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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 1 hour 9 min ago

Rapid Cerebral Metabolic Shift during Neonatal Sepsis Is Attenuated by Enteral Colostrum Supplementation in Preterm Pigs.

Wed, 16/01/2019 - 14:47
Related Articles Rapid Cerebral Metabolic Shift during Neonatal Sepsis Is Attenuated by Enteral Colostrum Supplementation in Preterm Pigs. Metabolites. 2019 Jan 11;9(1): Authors: Alinaghi M, Jiang PP, Brunse A, Sangild PT, Bertram HC Abstract Sepsis, the clinical manifestation of serious infection, may disturb normal brain development, especially in preterm infants with an immature brain. We hypothesized that neonatal sepsis induces systemic metabolic alterations that rapidly affect metabolic signatures in immature brain and cerebrospinal fluid (CSF). Cesarean-delivered preterm pigs systemically received 10⁸ CFU/kg Staphylococcus epidermidis (SE) and were provided total parenteral nutrition (n = 9) or enteral supplementation with bovine colostrum (n = 10) and compared with uninfected pigs receiving parenteral nutrition (n = 7). Plasma, CSF, and brain tissue samples were collected after 24 h and analyzed by ¹H NMR-based metabolomics. Both plasma and CSF metabolomes revealed SE-induced changes in metabolite levels that reflected a modified energy metabolism. Hence, increased plasma lactate, alanine, and succinate levels, as well as CSF lactate levels, were observed during SE infection (all p < 0.05, ANOVA analysis). Myo-inositol, a glucose derivative known for beneficial effects on lung maturation in preterm infants, was also increased in plasma and CSF following SE infection. Enteral colostrum supplementation attenuated the lactate accumulation in blood and CSF. Bloodstream infection in preterm newborns was found to induce a rapid metabolic shift in both plasma and CSF, which was modulated by colostrum feeding. PMID: 30641988 [PubMed]

Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis.

Wed, 16/01/2019 - 14:47
Related Articles Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis. Molecules. 2019 Jan 11;24(2): Authors: Xia T, Dong X, Jiang Y, Lin L, Dong Z, Shen Y, Xin H, Zhang Q, Qin L Abstract Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11β-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis. PMID: 30641909 [PubMed - in process]

Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients' Dried Blood Spots and Plasma.

Wed, 16/01/2019 - 14:47
Related Articles Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients' Dried Blood Spots and Plasma. Metabolites. 2019 Jan 11;9(1): Authors: Haijes HA, Willemsen M, Van der Ham M, Gerrits J, Pras-Raves ML, Prinsen HCMT, Van Hasselt PM, De Sain-van der Velden MGM, Verhoeven-Duif NM, Jans JJM Abstract In metabolic diagnostics, there is an emerging need for a comprehensive test to acquire a complete view of metabolite status. Here, we describe a non-quantitative direct-infusion high-resolution mass spectrometry (DI-HRMS) based metabolomics method and evaluate the method for both dried blood spots (DBS) and plasma. 110 DBS of 42 patients harboring 23 different inborn errors of metabolism (IEM) and 86 plasma samples of 38 patients harboring 21 different IEM were analyzed using DI-HRMS. A peak calling pipeline developed in R programming language provided Z-scores for ~1875 mass peaks corresponding to ~3835 metabolite annotations (including isomers) per sample. Based on metabolite Z-scores, patients were assigned a 'most probable diagnosis' by an investigator blinded for the known diagnoses of the patients. Based on DBS sample analysis, 37/42 of the patients, corresponding to 22/23 IEM, could be correctly assigned a 'most probable diagnosis'. Plasma sample analysis, resulted in a correct 'most probable diagnosis' in 32/38 of the patients, corresponding to 19/21 IEM. The added clinical value of the method was illustrated by a case wherein DI-HRMS metabolomics aided interpretation of a variant of unknown significance (VUS) identified by whole-exome sequencing. In summary, non-quantitative DI-HRMS metabolomics in DBS and plasma is a very consistent, high-throughput and nonselective method for investigating the metabolome in genetic disease. PMID: 30641898 [PubMed]

1H NMR based serum metabolic profiling reveals differentiating biomarkers in patients with diabetes and diabetes-related complication.

