PubMed

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]

A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers. Genet Med. 2018 Feb 08;: Authors: Wangler MF, Hubert L, Donti TR, Ventura MJ, Miller MJ, Braverman N, Gawron K, Bose M, Moser AB, Jones RO, Rizzo WB, Sutton VR, Sun Q, Kennedy AD, Elsea SH Abstract PurposePeroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD) are metabolic diseases with multisystem manifestations. Individuals with PBD-ZSD exhibit impaired peroxisomal biochemical functions and have abnormal levels of peroxisomal metabolites, but the broader metabolic impact of peroxisomal dysfunction and the utility of metabolomic methods is unknown.MethodsWe studied 19 individuals with clinically and molecularly characterized PBD-ZSD. We performed both quantitative peroxisomal biochemical diagnostic studies in parallel with untargeted small molecule metabolomic profiling in plasma samples with detection of >650 named compounds.ResultsThe cohort represented intermediate to mild PBD-ZSD subjects with peroxisomal biochemical alterations on targeted analysis. Untargeted metabolomic profiling of these samples revealed elevations in pipecolic acid and long-chain lysophosphatidylcholines, as well as an unanticipated reduction in multiple sphingomyelin species. These sphingomyelin reductions observed were consistent across the PBD-ZSD samples and were rare in a population of >1,000 clinical samples. Interestingly, the pattern or "PBD-ZSD metabolome" was more pronounced in younger subjects suggesting studies earlier in life reveal larger biochemical changes.ConclusionUntargeted metabolomics is effective in detecting mild to intermediate cases of PBD-ZSD. Surprisingly, dramatic reductions in plasma sphingomyelin are a consistent feature of the PBD-ZSD metabolome. The use of metabolomics in PBD-ZSD can provide insight into novel biomarkers of disease.GENETICS in MEDICINE advance online publication, 8 February 2018; doi:10.1038/gim.2017.262. PMID: 29419819 [PubMed - as supplied by publisher]

Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica. Microb Cell. 2017 Nov 22;5(2):74-87 Authors: Bazurto JV, Dearth SP, Tague ED, Campagna SR, Downs DM Abstract In Salmonella enterica, aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a substrate of the AICAR transformylase/IMP cyclohydrolase (PurH) enzyme. When purH is eliminated in an otherwise wild-type strain, AICAR accumulates and indirectly inhibits synthesis of the essential coenzyme thiamine pyrophosphate (TPP). In this study, untargeted metabolomics approaches were used to i) corroborate previously defined metabolite changes, ii) define the global consequences of AICAR accumulation and iii) investigate the metabolic effects of mutations that restore thiamine prototrophy to a purH mutant. The data showed that AICAR accumulation led to an increase in the global regulator cyclic AMP (cAMP) and that disrupting central carbon metabolism could decrease AICAR and/or cAMP to restore thiamine synthesis. A mutant (icc) blocked in cAMP degradation that accumulated cAMP but had wild-type levels of AICAR was used to identify changes in the purH metabolome that were a direct result of elevated cAMP. Data herein describe the use of metabolomics to identify the metabolic state of mutant strains and probe the underlying mechanisms used by AICAR to inhibit thiamine synthesis. The results obtained provide a cautionary tale of using metabolite concentrations as the only data to define the physiological state of a bacterial cell. PMID: 29417056 [PubMed]

Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples. Oncotarget. 2018 Jan 05;9(2):2678-2696 Authors: More TH, RoyChoudhury S, Christie J, Taunk K, Mane A, Santra MK, Chaudhury K, Rapole S Abstract Invasive ductal carcinoma (IDC) is the most common type of breast cancer and the leading cause of breast cancer related mortality. In the present study, metabolomic profiles of 72 tissue samples and 146 serum samples were analysed using targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM/MS) and untargeted gas chromatography mass spectrometry (GC-MS) approaches. Combination of univariate and multivariate statistical treatment identified significant alterations of 42 and 32 metabolites in tissue and serum samples of IDC, respectively when compared to control. Some of the metabolite changes from tissue were also reflected in serum, indicating a bi-directional interaction of metabolites in IDC. Additionally, 8 tissue metabolites and 9 serum metabolites showed progressive change from control to benign to IDC suggesting their possible role in malignant transformation. We have identified a panel of three metabolites viz. tryptophan, tyrosine, and creatine in tissue and serum, which could be useful in screening of IDC subjects from both control and benign. The metabolomic alterations in IDC showed perturbations in purine and pyrimidine metabolism, amino sugar metabolism, amino acid metabolism, fatty acid biosynthesis etc. Comprehensively, this study provides valuable insights into metabolic adaptations of IDC, which can help to identify diagnostic markers as well as potential therapeutic targets. PMID: 29416801 [PubMed]

