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Metabolites, Volume 9, Issue 10 (October 2019)

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Cover Story (view full-size image) Metabolomics uses high-throughput analytical techniques like MS and NMR to generate [...] Read more.
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Open AccessReview
Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics
Metabolites 2019, 9(10), 242; https://doi.org/10.3390/metabo9100242 - 21 Oct 2019
Viewed by 94
Abstract
Inborn errors of metabolism (IEMs) are a group of inherited diseases with variable incidences. IEMs are caused by disrupting enzyme activities in specific metabolic pathways by genetic mutations, either directly or indirectly by cofactor deficiencies, causing altered levels of compounds associated with these [...] Read more.
Inborn errors of metabolism (IEMs) are a group of inherited diseases with variable incidences. IEMs are caused by disrupting enzyme activities in specific metabolic pathways by genetic mutations, either directly or indirectly by cofactor deficiencies, causing altered levels of compounds associated with these pathways. While IEMs may present with multiple overlapping symptoms and metabolites, early and accurate diagnosis of IEMs is critical for the long-term health of affected subjects. The prevalence of IEMs differs between countries, likely because different IEM classifications and IEM screening methods are used. Currently, newborn screening programs exclusively use targeted metabolic assays that focus on limited panels of compounds for selected IEM diseases. Such targeted approaches face the problem of false negative and false positive diagnoses that could be overcome if metabolic screening adopted analyses of a broader range of analytes. Hence, we here review the prospects of using untargeted metabolomics for IEM screening. Untargeted metabolomics and lipidomics do not rely on predefined target lists and can detect as many metabolites as possible in a sample, allowing to screen for many metabolic pathways simultaneously. Examples are given for nontargeted analyses of IEMs, and prospects and limitations of different metabolomics methods are discussed. We conclude that dedicated studies are needed to compare accuracy and robustness of targeted and untargeted methods with respect to widening the scope of IEM diagnostics. Full article
(This article belongs to the Special Issue Metabolomics in the Study of Disease)
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Open AccessArticle
Characterization of Lipid Profiles after Dietary Intake of Polyunsaturated Fatty Acids Using Integrated Untargeted and Targeted Lipidomics
Metabolites 2019, 9(10), 241; https://doi.org/10.3390/metabo9100241 - 21 Oct 2019
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Abstract
Illuminating the comprehensive lipid profiles after dietary supplementation of polyunsaturated fatty acids (PUFAs) is crucial to revealing the tissue distribution of PUFAs in living organisms, as well as to providing novel insights into lipid metabolism. Here, we performed lipidomic analyses on mouse plasma [...] Read more.
Illuminating the comprehensive lipid profiles after dietary supplementation of polyunsaturated fatty acids (PUFAs) is crucial to revealing the tissue distribution of PUFAs in living organisms, as well as to providing novel insights into lipid metabolism. Here, we performed lipidomic analyses on mouse plasma and nine tissues, including the liver, kidney, brain, white adipose, heart, lung, small intestine, skeletal muscle, and spleen, with the dietary intake conditions of arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) as the ethyl ester form. We incorporated targeted and untargeted approaches for profiling oxylipins and complex lipids such as glycerol (phospho) lipids, sphingolipids, and sterols, respectively, which led to the characterization of 1026 lipid molecules from the mouse tissues. The lipidomic analysis indicated that the intake of PUFAs strongly impacted the lipid profiles of metabolic organs such as the liver and kidney, while causing less impact on the brain. Moreover, we revealed a unique lipid modulation in most tissues, where phospholipids containing linoleic acid were significantly decreased in mice on the ARA-supplemented diet, and bis(monoacylglycero)phosphate (BMP) selectively incorporated DHA over ARA and EPA. We comprehensively studied the lipid profiles after dietary intake of PUFAs, which gives insight into lipid metabolism and nutrition research on PUFA supplementation. Full article
(This article belongs to the Special Issue Metabolomic Applications in Animal Science)
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Open AccessArticle
Investigating the Protective Effect of Gross Saponins of Tribulus terrestris Fruit against Ischemic Stroke in Rat Using Metabolomics and Network Pharmacology
Metabolites 2019, 9(10), 240; https://doi.org/10.3390/metabo9100240 - 21 Oct 2019
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Abstract
Stroke is one of the leading causes of death and long-term disability worldwide. Gross saponins of Tribulus terrestris fruit (GSTTF) has been used for neuroprotective therapy on convalescents of ischemic stroke. But the related therapeutic mechanisms have not yet been well investigated. This [...] Read more.
Stroke is one of the leading causes of death and long-term disability worldwide. Gross saponins of Tribulus terrestris fruit (GSTTF) has been used for neuroprotective therapy on convalescents of ischemic stroke. But the related therapeutic mechanisms have not yet been well investigated. This study aimed to investigate the protective effects of GSTTF on ischemic stroke using metabolomics coupled with network pharmacology analysis. The rat urine sample was collected and profiled by an LC-MS-based metabolomics approach. The pathway analysis was performed based on the highlighted biomarkers, then the network pharmacology approach was applied to screen the potential therapeutic targets of GSTTF. Metabolomics analysis showed that a series of metabolic perturbations occurred in the middle cerebral artery occlusion (MCAO) group compared with the sham group. Gross saponins of Tribulus terrestris fruit can change the MCAO-induced urine metabolic deviations in a reverse manner via regulating multiple metabolic pathways. Two proteins, inducible nitric oxide synthase (NOS2) and glycogen synthase kinase-3 beta (GSK3B), were highlighted by the network pharmacology analysis, which may be the potential therapeutic targets for the GSTTF against ischemic stroke. This study provides an overview of the mechanism of MCAO-induced ischemic stroke and investigates the efficacy of GSTTF in the treatment of ischemic stroke. Further study is needed to reveal its underlying mechanisms more clearly. Full article
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Open AccessArticle
Comprehensive Understanding of the Bacterial Populations and Metabolites Profile of Fermented Feed by 16S rRNA Gene Sequencing and Liquid Chromatography–Mass Spectrometry
Metabolites 2019, 9(10), 239; https://doi.org/10.3390/metabo9100239 - 21 Oct 2019
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Abstract
The comprehensive bacterial populations and metabolites profile in fermented feed is unclear, which may have significant effects on the stability of fermented feed quality and animal gut health. In this study, 16S rRNA gene sequencing and liquid chromatography–mass spectrometry were used to explore [...] Read more.