Wed, 16/01/2019 - 14:47
Related Articles 1H NMR based serum metabolic profiling reveals differentiating biomarkers in patients with diabetes and diabetes-related complication. Diabetes Metab Syndr. 2019 Jan - Feb;13(1):290-298 Authors: Rawat A, Misra G, Saxena M, Tripathi S, Dubey D, Saxena S, Aggarwal A, Gupta V, Khan MY, Prakash A Abstract BACKGROUND: Diabetes is among the most prevalent diseases worldwide, of all the affected individuals a significant proportion of the population remains undiagnosed due to lack of specific symptoms early in this disorder and inadequate diagnostics. Diabetes and its associated sequela, i.e., comorbidity are associated with microvascular and macrovascular complications. As diabetes is characterized by an altered metabolism of key metabolites and regulatory pathways. Metabolic phenotyping can provide us with a better understanding of the unique set of regulatory perturbations that predispose to diabetes and its associated complication/comorbidities. METHODOLOGY: The present study utilizes the analytical platform NMR spectroscopy coupled with Random Forest statistical analysis to identify the discriminatory metabolites in diabetes (DB = 38) vs. diabetes-related complication (DC = 35) along with the healthy control (HC = 50) subjects. A combined and pairwise analysis was performed to identify the discriminatory metabolites responsible for class separation. The perturbed metabolites were further rigorously validated using t-test, AUROC analysis to examine the statistical significance of the identified metabolites. RESULTS: The DB and DC patients were well discriminated from HC. However, 15 metabolites were found to be significantly perturbed in DC patients compared to DB, the identified panel of metabolites are TCA cycle (succinate, citrate), methylamine metabolism (trimethylamine, methylamine, betaine), -intermediates; energy metabolites (glucose, lactate, pyruvate); and amino acids (valine, arginine, glutamate, methionine, proline, and threonine). CONCLUSION: The 1H NMR metabolomics may prove a promising technique to differentiate and predict diabetes and its complication on their onset or progression by determining the altered levels of the metabolites in serum. PMID: 30641714 [PubMed - in process]

Improve your Galaxy text life: The Query Tabular Tool.

Wed, 16/01/2019 - 14:47
Related Articles Improve your Galaxy text life: The Query Tabular Tool. F1000Res. 2018;7:1604 Authors: Johnson JE, Kumar P, Easterly C, Esler M, Mehta S, Eschenlauer AC, Hegeman AD, Jagtap PD, Griffin TJ Abstract Galaxy provides an accessible platform where multi-step data analysis workflows integrating disparate software can be run, even by researchers with limited programming expertise. Applications of such sophisticated workflows are many, including those which integrate software from different 'omic domains (e.g. genomics, proteomics, metabolomics). In these complex workflows, intermediate outputs are often generated as tabular text files, which must be transformed into customized formats which are compatible with the next software tools in the pipeline. Consequently, many text manipulation steps are added to an already complex workflow, overly complicating the process. In some cases, limitations to existing text manipulation are such that desired analyses can only be carried out using highly sophisticated processing steps beyond the reach of even advanced users and developers. For users with some SQL knowledge, these text operations could be combined into single, concise query on a relational database. As a solution, we have developed the Query Tabular Galaxy tool, which leverages a SQLite database generated from tabular input data. This database can be queried and manipulated to produce transformed and customized tabular outputs compatible with downstream processing steps. Regular expressions can also be utilized for even more sophisticated manipulations, such as find and replace and other filtering actions. Using several Galaxy-based multi-omic workflows as an example, we demonstrate how the Query Tabular tool dramatically streamlines and simplifies the creation of multi-step analyses, efficiently enabling complicated textual manipulations and processing. This tool should find broad utility for users of the Galaxy platform seeking to develop and use sophisticated workflows involving text manipulation on tabular outputs. PMID: 30519459 [PubMed - in process]

metabolomics; +34 new citations

Tue, 15/01/2019 - 17:38
34 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 2019/01/15PubMed comprises more than millions of 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.