Patients with Treatment-Requiring Chronic Graft versus Host Disease after Allogeneic Stem Cell Transplantation Have Altered Metabolic Profiles due to the Disease and Immunosuppressive Therapy: Potential Implication for Biomarkers. Front Immunol. 2017;8:1979 Authors: Reikvam H, Grønningsæter IS, Mosevoll KA, Lindås R, Hatfield K, Bruserud Ø Abstract Chronic graft versus host disease (cGVHD) is a common long-term complication after allogeneic hematopoietic stem cell transplantation. The objective of our study was to compare the metabolic profiles for allotransplant recipients and thereby identify metabolic characteristics of patients with treatment-requiring cGVHD. The study included 51 consecutive patients (29 men and 22 women; median age: 44 years, range: 15-66 years) transplanted with peripheral blood stem cells derived from human leukocyte antigen-matched family donors. All serum samples investigated by global metabolomic profiling were collected approximately 1 year posttransplant (median 358 days). Thirty-one of the 51 patients (61%) had cGVHD 1 year posttransplant. The affected organs were (number of patients) liver/bile duct (23), eyes (15), gastrointestinal tract (14), skin (13), mouth (10), lungs (3), and urogenital tract (1). We compared the metabolic profile for patients with and without cGVHD, and a Random Forrest Classification Analysis then resulted in 75% accuracy in differentiating the two groups. The 30 top-ranked metabolites from this comparison included increased levels of bile acids, several metabolites from the cytokine-responsive kynurenine pathway for tryptophan degradation, pro-inflammatory lipid metabolites, phenylalanine and tyrosine metabolites derived from the gut microbial flora, and metabolites reflecting increased oxidative stress. However, nine of these 30 top-ranked metabolites were probably altered due to cyclosporine or steroid treatment, and we therefore did a hierarchical clustering analysis including all 51 patients but only based on the other 21 cGVHD-specific metabolites. This analysis identified three patient subsets: one cluster included mainly patients without cGVHD and had generally low metabolite levels; another cluster included mainly patients with cGVHD (most patients with at least three affected organs) and high metabolite levels, and the last intermediate group including cGVHD patients with limited organ involvement. We conclude that allotransplant recipients with cGVHD have an altered metabolic profile caused both by the disease and its immunosuppressive treatment. PMID: 29416533 [PubMed]

Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm. Metabolomics. 2018;14(1):10 Authors: Luck M, Schmitt C, Talbi N, Gouya L, Caradeuc C, Puy H, Bertho G, Pallet N Abstract Introduction: Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease. Objectives: In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses. Methods: Urine 1H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained. Results: Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients. Conclusion: These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism. PMID: 29416446 [PubMed]

Evaluation of autophagy inducers in epithelial cells carrying the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator CFTR. Cell Death Dis. 2018 Feb 07;9(2):191 Authors: Zhang S, Stoll G, Pedro JMBS, Sica V, Sauvat A, Obrist F, Kepp O, Li Y, Maiuri L, Zamzami N, Kroemer G Abstract Cystic Fibrosis (CF) due to the ΔF508 mutation of cystic fibrosis transmembrane conductance regulator (CFTR) can be treated with a combination of cysteamine and Epigallocatechin gallate (EGCG). Since ECGC is not a clinically approved drug, we attempted to identify other compounds that might favourably interact with cysteamine to induce autophagy and thus rescuing the function of ΔF508 CFTR as a chloride channel in the plasma membrane. For this, we screened a compound library composed by chemically diverse autophagy inducers for their ability to enhance autophagic flux in the presence of cysteamine. We identified the antiarrhythmic Ca2+ channel blocker amiodarone, as an FDA-approved drug having the property to cooperate with cysteamine to stimulate autophagy in an additive manner. Amiodarone promoted the re-expression of ΔF508 CFTR protein in the plasma membrane of respiratory epithelial cells. Hence, amiodarone might be yet another compound for the etiological therapy of CF in patients bearing the ΔF508 CFTR mutation. PMID: 29415993 [PubMed - in process]

Related Articles Chromatographic Methods to Evaluate Nutritional Quality in Oat. Methods Mol Biol. 2017;1536:115-125 Authors: Montilla-Bascón G, Broeckling CD, Hoekenga OA, Prats E, Sorrells M, Isidro-Sánchez J Abstract Oats (A. sativa L.) have an important and positive role in human diet and health. The health benefits of oats are attributed to its multifunctional characteristic and nutritional profile, being an important source of soluble dietary fiber, well-balanced proteins, unsaturated fatty acids, vitamins, essential minerals, and a good source of natural antioxidants. These antioxidants include the avenanthramides (Avns) and avenalumic acids, which are unique to oats among cereals. High-performance liquid chromatography allows a simultaneous quantification of free amino acids and biogenic amines in oat samples as their OPA/FMOC-CL (o-phthalaldehyde/9-fluorenylmethoxycarbonyl chloride) derivatives. In addition, an ultra-performance liquid chromatography/mass spectrometry method was developed to quantify and characterize avenanthramides contained in oat samples. PMID: 28132146 [PubMed - indexed for MEDLINE]

