PubMed

Related Articles Cross-sectional serum metabolomic study of multiple forms of muscular dystrophy. J Cell Mol Med. 2018 Feb 14;: Authors: Spitali P, Hettne K, Tsonaka R, Sabir E, Seyer A, Hemerik JBA, Goeman JJ, Picillo E, Ergoli M, Politano L, Aartsma-Rus A Abstract Muscular dystrophies are characterized by a progressive loss of muscle tissue and/or muscle function. While metabolic alterations have been described in patients'-derived muscle biopsies, non-invasive readouts able to describe these alterations are needed in order to objectively monitor muscle condition and response to treatment targeting metabolic abnormalities. We used a metabolomic approach to study metabolites concentration in serum of patients affected by multiple forms of muscular dystrophy such as Duchenne and Becker muscular dystrophies, limb-girdle muscular dystrophies type 2A and 2B, myotonic dystrophy type 1 and facioscapulohumeral muscular dystrophy. We show that 15 metabolites involved in energy production, amino acid metabolism, testosterone metabolism and response to treatment with glucocorticoids were differentially expressed between healthy controls and Duchenne patients. Five metabolites were also able to discriminate other forms of muscular dystrophy. In particular, creatinine and the creatine/creatinine ratio were significantly associated with Duchenne patients performance as assessed by the 6-minute walk test and north star ambulatory assessment. The obtained results provide evidence that metabolomics analysis of serum samples can provide useful information regarding muscle condition and response to treatment, such as to glucocorticoids treatment. PMID: 29441734 [PubMed - as supplied by publisher]

Related Articles Metabolomics-based chemotaxonomy of root endophytic fungi for natural products discovery. Environ Microbiol. 2018 Feb 14;: Authors: Maciá-Vicente JG, Shi YN, Cheikh-Ali Z, Grün P, Glynou K, Haghi Kia S, Piepenbring M, Bode HB Abstract Fungi are prolific producers of natural products routinely screened for biotechnological applications, and those living endophytically within plants attract particular attention because of their purported chemical diversity. However, the harnessing of their biosynthetic potential is hampered by a large and often cryptic phylogenetic and ecological diversity, coupled with a lack of large-scale natural products' dereplication studies. To guide efforts to discover new chemistries among root-endophytic fungi, we analyzed the natural products produced by 822 strains using an untargeted UPLC-ESI-MS/MS-based approach and linked the patterns of chemical features to fungal lineages. We detected 17,809 compounds of which 7,951 were classified in 1,992 molecular families, whereas the remaining were considered unique chemistries. Our approach allowed to annotate 1,191 compounds with different degrees of accuracy, many of which had known fungal origins. Approximately 61% of the compounds were specific of a fungal order, and differences were observed across lineages in the diversity and characteristics of their chemistries. Chemical profiles also showed variable chemosystematic values across lineages, ranging from relative homogeneity to high heterogeneity among related fungi. Our results provide an extensive resource to dereplicate fungal natural products and may assist future discovery programs by providing a guide for the selection of target fungi. This article is protected by copyright. All rights reserved. PMID: 29441701 [PubMed - as supplied by publisher]

Related Articles Metabolomics and transcriptomics profiles reveal the dysregulation of the tricarboxylic acid cycle and related mechanisms in prostate cancer. Int J Cancer. 2018 Feb 14;: Authors: Shao Y, Ye G, Ren S, Piao HL, Zhao X, Lu X, Wang F, Wang M, Li J, Yin P, Xia T, Xu C, Yu JJ, Sun Y, Xu G Abstract Genetic alterations drive metabolic reprogramming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene-metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa. Significant accumulation of metabolic intermediates and enrichment of genes in the tricarboxylic acid (TCA) cycle were observed in tumor tissues, indicating TCA cycle hyperactivation in PCa tissues. Additionally, the levels of fumarate and malate were highly correlated with the Gleason score, tumor stage and expression of genes encoding related enzymes and were significantly related to the expression of genes involved in branched chain amino acid degradation. Using an integrated omics approach, we further revealed the potential anaplerotic routes from pyruvate, glutamine catabolism and branched chain amino acid (BCAA) degradation contributing to replenishing metabolites for TCA cycle. Integrated omics techniques enable the performance of network-based analyses to gain a comprehensive and in-depth understanding of PCa pathophysiology and may facilitate the development of new and effective therapeutic strategies. This article is protected by copyright. All rights reserved. PMID: 29441565 [PubMed - as supplied by publisher]

