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https://www.readbyqxmd.com/read/28230703/omics-and-cachexia
#1
Brigitte Twelkmeyer, Nicolas Tardif, Olav Rooyackers
PURPOSE OF REVIEW: The purpose of this review is to recapture recent advances in cachexia-related diseases, mainly cancer cachexia, and treatment using genomic, transcriptomics, proteomic, and metabolomics-related techniques. RECENT FINDINGS: From recent studies in the cancer cachexia field it is clear that the tumor has a direct effect on distant organs via its secretome. The affected pathways on the other hand were largely known from earlier studies with changes in energy-related pathways (mainly lipid metabolism) and the protein degradation pathways...
February 21, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28229591/ass1-is-a-metabolic-regulator-of-colorectal-cancer-pathogenicity
#2
Leslie A Bateman, Wan-Min Ku, Martin J Heslin, Carlo M Contreras, Christine F Skibola, Daniel K Nomura
Like many cancer types, colorectal cancers have dysregulated metabolism that promotes their pathogenic features. In this study, we used the activity-based protein profiling chemoproteomic platform to profile cysteine-reactive metabolic enzymes that are upregulated in primary human colorectal tumors. We identified argininosuccinate synthase 1 (ASS1) as an upregulated target in primary human colorectal tumors and show that pharmacological inhibition or genetic ablation of ASS1 impairs colorectal cancer colorectal pathogenicity...
February 23, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28228253/sirt6-suppresses-cancer-stem-like-capacity-in-tumors-with-pi3k-activation-independently-of-its-deacetylase-activity
#3
Rafael M Ioris, Mirco Galié, Giorgio Ramadori, Jason G Anderson, Anne Charollais, Georgia Konstantinidou, Xavier Brenachot, Ebru Aras, Algera Goga, Nicholas Ceglia, Carlos Sebastián, Denis Martinvalet, Raul Mostoslavsky, Pierre Baldi, Roberto Coppari
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive cancer cells bear mutations that activate phosphatidylinositol-3-kinase (PI3K) signaling, and overexpression of SIRT6 reduces growth, progression, and grade of breast cancer in a mouse model with PI3K activation. Tumor metabolomic and transcriptomic analyses reveal that SIRT6 overexpression dampens PI3K signaling and stem-like characteristics and causes metabolic rearrangements in this cancer model...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226774/modeling-non-clinical-and-clinical-drug-tests-in-gaucher-disease
#4
Clyde F Phelix, Allen K Bourdon, Greg Villareal, Richard G LeBaron, Clyde F Phelix, Allen K Bourdon, Greg Villareal, Richard G LeBaron, Richard G LeBaron, Clyde F Phelix, Allen K Bourdon, Greg Villareal
There is need for modeling biological systems to accelerate drug pipelines for treating metabolic diseases. The eliglustat treatment for Gaucher disease is approved by the FDA with a companion genomic test. The Transcriptome-To-Metabolome™ biosimulation technology was used to model, in silico, a standard non-clinical eliglustat test with an in vitro canine kidney cell system over-expressing a human gene; and a clinical test using human fibroblasts from control and Gaucher disease subjects. Protein homology modeling and docking studies were included to gather affinity parameters for the kinetic metabolic model...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225594/mass-spectral-feature-list-optimizer-ms-flo-a-tool-to-minimize-false-positive-peak-reports-in-untargeted-lc-ms-data-processing
#5
Brian C Defelice, Sajjan Singh Mehta, Stephanie Samra, Tomas Cajka, Benjamin Wancewicz, Johannes F Fahrmann, Oliver Fiehn
Untargeted metabolomics by liquid chromatography-mass spectrometry generates data rich chromatograms in form of m/z-retention time features. Managing such datasets is a bottleneck. Many popular data processing tools, including XCMS-online and MZmine2, yield numerous false positive peak detections. Flagging and removing such false peaks manually is a time consuming task and prone to human error. We present a web application, MS Feature List Optimizer (MS-FLO), to improve the quality of feature lists after initial processing to expedite the process of data curation...
February 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28220994/positional-enrichment-by-proton-analysis-pepa-a-one-dimensional-1-h-nmr-approach-for-13-c-stable-isotope-tracer-studies-in-metabolomics
#6
Maria Vinaixa, Miguel A Rodríguez, Suvi Aivio, Jordi Capellades, Josep Gómez, Nicolau Canyellas, Travis H Stracker, Oscar Yanes
A novel metabolomics approach for NMR-based stable isotope tracer studies called PEPA is presented, and its performance validated using human cancer cells. PEPA detects the position of carbon label in isotopically enriched metabolites and quantifies fractional enrichment by indirect determination of (13) C-satellite peaks using 1D-(1) H-NMR spectra. In comparison with (13) C-NMR, TOCSY and HSQC, PEPA improves sensitivity, accelerates the elucidation of (13) C positions in labeled metabolites and the quantification of the percentage of stable isotope enrichment...
