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Metabolites, Volume 10, Issue 6 (June 2020) – 50 articles

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Cover Story (view full-size image) Differentiation of preadipocytes into mature adipocytes is a highly complex cellular process which [...] Read more.
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Open AccessArticle
Modulation of the Tomato Fruit Metabolome by LED Light
Metabolites 2020, 10(6), 266; https://doi.org/10.3390/metabo10060266 - 26 Jun 2020
Viewed by 575
Abstract
Metabolic profiles of tomatoes change during ripening and light can modulate the activity of relevant biochemical pathways. We investigated the effects of light directly supplied to the fruits on the metabolome of the fruit pericarp during ripening. Mature green tomatoes were exposed to [...] Read more.
Metabolic profiles of tomatoes change during ripening and light can modulate the activity of relevant biochemical pathways. We investigated the effects of light directly supplied to the fruits on the metabolome of the fruit pericarp during ripening. Mature green tomatoes were exposed to well-controlled conditions with light as the only varying factor; control fruits were kept in darkness. In experiment 1 the fruits were exposed to either white light or darkness for 15 days. In experiment 2, fruits were exposed to different light spectra (blue, green, red, far-red, white) added to white background light for seven days. Changes in the global metabolome of the fruit pericarp were monitored using LCMS and GCMS (554 compounds in total). Health-beneficial compounds (carotenoids, flavonoids, tocopherols and phenolic acids) accumulated faster under white light compared to darkness, while alkaloids and chlorophylls decreased faster. Light also changed the levels of taste-related metabolites including glutamate and malate. The light spectrum treatments indicated that the addition of blue light was the most effective treatment in altering the fruit metabolome. We conclude that light during ripening of tomatoes can have various effects on the metabolome and may help with shaping the levels of key compounds involved in various fruit quality characteristics. Full article
(This article belongs to the Special Issue Metabolomics in Plant Environmental Physiology)
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Open AccessArticle
Vibrio harveyi Infection Significantly Alters Amino Acid and Carbohydrate Metabolism in Whiteleg Shrimp, Litopenaeus vannamei
Metabolites 2020, 10(6), 265; https://doi.org/10.3390/metabo10060265 - 25 Jun 2020
Viewed by 294
Abstract
Vibrio harveyi is one of the pathogens that threaten the shrimp farming industry. However, metabolic changes induced by V. harveyi infection in shrimp remain unknown. In this study, we first conducted high resolution-magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR)-based metabolomics studies on [...] Read more.
Vibrio harveyi is one of the pathogens that threaten the shrimp farming industry. However, metabolic changes induced by V. harveyi infection in shrimp remain unknown. In this study, we first conducted high resolution-magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR)-based metabolomics studies on gill, hepatopancreas, and haemolymph of V. harveyi-infected white leg shrimp, Litopenaeus vannamei. Using multivariate statistical analysis, we observed a clear separation between the early (3 and 9 h post-injection (hpi)) and late phases (24, 72 and 144 hpi) of the infection in all tissues. Moreover, metabolic changes in response to V. harveyi infection were faster in the haemolymph in the early phase and significantly changed in the late phase of the infection in the gills. Extensive changes were observed in the hepatopancreas, with 24 hpi being the turning point of progression from early to late phase infection in the hepatopancreas. V. harveyi infection increased the energy demand in L. vannamei and the amino acid and carbohydrate metabolism pathways also exhibited significant changes depending on the tissue. Thus, each tissue displayed different metabolic changes, depending on the progress of the infection. Full article
(This article belongs to the Section Environmental Science)
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Open AccessReview
Oxylipin Response to Acute and Chronic Exercise: A Systematic Review
Metabolites 2020, 10(6), 264; https://doi.org/10.3390/metabo10060264 - 25 Jun 2020
Viewed by 489
Abstract
Oxylipins are oxidized compounds of polyunsaturated fatty acids that play important roles in the body. Recently, metabololipidomic-based studies using advanced mass spectrometry have measured the oxylipins generated during acute and chronic physical exercise and described the related physiological effects. The objective of this [...] Read more.
Oxylipins are oxidized compounds of polyunsaturated fatty acids that play important roles in the body. Recently, metabololipidomic-based studies using advanced mass spectrometry have measured the oxylipins generated during acute and chronic physical exercise and described the related physiological effects. The objective of this systematic review was to provide a panel of the primary exercise-related oxylipins and their respective functions in healthy individuals. Searches were performed in five databases (Cochrane, PubMed, Science Direct, Scopus and Web of Science) using combinations of the Medical Subject Headings (MeSH) terms: “Humans”, “Exercise”, “Physical Activity”, “Sports”, “Oxylipins”, and “Lipid Mediators”. An adapted scoring system created in a previous study from our group was used to rate the quality of the studies. Nine studies were included after examining 1749 documents. Seven studies focused on the acute effect of physical exercise while two studies determined the effects of exercise training on the oxylipin profile. Numerous oxylipins are mobilized during intensive and prolonged exercise, with most related to the inflammatory process, immune function, tissue repair, cardiovascular and renal functions, and oxidative stress. Full article
(This article belongs to the Special Issue Fatty Acid Metabolism)
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Open AccessReview
Overview of Folic Acid Supplementation Alone or in Combination with Vitamin B12 in Dairy Cattle during Periparturient Period
Metabolites 2020, 10(6), 263; https://doi.org/10.3390/metabo10060263 - 25 Jun 2020
Viewed by 331
Abstract
The periparturient period is the period from three weeks before calving to three weeks post-calving. This period is important in terms of health, productivity and profitability, and is fundamental to successful lactation. During this period, the animal experiences stress because of hormonal changes [...] Read more.
The periparturient period is the period from three weeks before calving to three weeks post-calving. This period is important in terms of health, productivity and profitability, and is fundamental to successful lactation. During this period, the animal experiences stress because of hormonal changes due to pregnancy and the significant rise in milk production. In addition, a negative energy balance usually occurs, because the demand for nutrients to sustain milk production increases by more than the nutrient supply during the periparturient period. The immunity of dairy cattle is suppressed around parturition, which increases their susceptibility to infections. Special care regarding nutrition can reduce the risks of metabolism and immunity depression, which dairy cattle face during the periparturient span. Folic acid is relevant in this regard because of its critical role in the metabolism to maintain lactational performance and to improve health. Being a donor of one-carbon units, folic acid has a vital role in DNA and RNA biosynthesis. Generally, the folic acid requirements of dairy cattle can be met by the microbial synthesis in the rumen; however, in special cases, such as during the periparturient period, the requirement for this vitamin strictly increases. Vitamin B12 also has a critical role in the metabolism as a coenzyme of the enzyme methionine synthase for the transfer of a methyl group from folic acid to homocysteine for the regeneration of methionine. In the current review, we highlight the issues facing periparturient dairy cattle, and relevant knowledge and practices, and point out future research directions for utilization of the associated vitamins in ruminants, especially during the periparturient period. Full article
(This article belongs to the Special Issue Folate Absorption and Metabolism)
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Open AccessArticle
Plasma Lipid Profile Reveals Plasmalogens as Potential Biomarkers for Colon Cancer Screening
Metabolites 2020, 10(6), 262; https://doi.org/10.3390/metabo10060262 - 25 Jun 2020
Viewed by 513
Abstract
In this era of precision medicine, there is an increasingly urgent need for highly sensitive tests for detecting tumors such as colon cancer (CC), a silent disease where the first symptoms may take 10–15 years to appear. Mass spectrometry-based lipidomics is an emerging [...] Read more.
