Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

METABOLISM OF PSILOCYBIN AND PSILOCIN: CLINICAL AND FORENSIC TOXICOLOGICAL RELEVANCE.

Thu, 12/01/2017 - 13:47
Related Articles METABOLISM OF PSILOCYBIN AND PSILOCIN: CLINICAL AND FORENSIC TOXICOLOGICAL RELEVANCE. Drug Metab Rev. 2017 Jan 11;:1-21 Authors: Dinis-Oliveira RJ Abstract Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis. PMID: 28074670 [PubMed - as supplied by publisher]

Transcription factor Xpp1 is a switch between primary and secondary fungal metabolism.

Thu, 12/01/2017 - 13:47
Related Articles Transcription factor Xpp1 is a switch between primary and secondary fungal metabolism. Proc Natl Acad Sci U S A. 2017 Jan 10;: Authors: Derntl C, Kluger B, Bueschl C, Schuhmacher R, Mach RL, Mach-Aigner AR Abstract Fungi can produce a wide range of chemical compounds via secondary metabolism. These compounds are of major interest because of their (potential) application in medicine and biotechnology and as a potential source for new therapeutic agents and drug leads. However, under laboratory conditions, most secondary metabolism genes remain silent. This circumstance is an obstacle for the production of known metabolites and the discovery of new secondary metabolites. In this study, we describe the dual role of the transcription factor Xylanase promoter binding protein 1 (Xpp1) in the regulation of both primary and secondary metabolism of Trichoderma reesei Xpp1 was previously described as a repressor of xylanases. Here, we provide data from an RNA-sequencing analysis suggesting that Xpp1 is an activator of primary metabolism. This finding is supported by our results from a Biolog assay determining the carbon source assimilation behavior of an xpp1 deletion strain. Furthermore, the role of Xpp1 as a repressor of secondary metabolism is shown by gene expression analyses of polyketide synthases and the determination of the secondary metabolites of xpp1 deletion and overexpression strains using an untargeted metabolomics approach. The deletion of Xpp1 resulted in the enhanced secretion of secondary metabolites in terms of diversity and quantity. Homologs of Xpp1 are found among a broad range of fungi, including the biocontrol agent Trichoderma atroviride, the plant pathogens Fusarium graminearum and Colletotrichum graminicola, the model organism Neurospora crassa, the human pathogen Sporothrix schenckii, and the ergot fungus Claviceps purpurea. PMID: 28074041 [PubMed - as supplied by publisher]

Redox crisis underlies conditional light-dark lethality in cyanobacterial mutants that lack the circadian regulator, RpaA.

Thu, 12/01/2017 - 13:47
Related Articles Redox crisis underlies conditional light-dark lethality in cyanobacterial mutants that lack the circadian regulator, RpaA. Proc Natl Acad Sci U S A. 2017 Jan 10;: Authors: Diamond S, Rubin BE, Shultzaberger RK, Chen Y, Barber CD, Golden SS Abstract Cyanobacteria evolved a robust circadian clock, which has a profound influence on fitness and metabolism under daily light-dark (LD) cycles. In the model cyanobacterium Synechococcus elongatus PCC 7942, a functional clock is not required for diurnal growth, but mutants defective for the response regulator that mediates transcriptional rhythms in the wild-type, regulator of phycobilisome association A (RpaA), cannot be cultured under LD conditions. We found that rpaA-null mutants are inviable after several hours in the dark and compared the metabolomes of wild-type and rpaA-null strains to identify the source of lethality. Here, we show that the wild-type metabolome is very stable throughout the night, and this stability is lost in the absence of RpaA. Additionally, an rpaA mutant accumulates excessive reactive oxygen species (ROS) during the day and is unable to clear it during the night. The rpaA-null metabolome indicates that these cells are reductant-starved in the dark, likely because enzymes of the primary nighttime NADPH-producing pathway are direct targets of RpaA. Because NADPH is required for processes that detoxify ROS, conditional LD lethality likely results from inability of the mutant to activate reductant-requiring pathways that detoxify ROS when photosynthesis is not active. We identified second-site mutations and growth conditions that suppress LD lethality in the mutant background that support these conclusions. These results provide a mechanistic explanation as to why rpaA-null mutants die in the dark, further connect the clock to metabolism under diurnal growth, and indicate that RpaA likely has important unidentified functions during the day. PMID: 28074036 [PubMed - as supplied by publisher]

