PubMed

Comparative study of five different amine-derivatization methods for metabolite analyses by liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2019 Sep 10;:460536 Authors: Lkhagva A, Shen CC, Leung YS, Tai HC Abstract Current metabolomics research utilizes liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses to handle biological samples that contain thousands of quantifiable metabolites. However, no LC-MS/MS condition is suitable for directly analyzing all metabolites. An alternative approach is to derivatize metabolites to impart desirable properties such as better chromatographic separation, enhanced ionization efficiency, or fluorescence detection. An important category of metabolites is amine-containing compounds, which includes amino acids, neurotransmitters, alkaloids, biogenic amines, etc. Various derivatization methods have been developed for amine groups, but few studies have compared their relative strengths and weaknesses. We chose Dansyl-Cl, o-phthalaldehyde (OPA), Fmoc-Cl, Dabsyl-Cl, and Marfey's reagent to systematically compare their reactivity, absorbance, fluorescence, chromatographic separation, and ionization efficiencies under three pH conditions-2.6, 5.0, and 8.0. Their MS/MS fragmentation patterns were also examined under different collision energies. Overall, Dansyl-Cl is a very versatile derivatization method, generating products with fluorescence and high ionization efficiency. Fmoc-Cl is similarly useful under highly acidic chromatography conditions. Dabsyl-Cl may be a good alternative at weakly acidic and weakly basic conditions. OPA is a versatile fluorogenic reagent and its chemistry may be fine-tuned by incorporating different thiol molecules. Marfey's reagent is suboptimal in general, but its chiral property is useful for the separation of enantiomers. All five were applied to the analyses of Coptis chinensis, a Chinese medical herb, identifying hundreds of amine-containing metabolites through MS/MS analyses. None of the five methods is clearly superior, and their compound coverage profiles are rather distinct. A combination of multiple derivatization reagents is required for comprehensive coverage. Our comparative data provide useful guidelines for designing more efficient metabolomics experiments for different analytical goals. PMID: 31563299 [PubMed - as supplied by publisher]

35 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/29PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/27PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/26PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/25PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metabolomic profiling identifies novel biomarkers and mechanisms in human bladder cancer treated with submucosal injection of gemcitabine. Int J Mol Med. 2019 Sep 23;: Authors: Yang C, Sun X, Wang H, Lu T, Wu K, Guan Y, Tang J, Liang J, Sun R, Guo Z, Zheng S, Wu X, Jiang H, Jiang X, Zhong B, Niu X, Sun S, Wang X, Chen M, Fu G Abstract Bladder cancer (BCa) is a common urinary tract malignancy with frequent recurrences after initial resection. Submucosal injection of gemcitabine prior to transurethral resection of bladder tumor (TURBT) may prevent recurrence of urothelial cancer. However, the underlying mechanism remains unknown. In the present study, ultra‑performance liquid chromatography Q‑Exactive mass spectrometry was used to profile tissue metabolites from 12 BCa patients. The 48 samples included pre‑ and post‑gemcitabine treatment BCa tissues, as well as adjacent normal tissues. Principal component analysis (PCA) revealed that the metabolic profiles of pre‑gemcitabine BCa tissues differed significantly from those of pre‑gemcitabine normal tissues. A total of 34 significantly altered metabolites were further analyzed. Pathway analysis using MetaboAnalyst identified three metabolic pathways closely associated with BCa, including glutathione, purine and thiamine metabolism, while glutathione metabolism was also identified by the enrichment analysis using MetaboAnalyst. In search of the possible targets of gemcitabine, metabolite profiles were compared between the pre‑gemcitabine normal and post‑gemcitabine BCa tissues. Among the 34 metabolites associated with BCa, the levels of bilirubin and retinal recovered in BCa tissues treated with gemcitabine. When comparing normal bladder tissues with and without gemcitabine treatment, among the 34 metabolites associated with BCa, it was observed that histamine change may be associated with the prevention of relapse, whereas thiamine change may be involved in possible side effects. Therefore, by employing a hypothesis‑free tissue‑based metabolomics study, the present study investigated the metabolic signatures of BCa and found that bilirubin and retinal may be involved in the mechanism underlying the biomolecular action of submucosal injection of gemcitabine in urothelial BCa. PMID: 31545404 [PubMed - as supplied by publisher]

