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https://www.readbyqxmd.com/read/28231575/individual-biomarkers-using-molecular-personalized-medicine-approaches
#1
Hans P Zenner
Molecular personalized medicine tries to generate individual predictive biomarkers to assist doctors in their decision making. These are thought to improve the efficacy and lower the toxicity of a treatment. The molecular basis of the desired high-precision prediction is modern "omex" technologies providing high-throughput bioanalytical methods. These include genomics and epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, imaging, and functional analyses. In most cases, producing big data also requires a complex biomathematical analysis...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28230862/inactivation-of-lsd1-triggers-senescence-in-trophoblast-stem-cells-by-induction-of-sirt4
#2
Josefina Castex, Dominica Willmann, Toufike Kanouni, Laura Arrigoni, Yan Li, Marcel Friedrich, Michael Schleicher, Simon Wöhrle, Mark Pearson, Norbert Kraut, Michaël Méret, Thomas Manke, Eric Metzger, Roland Schüle, Thomas Günther
Coordination of energy metabolism is essential for homeostasis of stem cells, whereas an imbalance in energy homeostasis causes disease and accelerated aging. Here we show that deletion or enzymatic inactivation of lysine-specific demethylase 1 (Lsd1) triggers senescence in trophoblast stem cells (TSCs). Genome-wide transcriptional profiling of TSCs following Lsd1 inhibition shows gene set enrichment of aging and metabolic pathways. Consistently, global metabolomic and phenotypic analyses disclose an unbalanced redox status, decreased glutamine anaplerosis and mitochondrial function...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230703/omics-and-cachexia
#3
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/28230173/a-novel-physiological-role-for-cardiac-myoglobin-in-lipid-metabolism
#4
Ulrike B Hendgen-Cotta, Sonja Esfeld, Cristina Coman, Robert Ahrends, Ludger Klein-Hitpass, Ulrich Flögel, Tienush Rassaf, Matthias Totzeck
Continuous contractile activity of the heart is essential and the required energy is mostly provided by fatty acid (FA) oxidation. Myocardial lipid accumulation can lead to pathological responses, however the underlying mechanisms remain elusive. The role of myoglobin in dioxygen binding in cardiomyocytes and oxidative skeletal muscle has widely been appreciated. Our recent work established myoglobin as a protector of cardiac function in hypoxia and disease states. We here unravel a novel role of cardiac myoglobin in governing FA metabolism to ensure the physiological energy production through β-oxidation, preventing myocardial lipid accumulation and preserving cardiac functions...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230109/pentose-sugars-inhibit-metabolism-and-increase-expression-of-an-agrd-type-cyclic-pentapeptide-in-clostridium-thermocellum
#5
Tobin J Verbeke, Richard J Giannone, Dawn M Klingeman, Nancy L Engle, Thomas Rydzak, Adam M Guss, Timothy J Tschaplinski, Steven D Brown, Robert L Hettich, James G Elkins
Clostridium thermocellum could potentially be used as a microbial biocatalyst to produce renewable fuels directly from lignocellulosic biomass due to its ability to rapidly solubilize plant cell walls. While the organism readily ferments sugars derived from cellulose, pentose sugars from xylan are not metabolized. Here, we show that non-fermentable pentoses inhibit growth and end-product formation during fermentation of cellulose-derived sugars. Metabolomic experiments confirmed that xylose is transported intracellularly and reduced to the dead-end metabolite xylitol...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230078/unravelling-the-metabolic-impact-of-sbs-associated-microbial-dysbiosis-insights-from-the-piglet-short-bowel-syndrome-model
#6
Prue M Pereira-Fantini, Sean G Byars, James Pitt, Susan Lapthorne, Fiona Fouhy, Paul D Cotter, Julie E Bines
Liver disease is a major source of morbidity and mortality in children with short bowel syndrome (SBS). SBS-associated microbial dysbiosis has recently been implicated in the development of SBS-associated liver disease (SBS-ALD), however the pathological implications of this association have not been explored. In this study high-throughput sequencing of colonic content from the well-validated piglet SBS-ALD model was examined to determine alterations in microbial communities, and concurrent metabolic alterations identified in urine samples via targeted mass spectrometry approaches (GC-MS, LC-MS, FIA-MS) further uncovered impacts of microbial disturbance on metabolic outcomes in SBS-ALD...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229591/ass1-is-a-metabolic-regulator-of-colorectal-cancer-pathogenicity
#7
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/28229388/effects-of-boron-supplementation-on-peripartum-dairy-cows-health
#8
Abdullah Basoglu, Nuri Baspinar, Leonardo Tenori, Alessia Vignoli, Erdem Gulersoy
Although many different dietary studies on the prevention of negative energy balance related diseases are often encountered, this is the first study investigating the effects of boron supplementation on peripartum dairy cows' health in the light of an omics approach. Twenty-eight healthy cows (1 control and 3 experimental groups) were enrolled from 2 months before predicted calving until 2 months after calving. Experimental groups were assigned to receive boron at increasing doses as an oral bolus. Production parameters, biochemical profile, Nuclear Magnetic Resonance based metabolomics profile, and mRNA abundance of gluconeogenic enzymes and lipid oxidation genes were determined...