In this era of precision medicine, there is an increasingly urgent need for highly sensitive tests for detecting tumors such as colon cancer (CC), a silent disease where the first symptoms may take 10–15 years to appear. Mass spectrometry-based lipidomics is an emerging tool for such clinical diagnosis. We used ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry operating in high energy collision spectral acquisition mode (MSE) mode (UPLC-QTOF-MSE) and gas chromatography (GC) to investigate differences between the plasmatic lipidic composition of CC patients and control (CTR) subjects. Key enzymes in lipidic metabolism were investigated using immuno-based detection assays. Our partial least squares discriminant analysis (PLS-DA) resulted in a suitable discrimination between CTR and CC plasma samples. Forty-two statistically significant discriminating lipids were putatively identified. Ether lipids showed a prominent presence and accordingly, a decrease in glyceronephosphate O-acyltransferase (GNPAT) enzyme activity was found. A receiver operating characteristic (ROC) curve built for three plasmalogens of phosphatidylserine (PS), named PS(P-36:1), PS(P-38:3) and PS(P-40:5), presented an area under the curve (AUC) of 0.998, and sensitivity and specificity of 100 and 85.7% respectively. These results show significant differences in CC patients’ plasma lipid composition that may be useful in discriminating them from CTR individuals with a special role for plasmalogens. Full article
(This article belongs to the Section Metabolomic Profiling Technology)
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Open AccessArticle
The Biochemical Profile of Post-Mortem Brain from People Who Suffered from Epilepsy Reveals Novel Insights into the Etiopathogenesis of the Disease
Metabolites 2020, 10(6), 261; https://doi.org/10.3390/metabo10060261 - 23 Jun 2020
Viewed by 579
Abstract
Epilepsy not-otherwise-specified (ENOS) is one of the most common causes of chronic disorders impacting human health, with complex multifactorial etiology and clinical presentation. Understanding the metabolic processes associated with the disorder may aid in the discovery of preventive and therapeutic measures. Post-mortem brain [...] Read more.
Epilepsy not-otherwise-specified (ENOS) is one of the most common causes of chronic disorders impacting human health, with complex multifactorial etiology and clinical presentation. Understanding the metabolic processes associated with the disorder may aid in the discovery of preventive and therapeutic measures. Post-mortem brain samples were harvested from the frontal cortex (BA8/46) of people diagnosed with ENOS cases (n = 15) and age- and sex-matched control subjects (n = 15). We employed a targeted metabolomics approach using a combination of proton nuclear magnetic resonance (1H-NMR) and direct injection/liquid chromatography tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 72 metabolites using 1H-NMR and 159 using DI/LC-MS/MS. Among the 212 detected metabolites, 14 showed significant concentration changes between ENOS cases and controls (p < 0.05; q < 0.05). Of these, adenosine monophosphate and O-acetylcholine were the most commonly selected metabolites used to develop predictive models capable of discriminating between ENOS and unaffected controls. Metabolomic set enrichment analysis identified ethanol degradation, butyrate metabolism and the mitochondrial beta-oxidation of fatty acids as the top three significantly perturbed metabolic pathways. We report, for the first time, the metabolomic profiling of postmortem brain tissue form patients who died from epilepsy. These findings can potentially expand upon the complex etiopathogenesis and help identify key predictive biomarkers of ENOS. Full article
(This article belongs to the Special Issue Metabolomics in Human Tissues and Materials)
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Open AccessArticle
Revisiting Five Years of CASMI Contests with EPA Identification Tools
Metabolites 2020, 10(6), 260; https://doi.org/10.3390/metabo10060260 - 23 Jun 2020
Viewed by 462
Abstract
Software applications for high resolution mass spectrometry (HRMS)-based non-targeted analysis (NTA) continue to enhance chemical identification capabilities. Given the variety of available applications, determining the most fit-for-purpose tools and workflows can be difficult. The Critical Assessment of Small Molecule Identification (CASMI) contests were [...] Read more.
Software applications for high resolution mass spectrometry (HRMS)-based non-targeted analysis (NTA) continue to enhance chemical identification capabilities. Given the variety of available applications, determining the most fit-for-purpose tools and workflows can be difficult. The Critical Assessment of Small Molecule Identification (CASMI) contests were initiated in 2012 to provide a means to evaluate compound identification tools on a standardized set of blinded tandem mass spectrometry (MS/MS) data. Five CASMI contests have resulted in recommendations, publications, and invaluable datasets for practitioners of HRMS-based screening studies. The US Environmental Protection Agency’s (EPA) CompTox Chemicals Dashboard is now recognized as a valuable resource for compound identification in NTA studies. However, this application was too new and immature in functionality to participate in the five previous CASMI contests. In this work, we performed compound identification on all five CASMI contest datasets using Dashboard tools and data in order to critically evaluate Dashboard performance relative to that of other applications. CASMI data was accessed via the CASMI webpage and processed for use in our spectral matching and identification workflow. Relative to applications used by former contest participants, our tools, data, and workflow performed well, placing more challenge compounds in the top five of ranked candidates than did the winners of three contest years and tying in a fourth. In addition, we conducted an in-depth review of the CASMI structure sets and made these reviewed sets available via the Dashboard. Our results suggest that Dashboard data and tools would enhance chemical identification capabilities for practitioners of HRMS-based NTA. Full article
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Open AccessReview
A Systematic Review of Metabolomic and Lipidomic Candidates for Biomarkers in Radiation Injury
Metabolites 2020, 10(6), 259; https://doi.org/10.3390/metabo10060259 - 20 Jun 2020
Viewed by 381
Abstract
A large-scale nuclear event has the ability to inflict mass casualties requiring point-of-care and laboratory-based diagnostic and prognostic biomarkers to inform victim triage and appropriate medical intervention. Extensive progress has been made to develop post-exposure point-of-care biodosimetry assays and to identify biomarkers that [...] Read more.
