PubMed

Protocol Outlines for Parts 1 and 2 of the Prospective Endoscopy III Study for the Early Detection of Colorectal Cancer: Validation of a Concept Based on Blood Biomarkers. JMIR Res Protoc. 2016;5(3):e182 Authors: Rasmussen L, Wilhelmsen M, Christensen IJ, Andersen J, Jørgensen LN, Rasmussen M, Hendel JW, Madsen MR, Vilandt J, Hillig T, Klærke M, Münster AM, Andersen LM, Andersen B, Hornung N, Erlandsen EJ, Khalid A, Nielsen HJ Abstract BACKGROUND: Programs for population screening of colorectal cancer (CRC) have been implemented in several countries with fecal immunochemical testing (FIT) as the preferred platform. However, the major obstacle for a feces-based testing method is the limited compliance that reduces the clinical sensitivity for detection of participants with non-symptomatic CRC. Therefore, research approaches have been initiated to develop screening concepts based on biomarkers in blood. Preliminary results show that protein, genetic, epigenetic, and metabolomic components may be valuable in blood-based screening concepts, particularly when combinations of the various components appear to lead to significant improvements. OBJECTIVES: The protocol described in this paper focuses on the validation of concepts based on biomarkers in blood in a major population screened by FIT. METHODS: In Part 1, participants will be identified and included through the Danish CRC Screening Program comprising initial FIT and subsequent colonoscopy to those with a positive result. Blood samples will be collected from 8000 FIT-positive participants, who are offered subsequent colonoscopy. Findings and interventions at colonoscopy together with personal data including co-morbidity will be recorded. Blood samples and data will also be collected from 6000 arbitrarily chosen participants with negative FIT. In Part 2, blood samples and data will be collected from 30,000 FIT-negative participants three times within 4 years. The blood samples will be analyzed using various in-house and commercially available manual and automated analysis platforms. RESULTS: We anticipate Part 1 to terminate late August 2016 and Part 2 to terminate late September 2022. The results from Parts 1 and 2 will be presented within 12 to 18 months from termination. CONCLUSIONS: The purpose of this study is to improve the efficacy of identifying participants with neoplastic bowel lesions, to identify false negative participants, to identify participants at risk of interval neoplastic lesions, to improve the compliance in screening sessions, and to establish guidelines for out-patient follow-up of at-risk participants based on combinations of blood-based biomarkers. PMID: 27624815 [PubMed]

Porous extraction paddle: a solid phase extraction technique for studying the urine metabolome. Rapid Commun Mass Spectrom. 2016 Sep 14; Authors: Shao G, MacNeil M, Yao Y, Giese RW Abstract RATIONALE: A method was needed to accomplish solid phase extraction of a large urine volume in a convenient way where resources are limited, towards a goal of metabolome and xenobiotic exposome analysis at another, distant location. METHODS: A porous extraction paddle (PEP) was set up, comprising a porous nylon bag containing extraction particles that is flattened and immobilized between two stainless steel meshes. Stirring the PEP after attachment to a shaft of a motor mounted on the lid of the jar containing the urine accomplishes extraction. The bag contained a mixture of nonpolar and partly nonpolar particles to extract a diversity of corresponding compounds. RESULTS: Elution of a urine-exposed, water-washed PEP with aqueous methanol containing triethylammonium acetate (conditions intended to give a complete elution), followed by MALDI-TOF/TOF-MS, demonstrated that a diversity of compounds had been extracted ranging from uric acid to peptides. CONCLUSION: The PEP allows the user to extract a large liquid sample in a jar simply by turning on a motor. The technique will be helpful in conducting metabolomics and xenobiotic exposome studies of urine, encouraging the extraction of large volumes to set up a convenient repository sample (e.g. 2 g of exposed adsorbent in a cryovial) for shipment and re-analysis in various ways in the future, including scaled-up isolation of unknown chemicals for identification. PMID: 27624170 [PubMed - as supplied by publisher]