The comprehensive bacterial populations and metabolites profile in fermented feed is unclear, which may have significant effects on the stability of fermented feed quality and animal gut health. In this study, 16S rRNA gene sequencing and liquid chromatography–mass spectrometry were used to explore the bacterial populations and metabolites profile in the fermented feed incubated with probiotics (MF) or without probiotics (SF). The probiotics were a combination of Lactobacillus salivarius, Bacillus subtilis, and Saccharomyces cerevisiae. The pH and lactic acid levels were higher in MF than in SF (P < 0.05), while the total volatile fatty acid content was lower (P < 0.05). Interestingly, after fermentation, the most abundant bacterial genus in MF was Enterococcus, rather than the added probiotics Lactobacillus or Bacillus. Weissella and a few potential pathogens (Enterobacter, Escherichia-Shigella, and Pantoea) were dominant in SF (P < 0.05). Metabolomics analysis identified 32 different metabolites in the two types of fermented feed. These metabolites enriched in MF, such as maleic acid, phenylacetic acid, ethyl linoleate, dihomo-gamma-linolenic acid, and L-theanine had potential antimicrobial activities. Conclusively, the addition of probiotics enriched a few potentially beneficial microbes and small molecular compounds with antimicrobial activities, and inhibited the potential pathogens in fermented feed. Full article
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Open AccessArticle
Influence of Dietary Ingredients on Lean Body Percent, Uremic Toxin Concentrations, and Kidney Function in Senior-Adult Cats
Metabolites 2019, 9(10), 238; https://doi.org/10.3390/metabo9100238 - 19 Oct 2019
Viewed by 217
Abstract
The goal of this study was to determine if modification of currently available maintenance foods with alternative ingredients, botanicals (fruit and vegetables), and increased amounts of functional lipids (fish oil) would delay the age-associated decline in glomerular filtration rate (GFR) and lean body [...] Read more.
The goal of this study was to determine if modification of currently available maintenance foods with alternative ingredients, botanicals (fruit and vegetables), and increased amounts of functional lipids (fish oil) would delay the age-associated decline in glomerular filtration rate (GFR) and lean body mass (LBM) in senior-adult cats. Forty-four healthy cats (mean age, 12.2 years; range 10.7 to 14.0 years) were fed one of three foods (n = 14 or 15 per group) for six months: control food with 32.6% protein (as fed), or control food supplemented with increasing amounts of functional food bioactives: fish oil, fruit and vegetables, different protein sources, and <32.0% protein [functional foods one (FF1) and two (FF2)]. Senior-adult cats were compared before and after the feeding trial with 20 young-adult cats (mean age, 3.5 years; range 2.1 to 4.9 years). Compared with younger cats, older cats had decreased lean-body percent and serum albumin concentrations. Feeding FF1 and FF2 for six months increased lean-body percent, maintained serum albumin concentrations, increased GFR, decreased serum symmetric dimethylarginine (SDMA) concentrations, and decreased concentrations of the uremic toxin 3-indoxyl sulfate. These dietary changes may assist in offsetting sarcopenia and the chronic inflammation associated with aging in senior-adult cats. Full article
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Open AccessArticle
WebSpecmine: A Website for Metabolomics Data Analysis and Mining
Metabolites 2019, 9(10), 237; https://doi.org/10.3390/metabo9100237 - 19 Oct 2019
Viewed by 192
Abstract
Metabolomics data analysis is an important task in biomedical research. The available tools do not provide a wide variety of methods and data types, nor ways to store and share data and results generated. Thus, we have developed WebSpecmine to overcome the aforementioned [...] Read more.
Metabolomics data analysis is an important task in biomedical research. The available tools do not provide a wide variety of methods and data types, nor ways to store and share data and results generated. Thus, we have developed WebSpecmine to overcome the aforementioned limitations. WebSpecmine is a web-based application designed to perform the analysis of metabolomics data based on spectroscopic and chromatographic techniques (NMR, Infrared, UV-visible, and Raman, and LC/GC-MS) and compound concentrations. Users, even those not possessing programming skills, can access several analysis methods including univariate, unsupervised and supervised multivariate statistical analysis, as well as metabolite identification and pathway analysis, also being able to create accounts to store their data and results, either privately or publicly. The tool’s implementation is based in the R project, including its shiny web-based framework. Webspecmine is freely available, supporting all major browsers. We provide abundant documentation, including tutorials and a user guide with case studies. Full article
(This article belongs to the Special Issue Recent Advances in Metabolomics (IECM-3))
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Open AccessArticle
Assessing the Pre-Analytical Stability of Small-Molecule Metabolites in Cerebrospinal Fluid Using Direct-Infusion Metabolomics
Metabolites 2019, 9(10), 236; https://doi.org/10.3390/metabo9100236 - 18 Oct 2019
Viewed by 147
Abstract
Metabolomics studies aiming to find biomarkers frequently make use of historical or multicenter cohorts. These samples often have different pre-analytical conditions that potentially affect metabolite concentrations. We studied the effect of different storage conditions on the stability of small-molecule metabolites in cerebrospinal fluid [...] Read more.
Metabolomics studies aiming to find biomarkers frequently make use of historical or multicenter cohorts. These samples often have different pre-analytical conditions that potentially affect metabolite concentrations. We studied the effect of different storage conditions on the stability of small-molecule metabolites in cerebrospinal fluid to aid a reliable interpretation of metabolomics data. Three cerebrospinal fluid pools were prepared from surplus samples from the Amsterdam Dementia Cohort biobank. Aliquoted pools were exposed to different storage conditions to assess the temperature and freeze/thaw stability before final storage at −80 °C: storage up to four months at −20 °C and up to one week at either 5–8 °C or 18–22 °C and exposure to up to seven freeze/thaw cycles. Direct-infusion high-resolution mass spectrometry was performed, resulting in the identification of 1852 m/z peaks. To test the storage stability, principal component analyses, repeated measures analysis of variance, Kruskal–Wallis tests, and fold change analyses were performed, all demonstrating that small-molecule metabolites in the cerebrospinal fluid (CSF) are relatively unaffected by 1–3 freeze/thaw cycles, by storage at −20 °C up to two months, by storage at 5–8 °C for up to 72 h, or by storage at 18–22 °C for up to 8 h. This suggests that these differences do not affect the interpretation of potential small-molecule biomarkers in multicenter or historical cohorts and implies that these cohorts are suitable for biomarker studies. Full article
(This article belongs to the Special Issue Genetic Metabolic Diagnostics)
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Open AccessArticle
Targeted Metabolic Profiling of Methionine Cycle Metabolites and Redox Thiol Pools in Mammalian Plasma, Cells and Urine
Metabolites 2019, 9(10), 235; https://doi.org/10.3390/metabo9100235 - 18 Oct 2019
Viewed by 125
Abstract
The concentration of thiol and thioether metabolites in plasma has diagnostic value in genetic diseases of B-vitamin metabolism linked to methionine utilization. Among these, cysteine/cystine (Cys/CSSC) and glutathione/oxidized glutathione (GSH/GSSG) act as cellular redox buffers. A new LC-MS/MS method was developed for the [...] Read more.
