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1.
Yakugaku Zasshi ; 140(10): 1251-1258, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999204

RESUMO

Natural materials such as crude drugs and foods are mixtures composed of various metabolites. Metabolic profiling is often used to identify possible correlations between a compound's metabolic profile and pharmacologic activity. Direct-injection electron ionization-mass spectrometry (DI-EI-MS) is a novel metabolomics method useful for characterizing biological materials. This review demonstrates the establishment of a DI-EI-MS method for metabolic profiling using several closely related lichen species: Cladonia krempelhuberi, C. gracilis, C. pseudogymnopoda, and C. ramulosa. The qualitative DI-EI-MS method was used to profile major and/or minor constituents in extracts of lichen samples. Each lichen sample could be distinguished by altering the DI-EI-MS electron energy and examining the resulting data using one-way analysis of variance. We also attempted to predict pharmacologic activity using DI-EI-MS metabolomics. Blueberry leaf extracts inhibited the proliferation of adult T-cell leukemia (ATL) cells. Blueberry leaf extracts could be distinguished by principal component analysis based on the absolute intensity of characteristic fragment ions. Twenty cultivars were categorized into four species, and the most appropriate discriminative marker m/z value for identifying each cultivar was selected statistically. Components extracted based on DI-EI-MS analyses could be used to construct a model to predict ATL cell bioactivity. These data suggest that the novel DI-EI-MS metabolomics method is suitable for identifying species of natural materials and predicting their pharmacologic activity. This approach could enhance public health by facilitating evaluations of pharmacologic activity and functionality, leading to the elimination of counterfeit products.


Assuntos
Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Mirtilos Azuis (Planta)/química , Mirtilos Azuis (Planta)/metabolismo , Líquens/metabolismo , Metabolômica , Extratos Vegetais/farmacologia , Proliferação de Células/efeitos dos fármacos , Previsões , Humanos , Leucemia-Linfoma de Células T do Adulto/patologia , Espectrometria de Massas/métodos , Metabolômica/métodos , Extratos Vegetais/isolamento & purificação
2.
Nat Commun ; 11(1): 4830, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973134

RESUMO

Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.


Assuntos
Melanoma/metabolismo , Metabolômica/métodos , Microscopia/métodos , Análise Espectral Raman/métodos , Apoptose , Linhagem Celular Tumoral , Ácidos Graxos/metabolismo , Humanos , Gotículas Lipídicas , Metabolismo dos Lipídeos , Lipidômica , Lipídeos , Ácido Oleico , Estearoil-CoA Dessaturase/metabolismo , Transcriptoma
3.
PLoS One ; 15(8): e0238316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866201

RESUMO

BACKGROUND: Perinatally HIV-infected children on anti-retroviral treatment (ART) are reported to have metabolic abnormalities such as dyslipidemia, lipodystrophy, and insulin resistance which potentially increase the risk of diabetes, kidney, liver and cardiovascular disease. OBJECTIVE: To elucidate HIV-mediated metabolic complications that sustain even during ART in perinatally HIV-infected children. METHOD: We have carried out metabolic profiling of the plasma of treatment-naïve and ART-suppressed perinatally HIV-infected children and uninfected controls using 1H nuclear magnetic resonance (NMR) spectroscopy followed by statistical analysis and annotation. RESULT: Validated multivariate analysis showed clear distinction among our study groups. Our results showed elevated levels of lactate, glucose, phosphoenolpyruvic acid, propionic acid, 2-ketobutyric acid and tricarboxylic acid (TCA) cycle metabolites in untreated HIV-infected children compared to uninfected controls. ART normalized the levels of several metabolites, however the level of lactate, phosphoenolpyruvic acid, oxoglutaric acid, oxaloacetic acid, myoinositol and glutamine remained upregulated despite ART in HIV-infected children. Pathway analysis revealed perturbed propanoate metabolism, amino acid metabolism, glycolysis and TCA cycle in untreated and ART-suppressed HIV-infected children. CONCLUSION: Developing therapeutic strategies targeting metabolic abnormalities may be beneficial for preventing diabetes, cardiovascular disease or other associated complications in perinatally HIV-infected children.