Untargeted Metabolomics Strategies-Challenges and Emerging Directions. J Am Soc Mass Spectrom. 2016 Sep 13; Authors: Schrimpe-Rutledge AC, Codreanu SG, Sherrod SD, McLean JA Abstract Metabolites are building blocks of cellular function. These species are involved in enzyme-catalyzed chemical reactions and are essential for cellular function. Upstream biological disruptions result in a series of metabolomic changes and, as such, the metabolome holds a wealth of information that is thought to be most predictive of phenotype. Uncovering this knowledge is a work in progress. The field of metabolomics is still maturing; the community has leveraged proteomics experience when applicable and developed a range of sample preparation and instrument methodology along with myriad data processing and analysis approaches. Research focuses have now shifted toward a fundamental understanding of the biology responsible for metabolomic changes. There are several types of metabolomics experiments including both targeted and untargeted analyses. While untargeted, hypothesis generating workflows exhibit many valuable attributes, challenges inherent to the approach remain. This Critical Insight comments on these challenges, focusing on the identification process of LC-MS-based untargeted metabolomics studies-specifically in mammalian systems. Biological interpretation of metabolomics data hinges on the ability to accurately identify metabolites. The range of confidence associated with identifications that is often overlooked is reviewed, and opportunities for advancing the metabolomics field are described. Graphical Abstract ᅟ. PMID: 27624161 [PubMed - as supplied by publisher]

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/09/14PubMed comprises more than 24 million 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 2016/09/13PubMed comprises more than 24 million 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.

Application of LC-MS-based metabolomics method in differentiating septic survivors from non-survivors. Anal Bioanal Chem. 2016 Sep 10; Authors: Liu Z, Yin P, Amathieu R, Savarin P, Xu G Abstract Septic shock is the most severe form of sepsis, which is still one of the leading causes of death in the intensive care unit (ICU). Even though early prognosis and diagnosis are known to be indispensable for reaching an optimistic outcome, pathogenic complexities and the lack of specific treatment make it difficult to predict the outcome individually. In the present study, serum samples from surviving and non-surviving septic shock patients were drawn before clinical intervention at admission. Metabolic profiles of all the samples were analyzed by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. One thousand four hundred nineteen peaks in positive mode and 1878 peaks in negative mode were retained with their relative standard deviation (RSD) below 30 %, in which 187 metabolites were initially identified by retention time and database in the light of the exact molecular mass. Differences between samples from the survivors and the non-survivors were investigated using multivariate and univariate analysis. Finally, 43 significantly varied metabolites were found in the comparison between survivors and non-survivors. Concretely, metabolites in the tricarboxylic acid (TCA) cycle, amino acids, and several energy metabolism-related metabolites were up-regulated in the non-survivors, whereas those in the urea cycle and fatty acids were generally down-regulated. Metabolites such as lysine, alanine, and methionine did not present significant changes in the comparison. Six metabolites were further defined as primary discriminators differentiating the survivors from the non-survivors at the early stage of septic shock. Our findings reveal that LC-MS-based metabolomics is a useful tool for studying septic shock. Graphical abstract ᅟ. PMID: 27614981 [PubMed - as supplied by publisher]