Control of IgG glycosylation by in situ and real-time estimation of specific growth rate of CHO cells cultured in bioreactor.

Mon, 14/01/2019 - 14:24
Related Articles Control of IgG glycosylation by in situ and real-time estimation of specific growth rate of CHO cells cultured in bioreactor. Biotechnol Bioeng. 2019 Jan 13;: Authors: Li MY, Ebel B, Blanchard F, Paris C, Guedon E, Marc A Abstract The cell specific growth rate (µ) is a critical process parameter for antibody production processes performed by animal cell cultures, as it describes the cell growth and reflects the cell physiological state. When there are changes in these parameters, which are indicated by variations of µ, the synthesis and the quality of antibodies are often affected. Therefore, it is essential to monitor and control the variations of µ in order to assure the antibody production and achieve high product quality. In this study, a novel approach for on-line estimation of µ was developed based on the Process Analytical Technology (PAT) initiative by using an in situ dielectric spectroscopy. Critical moments, such as significant µ decreases, were successfully detected by this method, in association with changes in cell physiology as well as with an accumulation of non-glycosylated antibodies. Thus, this method was used to perform medium renewals at the appropriate time points, maintaining the values of µ close to its maximum. Using this method, we demonstrated that the physiological state of cells remained stable, the quantity and the glycosylation quality of antibodies were assured at the same time, leading to better process performances compared to the reference feed-harvest cell cultures carried out by using offline nutrient measurements. This article is protected by copyright. All rights reserved. PMID: 30636319 [PubMed - as supplied by publisher]

How Histone Deacetylase Inhibitors Alter the Secondary Metabolites of Botryosphaeria mamane, an Endophytic Fungus Isolated from Bixa orellana, L.

Sun, 13/01/2019 - 14:11
Related Articles How Histone Deacetylase Inhibitors Alter the Secondary Metabolites of Botryosphaeria mamane, an Endophytic Fungus Isolated from Bixa orellana, L. Chem Biodivers. 2019 Jan 12;: Authors: Triastuti A, Vansteelandt M, Barakat F, Trinel M, Jargeat P, Fabre N, Amasifuen C, Mejia K, Valentin A, Haddad M Abstract Fungi are talented organisms able to produce several natural products with a wide range of structural and pharmacological activities. The conventional fungal cultivation used in laboratories are too poor to mimic the natural habitats of fungi, and this can partially explain why most of the genes responsible for the production of metabolites are transcriptionally silenced. The use of Histone Deacetylase inhibitors (HDACis) to perturb fungal secondary biosynthetic machinery has proven to be an effective approach for discovering new fungal natural products. The present study relates the effects of suberoylanilidehydroxamic acid (SAHA) and valproate sodium (VS) on the metabolome of Botryosphaeria mamane, an endophytic fungus isolated from Bixa orellana. UHPLC-HRMS analysis integrated with four metabolomics tools: MS-DIAL, MS-FINDER, MetaboAnalyst and GNPS molecular networking, was established. This study highlighted that SAHA and VS changed metabolites in B. mamane, causing upregulation and downregulation of metabolites production. In addition, twelve compounds were detected in the extracts as metabolites structurally correlated to SAHA, indicating its important reactivity in the medium or its metabolism by the fungus. An addition of SAHA induced the production of eight metabolites while VS induced only two metabolites undetected in the control strain. This result illustrates the importance of adding HDACis to a fungal culture in order to induce metabolite production. PMID: 30636097 [PubMed - as supplied by publisher]

A gene expression map of shoot domains reveals regulatory mechanisms.