Assuntos
Infecções por HIV/metabolismo , Plasma/metabolismo , Antirretrovirais/uso terapêutico , Criança , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Metaboloma/fisiologia , Metabolômica/métodos , Projetos Piloto , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
4.
J Am Soc Mass Spectrom ; 31(10): 2013-2024, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32880453

RESUMO

As corona virus disease 2019 (COVID-19) is a rapidly growing public health crisis across the world, our knowledge of meaningful diagnostic tests and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is still evolving. This novel coronavirus disease COVID-19 can be diagnosed using RT-PCR, but inadequate access to reagents, equipment, and a nonspecific target has slowed disease detection and management. Precision medicine, individualized patient care, requires suitable diagnostics approaches to tackle the challenging aspects of viral outbreaks where many tests are needed in a rapid and deployable approach. Mass spectrometry (MS)-based technologies such as proteomics, glycomics, lipidomics, and metabolomics have been applied in disease outbreaks for identification of infectious disease agents such as virus and bacteria and the molecular phenomena associated with pathogenesis. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is widely used in clinical diagnostics in the United States and Europe for bacterial pathogen identification. Paper spray ionization mass spectrometry (PSI-MS), a rapid ambient MS technique, has recently open a new opportunity for future clinical investigation to diagnose pathogens. Ultra-high-pressure liquid chromatography coupled high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics have been employed in large-scale biomedical research to discriminate infectious pathogens and uncover biomarkers associated with pathogenesis. PCR-MS has emerged as a new technology with the capability to directly identify known pathogens from the clinical specimens and the potential to identify genetic evidence of undiscovered pathogens. Moreover, miniaturized MS offers possible applications with relatively fast, highly sensitive, and potentially portable ways to analyze for viral compounds. However, beneficial aspects of these rapidly growing MS technologies in pandemics like COVID-19 outbreaks has been limited. Hence, this perspective gives a brief of the existing knowledge, current challenges, and opportunities for MS-based techniques as a promising avenue in studying emerging pathogen outbreaks such as COVID-19.


Assuntos
Infecções por Coronavirus/etiologia , Lipidômica/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Pneumonia Viral/etiologia , Proteômica/métodos , Cromatografia Líquida de Alta Pressão , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Glicômica/métodos , Humanos , Pandemias , Reação em Cadeia da Polimerase , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
5.
Nat Commun ; 11(1): 4334, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859911

RESUMO

The metabolome includes not just known but also unknown metabolites; however, metabolite annotation remains the bottleneck in untargeted metabolomics. Ion mobility - mass spectrometry (IM-MS) has emerged as a promising technology by providing multi-dimensional characterizations of metabolites. Here, we curate an ion mobility CCS atlas, namely AllCCS, and develop an integrated strategy for metabolite annotation using known or unknown chemical structures. The AllCCS atlas covers vast chemical structures with >5000 experimental CCS records and ~12 million calculated CCS values for >1.6 million small molecules. We demonstrate the high accuracy and wide applicability of AllCCS with medium relative errors of 0.5-2% for a broad spectrum of small molecules. AllCCS combined with in silico MS/MS spectra facilitates multi-dimensional match and substantially improves the accuracy and coverage of both known and unknown metabolite annotation from biological samples. Together, AllCCS is a versatile resource that enables confident metabolite annotation, revealing comprehensive chemical and metabolic insights towards biological processes.