Related Articles Time-series lipidomic analysis of the oleaginous green microalga species Ettlia oleoabundans under nutrient stress. Biotechnol Biofuels. 2018;11:29 Authors: Matich EK, Ghafari M, Camgoz E, Caliskan E, Pfeifer BA, Haznedaroglu BZ, Atilla-Gokcumen GE Abstract Background: Microalgae are uniquely advantageous organisms cultured and harvested for several value-added biochemicals. A majority of these compounds are lipid-based, such as triacylglycerols (TAGs), which can be used for biofuel production, and their accumulation is most affected under nutrient stress conditions. As such, the balance between cellular homeostasis and lipid metabolism becomes more intricate to achieve efficiency in bioproduct synthesis. Lipidomics studies in microalgae are of great importance as biochemical diversity also plays a major role in lipid regulation among oleaginous species. Methods: The aim of this study was to analyze time-series changes in lipid families produced by microalga under different nutrient conditions and growth phases to gain comprehensive information at the cellular level. For this purpose, we worked with a highly adaptable, oleaginous, non-model green microalga species, Ettlia oleoabundans (a.k.a. Neochloris oleoabundans). Using a mass spectrometry-based untargeted and targeted metabolomics' approach, we analyzed the changes in major lipid families under both replete and deplete nitrogen and phosphorus conditions at four different time points covering exponential and stationary growth phases. Results: Comprehensive analysis of the lipid metabolism highlighted the accumulation of TAGs, which can be utilized for the production of biodiesel via transesterification, and depletion of chlorophylls and certain structural lipids required for photosynthesis, under nutrient deprived conditions. We also found a correlation between the depletion of digalactosyldiacylglycerols (DGDGs) and sulfoquinovosyldiacylglycerols (SQDGs) under nutrient deprivation. Conclusions: High accumulation of TAGs under nutrient limitation as well as a depletion of other lipids of interest such as phosphatidylglycerols (PGs), DGDGs, SQDGs, and chlorophylls seem to be interconnected and related to the microalgal photosynthetic efficiency. Overall, our results provided key biochemical information on the lipid regulation and physiology of a non-model green microalga, along with optimization potential for biodiesel and other value-added product synthesis. PMID: 29441127 [PubMed]

Related Articles Alanine Enhances Aminoglycosides-Induced ROS Production as Revealed by Proteomic Analysis. Front Microbiol. 2018;9:29 Authors: Ye JZ, Su YB, Lin XM, Lai SS, Li WX, Ali F, Zheng J, Peng B Abstract Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to manage antibiotic resistance. Our previous study demonstrated that alanine or/and glucose increased the killing efficacy of kanamycin on antibiotic-resistant bacteria, whose action is through up-regulating TCA cycle, increasing proton motive force and enhancing antibiotic uptake. Despite the fact that alanine altered several metabolic pathways, other mechanisms could be potentially involved in alanine-mediated kanamycin killing of bacteria which remains to be explored. In the present study, we adopted proteomic approach to analyze the proteome changes induced by exogenous alanine. Our results revealed that the expression of three outer membrane proteins was altered and the deletion of nagE and fadL decreased the intracellular kanamycin concentration, implying their possible roles in mediating kanamycin transport. More importantly, the integrated analysis of proteomic and metabolomic data pointed out that alanine metabolism could connect to riboflavin metabolism that provides the source for reactive oxygen species (ROS) production. Functional studies confirmed that alanine treatment together with kanamycin could promote ROS production that in turn potentiates the killing of antibiotic-resistant bacteria. Further investigation showed that alanine repressed the transcription of antioxidant-encoding genes, and alanine metabolism to riboflavin metabolism connected with riboflavin metabolism through TCA cycle, glucogenesis pathway and pentose phosphate pathway. Our results suggest a novel mechanism by which alanine facilitates kanamycin killing of antibiotic-resistant bacteria via promoting ROS production. PMID: 29441044 [PubMed]