February 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28220550/metabolomic-profiling-in-umbilical-venous-plasma-reveals-effects-of-dietary-rumen-protected-arginine-or-n-carbamylglutamate-supplementation-in-nutrient-restricted-hu-sheep-during-pregnancy
#7
L Sun, H Zhang, Y Fan, Y Guo, G Zhang, H Nie, F Wang
Maternal nutrient restriction during pregnancy is a major problem worldwide for human and animal production. Arginine (Arg) is critical to health, growth and reproduction. N-carbamylglutamate (NCG), a key enzyme in arginine synthesis, is not extensively degraded in rumen. The aim of this study was to investigate ameliorating effects of rumen-protected arginine (RP-Arg) and NCG supplementation on dietary in undernourished Hu sheep during gestation. From day 35 to 110 of gestation, 32 Hu ewes carrying twin foetuses were randomly divided into four groups: a control (CG) group (n = 8; fed 100% National Research Council (NRC) requirements for pregnant sheep), a nutrient-restricted (RG) group (n = 8; fed 50% NRC requirements, which included 50% mineral-vitamin mixture) and two treatment (Arg and NCG) groups (n = 8; fed 50% NRC requirements supplemented with 20 g/day RP-Arg or 5 g/day NCG, which included 50% mineral-vitamin mixture)...
February 20, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28220056/a-lipidomic-and-metabolomic-serum-signature-from-nonhuman-primates-exposed-to-ionizing-radiation
#8
Evan L Pannkuk, Evagelia C Laiakis, Tytus D Mak, Giuseppe Astarita, Simon Authier, Karen Wong, Albert J Fornace
INTRODUCTION: Due to dangers associated with potential accidents from nuclear energy and terrorist threats, there is a need for high-throughput biodosimetry to rapidly assess individual doses of radiation exposure. Lipidomics and metabolomics are becoming common tools for determining global signatures after disease or other physical insult and provide a "snapshot" of potential cellular damage. OBJECTIVES: The current study assesses changes in the nonhuman primate (NHP) serum lipidome and metabolome 7 days following exposure to ionizing radiation (IR)...
May 2016: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28219950/nutritional-modulation-of-mouse-and-human-liver-bud-growth-through-a-branched-amino-acid-metabolism
#9
Hiroyuki Koike, Ran-Ran Zhang, Yasuharu Ueno, Keisuke Sekine, Yun-Wen Zheng, Takanori Takebe, Hideki Taniguchi
Liver bud progenitors experience a transient amplification during early organ growth phase, yet the responsible mechanism was not fully understood. Collective evidence highlighted the specific requirements in stem cell metabolism for expanding organ progenitors during organogenesis and regeneration. Here, transcriptome analyses showed progenitors of mouse and human liver bud growth stage specifically expressed branched chain aminotransferase1 gene, a known breakdown enzyme of branched-chain amino acid (BCAA) for energy generation...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28215546/analysis-of-human-serum-metabolome-for-potential-biomarkers-identification-of-erosive-oral-lichen-planus
#10
Xu-Yan Yang, Shuai-Nan Zhang, Xu-Zhao Li, Yu Wang, Xiao-Dong Yin
BACKGROUND: Oral lichen planus (OLP) is a chronic auto-inflammatory mucositis and potentially oral premalignant lesion. Erosive OLP patients display the higher canceration rate as compared to the patients with non-erosive OLP. Identification of the potential biomarkers associated with erosive OLP may help to investigate the disease pathogenesis and to improve clinical treatment. METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) combined with pattern recognition approaches were integrated to acquire differentially expressed metabolites for the pathways analysis and elucidate mechanisms of disease...
February 16, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28213610/prebiotic-inulin-type-fructans-induce-specific-changes-in-the-human-gut-microbiota
#11
Doris Vandeputte, Gwen Falony, Sara Vieira-Silva, Jun Wang, Manuela Sailer, Stephan Theis, Kristin Verbeke, Jeroen Raes
OBJECTIVE: Contrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterisation of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (gas chromatography mass spectrometry) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and faecal metabolites profiles...