Assuntos
Espectrometria de Mobilidade Iônica/métodos , Metaboloma/fisiologia , Metabolômica/métodos , Algoritmos , Fenômenos Biológicos , Confiabilidade dos Dados , Bases de Dados Factuais , Redes e Vias Metabólicas , Software , Espectrometria de Massas em Tandem
6.
PLoS One ; 15(8): e0237579, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810196

RESUMO

OBJECTIVE: Patients with CAD have substantial residual risk of mortality, and whether hitherto unknown small-molecule metabolites and metabolic pathways contribute to this risk is unclear. We sought to determine the predictive value of plasma metabolomic profiling in patients with CAD. APPROACH AND RESULTS: Untargeted high-resolution plasma metabolomic profiling of subjects undergoing coronary angiography was performed using liquid chromatography/mass spectrometry. Metabolic features and pathways associated with mortality were identified in 454 subjects using metabolome-wide association studies and Mummichog, respectively, and validated in 322 subjects. A metabolomic risk score comprising of log-transformed HR estimates of metabolites that associated with mortality and passed LASSO regression was created and its performance validated. In 776 subjects (66.8 years, 64% male, 17% Black), 433 and 357 features associated with mortality (FDR-adjusted q<0.20); and clustered into 21 and 9 metabolic pathways in first and second cohorts, respectively. Six pathways (urea cycle/amino group, tryptophan, aspartate/asparagine, lysine, tyrosine, and carnitine shuttle) were common. A metabolomic risk score comprising of 7 metabolites independently predicted mortality in the second cohort (HR per 1-unit increase 2.14, 95%CI 1.62, 2.83). Adding the score to a model of clinical predictors improved risk discrimination (delta C-statistic 0.039, 95%CI -0.006, 0.086; and Integrated Discrimination Index 0.084, 95%CI 0.030, 0.151) and reclassification (continuous Net Reclassification Index 23.3%, 95%CI 7.9%, 38.2%). CONCLUSIONS: Differential regulation of six metabolic pathways involved in myocardial energetics and systemic inflammation is independently associated with mortality in patients with CAD. A novel risk score consisting of representative metabolites is highly predictive of mortality.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Metaboloma/fisiologia , Metabolômica/métodos , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Análise Química do Sangue/métodos , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Medição de Risco
7.
Ecotoxicol Environ Saf ; 205: 111102, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32836152

RESUMO

The increased production and environmental release of graphene nanoparticles has raised concerns about its environmental impact, but the effects of graphene on living organisms at the metabolic level remain unknown. In this study, we used matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)-based untargeted metabolomics to investigate the metabolic response of juvenile earthworms (Eisenia fetida) to graphene exposure in soil tests for the first time. Our results reveal that graphene-exposure significantly disturbs earthworm metabolome, and graphene toxicity on earthworm shows non-concentration-dependent effect. Alanine, phenylalanine, proline, glutamate, arginine, histidine, maltose, glucose, malate, succinate, myo-inositol, and spermidine were successfully screened as significantly change compounds in earthworms for the exposure of graphene. The heterogeneous distributions of these metabolites in earthworm were also clearly imaged by MALDI-MSI. Our MSI results fully showed that the metabolite expression levels in juvenile earthworms significantly changed (up-/down-regulation) after exposure to graphene nanoparticles. This work improves our understanding of graphene nanoparticle toxicity to juvenile earthworms and also enables the continued progression of MALDI-MSI-based metabolomics as an emerging, reliable, and rapid ecotoxicological tool for assessing contaminant toxicity.


Assuntos
Grafite/toxicidade , Oligoquetos/fisiologia , Poluentes do Solo/toxicidade , Alanina/metabolismo , Animais , Grafite/metabolismo , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Oligoquetos/efeitos dos fármacos , Solo/química , Poluentes do Solo/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
8.
Chemosphere ; 260: 127479, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32758777