Metabolic Profiling in Formalin-Fixed and Paraffin Embedded Prostate Cancer Tissues.

Thu, 12/01/2017 - 13:47
Related Articles Metabolic Profiling in Formalin-Fixed and Paraffin Embedded Prostate Cancer Tissues. Mol Cancer Res. 2017 Jan 10;: Authors: Cacciatore S, Zadra G, Bango C, Penney KL, Tyekucheva S, Yanes O, Loda M Abstract Metabolite profiling has significantly contributed to a deeper understanding of the biochemical metabolic networks and pathways in cancer cells. Metabolomics-based biomarker discovery would greatly benefit from the ability to interrogate retrospective annotated clinical specimens archived as formalin-fixed paraffin-embedded (FFPE) material. Mass spectrometry-based metabolomic analysis was performed in matched frozen and FFPE human prostate cancers as well as isogenic prostate cancer cell lines. A total of 352 and 460 metabolites were profiled in human tissues and cell lines, respectively. Classes and physical-chemical characteristics of the metabolites preserved in FFPE material were characterized and related to their preservation or loss following fixation and embedding. Metabolite classes were differentially preserved in archival FFPE tissues, regardless of the age of the block, compared to matched frozen specimen, ranging from maximal preservation of fatty acids (78%) to loss of the majority of peptides and steroids. Generally, FFPE samples showed a decrease of metabolites with functional groups, such as carboxamide. As an adjunct technique, metabolic profiles were also obtained in situ from FFPE tissue sections where metabolites were extracted in a manner that preserves tissue architecture. Despite the fact that selected metabolites were not retained after processing, global metabolic profiles obtained from FFPE can be used to predict biological states and study biological pathways. These results pave the way for metabolomics-based biomarker discovery/validation utilizing retrospective and clinically annotated FFPE collections. IMPLICATIONS: Metabolic profiles can be performed in archival tissue and may be used to complement other profiling methods such as gene expression for biomarker discovery or pathway analysis in the assessment of biologic states. PMID: 28074002 [PubMed - as supplied by publisher]

Recent developments in software tools for high-throughput in vitro ADME support with high-resolution MS.

Thu, 12/01/2017 - 13:47
Related Articles Recent developments in software tools for high-throughput in vitro ADME support with high-resolution MS. Bioanalysis. 2016 Aug;8(16):1723-33 Authors: Paiva A, Shou WZ Abstract The last several years have seen the rapid adoption of the high-resolution MS (HRMS) for bioanalytical support of high throughput in vitro ADME profiling. Many capable software tools have been developed and refined to process quantitative HRMS bioanalysis data for ADME samples with excellent performance. Additionally, new software applications specifically designed for quan/qual soft spot identification workflows using HRMS have greatly enhanced the quality and efficiency of the structure elucidation process for high throughput metabolite ID in early in vitro ADME profiling. Finally, novel approaches in data acquisition and compression, as well as tools for transferring, archiving and retrieving HRMS data, are being continuously refined to tackle the issue of large data file size typical for HRMS analyses. PMID: 27487387 [PubMed - indexed for MEDLINE]

Metabonomic study of the fruits of Alpinia oxyphylla as an effective treatment for chronic renal injury in rats.