A large-scale nuclear event has the ability to inflict mass casualties requiring point-of-care and laboratory-based diagnostic and prognostic biomarkers to inform victim triage and appropriate medical intervention. Extensive progress has been made to develop post-exposure point-of-care biodosimetry assays and to identify biomarkers that may be used in early phase testing to predict the course of the disease. Screening for biomarkers has recently extended to identify specific metabolomic and lipidomic responses to radiation using animal models. The objective of this review was to determine which metabolites or lipids most frequently experienced perturbations post-ionizing irradiation (IR) in preclinical studies using animal models of acute radiation sickness (ARS) and delayed effects of acute radiation exposure (DEARE). Upon review of approximately 65 manuscripts published in the peer-reviewed literature, the most frequently referenced metabolites showing clear changes in IR induced injury were found to be citrulline, citric acid, creatine, taurine, carnitine, xanthine, creatinine, hypoxanthine, uric acid, and threonine. Each metabolite was evaluated by specific study parameters to determine whether trends were in agreement across several studies. A select few show agreement across variable animal models, IR doses and timepoints, indicating that they may be ubiquitous and appropriate for use in diagnostic or prognostic biomarker panels. Full article
(This article belongs to the Special Issue Metabolomics/Lipidomics in Radiation Research)
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Open AccessCommunication
Microbial Metabolite Urolithin B Inhibits Recombinant Human Monoamine Oxidase A Enzyme
Metabolites 2020, 10(6), 258; https://doi.org/10.3390/metabo10060258 - 19 Jun 2020
Viewed by 483
Abstract
Urolithins are gut microbial metabolites derived from ellagitannins (ET) and ellagic acid (EA), and shown to exhibit anticancer, anti-inflammatory, anti-microbial, anti-glycative and anti-oxidant activities. Similarly, the parent molecules, ET and EA are reported for their neuroprotection and antidepressant activities. Due to the poor [...] Read more.
Urolithins are gut microbial metabolites derived from ellagitannins (ET) and ellagic acid (EA), and shown to exhibit anticancer, anti-inflammatory, anti-microbial, anti-glycative and anti-oxidant activities. Similarly, the parent molecules, ET and EA are reported for their neuroprotection and antidepressant activities. Due to the poor bioavailability of ET and EA, the in vivo functional activities cannot be attributed exclusively to these compounds. Elevated monoamine oxidase (MAO) activities are responsible for the inactivation of monoamine neurotransmitters in neurological disorders, such as depression and Parkinson’s disease. In this study, we examined the inhibitory effects of urolithins (A, B and C) and EA on MAO activity using recombinant human MAO-A and MAO-B enzymes. Urolithin B was found to be a better MAO-A enzyme inhibitor among the tested urolithins and EA with an IC50 value of 0.88 µM, and displaying a mixed mode of inhibition. However, all tested compounds exhibited higher IC50 (>100 µM) for MAO-B enzyme. Full article
(This article belongs to the Special Issue Nutrition, Microbiota and Metabolism)
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Open AccessArticle
Tumor Tissue-Specific Biomarkers of Colorectal Cancer by Anatomic Location and Stage
Metabolites 2020, 10(6), 257; https://doi.org/10.3390/metabo10060257 - 19 Jun 2020
Viewed by 412
Abstract
The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, [...] Read more.
The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, but this pre-validation phase is confounded by non-specific disease influences on the metabolome. We therefore propose that metabolite biomarker discovery would have greater success and higher reproducibility for CRC if the discovery phase was conducted in tumor tissues, to find metabolites that have higher specificity to the metabolic consequences of the disease, that are then validated in blood samples. This would thereby eliminate any non-tumor and/or body response effects to the disease. In this study, we performed comprehensive untargeted metabolomics analyses on normal (adjacent) colon and tumor tissues from CRC patients, revealing tumor tissue-specific biomarkers (n = 39/group). We identified 28 highly discriminatory tumor tissue metabolite biomarkers of CRC by orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate analyses (VIP > 1.5, p < 0.05). A stepwise selection procedure was used to identify nine metabolites that were the most predictive of CRC with areas under the curve (AUCs) of >0.96, using various models. We further identified five biomarkers that were specific to the anatomic location of tumors in the colon (n = 236). The combination of these five metabolites (S-adenosyl-L-homocysteine, formylmethionine, fucose 1-phosphate, lactate, and phenylalanine) demonstrated high differentiative capability for left- and right-sided colon cancers at stage I by internal cross-validation (AUC = 0.804, 95% confidence interval, CI 0.670–0.940). This study thus revealed nine discriminatory biomarkers of CRC that are now poised for external validation in a future independent cohort of samples. We also discovered a discrete metabolic signature to determine the anatomic location of the tumor at the earliest stage, thus potentially providing clinicians a means to identify individuals that could be triaged for additional screening regimens. Full article
(This article belongs to the Special Issue Metabolomics Analysis for Biomarker Discovery and Human Health)
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Open AccessArticle
The Zebra Mussel (Dreissena polymorpha) as a Model Organism for Ecotoxicological Studies: A Prior 1H NMR Spectrum Interpretation of a Whole Body Extract for Metabolism Monitoring
Metabolites 2020, 10(6), 256; https://doi.org/10.3390/metabo10060256 - 18 Jun 2020
Viewed by 315
Abstract
The zebra mussel (Dreissena polymorpha) represents a useful reference organism for the ecotoxicological study of inland waters, especially for the characterization of the disturbances induced by human activities. A nuclear magnetic resonance (NMR)-based metabolomic approach was developed on this species. The [...] Read more.
The zebra mussel (Dreissena polymorpha) represents a useful reference organism for the ecotoxicological study of inland waters, especially for the characterization of the disturbances induced by human activities. A nuclear magnetic resonance (NMR)-based metabolomic approach was developed on this species. The investigation of its informative potential required the prior interpretation of a reference 1H NMR spectrum of a lipid-free zebra mussel extract. After the extraction of polar metabolites from a pool of whole-body D. polymorpha powder, the resulting highly complex 1D 1H NMR spectrum was interpreted and annotated through the analysis of the corresponding 2D homonuclear and heteronuclear NMR spectra. The spectrum interpretation was completed and validated by means of sample spiking with 24 commercial compounds. Among the 238 detected 1H signals, 53% were assigned, resulting in the identification of 37 metabolites with certainty or high confidence, while 5 metabolites were only putatively identified. The description of such a reference spectrum and its annotation are expected to speed up future analyses and interpretations of NMR-based metabolomic studies on D. polymorpha and to facilitate further explorations of the impact of environmental changes on its physiological state, more particularly in the context of large-scale ecological and ecotoxicological studies. Full article
(This article belongs to the Section Environmental Science)
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Open AccessArticle
Comparison of Metabolomic Profiles of Organs in Mice of Different Strains Based on SPME-LC-HRMS
Metabolites 2020, 10(6), 255; https://doi.org/10.3390/metabo10060255 - 17 Jun 2020
Viewed by 531
Abstract
Given that the extent to which genetics alters the metabolomic profile of tissues is still poorly understood, the current study aimed to characterize and investigate the metabolite profiles of brain, liver, kidney and skeletal muscle of two common mouse inbred strains (BALB/c, C57BL/6) [...] Read more.
