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Comprehensive and Quantitative Profiling of the Human Sweat Submetabolome Using High-Performance Chemical Isotope Labeling LC-MS.
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Comprehensive and Quantitative Profiling of the Human Sweat Submetabolome Using High-Performance Chemical Isotope Labeling LC-MS.
Anal Chem. 2016 Jun 28;
Authors: Hooton K, Han W, Li L
Abstract
Human sweat can be noninvasively collected and used as a media for diagnosis of certain diseases as well as for drug detection. However, because of very low concentrations of endogenous metabolites present in sweat, metabolomic analysis of sweat with high coverage is difficult, making it less widely used for metabolomics research. In this work, a high-performance method for profiling the human sweat submetabolome based on chemical isotope labeling (CIL) LC-MS is reported. Sweat was collected using a gauze sponge style patch and extracted from the gauze by centrifugation and then derivatized using CIL. Differential (12)C- and (13)C-dansylation labeling was used to target the amine/phenol submetabolome. Because of large variations in the total amount of sweat metabolites in individual samples, sample amount normalization was first performed using LC-UV after dansylation. The (12)C-labeled individual sample was then mixed with an equal amount of (13)C-labeled pooled sample. The mixture was subjected to LC-MS analysis. Over 2707 unique metabolites were detected across 54 sweat samples from six individuals with an average of 2002±165 metabolites detected per sample from a total of 108 LC-MS runs. Using a dansyl standard library, we were able to identify 83 metabolites with high confidence; many of them have never been reported to be present in sweat. Using accurate mass search against human metabolome libraries, we putatively identified an additional 2411 metabolites. Uni- and multivariate analyses of these metabolites showed significant differences in the sweat submetabolomes between male and female, as well as between early and late exercise. These results demonstrate that the CIL LC-MS method described can be used to profile the human sweat submetabolome with high metabolomic coverage and high quantification accuracy to reveal metabolic differences in different sweat samples, thereby allowing the use of sweat as another human biofluid for comprehensive and quantitative metabolomics research.
PMID: 27351466 [PubMed - as supplied by publisher]
Metabolic clusters of breast cancer in relation to gene- and protein expression subtypes.
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Metabolic clusters of breast cancer in relation to gene- and protein expression subtypes.
Cancer Metab. 2016;4:12
Authors: Haukaas TH, Euceda LR, Giskeødegård GF, Lamichhane S, Krohn M, Jernström S, Aure MR, Lingjærde OC, Schlichting E, Garred Ø, Due EU, Mills GB, Sahlberg KK, Børresen-Dale AL, Bathen TF, Oslo Breast Cancer Consortium (OSBREAC)
Abstract
BACKGROUND: The heterogeneous biology of breast cancer leads to high diversity in prognosis and response to treatment, even for patients with similar clinical diagnosis, histology, and stage of disease. Identifying mechanisms contributing to this heterogeneity may reveal new cancer targets or clinically relevant subgroups for treatment stratification. In this study, we have merged metabolite, protein, and gene expression data from breast cancer patients to examine the heterogeneity at a molecular level.
METHODS: The study included primary tumor samples from 228 non-treated breast cancer patients. High-resolution magic-angle spinning magnetic resonance spectroscopy (HR MAS MRS) was performed to extract the tumors metabolic profiles further used for hierarchical cluster analysis resulting in three significantly different metabolic clusters (Mc1, Mc2, and Mc3). The clusters were further combined with gene and protein expression data.
RESULTS: Our result revealed distinct differences in the metabolic profile of the three metabolic clusters. Among the most interesting differences, Mc1 had the highest levels of glycerophosphocholine (GPC) and phosphocholine (PCho), Mc2 had the highest levels of glucose, and Mc3 had the highest levels of lactate and alanine. Integrated pathway analysis of metabolite and gene expression data uncovered differences in glycolysis/gluconeogenesis and glycerophospholipid metabolism between the clusters. All three clusters had significant differences in the distribution of protein subtypes classified by the expression of breast cancer-related proteins. Genes related to collagens and extracellular matrix were downregulated in Mc1 and consequently upregulated in Mc2 and Mc3, underpinning the differences in protein subtypes within the metabolic clusters. Genetic subtypes were evenly distributed among the three metabolic clusters and could therefore contribute to additional explanation of breast cancer heterogeneity.