February 17, 2017: Gut
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#12
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28208746/evidence-of-a-dha-signature-in-the-lipidome-and-metabolome-of-human-hepatocytes
#13
Veronica Ghini, Mattia Di Nunzio, Leonardo Tenori, Veronica Valli, Francesca Danesi, Francesco Capozzi, Claudio Luchinat, Alessandra Bordoni
Cell supplementation with bioactive molecules often causes a perturbation in the whole intracellular environment. Omics techniques can be applied for the assessment of this perturbation. In this study, the overall effect of docosahexaenoic acid (DHA) supplementation on cultured human hepatocyte lipidome and metabolome has been investigated using nuclear magnetic resonance (NMR) in combination with traditional techniques. The effect of two additional bioactives sharing with DHA the lipid-lowering effect-propionic acid (PRO) and protocatechuic acid (PCA)-has also been evaluated in the context of possible synergism...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208268/medical-swab-analysis-using-desorption-electrospray-ionization-mass-spectrometry-a-noninvasive-approach-for-mucosal-diagnostics
#14
Pamela Pruski, David A MacIntyre, Holly V Lewis, Paolo Inglese, Gonçalo D S Correia, Trevor T Hansel, Phillip R Bennett, Elaine Holmes, Zoltan Takats
Medical swabs are routinely used worldwide to sample human mucosa for microbiological screening with culture methods. These are usually time-consuming and have a narrow focus on screening for particular microorganism species. As an alternative, direct mass spectrometric profiling of the mucosal metabolome provides a broader window into the mucosal ecosystem. We present for the first time a minimal effort/minimal-disruption technique for augmenting the information obtained from clinical swab analysis with mucosal metabolome profiling using desorption electrospray ionization mass spectrometry (DESI-MS) analysis...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28208263/visualization-quantification-and-alignment-of-spectral-drift-in-population-scale-untargeted-metabolomics-data
#15
Jeramie D Watrous, Mir Henglin, Brian Claggett, Kim A Lehmann, Martin G Larson, Susan Cheng, Mohit Jain
Untargeted liquid-chromatography-mass spectrometry (LC-MS)-based metabolomics analysis of human biospecimens has become among the most promising strategies for probing the underpinnings of human health and disease. Analysis of spectral data across population scale cohorts, however, is precluded by day-to-day nonlinear signal drifts in LC retention time or batch effects that complicate comparison of thousands of untargeted peaks. To date, there exists no efficient means of visualization and quantitative assessment of signal drift, correction of drift when present, and automated filtering of unstable spectral features, particularly across thousands of data files in population scale experiments...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28207922/mass-spectrometry-for-the-discovery-of-biomarkers-of-sepsis
#16
REVIEW
Katelyn R Ludwig, Amanda B Hummon
Sepsis is a serious medical condition that occurs in 30% of patients in intensive care units (ICUs). Early detection of sepsis is key to prevent its progression to severe sepsis and septic shock, which can cause organ failure and death. Diagnostic criteria for sepsis are nonspecific and hinder a timely diagnosis in patients. Therefore, there is currently a large effort to detect biomarkers that can aid physicians in the diagnosis and prognosis of sepsis. Mass spectrometry is often the method of choice to detect metabolomic and proteomic changes that occur during sepsis progression...
February 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28207855/novel-approaches-for-the-taxonomic-and-metabolic-characterization-of-lactobacilli-integration-of-16s-rrna-gene-sequencing-with-maldi-tof-ms-and-1h-nmr
#17
Claudio Foschi, Luca Laghi, Carola Parolin, Barbara Giordani, Monica Compri, Roberto Cevenini, Antonella Marangoni, Beatrice Vitali
Lactobacilli represent a wide range of bacterial species with several implications for the human host. They play a crucial role in maintaining the ecological equilibrium of different biological niches and are essential for fermented food production and probiotic formulation. Despite the consensus about the 'health-promoting' significance of Lactobacillus genus, its genotypic and phenotypic characterization still poses several difficulties. The aim of this study was to assess the integration of different approaches, genotypic (16S rRNA gene sequencing), proteomic (MALDI-TOF MS) and metabolomic (1H-NMR), for the taxonomic and metabolic characterization of Lactobacillus species...
2017: PloS One
https://www.readbyqxmd.com/read/28207275/macrotermycins-a-d-glycosylated-macrolactams-from-a-termite-associated-amycolatopsis-sp-m39
#18
Christine Beemelmanns, Timothy R Ramadhar, Ki Hyun Kim, Jonathan L Klassen, Shugeng Cao, Thomas P Wyche, Yanpeng Hou, Michael Poulsen, Tim S Bugni, Cameron R Currie, Jon Clardy
Bioassay-guided metabolomic analyses led to the characterization of four new 20-membered glycosylated polyketide macrolactams, macrotermycins A-D, from a termite-associated actinomycete, Amycolatopsis sp. M39. M39's sequenced genome revealed the macrotermycin's putative biosynthetic gene cluster. Macrotermycins A and C had antibacterial activity against human-pathogenic Staphylococcus aureus and, of greater ecological relevance, they also had selective antifungal activity against a fungal parasite of the termite fungal garden...
February 16, 2017: Organic Letters
https://www.readbyqxmd.com/read/28201987/an-integrative-metabolomics-and-transcriptomics-study-to-identify-metabolic-alterations-in-aged-skin-of-humans-in-vivo
#19
Andreas Kuehne, Janosch Hildebrand, Joern Soehle, Horst Wenck, Lara Terstegen, Stefan Gallinat, Anja Knott, Marc Winnefeld, Nicola Zamboni
BACKGROUND: Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterations like DNA-methylation changes, metabolic adaptations have been recently linked to impaired skin function in elder humans. Understanding of these metabolic adaptations in aged skin is of special interest to devise topical treatments that potentially reverse or alleviate age-dependent skin deterioration and the occurrence of skin disorders...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28199350/25-hydroxyvitamin-d3-and-1-25-dihydroxyvitamin-d3-exert-distinct-effects-on-human-skeletal-muscle-function-and-gene-expression
#20
Zaki K Hassan-Smith, Carl Jenkinson, David J Smith, Ivan Hernandez, Stuart A Morgan, Nicola J Crabtree, Neil J Gittoes, Brian G Keevil, Paul M Stewart, Martin Hewison
Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers...
2017: PloS One
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