NMR Spectroscopy for Metabolomics Research

Metabolites, Journal Year: 2019, Volume and Issue: 9(7), P. 123 - 123

Published: June 27, 2019

Over the past two decades, nuclear magnetic resonance (NMR) has emerged as one of three principal analytical techniques used in metabolomics (the other being gas chromatography coupled to mass spectrometry (GC-MS) and liquid with single-stage (LC-MS)). The relative ease sample preparation, ability quantify metabolite levels, high level experimental reproducibility, inherently nondestructive nature NMR spectroscopy have made it preferred platform for long-term or large-scale clinical metabolomic studies. These advantages, however, are often outweighed by fact that most techniques, including both LC-MS GC-MS, more sensitive than NMR, lower limits detection typically 10 100 times better. This review is intended introduce readers field NMR-based highlight advantages disadvantages It will also explore some unique strengths metabolomics, particularly regard isotope selection/detection, mixture deconvolution via 2D spectroscopy, automation, noninvasively analyze native tissue specimens. Finally, this a number emerging technologies strengthen its utility overcome inherent limitations applications.

Language: Английский

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Metabolomics for Investigating Physiological and Pathophysiological Processes

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(4), P. 1819 - 1875

Published: Aug. 22, 2019

Metabolomics uses advanced analytical chemistry techniques to enable the high-throughput characterization of metabolites from cells, organs, tissues, or biofluids. The rapid growth in metabolomics is leading a renewed interest metabolism and role that small molecule play many biological processes. As result, traditional views as being simply “bricks mortar” cells just fuel for cellular energetics are upended. Indeed, appear have much more varied far important roles signaling molecules, immune modulators, endogenous toxins, environmental sensors. This review explores how yielding new insights into number physiological In particular, major focus on illustrating discoveries made through improving our understanding both normal physiology pathophysiology diseases. These influence organ function, nutrient sensing, gut physiology. Collectively, this work unified system-wide perspective biology wherein metabolites, proteins, genes understood interact synergistically modify actions functions organelles, organisms.

Language: Английский

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Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Cell stem cell, Journal Year: 2020, Volume and Issue: 26(6), P. 862 - 879.e11

Published: May 26, 2020

Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and endothelial also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs MTs with CFs sarcomeric structures T-tubules, enhanced contractility, mitochondrial respiration were electrophysiologically more mature than without CFs. Interactions mediating included coupling between through connexin 43 (CX43) gap junctions increased intracellular cyclic AMP (cAMP). Scaled production thousands hiPSC-MTs was highly reproducible across lines differentiated cell batches. containing healthy-control hiPSC-CFs patients arrhythmogenic cardiomyopathy strikingly recapitulated features the disease. Our MT model thus a simple versatile platform for modeling multicellular diseases will facilitate industry academic engagement high-throughput molecular screening.

Language: Английский

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Recent advances in the application of metabolomics for food safety control and food quality analyses

Critical Reviews in Food Science and Nutrition, Journal Year: 2020, Volume and Issue: 61(9), P. 1448 - 1469

Published: May 22, 2020

As one of the omics fields, metabolomics has unique advantages in facilitating understanding physiological and pathological activities biology, physiology, pathology, food science. In this review, based on developments analytical chemistry tools, cheminformatics, bioinformatics methods, we highlight current applications safety, authenticity quality, traceability. Additionally, combined use with other techniques for "foodomics" is comprehensively described. Finally, latest advances, practical challenges limitations, requirements related to application are critically discussed, providing new insight into analysis.

Language: Английский

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Recent advances in metabolomics analysis for early drug development

Drug Discovery Today, Journal Year: 2022, Volume and Issue: 27(6), P. 1763 - 1773

Published: Feb. 24, 2022

The pharmaceutical industry adapted proteomics and other 'omics technologies for drug research early following their initial introduction. Although metabolomics lacked behind in this development, it has now become an accepted widely applied approach development. Over the past few decades, evolved from a pure exploratory tool to more mature quantitative biochemical technology. Several metabolomics-based platforms are during phases of discovery. Metabolomics analysis assists definition physiological response target engagement (TE) markers as well elucidation mode action (MoA) candidates under investigation. In review, we highlight recent examples novel developments analyses

Language: Английский

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Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Medicinal Research Reviews, Journal Year: 2022, Volume and Issue: 42(4), P. 1518 - 1544