CONCLUSIONS: Three naturally occurring metabolic clusters of breast cancer were detected among primary tumors from non-treated breast cancer patients. The clusters expressed differences in breast cancer-related protein as well as genes related to extracellular matrix and metabolic pathways known to be aberrant in cancer. Analyses of metabolic activity combined with gene and protein expression provide new information about the heterogeneity of breast tumors and, importantly, the metabolic differences infer that the clusters may be susceptible to different metabolically targeted drugs.
PMID: 27350877 [PubMed]
Positive effects of proline addition on the central metabolism of wild-type and lactic acid-producing Saccharomyces cerevisiae strains.
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Positive effects of proline addition on the central metabolism of wild-type and lactic acid-producing Saccharomyces cerevisiae strains.
Bioprocess Biosyst Eng. 2016 Jun 27;
Authors: Nugroho RH, Yoshikawa K, Matsuda F, Shimizu H
Abstract
In Saccharomyces cerevisiae, proline is a stress protectant interacting with other substrate uptake systems against oxidative stress under low pH conditions. In this study, we performed metabolomics analysis to investigate the response associated with an increase in cell growth rates and maximum densities when cells were treated with proline under normal and acid stress conditions. Metabolome data show that concentrations of components of central metabolism are increased in proline-treated S. cerevisiae. No consumption of proline was observed, suggesting that proline does not act as a nutrient but regulates metabolic state and growth of cells. Treatment of lactic acid-producing yeast with proline during lactic acid bio-production improved growth rate and increased the final concentration of lactic acid.
PMID: 27350544 [PubMed - as supplied by publisher]
Multiple gut-liver axis abnormalities in children with obesity with and without hepatic involvement.
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Multiple gut-liver axis abnormalities in children with obesity with and without hepatic involvement.
Pediatr Obes. 2016 Jun 28;
Authors: Guercio Nuzio S, Di Stasi M, Pierri L, Troisi J, Poeta M, Bisogno A, Belmonte F, Tripodi M, Di Salvio D, Massa G, Savastano R, Cavallo P, Boffardi M, Ziegenhardt D, Bergheim I, Mandato C, Vajro P
Abstract
BACKGROUND: Gut-liver axis (GLA) dysfunction appears to play a role in obesity and obesity-related hepatic complications.
OBJECTIVES: This study sought to concurrently explore several GLA components in a paediatric obese population with/without liver disease.
METHODS: Thirty-two children (mean age 11.2 years) were enrolled: nine controls with normal weight and 23 patients with obesity (OB+). Of the 23 patients OB(+), 12 had not steatosis (ST-), and 11 had steatosis (ST+) (associated [n = 8] or not [n = 3] with hypertransaminasaemia [ALT +/-]). Subjects were characterized by using auxologic, ultrasonographic and laboratory parameters. A glucose hydrogen breath test was performed to test for small intestinal bacterial overgrowth, a urinary lactulose/mannitol ratio (LMR) was obtained to assess intestinal permeability, and tests for transaminases, blood endogenous ethanol, endotoxin and faecal calprotectin were also conducted.
RESULTS: Eleven out of 23 patients OB(+) (p < 0.05) exhibited pathological (>90th percentile of the control group values) LMR, with values paralleling the grade of liver involvement (normal weight < OB[+] < OB[+]ST[+]ALT[-] < OB[+)]ST[+]ALT[+] [p < 0.05]). LMR significantly correlated with ethanolaemia (r = 0.38, p = 0.05) and endotoxaemia (r = 0.48, p = 0.015) concentrations. Increased permeability was a risk factor for the development of steatosis (p < 0.002). SIBO was present only in patients with obesity. Faecal calprotectin concentrations were within normal limits in all subjects.