Related Articles Metabolomics and Microbial Composition Increase Insight into the Impact of Dietary Differences in Cirrhosis. Liver Int. 2019 Sep 23;: Authors: Cox IJ, Idiliman R, Fagan A, Turan D, Ajayi L, Le Guennec AD, Taylor-Robinson SD, Karakaya F, Gavis E, Andrew Atkinson R, Williams R, Sikaroodi M, Nizam S, Gillevet PM, Bajaj JS Abstract BACKGROUND & AIMS: Dietary changes can modulate gut microbiota and interact with cirrhosis. Our prior study demonstrated that microbial diversity was higher in Turkish versus USA cirrhotics, which was associated with lower risk of 90-day hospitalizations. We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets. METHODS: 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied. Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake while Americans consumed a Western diet. Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries. Correlation network differences between microbiota and metabolites in cirrhotics from Turkey versus USA were evaluated. RESULTS: Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in Turkey compared to USA cirrhotics. Plasma metabolomics demonstrated higher relative lactate levels in Turkey versus USA. The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and USA, with reduced lipids and phosphocholines. Phosphocholines were significantly lower in patients hospitalized in 90 days (p=0.03). Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients. CONCLUSIONS: A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis. These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk. PMID: 31544308 [PubMed - as supplied by publisher]

Related Articles Characterization of chemical constituents and absorbed components, screening the active components of gelanxinning capsule and an evaluation of therapeutic effects by ultrahigh performance liquid chromatography with quadrupole time-of-flight mass spectrometry. J Sep Sci. 2019 Sep 22;: Authors: Gao X, Hu X, Zhang Q, Wang X, Wen X, Wang Y, Zhang Y, Sun W Abstract It revealed the potential biomarker and pathway of gelanxinning capsule on rat model with coronary heart disease, which aims to clarify holistic therapeutic effect and predict quality-markers of gelanxinning capsule. Ultrahigh performance liquid chromatography-mass spectrometry based on metabolomics technique was used to find the biomarkers and related metabolic pathways of coronary heart disease model, which evaluates the intervention effect of gelanxinning capsule. Using serum pharmacochemistry of traditional Chinese medicine and Pearson correlation analysis, effective ingredients in serum is analyzed to characterize the activity of gelanxinning capsule on coronary heart disease under valid state. A total of 20 biomarkers from coronary heart disease were identified and 12 of them were regulated by gelanxinning capsule treatment, which is mainly involved in sphingolipid metabolism and glycerophospholipid metabolism. With the high sensitivity liquid chromatography-mass spectrometry technology, a total of 46 compounds from gelanxinning capsule were identified in vitro and 25 of them were absorbed in blood. The correlation analysis of serum biomarkers and absorbed components was used to find 11 compounds as quality-markers to be responsible for the efficacy of gelanxinning capsule. This strategy was successfully applied to screening of potential mechanism and quality-markers from herbal medicine.<PE-FRONTEND> This article is protected by copyright. All rights reserved. PMID: 31544307 [PubMed - as supplied by publisher]