Sun, 13/01/2019 - 14:11
Related Articles A gene expression map of shoot domains reveals regulatory mechanisms. Nat Commun. 2019 Jan 11;10(1):141 Authors: Tian C, Wang Y, Yu H, He J, Wang J, Shi B, Du Q, Provart NJ, Meyerowitz EM, Jiao Y Abstract Gene regulatory networks control development via domain-specific gene expression. In seed plants, self-renewing stem cells located in the shoot apical meristem (SAM) produce leaves from the SAM peripheral zone. After initiation, leaves develop polarity patterns to form a planar shape. Here we compare translating RNAs among SAM and leaf domains. Using translating ribosome affinity purification and RNA sequencing to quantify gene expression in target domains, we generate a domain-specific translatome map covering representative vegetative stage SAM and leaf domains. We discuss the predicted cellular functions of these domains and provide evidence that dome seemingly unrelated domains, utilize common regulatory modules. Experimental follow up shows that the RABBIT EARS and HANABA TARANU transcription factors have roles in axillary meristem initiation. This dataset provides a community resource for further study of shoot development and response to internal and environmental signals. PMID: 30635575 [PubMed - in process]

Recent advances and perspectives of metabolomics-based investigations in Parkinson's disease.

Sun, 13/01/2019 - 14:11
Related Articles Recent advances and perspectives of metabolomics-based investigations in Parkinson's disease. Mol Neurodegener. 2019 Jan 11;14(1):3 Authors: Shao Y, Le W Abstract Parkinson's disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system (CNS), which affects mostly older adults. In recent years, the incidence of PD has been dramatically increasing with the aging population expanding. Due to the lack of effective biomarkers, the accurate diagnosis and precise treatment of PD are currently compromised. Notably, metabolites have been considered as the most direct reflection of the physiological and pathological conditions in individuals and represent attractive candidates to provide deep insights into disease phenotypes. By profiling the metabolites in biofluids (cerebrospinal fluid, blood, urine), feces and brain tissues, metabolomics has become a powerful and promising tool to identify novel biomarkers and provide valuable insights into the etiopathogenesis of neurological diseases. In this review, we will summarize the recent advancements of major analytical platforms implemented in metabolomics studies, dedicated to the improvement and extension of metabolome coverage for in-depth biological research. Based on the current metabolomics studies in both clinical populations and experimental PD models, this review will present new findings in metabolomics biomarkers research and abnormal metabolic pathways in PD, and will discuss the correlation between metabolomic changes and clinical conditions of PD. A better understanding of the biological underpinning of PD pathogenesis might offer novel diagnostic, prognostic, and therapeutic approaches to this devastating disease. PMID: 30634989 [PubMed - in process]

Association between serum haptoglobin and carotid arterial functions: usefulness of a targeted metabolomics approach.

Sun, 13/01/2019 - 14:11
Related Articles Association between serum haptoglobin and carotid arterial functions: usefulness of a targeted metabolomics approach. Cardiovasc Diabetol. 2019 Jan 11;18(1):8 Authors: Wang S, Wang J, Zhang R, Zhao A, Zheng X, Yan D, Jiang F, Jia W, Hu C, Jia W Abstract BACKGROUND: Serum haptoglobin (Hp) has been closely associated with cardio-cerebrovascular diseases. We investigated a metabolic profile associated with circulating Hp and carotid arterial functions via a targeted metabolomics approach to provide insight into potential mechanisms. METHODS: A total of 240 participants, including 120 patients with type 2 diabetes mellitus (T2DM) and 120 non-diabetes mellitus (non-DM) subjects were recruited in this study. Targeted metabolic profiles of serum metabolites were determined using an AbsoluteIDQ™ p180 Kit (BIOCRATES Life Sciences AG, Innsbruck, Austria). Ultrasound of the bilateral common carotid artery was used to measure intima-media thickness and inter-adventitial diameter. Serum Hp levels were tested by enzyme-linked immunosorbent assay. RESULTS: Serum Hp levels in T2DM patients and non-DM subjects were 103.40 (72.46, 131.99) mg/dL and 100.20 (53.99, 140.66) mg/dL, respectively. Significant differences of 19 metabolites and 17 metabolites were found among serum Hp tertiles in T2DM patients and non-DM subjects, respectively (P < 0.05). Of these, phosphatidylcholine acyl-alkyl C32:2 (PC ae C32:2) was the common metabolite observed in two populations, which was associated with the serum Hp groups and lipid traits (P < 0.05). Furthermore, the metabolite ratios of two acidic amino acids, including aspartate to PC ae C32:2 (Asp/PC ae C32:2) and glutamate to PC ae C32:2 (Glu/PC ae C32:2) were correlated with serum Hp, carotid arterial functions and other biochemical index in both populations significantly (P < 0.05). CONCLUSIONS: Targeted metabolomics analyses might provide a new insight into the potential mechanisms underlying the association between serum Hp and carotid arterial functions. PMID: 30634984 [PubMed - in process]