Related Articles Metabolomics Based Identification of SIRT5 and Protein Kinase C Epsilon Regulated Pathways in Brain. Front Neurosci. 2018;12:32 Authors: Koronowski KB, Khoury N, Morris-Blanco KC, Stradecki-Cohan HM, Garrett TJ, Perez-Pinzon MA Abstract The role of Sirtuins in brain function is emerging, yet little is known about SIRT5 in this domain. Our previous work demonstrates that protein kinase C epsilon (PKCε)-induced protection from focal ischemia is lost in SIRT5-/- mice. Thus, metabolic regulation by SIRT5 contributes significantly to ischemic tolerance. The aim of this study was to identify the SIRT5-regulated metabolic pathways in the brain and determine which of those pathways are linked to PKCε. Our results show SIRT5 is primarily expressed in neurons and endothelial cells in the brain, with mitochondrial and extra-mitochondrial localization. Pathway and enrichment analysis of non-targeted primary metabolite profiles from Sirt5-/- cortex revealed alterations in several pathways including purine metabolism (urea, adenosine, adenine, xanthine), nitrogen metabolism (glutamic acid, glycine), and malate-aspartate shuttle (malic acid, glutamic acid). Additionally, perturbations in β-oxidation and carnitine transferase (pentadecanoic acid, heptadecanoic acid) and glutamate transport and glutamine synthetase (urea, xylitol, adenine, adenosine, glycine, glutamic acid) were predicted. Metabolite changes in SIRT5-/- coincided with alterations in expression of amino acid (SLC7A5, SLC7A7) and glutamate (EAAT2) transport proteins as well as key enzymes in purine (PRPS1, PPAT), fatty acid (ACADS, HADHB), glutamine-glutamate (GAD1, GLUD1), and malate-aspartate shuttle (MDH1) metabolic pathways. Moreover, PKCε activation induced alternations in purine metabolites (urea, glutamine) that overlapped with putative SIRT5 pathways in WT but not in SIRT5-/- mice. Finally, we found that purine metabolism is a common metabolic pathway regulated by SIRT5, PKCε and ischemic preconditioning. These results implicate Sirt5 in the regulation of pathways central to brain metabolism, with links to ischemic tolerance. PMID: 29440987 [PubMed]

Related Articles Biofluid Metabolomics in Preterm Birth Research. Reprod Sci. 2018 Jan 01;:1933719118756748 Authors: Gil AM, Duarte D Abstract This article presents an account of the research carried out so far in the use of metabolomics to find biomarkers of preterm birth (PTB) in fetal, maternal, and newborn biofluids. Metabolomic studies have employed mainly nuclear magnetic resonance spectroscopy or mass spectrometry-based methodologies to analyze, on one hand, prenatal biofluids (amniotic fluid, maternal urine/maternal blood, cervicovaginal fluid) to identify predictive biomarkers of PTB, and on the other hand, biofluids collected at or after birth (amniotic fluid, umbilical cord blood, newborn urine, and newborn blood, maternal blood, or breast milk) to assess and follow up the health status of PTB babies. Besides advancing on the biochemical knowledge of PTB metabolism mainly during the in utero period and at birth, the work carried out has also helped to identify important requirements related to experimental design and analytical protocol that need to be addressed, if translation of these biomarkers to the clinic is to be envisaged. An outlook of possible future developments for the translation of laboratory results to the clinic is presented. PMID: 29439621 [PubMed - as supplied by publisher]