February 22, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28229225/implications-of-sdhb-genetic-testing-in-patients-with-sporadic-pheochromocytoma
#9
Aurelie Maignan, Carole Guerin, Valentin Julliard, Nunzia-Cinzia Paladino, Edward Kim, Philippe Roche, Fréderic Castinetti, Wassim Essamet, Julien Mancini, Alessio Imperiale, Roderick Clifton-Bligh, Pauline Romanet, Anne Barlier, Karel Pacak, Fréderic Sebag, David Taïeb
PURPOSE: Succinate dehydrogenase B (SDHB) associated pheochromocytomas (PHEOs) are associated with a higher risk of tumor aggressiveness and malignancy. The aim of the present study was to evaluate (1) the frequency of germline SDHB mutations in apparently sporadic patients with PHEO who undergo preoperative genetic testing and (2) the ability to predict pathogenic mutations. METHODS: From 2012 to 2016, 82 patients underwent a PHEO surgical resection. Sixteen were operated in the context of hereditary PHEO and were excluded from analysis...
February 22, 2017: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/28228253/sirt6-suppresses-cancer-stem-like-capacity-in-tumors-with-pi3k-activation-independently-of-its-deacetylase-activity
#10
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/28227255/multi-omic-approaches-for-characterization-of-hepatocellular-carcinoma
#11
Habtom W Ressom, Cristina Di Poto, Alessia Ferrarini, Yunli Hu, Mohammad R Nezami Ranjbar, Ehwang Song, Rency S Varghese, Minkun Wang, Shiyue Zhou, Rui Zhu, Yiming Zuo, Mahlet G Tadesse, Yehia Mechref, Habtom W Ressom, Cristina Di Poto, Alessia Ferrarini, Yunli Hu, Mohammad R Nezami Ranjbar, Ehwang Song, Rency S Varghese, Minkun Wang, Shiyue Zhou, Rui Zhu, Yiming Zuo, Mahlet G Tadesse, Yehia Mechref, Mahlet G Tadesse, Shiyue ZhOU, Rui Zhu, Yehia Mechref, Alessia Ferrarini, Cristina Di Poto, Yiming Zuo, Habtom W Ressom, Mohammad R Nezami Ranjbar, Ehwang Song, Minkun Wang, Rency S Varghese, Yunli Hu
Multi-omic approaches offer the opportunity to characterize complex diseases such as cancer at various molecular levels. In this paper, we present transcriptomic, proteomic/glycoproteomic, glycomic, and metabolomic (TPGM) data we acquired by analysis of liver tissues from hepatocellular carcinoma (HCC) cases and patients with liver cirrhosis. We evaluated changes in the levels of transcripts, proteins, glycans, and metabolites between tumor and cirrhotic tissues by statistical methods. We demonstrated the potential of multi-omic approaches and network analysis to investigate the interactions among these biomolecules in the progression of liver cirrhosis to HCC...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226774/modeling-non-clinical-and-clinical-drug-tests-in-gaucher-disease
#12
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/28225596/top-down-metabolomic-approaches-for-nitrogen-containing-metabolites
#13
Ryo Nakabayashi, Kei Hashimoto, Kiminori Toyooka, Kazuki Saito
Streamlining the processes that reveal heteroatom-containing metabolites and their biosynthetic genes is essential in integrated metabolomics studies. These metabolites are especially targeted for their potential pharmaceutical activities. By using a Fourier-transform ion cyclotron resonance-mass spectrometry (FTICR-MS) instrument, we provide top-down targeted metabolomic analyses using ultrahigh-resolution liquid chromatography-mass spectrometry (LC-MS), high-resolution matrix-assisted laser desorption/ionization (MALDI), and high-resolution imaging mass spectrometry (IMS) with (15)N labeling of nitrogen-containing metabolites...
