PubMed

Urinary Biomarkers of Whole Grain Wheat Intake Identified by Non-targeted and Targeted Metabolomics Approaches. Sci Rep. 2016 Nov 02;6:36278 Authors: Zhu Y, Wang P, Sha W, Sang S Abstract Mounting evidence suggests that whole grain (WG) intake plays an important role in chronic disease prevention. However, numerous human studies have failed to produce clear-cut conclusions on this topic. Here, a combination of non-targeted and targeted metabolomics approaches, together with kinetic studies, was used to investigate biomarkers of WG wheat intake and further explore the diet-disease associations. Via these integrated approaches, forty-one compounds were identified as the most discriminating endogenous metabolites after WG versus refined grain (RG) wheat bread consumption. The corresponding biological assessment of these endogenous changes suggests that, in contrast to RG consumption, WG wheat consumption may facilitate antioxidant defense systems and moderate the risk factors of cancer, cardiovascular diseases, and other chronic diseases. A panel of urinary markers consisting of seven alkylresorcinol metabolites and five benzoxazinoid derivatives as specific biomarkers, as well as five phenolic acid derivatives, was also established to cover multiple time points and longer time periods for correctly and objectively monitoring WG wheat intake. Through these findings, we have established a comprehensive biomarker pool to better assess WG wheat consumption, and to monitor the endogenous changes that are linked to health effects of WG wheat consumption. PMID: 27805021 [PubMed - in process]

Related Articles Profiling of Altered Metabolomic States in Nicotiana tabacum Cells Induced by Priming Agents. Front Plant Sci. 2016;7:1527 Authors: Mhlongo MI, Steenkamp PA, Piater LA, Madala NE, Dubery IA Abstract Metabolomics has developed into a valuable tool for advancing our understanding of plant metabolism. Plant innate immune defenses can be activated and enhanced so that, subsequent to being pre-sensitized, plants are able to launch a stronger and faster defense response upon exposure to pathogenic microorganisms, a phenomenon known as priming. Here, three contrasting chemical activators, namely acibenzolar-S-methyl, azelaic acid and riboflavin, were used to induce a primed state in Nicotiana tabacum cells. Identified biomarkers were then compared to responses induced by three phytohormones-abscisic acid, methyljasmonate, and salicylic acid. Altered metabolomes were studied using a metabolite fingerprinting approach based on liquid chromatography and mass spectrometry. Multivariate data models indicated that these inducers cause time-dependent metabolic perturbations in the cultured cells and revealed biomarkers of which the levels are affected by these agents. A total of 34 metabolites were annotated from the mass spectral data and online databases. Venn diagrams were used to identify common biomarkers as well as those unique to a specific agent. Results implicate 20 cinnamic acid derivatives conjugated to (i) quinic acid (chlorogenic acids), (ii) tyramine, (iii) polyamines, or (iv) glucose as discriminatory biomarkers of priming in tobacco cells. Functional roles for most of these metabolites in plant defense responses could thus be proposed. Metabolites induced by the activators belong to the early phenylpropanoid pathway, which indicates that different stimuli can activate similar pathways but with different metabolite fingerprints. Possible linkages to phytohormone-dependent pathways at a metabolomic level were indicated in the case of cells treated with salicylic acid and methyljasmonate. The results contribute to a better understanding of the priming phenomenon and advance our knowledge of cinnamic acid derivatives as versatile defense metabolites. PMID: 27803705 [PubMed - in process]