Related Articles Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis. Nutrients. 2018 Feb 10;10(2): Authors: Baldassarre ME, Di Mauro A, Tafuri S, Rizzo V, Gallone MS, Mastromarino P, Capobianco D, Laghi L, Zhu C, Capozza M, Laforgia N Abstract INTRODUCTION: To investigate the effectiveness and the safety of a probiotic-mixture (Vivomixx®, Visbiome®, DeSimone Formulation®; Danisco-DuPont, Madison, WI, USA) for the treatment of infantile colic in breastfed infants, compared with a placebo. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in exclusively breastfed infants with colic, randomly assigned to receive a probiotic-mixture or a placebo for 21 days. A structured diary of gastrointestinal events of the infants was given to the parents to complete. Samples of feces were also collected to evaluate microbial content and metabolome using fecal real-time polymerase chain reaction (qPCR) and Nuclear magnetic resonance (NMR)-based analysis. Study registered at ClinicalTrials.gov (NCT01869426). RESULTS: Fifty-three exclusively-breastfed infants completed three weeks of treatment with a probiotic-mixture (n = 27) or a placebo (n = 26). Infants receiving the probiotic-mixture had less minutes of crying per day throughout the study by the end of treatment period (68.4 min/day vs. 98.7 min/day; p = 0.001). A higher rate of infants from the probiotic-mixture group responded to treatment (defined by reduction of crying times of ≥50% from baseline), on day 14, 12 vs. 5 (p = 0.04) and on day 21, 26 vs. 17 (p = 0.001). A higher quality of life, assessed by a 10-cm visual analogue scale, was reported by parents of the probiotic-mixture group on day 14, 7.1 ± 1.2 vs. 7.7 ± 0.9 (p = 0.02); and on day 21, 6.7 ± 1.6 vs. 5.9 ± 1.0 (p = 0.001). No differences between groups were found regarding anthropometric data, bowel movements, stool consistency or microbiota composition. Probiotics were found to affect the fecal molecular profile. No adverse events were reported. CONCLUSIONS: Administration of a probiotic-mixture appears safe and reduces inconsolable crying in exclusively breastfed infants. PMID: 29439395 [PubMed - in process]

17 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 2018/02/14PubMed 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.

17 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 2018/02/14PubMed 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.

28 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 2018/02/13PubMed 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.

Airway Inflammation and Inflammatory Biomarkers. Semin Respir Crit Care Med. 2018 Feb;39(1):56-63 Authors: Lim HF, Nair P Abstract Severe asthma is a complex disease consisting of different endotypes with different inflammatory and clinicopathological characteristics due to the heterogeneity of immune responses and smooth muscle dysfunction. There is an unmet clinical need to develop and to validate biomarkers that can differentiate between the asthma endotypes and guide clinical management, particularly since the availability of biologicals directed against T2 cytokines. The presence of a "Th2 endotype" is currently assessed in clinical practice using markers, such as eosinophil count in sputum or blood, fraction of exhaled nitric oxide, and immunoglobulin E. Individually or in combination, they may help to identify, for example, if the dominant effector protein is interleukin (IL) 5, IL13, or IgE. There is no reliable marker of a "non-Th2 endotype" although sputum neutrophil may provide some indication. The unbiased systems biology approach to severe asthma endotyping which integrates omics signatures and clinical data using large cohort studies may provide more comprehensive information than simple cellular measurements. Novel imaging techniques, such as hyperpolarized noble gas magnetic resonance imaging and computed tomography parametric response maps and metabolomics profiling in breath and other body fluids are also being evaluated as potential biomarkers to guide therapy and to assess prognosis. PMID: 29427986 [PubMed - in process]