Thu, 12/01/2017 - 13:47
Related Articles Metabonomic study of the fruits of Alpinia oxyphylla as an effective treatment for chronic renal injury in rats. J Pharm Biomed Anal. 2016 May 30;124:236-45 Authors: Li YH, Tan YF, Cai HD, Zhang JQ Abstract Alpinia oxyphylla (Zingiberaceae) is a well-known medicinal plant. Its fruit ("Yi-Zhi-Ren" in Chinese) is used as an anti-diuretic and traditionally used for the treatment of enuresis and reduce urination. Chronic kidney disease (CKD) is a disease with the characteristic of the slowly loss of kidney function and has a prevalence of up to 7-10% in adults. Recent advances in its etiology and pathogenesis are providing more speculative hypotheses focused on integral systems. Using a UPLC-QTOF-MS/MS-based metabolomic platform, we explored the changes of metabolic profiling in plasma/urine simultaneously between chronic kidney disease (CKD) induced from adenine excess and the protective effects of A. oxyphylla extract (AOE). The total twenty-one metabolites (twelve in urine and nine in plasma), up-regulated or down-regulated, were identified and contributed to CKD progress. Among these biomarkers, agmatine, CAMP, 7-methylguanine, hippuric acid, indoxyl sulfate, asparagines, kynurenic acid and p-cresol sulfate were restored back to the control-like level after the treatment of AOE (p<0.05 or 0.01), These findings may be promising to yield a valuable insight into the pathophysiology of CKD and serve as characteristics to explain the mechanisms of AOE. PMID: 26966897 [PubMed - indexed for MEDLINE]

Analytical strategies to assess the functional metabolome of vitamin E.

Thu, 12/01/2017 - 13:47
Related Articles Analytical strategies to assess the functional metabolome of vitamin E. J Pharm Biomed Anal. 2016 May 30;124:399-412 Authors: Torquato P, Ripa O, Giusepponi D, Galarini R, Bartolini D, Wallert M, Pellegrino R, Cruciani G, Lorkowski S, Birringer M, Mazzini F, Galli F Abstract After more than 90 years from its discovery and thousands of papers published, the physiological roles of vitamin E (tocopherols and tocotrienols) are still not fully clarified. In the last few decades, the enzymatic metabolism of this vitamin has represented a stimulating subject of research. Its elucidation has opened up new horizons to the interpretation of the biological function of that class of molecules. The identification of specific properties for some of the physiological metabolites and the definition of advanced analytical techniques to assess the human metabolome of this vitamin in vivo, have paved the way to a series of hypotheses on the functional implications that this metabolism may have far beyond its catabolic role. The present review collects the available information on the most relevant analytical strategies employed to assess the status and metabolism of vitamin E in humans as well as in other model systems. A particular focus is dedicated to the analytical methods used to measure vitamin E metabolites, and particularly long-chain metabolites, in biological fluids and tissues. Preliminary information on a new LC-APCI-MS/MS method to measure these metabolites in human serum is reported. PMID: 26947319 [PubMed - indexed for MEDLINE]

1H NMR Metabolomics Reveals Association of High Expression of Inositol 1, 4, 5 Trisphosphate Receptor and Metabolites in Breast Cancer Patients.