CONCLUSIONS: Increased permeability, endogenous ethanol and systemic endotoxin concentrations reflect some GLA dysfunction in obesity and its hepatic complications. Pending further results to establish their potential causative roles, the modulation of the GLA appears to represent a possible target for the prevention and treatment of these conditions.
PMID: 27350543 [PubMed - as supplied by publisher]
GC-TOF/MS-based metabolomics approach to study the cellular immunotoxicity of deoxynivalenol on murine macrophage ANA-1 cells.
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GC-TOF/MS-based metabolomics approach to study the cellular immunotoxicity of deoxynivalenol on murine macrophage ANA-1 cells.
Chem Biol Interact. 2016 Jun 24;
Authors: Ji J, Sun J, Pi F, Zhang S, Sun C, Wang X, Zhang Y, Sun X
Abstract
Gas chromatography-time of fly/mass spectrum (GC-TOF/MS) based complete murine macrophage ANA-1 cell metabolome strategy, including the endo-metabolome and the exo-metabolome, ANA-1 cell viability assays and apoptosis induced by diverse concentrations of DON were evaluated for selection of an optimized dose for in-depth metabolomic research. Using the optimized chromatography and mass spectrometry parameters, the metabolites detected by GC-TOF/MS were identified and processed with multivariate statistical analysis, including principal componentanalysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) analysis. The data setswere screened with a t-test (P) value < 0.05, VIP value > 1, similarity value > 500, leaving 16 exo-metabolite variables and 11 endo-metabolite variables for further pathway analysis. Implementingthe integration of key metabolic pathways, the metabolism pathways were categorized into two dominating types, metabolism of amino acid and glycometabolism. Glycine, serine and threonine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism were the significant amino acidsaffected by the metabolic pathways, indicating statistically significant fold changes including pyruvate, serine, glycine, lactate and threonine. Glycolysis or gluconeogenesis, starch and sucrose metabolism, and galactose metabolism, belonging to glycometabolism, were the pathways that were found to be primarily affected, resulting in abnormal metabolites such as glucose-1P, Glucose, gluconic acid, myo-inositol, sorbitol and glycerol.
PMID: 27350164 [PubMed - as supplied by publisher]
The National Institutes of Health Human Microbiome Project.
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The National Institutes of Health Human Microbiome Project.
Semin Fetal Neonatal Med. 2016 Jun 24;
Authors: Proctor LM
Abstract
This overview describes the impetus for and the goals of the National Institutes of Health (NIH)'s Human Microbiome Project (HMP) and the research resources available through the HMP. As the HMP also serves as a catalyst for human microbiome research at the NIH, NIH Institutes and Centers support for this field is also briefly addressed.
PMID: 27350143 [PubMed - as supplied by publisher]
Identification of bacterial species by untargeted NMR spectroscopy of the exo-metabolome.
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Identification of bacterial species by untargeted NMR spectroscopy of the exo-metabolome.
Analyst. 2016 Jun 28;
Authors: Palama TL, Canard I, Rautureau GJ, Mirande C, Chatellier S, Elena-Herrmann B
Abstract
Identification of bacterial species is a crucial bottleneck for clinical diagnosis of infectious diseases. Quick and reliable identification is a key factor to provide suitable antibiotherapies and avoid the development of multiple-drug resistance. We propose a novel nuclear magnetic resonance (NMR)-based metabolomics strategy for rapid discrimination and identification of several bacterial species that relies on untargeted metabolic profiling of supernatants from bacterial culture media. We show that six bacterial species (Gram negative: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis; Gram positive: Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus saprophyticus) can be well discriminated from multivariate statistical analysis, opening new prospects for NMR applications to microbial clinical diagnosis.