The concentration of thiol and thioether metabolites in plasma has diagnostic value in genetic diseases of B-vitamin metabolism linked to methionine utilization. Among these, cysteine/cystine (Cys/CSSC) and glutathione/oxidized glutathione (GSH/GSSG) act as cellular redox buffers. A new LC-MS/MS method was developed for the simultaneous detection of cystathionine (Cysta), methionine (Met), methionine sulfoxide (MSO), creatinine and the reduced and oxidized pairs of homocysteine (Hcy/HSSH), cysteine (Cys/CSSC) and glutathione (GSH/GSSG). A one-step thiol-blocking protocol with minimal sample preparation was established to determine redox thiol pairs in plasma and cells. The concentrations of diagnostic biomarkers Hcy, Met, Cysta, and Cys in a cohort of healthy adults (n = 53) agreed with reference ranges and published values. Metabolite concentrations were also validated in commercial samples of human, mouse, rat and Beagle dog plasma and by the use of a standardized ERNDIM quality control. Analysis of fibroblasts, endothelial and epithelial cells, human embryonic stem cells, and cancer cell lines showed cell specificity for both the speciation and concentration of thiol and thioether metabolites. This LC-MS/MS platform permits the fast and simultaneous quantification of 10 thiol and thioether metabolites and creatinine using 40 µL plasma, urine or culture medium, or 500,000 cells. The sample preparation protocols are directly transferable to automated metabolomic platforms. Full article
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Open AccessReview
Adapting to the Airways: Metabolic Requirements of Pseudomonas aeruginosa during the Infection of Cystic Fibrosis Patients
Metabolites 2019, 9(10), 234; https://doi.org/10.3390/metabo9100234 - 16 Oct 2019
Viewed by 346
Abstract
Pseudomonas aeruginosa is one of the major causes of morbidity and mortality of cystic fibrosis patients. During the infection, the bacteria colonize the nutritional rich lung mucus, which is present in the airway secretions in the patients, and they adapt their phenotype accordingly [...] Read more.
Pseudomonas aeruginosa is one of the major causes of morbidity and mortality of cystic fibrosis patients. During the infection, the bacteria colonize the nutritional rich lung mucus, which is present in the airway secretions in the patients, and they adapt their phenotype accordingly to the lung environment. In the airways, P. aeruginosa undergoes a broad metabolic rewiring as a consequence of the nutritional and stressful complexity of the lungs. However, the role of such metabolic rewiring on the infection outcome is poorly understood. Here, we review the metabolic evolution of clinical strains of P. aeruginosa during a cystic fibrosis lung infection and the metabolic functions operating in vivo under patho-physiological conditions. Finally, we discuss the perspective of modeling the cystic fibrosis environment using genome scale metabolic models of P. aeruginosa. Understanding the physiological changes occurring during the infection may pave the way to a more effective treatment for P. aeruginosa lung infections. Full article
(This article belongs to the Special Issue Metabolic Profiling of Cystic Fibrosis Pathogens)
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Open AccessReview
Mitochondrial Dysfunction in the Transition from NASH to HCC
Metabolites 2019, 9(10), 233; https://doi.org/10.3390/metabo9100233 - 16 Oct 2019
Viewed by 266
Abstract
The liver constantly adapts to meet energy requirements of the whole body. Despite its remarkable adaptative capacity, prolonged exposure of liver cells to harmful environmental cues (such as diets rich in fat, sugar, and cholesterol) results in the development of chronic liver diseases [...] Read more.
The liver constantly adapts to meet energy requirements of the whole body. Despite its remarkable adaptative capacity, prolonged exposure of liver cells to harmful environmental cues (such as diets rich in fat, sugar, and cholesterol) results in the development of chronic liver diseases (including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)) that can progress to hepatocellular carcinoma (HCC). The pathogenesis of these diseases is extremely complex, multifactorial, and poorly understood. Emerging evidence suggests that mitochondrial dysfunction or maladaptation contributes to detrimental effects on hepatocyte bioenergetics, reactive oxygen species (ROS) homeostasis, endoplasmic reticulum (ER) stress, inflammation, and cell death leading to NASH and HCC. The present review highlights the potential contribution of altered mitochondria function to NASH-related HCC and discusses how agents targeting this organelle could provide interesting treatment strategies for these diseases. Full article
(This article belongs to the Special Issue Mitochondria and Metabolism in Disorders)
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Open AccessArticle
Study of Fecal and Urinary Metabolite Perturbations Induced by Chronic Ethanol Treatment in Mice by UHPLC-MS/MS Targeted Profiling
Metabolites 2019, 9(10), 232; https://doi.org/10.3390/metabo9100232 - 16 Oct 2019
Viewed by 137
Abstract
Alcoholic liver disease (ALD) as a consequence of ethanol chronic consumption could lead to hepatic cirrhosis that is linked to high morbidity and mortality. Disease diagnosis is still very challenging and usually clear findings are obtained in the later stage of ALD. The [...] Read more.
Alcoholic liver disease (ALD) as a consequence of ethanol chronic consumption could lead to hepatic cirrhosis that is linked to high morbidity and mortality. Disease diagnosis is still very challenging and usually clear findings are obtained in the later stage of ALD. The profound effect of ethanol on metabolism can be depicted using metabolomics; thus, the discovery of novel biomarkers could shed light on the initiation and the progression of the ALD, serving diagnostic purposes. In the present study, Hydrophilic Interaction Liquid Chromatography tandem Mass Spectrometry HILIC-MS/MS based metabolomics analyisis of urine and fecal samples of C57BL/6 mice of both sexes at two sampling time points was performed, monitoring the effect of eight-week ethanol consumption. The altered hepatic metabolism caused by ethanol consumption induces extensive biochemical perturbations and changes in gut microbiota population on a great scale. Fecal samples were proven to be a suitable specimen for studying ALD since it was more vulnerable to the metabolic changes in comparison to urine samples. The metabolome of male mice was affected on a greater scale than the female metabolome due to ethanol exposure. Precursor small molecules of essential pathways of energy production responded to ethanol exposure. A meaningful correlation between the two studied specimens demonstrated the impact of ethanol in endogenous and symbiome metabolism. Full article
(This article belongs to the Special Issue Metabolomics Methodologies and Applications)
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Open AccessArticle
Comparative Metabolomics Unravel the Effect of Magnesium Oversupply on Tomato Fruit Quality and Associated Plant Metabolism
Metabolites 2019, 9(10), 231; https://doi.org/10.3390/metabo9100231 - 16 Oct 2019
Viewed by 134
Abstract
In general, greenhouse cultivation involves the rampant application of chemical fertilizers, with the aim of achieving high yields. Oversaturation with mineral nutrients that aid plant growth, development, and yield may lead to abiotic stress conditions. We explore the effects of excess magnesium on [...] Read more.
