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

Toward a Taxonomy for Multi-Omics Science? Terminology Development for Whole Genome Study Approaches by Omics Technology and Hierarchy.

Thu, 09/03/2017 - 14:32
Related Articles Toward a Taxonomy for Multi-Omics Science? Terminology Development for Whole Genome Study Approaches by Omics Technology and Hierarchy. OMICS. 2017 Jan;21(1):1-16 Authors: Pirih N, Kunej T Abstract Omics is a form of high-throughput systems science. However, taxonomies for omics studies are limited, inviting us to rethink new ways in which we classify, prioritize, and rank various omics systems science studies. In this overarching context, the genome-wide study approaches have proliferated in number and popularity over the past decade. However, their hierarchy is not well organized and the development of attendant terminology is not controlled. In the present study, we searched the literature in PubMed and the Web of Science databases published from March 1999 to September 2016 using the keywords, including genome-wide, association, whole genome, transcriptome-wide, metabolome, epigenome, and phenome. We identified the whole genome study approaches and sorted them according to the omics technology types (genomics, proteomics, and so on) and hierarchy. Thirty-four studies from over 90 publications were sorted into 10 omics groups: DNA level, transcriptomics, proteomics, interactomics, metabolomics, epigenomics, miRNomics/ncRNomics, phenomics, environmental omics, and pharmacogenomics. We suggest here modifications of terminology for study approaches, which share the same acronyms such as EWAS for epigenome-wide association and environment-wide association studies, and MWAS for methylome-wide association and metabolome-wide association studies. Taken together, our study presented here provides the first systematic review and analyses of whole genome approaches and presents a baseline for further controlled terminology development, with a view to a new taxonomy for omics and multi-omics studies in the future. Finally, we call for greater dialogue and collaboration across diverse omics knowledge domains and applications, for example, across plants, animals, clinical medicine, and ecology. PMID: 28271979 [PubMed - in process]

Branched-Chain Amino Acids as Predictors for Individual Differences of Cisplatin Nephrotoxicity in Rats: A Pharmacometabonomics Study.

Thu, 09/03/2017 - 14:32
Related Articles Branched-Chain Amino Acids as Predictors for Individual Differences of Cisplatin Nephrotoxicity in Rats: A Pharmacometabonomics Study. J Proteome Res. 2017 Mar 08;: Authors: Zhang P, Li W, Chen J, Li R, Zhang Z, Huang Y, Xu F Abstract Nephrotoxicity is the dose-limiting adverse effect of cisplatin with large individual differences. Up to now, little has been done on how to recognize and predict the individual differences either in preclinical or clinical research. In the present study, important post-dose indicators were screened out first and integrated into a grouping factor, according to which rats were recognized as low or high sensitive individuals. Then, mass spectrometry-based untargeted metabolomics approach was performed to dissect the metabolic differences in pre-dose serum of the two groups. Eventually, branched-chain amino acids (BCAAs) were found to be most significant with the lowest p value of Mann-Whitney U test and the highest area under receiving operating characteristic curve (AUC-ROC). The findings were further confirmed by absolute quantitation of BCAAs using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Binary logistic regression (BLR) showed that in the discovery set absolute BCAA contents in rat pre-dose serum could predict cisplatin nephrotoxicity with the accuracy of 85%. This result was validated by another two independent external validation sets with the accuracy of 81.8% and 78.8%, respectively. This study could provide new insight into cisplatin nephrotoxicity and may help expedite personalized medicine of cisplatin or other antitumor drugs in future clinical studies. PMID: 28271897 [PubMed - as supplied by publisher]

Proximity labeling of interacting proteins: Application of BioID as a discovery tool.

Thu, 09/03/2017 - 14:32
Related Articles Proximity labeling of interacting proteins: Application of BioID as a discovery tool. Proteomics. 2017 Mar 08;: Authors: Li P, Li J, Wang L, Di LJ Abstract Protein performs biochemical functions by forming complexes, or protein-protein interactions (PPIs). Many different approaches, such as phage display and yeast hybridization etc. were developed to illustrate the PPIs, and disclose the composition and organization of protein complexes. However, none of these approaches are based on the real-time and in vivo PPI analysis. Proximity dependent labeling of interacting proteins (PDL) has recently been proposed by taking advantage of several enzymes, which are capable of attaching the known reactive groups to the nearby proteins covalently. Among the PDL methods, BioID is the earliest and the most widely used one and has been upgraded from its prototype, making it an extremely convenient research tool. In this review, we describe the BioID technology development, its potential applications according to the nature of the target protein, and some recent efforts to circumvent the technical limitations. Moreover, some comparable PDL methods are introduced, including SPPLAT, EMARS, APEX and IPL etc., and we propose that systematic comparison of the working radius of these methods may be helpful to develop a tool box, from which the right method can be selected for a given target protein for PPI research. This article is protected by copyright. All rights reserved. PMID: 28271636 [PubMed - as supplied by publisher]

Functional Diversity of Transcriptional Regulators in the Cyanobacterium Synechocystis sp. PCC 6803.