Quantitative analysis of core fucosylation of serum proteins in liver diseases by LC-MS-MRM. J Proteomics. 2018 Feb 07;: Authors: Ma J, Sanda M, Wei R, Zhang L, Goldman R Abstract Aberrant core fucosylation of proteins has been linked to liver diseases. In this study, we carried out multiple reaction monitoring (MRM) quantification of core fucosylated N-glycopeptides of serum proteins partially deglycosylated by a combination of endoglycosidases (endoF1, endoF2, and endoF3). To minimize variability associated with the preparatory steps, the analysis was performed without enrichment of glycopeptides or fractionation of serum besides the nanoRP chromatography. Specifically, we quantified core fucosylation of 22 N-glycopeptides derived from 17 proteins together with protein abundance of these glycoproteins in a cohort of 45 participants (15 disease-free control, 15 fibrosis and 15 cirrhosis patients) using a multiplex nanoUPLC-MS-MRM workflow. We find increased core fucosylation of 5 glycopeptides at the stage of liver fibrosis (i.e., N630 of serotransferrin, N107 of alpha-1-antitrypsin, N253 of plasma protease C1 inhibitor, N397 of ceruloplasmin, and N86 of vitronectin), increase of additional 6 glycopeptides at the stage of cirrhosis (i.e., N138 and N762 of ceruloplasmin, N354 of clusterin, N187 of hemopexin, N71 of immunoglobulin J chain, and N127 of lumican), while the degree of core fucosylation of 10 glycopeptides did not change. Interestingly, although we observe an increase in the core fucosylation at N86 of vitronectin in liver fibrosis, core fucosylation decreases on the N169 glycopeptide of the same protein. Our results demonstrate that the changes in core fucosylation are protein and site specific during the progression of fibrotic liver disease and independent of the changes in the quantity of N-glycoproteins. It is expected that the fully optimized multiplex LC-MS-MRM assay of core fucosylated glycopeptides will be useful for the serologic assessment of the fibrosis of liver. BIOLOGICAL SIGNIFICANCE: We have quantified the difference in core fucosylation among three comparison groups (healthy control, fibrosis and cirrhosis patients) using a sensitive and selective LC-MS-MRM method. Despite an overall increase in core fucosylation of many of the glycoproteins that we examined, core fucosylation changed in a protein- and site-specific manner. Moreover, increased and decreased fucosylation was observed on different N-glycopeptides of the same protein. Altered core fucosylation of N-glycopeptides might be used as an alternative serologic assay for the evaluation of fibrotic liver disease. PMID: 29427759 [PubMed - as supplied by publisher]

Mycotoxin biosynthesis and central metabolism are two interlinked pathways in Fusarium graminearum, as demonstrated by the extensive metabolic changes induced by caffeic acid exposure. Appl Environ Microbiol. 2018 Feb 02;: Authors: Atanasova-Penichon V, Legoahec L, Bernillon S, Deborde C, Maucourt M, Verdal-Bonnin MN, Pinson-Gadais L, Ponts N, Moing A, Richard-Forget F Abstract Fusarium graminearum is a major plant pathogen that causes devastating diseases of cereals and produces type B trichothecene mycotoxins (TCTB) in infected grains. A comprehensive understanding of the molecular and biochemical mechanisms underlying the regulation of TCTB biosynthesis is required for improving strategies to control the TCTB contamination of crops and ensuring that these strategies do not favor the production of other toxic metabolites by F. graminearum Elucidation of the association of TCTB biosynthesis with other central and specialized processes was the focus of this study. Combined 1H-NMR and LC-QTOF-MS analyses were used to compare the exo- and endo- metabolomes of F. graminearum grown in toxin-inducing and repressing caffeic acid-conditions. Ninety-five metabolites were putatively or unambiguously identified including 26 primary and 69 specialized metabolites. Our data demonstrated that the inhibition of TCTB production induced by caffeic acid exposure was associated with significant changes in secondary and primary metabolism of F. graminearum although the fungal growth was not affected. The main metabolic changes were an increase in the accumulation of several polyketides including toxic ones, alterations in the tricarboxylic organic acid cycle and modifications in the metabolism of several amino-acids and sugars. While these findings provide insights into the mechanisms that govern the inhibition of TCTB production by caffeic acid, they also demonstrate the interdependence between the biosynthetic pathway of TCTB and several primary and specialized metabolic pathways. These results provide further evidence of the multifaceted role of TCTB in the life cycle of F. graminearumIMPORTANCEFusarium graminearum is a major plant pathogen that causes devastating diseases of cereal crops and produces type B trichothecene (TCTB) mycotoxins in infected grains. The best way to restrict consumer exposure to TCTB is to limit their production before harvest, which requires increasing the knowledge on the mechanisms that regulate their biosynthesis. Using a metabolomics approach, we investigated the interconnection between the TCTB production and several fungal metabolic pathways. We demonstrated that alteration in the TCTB biosynthetic pathway can have a significant impact on other metabolic pathways including the biosynthesis of toxic polyketides and vice versa These findings open new avenues for identifying fungal targets for the design of molecules with anti-mycotoxin properties and therefore improving sustainable strategies to fight against F. graminearum-caused diseases. Our data further demonstrate that analyses should consider all fungal toxic metabolites rather than the targeted family of mycotoxins when assessing the efficacy of control strategies. PMID: 29427428 [PubMed - as supplied by publisher]