Wed, 11/01/2017 - 13:27
1H NMR Metabolomics Reveals Association of High Expression of Inositol 1, 4, 5 Trisphosphate Receptor and Metabolites in Breast Cancer Patients. PLoS One. 2017;12(1):e0169330 Authors: Singh A, Sharma RK, Chagtoo M, Agarwal G, George N, Sinha N, Godbole MM Abstract 1H NMR is used to detect alterations in metabolites and their linkage to metabolic processes in a number of pathological conditions including breast cancer. Inositol 1, 4, 5 trisphosphate (IP3R) receptor is an intracellular calcium channel known to regulate metabolism and cellular bioenergetics. Its expression is up regulated in a number of cancers. However, its linkage to metabolism in disease conditions has not been evaluated. This study was designed to determine the association if any, of these metabolites with altered expression of IP3R in breast cancer. We used 1H NMR to identify metabolites in the serum of breast cancer patients (n = 27) and performed Real-time Polymerase Chain Reaction analysis for quantifying the expression of IP3R type 3 and type 2 in tissues from breast cancer patients (n = 40). Principal Component Analysis (PCA) and Partial Least Square-Discriminant Analysis (PLS-DA) clearly distinguished patients with high/low IP3R expression from healthy subjects. The present study revealed high expression of IP3R type 2 and type 3 in human breast tumor tissue compared to adjacent non-tumorous tissue. Moreover, patients with ≥ 2-fold increase in IP3R (high IP3R group) had significantly higher concentration of metabolic intermediates compared to those with < 2-fold increase in IP3R (low IP3R group). We observed an increase in lipoprotein content and the levels of metabolites like lactate, lysine and alanine and a decrease in the levels of pyruvate and glucose in serum of high IP3R group patients when compared to those in healthy subjects. Receiver operating characteristic (ROC) curve analysis was performed to show the clinical utility of metabolites. In addition to the human studies, functional relevance of IP3Rs in causing metabolic disruption was observed in MCF-7 and MDA MB-231 cells. Results from our studies bring forth the importance of metabolic (or metabolomics) profiling of serum by 1H NMR in conjunction with tissue expression studies for characterizing breast cancer patients. The results from this study provide new insights into relationship of breast cancer metabolites with IP3R. PMID: 28072864 [PubMed - in process]

Protective Effects of Dexrazoxane against Doxorubicin-Induced Cardiotoxicity: A Metabolomic Study.

Wed, 11/01/2017 - 13:27
Protective Effects of Dexrazoxane against Doxorubicin-Induced Cardiotoxicity: A Metabolomic Study. PLoS One. 2017;12(1):e0169567 Authors: QuanJun Y, GenJin Y, LiLi W, YongLong H, Yan H, Jie L, JinLu H, Jin L, Run G, Cheng G Abstract Cardioprotection of dexrazoxane (DZR) against doxorubicin (DOX)-induced cardiotoxicity is contentious and the indicator is controversial. A pairwise comparative metabolomics approach was used to delineate the potential metabolic processes in the present study. Ninety-six BALB/c mice were randomly divided into two supergroups: tumor and control groups. Each supergroup was divided into control, DOX, DZR, and DOX plus DZR treatment groups. DOX treatment resulted in a steady increase in 5-hydroxylysine, 2-hydroxybutyrate, 2-oxoglutarate, 3-hydroxybutyrate, and decrease in glucose, glutamate, cysteine, acetone, methionine, asparate, isoleucine, and glycylproline.DZR treatment led to increase in lactate, 3-hydroxybutyrate, glutamate, alanine, and decrease in glucose, trimethylamine N-oxide and carnosine levels. These metabolites represent potential biomarkers for early prediction of cardiotoxicity of DOX and the cardioprotective evaluation of DZR. PMID: 28072830 [PubMed - in process]

Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast.

Wed, 11/01/2017 - 13:27
Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast. PLoS Comput Biol. 2017 Jan;13(1):e1005297 Authors: Gonçalves E, Raguz Nakic Z, Zampieri M, Wagih O, Ochoa D, Sauer U, Beltrao P, Saez-Rodriguez J Abstract Cells react to extracellular perturbations with complex and intertwined responses. Systematic identification of the regulatory mechanisms that control these responses is still a challenge and requires tailored analyses integrating different types of molecular data. Here we acquired time-resolved metabolomics measurements in yeast under salt and pheromone stimulation and developed a machine learning approach to explore regulatory associations between metabolism and signal transduction. Existing phosphoproteomics measurements under the same conditions and kinase-substrate regulatory interactions were used to in silico estimate the enzymatic activity of signalling kinases. Our approach identified informative associations between kinases and metabolic enzymes capable of predicting metabolic changes. We extended our analysis to two studies containing transcriptomics, phosphoproteomics and metabolomics measurements across a comprehensive panel of kinases/phosphatases knockouts and time-resolved perturbations to the nitrogen metabolism. Changes in activity of transcription factors, kinases and phosphatases were estimated in silico and these were capable of building predictive models to infer the metabolic adaptations of previously unseen conditions across different dynamic experiments. Time-resolved experiments were significantly more informative than genetic perturbations to infer metabolic adaptation. This difference may be due to the indirect nature of the associations and of general cellular states that can hinder the identification of causal relationships. This work provides a novel genome-scale integrative analysis to propose putative transcriptional and post-translational regulatory mechanisms of metabolic processes. PMID: 28072816 [PubMed - in process]

Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR-based metabolomics analysis.

Wed, 11/01/2017 - 13:27
Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR-based metabolomics analysis. J Neurochem. 2017 Jan 10;: Authors: Cruz T, Gleizes M, Balayssac S, Mornet E, Marsal G, Millán JL, Malet-Martino M, Nowak LG, Gilard V, Fonta C Abstract Tissue Nonspecific Alkaline Phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However TNAP's role in the nervous system remains poorly understood. In order to investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue. For this purpose we used (1) H- and (31) P NMR to analyze the brain metabolome of Alpl (Akp2) mice null for TNAP function, a well-described model of infantile HPP. Among 39 metabolites identified in brain extracts of one week-old animals, 8 displayed significantly different concentration in Akp2(-/-) compared to Akp2(+/+) and Akp2(+/-) mice: cystathionine, adenosine, GABA, methionine, histidine, 3-methylhistidine, N-acetylaspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG), with cystathionine and adenosine levels displaying the strongest alteration. These metabolites identify several biochemical processes that directly or indirectly involve TNAP function, in particular through the regulation of ecto-nucleotide levels and of pyridoxal phosphate-dependent enzymes. Some of these metabolites are involved in neurotransmission (GABA, adenosine), in myelin synthesis (NAA, NAAG), and in the methionine cycle and transsulfuration pathway (cystathionine, methionine). Their disturbances may contribute to the neurodevelopmental and neurological phenotype of HPP. This article is protected by copyright. All rights reserved. PMID: 28072448 [PubMed - as supplied by publisher]

Plasma Amino Acid Profile in Patients with Aortic Dissection.

Wed, 11/01/2017 - 13:27
Plasma Amino Acid Profile in Patients with Aortic Dissection. Sci Rep. 2017 Jan 10;7:40146 Authors: Wang L, Liu S, Yang W, Yu H, Zhang L, Ma P, Wu P, Li X, Cho K, Xue S, Jiang B Abstract Aortic dissection (AD), a severe cardiovascular disease with the characteristics of high mortality, is lack of specific clinical biomarkers. In order to facilitate the diagnosis of AD, we investigated plasma amino acid profile through metabolomics approach. Total 33 human subjects were enrolled in the study: 11 coronary heart disease (CHD) patients without aortic lesion and 11 acute AD and 11 chronic AD. Amino acids were identified in plasma using liquid chromatography and mass spectrometry (LC-MS/MS), and were further subjected to multiple logistic regression analysis. The score plots of principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) showed clear discrimination of CHD patients with AD, acute AD or chronic AD patients, respectively. The contents of histidine, glycine, serine, citrate, ornithine, hydroxyproline, proline and sarcosine were significant different in acute AD patients comparing with CHD patients. The levels of citrate, GABA, glutamate and cysteine were significant different in chronic AD patients comparing with CHD patients. The contents of glutamate and phenylalanine were significant changed in acute AD patients comparing with chronic AD patients. Plasma aminograms were significantly altered in patients with AD comparing with CHD, especially in acute AD, suggesting amino acid profile is expected to exploit a novel, non-invasive, objective diagnosis for AD. PMID: 28071727 [PubMed - in process]

NMR-based metabolomics reveals brain region-specific metabolic alterations in streptozotocin-induced diabetic rats with cognitive dysfunction.