Related Articles Metabolic Insights Into the Effects of Nutrient Stress on Lactobacillus plantarum B21. Front Mol Biosci. 2019;6:75 Authors: Parlindungan E, May BK, Jones OAH Abstract Lactobacillus plantarum B21 is a strain of lactic acid bacteria first isolated from a fermented meat product from Vietnam. It is also a promising biopreservative with potential use in the food industry as it is a source of a novel bacteriocin (Plantacyclin B21AG) which has inhibitory effects against a wide range of species, including several pathogenic and spoilage strains. Nutrient stress is known to increase the survivability, storage stability, and bacteriocin production capability of L. plantarum B21 during industrial processing. It is however, unknown what the underlying biochemical responses that control these abilities are. This study therefore investigates the metabolite profiles of L. plantarum B21 using NMR spectroscopy and GC-MS to further understand the biochemical responses of this strain to various stress events. Unstressed cells were found to use glucose as their primary energy source with high concentrations of metabolites involved in glycolysis and organic acid synthesis, such as lactic acid, acetic acid, propanoic acid, malic acid, and 2-butenedioic acid being present in these cells. In contrast, large numbers of metabolites involved in amino acid metabolism including alanine, glutamic acid, aspartic acid, valine, proline, and norleucine were upregulated in glucose stressed cells, indicating that they were using amino acids as their main source of energy. Differences in levels of fatty acids, particularly octadecenoic acid, tetracosanoic acid, and 7-hexadecenoic acid were also observed between stressed and unstressed cells. The results from this study provide insight on the biochemical response of this bacterial strain to stresses commonly found during industrial processing. PMID: 31544106 [PubMed]

Related Articles Exploring Radiation Response in Two Head and Neck Squamous Carcinoma Cell Lines Through Metabolic Profiling. Front Oncol. 2019;9:825 Authors: Lindell Jonsson E, Erngren I, Engskog M, Haglöf J, Arvidsson T, Hedeland M, Petterson C, Laurell G, Nestor M Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide. Radiotherapy, with or without surgery, represents the major approach to curative treatment. However, not all tumors are equally sensitive to irradiation. It is therefore of interest to apply newer system biology approaches (e.g., metabolic profiling) in squamous cancer cells with different radiosensitivities in order to provide new insights on the mechanisms of radiation response. In this study, two cultured HNSCC cell lines from the same donor, UM-SCC-74A and UM-SCC-74B, were first genotyped using Short Tandem Repeat (STR), and assessed for radiation response by the means of clonogenic survival and growth inhibition assays. Thereafter, cells were cultured, irradiated and collected for subsequent metabolic profiling analyses using liquid chromatography-mass spectrometry (LC-MS). STR verified the similarity of UM-SCC-74A and UM-SCC-74B cells, and three independent assays proved UM-SCC-74B to be clearly more radioresistant than UM-SCC-74A. The LC-MS metabolic profiling demonstrated significant differences in the intracellular metabolome of the two cell lines before irradiation, as well as significant alterations after irradiation. The most important differences between the two cell lines before irradiation were connected to nicotinic acid and nicotinamide metabolism and purine metabolism. In the more radiosensitive UM-SCC-74A cells, the most significant alterations after irradiation were linked to tryptophan metabolism. In the more radioresistant UM-SCC-74B cells, the major alterations after irradiation were connected to nicotinic acid and nicotinamide metabolism, purine metabolism, the methionine cycle as well as the serine, and glycine metabolism. The data suggest that the more radioresistant cell line UM-SCC-74B altered the metabolism to control redox-status, manage DNA-repair, and change DNA methylation after irradiation. This provides new insights on the mechanisms of radiation response, which may aid future identification of biomarkers associated with radioresistance of cancer cells. PMID: 31544064 [PubMed]

Related Articles Metabolomics Based Study of the Antileishmanial Activity of Xanthium strumarium Leaf Extract on Promastigotes Phases of Leishmania major by Proton NMR Spectroscopy. Iran J Parasitol. 2019 Apr-Jun;14(2):258-268 Authors: Ahmadi M, Akbari Z, Alikhani M, Hajhossiani R, Zamani Z, Arjmand M Abstract Background: Xanthium strumarium L. is extensively used as a traditional herb to treat many diseases and is also known as a source of phytochemicals. It has been used traditionally to treat trypanosomiasis, malaria fever, eczema, cancer, ulcer, fever, herpes headache, and skin lesion such as leishmaniasis. In this preliminary study, nuclear magnetic resonance (NMR)-metabolomics approaches was used to evaluate the inhibitory effects and metabolic alterations caused by leaf extract of X. strumarium on the stationary phases of promastigotes in Leishmania major. Methods: The promastigotes were cultured in Biochemistry Laboratory at Pasteur Institute of Iran in 2017, stationary phases were obtained from 5 to 6 day-old cultures and treated with different concentrations of the plant's extract. Antileishmanial activity was assayed by MTT method and cell metabolites were extracted. 1H NMR spectroscopy was applied, and outliers were separated using multivariate statistical analysis. Results: The most affected metabolic pathways in the experimental groups were limited to amino sugar and nucleotide sugar metabolism, cyanoamino acid metabolism, starch and sucrose metabolism, butanoate metabolism, and galactose metabolism. Conclusion: The ethanolic leaf extract of X. strumarium is a potent growth inhibitor of Leishmania major and can affect vital metabolic pathways of Leishmania promastigotes. The assay provided new perspectives on the development of novel treatment strategies for leishmanial activity derived from natural products. PMID: 31543914 [PubMed]