In general, greenhouse cultivation involves the rampant application of chemical fertilizers, with the aim of achieving high yields. Oversaturation with mineral nutrients that aid plant growth, development, and yield may lead to abiotic stress conditions. We explore the effects of excess magnesium on tomato plant metabolism, as well as tomato fruit quality using non-targeted mass spectrometry (MS)-based metabolomic approaches. Tomato plants were subjected to three different experiments, including high magnesium stress (MgH), extremely high magnesium stress (MgEH), and a control with optimal nutrient levels. Leaves, roots, and fruits were harvested at 16 weeks following the treatment. A metabolic pathway analysis showed that the metabolism induced by Mg oversupply was remarkably different between the leaf and root. Tomato plants allocated more resources to roots by upregulating carbohydrate and polyamine metabolism, while these pathways were downregulated in leaves. Mg oversupply affects the fruit metabolome in plants. In particular, the relative abundance of threonic acid, xylose, fucose, glucose, fumaric acid, malic acid, citric acid, oxoglutaric acid, threonine, glutamic acid, phenylalanine, and asparagine responsible for the flavor of tomato fruits was significantly decreased in the presence of Mg oversupply. Altogether, we concluded that Mg oversupply leads to drastically higher metabolite transport from sources (fully expanded leaves) to sinks (young leaves and roots), and thus, produces unfavorable outcomes in fruit quality and development. Full article
(This article belongs to the Special Issue Plant Metabolomics)
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Open AccessArticle
Alterations in Exercise-Induced Plasma Adenosine Triphosphate Concentration in Highly Trained Athletes in a One-Year Training Cycle
Metabolites 2019, 9(10), 230; https://doi.org/10.3390/metabo9100230 - 16 Oct 2019
Viewed by 128
Abstract
This study aimed to assess the effect of training loads on plasma adenosine triphosphate responsiveness in highly trained athletes in a 1 y cycle. Highly trained futsal players (11 men, age range 20–31 y), endurance athletes (11 men, age range 18–31 y), sprinters [...] Read more.
This study aimed to assess the effect of training loads on plasma adenosine triphosphate responsiveness in highly trained athletes in a 1 y cycle. Highly trained futsal players (11 men, age range 20–31 y), endurance athletes (11 men, age range 18–31 y), sprinters (11 men, age range 21–30 y), and control group (11 men, age range 22–34 y) were examined across four characteristic training phases in response to an incremental treadmill test until exhaustion. A considerably higher exercise and post-exercise plasma adenosine triphosphate concentrations were observed in consecutive training phases in highly trained athletes, with the highest values reached after the competitive period. No differences in plasma adenosine triphosphate concentrations were found in the control group during the 1 y cycle. Sprinters showed a higher absolute and net increase in plasma adenosine triphosphate concentration by 60–114% during exercise in consecutive training phases than futsal players (63–101%) and endurance athletes (64–95%). In this study, we demonstrated that exercise-induced adenosine triphosphate concentration significantly changes in highly trained athletes over an annual training cycle. The obtained results showed that high-intensity but not low- to moderate-intensity training leads to an increased adenosine triphosphate response to exercise, suggesting an important role of ATP for vascular plasticity. Full article
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Open AccessArticle
Metabolite Changes in an Estuarine Annelid Following Sublethal Exposure to a Mixture of Zinc and Boscalid
Metabolites 2019, 9(10), 229; https://doi.org/10.3390/metabo9100229 - 15 Oct 2019
Viewed by 193
Abstract
Environmental pollutants such as heavy metals and fungicides pose a serious threat to waterways worldwide. Toxicological assessment of such contaminants is usually conducted using single compound exposures, as it is challenging to understand the effect of mixtures on biota using standard ecotoxicological methods; [...] Read more.
Environmental pollutants such as heavy metals and fungicides pose a serious threat to waterways worldwide. Toxicological assessment of such contaminants is usually conducted using single compound exposures, as it is challenging to understand the effect of mixtures on biota using standard ecotoxicological methods; whereas complex chemical mixtures are more probable in ecosystems. This study exposed Simplisetia aequisetis (an estuarine annelid) to sublethal concentrations of a metal (zinc) and a fungicide (boscalid), both singly and as a mixture, for two weeks. Metabolomic analysis via gas and liquid chromatography-mass spectrometry was used to measure the stress response(s) of the organism following exposure. A total of 75 metabolites, including compounds contributing to the tricarboxylic acid cycle, the urea cycle, and a number of other pathways, were identified and quantified. The multiplatform approach identified distinct metabolomic responses to each compound that differed depending on whether the substance was presented singly or as a mixture, indicating a possible antagonistic effect. The study demonstrates that metabolomics is able to elucidate the effects and mode of action of contaminants and can identify possible outcomes faster than standard ecotoxicological endpoints, such as growth and reproduction. Metabolomics therefore has a possible future role in biomonitoring and ecosystem health assessments. Full article
(This article belongs to the Special Issue Metabolomics 2019)
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Open AccessArticle
Hepatic Metabolic Derangements Triggered by Hyperthermia: An In Vitro Metabolomic Study
Metabolites 2019, 9(10), 228; https://doi.org/10.3390/metabo9100228 - 15 Oct 2019
Viewed by 157
Abstract
Background and aims: Liver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the [...] Read more.
Background and aims: Liver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the in vitro metabolic response of primary mouse hepatocytes (PMH, n = 10) to a heat stress stimulus, i.e., after 24 h exposure to 40.5 °C. Metabolomic profiling of both intracellular metabolites and volatile metabolites in the extracellular medium of PMH was performed. Results: Multivariate analysis showed alterations in levels of 22 intra- and 59 extracellular metabolites, unveiling the capability of the metabolic pattern to discriminate cells exposed to heat stress from cells incubated at normothermic conditions (37 °C). Hyperthermia caused a considerable loss of cell viability that was accompanied by significant alterations in the tricarboxylic acid cycle, amino acids metabolism, urea cycle, glutamate metabolism, pentose phosphate pathway, and in the volatile signature associated with the lipid peroxidation process. Conclusion: These results provide novel insights into the mechanisms underlying hyperthermia-induced hepatocellular damage. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
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Open AccessArticle
Lomatogonium Rotatum for Treatment of Acute Liver Injury in Mice: A Metabolomics Study
Metabolites 2019, 9(10), 227; https://doi.org/10.3390/metabo9100227 - 14 Oct 2019
Viewed by 157
Abstract
Lomatogonium rotatum (L.) Fries ex Nym (LR) is used as a traditional Mongolian medicine to treat liver and bile diseases. This study aimed to investigate the hepatoprotective effect of LR on mice with CCl4-induced acute liver injury through conventional assays and [...] Read more.