Wed, 11/01/2017 - 13:27
Related Articles NMR-based metabolomics reveals brain region-specific metabolic alterations in streptozotocin-induced diabetic rats with cognitive dysfunction. Metab Brain Dis. 2017 Jan 09;: Authors: Zheng H, Lin Q, Wang D, Xu P, Zhao L, Hu W, Bai G, Yan Z, Gao H Abstract Diabetes mellitus (DM) can result in cognitive dysfunction, but its potential metabolic mechanisms remain unclear. In the present study, we analyzed the metabolite profiling in eight different brain regions of the normal rats and the streptozotocin (STZ)-induced diabetic rats accompanied by cognitive dysfunction using a (1)H NMR-based metabolomic approach. A mixed linear model analysis was performed to assess the effects of DM, brain region and their interaction on metabolic changes. We found that different brain regions in rats displayed significant metabolic differences. In addition, the hippocampus was more susceptible to DM compared with other brain regions in rats. More interestingly, significant interaction effects of DM and brain region were observed on alanine, creatine/creatine-phosphate, lactate, succinate, aspartate, glutamate, glutamine, γ-aminobutyric acid, glycine, choline, N-acetylaspartate, myo-inositol and taurine. Based on metabolic pathway analysis, we speculate that cognitive dysfunction in the STZ-induced diabetic rats may be associated with brain region-specific metabolic alterations involving energy metabolism, neurotransmitters, membrane metabolism and osmoregulation. PMID: 28070703 [PubMed - as supplied by publisher]

Stable isotope profiles reveal active production of VOCs from human-associated microbes.

Wed, 11/01/2017 - 13:27
Related Articles Stable isotope profiles reveal active production of VOCs from human-associated microbes. J Breath Res. 2017 Jan 10;: Authors: Phan J, Meinardi S, Barletta B, Blake D, Whiteson K Abstract Volatile organic compounds (VOCs) measured from exhaled breath have great promise for the diagnosis of bacterial infections. However, determining human or microbial origin of VOCs detected in breath remains a great challenge. For example, the microbial fermentation product 2,3-butanedione was recently found in the breath of CF patients; parallel culture-independent metagenomic sequencing of the same samples revealed that Streptococcus and Rothia spp. have the genetic capacity to produce 2,3-butanedione. To investigate whether the genetic capacity found in metagenomes translates to bacterial production of a VOC of interest such as 2,3-butanedione, we fed stable isotopes to three bacterial strains isolated from Cystic Fibrosis (CF) patients: two Gram-positive bacteria, Rothia mucilaginosa and Streptococcus salivarius, and a dominant opportunistic Gram-negative pathogen, Pseudomonas aeruginosa. Culture headspaces were collected and analyzed using a gas chromatographic system to quantify the abundance of VOCs of interest; mass spectroscopy was used to determine whether the stable isotope label had been incorporated. Our results show that R. mucilaginosa and S. salivarius consumed D-Glucose-13C6 to produce labeled 2,3-butanedione. R. mucilaginosa and S. salivarius also produced labeled acetaldehyde and ethanol when grown with 2H2O. Additionally, we find that P. aeruginosa growth and dimethyl sulfide production are increased when exposed to lactic acid in culture. These results highlight the importance VOCs produced by P. aeruginosa, R. mucilaginosa, and S. salivarius as nutrients and signals in microbial communities, and as potential biomarkers in a CF infection. PMID: 28070022 [PubMed - as supplied by publisher]

Analytes related to erythrocyte metabolism are reliable biomarkers for preanalytical error due to delayed plasma processing in metabolomics studies.