Metabolite profiling in Trigonella seeds via UPLC-MS and GC-MS analyzed using multivariate data analyses. Anal Bioanal Chem. 2016 Sep 10; Authors: Farag MA, Rasheed DM, Kropf M, Heiss AG Abstract Trigonella foenum-graecum is a plant of considerable value for its nutritive composition as well as medicinal effects. This study aims to examine Trigonella seeds using a metabolome-based ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) in parallel to gas chromatography-mass spectrometry (GC-MS) coupled with multivariate data analyses. The metabolomic differences of seeds derived from three Trigonella species, i.e., T. caerulea, T. corniculata, and T. foenum-graecum, were assessed. Under specified conditions, we were able to identify 93 metabolites including 5 peptides, 2 phenolic acids, 22 C/O-flavonoid conjugates, 26 saponins, and 9 fatty acids using UPLC-MS. Several novel dipeptides, saponins, and flavonoids were found in Trigonella herein for the first time. Samples were classified via unsupervised principal component analysis (PCA) followed by supervised orthogonal projection to latent structures-discriminant analysis (OPLS-DA). A distinct separation among the investigated Trigonella species was revealed, with T. foenum-graecum samples found most enriched in apigenin-C-glycosides, viz. vicenins 1/3 and 2, compared to the other two species. In contrast to UPLC-MS, GC-MS was less efficient to classify specimens, with differences among specimens mostly attributed to fatty acyl esters. GC-MS analysis of Trigonella seed extracts led to the identification of 91 metabolites belonging mostly to fatty acyl esters, free fatty acids followed by organic acids, sugars, and amino acids. This study presents the first report on primary and secondary metabolite compositional differences among Trigonella seeds via a metabolomics approach and reveals that, among the species examined, the official T. foenum-graecum presents a better source of Trigonella secondary bioactive metabolites. PMID: 27614978 [PubMed - as supplied by publisher]

Related Articles Applying mini-bore HPAEC-MS/MS for the characterization and quantification of Fc N-glycans from heterogeneously glycosylated IgGs. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Aug 9;1033-1034:342-352 Authors: Maier M, Reusch D, Bruggink C, Bulau P, Wuhrer M, Mølhøj M Abstract High-performance anion-exchange chromatography (HPAEC) coupled to pulsed amperometric detection (PAD) is a highly sensitive method for the analysis of oligosaccharides without the need for prior derivatization. However, the method suffers from the lack of chemical information with peak assignments based on the retention times of authentic standards or known peaks of reference materials. Here we applied HPAEC coupled on-line with electrospray ion trap mass spectrometry (HPAEC-MS) using a prototype mini-bore (1mm I.D.) CarboPac PA200 column and challenged the analytical separation based method for the structural assignment of heterogeneous mixtures of N-glycans derived from immunoglobulin G from human plasma, glyco-engineered CHO cells, and Sp2/0 mouse myeloma cells. Compared to an analytical scale 3mm I.D. column, the mini-bore column demonstrated a superior performance with up to 8-fold improved limit of detection for specific N-glycans determined by PAD. Quantitative evaluation by extracted ion current chromatograms revealed detection limits in the 50-100 femtomole range using ion trap MS operated in positive ionization mode. In our hands HPAEC-MS/MS allowed the detection and quantification of even low abundant glycan species including biantennary complex-type, high mannose, hybrid and hybrid bisected structures. In comparison to the detection of N-glycans as lithiated or sodiated adducts, we obtained a 65-fold improved signal-to-noise ratio with protonated ions only. Relative quantitative evaluation by single ion current chromatograms was successfully applied and demonstrated an excellent performance with respect to selectivity in the relative quantification of heterogeneous samples of N-glycans compared to HPAEC-PAD and HILIC-UPLC of 2-AB labelled N-glycans. PMID: 27614258 [PubMed - as supplied by publisher]

Related Articles Nonalcoholic Steatohepatitis is associated with a state of betaine-insufficiency. Liver Int. 2016 Sep 10; Authors: Sookoian S, Puri P, Castaño GO, Scian R, Mirshahi F, Sanyal AJ, Pirola CJ Abstract BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) develops from a complex process, which includes changes in the liver methylome. Betaine plays a pivotal role in the regulation of methylogenesis. We performed a two-stage case-control study, which included patients with biopsy-proven NAFLD in order to explore circulating levels of betaine and its association with the histological spectrum. We also explored the association between a missense p.Ser646Pro variant in DMGDH (dimethylglycine dehydrogenase mitochondrial) and NAFLD severity (n =390). RESULTS: In the discovery phase (n = 48), betaine levels were associated with the disease severity (p = 0.0030), including liver inflammation (Spearman R: - 0.51, p = 0.001), ballooning degeneration (R: - 0.50, p = 0.01), and fibrosis (R: - 0.54, p = 0.0008). Betaine levels were significantly decreased in nonalcoholic steatohepatitis (NASH) in comparison with nonalcoholic fatty liver (NAFL). Further replication (n = 51) showed that betaine levels were associated with advanced NAFLD (p = 0.0085), and patients with NASH had a 1.26-fold decrease in betaine levels compared with those with NAFL. The rs1805074 was significantly associated with the disease severity (p = 0.011). CONCLUSION: NAFLD severity is associated with a state of betaine-insufficiency. This article is protected by copyright. All rights reserved. PMID: 27614103 [PubMed - as supplied by publisher]

