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HUMAN METABOLOM

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https://www.readbyqxmd.com/read/28632924/metabolomics-as-a-driver-in-advancing-precision-medicine-in-sepsis
#1
Michelle Eckerle, Lilliam Ambroggio, Michael Puskarich, Brent Winston, Alan E Jones, Theodore J Standiford, Kathleen A Stringer
OBJECTIVE: The objective of this review is to explain the science of metabolomics-a science of systems biology that measures and studies endogenous small molecules (metabolites) that are present in a single biological sample-and its application to the diagnosis and treatment of sepsis. In addition, we discuss how discovery through metabolomics can contribute to the development of precision medicine targets for this complex disease state and the potential avenues for those new discoveries to be applied in the clinical environment...
June 20, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28629125/metabolomic-profiling-of-bile-acids-in-clinical-and-experimental-samples-of-alzheimer-s-disease
#2
Xiaobei Pan, Christopher T Elliott, Bernadette McGuinness, Peter Passmore, Patrick G Kehoe, Christian Hölscher, Paula L McClean, Stewart F Graham, Brian D Green
Certain endogenous bile acids have been proposed as potential therapies for ameliorating Alzheimer's disease (AD) but their role, if any, in the pathophysiology of this disease is not currently known. Given recent evidence of bile acids having protective and anti-inflammatory effects on the brain, it is important to establish how AD affects levels of endogenous bile acids. Using LC-MS/MS, this study profiled 22 bile acids in brain extracts and blood plasma from AD patients (n = 10) and age-matched control subjects (n = 10)...
June 17, 2017: Metabolites
https://www.readbyqxmd.com/read/28628333/coupling-targeted-and-untargeted-mass-spectrometry-for-metabolome-microbiome-wide-association-studies-of-human-fecal-samples
#3
Alexey V Melnik, Pieter C Dorrestein, Ricardo R da Silva, Embriette R Hyde, Alexander A Aksenov, Fernando Vargas, Amina Bouslimani, Ivan Protsyuk, Alan Jarmusch, Anupriya Tripathi, Theodore Alexandrov, Rob Knight
Increasing appreciation of the gut microbiome's role in health motivates understanding the molecular composition of human feces. To analyze such complex samples, we developed a platform coupling targeted and untargeted metabolomics. The approach is facilitated through split flow from one UPLC, joint timing triggered by contact closure relays and a script to retrieve the data. It is designed to detect specific metabolites of interest with high sensitivity, allows for correction of targeted information, enables better quantitation thus providing an advanced analytical tool for exploratory studies...
June 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28628112/gut-microbiome-and-serum-metabolome-alterations-in-obesity-and-after-weight-loss-intervention
#4
Ruixin Liu, Jie Hong, Xiaoqiang Xu, Qiang Feng, Dongya Zhang, Yanyun Gu, Juan Shi, Shaoqian Zhao, Wen Liu, Xiaokai Wang, Huihua Xia, Zhipeng Liu, Bin Cui, Peiwen Liang, Liuqing Xi, Jiabin Jin, Xiayang Ying, Xiaolin Wang, Xinjie Zhao, Wanyu Li, Huijue Jia, Zhou Lan, Fengyu Li, Rui Wang, Yingkai Sun, Minglan Yang, Yuxin Shen, Zhuye Jie, Junhua Li, Xiaomin Chen, Huanzi Zhong, Hailiang Xie, Yifei Zhang, Weiqiong Gu, Xiaxing Deng, Baiyong Shen, Xun Xu, Huanming Yang, Guowang Xu, Yufang Bi, Shenghan Lai, Jian Wang, Lu Qi, Lise Madsen, Jiqiu Wang, Guang Ning, Karsten Kristiansen, Weiqing Wang
Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28627779/new-horizon-for-breast-cancer-biomarker-discoveries-what-might-the-liquid-biopsy-of-nipple-aspirate-fluid-hold
#5
Ferdinando Mannello
The existence of cellular, molecular and biochemical heterogeneity of human breast cancers reveals the intricacy of biomarkers complexity, stimulating studies on new approaches (like "liquid biopsies") for the improvements in precision medicine. Breast cancer is recognized as a leading cause of morbidity and mortality worldwide with tumors significantly diverse and containing many types of cells showing different genetic and epigenetic profiles. In this field, the technology of Liquid Biopsy (applied to a fluid produced by breast gland, named nipple aspirate fluids, NAF) highlights the power of combining basic and clinical research...