PMID: 27349704 [PubMed - as supplied by publisher]
A UHPLC-TOF/MS method based metabonomic study of total ginsenosides effects on Alzheimer disease mouse model.
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A UHPLC-TOF/MS method based metabonomic study of total ginsenosides effects on Alzheimer disease mouse model.
J Pharm Biomed Anal. 2015 Nov 10;115:174-82
Authors: Gong Y, Liu Y, Zhou L, Di X, Li W, Li Q, Bi K
Abstract
A metabonomic method was established to find potential biomarkers and study the metabolism disturbance in Alzheimer disease animal model. Total ginsenosides, as potential agent in neuroprotection and anti-inflammation, was also studied to learn the regulation mechanism to plasma metabolites in model animals. In experiment, amyloid beta 1-42 was occupied to form Alzheimer disease animal model. After drug administration, animals were evaluated by Morris water maze behavior test and sacrificed. Plasma samples were then analyzed using UHPLC-TOF/MS method to determine the endogenous metabolites. Behavior test results revealed that the spatial learning and memory abilities were deficit in model mice, and total ginsenosides could improve cognition abilities in dose-dependent manners. Principal component analysis showed that model and sham were divided into two groups, which means the metabolic network of mice was disturbed after modeling. Accordingly, 19 biomarkers were found and identified. In model group, the levels of proline, valine, tryptophan, LPC (14:0), LPC (15:0), LPC (15:1), LPC (17:0), LPC (18:2), LPC (18:3) and LPC (20:4) were up-regulated, while the levels of acetylcarnitine, palmitoylcarnitine, vaccenylcarnitine, phytosphingosine, N-eicosanoylethanolamine, hexadecenoic acid, docosahexaenoic acid, docosapentaenoic acid and octadecadienoic acid were down-regulated. The levels of these metabolites were recovered in different degrees after total ginsenosides administration. Combining with behavior study results, total ginsenosides could ameliorate both cognition symptoms and metabolic changes in model animals. This metabonomic approach provided a feasible way to understand the endogenous alterations of AD and to study the pharmacodynamic activity of novel agents.
PMID: 26210744 [PubMed - indexed for MEDLINE]
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Metabolomic profiles of current cigarette smokers.
Metabolomic profiles of current cigarette smokers.
Mol Carcinog. 2016 Jun 24;
Authors: Hsu PC, Lan RS, Brasky TM, Marian C, Cheema AK, Ressom HW, Loffredo CA, Pickworth WB, Shields PG
Abstract
Smoking-related biomarkers for lung cancer and other diseases are needed to enhance early detection strategies and to provide a science base for tobacco product regulation. An untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF MS) totaling 957 assays was used in a novel experimental design where 105 current smokers smoked 2 cigarettes one hour apart. Blood was collected immediately before and after each cigarette allowing for within-subject replication. Dynamic changes of the metabolomic profiles from smokers' four blood samples were observed and biomarkers affected by cigarette smoking were identified. Thirty-one metabolites were definitively shown to be affected by acute effect of cigarette smoking, uniquely including menthol-glucuronide, the reduction of glutamate, oleamide, and 13 glycerophospholipids. This first time identification of a menthol metabolite in smokers' blood serves as proof-of-principle for using metabolomics to identify new tobacco-exposure biomarkers, and also provides new opportunities in studying menthol-containing tobacco products in humans. Gender and race differences also were observed. Network analysis revealed 12 molecules involved in cancer, notably inhibition of cAMP. These novel tobacco-related biomarkers provide new insights to the effects of smoking which may be important in carcinogenesis but not previously linked with tobacco-related diseases. This article is protected by copyright. All rights reserved.
PMID: 27341184 [PubMed - as supplied by publisher]
Mass spectrometry imaging for plant biology: a review.
Mass spectrometry imaging for plant biology: a review.