Given that the extent to which genetics alters the metabolomic profile of tissues is still poorly understood, the current study aimed to characterize and investigate the metabolite profiles of brain, liver, kidney and skeletal muscle of two common mouse inbred strains (BALB/c, C57BL/6) and one outbred stock (CD1) for strain-specific differences. Male mice (n = 15) at the age of 12 weeks were used: BALB/c (n = 5), C57BL/6 (n = 5) and CD1 (n = 5). Solid phase microextraction (SPME) was applied for the extraction of analytes from the tissues. SPME fibers (approximately 0.2 mm in diameter) coated with a biocompatible sorbent (4 mm length of hydrophilic-lipophilic balanced particles) were inserted into each organ immediately after euthanasia. Samples were analyzed using liquid chromatography coupled to a Q-Exactive Focus Orbitrap mass spectrometer. Distinct interstrain differences in the metabolomic patterns of brain and liver tissue were revealed. The metabolome of kidney and muscle tissue in BALB/c mice differed greatly from C57BL/6 and CD1 strains. The main compounds differentiating all the targeted organs were alpha-amino acids, purine nucleotides and fatty acid esters. The results of the study indicate that the baseline metabolome of organs, as well as different metabolic pathways, vary widely among general-purpose models of laboratory mice commonly used in biomedical research. Full article
(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research)
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Open AccessReview
The Cardiac Lipidome in Models of Cardiovascular Disease
Metabolites 2020, 10(6), 254; https://doi.org/10.3390/metabo10060254 - 17 Jun 2020
Viewed by 476
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide. There are numerous factors involved in the development of CVD. Among these, lipids have an important role in maintaining the myocardial cell structure as well as cardiac function. Fatty acids (FA) are utilized [...] Read more.
Cardiovascular disease (CVD) is the leading cause of death worldwide. There are numerous factors involved in the development of CVD. Among these, lipids have an important role in maintaining the myocardial cell structure as well as cardiac function. Fatty acids (FA) are utilized for energy, but also contribute to the pathogenesis of CVD and heart failure. Advances in mass spectrometry methods have enabled the comprehensive analysis of a plethora of lipid species from a single sample comprised of a heterogeneous population of lipid molecules. Determining cardiac lipid alterations in different models of CVD identifies novel biomarkers as well as reveals molecular mechanisms that underlie disease development and progression. This information could inform the development of novel therapeutics in the treatment of CVD. Herein, we provide a review of recent studies of cardiac lipid profiles in myocardial infarction, obesity, and diabetic and dilated cardiomyopathy models of CVD by methods of mass spectrometry analysis. Full article
(This article belongs to the Special Issue Advances in Lipidomics: Biomedicine, Nutrients and Methodology)
Open AccessReview
A Metabolic Perspective and Opportunities in Pharmacologically Important Safflower
Metabolites 2020, 10(6), 253; https://doi.org/10.3390/metabo10060253 - 17 Jun 2020
Viewed by 302
Abstract
Safflower (Carthamus tinctorius L.) has long been grown as a crop due to its commercial utility as oil, animal feed, and pharmacologically significant secondary metabolites. The integration of omics approaches, including genomics, transcriptomics, metabolomics, and proteomics datasets, has provided more comprehensive knowledge [...] Read more.
Safflower (Carthamus tinctorius L.) has long been grown as a crop due to its commercial utility as oil, animal feed, and pharmacologically significant secondary metabolites. The integration of omics approaches, including genomics, transcriptomics, metabolomics, and proteomics datasets, has provided more comprehensive knowledge of the chemical composition of crop plants for multiple applications. Knowledge of a metabolome of plant is crucial to optimize the evolution of crop traits, improve crop yields and quality, and ensure nutritional and health factors that provide the opportunity to produce functional food or feedstuffs. Safflower contains numerous chemical components that possess many pharmacological activities including central nervous, cardiac, vascular, anticoagulant, reproductive, gastrointestinal, antioxidant, hypolipidemic, and metabolic activities, providing many other human health benefits. In addition to classical metabolite studies, this review focuses on several metabolite-based working techniques and updates to provide a summary of the current medical applications of safflower. Full article
(This article belongs to the Section Plant Science)
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Open AccessArticle
Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model
Metabolites 2020, 10(6), 252; https://doi.org/10.3390/metabo10060252 - 17 Jun 2020
Viewed by 412
Abstract
Long-term exposures to low dose space radiation may have adverse effects on human health during missions in deep space. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as biomarkers of organ- and tissue-specific radiation injury, particularly of [...] Read more.
Long-term exposures to low dose space radiation may have adverse effects on human health during missions in deep space. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as biomarkers of organ- and tissue-specific radiation injury, particularly of injuries that appear weeks or months after radiation exposure. To assess the feasibility of using plasma metabolic and lipidomic profiles as biomarkers of injury from space radiation, we used a mouse model of exposure to low doses of oxygen ions (16O) and protons (1H). Plasma profiles were compared with those of mice exposed to γ-rays as a reference set. Our results demonstrate major changes in glycerophospholipid metabolism, amino acid metabolism, as well as fatty acid metabolism. We also observed dyslipidemia and lipid peroxidation, suggesting an inflammatory phenotype with possible long-term consequences to overall health upon exposure to low doses of high linear energy transfer (LET) radiation. Full article
(This article belongs to the Special Issue Integrative-Metabolomics in Epidemiological Studies)
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Open AccessCommunication
Pursuing Experimental Reproducibility: An Efficient Protocol for the Preparation of Cerebrospinal Fluid Samples for NMR-Based Metabolomics and Analysis of Sample Degradation
Metabolites 2020, 10(6), 251; https://doi.org/10.3390/metabo10060251 - 16 Jun 2020
Viewed by 286
Abstract
NMR-based metabolomics investigations of human biofluids offer great potential to uncover new biomarkers. In contrast to protocols for sample collection and biobanking, procedures for sample preparation prior to NMR measurements are still heterogeneous, thus compromising the comparability of the resulting data. Herein, we [...] Read more.