Related Articles Symptom Science: Repurposing Existing Omics Data. Biol Res Nurs. 2016 Sep 9; Authors: Osier ND, Imes CC, Khalil H, Zelazny J, Johansson AE, Conley YP Abstract Omics approaches, including genomics, transcriptomics, proteomics, epigenomics, microbiomics, and metabolomics, generate large data sets. Once they have been used to address initial study aims, these large data sets are extremely valuable to the greater research community for ancillary investigations. Repurposing available omics data sets provides data to address research questions, generate and test hypotheses, replicate findings, and conduct mega-analyses. Many well-characterized, longitudinal, epidemiological studies collected extensive phenotype data related to symptom occurrence and severity. While the main phenotype of interest for many of these studies was often not symptom related, these data were collected to better understand the primary phenotype of interest. A search for symptom data (i.e., cognitive impairment, fatigue, gastrointestinal distress/nausea, sleep, and pain) in the database of genotypes and phenotypes (dbGaP) revealed many studies that collected symptom and omics data. There is thus a real possibility for nurse scientists to be able to look at symptom data over time from thousands of individuals and use omics data to identify key biological underpinnings that account for the development and severity of symptoms without recruiting participants or generating any new data. The purpose of this article is to introduce the reader to resources that provide omics data to the research community for repurposing, provide guidance on using these databases, and encourage the use of these data to move symptom science forward. PMID: 27613438 [PubMed - as supplied by publisher]

Related Articles Acute Exposure to Pacific Ciguatoxin Reduces Electroencephalogram Activity and Disrupts Neurotransmitter Metabolic Pathways in Motor Cortex. Mol Neurobiol. 2016 Sep 10; Authors: Kumar G, Au NP, Lei EN, Mak YL, Chan LL, Lam MH, Chan LL, Lam PK, Ma CH Abstract Ciguatera fish poisoning (CFP) is a common human food poisoning caused by consumption of ciguatoxin (CTX)-contaminated fish affecting over 50,000 people worldwide each year. CTXs are classified depending on their origin from the Pacific (P-CTXs), Indian Ocean (I-CTXs), and Caribbean (C-CTXs). P-CTX-1 is the most toxic CTX known and the major source of CFP causing an array of neurological symptoms. Neurological symptoms in some CFP patients last for several months or years; however, the underlying electrophysiological properties of acute exposure to CTXs remain unknown. Here, we used CTX purified from ciguatera fish sourced in the Pacific Ocean (P-CTX-1). Delta and theta electroencephalography (EEG) activity was reduced remarkably in 2 h and returned to normal in 6 h after a single exposure. However, second exposure to P-CTX-1 induced not only a further reduction in EEG activities but also a 2-week delay in returning to baseline EEG values. Ciguatoxicity was detected in the brain hours after the first and second exposure by mouse neuroblastoma assay. The spontaneous firing rate of single motor cortex neuron was reduced significantly measured by single-unit recording with high spatial resolution. Expression profile study of neurotransmitters using targeted profiling approach based on liquid chromatography-tandem mass spectrometry revealed an imbalance between excitatory and inhibitory neurotransmitters in the motor cortex. Our study provides a possible link between the brain oscillations and neurotransmitter release after acute exposure to P-CTX-1. Identification of EEG signatures and major metabolic pathways affected by P-CTX-1 provides new insight into potential biomarker development and therapeutic interventions. PMID: 27613284 [PubMed - as supplied by publisher]