Phytochem Rev. 2016;15:445-488
Authors: Boughton BA, Thinagaran D, Sarabia D, Bacic A, Roessner U
Abstract
Mass spectrometry imaging (MSI) is a developing technique to measure the spatio-temporal distribution of many biomolecules in tissues. Over the preceding decade, MSI has been adopted by plant biologists and applied in a broad range of areas, including primary metabolism, natural products, plant defense, plant responses to abiotic and biotic stress, plant lipids and the developing field of spatial metabolomics. This review covers recent advances in plant-based MSI, general aspects of instrumentation, analytical approaches, sample preparation and the current trends in respective plant research.
PMID: 27340381 [PubMed - as supplied by publisher]
Vitamins, metabolomics, and prostate cancer.
Vitamins, metabolomics, and prostate cancer.
World J Urol. 2016 Jun 23;
Authors: Mondul AM, Weinstein SJ, Albanes D
Abstract
PURPOSE: How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk.
METHODS: Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes.
RESULTS: Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease.
CONCLUSIONS: Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.
PMID: 27339624 [PubMed - as supplied by publisher]
A Predictive Metabolic Signature for the Transition from Gestational Diabetes to Type 2 Diabetes.
A Predictive Metabolic Signature for the Transition from Gestational Diabetes to Type 2 Diabetes.
Diabetes. 2016 Jun 23;
Authors: Allalou A, Nalla A, Prentice KJ, Liu Y, Zhang M, Dai FF, Ning JX, Osborne LR, Cox BJ, Gunderson EP, Wheeler MB
Abstract
Gestational diabetes (GDM) affects 3-14% of pregnancies, 20-50% of which progress to T2D within 5 years. This study sought to develop a metabolomics signature to predict the transition from GDM to T2D. A prospective cohort of 1035 women with GDM pregnancy were enrolled at 6-9 weeks post-partum (baseline) and screened for T2D annually for 2 years. Of 1,010 without T2D at baseline, 113 progressed to T2D within 2 years. Another 17 developed T2D between 2-4 years. A nested case-control design utilized 122 incident cases matched to non-cases by age, pre-pregnancy BMI and race/ethnicity. We conducted metabolomics with baseline fasting plasma and identified 21 metabolites that significantly differed by incident T2D status. Machine learning optimization resulted in a decision tree modeling that predicted T2D incidence with a discriminative power of 83.0% in the training set and 76.9% in an independent testing set, being far superior to fasting plasma glucose alone. The ADA recommends T2D screening early post-partum via OGTT after GDM, a time consuming and inconvenient procedure. Our metabolomics signature predicted T2D incidence from a single fasting sample. This study represents the first metabolomics study of the transition from GDM to T2D validated in an independent testing set, facilitating early interventions.
PMID: 27338739 [PubMed - as supplied by publisher]
Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics.
Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics.
Nutrients. 2016;8(6)
Authors: Li Q, Gu W, Ma X, Liu Y, Jiang L, Feng R, Liu L
Abstract
Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP.
PMID: 27338465 [PubMed - in process]
Genomic and Epigenomic Alterations in Cancer.
Genomic and Epigenomic Alterations in Cancer.
Am J Pathol. 2016 Jul;186(7):1724-35
Authors: Chakravarthi BV, Nepal S, Varambally S
Abstract
Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research.
PMID: 27338107 [PubMed - in process]
Metabolomic study on the faecal extracts of atherosclerosis mice and its application in a Traditional Chinese Medicine.