Related Articles Multi-Omics Analysis of Fatty Alcohol Production in Engineered Yeasts Saccharomyces cerevisiae and Yarrowia lipolytica. Front Genet. 2019;10:747 Authors: Dahlin J, Holkenbrink C, Marella ER, Wang G, Liebal U, Lieven C, Weber D, McCloskey D, Ebert BE, Herrgård MJ, Blank LM, Borodina I Abstract Fatty alcohols are widely used in various applications within a diverse set of industries, such as the soap and detergent industry, the personal care, and cosmetics industry, as well as the food industry. The total world production of fatty alcohols is over 2 million tons with approximately equal parts derived from fossil oil and from plant oils or animal fats. Due to the environmental impact of these production methods, there is an interest in alternative methods for fatty alcohol production via microbial fermentation using cheap renewable feedstocks. In this study, we aimed to obtain a better understanding of how fatty alcohol biosynthesis impacts the host organism, baker's yeast Saccharomyces cerevisiae or oleaginous yeast Yarrowia lipolytica. Producing and non-producing strains were compared in growth and nitrogen-depletion cultivation phases. The multi-omics analysis included physiological characterization, transcriptome analysis by RNAseq, 13Cmetabolic flux analysis, and intracellular metabolomics. Both species accumulated fatty alcohols under nitrogen-depletion conditions but not during growth. The fatty alcohol-producing Y. lipolytica strain had a higher fatty alcohol production rate than an analogous S. cerevisiae strain. Nitrogen-depletion phase was associated with lower glucose uptake rates and a decrease in the intracellular concentration of acetyl-CoA in both yeast species, as well as increased organic acid secretion rates in Y. lipolytica. Expression of the fatty alcohol-producing enzyme fatty acyl-CoA reductase alleviated the growth defect caused by deletion of hexadecenal dehydrogenase encoding genes (HFD1 and HFD4) in Y. lipolytica. RNAseq analysis showed that fatty alcohol production triggered a cell wall stress response in S. cerevisiae. RNAseq analysis also showed that both nitrogen-depletion and fatty alcohol production have substantial effects on the expression of transporter encoding genes in Y. lipolytica. In conclusion, through this multi-omics study, we uncovered some effects of fatty alcohol production on the host metabolism. This knowledge can be used as guidance for further strain improvement towards the production of fatty alcohols. PMID: 31543895 [PubMed]

Related Articles Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction. Cell Metab. 2019 Sep 17;: Authors: Chen S, Henderson A, Petriello M, Romano KA, Gearing M, Miao J, Schell M, Sandoval-EspinolaEspinola WJ, Tao J, Sha B, Graham M, Crooke R, Kleinridders A, Balskus EP, Rey FE, Morris A, Biddinger SB Abstract The gut-microbe-derived metabolite trimethylamine N-oxide (TMAO) is increased by insulin resistance and associated with several sequelae of metabolic syndrome in humans, including cardiovascular, renal, and neurodegenerative disease. The mechanism by which TMAO promotes disease is unclear. We now reveal the endoplasmic reticulum stress kinase PERK (EIF2AK3) as a receptor for TMAO: TMAO binds to PERK at physiologically relevant concentrations; selectively activates the PERK branch of the unfolded protein response; and induces the transcription factor FoxO1, a key driver of metabolic disease, in a PERK-dependent manner. Furthermore, interventions to reduce TMAO, either by manipulation of the gut microbiota or by inhibition of the TMAO synthesizing enzyme, flavin-containing monooxygenase 3, can reduce PERK activation and FoxO1 levels in the liver. Taken together, these data suggest TMAO and PERK may be central to the pathogenesis of the metabolic syndrome. PMID: 31543404 [PubMed - as supplied by publisher]