Related Articles Poria Attenuates Idiosyncratic Liver Injury Induced by Polygoni Multiflori Radix Praeparata. Front Pharmacol. 2016;7:386 Authors: Gao D, Pang JY, Zhang CE, Li CY, Tu C, Zhang HZ, Niu M, Xiong Y, Xiao XH, Zhao KJ, Gao WW, Wang JB Abstract The hepatotoxicity induced by Polygoni Multiflori Radix Praeparata (PM) has aroused great concern throughout the world. Hence, it is worthwhile to perform studies on the detoxification with the combined use of medicinal herbs based on the compatibility theory of traditional Chinese medicine. In this work, the rat model of PM/LPS-induced idiosyncratic liver injury was used. The effects of Poria, Licorice, and Panax notoginseng on rats of PM/LPS-induced liver injury were investigated respectively, hoping to find the most effective herbal medicine to reduce the hepatotoxicity. According to results of biochemical and histological tests, PM could induce the idiosyncratic hepatotoxicity of rats which presented modest inflammation triggered by non-injurious dose of lipopolysaccharide (LPS). We also found that the combined use of Poria and PM in the ratio of 1:2 could significantly ameliorate the PM/LPS-induced liver injury and systemic inflammation. Furthermore, UPLC/QTOF-MS-based metabolomics was performed to identify possible biomarkers and underlying biological pathways. Ten metabolites were expressed differentially among LPS, PM/LPS, and detoxification-treated groups in terms of PCA and OPLS-DA analysis, which could be potential biomarkers. MetaboAnalyst and pathway enrichment analysis revealed that alterations of these metabolites were primarily involved in three pathways: arginine and proline metabolism, primary bile acid biosynthesis and sphingolipid metabolism. This research provides systematic experimental evidences for the hepatoprotective effect of Poria against PM/LPS-induced liver injury for the first time. And these findings may help better understand the underlying mechanisms of pathophysiologic changes in PM/LPS-induced liver injury. PMID: 27803670 [PubMed - in process]

Related Articles Immunological Mechanisms Underneath the Efficacy of Cancer Therapy. Cancer Immunol Res. 2016 Nov;4(11):895-902 Authors: Galluzzi L, Zitvogel L, Kroemer G Abstract Accumulating preclinical and clinical evidence indicates that the success of several anticancer agents-including some conventional chemotherapeutics, targeted anticancer agents as well as specific forms of radiotherapy-depends (at least in part) on their ability to stimulate anticancer immune responses. Such immunostimulatory effects can be "on-target," i.e., they originate within cancer cells, or "off-target," i.e., they develop from a heretofore unsuspected interaction between cancer therapy and the immune system. Here, we briefly discuss the immunologic mechanisms that underlie the efficacy of some forms of cancer therapy, as we highlight the rationale for combining these treatment modalities with immunotherapy to achieve superior therapeutic effects. Cancer Immunol Res; 4(11); 895-902. ©2016 AACR. PMID: 27803050 [PubMed - in process]

Related Articles Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients. Blood. 2016 Nov 1;: Authors: Fucikova J, Truxova I, Hensler M, Becht E, Kasikova L, Moserova I, Vosahlikova S, Klouckova J, Church SE, Cremer I, Kepp O, Kroemer G, Galluzzi L, Salek C, Spisek R Abstract Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called "damage-associated molecular patterns", DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death (ICD) to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from acute myeloid leukemia (AML) patients exposed multiple DAMPs including calreticulin (CRT), heat-shock protein 70 (HSP70) and HSP90 on their plasma membrane irrespective of treatment. In these patients, high levels of surface-exposed (ecto-)CRT correlated with an increased proportion of natural killer (NK) cells and effector memory CD4(+) and CD8(+) T cells in the periphery. Moreover, CRT exposure on the plasma membrane of malignant blasts positively correlated with the frequency of circulating T cells specific for leukemia-associated antigens (LAAs), indicating that ecto-CRT favors the initiation of anticancer immunity in AML patients. Finally, while the levels of ecto-HSP70, ecto-HSP90 and ecto-CRT were all associated with improved relapse-free survival, only CRT exposure significantly correlated with superior overall survival. Thus, CRT exposure represents a novel powerful prognostic biomarker for AML patients, reflecting the activation of a clinically relevant AML-specific immune response. PMID: 27802968 [PubMed - as supplied by publisher]