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Metabolomic study on the faecal extracts of atherosclerosis mice and its application in a Traditional Chinese Medicine.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Dec 15;1007:140-8
Authors: Tian F, Gu L, Si A, Yao Q, Zhang X, Zhao J, Hu D
Abstract
The intestinal microbiota and their metabolites are closely related to the formation of atherosclerosis (AS). In this study, a metabolomic approach based on the reversed-phase liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) platform was established to analyze the metabolic profiling of fecal extracts from AS mice model. The established metabolomic platform was also used for clearing the effective mechanism of a Traditional Chinese Medicine (TCM) named Sishen granule (SSKL). Totally, sixteen potential biomarkers in faeces of AS mice were identified and 5 of them could be reversed by SSKL. Through functional analysis of these biomarkers and the established network, lipid metabolism, cholesterol metabolism, energy cycle, and inflammation reaction were considered as the most relevant pathological changes in gastrointestinal tract of AS mice. The metabolomic study not only revealed the potential biomarkers in AS mice' faeces but also supplied a systematic view of the pathological changes in gastrointestinal metabolite in AS mice. This metabolomic study also demonstrated that SSKL had the therapeutic effectiveness on AS through partly reversing the lipid metabolism, inflammation and energy metabolism.
PMID: 26596842 [PubMed - indexed for MEDLINE]
Effects of berberine and pomegranate seed oil on plasma phospholipid metabolites associated with risks of type 2 diabetes mellitus by U-HPLC/Q-TOF-MS.
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Effects of berberine and pomegranate seed oil on plasma phospholipid metabolites associated with risks of type 2 diabetes mellitus by U-HPLC/Q-TOF-MS.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Dec 15;1007:110-20
Authors: Wu X, Li Y, Wang Q, Li W, Feng Y
Abstract
A rapid and reliable ultra-performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry (U-HPLC/Q-TOF-MS) has been firstly used to analyze the changes of plasma phospholipids, in type 2 diabetes mellitus (T2DM) mice after administration of berberine and pomegranate seed oil (PSO). The separation of plasma phospholipids was carried out on an Acquity U-HPLC BEH C18 column (2.1mm×50mm, 1.7μm, Waters) by linear gradient elution using a mobile phase consisting of 10mM ammonium formate in water and acetonitrile: isopropanol (1:1, v/v) mixed solution added by 0.25% water and 10mM ammonium formate. The method demonstrated a good precision and reproducibility. Linear regression analysis showed a good linearity. And potential biomarkers were discovered based on their mass spectra and chemometrics methods. The results demonstrated that the proposed U-HPLC/Q-TOF-MS method was successfully applied to analyze the dynamic changes of phospholipids components in plasma of T2DM mice after drug treatment and could provide a useful data base for meriting further study in humans and investigating pharmacological actions of drugs.
PMID: 26590882 [PubMed - indexed for MEDLINE]
Gas chromatography coupled to atmospheric pressure ionization mass spectrometry (GC-API-MS): review.
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Gas chromatography coupled to atmospheric pressure ionization mass spectrometry (GC-API-MS): review.
Anal Chim Acta. 2015 Sep 3;891:43-61
Authors: Li DX, Gan L, Bronja A, Schmitz OJ
Abstract
Although the coupling of GC/MS with atmospheric pressure ionization (API) has been reported in 1970s, the interest in coupling GC with atmospheric pressure ion source was expanded in the last decade. The demand of a "soft" ion source for preserving highly diagnostic molecular ion is desirable, as compared to the "hard" ionization technique such as electron ionization (EI) in traditional GC/MS, which fragments the molecule in an extensive way. These API sources include atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI), atmospheric pressure laser ionization (APLI), electrospray ionization (ESI) and low temperature plasma (LTP). This review discusses the advantages and drawbacks of this analytical platform. After an introduction in atmospheric pressure ionization the review gives an overview about the history and explains the mechanisms of various atmospheric pressure ionization techniques used in combination with GC such as APCI, APPI, APLI, ESI and LTP. Also new developments made in ion source geometry, ion source miniaturization and multipurpose ion source constructions are discussed and a comparison between GC-FID, GC-EI-MS and GC-API-MS shows the advantages and drawbacks of these techniques. The review ends with an overview of applications realized with GC-API-MS.