Related Articles High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds. Sci Transl Med. 2018 02 21;10(429): Authors: Zampieri M, Szappanos B, Buchieri MV, Trauner A, Piazza I, Picotti P, Gagneux S, Borrell S, Gicquel B, Lelievre J, Papp B, Sauer U Abstract Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolome profiling strategy to classify the MoAs of bioactive compounds. The method predicted MoA-specific metabolic responses in the nonpathogenic bacterium Mycobacterium smegmatis after treatment with 62 reference compounds with known MoAs and different metabolic and nonmetabolic targets. We then analyzed a library of 212 new antimycobacterial compounds with unknown MoAs from a drug discovery effort by the pharmaceutical company GlaxoSmithKline (GSK). More than 70% of these new compounds induced metabolic responses in M. smegmatis indicative of known MoAs, seven of which were experimentally validated. Only 8% (16) of the compounds appeared to target unconventional cellular processes, illustrating the difficulty in discovering new antibiotics with different MoAs among compounds used as monotherapies. For six of the GSK compounds with potentially new MoAs, the metabolome profiles suggested their ability to interfere with trehalose and lipid metabolism. This was supported by whole-genome sequencing of spontaneous drug-resistant mutants of the pathogen Mycobacterium tuberculosis and in vitro compound-proteome interaction analysis for one of these compounds. Our compendium of drug-metabolome profiles can be used to rapidly query the MoAs of uncharacterized antimicrobial compounds and should be a useful resource for the drug discovery community. PMID: 29467300 [PubMed - indexed for MEDLINE]

Metabolomics and physiological analyses reveal β-sitosterol as an important plant growth regulator inducing tolerance to water stress in white clover. Planta. 2019 Sep 21;: Authors: Li Z, Cheng B, Yong B, Liu T, Peng Y, Zhang X, Ma X, Huang L, Liu W, Nie G Abstract MAIN CONCLUSION: β-sitosterol influences amino acids, carbohydrates, organic acids, and other metabolite metabolism and homeostasis largely contributing to better tolerance to water stress in white clover. β-sitosterol (BS) could act as an important plant growth regulator when plants are subjected to harsh environmental conditions. Objective of this study was to examine effects of BS on growth and water stress tolerance in white clover based on physiological responses and metabolomics. White clover was pretreated with or without BS and then subjected to water stress for 7 days in controlled growth chambers. Physiological analysis demonstrated that exogenous application of BS (120 μM) could significantly improve stress tolerance associated with better growth performance and photosynthesis, higher leaf relative water content, and less oxidative damage in white clover in response to water stress. Metabolic profiling identified 78 core metabolites involved in amino acids, organic acids, sugars, sugar alcohols, and other metabolites in leaves of white clover. For sugars and sugar alcohol metabolism, the BS treatment enhanced the accumulation of fructose, glucose, maltose, and myo-inositol contributing to better antioxidant capacity, growth maintenance, and osmotic adjustment in white clover under water stress. The application of BS was inclined to convert glutamic acid into proline, 5-oxoproline, and chlorophyll instead of going to pyruvate and alanine; the BS treatment did not significantly affect intermediates of tricarboxylic acid cycle (citrate, aconitate, and malate), but promoted the accumulation of other organic acids including lactic acid, glycolic acid, glyceric acid, shikimic acid, galacturonic acid, and quinic acid in white clover subjected to water stress. In addition, cysteine, an important antioxidant metabolite, was also significantly improved by BS in white clover under water stress. These altered amino acids and organic acids metabolism could play important roles in growth maintenance and modulation of osmotic and redox balance against water stress in white clover. Current findings provide a new insight into BS-induced metabolic homeostasis related to growth and water stress tolerance in plants. PMID: 31542810 [PubMed - as supplied by publisher]