Ion-neutral Clustering of Bile Acids in Electrospray Ionization Across UPLC Flow Regimes. J Am Soc Mass Spectrom. 2018 Feb 09;: Authors: Brophy P, Broeckling CD, Murphy J, Prenni JE Abstract Bile acid authentic standards were used as model compounds to quantitatively evaluate complex in-source phenomenon on a UPLC-ESI-TOF-MS operated in the negative mode. Three different diameter columns and a ceramic-based microfluidic separation device were utilized, allowing for detailed descriptions of bile acid behavior across a wide range of flow regimes and instantaneous concentrations. A custom processing algorithm based on correlation analysis was developed to group together all ion signals arising from a single compound; these grouped signals produce verified compound spectra for each bile acid at each on-column mass loading. Significant adduction was observed for all bile acids investigated under all flow regimes and across a wide range of bile acid concentrations. The distribution of bile acid containing clusters was found to depend on the specific bile acid species, solvent flow rate, and bile acid concentration. Relative abundancies of each cluster changed non-linearly with concentration. It was found that summing all MS level (low collisional energy) ions and ion-neutral adducts arising from a single compound improves linearity across the concentration range (0.125-5 ng on column) and increases the sensitivity of MS level quantification. The behavior of each cluster roughly follows simple equilibrium processes consistent with our understanding of electrospray ionization mechanisms and ion transport processes occurring in atmospheric pressure interfaces. Graphical Abstract ᅟ. PMID: 29427066 [PubMed - as supplied by publisher]

Compositional marker in vivo reveals intramyocellular lipid turnover during fasting-induced lipolysis. Sci Rep. 2018 Feb 09;8(1):2750 Authors: Thankamony A, Kemp GJ, Koulman A, Bokii V, Savage DB, Boesch C, Hodson L, Dunger DB, Sleigh A Abstract Intramyocellular lipid (IMCL) is of particular metabolic interest, but despite many proton magnetic resonance spectroscopy (1H MRS) studies reporting IMCL content measured by the methylene (CH2) resonance signal, little is known about its composition. Here we validated IMCL CH3:CH2 ratio as a compositional marker using 1H MRS at short echo time, and investigated IMCL content and composition during a 28-hour fast in 24 healthy males. Increases in IMCL CH2 relative to the creatine and phosphocreatine resonance (Cr) at 3.0 ppm (an internal standard) correlated with circulating free fatty acid (FA) concentrations, supporting the concept of increased FA influx into IMCL. Significant decreases in IMCL CH3:CH2 ratio indicated a less unsaturated IMCL pool after fasting, and this compositional change related inversely to IMCL baseline composition, suggesting a selective efflux of unsaturated shorter-chain FA from the IMCL pool. This novel in vivo evidence reveals IMCL turnover during extended fasting, consistent with the concept of a flexible, responsive myocellular lipid store. There were also differences between soleus and tibialis anterior in basal IMCL composition and in response to fasting. We discuss the potential of this marker for providing insights into normal physiology and mechanisms of disease. PMID: 29426847 [PubMed - in process]

16 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 2018/02/10PubMed 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.