NMR-based metabolomics investigations of human biofluids offer great potential to uncover new biomarkers. In contrast to protocols for sample collection and biobanking, procedures for sample preparation prior to NMR measurements are still heterogeneous, thus compromising the comparability of the resulting data. Herein, we present results of an investigation of the handling of cerebrospinal fluid (CSF) samples for NMR metabolomics research. Origins of commonly observed problems when conducting NMR experiments on this type of sample are addressed, and suitable experimental conditions in terms of sample preparation and pH control are discussed. Sample stability was assessed by monitoring the degradation of CSF samples by NMR, hereby identifying metabolite candidates, which are potentially affected by sample storage. A protocol was devised yielding consistent spectroscopic data as well as achieving overall sample stability for robust analysis. We present easy to adopt standard operating procedures with the aim to establish a shared sample handling strategy that facilitates and promotes inter-laboratory comparison, and the analysis of sample degradation provides new insights into sample stability. Full article
(This article belongs to the Section Metabolomic Profiling Technology)
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Open AccessArticle
Photosynthetic Co-production of Succinate and Ethylene in a Fast-Growing Cyanobacterium, Synechococcus elongatus PCC 11801
Metabolites 2020, 10(6), 250; https://doi.org/10.3390/metabo10060250 - 16 Jun 2020
Viewed by 411
Abstract
Cyanobacteria are emerging as hosts for photoautotrophic production of chemicals. Recent studies have attempted to stretch the limits of photosynthetic production, typically focusing on one product at a time, possibly to minimise the additional burden of product separation. Here, we explore the simultaneous [...] Read more.
Cyanobacteria are emerging as hosts for photoautotrophic production of chemicals. Recent studies have attempted to stretch the limits of photosynthetic production, typically focusing on one product at a time, possibly to minimise the additional burden of product separation. Here, we explore the simultaneous production of two products that can be easily separated: ethylene, a gaseous product, and succinate, an organic acid that accumulates in the culture medium. This was achieved by expressing a single copy of the ethylene forming enzyme (efe) under the control of PcpcB, the inducer-free super-strong promoter of phycocyanin β subunit. We chose the recently reported, fast-growing and robust cyanobacterium, Synechococcus elongatus PCC 11801, as the host strain. A stable recombinant strain was constructed using CRISPR-Cpf1 in a first report of markerless genome editing of this cyanobacterium. Under photoautotrophic conditions, the recombinant strain shows specific productivities of 338.26 and 1044.18 μmole/g dry cell weight/h for ethylene and succinate, respectively. These results compare favourably with the reported productivities for individual products in cyanobacteria that are highly engineered. Metabolome profiling and 13C labelling studies indicate carbon flux redistribution and suggest avenues for further improvement. Our results show that S. elongatus PCC 11801 is a promising candidate for metabolic engineering. Full article
(This article belongs to the Special Issue Metabolic Engineering and Synthetic Biology Volume 2)
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Open AccessReview
Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective
Metabolites 2020, 10(6), 249; https://doi.org/10.3390/metabo10060249 - 15 Jun 2020
Viewed by 497
Abstract
The tumor microenvironment (TME) comprises complex interactions of multiple cell types that determines cell behavior and metabolism such as nutrient competition and immune suppression. We discuss the various types of heterogeneity that exist in solid tumors, and the complications this invokes for studies [...] Read more.
The tumor microenvironment (TME) comprises complex interactions of multiple cell types that determines cell behavior and metabolism such as nutrient competition and immune suppression. We discuss the various types of heterogeneity that exist in solid tumors, and the complications this invokes for studies of TME. As human subjects and in vivo model systems are complex and difficult to manipulate, simpler 3D model systems that are compatible with flexible experimental control are necessary for studying metabolic regulation in TME. Stable Isotope Resolved Metabolomics (SIRM) is a valuable tool for tracing metabolic networks in complex systems, but at present does not directly address heterogeneous metabolism at the individual cell level. We compare the advantages and disadvantages of different model systems for SIRM experiments, with a focus on lung cancer cells, their interactions with macrophages and T cells, and their response to modulators in the immune microenvironment. We describe the experimental set up, illustrate results from 3D cultures and co-cultures of lung cancer cells with human macrophages, and outline strategies to address the heterogeneous TME. Full article
(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research)
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Open AccessArticle
Profiling of Volatile Organic Compounds in Wild Indigenous Medicinal Ginger (Zingiber barbatum Wall.) from Myanmar
Metabolites 2020, 10(6), 248; https://doi.org/10.3390/metabo10060248 - 15 Jun 2020
Viewed by 342
Abstract
The emissions of volatile organic compounds (VOCs) strongly depend on the plant species and are differently represented in specific taxa. VOCs have a degree of chemical diversity and also can serve as chemotaxonomic markers. Zingiber barbatum Wall. is a wild medicinal ginger plant [...] Read more.
The emissions of volatile organic compounds (VOCs) strongly depend on the plant species and are differently represented in specific taxa. VOCs have a degree of chemical diversity and also can serve as chemotaxonomic markers. Zingiber barbatum Wall. is a wild medicinal ginger plant endemic to Myanmar whose VOC composition has never been screened before. In this study, we screened the rhizome of Z. barbatum to identify the VOC composition by the application of gas chromatography combined with time-of-flight-mass spectrometry (GC-TOF-MS). The resulting VOC profile of Z. barbatum showed that it consists mainly of monoterpenes (21%) and sesquiterpenes (30%). Intraspecific similarities and dissimilarities were found to exist between Z. barbatum genotypes in terms of VOC composition. Four accessions (ZO191, ZO223, ZO217, and the control accession ZO105) collected from the Shan State and Mandalay region of Myanmar were found to share a similar VOC profile, while two accessions (ZO64 and ZO160) collected from the Bago region were found to vary in their VOC profiles compared with the control accession. The two identified compounds, i.e., α-bergamotene and β-(E)-guaiene may serve as discriminative chemical markers for the characterization of Z. barbatum species collected in these three geographical regions of Myanmar. This study represents a first attempt to identify and describe the VOCs in the medicinal species Z. barbatum that have not been reported to date. Full article
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Open AccessArticle
A Tale of Two Biomarkers: Untargeted 1H NMR Metabolomic Fingerprinting of BHBA and NEFA in Early Lactation Dairy Cows
Metabolites 2020, 10(6), 247; https://doi.org/10.3390/metabo10060247 - 15 Jun 2020
Viewed by 306
Abstract
Disorders of energy metabolism, which can result from a failure to adapt to the period of negative energy balance immediately after calving, have significant negative effects on the health, welfare and profitability of dairy cows. The most common biomarkers of energy balance in [...] Read more.