Lomatogonium rotatum (L.) Fries ex Nym (LR) is used as a traditional Mongolian medicine to treat liver and bile diseases. This study aimed to investigate the hepatoprotective effect of LR on mice with CCl4-induced acute liver injury through conventional assays and metabolomics analysis. This study consisted of male mice (n = 23) in four groups (i.e., control, model, positive control, and LR). The extract of whole plant of LR was used to treat mice in the LR group. Biochemical and histological assays (i.e., serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and histological changes of liver tissue) were used to evaluate LR efficacy, and metabolomics analysis based on GC-MS and LC-MS was conducted to reveal metabolic changes. The conventional analysis and metabolomic profiles both suggested that LR treatment could protect mice against CCl4-induced acute liver injury. The affected metabolic pathways included linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, CoA biosynthesis, glycerophospholipid metabolism, the TCA cycle, and purine metabolism. This study identified eight metabolites, including phosphopantothenic acid, succinic acid, AMP, choline, glycerol 3-phosphate, linoleic acid, arachidonic acid, and DHA, as potential biomarkers for evaluating hepatoprotective effect of LR. This metabolomics study may shed light on possible mechanisms of hepatoprotective effect of LR. Full article
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Open AccessArticle
Korean Traditional Medicine (Jakyakgamcho-tang) Ameliorates Colitis by Regulating Gut Microbiota
Metabolites 2019, 9(10), 226; https://doi.org/10.3390/metabo9100226 - 14 Oct 2019
Viewed by 159
Abstract
The objective of this study was to examine the anti-colitis activity of Jakyakgamcho-tang (JGT) in dextran sulfate sodium (DSS)-induced colitis and explore changes of the gut microbial community using 16S rRNA amplicon sequencing and metabolomics approaches. It was found that treatment with JGT [...] Read more.
The objective of this study was to examine the anti-colitis activity of Jakyakgamcho-tang (JGT) in dextran sulfate sodium (DSS)-induced colitis and explore changes of the gut microbial community using 16S rRNA amplicon sequencing and metabolomics approaches. It was found that treatment with JGT or 5-aminosalicylic acid (5-ASA) alleviated the severity of colitis symptoms by suppressing inflammatory cytokine levels of IL-6, IL-12, and IFN-γ. The non-metric multidimensional scaling analysis of gut microbiome revealed that JGT groups were clearly separated from the DSS group, suggesting that JGT administration altered gut microbiota. The operational taxonomic units (OTUs) that were decreased by DSS but increased by JGT include Akkermansia and Allobaculum. On the other hand, OTUs that were increased by DSS but decreased by 5-ASA or JGT treatments include Bacteroidales S24-7, Ruminococcaceae, and Rikenellaceae, and the genera Bacteroides, Parabacteroides, Oscillospira, and Coprobacillus. After JGT administration, the metabolites, including most amino acids and lactic acid that were altered by colitis induction, became similar to those of the control group. This study demonstrates that JGT might have potential to effectively treat colitis by restoring dysbiosis of gut microbiota and host metabolites. Full article
(This article belongs to the Special Issue Metabolomics and Microbiota Metabolism)
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Open AccessArticle
Comparative Transcriptome and Metabolic Profiling Analysis of Buckwheat (Fagopyrum Tataricum (L.) Gaertn.) under Salinity Stress
Metabolites 2019, 9(10), 225; https://doi.org/10.3390/metabo9100225 - 14 Oct 2019
Viewed by 183
Abstract
Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) is a nutritional crop, which has high flavonoid content. However, buckwheat is a salt sensitive glycophyte cereal crop and the growth and grain yield of buckwheat are significantly affected by soil salinity. In this study, we [...] Read more.
Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) is a nutritional crop, which has high flavonoid content. However, buckwheat is a salt sensitive glycophyte cereal crop and the growth and grain yield of buckwheat are significantly affected by soil salinity. In this study, we performed a comprehensive analysis of the transcriptome and metabolome of salt treated-buckwheat to understand the effects of salinity on buckwheat. A total of 50,681,938 clean reads were acquired from all samples. We acquired 94,950 unigenes with a mean length of 1133 bp and N50 length of 1900 bp assembly. Of these, 63,305 unigenes (66.7%) were matched in public databases. Comparison of the transcriptome expression patterns between control and salt treated groups showed that 4098 unigenes were up-regulated and 3292 unigenes were down-regulated significantly. Further, we found that genes involved with amino acid, lipid and nucleotide metabolism were most responsive to salt stress. Additionally, many genes involved in secondary metabolite biosynthesis changed significantly following treatment. Those affected included phenylpropanoid biosynthesis and flavonoid biosynthesis. Chromatographic analysis was used to examine the differences in concentration of flavonoids, carotenoids, amino acids and organic acids in the samples following treatment. There was a significant increase in rutin (12.115 mg/g dry weight), following salt stress; whereas, six carotenoids (lutein, zeaxanthin, 13Z-β-carotene, α-carotene, E-β-carotene and 9Z-β-carotene) did not significantly respond to salt stress. Ultimately, our data acts as a valuable resource for future research on buckwheat and can be used as the basis for future analysis focused on gene-to-metabolite networks in buckwheat. Full article
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Open AccessArticle
Metabolomics Approach Reveals the Effects of Breed and Feed on the Composition of Chicken Eggs
Metabolites 2019, 9(10), 224; https://doi.org/10.3390/metabo9100224 - 13 Oct 2019
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Abstract
Chicken eggs provide essential nutrients to consumers around the world. Although both genetic and environmental factors influence the quality of eggs, it is unclear how these factors affect the egg traits including egg metabolites. In this study, we investigated breed and feed effects [...] Read more.
Chicken eggs provide essential nutrients to consumers around the world. Although both genetic and environmental factors influence the quality of eggs, it is unclear how these factors affect the egg traits including egg metabolites. In this study, we investigated breed and feed effects on 10 egg traits, using two breeds (Rhode Island Red and Australorp) and two feed conditions (mixed feed and fermented feed). We also used gas chromatography–mass spectrometry (GC–MS/MS) to analyze 138 yolk and 132 albumen metabolites. Significant breed effects were found on yolk weight, eggshell weight, eggshell colors, and one albumen metabolite (ribitol). Three yolk metabolites (erythritol, threitol, and urea) and 12 albumen metabolites (erythritol, threitol, ribitol, linoleic acid, isoleucine, dihydrouracil, 4-hydroxyphenyllactic acid, alanine, glycine, N-butyrylglycine, pyruvic acid, and valine) were significantly altered by feed, and a significant interaction between breed and feed was discovered in one albumen metabolite (N-butyrylglycine). Yolk and albumin had higher levels of sugar alcohols when hens were fed a fermented diet, which indicates that sugar alcohol content can be transferred from diet into eggs. Linoleic acid was also enriched in albumen under fermented feed conditions. This study shows that yolk and albumen metabolites will be affected by breed and feed, which is the first step towards manipulating genetic and environmental factors to create “designer eggs.” Full article
(This article belongs to the Special Issue Metabolomic Applications in Animal Science)
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Open AccessArticle
Metabolomic Profiling and Cytotoxic Tetrahydrofurofuran Lignans Investigations from Premna odorata Blanco
Metabolites 2019, 9(10), 223; https://doi.org/10.3390/metabo9100223 - 13 Oct 2019
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Abstract
Metabolomic profiling of different Premna odorata Blanco (Lamiaceae) organs, bark, wood, young stems, flowers, and fruits dereplicated 20, 20, 10, 20, and 20 compounds, respectively, using LC–HRESIMS. The identified metabolites (134) belonged to different chemical classes, including iridoids, flavones, [...] Read more.