Recent Advances on Nucleolar Functions in Health and Disease.

Sun, 13/01/2019 - 14:11
Related Articles Recent Advances on Nucleolar Functions in Health and Disease. Arch Iran Med. 2018 Dec 01;21(12):600-607 Authors: Bahadori M, Azizi MH, Dabiri S Abstract The nucleolus is an internuclear organelle without a visible membrane via the light microscope inside the cell nucleus. It is the main site for synthesis of ribosome as a complex machine for coordinating protein production. It forms around a specific chromosomal feature called the nucleolar organizing region (NOR) which possesses numerous ribosomal DNA (rDNA). Although the nucleolus is best known as coordinator of ribosomal biogenesis and protein synthesis, recently, there is exciting awareness both on better understanding of ribosome biogenesis and non-ribosomal nucleolar functions. A great amount of research has clearly indicated that the nucleolus has functional activities in both ribosomal and non-ribosomal conditions such as development, aging, cell cycle, gene stability, lifespan regulation, and progeria. Through recent sophisticated and advanced technologies such as genomics, proteomics, metabolomics, advances of knowledge in RNA species and new approaches in microscopic analysis methods, researchers have shown that perturbation in the nucleolar structure and function (nucleolar stress) have been associated with human diseases including cancer, viral infection, cardiovascular and neurodegenerative diseases. In this review, we discuss the impact of current research providing new information regarding nucleolar roles and functions in some human diseases and aging. PMID: 30634859 [PubMed - in process]

Alteration of Metabolic Pathways in Osteoarthritis.

Sun, 13/01/2019 - 14:11
Related Articles Alteration of Metabolic Pathways in Osteoarthritis. Metabolites. 2019 Jan 09;9(1): Authors: Zhai G Abstract Sir Archibald Edward Garrod, who pioneered the field of inborn errors of metabolism and first elucidated the biochemical basis of alkaptonuria over 100 years ago, suggested that inborn errors of metabolism were "merely extreme examples of variations of chemical behavior which are probably everywhere present in minor degrees, just as no two individuals of a species are absolutely identical in bodily structure neither are their chemical processes carried out on exactly the same lines", and that this "chemical individuality [confers] predisposition to and immunities from various mishaps which are spoken of as diseases". Indeed, with advances in analytical biochemistry, especially the development of metabolomics in the post-genomic era, emerging data have been demonstrating that the levels of many metabolites do show substantial interindividual variation, and some of which are likely to be associated with common diseases, such as osteoarthritis (OA). Much work has been reported in the literature on the metabolomics of OA in recent years. In this narrative review, we provided an overview of the identified alteration of metabolic pathways in OA and discussed the role of those identified metabolites and related pathways in OA diagnosis, prognosis, and treatment. PMID: 30634493 [PubMed]

Comparative Analyses of Metabolomic Fingerprints and Cytotoxic Activities of Soft Corals from the Colombian Caribbean.