Disorders of energy metabolism, which can result from a failure to adapt to the period of negative energy balance immediately after calving, have significant negative effects on the health, welfare and profitability of dairy cows. The most common biomarkers of energy balance in dairy cows are β-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA). While elevated concentrations of these biomarkers are associated with similar negative health and production outcomes, the phenotypic and genetic correlations between them are weak. In this study, we used an untargeted 1H NMR metabolomics approach to investigate the serum metabolomic fingerprints of BHBA and NEFA. Serum samples were collected from 298 cows in early lactation (calibration dataset N = 248, validation N = 50). Metabolomic fingerprinting was done by regressing 1H NMR spectra against BHBA and NEFA concentrations (determined using colorimetric assays) using orthogonal partial least squares regression. Prediction accuracies were high for BHBA models, and moderately high for NEFA models (R2 of external validation of 0.88 and 0.75, respectively). We identified 16 metabolites that were significantly (variable importance of projection score > 1) correlated with the concentration of one or both biomarkers. These metabolites were primarily intermediates of energy, phospholipid, and/or methyl donor metabolism. Of the significant metabolites identified; (1) two (acetate and creatine) were positively correlated with BHBA but negatively correlated with NEFA, (2) nine had similar associations with both BHBA and NEFA, (3) two were correlated with only BHBA concentration, and (4) three were only correlated with NEFA concentration. Overall, our results suggest that BHBA and NEFA are indicative of similar metabolic states in clinically healthy animals, but that several significant metabolic differences exist that help to explain the weak correlations between them. We also identified several metabolites that may be useful intermediate phenotypes in genomic selection for improved metabolic health. Full article
(This article belongs to the Special Issue Metabolomic Applications in Animal Science)
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Open AccessReview
Review of Oxepine-Pyrimidinone-Ketopiperazine Type Nonribosomal Peptides
Metabolites 2020, 10(6), 246; https://doi.org/10.3390/metabo10060246 - 15 Jun 2020
Viewed by 266
Abstract
Recently, a rare class of nonribosomal peptides (NRPs) bearing a unique Oxepine-Pyrimidinone-Ketopiperazine (OPK) scaffold has been exclusively isolated from fungal sources. Based on the number of rings and conjugation systems on the backbone, it can be further categorized into three types A, B, [...] Read more.
Recently, a rare class of nonribosomal peptides (NRPs) bearing a unique Oxepine-Pyrimidinone-Ketopiperazine (OPK) scaffold has been exclusively isolated from fungal sources. Based on the number of rings and conjugation systems on the backbone, it can be further categorized into three types A, B, and C. These compounds have been applied to various bioassays, and some have exhibited promising bioactivities like antifungal activity against phytopathogenic fungi and transcriptional activation on liver X receptor α. This review summarizes all the research related to natural OPK NRPs, including their biological sources, chemical structures, bioassays, as well as proposed biosynthetic mechanisms from 1988 to March 2020. The taxonomy of the fungal sources and chirality-related issues of these products are also discussed. Full article
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Open AccessArticle
Exhaled Volatile Organic Compounds during Inflammation Induced by TNF-α in Ventilated Rats
Metabolites 2020, 10(6), 245; https://doi.org/10.3390/metabo10060245 - 15 Jun 2020
Viewed by 300
Abstract
Systemic inflammation alters the composition of exhaled breath, possibly helping clinicians diagnose conditions such as sepsis. We therefore evaluated changes in exhaled breath of rats given tumor necrosis factor-alpha (TNF-α). Thirty male Sprague-Dawley rats were randomly assigned to three groups (n = 10 [...] Read more.
Systemic inflammation alters the composition of exhaled breath, possibly helping clinicians diagnose conditions such as sepsis. We therefore evaluated changes in exhaled breath of rats given tumor necrosis factor-alpha (TNF-α). Thirty male Sprague-Dawley rats were randomly assigned to three groups (n = 10 each) with intravenous injections of normal saline (control), 200 µg·kg−1 bodyweight TNF-α (TNF-α-200), or 600 µg·kg−1 bodyweight TNF-α (TNF-α-600), and were observed for 24 h or until death. Animals were ventilated with highly-purified synthetic air to analyze exhaled air by multicapillary column–ion mobility spectrometry. Volatile organic compounds (VOCs) were identified from a database. We recorded blood pressure and cardiac output, along with cytokine plasma concentrations. Control rats survived the 24 h observation period, whereas mean survival time decreased to 22 h for TNF-α-200 and 23 h for TNF-α-600 rats. Mean arterial pressure decreased in TNF-α groups, whereas IL-6 increased, consistent with mild to moderate inflammation. Hundreds of VOCs were detected in exhalome. P-cymol increased by a factor-of-two 4 h after injection of TNF-α-600 compared to the control and TNF-α-200. We found that 1-butanol and 1-pentanol increased in both TNF-α groups after 20 h compared to the control. As breath analysis distinguishes between two doses of TNF-α and none, we conclude that it might help clinicians identify systemic inflammation. Full article
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Open AccessArticle
Allelopathic Potential of Rice and Identification of Published Allelochemicals by Cloud-Based Metabolomics Platform
Metabolites 2020, 10(6), 244; https://doi.org/10.3390/metabo10060244 - 15 Jun 2020
Viewed by 480
Abstract
The methanol extracts of nine popular cultivated Vietnamese rice cultivars (Oryza sativa L.cv. OM 2395, 5451, 6976, 380, 5930, 4498, 3536, N406, and 7347) were used to explore their allelopathic potential on barnyardgrass (Echinochola crus-galli L.). At 0.1 g mL−1 [...] Read more.