June 19, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28627174/integrative-analysis-of-renal-ischemia-reperfusion-injury-and-remote-ischemic-preconditioning-in-mice
#6
Kumsun Cho, Sang-Il Min, Sanghyun Ahn, Seung-Kee Min, Curie Ahn, Kyung-Sang Yu, In-Jin Jang, Joo-Youn Cho, Jongwon Ha
Remote ischemic preconditioning (RIPC) is a strategy to induce resistance in a target organ against the oxidative stress and injury caused by ischemia and reperfusion (IR). RIPC harnesses the body's endogenous protective capabilities through brief episodes of IR applied in organs remote from the target. Few studies have analyzed this phenomenon in the kidney. Furthermore, the window of protection representing RIPC efficacy has not been fully elucidated. Here, we performed a multi-omics study to specify those associated with protective effects of RIPC against the IR injury...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28624737/optical-properties-of-the-human-lens-constituents
#7
Ekaterina A Zelentsova, Lyudmila V Yanshole, Anjella Zh Fursova, Yuri P Tsentalovich
The absorption and fluorescence properties of the metabolomic (MET), water-soluble and urea-soluble protein fractions from the middle-age, aged, and cataractous human lenses have been measured. At 280nm and 300nm the major lens absorbers are crystallins, which absorb more than 90% of light in the UV-B region (280-315nm). In middle-aged lenses, the absorption at 360nm is mostly provided by UV filters contained in the MET fraction. With aging, and especially with the cataract development, the absorption of MET fraction in UV-A region (315-400nm) decreases due to the drop of the UV filter concentration, while the absorption of protein fractions increases due to the accumulation of post-translational modifications...
June 3, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28622780/-iron-metabolism
#8
S Vaulont
Iron is an essential trace element ensuring many functions in the body. However, excess iron can be toxic with deleterious consequences on function and tissue integrity. The understanding of the molecular and cellular mechanisms allowing iron level to be kept at physiological concentration has greatly progressed in recent years, in particular with the identification of the iron-regulatory hormone, hepcidin and its receptor ferroportin, the sole iron exporter known to date. This discovery has improved our ability to diagnose and manage iron disorders and offered new therapeutic perspectives for an important class of human diseases...
May 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28622688/integration-of-metabolomics-transcriptomics-and-microrna-expression-profiling-reveals-a-mir-143-hk2-glucose-network-underlying-zinc-deficiency-associated-esophageal-neoplasia
#9
Louise Y Fong, Ruiyan Jing, Karl J Smalley, Cristian Taccioli, Johannes Fahrmann, Dinesh K Barupal, Hansjuerg Alder, John L Farber, Oliver Fiehn, Carlo M Croce
Esophageal squamous cell carcinoma (ESCC) in humans is a deadly disease associated with dietary zinc (Zn)-deficiency. In the rat esophagus, Zn-deficiency induces cell proliferation, alters mRNA and microRNA gene expression, and promotes ESCC. We investigated whether Zn-deficiency alters cell metabolism by evaluating metabolomic profiles of esophageal epithelia from Zn-deficient and replenished rats vs sufficient rats, using untargeted gas chromatography time-of-flight mass spectrometry (n = 8/group). The Zn-deficient proliferative esophagus exhibits a distinct metabolic profile with glucose down 153-fold and lactic acid up 1...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614058/egr1-regulates-cellular-metabolism-and-survival-in-endocrine-resistant-breast-cancer
#10
Ayesha N Shajahan-Haq, Simina M Boca, Lu Jin, Krithika Bhuvaneshwar, Yuriy Gusev, Amrita K Cheema, Diane D Demas, Kristopher S Raghavan, Ryan Michalek, Subha Madhavan, Robert Clarke
About 70% of all breast cancers are estrogen receptor alpha positive (ER+; ESR1). Many are treated with antiestrogens. Unfortunately, de novo and acquired resistance to antiestrogens is common but the underlying mechanisms remain unclear. Since growth of cancer cells is dependent on adequate energy and metabolites, the metabolomic profile of endocrine resistant breast cancers likely contains features that are deterministic of cell fate. Thus, we integrated data from metabolomic and transcriptomic analyses of ER+ MCF7-derived breast cancer cells that are antiestrogen sensitive (LCC1) or resistant (LCC9) that resulted in a gene-metabolite network associated with EGR1 (early growth response 1)...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28613827/tuning-metabolome-coverage-in-reversed-phase-lc-ms-metabolomics-of-meoh-extracted-samples-using-the-reconstitution-solvent-composition
#11
Anna Lindahl, Siv Sääf, Janne Lehtiö, Anders Nordström
Considering the physicochemical diversity of the metabolome, untargeted metabolomics will inevitably discriminate against certain compound classes. Efforts are nevertheless made to maximize the metabolome coverage. Contrary to the main steps of a typical liquid chromatography-mass spectrometry (LC-MS) metabolomics workflow, such as metabolite extraction, the sample reconstitution step has not been optimized for maximal metabolome coverage. This sample concentration step typically occurs after metabolite extraction, when dried samples are reconstituted in a solvent for injection on column...
