to develop in a normalized environment that remains supported by adjacent stroma. Our objective was to determine the effect of nutritional Stair-Step diet on the ovarian microenvironment (follicle development, steroid, and cytokine production) through in vitro culture of bovine ovarian cortex. To accomplish this, ovarian cortical pieces were removed from heifers undergoing two different nutritionally developed schemes prior to puberty: Control (traditional nutrition development) and Stair-Step (feeding and restriction during development) that were cut into approximately 0.5-1 mm3 pieces. These pieces were subsequently passed through a series of washes and positioned on a tissue culture insert that is set into a well containing Waymouth's culture medium. Ovarian cortex was cultured for 7 days with daily culture media changes. Histological sectioning was performed to determine follicle stage changes before and after the culture to determine effects of nutrition and impact of culture without additional treatment. Cortex culture medium was pooled over days to measure steroids, steroid metabolites, and cytokines. There were tendencies for increased steroid hormones in ovarian microenvironment that allowed for follicle progression in the Stair-Step versus Control ovarian cortex cultures. The ovarian cortex culture technique allows for a better understanding of the ovarian microenvironment, and how alterations in endocrine secretion may affect follicle progression and growth from both in vivo and in vitro treatments. This culture method may also prove beneficial for testing potential therapeutics that may improve follicle progression in women to promote fertility.


Asunto(s)
Ovario/fisiología , Técnicas de Cultivo de Tejidos/métodos , Animales , Bovinos , Quimiocinas/metabolismo , Medios de Cultivo , Femenino , Imagenología Tridimensional , Metaboloma , Oocitos/citología , Folículo Ovárico/citología , Ovario/citología , Coloración y Etiquetado , Esteroides/metabolismo
19.
Environ Pollut ; 275: 116641, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33611208

RESUMEN

Chemical pollutants, such as pesticides, often leach into aquatic environments and impact non-target organisms. Marine invertebrates have complex life cycles with multiple life-history stages. Exposure to pesticides during one life-history stage potentially influences subsequent stages; a process known as a carry-over effect. Here, we investigated carry-over effects on the jellyfish Aurelia coerulea. We exposed polyps to individual and combined concentrations of atrazine (2.5 µg/L) and chlorpyrifos (0.04 µg/L) for four weeks, after which they were induced to strobilate. The resultant ephyrae were then redistributed and exposed to either the same conditions as their parent-polyps or to filtered seawater to track potential carry-over effects. The percentage of deformities, ephyrae size, pulsation and respiration rates, as well as the metabolic profile of the ephyrae, were measured. We detected a subtle carry-over effect in two metabolites, acetoacetate and glycerophosphocholine, which are precursors of the neurotransmitter acetylcholine, important for energy metabolism and osmoregulation of the ephyrae. Although these carry-over effects were not reflected in the other response variables in the short-term, a persistent reduction of these two metabolites could have negative physiological consequences on A. coerulea jellyfish in the long-term. Our results highlight the importance of considering more than one life-history stage in ecotoxicology, and measuring a range of variables with different sensitivities to detect sub-lethal effects caused by anthropogenic stressors. Furthermore, since we identified few effects when using pesticides concentrations corresponding to Australian water quality guidelines, we suggest that future studies consider concentrations detected in the environment, which are higher than the water quality guidelines, to obtain a more realistic scenario by possible risk from pesticide exposure.


Asunto(s)
Plaguicidas , Escifozoos , Contaminantes Químicos del Agua , Animales , Australia , Ecotoxicología , Metaboloma , Plaguicidas/toxicidad , Contaminantes Químicos del Agua/toxicidad
20.
Ecotoxicol Environ Saf ; 212: 111989, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33524913

RESUMEN

Drinking water exposure to microcystin-leucine-arginine (MC-LR), the most widely occurring cyanotoxins, poses a highly potential risk for human health. However, the health risk of MC-LR exposure at current guideline value in drinking water has not yet entirely evaluated. In the current study, we used 1H NMR-based metabolomics combined with targeted metabolic profiling by GC/LC-MS to explore the toxic effects of MC-LR exposure at environmentally relevant concentrations via drinking water in rats. The results revealed that multiple biological consequences of MC-LR exposure on host metabolism in rats. Both relatively low and high doses of MC-LR used here induced hepatic lipogenesis and inflammation. While only relatively high dose MC-LR (10 µg/L) in drinking water caused more metabolic disorders including inhibition of gluconeogenesis and promotion of ß-oxidation of fatty acid. Although the dose of 1.0 µg/L MC-LR is extremely low for rats, alterations of metabolic profiles were unexpectedly found in rat liver and serum, alarming potential health risk of MC-LR at the WHO guideline level.


Asunto(s)
Agua Potable/química , Microcistinas/toxicidad , Animales , Cromatografía Liquida , Agua Potable/análisis , Hígado/efectos de los fármacos , Masculino , Metaboloma , Metabolómica , Ratas
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