Metabolomic profiling of different Premna odorata Blanco (Lamiaceae) organs, bark, wood, young stems, flowers, and fruits dereplicated 20, 20, 10, 20, and 20 compounds, respectively, using LC–HRESIMS. The identified metabolites (134) belonged to different chemical classes, including iridoids, flavones, phenyl ethanoids, and lignans. A phytochemical investigation of P. odorata bark afforded one new tetrahydrofurofuran lignan, 4β-hydroxyasarinin 35, along with fourteen known compounds. The structure of the new compound was confirmed using extensive 1D and 2D NMR, and HRESIMS analyses. A cytotoxic investigation of compounds 3538 against the HL-60, HT-29, and MCF-7 cancer cell lines, using the MTT assay showed that compound 35 had cytotoxic effects against HL-60 and MCF-7 with IC50 values of 2.7 and 4.2 µg/mL, respectively. A pharmacophore map of compounds 35 showed two hydrogen bond acceptor (HBA) aligning the phenoxy oxygen atoms of benzodioxole moieties, two aromatic ring features vectored on the two phenyl rings, one hydrogen bond donor (HBD) feature aligning the central hydroxyl group and thirteen exclusion spheres which limit the boundaries of sterically inaccessible regions of the target’s active site. Full article
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Open AccessArticle
Chemical Diversity and Classification of Secondary Metabolites in Nine Bryophyte Species
Metabolites 2019, 9(10), 222; https://doi.org/10.3390/metabo9100222 - 11 Oct 2019
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Abstract
The central aim in ecometabolomics and chemical ecology is to pinpoint chemical features that explain molecular functioning. The greatest challenge is the identification of compounds due to the lack of constitutive reference spectra, the large number of completely unknown compounds, and bioinformatic methods [...] Read more.
The central aim in ecometabolomics and chemical ecology is to pinpoint chemical features that explain molecular functioning. The greatest challenge is the identification of compounds due to the lack of constitutive reference spectra, the large number of completely unknown compounds, and bioinformatic methods to analyze the big data. In this study we present an interdisciplinary methodological framework that extends ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) with data-dependent acquisition (DDA-MS) and the automated in silico classification of fragment peaks into compound classes. We synthesize findings from a prior study that explored the influence of seasonal variations on the chemodiversity of secondary metabolites in nine bryophyte species. Here we reuse and extend the representative dataset with DDA-MS data. Hierarchical clustering, heatmaps, dbRDA, and ANOVA with post-hoc Tukey HSD were used to determine relationships of the study factors species, seasons, and ecological characteristics. The tested bryophytes showed species-specific metabolic responses to seasonal variations (50% vs. 5% of explained variation). Marchantia polymorpha, Plagiomnium undulatum, and Polytrichum strictum were biochemically most diverse and unique. Flavonoids and sesquiterpenoids were upregulated in all bryophytes in the growing seasons. We identified ecological functioning of compound classes indicating light protection (flavonoids), biotic and pathogen interactions (sesquiterpenoids, flavonoids), low temperature and desiccation tolerance (glycosides, sesquiterpenoids, anthocyanins, lactones), and moss growth supporting anatomic structures (few methoxyphenols and cinnamic acids as part of proto-lignin constituents). The reusable bioinformatic framework of this study can differentiate species based on automated compound classification. Our study allows detailed insights into the ecological roles of biochemical constituents of bryophytes with regard to seasonal variations. We demonstrate that compound classification can be improved with adding constitutive reference spectra to existing spectral libraries. We also show that generalization on compound classes improves our understanding of molecular ecological functioning and can be used to generate new research hypotheses. Full article
(This article belongs to the Special Issue Ecometabolomics)
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Open AccessCommunication
Sphingolipid Metabolism Perturbations in Rett Syndrome
Metabolites 2019, 9(10), 221; https://doi.org/10.3390/metabo9100221 - 10 Oct 2019
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Abstract
Rett syndrome is a severe neurodevelopmental disorder affecting mostly females and is caused by loss-of-function mutations in the MECP2 gene that encoded the methyl-CpG-binding protein 2. The pathogenetic mechanisms of Rett syndrome are not completely understood and metabolic derangements are emerging as features [...] Read more.
Rett syndrome is a severe neurodevelopmental disorder affecting mostly females and is caused by loss-of-function mutations in the MECP2 gene that encoded the methyl-CpG-binding protein 2. The pathogenetic mechanisms of Rett syndrome are not completely understood and metabolic derangements are emerging as features of Rett syndrome. We performed a semi-quantitative tandem mass spectrometry-based analysis that measured over 900 metabolites on blood samples from 14 female subjects with Rett syndrome carrying MECP2 mutations. The metabolic profiling revealed alterations in lipids, mostly involved in sphingolipid metabolism, and sphinganine/sphingosine, that are known to have a neurotrophic role. Further investigations are required to understand the mechanisms underlying such perturbations and their significance in the disease pathogenesis. Nevertheless, these metabolites are attractive for studies on the disease pathogenesis and as potential disease biomarkers. Full article
(This article belongs to the Special Issue Genetic Metabolic Diagnostics)
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Open AccessArticle
Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease
Metabolites 2019, 9(10), 220; https://doi.org/10.3390/metabo9100220 - 10 Oct 2019
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Abstract
Primary mitochondrial disease (PMD) is a large group of genetic disorders directly affecting mitochondrial function. Although next generation sequencing technologies have revolutionized the diagnosis of these disorders, biochemical tests remain essential and functional confirmation of the critical genetic diagnosis. While enzymological testing of [...] Read more.