Related Articles Human corneal cell culture models for drug toxicity studies. Drug Deliv Transl Res. 2016 Sep 9; Authors: Rönkkö S, Vellonen KS, Järvinen K, Toropainen E, Urtti A Abstract In vivo toxicity and absorption studies of topical ocular drugs are problematic, because these studies involve invasive tissue sampling and toxic effects in animal models. Therefore, different human corneal models ranging from simple monolayer cultures to three-dimensional models have been developed for toxicological prediction with in vitro models. Each system has its own set of advantages and disadvantages. Use of non-corneal cells, inadequate characterization of gene-expression profiles, and accumulation of genomic aberrations in human corneal models are typical drawbacks that decrease their reliability and predictive power. In the future, further improvements are needed for verifying comparable expression profiles and cellular properties of human corneal models with their in vivo counterparts. A rapidly expanding stem cell technology combined with tissue engineering may give future opportunities to develop new tools in drug toxicity studies. One approach may be the production of artificial miniature corneas. In addition, there is also a need to use large-scale profiling approaches such as genomics, transcriptomics, proteomics, and metabolomics for understanding of the ocular toxicity. PMID: 27613190 [PubMed - as supplied by publisher]

Related Articles Investigation of Endosome and Lysosome Biology by Ultra pH-Sensitive Nanoprobes. Adv Drug Deliv Rev. 2016 Sep 6; Authors: Wang C, Zhao T, Li Y, Huang G, White MA, Gao J Abstract Endosomes and lysosomes play a critical role in various aspects of cell physiology such as nutrient sensing, receptor recycling, protein/lipid catabolism, and cell death. In drug delivery, endosomal release of therapeutic payloads from nanocarriers is also important in achieving efficient delivery of drugs to reach their intracellular targets. Recently, we invented a library of ultra pH-sensitive (UPS) nanoprobes with exquisite fluorescence response to subtle pH changes. The UPS nanoprobes also displayed strong pH-specific buffer effect over small molecular bases with broad pH responses (e.g., chloroquine and NH4Cl). Tunable pH transitions from 7.4 to 4.0 of UPS nanoprobes cover the entire physiological pH of endocytic organelles (e.g., early and late endosomes) and lysosomes. These unique physico-chemical properties of UPS nanoprobes allowed a 'detect and perturbation' strategy for the investigation of luminal pH in cell signaling and metabolism, which introduces a nanotechnology-enabled paradigm for the biological studies of endosomes and lysosomes. PMID: 27612550 [PubMed - as supplied by publisher]

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 2016/09/10PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metabolomic profiling of brain from infants who died from Sudden Infant Death Syndrome reveals novel predictive biomarkers. J Perinatol. 2016 Sep 8; Authors: Graham SF, Chevallier OP, Kumar P, Türko Gcaron Lu O, Bahado-Singh RO Abstract OBJECTIVE: Sudden Infant Death Syndrome (SIDS) is defined as the sudden death of an infant <1 year of age that cannot be explained following a thorough investigation. Currently, no reliable clinical biomarkers are available for the prediction of infants who will die of SIDS. STUDY DESIGN: This study aimed to profile the medulla oblongata from postmortem human brain from SIDS victims (n=16) and compare their profiles with that of age-matched controls (n=7). RESULTS: Using LC-Orbitrap-MS, we detected 12 710 features in electrospray ionization positive (ESI+) mode and 8243 in ESI- mode from polar extracts of brain. Five features acquired in ESI+ mode produced a predictive model for SIDS with an area under the receiver operating characteristic curve (AUC) of 1 (confidence interval (CI): 0.995-1) and a predictive power of 97.4%. Three biomarkers acquired in ESI- mode produced a predictive model with an AUC of 0.866 (CI: 0.767-0.942) and a predictive power of 77.6%. We confidently identified 5 of these features (l-(+)-ergothioneine, nicotinic acid, succinic acid, adenosine monophosphate and azelaic acid) and putatively identify another 4 out of the 15 in total. CONCLUSIONS: This study underscores the potential value of metabolomics for studying SIDS. Further characterization of the metabolome of postmortem SIDS brains could lead to the identification of potential antemortem biomarkers for novel prevention strategies for SIDS.Journal of Perinatology advance online publication, 8 September 2016; doi:10.1038/jp.2016.139. PMID: 27608295 [PubMed - as supplied by publisher]

Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a Posttraumatic Stress Disorder Mouse Model. Mol Neuropsychiatry. 2016 May;2(1):46-59 Authors: Kao CY, He Z, Henes K, Asara JM, Webhofer C, Filiou MD, Khaitovich P, Wotjak CT, Turck CW Abstract Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo (15)N metabolic labeling combined with mass spectrometry in the prelimbic cortex (PrL), anterior cingulate cortex (ACC), basolateral amygdala, central nucleus of the amygdala and CA1 of the hippocampus between shocked and nonshocked (control) mice, with and without fluoxetine treatment. In silico pathway analyses revealed an upregulation of the citric acid cycle pathway in PrL, and downregulation in ACC and nucleus accumbens (NAc). Chronic fluoxetine treatment prevented decreased citric acid cycle activity in NAc and ACC and ameliorated conditioned fear response in shocked mice. Our results shed light on the role of energy metabolism in PTSD pathogenesis and suggest potential therapy through mitochondrial targeting. PMID: 27606320 [PubMed]

Post-acquisition filtering of salt cluster artefacts for LC-MS based human metabolomic studies. J Cheminform. 2016;8(1):44 Authors: McMillan A, Renaud JB, Gloor GB, Reid G, Sumarah MW Abstract Liquid chromatography-high resolution mass spectrometry (LC-MS) has emerged as one of the most widely used platforms for untargeted metabolomics due to its unparalleled sensitivity and metabolite coverage. Despite its prevalence of use, the proportion of true metabolites identified in a given experiment compared to background contaminants and ionization-generated artefacts remains poorly understood. Salt clusters are well documented artefacts of electrospray ionization MS, recognized by their characteristically high mass defects (for this work simply generalized as the decimal numbers after the nominal mass). Exploiting this property, we developed a method to identify and remove salt clusters from LC-MS-based human metabolomics data using mass defect filtering. By comparing the complete set of endogenous metabolites in the human metabolome database to actual plasma, urine and stool samples, we demonstrate that up to 28.5 % of detected features are likely salt clusters. These clusters occur irrespective of ionization mode, column type, sweep gas and sample type, but can be easily removed post-acquisition using a set of R functions presented here. Our mass defect filter removes unwanted noise from LC-MS metabolomics datasets, while retaining true metabolites, and requires only a list of m/z and retention time values. Reducing the number of features prior to statistical analyses will result in more accurate multivariate modeling and differential feature selection, as well as decreased reporting of unknowns that often constitute the largest proportion of human metabolomics data. PMID: 27606010 [PubMed]