Related Articles Metabolite and Microbiome Interplay in Cancer Immunotherapy. Cancer Res. 2016 Nov 1;76(21):6146-6152 Authors: Johnson CH, Spilker ME, Goetz L, Peterson SN, Siuzdak G Abstract The role of the host microbiome has come to the forefront as a potential modulator of cancer metabolism and could be a future target for precision medicine. A recent study revealed that in colon cancer, bacteria form polysaccharide matrices called biofilms at a high frequency in the proximal colon. Comprehensive untargeted and stable isotope-assisted metabolomic analysis revealed that the bacteria utilize polyamine metabolites produced from colon adenomas/carcinomas to build these protective biofilms and may contribute to inflammation and proliferation observed in colon cancer. This study highlighted the importance of finding the biological origin of a metabolite and assessing its metabolism and mechanism of action. This led to a better understanding of host and microbial interactions, thereby aiding therapeutic design for cancer. In this review, we will discuss methodologies for identifying the biological origin and roles of metabolites in cancer progression and discuss the interactions of the microbiome and metabolites in immunity and cancer treatment, focusing on the flourishing field of cancer immunotherapy. Cancer Res; 76(21); 6146-52. ©2016 AACR. PMID: 27729325 [PubMed - in process]

Related Articles Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children. Mol Syst Biol. 2016 Mar 24;12(3):861 Authors: Bauer T, Trump S, Ishaque N, Thürmann L, Gu L, Bauer M, Bieg M, Gu Z, Weichenhan D, Mallm JP, Röder S, Herberth G, Takada E, Mücke O, Winter M, Junge KM, Grützmann K, Rolle-Kampczyk U, Wang Q, Lawerenz C, Borte M, Polte T, Schlesner M, Schanne M, Wiemann S, Geörg C, Stunnenberg HG, Plass C, Rippe K, Mizuguchi J, Herrmann C, Eils R, Lehmann I Abstract Epigenetic mechanisms have emerged as links between prenatal environmental exposure and disease risk later in life. Here, we studied epigenetic changes associated with maternal smoking at base pair resolution by mapping DNA methylation, histone modifications, and transcription in expectant mothers and their newborn children. We found extensive global differential methylation and carefully evaluated these changes to separate environment associated from genotype-related DNA methylation changes. Differential methylation is enriched in enhancer elements and targets in particular "commuting" enhancers having multiple, regulatory interactions with distal genes. Longitudinal whole-genome bisulfite sequencing revealed that DNA methylation changes associated with maternal smoking persist over years of life. Particularly in children prenatal environmental exposure leads to chromatin transitions into a hyperactive state. Combined DNA methylation, histone modification, and gene expression analyses indicate that differential methylation in enhancer regions is more often functionally translated than methylation changes in promoters or non-regulatory elements. Finally, we show that epigenetic deregulation of a commuting enhancer targeting c-Jun N-terminal kinase 2 (JNK2) is linked to impaired lung function in early childhood. PMID: 27013061 [PubMed - indexed for MEDLINE]