Wed, 11/01/2017 - 13:27
Related Articles Analytes related to erythrocyte metabolism are reliable biomarkers for preanalytical error due to delayed plasma processing in metabolomics studies. Clin Chim Acta. 2017 Jan 06;: Authors: Jain M, Kennedy AD, Elsea SH, Miller MJ Abstract INTRODUCTION: Delaying plasma separation after phlebotomy (processing delay) can cause perturbations of numerous small molecule analytes. This poses a major challenge to the clinical application of metabolomics analyses. We define the analyte changes that occur during processing delays and generate a model for the post hoc detection of this preanalytical error. METHODS: Using an untargeted metabolomics platform we analyzed EDTA-preserved plasma specimens harvested after processing delays lasting from minutes to days. Identified biomarkers were tested on (i) a test-set of samples exposed to either minimal (n=28) or long delays (n=40) and (ii) samples collected in a clinical setting for metabolomics analysis (n=141). RESULTS: A total of 149 of 803 plasma analytes changed significantly during processing delays lasting 0-20h. Biomarkers related to erythrocyte metabolism, e.g., 5-oxoproline, lactate, and an ornithine/arginine ratio, were the strongest predictors of plasma separation delays, providing 100% diagnostic accuracy in the test set.Together these biomarkers could accurately predict processing delays >2h in a pilot study and we found evidence of sample mishandling in 4 of 141 clinically derived specimens. CONCLUSIONS: Due to the widespread effects of processing delays, we propose that erythrocyte metabolism creates a reproducible signal that can identify mishandled specimens in metabolomics studies. PMID: 28069401 [PubMed - as supplied by publisher]

Proteomics as an innovative tool to investigate frontotemporal disorders.

Wed, 11/01/2017 - 13:27
Related Articles Proteomics as an innovative tool to investigate frontotemporal disorders. Proteomics Clin Appl. 2016 Apr;10(4):457-69 Authors: Agresta AM, De Palma A, Bardoni A, Salvini R, Iadarola P, Mauri PL Abstract Neurodegenerative diseases are characterized by slow progressive loss of one or more functions of the CNS. Worldwide, the number of people affected by neurodegeneration is dramatically high and the social impact is upsetting. While being a heterogeneous group of diseases, most of these pathologies manifest similar clinical features and illness progression, thus making their diagnosis elusive. With its ability to meet the needs of neurodegenerative research, proteomics could help facilitate the diagnosis of these disorders. This strategy, recently emerged as complementary to genomics, has led in the last years to substantial achievements in deciphering molecular mechanisms and the follow-up of neurodegenerative diseases. Specifically, aim of this review is to cover the main proteomic investigations realized in the field of familial frontotemporal dementias. This disorder is less common than Alzheimer's disease and disproportionately affects younger individuals, thus representing a major psychological and economic burden for both patients and families. Although early and accurate differential diagnosis of frontotemporal dementias is crucial because of its implications for heritability, prognosis, therapeutics, and environmental management of patients, the investigative methods currently available to clinicians are incomplete. Certainly, the development of a focused therapy cannot be separated from the investigation of biochemical pathways involved in the pathogenesis. PMID: 27061321 [PubMed - indexed for MEDLINE]

A metabonomic investigation on the biochemical perturbation in post-stroke patients with depressive disorder (PSD).

Wed, 11/01/2017 - 13:27
Related Articles A metabonomic investigation on the biochemical perturbation in post-stroke patients with depressive disorder (PSD). Metab Brain Dis. 2016 Apr;31(2):279-87 Authors: Ding X, Liu R, Li W, Ni H, Liu Y, Wu D, Yang S, Liu J, Xiao B, Liu S Abstract A metabonomics study based on GC/MS and multivariate statistical analysis was performed involving 28 post stroke depressed (PSD) patients, 27 post-stroke non-depressed (PSND) patients and 33 healthy subjects to investigate the biochemical perturbation in their plasma samples. The outcome of this study showed that there was distinctive metabolic profile for PSD patients. Seven sentinel metabolites showed marked perturbations in PSD patients' blood. The introduction of metabonomics approach may provide a novel metabonomic insight about PSD and the sentinel metabolites for classifying PSD. PMID: 26537495 [PubMed - indexed for MEDLINE]

Bacterial spoilers of food: behavior, fitness and functional properties.