Characterization of the metabolic profile associated with serum 25-hydroxyvitamin D: a cross-sectional analysis in population-based data. Int J Epidemiol. 2016 Sep 7; Authors: Vogt S, Wahl S, Kettunen J, Breitner S, Kastenmüller G, Gieger C, Suhre K, Waldenberger M, Kratzsch J, Perola M, Salomaa V, Blankenberg S, Zeller T, Soininen P, Kangas AJ, Peters A, Grallert H, Ala-Korpela M, Thorand B Abstract BACKGROUND: Numerous observational studies have observed associations between vitamin D deficiency and cardiometabolic diseases, but these findings might be confounded by obesity. A characterization of the metabolic profile associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in general and stratified by abdominal obesity, may help to untangle the relationship between vitamin D, obesity and cardiometabolic health. METHODS: Serum metabolomics measurements were obtained from a nuclear magnetic resonance spectroscopy (NMR)- and a mass spectrometry (MS)-based platform. The discovery was conducted in 1726 participants of the population-based KORA-F4 study, in which the associations of the concentrations of 415 metabolites with 25(OH)D levels were assessed in linear models. The results were replicated in 6759 participants (NMR) and 609 (MS) participants, respectively, of the population-based FINRISK 1997 study. RESULTS: Mean [standard deviation (SD)] 25(OH)D levels were 15.2 (7.5) ng/ml in KORA F4 and 13.8 (5.9) ng/ml in FINRISK 1997; 37 metabolites were associated with 25(OH)D in KORA F4 at P < 0.05/415. Of these, 30 associations were replicated in FINRISK 1997 at P < 0.05/37. Among these were constituents of (very) large very-low-density lipoprotein and small low-density lipoprotein subclasses and related measures like serum triglycerides as well as fatty acids and measures reflecting the degree of fatty acid saturation. The observed associations were independent of waist circumference and generally similar in abdominally obese and non-obese participants. CONCLUSIONS: Independently of abdominal obesity, higher 25(OH)D levels were associated with a metabolite profile characterized by lower concentrations of atherogenic lipids and a higher degree of fatty acid polyunsaturation. These results indicate that the relationship between vitamin D deficiency and cardiometabolic diseases is unlikely to merely reflect obesity-related pathomechanisms. PMID: 27605587 [PubMed - as supplied by publisher]

Comparative mass spectrometry-based metabolomics strategies for the investigation of microbial secondary metabolites. Nat Prod Rep. 2016 Sep 7; Authors: Covington BC, McLean JA, Bachmann BO Abstract Covering: 2000 to 2016The labor-intensive process of microbial natural product discovery is contingent upon identifying discrete secondary metabolites of interest within complex biological extracts, which contain inventories of all extractable small molecules produced by an organism or consortium. Historically, compound isolation prioritization has been driven by observed biological activity and/or relative metabolite abundance and followed by dereplication via accurate mass analysis. Decades of discovery using variants of these methods has generated the natural pharmacopeia but also contributes to recent high rediscovery rates. However, genomic sequencing reveals substantial untapped potential in previously mined organisms, and can provide useful prescience of potentially new secondary metabolites that ultimately enables isolation. Recently, advances in comparative metabolomics analyses have been coupled to secondary metabolic predictions to accelerate bioactivity and abundance-independent discovery work flows. In this review we will discuss the various analytical and computational techniques that enable MS-based metabolomic applications to natural product discovery and discuss the future prospects for comparative metabolomics in natural product discovery. PMID: 27604382 [PubMed - as supplied by publisher]

Related Articles mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells. Cancer Cell. 2016 Apr 11;29(4):548-62 Authors: Pusapati RV, Daemen A, Wilson C, Sandoval W, Gao M, Haley B, Baudy AR, Hatzivassiliou G, Evangelista M, Settleman J Abstract Although glycolysis is substantially elevated in many tumors, therapeutic targeting of glycolysis in cancer patients has not yet been successful, potentially reflecting the metabolic plasticity of tumor cells. In various cancer cells exposed to a continuous glycolytic block, we identified a recurrent reprogramming mechanism involving sustained mTORC1 signaling that underlies escape from glycolytic addiction. Active mTORC1 directs increased glucose flux via the pentose phosphate pathway back into glycolysis, thereby circumventing a glycolysis block and ensuring adequate ATP and biomass production. Combined inhibition of glycolysis and mTORC1 signaling disrupted metabolic reprogramming in tumor cells and inhibited their growth in vitro and in vivo. These findings reveal novel combinatorial therapeutic strategies to realize the potential benefit from targeting the Warburg effect. PMID: 27052953 [PubMed - indexed for MEDLINE]