Related Articles A coastal and an interior Douglas fir provenance exhibit different metabolic strategies to deal with drought stress. Tree Physiol. 2016 Feb;36(2):148-63 Authors: Du B, Jansen K, Kleiber A, Eiblmeier M, Kammerer B, Ensminger I, Gessler A, Rennenberg H, Kreuzwieser J Abstract Drought is a major environmental stress affecting growth and vitality of forest ecosystems. In the present study, foliar nitrogen (N) and carbon (C) metabolism of two Douglas fir (Pseudotsuga menziesii) provenances with assumed different drought tolerance were investigated. We worked with 1-year-old seedlings of the interior provenance Fehr Lake (FEHR) originating from a dry environment and the coastal provenance Snoqualmie (SNO) from a more humid origin. Total C and N, structural N and the concentrations of soluble protein, total amino acids (TAAs) and individual amino acids as well as the relative abundance of polar, low-molecular-weight metabolites including antioxidants were determined in current-year needles exposed either to 42 days of drought or to 42 days drought plus 14 days of rewatering. The seedlings reacted in a provenance-specific manner to drought stress. Coastal provenance SNO showed considerably increased contents of TAAs, which were caused by increased abundance of the quantitatively most important amino acids arginine, ornithine and lysine. Additionally, the polyamine putrescine accumulated exclusively in drought-stressed trees of this provenance. In contrast, the interior provenance FEHR showed the opposite response, i.e., drastically reduced concentrations of these amino acids. However, FEHR showed considerably increased contents of pyruvate-derived and aromatic amino acids, and also higher drought-induced levels of the antioxidants ascorbate and α-tocopherol. In response to drought, both provenances produced large amounts of carbohydrates, such as glucose and fructose, most likely as osmolytes that can readily be metabolized for protection against osmotic stress. We conclude that FEHR and SNO cope with drought stress in a provenance-specific manner: the coastal provenance SNO was mainly synthesizing N-based osmolytes, a reaction not observed in the interior provenance FEHR; instead, the latter increased the levels of scavengers of reactive oxygen species. Our results underline the importance of provenance-specific reactions to abiotic stress. PMID: 26491053 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic study of urinary polyamines in rat exposed to 915 MHz radiofrequency identification signal. Amino Acids. 2016 Jan;48(1):213-7 Authors: Paik MJ, Kim HS, Lee YS, Choi HD, Pack JK, Kim N, Ahn YH Abstract Metabolomic analysis of urinary polyamines (PAs) from rat exposed to 915 MHz radiofrequency identification (RFID) signal for 8 h/day for 2 weeks was performed by gas chromatography-mass spectrometry as N-ethoxycarbonyl/N-pentafluoropropionyl derivatives. Large alterations in nine PA levels including four aliphatic and five acetylated PAs were monitored in sham-exposed and RFID-exposed groups. Total PA and urinary levels of N (1)-acetylputrescine, N (1)-acetylcadaverine, putrescine, cadaverine, N (1)-acetylspermidine, N (8)-acetylspermidine, spermidine and spermine were reduced, whereas N (1)-acetylspermine was significantly increased after sham and RFID exposure compared with those before exposure. Their levels were normalized to the corresponding group means before exposure and then plotted into star symbol patterns. N (1)-Acetylspermine after RFID exposure was 54 % higher compared to the level before RFID exposure, while it was elevated by only 17 % in the sham group. The results suggest that 915 MHz RFID exposure may induce metabolic disturbance of PA. It may also elevate spermidine/spermine acetyltransferase (SSAT) activity. Thus, the present metabolic profiling combined with star pattern recognition method might be useful for understanding the complexity of biochemical events after exposure to RFID signal. PMID: 26319644 [PubMed - indexed for MEDLINE]

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 2016/11/02PubMed 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.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/11/01PubMed 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.

29 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 2016/10/30PubMed 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.

Metabolic phenotyping of urine for discriminating alcohol-dependent from social drinkers and alcohol-naive subjects. Drug Alcohol Depend. 2016 Oct 18;169:80-84 Authors: Mostafa H, Amin AM, Teh CH, Murugaiyah V, Arif NH, Ibrahim B Abstract BACKGROUND: Alcohol-dependence (AD) is a ravaging public health and social problem. AD diagnosis depends on questionnaires and some biomarkers, which lack specificity and sensitivity, however, often leading to less precise diagnosis, as well as delaying treatment. This represents a great burden, not only on AD individuals but also on their families. Metabolomics using nuclear magnetic resonance spectroscopy (NMR) can provide novel techniques for the identification of novel biomarkers of AD. These putative biomarkers can facilitate early diagnosis of AD. OBJECTIVES: To identify novel biomarkers able to discriminate between alcohol-dependent, non-AD alcohol drinkers and controls using metabolomics. METHOD: Urine samples were collected from 30 alcohol-dependent persons who did not yet start AD treatment, 54 social drinkers and 60 controls, who were then analysed using NMR. Data analysis was done using multivariate analysis including principal component analysis (PCA) and orthogonal partial least square-discriminate analysis (OPLS-DA), followed by univariate and multivariate logistic regression to develop the discriminatory model. The reproducibility was done using intraclass correlation coefficient (ICC). RESULTS: The OPLS-DA revealed significant discrimination between AD and other groups with sensitivity 86.21%, specificity 97.25% and accuracy 94.93%. Six biomarkers were significantly associated with AD in the multivariate logistic regression model. These biomarkers were cis-aconitic acid, citric acid, alanine, lactic acid, 1,2-propanediol and 2-hydroxyisovaleric acid. The reproducibility of all biomarkers was excellent (0.81-1.0). CONCLUSION: This study revealed that metabolomics analysis of urine using NMR identified AD novel biomarkers which can discriminate AD from social drinkers and controls with high accuracy. PMID: 27788404 [PubMed - as supplied by publisher]

