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

PubMed

Multiple gut-liver axis abnormalities in children with obesity with and without hepatic involvement.

Thu, 30/06/2016 - 00:22
Related Articles 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.

Thu, 30/06/2016 - 00:22
Related Articles 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.

Thu, 30/06/2016 - 00:22
Related Articles 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.

Thu, 30/06/2016 - 00:22
Related Articles 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.

Thu, 30/06/2016 - 00:22
Related Articles 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]

metabolomics; +18 new citations

Tue, 28/06/2016 - 17:17
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 2016/06/28PubMed 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 profiles of current cigarette smokers.

Sat, 25/06/2016 - 14:23
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.

Sat, 25/06/2016 - 14:23
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.

Sat, 25/06/2016 - 14:23
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.

Sat, 25/06/2016 - 14:23
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.

Sat, 25/06/2016 - 14:23
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.

Sat, 25/06/2016 - 14:23
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.

Sat, 25/06/2016 - 14:23
Related Articles 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.

Sat, 25/06/2016 - 14:23
Related Articles 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.

Sat, 25/06/2016 - 14:23
Related Articles 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.

Sat, 25/06/2016 - 14:23
Related Articles 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.

Sat, 25/06/2016 - 14:23
Related Articles 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]

Monitoring Metabolite Profiles of Cannabis sativa L. Trichomes during Flowering Period Using 1H NMR-Based Metabolomics and Real-Time PCR.

Fri, 24/06/2016 - 13:55
Monitoring Metabolite Profiles of Cannabis sativa L. Trichomes during Flowering Period Using 1H NMR-Based Metabolomics and Real-Time PCR. Planta Med. 2016 Jun 23; Authors: Happyana N, Kayser O Abstract Cannabis sativa trichomes are glandular structures predominantly responsible for the biosynthesis of cannabinoids, the biologically active compounds unique to this plant. To the best of our knowledge, most metabolomic works on C. sativa that have been reported previously focused their investigations on the flowers and leaves of this plant. In this study, (1)H NMR-based metabolomics and real-time PCR analysis were applied for monitoring the metabolite profiles of C. sativa trichomes, variety Bediol, during the last 4 weeks of the flowering period. Partial least squares discriminant analysis models successfully classified metabolites of the trichomes based on the harvest time. Δ (9)-Tetrahydrocannabinolic acid (1) and cannabidiolic acid (2) constituted the vital differential components of the organic preparations, while asparagine, glutamine, fructose, and glucose proved to be their water-extracted counterparts. According to RT-PCR analysis, gene expression levels of olivetol synthase and olivetolic acid cyclase influenced the accumulation of cannabinoids in the Cannabis trichomes during the monitoring time. Moreover, quantitative (1)H NMR and RT-PCR analysis of the Cannabis trichomes suggested that the gene regulation of cannabinoid biosynthesis in the C. sativa variety Bediol is unique when compared with other C. sativa varieties. PMID: 27336318 [PubMed - as supplied by publisher]

CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells.

Fri, 24/06/2016 - 13:55
CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells. Open Biol. 2016 Jun;6(6) Authors: Gao D, Rahbar R, Fish EN Abstract In earlier studies, we showed that CCL5 enhances proliferation and survival of MCF-7 breast cancer cells in an mTOR-dependent manner and we provided evidence that, for T cells, CCL5 activation of CCR5 results in increased glycolysis and enhanced ATP production. Increases in metabolic activity of cancer cells, specifically increased glycolytic activity and increased expression of glucose transporters, are associated with tumour progression. In this report, we provide evidence that CCL5 enhances the proliferation of human breast cancer cell lines (MDA-MB-231, MCF-7) and mouse mammary tumour cells (MMTV-PyMT), mediated by CCR5 activation. Concomitant with enhanced proliferation we show that CCL5 increases cell surface expression of the glucose transporter GLUT1, and increases glucose uptake and ATP production by these cells. Blocking CCL5-inducible glucose uptake abrogates the enhanced proliferation induced by CCL5. We provide evidence that increased glucose uptake is associated with enhanced glycolysis, as measured by extracellular acidification. Moreover, CCL5 enhances the invasive capacity of these breast cancer cells. Using metabolomics, we demonstrate that the metabolic signature of CCL5-treated primary mouse mammary tumour cells reflects increased anabolic metabolism. The implications are that CCL5-CCR5 interactions in the tumour microenvironment regulate metabolic events, specifically glycolysis, to promote tumour proliferation and invasion. PMID: 27335323 [PubMed - in process]

[Development of Precision Medicine in the Surgical Treatment of Lung Cancer].

Fri, 24/06/2016 - 13:55
[Development of Precision Medicine in the Surgical Treatment of Lung Cancer]. Zhongguo Fei Ai Za Zhi. 2016 Jun 20;19(6):318-20 Authors: Tan F, Li N, Gao S, He J Abstract Precision medicine is to developing the most appropriate individualized treatment for each patient based on the macro to the micro level of individual differences. Genomic, proteomics, metabolomics data, and other big data analysis methods are the essence of precision medicine. Precision medicine brings the hope to overcome cancer. Among all kinds of tumors, lung cancer is the biggest threat to human. This paper reviewed the development of precision medicine in the surgical treatment of lung cancer. PMID: 27335287 [PubMed - in process]

Pages