CRISPR/Cas9-mediated efficient targeted mutagenesis of RAS in Salvia miltiorrhiza. Phytochemistry. 2018 Jan 30;148:63-70 Authors: Zhou Z, Tan H, Li Q, Chen J, Gao S, Wang Y, Chen W, Zhang L Abstract The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated) system is a powerful genome editing tool that has been used in many species. In this study, we focused on the phenolic acid metabolic pathway in the traditional Chinese medicinal herb Salvia miltiorrhiza, using the CRISPR/Cas9 system to edit the rosmarinic acid synthase gene (SmRAS) in the water-soluble phenolic acid biosynthetic pathway. The single guide RNA (sgRNA) was designed to precisely edit the most important SmRAS gene, which was selected from 11 family members through a bioinformatics analysis. The sequencing results showed that the genomes of 50% of the transgenic regenerated hairy roots had been successfully edited. Five biallelic mutants, two heterozygous mutants and one homozygous mutant were obtained from 16 independent transgenic hairy root lines when the sgRNA was driven by the Arabidopsis U6 promoter, while no mutants were obtained from 13 independent transgenic hairy root lines when the sgRNA was driven by the rice U3 promoter. Subsequently, expression and metabolomics analysis showed that the contents of phenolic acids, including rosmarinic acid (RA) and lithospermic acid B, and the RAS expression level were decreased in the successfully edited hairy root lines, particularly in the homozygous mutants. In addition, the level of the RA precursor 3,4-dihydroxyphenyllactic acid clearly increased. These results indicated that the CRISPR/Cas9 system can be utilized to identify important genes in a gene family with the assistance of bioinformatics analysis and that this new technology is an efficient and specific tool for genome editing in S. miltiorrhiza. This new system presents a promising potential method to regulate plant metabolic networks and improve the quality of traditional Chinese medicinal herbs. PMID: 29421512 [PubMed - as supplied by publisher]

Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke. J Am Coll Cardiol. 2018 Feb 13;71(6):620-632 Authors: Holmes MV, Millwood IY, Kartsonaki C, Hill MR, Bennett DA, Boxall R, Guo Y, Xu X, Bian Z, Hu R, Walters RG, Chen J, Ala-Korpela M, Parish S, Clarke RJ, Peto R, Collins R, Li L, Chen Z, China Kadoorie Biobank Collaborative Group Abstract BACKGROUND: Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes. OBJECTIVES: This study sought to investigate the associations of plasma metabolic markers with risks of incident MI, ischemic stroke (IS), and intracerebral hemorrhage (ICH). METHODS: In a nested case-control study (912 MI, 1,146 IS, and 1,138 ICH cases, and 1,466 common control subjects) 30 to 79 years of age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 metabolic markers in baseline plasma samples. Logistic regression was used to estimate adjusted odds ratios (ORs) for a 1-SD higher metabolic marker. RESULTS: Very low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and IS. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with ICH. Cholesterol in large HDL was inversely associated with MI and IS (OR: 0.79 and 0.88, respectively), whereas cholesterol in small HDL was not (OR: 0.99 and 1.06, respectively). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for IS. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all 3 diseases. The 225 metabolic markers showed concordant associations between MI and IS, but not with ICH. CONCLUSIONS: Lipoproteins and lipids showed similar associations with MI and IS, but not with ICH. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several non-lipid-related metabolites associated with all 3 diseases. PMID: 29420958 [PubMed - in process]

High-pressure photon ionization time-of-flight mass spectrometry combined with dynamic purge-injection for rapid analysis of volatile metabolites in urine. Anal Chim Acta. 2018 May 30;1008:74-81 Authors: Wang Y, Hua L, Jiang J, Xie Y, Hou K, Li Q, Wu C, Li H Abstract Small molecule metabolites are widely used as biomarkers in the research field of metabolomics for disease diagnosis and exposure assessment. As a readily available biofluid containing plenty of volatile organic metabolites (VOMs), urine is ideal for non-invasive metabolomic analysis; however, there is still lack of rapid analysis method for VOMs in urine. Here we report a kind of rapid method for urine analysis by employing high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) combined with dynamic purge-injection. Various types of metabolites, such as ketones, alcohols, acids, sulfides, pyrroles and amines were detected directly by simple acidification or alkalization of urines. It is noteworthy that nitrogen-containing compounds, especially polar amines, could be ultrasensitively measured without any derivatization. The analytical capability of the direct HPPI-MS technique was demonstrated by analyzing five valuable metabolites, i.e., toluene, 2,5-dimethylpyrrole, trimethlyamine, styrene, and p-xylene, which exhibited relatively low limits of detection, wide linear range and satisfactory repeatability. Being highly sensitive and humidity-friendly, the whole analytical procedure is easily operated in less than 6 min. Interestingly, a new biomarker 2,5-dimethylpyrrole was exclusively found in the smoker's urine sample besides toluene. The work presents a novel tool for rapid nontarget disease biomarkers screening or target monitoring of specific compounds through the investigation of volatile metabolites in urine. PMID: 29420946 [PubMed - in process]