Assessment of key plasma metabolites in combat casualties. J Trauma Acute Care Surg. 2016 Oct 25; Authors: Lusczek ER, Muratore SL, Dubick MA, Beilman GJ Abstract BACKGROUND: Previous studies have indicated that hemorrhagic shock and injury cause significant early changes in metabolism. Recently, global changes in metabolism have been described using metabolomics in animal models and civilian trauma. We evaluated metabolic changes associated with combat injury to identify early biomarkers and aid in triage. METHODS: Plasma obtained at Emergency Department (ED) presentation and intervals thereafter from patients injured during combat operations in Iraq (n=78) were compared to healthy control subjects (n=40). Using proton Nuclear Magnetic Resonance, water-soluble metabolites were detected and quantified. Resulting metabolic profiles were analyzed with partial least squares discriminant analysis (PLS-DA), ROC, and cluster analyses to identify features of combat injury and mortality. RESULTS: Significant alterations to metabolism resulted from traumatic injury. Metabolic profiles of injured patients differed from those of healthy controls, driven by increased 5-aminolevulinate and hypoxanthine that persisted through 24 hours. Among combat-injured patients, increased succinate and malonate best discriminated between those who survived from those who did not. Higher levels of succinate and hypoxanthine were associated with increased injury severity. ROC analysis showed that these metabolites had equivalent or superior performance to lactate in distinguishing the presence of trauma, injury severity, and mortality. CONCLUSIONS: Combat injury is associated with several changes at the metabolic level compared to healthy individuals. Novel potential biomarkers of mortality (succinate, malonate), injury severity (succinate, hypoxanthine), and the presence of trauma (hypoxanthine, 5-aminolevulinate) perform as well as or better than the common clinical standard, lactate. LEVEL OF EVIDENCE: Level III STUDY TYPE: Prognostic. PMID: 27787435 [PubMed - as supplied by publisher]

Fecal metabolomics in pediatric spondyloarthritis implicate decreased metabolic diversity and altered tryptophan metabolism as pathogenic factors. Genes Immun. 2016 Oct 27;: Authors: Stoll ML, Kumar R, Lefkowitz EJ, Cron RQ, Morrow CD, Barnes S Abstract We have previously shown alterations in the composition of the gut microbiota in children with enthesitis-related arthritis (ERA). To explore the mechanisms by which an altered microbiota might predispose to arthritis, we performed metabolomic profiling of fecal samples of children with ERA. Fecal samples were collected from two cohorts of children with ERA and healthy control subjects. Nano-liquid chromatography-mass spectroscopy (LC-MS) was performed on the fecal water homogenates with identification based upon mass: charge ratios. Sequencing of the 16S ribosomal DNA (rDNA) on the same stool specimens was performed. In both sets of subjects, patients demonstrated lower diversity of ions and under-representation of multiple metabolic pathways, including the tryptophan metabolism pathway. For example, in the first cohort, out of 1500 negatively charged ions, 154 were lower in ERA patients, compared with only one that was higher. Imputed functional annotation of the 16S ribosomal DNA sequence data demonstrated significantly fewer microbial genes associated with metabolic processes in the patients compared with the controls (77 million versus 58 million, P=0.050). Diminished metabolic diversity and alterations in the tryptophan metabolism pathway may be a feature of ERA.Genes and Immunity advance online publication, 27 October 2016; doi:10.1038/gene.2016.38. PMID: 27786174 [PubMed - as supplied by publisher]