The methanol extracts of nine popular cultivated Vietnamese rice cultivars (Oryza sativa L.cv. OM 2395, 5451, 6976, 380, 5930, 4498, 3536, N406, and 7347) were used to explore their allelopathic potential on barnyardgrass (Echinochola crus-galli L.). At 0.1 g mL−1, OM 5930, OM 4498, and OM 6976 correlatively possessed greatest phytotoxicity on barnyardgrass shoot (98.77%, 90.75%, and 87.17%) and root (99.39%, 92.83%, and 86.56%) growth. The following study aimed to detect previously-known allelochemicals in those rice using XCMS online cloud-based metabolomics platform. Twenty allelochemicals were semi-quantified and seven of them were detected predominantly and five was putatively confirmed in OM 5930 (mg/ 100g fresh rice) as salicylic acid (5.0076), vanillic acid (0.1246), p-coumaric acid (0.1590), 2,4-dimethoxybenzoic acid (0.1045), and cinnamic acid (3.3230). These compounds were active at concentrations greater than 0.5 mM and the average EC50 were 1.24 mM. The results indicated that OM 5930 may use as promising candidates in weed biological control for rice production. Full article
(This article belongs to the Section Plant Science)
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Open AccessReview
Machine Learning Applications for Mass Spectrometry-Based Metabolomics
Metabolites 2020, 10(6), 243; https://doi.org/10.3390/metabo10060243 - 13 Jun 2020
Viewed by 867
Abstract
The metabolome of an organism depends on environmental factors and intracellular regulation and provides information about the physiological conditions. Metabolomics helps to understand disease progression in clinical settings or estimate metabolite overproduction for metabolic engineering. The most popular analytical metabolomics platform is mass [...] Read more.
The metabolome of an organism depends on environmental factors and intracellular regulation and provides information about the physiological conditions. Metabolomics helps to understand disease progression in clinical settings or estimate metabolite overproduction for metabolic engineering. The most popular analytical metabolomics platform is mass spectrometry (MS). However, MS metabolome data analysis is complicated, since metabolites interact nonlinearly, and the data structures themselves are complex. Machine learning methods have become immensely popular for statistical analysis due to the inherent nonlinear data representation and the ability to process large and heterogeneous data rapidly. In this review, we address recent developments in using machine learning for processing MS spectra and show how machine learning generates new biological insights. In particular, supervised machine learning has great potential in metabolomics research because of the ability to supply quantitative predictions. We review here commonly used tools, such as random forest, support vector machines, artificial neural networks, and genetic algorithms. During processing steps, the supervised machine learning methods help peak picking, normalization, and missing data imputation. For knowledge-driven analysis, machine learning contributes to biomarker detection, classification and regression, biochemical pathway identification, and carbon flux determination. Of important relevance is the combination of different omics data to identify the contributions of the various regulatory levels. Our overview of the recent publications also highlights that data quality determines analysis quality, but also adds to the challenge of choosing the right model for the data. Machine learning methods applied to MS-based metabolomics ease data analysis and can support clinical decisions, guide metabolic engineering, and stimulate fundamental biological discoveries. Full article
(This article belongs to the Special Issue Metabolic Engineering and Synthetic Biology Volume 2)
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Open AccessArticle
Antibiotic-Induced Changes in Microbiome-Related Metabolites and Bile Acids in Rat Plasma
Metabolites 2020, 10(6), 242; https://doi.org/10.3390/metabo10060242 - 11 Jun 2020
Viewed by 360
Abstract
Various environmental factors can alter the gut microbiome’s composition and functionality, and modulate host health. In this study, the effects of oral and parenteral administration of two poorly bioavailable antibiotics (i.e., vancomycin and streptomycin) on male Wistar Crl/Wi(Han) rats for 28 days were [...] Read more.
Various environmental factors can alter the gut microbiome’s composition and functionality, and modulate host health. In this study, the effects of oral and parenteral administration of two poorly bioavailable antibiotics (i.e., vancomycin and streptomycin) on male Wistar Crl/Wi(Han) rats for 28 days were compared to distinguish between microbiome-derived or -associated and systemic changes in the plasma metabolome. The resulting changes in the plasma metabolome were compared to the effects of a third reference compound, roxithromycin, which is readily bioavailable. A community analysis revealed that the oral administration of vancomycin and roxithromycin in particular leads to an altered microbial population. Antibiotic-induced changes depending on the administration routes were observed in plasma metabolite levels. Indole-3-acetic acid (IAA) and hippuric acid (HA) were identified as key metabolites of microbiome modulation, with HA being the most sensitive. Even though large variations in the plasma bile acid pool between and within rats were observed, the change in microbiome community was observed to alter the composition of the bile acid pool, especially by an accumulation of taurine-conjugated primary bile acids. In-depth investigation of the relationship between microbiome variability and their functionality, with emphasis on the bile acid pool, will be necessary to better assess the potential adverseness of environmentally induced microbiome changes. Full article
(This article belongs to the Special Issue Metabolomics and Microbiota Metabolism)
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Open AccessArticle
Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation
Metabolites 2020, 10(6), 241; https://doi.org/10.3390/metabo10060241 - 10 Jun 2020
Viewed by 508
Abstract
Changes in the plasma metabolic profile were characterised in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease-modifying anti-rheumatic drug (cDMARD) therapy. Plasma samples collected in an early RA randomised strategy study (NCT00920478) that compared clinical (DAS) disease activity assessment with [...] Read more.
Changes in the plasma metabolic profile were characterised in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease-modifying anti-rheumatic drug (cDMARD) therapy. Plasma samples collected in an early RA randomised strategy study (NCT00920478) that compared clinical (DAS) disease activity assessment with musculoskeletal ultrasound assessment (MSUS) to drive treatment decisions were subjected to untargeted metabolomic analysis. Metabolic profiles were collected at pre- and three months post-commencement of nonbiologic cDMARD. Metabolites that changed in association with changes in the DAS44 score were identified at the three-month timepoint. A total of nine metabolites exhibited a clear correlation with a reduction in DAS44 score following cDMARD commencement, particularly itaconate, its derived anhydride and a derivative of itaconate CoA. Increasing itaconate correlated with improved DAS44 score and decreasing levels of C-reactive protein (CRP). cDMARD treatment effects invoke consistent changes in plasma detectable metabolites, that in turn implicate clinical disease activity with macrophages. Such changes inform RA pathogenesis and reveal for the first time a link between itaconate production and resolution of inflammatory disease in humans. Quantitative metabolic biomarker-based tests of clinical change in state are feasible and should be developed around the itaconate pathway. Full article
(This article belongs to the Special Issue Metabolomics Analysis for Biomarker Discovery and Human Health)
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Open AccessArticle
Feasibility of Mass-Spectrometry to Lower Cost and Blood Volume Requirements for Assessment of B Vitamins in Patients Undergoing Bariatric Surgery
Metabolites 2020, 10(6), 240; https://doi.org/10.3390/metabo10060240 - 10 Jun 2020
Viewed by 340
Abstract
Bariatric surgery induces deficiencies in a combination of B vitamins. However, high costs and a large blood volume requirement are barriers to routine screening. We adapted and validated a method coupling tandem mass spectrometry (MS/MS) with high-performance liquid chromatography (HPLC) to facilitate cost-effective [...] Read more.