RESUMO

The presence of pharmaceuticals and personal care products (PPCPs) in natural water resources due to incomplete removal in Wastewater Treatment Plants (WWTPs) is a serious environmental concern at present. In this work, the effects of three pharmaceuticals (propranolol, triclosan, and nimesulide) on Gammarus pulex metabolic profiles at different doses and times of exposure have been investigated by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). The complex data sets generated in the different exposure experiments were analyzed with the ROIMCR procedure, based on the selection of the MS regions of interest (ROI) data and on their analysis by the Multivariate Curve-Resolution Alternating Least Squares (MCR-ALS) chemometrics method. This approach, allowed the resolution and identification of the metabolites present in the analyzed samples, as well as the estimation of their concentration changes due to the exposure experiments. ANOVA Simultaneous Component Analysis (ASCA) and Partial Least Squares Discriminant Analysis (PLS-DA) were then conducted to assess the changes in the concentration of the metabolites for the three pharmaceuticals at the different conditions of exposure. The three tested pharmaceuticals changed the concentrations of metabolites, which were related to different KEGG functional classes. These changes summarize the biochemical response of Gammarus pulex to the exposure by the three investigated pharmaceuticals. Possible pathway alterations related to protein synthesis and oxidative stress were observed in the concentration of identified metabolites.


Assuntos
Anfípodes/fisiologia , Propranolol/toxicidade , Sulfonamidas/toxicidade , Triclosan/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cromatografia Líquida/métodos , Análise dos Mínimos Quadrados , Espectrometria de Massas/métodos , Metaboloma , Metabolômica/métodos , Preparações Farmacêuticas , Águas Residuárias
9.
Sci Rep ; 10(1): 11746, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678173

RESUMO

Category A and B biothreat agents are deemed to be of great concern by the US Centers for Disease Control and Prevention (CDC) and include the bacteria Francisella tularensis, Yersinia pestis, Burkholderia mallei, and Brucella species. Underscored by the impact of the 2020 SARS-CoV-2 outbreak, 2016 Zika pandemic, 2014 Ebola outbreak, 2001 anthrax letter attacks, and 1984 Rajneeshee Salmonella attacks, the threat of future epidemics/pandemics and/or terrorist/criminal use of pathogenic organisms warrants continued exploration and development of both classic and alternative methods of detecting biothreat agents. Volatile organic compounds (VOCs) comprise a large and highly diverse group of carbon-based molecules, generally related by their volatility at ambient temperature. Recently, the diagnostic potential of VOCs has been realized, as correlations between the microbial VOC metabolome and specific bacterial pathogens have been identified. Herein, we describe the use of microbial VOC profiles as fingerprints for the identification of biothreat-relevant microbes, and for differentiating between a kanamycin susceptible and resistant strain. Additionally, we demonstrate microbial VOC profiling using a rapid-throughput VOC metabolomics method we refer to as 'simultaneous multifiber headspace solid-phase microextraction' (simulti-hSPME). Finally, through VOC analysis, we illustrate a rapid non-invasive approach to the diagnosis of BALB/c mice infected with either F. tularensis SCHU S4 or Y. pestis CO92.


Assuntos
Metabolômica/métodos , Tularemia/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Animais , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Surtos de Doenças , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência Microbiana a Medicamentos/genética , Feminino , Francisella tularensis/efeitos dos fármacos , Francisella tularensis/isolamento & purificação , Francisella tularensis/metabolismo , Canamicina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Microextração em Fase Sólida , Tularemia/microbiologia , Tularemia/patologia , Tularemia/veterinária , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/isolamento & purificação , Yersinia pestis/efeitos dos fármacos , Yersinia pestis/isolamento & purificação , Yersinia pestis/metabolismo
10.
Cell Metab ; 32(2): 188-202.e5, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32610096

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Exossomos/metabolismo , Gangliosídeo G(M3)/sangue , Gangliosídeos/sangue , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Adulto , Idoso , Betacoronavirus , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Diglicerídeos/sangue , Feminino , Humanos , Masculino , Metaboloma/fisiologia , Metabolômica/métodos , Pessoa de Meia-Idade , Pandemias , Esfingomielinas/sangue , Espectrometria de Massas em Tandem , Adulto Jovem
11.
BMC Bioinformatics ; 21(1): 283, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620072