Metabolomics coupled with SystemsDock reveal the protective effect and the potential active components of Naozhenning granule against traumatic brain injury. J Ethnopharmacol. 2019 Sep 19;:112247 Authors: Cao J, Duan Y, Liu Y, Liu H, Wei C, Wang J, Qin X, Wang X, Li Z Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Naozhenning granule (NZN), a widely traditional Chinese medicine (TCM) prescription with a long history of clinical, which is mainly used in the treatment of concussion, cerebral post-traumatic syndrome, consists of Di Huang (Radix of Rehmannia glutinosa (Gaertn.) DC.), Dang Gui (Radix of Angelica sinensis (Oliv.) Diels), Chen Pi (Pericarpium of Citrus reticulata Blanco), Danshen (Radix of Salvia Miltiorrhiza Bunge.), Di Long (Pheretima aspergillum (E. Perrier)), Mu Dan Pi (Cortex of Paeonia suffruticosa Andrews), Suan Zao Ren (Semen of Ziziphus jujuba Mill.), Chuan Xiong (Rhizoma of Ligusticum striatum DC.), Zhu Ru (Phyllostachys nigra (Lodd. Ex Lindl.) Munro), Bai Zi Ren (Semen of Platycladus orientalis (L.) Franco) and Fu Ling (sclerotium of Poria cocos (Schw.)Wolf). AIM OF THE STUDY: This study aimed to unravel the mechanism and material basis of NZN against traumatic brain injury. MATERIALS AND METHODS: In this study, a 1H nuclear magnetic resonance (NMR) based metabolomic approach combined with systemsDock was employed to study the protective effect of NZN against traumatic brain injury using a cerebral concussion rat model. The morris water maze test and biochemical indexes were used to evaluate the efficacy of NZN. RESULTS: The results of morris water maze test suggested NZN can improve the spatial learning and memory of model rats, and the superoxide dismutas (SOD) and malonyldialdehyde (MDA) level indicated that the effect of NZN was related with the regulation of oxidative stress. Multivariate analysis revealed that the effect of NZN was related with regulation of 18 brain metabolites, and the corresponding metabolic pathways were further revealed by MetPA analysis. 13 serum absorbed components were found to hit the targets both related with the metabolic regulation and cerebral trauma through systemsDock-aided molecular docking experiments, and these compounds might be served as the active compounds in NZN against cerebral trauma. CONCLUSION: 1H-NMR based metabolomics and molecular docking provided the insights for the synergistic mechanisms and the potential active compounds of NZN in treating cerebral trauma. However, the bioactive compounds and their synergistic effect need to be further validated. PMID: 31542470 [PubMed - as supplied by publisher]

Comparative serum metabolomics between SCID mice and BALB/c mice with or without Schistosoma japonicum infection: clues to the abnormal growth and development of schistosome in SCID mice. Acta Trop. 2019 Sep 19;:105186 Authors: Liu R, Ye F, Zhong QP, Wang SH, Chai T, Dong HF, Ming Z Abstract The small blood flukes of genus Schistosoma, which cause one of the most prevalent and serious parasitic zoonosis schistosomiasis, are dependent on immune-related factors of their mammalian host to facilitate their growth and development, and the formation of granulomatous pathology caused by eggs deposited in host's liver and intestinal wall. Schistosome development is hampered in the mice lacking just T cells, and is even more heavily retarded in the severe combined immunodeficient (SCID) mice lacking both T and B lymphocytes. Nevertheless, it's still not clear about the underlying regulatory molecular mechanisms of schistosome growth and development by host's immune system. This study, therefore, detected and compared the serum metabolic profiles between the immunodeficient mice and immunocompetent mice (SCID mice vs. BALB/c mice) before and after S. japonicum infection (on the thirty-fifth day post infection using liquid chromatography-mass spectrometry (LC-MS). Totally, 705 ion features in electrospray ionization in positive-ion mode (ESI+) and 242 ion features in ESI- mode were identified, respectively. First, distinct serum metabolic profiles were identified between SCID mice and BALB/c mice without S. japonicum worms infection. Second, uniquely perturbed serum metabolites and their enriched pathways were also obtained between SCID mice and BALB/c mice after S. japonicum infection, which included differential metabolites due to both species differences and differential responses to S. japonicum infection. The metabolic pathways analysis revealed that arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, alpha-linolenic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and purine metabolism were enriched based on the differential serum metabolites between SCID mice and BALB/c mice after S. japonicum infection, which was addressed to be related to the retarded growth and development of S. japonicum in SCID mice. These findings provide new clues to the underlying molecular events of host's systemic metabolic changes on the growth and development of S. japonicum worms, and also provide quite promising candidates for exploitation of drugs or vaccines against schistosome and schistosomiasis. PMID: 31542371 [PubMed - as supplied by publisher]