June 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28611768/innate-immunity-and-breast-milk
#12
REVIEW
Nicole Theresa Cacho, Robert M Lawrence
Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611296/does-the-1h-nmr-plasma-metabolome-reflect-the-host-tumor-interactions-in-human-breast-cancer
#13
Vincent Richard, Raphaël Conotte, David Mayne, Jean-Marie Colet
Breast cancer (BC) is the most common diagnosed cancer and the leading cause of cancer death in women worldwide. There is an obvious need for a better understanding of BC biology. Alterations in the serum metabolome of BC patients have been identified but their clinical significance remains elusive. We evaluated by 1H-Nuclear Magnetic Resonance (1H-NMR) spectroscopy, filtered plasma metabolome of 50 early (EBC) and 15 metastatic BC (MBC) patients. Using Principal Component Analysis, Partial Least-Squares Discriminant Analysis and Hierarchical Clustering we show that plasma levels of glucose, lactate, pyruvate, alanine, leucine, isoleucine, glutamate, glutamine, valine, lysine, glycine, threonine, tyrosine, phenylalanine, acetate, acetoacetate, β-hydroxy-butyrate, urea, creatine and creatinine are modulated across patients clusters...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28607147/loss-of-the-clock-protein-per2-shortens-the-erythrocyte-life-span-in-mice
#14
Qi Sun, Yue Zhao, Yunxia Yang, Xiao Yang, Minghui Li, Xi Xu, Dan Weng, Junsong Wang, Jianfa Zhang
Cell proliferation and release from the bone marrow have been demonstrated to be controlled by circadian rhythms in both humans and mice. However, it is unclear whether local circadian clocks in the bone marrow influence physiological functions and life span of erythrocytes. Here, we report that loss of the clock gene Per2 significantly decreased erythrocyte life span. Mice deficient in Per2 were more susceptible to acute stresses in the erythrocytes, becoming severely anemic upon phenylhydrazine, osmotic, and H2O2 challenges...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28605027/phenotyping-of-gut-microbiota-focus-on-capillary-electrophoresis
#15
Manuel Ferrer, Beata Anna Raczkowska, Mónica Martínez-Martínez, Coral Barbas, David Rojo
The analysis of the microbial metabolome is crucial to fully understand the symbiotic relation between humans and microbes. That is why an explosion of metabolomics took place in the area. So far, at least several hundreds of microbial metabolites have been shown to be statistically altered when humans undergo a plethora of commonly faced perturbations. NMR and MS, usually coupled with GC, LC and CE have revealed their identities. CE is a robust analytical platform for the analysis of polar and ionic metabolites that are essential in order to assess the cells' activity...
June 12, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28603698/crimean-congo-hemorrhagic-fever-tick-host-virus-interactions
#16
REVIEW
Anna Papa, Katerina Tsergouli, Katerina Tsioka, Ali Mirazimi
Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans by bite of infected ticks or by direct contact with blood or tissues of viremic patients or animals. It causes to humans a severe disease with fatality up to 30%. The current knowledge about the vector-host-CCHFV interactions is very limited due to the high-level containment required for CCHFV studies. Among ticks, Hyalomma spp. are considered the most competent virus vectors. CCHFV evades the tick immune response, and following its replication in the lining of the tick's midgut, it is disseminated by the hemolymph in the salivary glands and reproductive organs...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28600214/validation-of-onchocerciasis-biomarker-n-acetyltyramine-o-glucuronide-natog
#17
Daniel Globisch, Lisa M Eubanks, Ryan J Shirey, Kenneth M Pfarr, Samuel Wanji, Alexander Y Debrah, Achim Hoerauf, Kim D Janda
The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach...
May 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28600026/metabolitepredict-a-de-novo-human-metabolomics-prediction-system-and-its-applications-in-rheumatoid-arthritis
#18
QuanQiu Wang, Rong Xu
Human metabolomics has great potential in disease mechanism understanding, early diagnosis, and therapy. Existing metabolomics studies are often based on profiling patient biofluids and tissue samples and are difficult owing to the challenges of sample collection and data processing. Here, we report an alternative approach and developed a computation-based prediction system, MetabolitePredict, for disease metabolomics biomarker prediction. We applied MetabolitePredict to identify metabolite biomarkers and metabolite targeting therapies for rheumatoid arthritis (RA), a last-lasting complex disease with multiple genetic and environmental factors involved...
June 6, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28599201/serum-metabolome-biomarkers-associate-low-level-environmental-perfluorinated-compound-exposure-with-oxidative-nitrosative-stress-in-humans
#19
Xiaofei Wang, Liangpo Liu, Weibing Zhang, Jie Zhang, Xiaoyan Du, Qingyu Huang, Meiping Tian, Heqing Shen
Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort...
June 6, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28598965/metabolic-network-segmentation-a-probabilistic-graphical-modeling-approach-to-identify-the-sites-and-sequential-order-of-metabolic-regulation-from-non-targeted-metabolomics-data
#20
Andreas Kuehne, Urs Mayr, Daniel C Sévin, Manfred Claassen, Nicola Zamboni
In recent years, the number of large-scale metabolomics studies on various cellular processes in different organisms has increased drastically. However, it remains a major challenge to perform a systematic identification of mechanistic regulatory events that mediate the observed changes in metabolite levels, due to complex interdependencies within metabolic networks. We present the metabolic network segmentation (MNS) algorithm, a probabilistic graphical modeling approach that enables genome-scale, automated prediction of regulated metabolic reactions from differential or serial metabolomics data...
June 9, 2017: PLoS Computational Biology
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