RESUMO

BACKGROUND: The problem of assessing associations between multiple omics data including genomics and metabolomics data to identify biomarkers potentially predictive of complex diseases has garnered considerable research interest nowadays. A popular epidemiology approach is to consider an association of each of the predictors with each of the response using a univariate linear regression model, and to select predictors that meet a priori specified significance level. Although this approach is simple and intuitive, it tends to require larger sample size which is costly. It also assumes variables for each data type are independent, and thus ignores correlations that exist between variables both within each data type and across the data types. RESULTS: We consider a multivariate linear regression model that relates multiple predictors with multiple responses, and to identify multiple relevant predictors that are simultaneously associated with the responses. We assume the coefficient matrix of the responses on the predictors is both row-sparse and of low-rank, and propose a group Dantzig type formulation to estimate the coefficient matrix. CONCLUSION: Extensive simulations demonstrate the competitive performance of our proposed method when compared to existing methods in terms of estimation, prediction, and variable selection. We use the proposed method to integrate genomics and metabolomics data to identify genetic variants that are potentially predictive of atherosclerosis cardiovascular disease (ASCVD) beyond well-established risk factors. Our analysis shows some genetic variants that increase prediction of ASCVD beyond some well-established factors of ASCVD, and also suggest a potential utility of the identified genetic variants in explaining possible association between certain metabolites and ASCVD.


Assuntos
Genômica/métodos , Metabolômica/métodos , Aterosclerose/genética , Variação Genética , Humanos , Modelos Lineares , Análise Multivariada
12.
Nat Protoc ; 15(8): 2538-2567, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32681152

RESUMO

Metabolic profiling of biological samples provides important insights into multiple physiological and pathological processes but is hindered by a lack of automated annotation and standardized methods for structure elucidation of candidate disease biomarkers. Here we describe a system for identifying molecular species derived from nuclear magnetic resonance (NMR) spectroscopy-based metabolic phenotyping studies, with detailed information on sample preparation, data acquisition and data modeling. We provide eight different modular workflows to be followed in a recommended sequential order according to their level of difficulty. This multi-platform system involves the use of statistical spectroscopic tools such as Statistical Total Correlation Spectroscopy (STOCSY), Subset Optimization by Reference Matching (STORM) and Resolution-Enhanced (RED)-STORM to identify other signals in the NMR spectra relating to the same molecule. It also uses two-dimensional NMR spectroscopic analysis, separation and pre-concentration techniques, multiple hyphenated analytical platforms and data extraction from existing databases. The complete system, using all eight workflows, would take up to a month, as it includes multi-dimensional NMR experiments that require prolonged experiment times. However, easier identification cases using fewer steps would take 2 or 3 days. This approach to biomarker discovery is efficient and cost-effective and offers increased chemical space coverage of the metabolome, resulting in faster and more accurate assignment of NMR-generated biomarkers arising from metabolic phenotyping studies. It requires a basic understanding of MATLAB to use the statistical spectroscopic tools and analytical skills to perform solid phase extraction (SPE), liquid chromatography (LC) fraction collection, LC-NMR-mass spectroscopy and one-dimensional and two-dimensional NMR experiments.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Extração em Fase Sólida , Fluxo de Trabalho
13.
Aquat Toxicol ; 226: 105560, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32659603

RESUMO

Triclosan (TCS) is commonly used in home and personal care products (HPCPs), which causes it to be ubiquitously detected in aquatic environments. The toxicity of triclosan to aquatic organisms can vary at different pH values because the ionization states of TCS affect its bioaccumulation properties. The objective of this study was to examine the pH-dependent toxicity of TCS on embryonic zebrafish (Danio rerio) using a metabolomic profiling method based on gas chromatography-mass spectrometry (GC-MS). Exposure experiments were conducted on zebrafish embryos at three pH conditions (6, 7, and 8) and two TCS concentrations (30 µg/L and 300 µg/L). Metabolic profiles were obtained by extracting intracellular metabolites. Univariate (One-way ANOVA) and multivariate (PLS-DA) analyses were conducted to determine the metabolomic changes in TCS-treated embryos. Changes in the metabolic profile revealed that interference in biological pathways were induced by mostly ionized TCS (low pH) and high TCS concentrations. Also, fold changes in metabolite profiles showed that the TCS toxicity was a function of pH. Metabolites including urea, D-glucose, D-galactose, phenylalanine, L-glutamic acid, citric acid, and phosphoric acid showed significant changes under different pH conditions (p-value < 0.05). Our metabolomics study revealed that the responses of metabolites to TCS toxicity were pH-dependent. The differences of the responses could be attributed to the bioaccumulation capability of TCS, which increased as the ionized TCS proportion increased under low pH conditions.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Triclosan/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/metabolismo , Concentração de Íons de Hidrogênio , Metabolômica/métodos , Peixe-Zebra/crescimento & desenvolvimento
16.
PLoS One ; 15(7): e0236588, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706804