Wed, 11/01/2017 - 13:27
Related Articles Bacterial spoilers of food: behavior, fitness and functional properties. Food Microbiol. 2015 Feb;45(Pt A):45-53 Authors: Remenant B, Jaffrès E, Dousset X, Pilet MF, Zagorec M Abstract Most food products are highly perishable as they constitute a rich nutrient source for microbial development. Among the microorganisms contaminating food, some present metabolic activities leading to spoilage. In addition to hygienic rules to reduce contamination, various treatments are applied during production and storage to avoid the growth of unwanted microbes. The nature and appearance of spoilage therefore depend on the physiological state of spoilers and on their ability to resist the processing/storage conditions and flourish on the food matrix. Spoilage also relies on the interactions between the microorganisms composing the ecosystems encountered in food. The recent rapid increase in publicly available bacterial genome sequences, as well as the access to high-throughput methods, should lead to a better understanding of spoiler behavior and to the possibility of decreasing food spoilage. This review lists the main bacterial species identified as food spoilers, their ability to develop during storage and/or processing, and the functions potentially involved in spoilage. We have also compiled an inventory of the available genome sequences of species encompassing spoilage strains. Combining in silico analysis of genome sequences with experimental data is proposed in order to understand and thus control the bacterial spoilage of food better. PMID: 25481061 [PubMed - indexed for MEDLINE]

metabolomics; +18 new citations

Tue, 10/01/2017 - 12:22
18 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 2017/01/10PubMed 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.

Dose-response characteristics of Clematis triterpenoid saponins and clematichinenoside AR in rheumatoid arthritis rats by liquid chromatography/mass spectrometry-based serum and urine metabolomics.

Mon, 09/01/2017 - 14:13
Related Articles Dose-response characteristics of Clematis triterpenoid saponins and clematichinenoside AR in rheumatoid arthritis rats by liquid chromatography/mass spectrometry-based serum and urine metabolomics. J Pharm Biomed Anal. 2016 Dec 29;136:81-91 Authors: Li R, Guo LX, Li Y, Chang WQ, Liu JQ, Liu LF, Xin GZ Abstract Clematidis Radix et Rhizoma is a traditional Chinese medicine widely used for treating arthritic disease. Clematis triterpenoid saponins (TS) and clematichinenoside AR (C-AR) have been considered to be responsible for its antiarthritic effects. However, the underling mechanism is still unclear because of their low bioavailability. To address of this issue, metabolomics tools were performed to determine metabolic variations associated with rheumatoid arthritis (RA) and responses to Clematis TS, C-AR and positive drug (Triptolide, TP) treatments. This metabolomics investigation of RA was conducted in collagen-induced arthritis (CIA) rats. Liquid chromatography/mass spectrometry and multivariate statistical tools were used to identify the alteration of serum and urine metabolites associated with RA and responses to drug treatment. As a result, 45 potential metabolites associated with RA were identified. After treatment, a total of 24 biomarkers were regulated to normal like levels. Among these, PC(18:0/20:4), 9,11-octadecadienoic acid, arachidonic acid, 1-methyladenosine, valine, hippuric acid and pantothenic acid etc, were reversed in Clematis TS and C-AR groups. Tetrahydrocortisol was regulated to normal levels in Clematis TS and TP groups, while 3,7,12-trihydroxycholan-24-oic acid was regulated in C-AR and TP groups. Biomarkers like citric acid, p-cresol glucuronide, creatinine, cortolone were reversed in TP group. PMID: 28064091 [PubMed - as supplied by publisher]

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