Sun, 13/01/2019 - 14:11
Related Articles Comparative Analyses of Metabolomic Fingerprints and Cytotoxic Activities of Soft Corals from the Colombian Caribbean. Mar Drugs. 2019 Jan 09;17(1): Authors: Santacruz L, Thomas OP, Duque C, Puyana M, Tello E Abstract Soft corals (Cnidaria, Anthozoa, Octocorallia) are a diverse group of marine invertebrates that inhabit various marine environments in tropical and subtropical areas. Several species are recognized as prolific sources of compounds with a wide array of biological activities. Recent advances in analytical techniques, supported by robust statistical analyses, have allowed the analysis and characterization of the metabolome present in a single living organism. In this study, a liquid chromatography-high resolution mass spectrometry metabolomic approach was applied to analyze the metabolite composition of 28 soft corals present in the Caribbean coast of Colombia. Multivariate data analysis was used to correlate the chemical fingerprints of soft corals with their cytotoxic activity against tumor cell lines for anticancer purpose. Some diterpenoids were identified as specific markers to discriminate between cytotoxic and non-cytotoxic crude extracts of soft corals against tumor cell lines. In the models generated from the comparative analysis of PLS-DA for tumor lines, A549 and SiHa, the diterpene 13-keto-1,11-dolabell-3(E),7(E),12(18)-triene yielded a high score in the variable importance in projection. These results highlight the potential of metabolomic approaches towards the identification of cytotoxic agents against cancer of marine origin. This workflow can be useful in several studies, mainly those that are time consuming, such as traditional bioprospecting of marine natural products. PMID: 30634471 [PubMed - in process]

Assessment of l-Asparaginase Pharmacodynamics in Mouse Models of Cancer.

Sun, 13/01/2019 - 14:11
Related Articles Assessment of l-Asparaginase Pharmacodynamics in Mouse Models of Cancer. Metabolites. 2019 Jan 09;9(1): Authors: Horvath TD, Chan WK, Pontikos MA, Martin LA, Du D, Tan L, Konopleva M, Weinstein JN, Lorenzi PL Abstract l-asparaginase (ASNase) is a metabolism-targeted anti-neoplastic agent used to treat acute lymphoblastic leukemia (ALL). ASNase's anticancer activity results from the enzymatic depletion of asparagine (Asn) and glutamine (Gln), which are converted to aspartic acid (Asp) and glutamic acid (Glu), respectively, in the blood. Unfortunately, accurate assessment of the in vivo pharmacodynamics (PD) of ASNase is challenging because of the following reasons: (i) ASNase is resilient to deactivation; (ii) ASNase catalytic efficiency is very high; and (iii) the PD markers Asn and Gln are depleted ex vivo in blood samples containing ASNase. To address those issues and facilitate longitudinal studies in individual mice for ASNase PD studies, we present here a new LC-MS/MS bioanalytical method that incorporates rapid quenching of ASNase for measurement of Asn, Asp, Gln, and Glu in just 10 µL of whole blood, with limits of detection (s:n ≥ 10:1) estimated to be 2.3, 3.5, 0.8, and 0.5 µM, respectively. We tested the suitability of the method in a 5-day, longitudinal PD study in mice and found the method to be simple to perform with sufficient accuracy and precision for whole blood measurements. Overall, the method increases the density of data that can be acquired from a single animal and will facilitate optimization of novel ASNase treatment regimens and/or the development of new ASNase variants with desired kinetic properties. PMID: 30634463 [PubMed]

metabolomics; +18 new citations

Sat, 12/01/2019 - 13:49
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 2019/01/12PubMed comprises more than millions of 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.

metabolomics; +23 new citations

Fri, 11/01/2019 - 16:34
23 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 2019/01/11PubMed comprises more than millions of 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.

metabolomics; +23 new citations

Fri, 11/01/2019 - 13:34
23 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 2019/01/11PubMed comprises more than millions of 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.

metabolomics; +18 new citations

Thu, 10/01/2019 - 16:25
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 2019/01/10PubMed comprises more than millions of 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.

metabolomics; +18 new citations

Thu, 10/01/2019 - 13:25
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 2019/01/10PubMed comprises more than millions of 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.

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