Published: March 10, 2022

Abstract Diabetic kidney disease (DKD) is one of the most prevalent comorbidities diabetes mellitus and leading cause end‐stage renal (ESRD). DKD results from chronic exposure to hyperglycemia, progressive alterations in structure function. The early development clinically silent when albuminuria detected lesions are often at advanced stages, rapid function decline towards ESRD. progression can be arrested or substantially delayed if addressed stages. A major limitation current methods absence non‐albuminuric phenotypes diabetic nephropathy, which becomes increasingly lacks focused therapy. Metabolomics an ever‐evolving omics technology that enables study metabolites, downstream products every biochemical event occurs organism. disclosures complex metabolic networks provide knowledge very foundation several physiological pathophysiological processes, ultimately identification diseases' unique signatures. In this sense, metabolomics a promising tool not only for diagnosis but also pre‐disease states would confer personalized clinical practice. Herein, use as identify signature tubule interstitial diagnose predict time‐course will discussed. addition, proficiency limitations currently available high‐throughput metabolomic techniques

Language: Английский

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Studying Metabolism by NMR-Based Metabolomics

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: April 27, 2022

During the past few decades, direct analysis of metabolic intermediates in biological samples has greatly improved understanding processes. The most used technologies for these advances have been mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. NMR is traditionally to elucidate molecular structures now extended complex mixtures, as samples: NMR-based metabolomics. There are however other areas small molecule biochemistry which equally powerful. These include quantification metabolites (qNMR); use stable isotope tracers determine fate drugs or nutrients, unravelling new pathways, flux through pathways; metabolite-protein interactions regulation pharmacological effects. Computational tools resources automating spectra extracting meaningful biochemical information developed tandem contributes a more detailed systems biochemistry. In this review, we highlight contribution biochemistry, specifically studies by reviewing state-of-the-art methodologies spectroscopy future directions.

Language: Английский

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Shear Stress Regulation of Endothelial Glycocalyx Structure Is Determined by Glucobiosynthesis

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2019, Volume and Issue: 40(2), P. 350 - 364

Published: Dec. 12, 2019

Endothelial cells exposed to laminar shear stress express a thick glycocalyx on their surface that plays an important role in reducing vascular permeability and endothelial anti-inflammatory, antithrombotic, antiangiogenic properties. Production maintenance of this layer is dependent cellular carbohydrate synthesis, but its regulation still unknown. Approach Results: Here, we show biosynthesis the major structural component glycocalyx, hyaluronan, regulated by shear. Both vitro as well vivo, hyaluronan expression increased reduced when oscillatory flow, which KLF2 (Krüppel-like Factor 2). Using CRISPR-CAS9 edited small tetracysteine tag endogenous HAS2 (hyaluronan synthase 2), demonstrated translocation cell membrane during Hyaluronan production was shown be further driven availability substrates UDP-glucosamine UDP-glucuronic acid. inhibits glycolysis allows for glucose intermediates shuttle into hexosamine- glucuronic acid pathways, measured using nuclear magnetic resonance analysis combination with 13C-labeled glucose.These data demonstrate how function functional adaptation coupled KLF2-mediated glycolysis.

Language: Английский

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The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

Antioxidants, Journal Year: 2020, Volume and Issue: 9(10), P. 966 - 966

Published: Oct. 9, 2020

As a carrier of many biologically active compounds, blood is exposed to oxidants greater extent than the intracellular environment. Serum albumin plays key role in antioxidant defence under both normal and oxidative stress conditions. This review evaluates data published literature from our own research on mechanisms enzymatic non-enzymatic activities that determine its participation redox modulation plasma intercellular fluid. For first time, results numerous clinical, biochemical, spectroscopic computational experiments devoted study allosteric functional properties protein associated with are analysed. It has been concluded it fundamentally possible regulate various ligands, binding and/or features by changing status. The perspectives for using practice discussed.

Language: Английский

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Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: Sept. 20, 2021

Personalized medicine is probably the most promising area being developed in modern medicine. This approach attempts to optimize therapies and patient care based on individual characteristics. Its success highly depends way characterization of disease its evolution, patient’s classification, follow-up treatment could be optimized. Thus, personalized must combine innovative tools measure, integrate model data. Towards this goal, clinical metabolomics appears as ideally suited obtain relevant information. Indeed, signature brings crucial insight stratify patients according their responses a pathology and/or treatment, provide prognostic diagnostic biomarkers, improve therapeutic outcomes. However, translation from laboratory studies practice remains subsequent challenge. Nuclear magnetic resonance spectroscopy (NMR) mass spectrometry (MS) are two key platforms for measurement metabolome. NMR has several advantages features that essential metabolomics. inherently very robust, reproducible, unbiased, quantitative, informative at structural molecular level, requires little sample preparation reduced data processing. also well adapted large cohorts, multi-sites longitudinal studies. review focus potential context Starting with current status NMR-based level highlighting strengths, weaknesses challenges, article explores how, far initial “opposition” or “competition”, MS have been integrated demonstrated great complementarity, terms classification biomarker identification. Finally, perspective discussion provides into methodological developments significantly raise more resolutive, sensitive accessible tool applications point-of-care diagnosis. Thanks these advances, strong join other analytical currently used settings.

Language: Английский

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