Related Articles Cardiovascular Risk Factors Associated with Blood Metabolite Concentrations and Their Alterations over a 4-Year Period in a Population-Based Cohort. Circ Cardiovasc Genet. 2016 Oct 26;: Authors: Lacruz ME, Kluttig A, Tiller D, Medenwald D, Giegling I, Rujescu D, Prehn C, Adamski J, Frantz S, Greiser KH, Emeny RT, Kastenmüller G, Haerting J Abstract BACKGROUND: -The effects of lifestyle risk-factors considered collectively on the human metabolism are so far unknown. We aim to investigate the association of these risk-factors with metabolites and their changes over 4 years. METHODS AND RESULTS: -163 metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45-83 at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lyso-phosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (BMI, alcohol consumption, smoking, diet and exercise). Multilevel or simple linear regression modelling adjusted for relevant covariates was used for the evaluation of cross-sectional and longitudinal associations respectively, multiple testing correction was based on false discovery rate. BMI, alcohol and smoking were associated with lipid metabolism (reduced lyso- and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk-factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI, and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines. CONCLUSIONS: -This study showed sex-specific effects of lifestyle risks factors on human metabolism and highlighted their long-term metabolic consequences. PMID: 27784734 [PubMed - as supplied by publisher]

Related Articles Preanalytics in urinalysis. Clin Biochem. 2016 Oct 23;: Authors: Delanghe JR, Speeckaert MM Abstract Urine contains an enormous amount of information. Well-standardized procedures for collection, transport, sample preparation and analysis should become the basis of an effective diagnostic strategy for urinalysis. As reproducibility of urinalysis has been greatly improved due to recent technological progress, preanalytical requirements of urinalysis have gained importance and have become stricter. Since the patients themselves often collect urine specimens, urinalysis is very susceptible to preanalytical issues. Various collection methods and inappropriate specimen transport can cause important preanalytical errors. In addition to the insurance of correct collection, the clinical laboratory should optimize transport and sample preservation. Errors due to variation in diuresis may be corrected by recalculating the results using dilution parameters (e.g. osmolality, creatinine, conductivity, urine density). Next to the use of a primary urine container, it is recommended to split the original urine sample into various smaller aliquots for morphological, microbiological and chemical analyses, decreasing the risk of contamination. The use of preservatives may be helpful for particular analytes. A universal urine preservative however does not exist. Preanalytical aspects are also of major importance for newer urinalysis applications (e.g. metabolomics). PMID: 27784640 [PubMed - as supplied by publisher]

Related Articles Gas chromatography/mass spectrometry-based urine metabolome study in children for inborn errors of metabolism: An Indian experience. Clin Biochem. 2016 Oct 23;: Authors: Hampe MH, Panaskar SN, Yadav AA, Ingale PW Abstract OBJECTIVE: The present study highlights the feasibility of gas chromatography/mass spectrometry (GC/MS)-based analysis for simultaneous detection of >200 marker metabolites in urine found in characteristic pattern in inborn errors of metabolism (IEM) in India. DESIGN AND METHODS: During this retrospective study conducted from July 2013 to January 2016, we collected urine specimens on filter papers from Indian children across the country along with relevant demographic and clinical data. The laboratory technique involved urease pretreatment followed by deproteinization, derivatization, and subsequent computer-aided analysis of organic acids, amino acids, fatty acids, and sugars by GC/MS, which enable chemical diagnosis of IEM. RESULTS: Totally 23,140 patients were investigated for IEM with an estimated frequency of about 1.40%, that is, 323 positive cases. Most frequent disorders observed were of primary lactic acidemia (27.2%) and organic acidemia (methylmalonic aciduria, glutaric acidemia type I, propionic aciduria, etc.) followed by aminoacidopathies (maple syrup urine disease, phenylketonuria, tyrosinemia, etc.). Furthermore, alkaptonuria, canavan disease, and 4-hydroxybutyric aciduria were also diagnosed. Prompt treatment following diagnosis led to a better outcome in a considerable number of patients. CONCLUSIONS: GC/MS with one-step metabolomics enables quick detection, accurate identification, and precise quantification of a wide range of urinary markers that may not be discovered using existing newborn screening programs. The technique is effective as a second-tier test to other established screening technologies, as well as one-step primary screening tool for a wide spectrum of IEM. PMID: 27784639 [PubMed - as supplied by publisher]