Related Articles Serum Metabolomic Profiles Identify ER-Positive Early Breast Cancer Patients at Increased Risk of Disease Recurrence in a Multicenter Population. Clin Cancer Res. 2017 Mar 15;23(6):1422-1431 Authors: Hart CD, Vignoli A, Tenori L, Uy GL, Van To T, Adebamowo C, Hossain SM, Biganzoli L, Risi E, Love RR, Luchinat C, Di Leo A Abstract Purpose: Detecting signals of micrometastatic disease in patients with early breast cancer (EBC) could improve risk stratification and allow better tailoring of adjuvant therapies. We previously showed that postoperative serum metabolomic profiles were predictive of relapse in a single-center cohort of estrogen receptor (ER)-negative EBC patients. Here, we investigated this further using preoperative serum samples from ER-positive, premenopausal women with EBC who were enrolled in an international phase III trial.Experimental Design: Proton nuclear magnetic resonance (NMR) spectroscopy of 590 EBC samples (319 with relapse or ≥6 years clinical follow-up) and 109 metastatic breast cancer (MBC) samples was performed. A Random Forest (RF) classification model was built using a training set of 85 EBC and all MBC samples. The model was then applied to a test set of 234 EBC samples, and a risk of recurrence score was generated on the basis of the likelihood of the sample being misclassified as metastatic.Results: In the training set, the RF model separated EBC from MBC with a discrimination accuracy of 84.9%. In the test set, the RF recurrence risk score correlated with relapse, with an AUC of 0.747 in ROC analysis. Accuracy was maximized at 71.3% (sensitivity, 70.8%; specificity, 71.4%). The model performed independently of age, tumor size, grade, HER2 status and nodal status, and also of Adjuvant! Online risk of relapse score.Conclusions: In a multicenter group of EBC patients, we developed a model based on preoperative serum metabolomic profiles that was prognostic for disease recurrence, independent of traditional clinicopathologic risk factors. Clin Cancer Res; 23(6); 1422-31. ©2017 AACR. PMID: 28082280 [PubMed - indexed for MEDLINE]

Related Articles Mining Microbial Signals for Enhanced Biodiscovery of Secondary Metabolites. Methods Mol Biol. 2017;1539:287-300 Authors: Reen FJ, Gutiérrez-Barranquero JA, O'Gara F Abstract The advent of metagenomics based biodiscovery has provided researchers with previously unforeseen access to the rich tapestry of natural bioactivity that exists in the biosphere. Unhindered by the "culturable bottleneck" that has severely limited the translation of the genetic potential that undoubtedly exists in nature, metagenomics nonetheless requires ongoing technological developments to maximize its efficacy and applicability to the discovery of new chemical entities.Here we describe methodologies for the detection and isolation of quorum sensing (QS) signal molecules from metagenomics libraries. QS signals have already shown considerable potential for the activation and "awakening" of biosynthetic gene clusters, bridging the existing divide between the natural product repertoire and the natural biosynthetic biodiversity hinted at by nature's blueprint. The QS pipeline from high-throughput robotics to functional screening and hit isolation is detailed, highlighting the multidisciplinary nature of progressive biodiscovery programs. PMID: 27900698 [PubMed - indexed for MEDLINE]

Related Articles Retrospective analysis of pesticide metabolites in urine using liquid chromatography coupled to high-resolution mass spectrometry. Talanta. 2016 Nov 01;160:547-555 Authors: López A, Dualde P, Yusà V, Coscollà C Abstract A comprehensive retrospective analysis of pesticide metabolites in urine was developed, using liquid chromatography coupled to Orbitrap high-resolution mass spectrometry (UHPLC-HRMS) that includes both post-run target (suspect screening) and non-target screening. An accurate-mass database comprising 263 pesticide metabolites was built and used for the post-run screening analysis. For non-target analysis, a "fragmentation-degradation" relationship strategy was selected. The proposed methodology was applied to 49 real urine samples from pregnant women. In the post-target analysis 26 pesticide metabolites were tentatively identified, 8 of which (2-diethylamino-6-methyl-pyrimidinol; 3-ketocarbofuran; 4,6-dimethoxy-2-pyrimidinamine; 4-hydroxy-2-isporopyl-6-methylpyrimidine; diethyl malate; diethyl maleate; N-(2-Ethyl-6-methylphenyl)-2-hydroxyacetamide and propachlor oxanilic acid ) were confirmed using analytical standards. Likewise, one unknown degradation product, methyl-N-phenylcarbamate was elucidated in the non-target screening. Finally, the real urine samples were grouped according to their origin applying a metabolomic approach. PMID: 27591649 [PubMed - indexed for MEDLINE]

31 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 2018/02/08PubMed 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.