Primary mitochondrial disease (PMD) is a large group of genetic disorders directly affecting mitochondrial function. Although next generation sequencing technologies have revolutionized the diagnosis of these disorders, biochemical tests remain essential and functional confirmation of the critical genetic diagnosis. While enzymological testing of the mitochondrial oxidative phosphorylation (OXPHOS) complexes remains the gold standard, oxygraphy could offer several advantages. To this end, we compared the diagnostic performance of both techniques in a cohort of 34 genetically defined PMD patient fibroblast cell lines. We observed that oxygraphy slightly outperformed enzymology for sensitivity (79 ± 17% versus 68 ± 15%, mean and 95% CI), and had a better discriminatory power, identifying 58 ± 17% versus 35 ± 17% as “very likely” for oxygraphy and enzymology, respectively. The techniques did, however, offer synergistic diagnostic prediction, as the sensitivity rose to 88 ± 11% when considered together. Similarly, the techniques offered varying defect specific information, such as the ability of enzymology to identify isolated OXPHOS deficiencies, while oxygraphy pinpointed PDHC mutations and captured POLG mutations that were otherwise missed by enzymology. In summary, oxygraphy provides useful information for the diagnosis of PMD, and should be considered in conjunction with enzymology for the diagnosis of PMD. Full article
(This article belongs to the Special Issue Genetic Metabolic Diagnostics)
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Open AccessArticle
In Silico Optimization of Mass Spectrometry Fragmentation Strategies in Metabolomics
Metabolites 2019, 9(10), 219; https://doi.org/10.3390/metabo9100219 - 09 Oct 2019
Viewed by 368
Abstract
Liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) is widely used in identifying small molecules in untargeted metabolomics. Various strategies exist to acquire MS/MS fragmentation spectra; however, the development of new acquisition strategies is hampered by the lack of simulators that let [...] Read more.
Liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) is widely used in identifying small molecules in untargeted metabolomics. Various strategies exist to acquire MS/MS fragmentation spectra; however, the development of new acquisition strategies is hampered by the lack of simulators that let researchers prototype, compare, and optimize strategies before validations on real machines. We introduce Virtual Metabolomics Mass Spectrometer (ViMMS), a metabolomics LC-MS/MS simulator framework that allows for scan-level control of the MS2 acquisition process in silico. ViMMS can generate new LC-MS/MS data based on empirical data or virtually re-run a previous LC-MS/MS analysis using pre-existing data to allow the testing of different fragmentation strategies. To demonstrate its utility, we show how ViMMS can be used to optimize N for Top-N data-dependent acquisition (DDA) acquisition, giving results comparable to modifying N on the mass spectrometer. We expect that ViMMS will save method development time by allowing for offline evaluation of novel fragmentation strategies and optimization of the fragmentation strategy for a particular experiment. Full article
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Open AccessArticle
Metabolomic Analysis Reveals Unique Biochemical Signatures Associated with Protection from Radiation Induced Lung Injury by Lack of cd47 Receptor Gene Expression
Metabolites 2019, 9(10), 218; https://doi.org/10.3390/metabo9100218 - 08 Oct 2019
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Abstract
The goal of this study was to interrogate biochemical profiles manifested in mouse lung tissue originating from wild type (WT) and cd47 null mice with the aim of revealing the in vivo role of CD47 in the metabolic response to ionizing radiation, especially [...] Read more.
The goal of this study was to interrogate biochemical profiles manifested in mouse lung tissue originating from wild type (WT) and cd47 null mice with the aim of revealing the in vivo role of CD47 in the metabolic response to ionizing radiation, especially changes related to the known association of CD47 deficiency with increased tissue viability and survival. For this objective, we performed global metabolomic analysis in mouse lung tissue collected from (C57Bl/6 background) WT and cd47 null mice with and without exposure to 7.6 Gy whole body radiation. Principal component analysis and hierarchical clustering revealed a consistent separation between genotypes following radiation exposure. Random forest analysis also revealed a unique biochemical signature in WT and cd47 null mice following treatment. Our data show that cd47 null irradiated lung tissue activates a unique set of metabolic pathways that facilitate the handling of reactive oxygen species, lipid metabolism, nucleotide metabolism and nutrient metabolites which may be regulated by microbial processing. Given that cd47 has pleiotropic effects on responses to ionizing radiation, we not only propose this receptor as a therapeutic target but postulate that the biomarkers regulated in this study associated with radioprotection are potential mitigators of radiation-associated pathologies, including the onset of pulmonary disease. Full article
(This article belongs to the Special Issue Metabolomics in the Study of Disease)
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Open AccessArticle
The Influence of Drying Temperatures on the Metabolic Profiles and Antioxidant Activity of Manilkara zapota Leaves
Metabolites 2019, 9(10), 217; https://doi.org/10.3390/metabo9100217 - 06 Oct 2019
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Abstract
In the present study, the leaves of Manilkara zapota (L.) P. Royen (Sapotaceae), an evergreen tree recognized for its medicinal properties in Southern Mexico, were used as a model to study the effect of different drying temperatures on its metabolic profile and therefore, [...] Read more.
In the present study, the leaves of Manilkara zapota (L.) P. Royen (Sapotaceae), an evergreen tree recognized for its medicinal properties in Southern Mexico, were used as a model to study the effect of different drying temperatures on its metabolic profile and therefore, its antioxidant potential. For this purpose, a methanol extraction of leaves dried at room temperature (25 °C) or by heat convection (50, 75 and 100 °C) were compared in terms of drying efficiency, yield of extraction, total phenol content, 1H-NMR metabolic profile, and DPPH antioxidant activity. The drying curves enabled the fact to be uncovered that drying efficiency improves with increase of temperature, as does the level of total phenols and antioxidant activity. A metabolomics approach using principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) of the corresponding 1H-NMR profiles allowed the impact of the drying temperature on their metabolic profile to be documented and also, caffeic acid and epicatechin as main secondary metabolites contributing to the antioxidant activity of M. zapota to be identified. Full article
(This article belongs to the Special Issue Plant Metabolomics)
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Open AccessArticle
The Absence of Pyruvate Kinase Affects Glucose-Dependent Carbon Catabolite Repression in Bacillus subtilis
Metabolites 2019, 9(10), 216; https://doi.org/10.3390/metabo9100216 - 04 Oct 2019
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Abstract
Pyruvate is a key intermediate of diverse metabolic pathways of central carbon metabolism. In addition to being the end product of glycolysis, pyruvate is an essential carbon distribution point to oxidative metabolism, amino acid and fatty acid syntheses, and overflow metabolite production. Hence, [...] Read more.