RESUMO

Xanthoceras sorbifolia, a medicinal and oil-rich woody plant, has great potential for biodiesel production. However, little study explores the link between gene expression level and metabolite accumulation of X. sorbifolia in response to cold stress. Herein, we performed both transcriptomic and metabolomic analyses of X. sorbifolia seedlings to investigate the regulatory mechanism of resistance to low temperature (4 °C) based on physiological profile analyses. Cold stress resulted in a significant increase in the malondialdehyde content, electrolyte leakage and activity of antioxidant enzymes. A total of 1,527 common differentially expressed genes (DEGs) were identified, of which 895 were upregulated and 632 were downregulated. Annotation of DEGs revealed that amino acid metabolism, glycolysis/gluconeogenesis, starch and sucrose metabolism, galactose metabolism, fructose and mannose metabolism, and the citrate cycle (TCA) were strongly affected by cold stress. In addition, DEGs within the plant mitogen-activated protein kinase (MAPK) signaling pathway and TF families of ERF, WRKY, NAC, MYB, and bHLH were transcriptionally activated. Through metabolomic analysis, we found 51 significantly changed metabolites, particularly with the analysis of primary metabolites, such as sugars, amino acids, and organic acids. Moreover, there is an overlap between transcript and metabolite profiles. Association analysis between key genes and altered metabolites indicated that amino acid metabolism and sugar metabolism were enhanced. A large number of specific cold-responsive genes and metabolites highlight a comprehensive regulatory mechanism, which will contribute to a deeper understanding of the highly complex regulatory program under cold stress in X. sorbifolia.


Assuntos
Resposta ao Choque Frio/genética , Metaboloma , Metabolômica/métodos , Sapindaceae/metabolismo , Transcriptoma , Aminoácidos/metabolismo , Catalase/metabolismo , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Malondialdeído/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Análise de Componente Principal , RNA de Plantas/genética , RNA de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sapindaceae/genética , Transdução de Sinais/genética , Superóxido Dismutase/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Food Chem ; 332: 127377, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619942

RESUMO

In this study, paper spray ionization (PSI) coupled to high-resolution mass spectrometry has been used to identify secondary metabolites from ethanol extracts of Averrhoa carambola L. bark (ABE). Various phytoconstituents including phenolic acids, flavonoids, xanthones and terpenoids were identified from the bark. ABE shows potential antioxidant activity as well as markedly inhibited α-glucosidase, elastase, and tyrosinase enzyme activities in a concentration-dependent fashion, respectively. ABE significantly inhibited α-glucosidase at lower concentration (IC50: 7.15 ± 0.06 µg/mL). Identified compounds were tested to understand the biological activity of ABE. Experimental results suggest that norathyriol, one of the identified compounds, has significant α-glucosidase (IC50: 0.81 ± 0.01 µg/mL) inhibition and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities (IC50: 4.90 ± 0.09 µg/mL). At a dose of 100 mg/kg, ABE significantly decreased the postprandial blood glucose level in oral glucose tolerance test (OGTT). This study shows that carambola bark can be a potential source of bioactive compounds.