Accumulation of sugars and nucleosides in response to high salt and butanol stress in 1-butanol producing Synechococcus elongatus. J Biosci Bioeng. 2019 Sep 18;: Authors: Fathima AM, Laviña WA, Putri SP, Fukusaki E Abstract 1-Butanol production using photosynthetic organisms such as cyanobacteria has garnered interest among researchers due to its high potential as a sustainable biofuel. Previously, the cyanobacterium Synechococcus elongatus PCC 7942 was engineered to produce 1-butanol through the introduction of a modified CoA-dependent pathway. S. elongatus strain DC11, a high producer of 1-butanol, was constructed based on metabolomics-assisted strain engineering. DC11 can reach a production titer of 418.7 mg/L in 6 days, cutting the production time in half compared to the previously constructed DC7. Regardless, the final 1-butanol titer of DC11 was still low compared to other microbial hosts. Sensitivity towards 1-butanol of the producing strain has been known as one of main hurdles for improving cyanobacterial production system. Thus, to improve cyanobacterial-based 1-butanol production in the future, we employed the metabolomics approach to study the intrinsic effect of improved 1-butanol productivity in DC11. This study focused on metabolite profiling of DC11 using LC/MS/MS. Results showed that there is an accumulation of disaccharide-P and sucrose/trehalose in DC11 compared to the DC7. These metabolites were previously reported to have a role in salt and alcohol stress response in cyanobacteria and therefore, DC11 was subjected to 0.2 M of NaCl and 1000 mg/L of 1-butanol for further investigation. DC11 with stress treatment showed a more prominent accumulation of sugars and nucleosides compared to control. The results obtained from this study may be beneficial for future strain improvement strategies in S. elongatus, particularly addressing the metabolic response of this strain upon 1-butanol stress. PMID: 31542348 [PubMed - as supplied by publisher]

Metabolic Profiling Associates with Disease Severity in Non-Ischemic Dilated Cardiomyopathy. J Card Fail. 2019 Sep 18;: Authors: Verdonschot JAJ, Wang P, van Bilsen M, Hazebroek MR, Merken JJ, Vanhoutte EK, Henkens MTHM, van den Wijngaard A, Glatz JFC, Krapels IPC, Brunner HG, Heymans SRB, Bierau J Abstract AIMS: Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in non-ischemic dilated cardiomyopathy (DCM) patients and compared its incremental value on top of NT-proBNP. METHODS AND RESULTS: A total of 149 metabolites were measured in plasma and urine samples of 273 DCM patients with different stages of disease (DCM patients with LVRR (normal LVEF), n=70; asymptomatic DCM, n=72 and symptomatic DCM, n=131). Acylcarnitines, sialic acid, and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by uni-biomarker linear regression, sPLSDA, Random Forest and conditional Random Forest analyses. However, the absolute difference of the metabolic profile among groups was marginal. A decision tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish DCM patients with LVRR from symptomatic DCM (AUC 0.813±0.138 versus 0.739±0.114; p=0.02). CONCLUSION: Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in non-ischemic DCM. PMID: 31541741 [PubMed - as supplied by publisher]