Pyruvate is a key intermediate of diverse metabolic pathways of central carbon metabolism. In addition to being the end product of glycolysis, pyruvate is an essential carbon distribution point to oxidative metabolism, amino acid and fatty acid syntheses, and overflow metabolite production. Hence, a tight regulation of pyruvate kinase (Pyk) activity is of great importance. This study aimed to analyze targeted metabolites from several pathways and possible changes in Bacillus subtilis lacking Pyk. Wild type and Δpyk cells were cultivated in chemically defined medium with glucose and pyruvate as carbon sources, and the extracted metabolites were analyzed by 1H-NMR, GC-MS, HPLC-MS, and LC-MS/MS. The results showed that the perturbation created in the pyruvate node drove an adaptation to new conditions by altering the nutritional compounds’ consumption. In Δpyk, pyruvate, which is subject to glucose-dependent carbon catabolite repression, did not comply with the hierarchy in carbon source utilization. Other metabolic alterations were observed such as the higher secretion of the overflow metabolites acetoin and 2,3-butanediol by Δpyk. Our results help to elucidate the regulatory transport of glucose and pyruvate in B. subtilis and possible metabolic reroute to alternative pathways in the absence of Pyk. Full article
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Open AccessCommunication
Extensive Metabolic Profiles of Leaves and Stems from the Medicinal Plant Dendrobium officinale Kimura et Migo
Metabolites 2019, 9(10), 215; https://doi.org/10.3390/metabo9100215 - 04 Oct 2019
Cited by 1 | Viewed by 226
Abstract
Dendrobium officinale Kimura et Migo is a commercially and pharmacologically highly prized species widely used in Western Asian countries. In contrast to the extensive genomic and transcriptomic resources generated in this medicinal species, detailed metabolomic data are still missing. Herein, using the widely [...] Read more.
Dendrobium officinale Kimura et Migo is a commercially and pharmacologically highly prized species widely used in Western Asian countries. In contrast to the extensive genomic and transcriptomic resources generated in this medicinal species, detailed metabolomic data are still missing. Herein, using the widely targeted metabolomics approach, we detect 649 diverse metabolites in leaf and stem samples of D. officinale. The majority of these metabolites were organic acids, amino acids and their derivatives, nucleotides and their derivatives, and flavones. Though both organs contain similar metabolites, the metabolite profiles were quantitatively different. Stems, the organs preferentially exploited for herbal medicine, contained larger concentrations of many more metabolites than leaves. However, leaves contained higher levels of polyphenols and lipids. Overall, this study reports extensive metabolic data from leaves and stems of D. officinale, providing useful information that supports ongoing genomic research and discovery of bioactive compounds. Full article
(This article belongs to the Special Issue Metabolomics Tools to Accelerate Natural Product Discovery)
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Open AccessArticle
Metabolomic Markers for the Early Selection of Coffea canephora Plants with Desirable Cup Quality Traits
Metabolites 2019, 9(10), 214; https://doi.org/10.3390/metabo9100214 - 04 Oct 2019
Viewed by 297
Abstract
Genetic improvement of coffee plants represents a great challenge for breeders. Conventional breeding takes a too long time for responding timely to market demands, climatic variations and new biological threads. The correlation of genetic markers with the plant phenotype and final product quality [...] Read more.
Genetic improvement of coffee plants represents a great challenge for breeders. Conventional breeding takes a too long time for responding timely to market demands, climatic variations and new biological threads. The correlation of genetic markers with the plant phenotype and final product quality is usually poor. Additionally, the creation and use of genetically modified organisms (GMOs) are often legally restricted and rejected by customers that demand natural products. Therefore, we developed a non-targeted metabolomics approach to accelerate conventional breeding. Our main idea was to identify highly heritable metabolites in Coffea canephora seedlings, which are linked to coffee cup quality. We employed a maternal half-sibs approach to estimate the metabolites heritability in open-pollinated plants in both leaves and fruits at an early plant development stage. We evaluated the cup quality of roasted beans and correlated highly heritable metabolites with sensory quality traits of the coffee beverage. Our results provide new insights about the heritability of metabolites of C. canephora plants. Furthermore, we found strong correlations between highly heritable metabolites and sensory traits of coffee beverage. We revealed metabolites that serve as predictive metabolite markers at an early development stage of coffee plants. Informed decisions can be made on plants of six months old, compared to 3.5 to 5 years using conventional selection methods. The metabolome-wide association study (MWAS) drastically accelerates the selection of C. canephora plants with desirable characteristics and represents a novel approach for the focused breeding of crops. Full article
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Open AccessArticle
Reactive Carbonyl Species as Potential Pro-Oxidant Factors Involved in Lichen Planus Pathogenesis
Metabolites 2019, 9(10), 213; https://doi.org/10.3390/metabo9100213 - 03 Oct 2019
Viewed by 224
Abstract
The constant generation of reactive carbonyl species (RCSs) by lipid peroxidation during aerobic metabolism denotes their involvement in cell homeostasis. Skin represents the largest organ of the body that is exposed to lipid peroxidation. Previous studies have suggested the involvement of oxidative stress [...] Read more.
The constant generation of reactive carbonyl species (RCSs) by lipid peroxidation during aerobic metabolism denotes their involvement in cell homeostasis. Skin represents the largest organ of the body that is exposed to lipid peroxidation. Previous studies have suggested the involvement of oxidative stress in the development of lichen planus (LP), a chronic inflammatory skin condition with a complex pathogenesis. The aim of our study is to investigate a panel of pro-oxidants (4-hydroxy-nonenal (4-HNE), thiobarbituric acid reactive substances (TBARS), and malondialdehyde (MDA)), the total antioxidant status (TAS), and thiol-disulfide homeostasis parameters (TDHP), including total thiol (TT), native thiol (NT), disulfides (DS), DS/NT ratio, DS/TT ratio, and NT/TT ratio. The comparative determinations of serum levels of 4-HNE, TBARS, and MDA in patients with LP (n = 31) and controls (n = 26) show significant differences between the two groups (4-HNE: 7.81 ± 1.96 µg/mL vs. 6.15 ± 1.17 µg/mL, p < 0.05, TBARS: 4.23 ± 0.59 µmol/L vs. 1.99 ± 0.23 µmol/L, p < 0.05, MDA: 32.3 ± 6.26 ng/mL vs. 21.26 ± 2.36 ng/mL). The serum levels of TAS are lower in LP patients compared to the control group (269.83 ± 42.63 µmol/L vs. 316.46 ± 28.76 µmol/L, p < 0.05). The serum levels of TDHP are altered in LP patients compared to controls (NT: 388.10 ± 11.32 µmol/L vs. 406.85 ± 9.32., TT: 430.23 ± 9.93 µmol/L vs. 445.88 ± 9.01 µmol/L, DS: 21.06 ± 1.76 µmol/L vs. 19.52 ± 0.77µmol/L). Furthermore, a negative association between pro-oxidants and TAS is identified (4-HNE – rho = −0.83, p < 0.01, TBARS – rho = −0.63, p < 0.01, and MDA – rho = −0.69, p < 0.01). Understanding the mechanisms by which bioactive aldehydes exert their biological effects on the skin could help define effective therapeutical strategies to counteract the cytotoxic effects of these reactive metabolic intermediates. Full article
(This article belongs to the Special Issue Metabolomics in the Study of Disease)
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