Related Articles Screening and verifying endometrial carcinoma diagnostic biomarkers based on a urine metabolomic profiling study using UPLC-Q-TOF/MS. Clin Chim Acta. 2016 Oct 23;: Authors: Shao X, Wang K, Liu X, Gu C, Zhang P, Xie J, Liu W, Sun L, Chen T, Li Y Abstract BACKGROUND: Endometrial carcinoma (EOC) is a gynecological disease with one of the highest worldwide incidences. Due to the lack of typical clinical symptoms and limited sensitive screening methods used to diagnose endometrial carcinoma, the disease is easily neglected before patients are aware of its presence. Therefore, EOC results in serious impacts on women's lives and health. We screened diagnostic biomarkers of EOC with a noninvasive method that compared healthy individuals and endometrial hyperplasia (EOH) patients. METHODS: The morning urine of 25 healthy individuals, 25 patients with EOC and 10 patients with EOH were analyzed using an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) platform. Metabolomics data were used to screen the different metabolites according to PCA and PLS-DA analyses. Furthermore, the screened biomarkers of the newly diagnosed EOC and EOH candidates and healthy individuals were verified using the predictive model of the support vector machine (SVM) to obtain EOC diagnostic biomarkers. RESULTS: An EOC diagnostic biomarker group was found according to the metabolomics method. Five diagnostic biomarkers, including porphobilinogen, acetylcysteine, N-acetylserine, urocanic acid and isobutyrylglycine, were significantly changed in the EOC patients. Among them, porphobilinogen and acetylcysteine were significantly down-regulated, while N-acetylserine, urocanic acid and isobutyrylglycine were significantly up-regulated. CONCLUSIONS: Disturbances in these biomarkers have negative impacts on the body's metabolic functioning. The EOC diagnostic biomarker group can provide a clinical reference for diagnosing EOC and insight into the diagnosis of other diseases in the clinic. PMID: 27784637 [PubMed - as supplied by publisher]

Recent advances in CE-MS coupling: Instrumentation, methodology, and applications. Electrophoresis. 2016 Oct 26;: Authors: Týčová A, Ledvina V, Klepárník K Abstract This review focuses on the latest development of microseparation electromigration methods in capillaries and microfluidic devices coupled with MS for detection and identification of important analytes. It is a continuation of the review article on the same topic by Kleparnik (Electrophoresis 2015, 36, 159-178). A wide selection of 161 relevant articles covers the literature published from June 2014 till May 2016. New improvements in the instrumentation and methodology of MS interfaced with capillary or microfluidic versions of zone electrophoresis, isotachophoresis, and isoelectric focusing are described in detail. The most frequently implemented MS ionization methods include electrospray ionization, matrix-assisted desorption/ionization and inductively coupled plasma ionization. Although the main attention is paid to the development of instrumentation and methodology, representative examples illustrate also applications in the proteomics, glycomics, metabolomics, biomarker research, forensics, pharmacology, food analysis, and single-cell analysis. The combinations of MS with capillary versions of electrochromatography, and micellar electrokinetic chromatography are not included. PMID: 27783411 [PubMed - as supplied by publisher]