Assuntos
Antioxidantes/metabolismo , Averrhoa/metabolismo , Espectrometria de Massas , Metabolômica/métodos , Monofenol Mono-Oxigenase/metabolismo , Elastase Pancreática/metabolismo , alfa-Glucosidases/metabolismo
18.
Food Chem ; 332: 127424, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619947

RESUMO

Celery (Apium graveolens L. var dulce) is a widely cultivated vegetable which is popularly consumed due to its nutrient content and contains bioactive metabolites with positive effects on human physiology. In this study, 1H NMR spectroscopy coupled with multivariate statistical analyses was used to distinguish celery stem and leaf samples from different geographical origins. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to investigate the differences between celery extracts from three geographical origins: Australia, Taiwan and China. Sugars, amino acids and organic acids were found to contribute significantly to the differentiation between origins, with mannitol identified as an important discriminating metabolite. It was demonstrated that NMR-based metabolomics is an effective approach for establishing reliable metabolomic fingerprints and profiles, enabling the identification of metabolite biomarkers for the possible discrimination of geographical origin.


Assuntos
Apium/química , Metabolômica/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Aminoácidos/análise , Apium/metabolismo , Austrália , China , Análise Discriminante , Humanos , Análise dos Mínimos Quadrados , Manitol/análise , Manitol/metabolismo , Análise Multivariada , Folhas de Planta/química , Análise de Componente Principal , Verduras/química , Verduras/metabolismo
19.
Food Chem ; 332: 127415, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619945

RESUMO

This study aimed to investigate the combined effect of storage at 4 °C (10-days) and in vitro gastrointestinal digestion on the phytochemical profile of red beet (Beta vulgaris) and amaranth (Amaranthus sp.) microgreens. The untargeted profiling based on UHPLC-QTOF metabolomics allowed annotating 316 compounds, comprising mainly polyphenols and lipids. An impact of storage on the total phenolic content (TPC) was observed, with a maximum increase at 10-days of storage for both red beet (+1.3-fold) and amaranth (+1.1-fold). On the other hand, in vitro digestion of both red beet and amaranth microgreens produced a significant increase in TPC (36-88%), CUPRAC (27-40%), DPPH (6-43%), and BC (41-57%) to reach the maximum at 10 days of storage. Tyrosinase inhibitory potential also decreased following digestion. The combination of biochemical changes occurring in microgreen immature plants (likely in response to the harvest stress) with changes during digestion, determined the actual functional value of microgreens.


Assuntos
Amaranthus/química , Beta vulgaris/química , Metabolômica/métodos , Amaranthus/metabolismo , Beta vulgaris/metabolismo , Cromatografia Líquida de Alta Pressão , Temperatura Baixa , Digestão , Análise Discriminante , Armazenamento de Alimentos , Análise dos Mínimos Quadrados , Espectrometria de Massas , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Fenóis/química , Fenóis/metabolismo
20.
Food Chem ; 332: 127412, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32623128

RESUMO

In this study, metabolomics and proteomics were employed to investigate the change mechanism of nonvolatile compounds during white tea processing. A total of 99 nonvolatile compounds were identified, among which the contents of 13 free amino acids, caffeine, theaflavins, 7 nucleosides and nucleotides, and 5 flavone glycosides increased significantly, while the contents of theanine, catechins, theasinesins, 3 proanthocyanidins, and phenolic acids decreased significantly during the withering period. The results of proteomics indicated that the degradation of proteins accounted for the increase in free amino acid levels; the weakened biosynthesis, in addition to oxidation, also contributed to the decrease in flavonoid levels; the degradation of ribonucleic acids contributed to the increase in nucleoside and nucleotide levels during the withering period. In addition, the drying process was found to slightly promote the formation of white tea taste. Our study provides a novel characterization of white tea taste formation during processing.


Assuntos
Camellia sinensis/química , Metabolômica/métodos , Chá/química , Alcaloides/análise , Alcaloides/metabolismo , Camellia sinensis/metabolismo , Catecóis/análise , Catecóis/metabolismo , Flavonoides/análise , Flavonoides/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Análise de Componente Principal , Proteômica , Chá/metabolismo
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