Bariatric surgery induces deficiencies in a combination of B vitamins. However, high costs and a large blood volume requirement are barriers to routine screening. We adapted and validated a method coupling tandem mass spectrometry (MS/MS) with high-performance liquid chromatography (HPLC) to facilitate cost-effective analysis for simultaneous detection of B vitamins in low volumes of plasma. Based on existing methods, pooled plasma was extracted using hexane and acetonitrile and seven B vitamin analytes were separated using HPLC. Detection was performed with an Agilent 6460 triple quadrupole tandem mass spectrometer (MS/MS) using electrospray ionization in the positive ion mode. We evaluated linearity, recovery, precision, and limit of detection, as well as costs of the assay. We evaluated seven B vitamins from plasma; five (riboflavin, nicotinamide, pantothenic acid, pyridoxine, and biotin) were detected and quantified with precision and linearity. Recovery ranged from 63 to 81% for each of the vitamins, except for nicotinamide—the recovery of which was suppressed to 40%, due to plasma matrix effects. We demonstrated the feasibility of the HPLC–MS/MS method for use in patients who undergo bariatric surgery by analyzing pooled plasma from patients with a lower cost and blood volume than had we sent the samples to a commercial laboratory. It is advantageous and feasible, in terms of low cost and blood volume requirement, to simultaneously measure plasma concentrations of B vitamins using HPLC–MS/MS. With further improvements, the method may enable personalized nutritional assessment for the nutritionally compromised, bariatric surgery population. Full article
(This article belongs to the Special Issue Metabolomic Profiles in Nutrition and Metabolic Health)
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Open AccessReview
Ecometabolomics for a Better Understanding of Plant Responses and Acclimation to Abiotic Factors Linked to Global Change
Metabolites 2020, 10(6), 239; https://doi.org/10.3390/metabo10060239 - 09 Jun 2020
Viewed by 443
Abstract
The number of ecometabolomic studies, which use metabolomic analyses to disentangle organisms’ metabolic responses and acclimation to a changing environment, has grown exponentially in recent years. Here, we review the results and conclusions of ecometabolomic studies on the impacts of four main drivers [...] Read more.
The number of ecometabolomic studies, which use metabolomic analyses to disentangle organisms’ metabolic responses and acclimation to a changing environment, has grown exponentially in recent years. Here, we review the results and conclusions of ecometabolomic studies on the impacts of four main drivers of global change (increasing frequencies of drought episodes, heat stress, increasing atmospheric carbon dioxide (CO2) concentrations and increasing nitrogen (N) loads) on plant metabolism. Ecometabolomic studies of drought effects confirmed findings of previous target studies, in which most changes in metabolism are characterized by increased concentrations of soluble sugars and carbohydrate derivatives and frequently also by elevated concentrations of free amino acids. Secondary metabolites, especially flavonoids and terpenes, also commonly exhibited increased concentrations when drought intensified. Under heat and increasing N loads, soluble amino acids derived from glutamate and glutamine were the most responsive metabolites. Foliar metabolic responses to elevated atmospheric CO2 concentrations were dominated by greater production of monosaccharides and associated synthesis of secondary metabolites, such as terpenes, rather than secondary metabolites synthesized along longer sugar pathways involving N-rich precursor molecules, such as those formed from cyclic amino acids and along the shikimate pathway. We suggest that breeding for crop genotypes tolerant to drought and heat stress should be based on their capacity to increase the concentrations of C-rich compounds more than the concentrations of smaller N-rich molecules, such as amino acids. This could facilitate rapid and efficient stress response by reducing protein catabolism without compromising enzymatic capacity or increasing the requirement for re-transcription and de novo biosynthesis of proteins. Full article
(This article belongs to the Special Issue Ecometabolomics)
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Open AccessArticle
Chemotaxonomic Profiling of Canadian Alternaria Populations Using High-Resolution Mass Spectrometry
Metabolites 2020, 10(6), 238; https://doi.org/10.3390/metabo10060238 - 09 Jun 2020
Viewed by 352
Abstract
Alternaria spp. occur as plant pathogens worldwide under field and storage conditions. They lead to food spoilage and also produce several classes of secondary metabolites that contaminate the food production chain. From a food safety perspective, the major challenge of assessing the risk [...] Read more.
Alternaria spp. occur as plant pathogens worldwide under field and storage conditions. They lead to food spoilage and also produce several classes of secondary metabolites that contaminate the food production chain. From a food safety perspective, the major challenge of assessing the risk of Alternaria contamination is the lack of a clear consensus on their species-level taxonomy. Furthermore, there are currently no reliable DNA sequencing methods to allow for differentiation of the toxigenic potential of these fungi. Our objective was to determine which species of Alternaria exist in Canada, and to describe the compounds they make. To address these issues, we performed metabolomic profiling using liquid chromatography high-resolution mass spectrometry (LC-HRMS) on 128 Canadian strains of Alternaria to determine their chemotaxonomy. The Alternaria strains were analyzed using principal component analysis (PCA) and unbiased k-means clustering to identify metabolites with significant differences (p < 0.001) between groups. Four populations or ‘chemotypes’ were identified within the strains studied, and several known secondary metabolites of Alternaria were identified as distinguishing metabolites, including tenuazonic acid, phomapyrones, and altenuene. Though species-level identifications could not be concluded for all groups through metabolomics alone, A. infectoria was able to be identified as a distinct population. Full article
(This article belongs to the Section Plant Science)
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Open AccessArticle
QSRR Automator: A Tool for Automating Retention Time Prediction in Lipidomics and Metabolomics
Metabolites 2020, 10(6), 237; https://doi.org/10.3390/metabo10060237 - 09 Jun 2020
Viewed by 440
Abstract
The use of retention time is often critical for the identification of compounds in metabolomic and lipidomic studies. Standards are frequently unavailable for the retention time measurement of many metabolites, thus the ability to predict retention time for these compounds is highly valuable. [...] Read more.
The use of retention time is often critical for the identification of compounds in metabolomic and lipidomic studies. Standards are frequently unavailable for the retention time measurement of many metabolites, thus the ability to predict retention time for these compounds is highly valuable. A number of studies have applied machine learning to predict retention times, but applying a published machine learning model to different lab conditions is difficult. This is due to variation between chromatographic equipment, methods, and columns used for analysis. Recreating a machine learning model is likewise difficult without a dedicated bioinformatician. Herein we present QSRR Automator, a software package to automate retention time prediction model creation and demonstrate its utility by testing data from multiple chromatography columns from previous publications and in-house work. Analysis of these data sets shows similar accuracy to published models, demonstrating the software’s utility in metabolomic and lipidomic studies. Full article
(This article belongs to the Section Bioinformatics and Data Analysis)
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