PMID: 26388363 [PubMed - indexed for MEDLINE]
Evolutionary Divergence of Gene and Protein Expression in the Brains of Humans and Chimpanzees.
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Evolutionary Divergence of Gene and Protein Expression in the Brains of Humans and Chimpanzees.
Genome Biol Evol. 2015 Aug;7(8):2276-88
Authors: Bauernfeind AL, Soderblom EJ, Turner ME, Moseley MA, Ely JJ, Hof PR, Sherwood CC, Wray GA, Babbitt CC
Abstract
Although transcriptomic profiling has become the standard approach for exploring molecular differences in the primate brain, very little is known about how the expression levels of gene transcripts relate to downstream protein abundance. Moreover, it is unknown whether the relationship changes depending on the brain region or species under investigation. We performed high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses on two regions of the human and chimpanzee brain: The anterior cingulate cortex and caudate nucleus. In both brain regions, we found a lower correlation between mRNA and protein expression levels in humans and chimpanzees than has been reported for other tissues and cell types, suggesting that the brain may engage extensive tissue-specific regulation affecting protein abundance. In both species, only a few categories of biological function exhibited strong correlations between mRNA and protein expression levels. These categories included oxidative metabolism and protein synthesis and modification, indicating that the expression levels of mRNA transcripts supporting these biological functions are more predictive of protein expression compared with other functional categories. More generally, however, the two measures of molecular expression provided strikingly divergent perspectives into differential expression between human and chimpanzee brains: mRNA comparisons revealed significant differences in neuronal communication, ion transport, and regulatory processes, whereas protein comparisons indicated differences in perception and cognition, metabolic processes, and organization of the cytoskeleton. Our results highlight the importance of examining protein expression in evolutionary analyses and call for a more thorough understanding of tissue-specific protein expression levels.
PMID: 26163674 [PubMed - indexed for MEDLINE]
Lipidomic analysis of plasma lipoprotein fractions in myocardial infarction-prone rabbits.
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Lipidomic analysis of plasma lipoprotein fractions in myocardial infarction-prone rabbits.
J Biosci Bioeng. 2015 Oct;120(4):476-82
Authors: Takeda H, Koike T, Izumi Y, Yamada T, Yoshida M, Shiomi M, Fukusaki E, Bamba T
Abstract
Lipids play important roles in the body and are transported to various tissues via lipoproteins. It is commonly assumed that alteration of lipid levels in lipoproteins leads to dyslipidemia and serious diseases such as coronary artery disease (CAD). However, lipid compositions in each lipoprotein fraction induced by lipoprotein metabolism are poorly understood. Lipidomics, which involves the comprehensive and quantitative analysis of lipids, is expected to provide valuable information regarding the pathogenic mechanism of CAD. Here, we performed a lipidomic analysis of plasma and its lipoprotein fractions in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. In total, 172 lipids in plasma obtained from normal and WHHLMI rabbits were quantified with high throughput and accuracy using supercritical fluid chromatography hybrid quadrupole-Orbitrap mass spectrometry (SFC/Q-Orbitrap-MS). Plasma levels of each lipid class (i.e., phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, ceramide, triacylglycerol, diacylglycerol, and cholesterol ester, except for free fatty acids) in 21-month-old WHHLMI rabbits were significantly higher than those in normal rabbits. High levels of functional lipids, such as alkyl-phosphatidylcholines, phospholipids including ω-6 fatty acids, and plasmalogens, were also observed in WHHLMI rabbit plasma. In addition, high-resolution lipidomic analysis using very low density lipoprotein (VLDL) and low density lipoprotein (LDL) provided information on the specific molecular species of lipids in each lipoprotein fraction. In particular, higher levels of phosphatidylethanolamine plasmalogens were detected in LDL than in VLDL. Our lipidomics approach for plasma lipoprotein fractions will be useful for in-depth studies on the pathogenesis of CAD.
PMID: 26162515 [PubMed - indexed for MEDLINE]