February 22, 2017: Analytical Chemistry
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
#14
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/28225587/compms2miner-an-automatable-metabolite-identification-visualization-and-data-sharing-r-package-for-high-resolution-lc-ms-datasets
#15
William Matthew Bell Edmands, Lauren M Petrick, Dinesh Kumar Barupal, Augustin Scalbert, Mark Wilson, Jeffrey Wickliffe, Stephen M Rappaport
A long-standing challenge of untargeted metabolomic profiling by ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) is efficient transition from unknown mass spectral features to confident metabolite annotations. The compMS2Miner (Comprehensive MS2 Miner) package was developed in the R language to facilitate rapid, comprehensive feature annotation using a peak-picker-output and MS2 data files as inputs. The number of MS2 spectra that can be collected during a metabolomic profiling experiment far outweigh the amount of time required for pain-staking manual interpretation, therefore a degree of software workflow autonomy is required for broad-scale metabolite annotation...
February 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28225098/urinary-metabolic-signatures-and-early-triage-of-acute-radiation-exposure-in-rat-model
#16
Mingxiao Zhao, Kim Kt Lau, Xian Zhou, Jianfang Wu, Jun Yang, Chang Wang
After a large-scale radiological accident, early-response biomarkers to assess radiation exposure over a broad dose range are not only the basis of rapid radiation triage, but are also the key to the rational use of limited medical resources and to the improvement of treatment efficiency. Because of its high throughput, rapid assays and minimally invasive sample collection, metabolomics has been applied to research into radiation exposure biomarkers in recent years. Due to the complexity of radiobiological effects, most of the potential biomarkers are both dose-dependent and time-dependent...
February 22, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28225065/a-comprehensive-analysis-of-metabolomics-and-transcriptomics-in-cervical-cancer
#17
Kai Yang, Bairong Xia, Wenjie Wang, Jinlong Cheng, Mingzhu Yin, Hongyu Xie, Junnan Li, Libing Ma, Chunyan Yang, Ang Li, Xin Fan, Harman S Dhillon, Yan Hou, Ge Lou, Kang Li
Cervical cancer (CC) still remains a common and deadly malignancy among females in developing countries. More accurate and reliable diagnostic methods/biomarkers should be discovered. In this study, we performed a comprehensive analysis of metabolomics (285 samples) and transcriptomics (52 samples) on the potential diagnostic implication and metabolic characteristic description in cervical cancer. Sixty-two metabolites were different between CC and normal controls (NOR), in which 5 metabolites (bilirubin, LysoPC(17:0), n-oleoyl threonine, 12-hydroxydodecanoic acid and tetracosahexaenoic acid) were selected as candidate biomarkers for CC...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224908/comparison-of-multivariate-curve-resolution-strategies-in-quantitative-lcxlc-application-to-the-quantification-of-furanocoumarins-in-apiaceous-vegetables
#18
Daniel W Cook, Mackenzie L Burnham, David C Harmes, Dwight R Stoll, Sarah C Rutan
Comprehensive two-dimensional liquid chromatography (LC × LC) has been gaining popularity for the analysis of complex samples in a wide range of fields including metabolomics, environmental analysis, and food analysis. While LC × LC can provide greater chromatographic resolution than one-dimensional LC (1D-LC), overlapping peaks are often still present in separations of complex samples, a problem that can be alleviated by chemometric curve resolution techniques such as multivariate curve resolution-alternating least squares (MCR-ALS)...
April 8, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28223996/untargeted-metabotyping-lolium-perenne-reveals-population-level-variation-in-plant-flavonoids-and-alkaloids
#19
Mingshu Cao, Karl Fraser, Chris Jones, Alan Stewart, Thomas Lyons, Marty Faville, Brent Barrett
Metabolomics provides a powerful platform to characterize plants at the biochemical level, allowing a search for underlying genes and associations with higher level complex traits such as yield and nutritional value. Efficient and reliable methods to characterize metabolic variation in economically important species are considered of high value to the evaluation and prioritization of germplasm and breeding lines. In this investigation, a large-scale metabolomic survey was performed on a collection of diverse perennial ryegrass (Lolium perenne L...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28223686/metabolic-profiling-of-presymptomatic-huntington-s-disease-sheep-reveals-novel-biomarkers
#20
Debra J Skene, Benita Middleton, Cara K Fraser, Jeroen L A Pennings, Timothy R Kuchel, Skye R Rudiger, C Simon Bawden, A Jennifer Morton
The pronounced cachexia (unexplained wasting) seen in Huntington's disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea...
February 22, 2017: Scientific Reports
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