Thu, 09/03/2017 - 14:32
Related Articles Functional Diversity of Transcriptional Regulators in the Cyanobacterium Synechocystis sp. PCC 6803. Front Microbiol. 2017;8:280 Authors: Shi M, Zhang X, Pei G, Chen L, Zhang W Abstract Functions of transcriptional regulators (TRs) are still poorly understood in the model cyanobacterium Synechocystis sp. PCC 6803. To address the issue, we constructed knockout mutants for 32 putative TR-encoding genes of Synechocystis, and comparatively analyzed their phenotypes under autotrophic growth condition and metabolic profiles using liquid chromatography-mass spectrometry-based metabolomics. The results showed that only four mutants of TR genes, sll1872 (lytR), slr0741 (phoU), slr0395 (ntcB), and slr1871 (pirR), showed differential growth patterns in BG11 medium when compared with the wild type; however, in spite of no growth difference observed for the remaining TR mutants, metabolomic profiling showed that they were different at the metabolite level, suggesting significant functional diversity of TRs in Synechocystis. In addition, an integrative metabolomic and gene families' analysis of all TR mutants led to the identification of five pairs of TR genes that each shared close relationship in both gene families and metabolomic clustering trees, suggesting possible conserved functions of these TRs during evolution. Moreover, more than a dozen pairs of TR genes with different origin and evolution were found with similar metabolomic profiles, suggesting a possible functional convergence of the TRs during genome evolution. Finally, a protein-protein network analysis was performed to predict regulatory targets of TRs, allowing inference of possible regulatory gene targets for 4 out of five pairs of TRs. This study provided new insights into the regulatory functions and evolution of TR genes in Synechocystis. PMID: 28270809 [PubMed - in process]

Targeted Metabolomic Analysis of Soluble Lysates from Platelets of Patients with Mild Cognitive Impairment and Alzheimer's Disease Compared to Healthy Controls: Is PC aeC40:4 a Promising Diagnostic Tool?

Thu, 09/03/2017 - 14:32
Related Articles Targeted Metabolomic Analysis of Soluble Lysates from Platelets of Patients with Mild Cognitive Impairment and Alzheimer's Disease Compared to Healthy Controls: Is PC aeC40:4 a Promising Diagnostic Tool? J Alzheimers Dis. 2017 Feb 28;: Authors: Oberacher H, Arnhard K, Linhart C, Diwo A, Marksteiner J, Humpel C Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system. The use of biological fluids in AD diagnosis remains limited to the analysis of specific protein biomarkers in cerebrospinal fluid. However, metabolomic analysis has recently revealed several metabolites in plasma, especially phosphatidylcholines (PC), as putative biomarkers specific for AD. Following on previous reports of platelet abnormalities in AD, we hypothesized that platelets metabolites released in plasma may offer new biomarkers in AD. The aim of the present study was to apply targeted metabolomics to compare metabolites in soluble lysates of platelets from healthy controls (CO), patients with mild cognitive impairment (MCI), and patients with AD in a cohort of 90 subjects. Quantitative data were obtained for 91 metabolites. Among these, the lipid PC aeC40:4 significantly differentiated AD from CO (p = 0.0009), while four other lipids (PC aaC32:0, PC ae C32:2, PC aeC34:1, and SM(OH)C14:1) differentiated patients with MCI from CO. The combination of three phosphatidylcholines (PC aeC32:2, PC aeC34:1, PCaaC36:5), two lyso-phosphatidylcholines (lysoPC aC18:1, lysoPC aC16:0), and one sphingomyelin (SM(OH) C14:1) constructed a valuable prediction model using the C4.5 decision tree. The diagnosis accuracy for AD versus CO and MCI was 85%. In a blinded follow up conversion study, we could verify the clinical diagnosis in 19 out of 20 cases. We propose that soluble platelet PCaeC40:4 is a promising marker to diagnose AD with a cut-off of <0.30μM and that platelets undergo metabolic processes during AD progression. PMID: 28269764 [PubMed - as supplied by publisher]

Modeling non-clinical and clinical drug tests in Gaucher disease.

Thu, 09/03/2017 - 14:32
Related Articles Modeling non-clinical and clinical drug tests in Gaucher disease. Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:1434-1438 Authors: Phelix CF, Bourdon AK, Villareal G, LeBaron RG Abstract 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. Pharmacodynamics and metabolomics analyses of the results replicated published findings and demonstrated that processing and transport of lysosomal proteins alone cannot explain the metabolic disorder. This technology shows promise for application to other diseases. PMID: 28268595 [PubMed - in process]

Microbiota-based Signature of Gingivitis Treatments: A Randomized Study.

Thu, 09/03/2017 - 14:32
Related Articles Microbiota-based Signature of Gingivitis Treatments: A Randomized Study. Sci Rep. 2016 Apr 20;6:24705 Authors: Huang S, Li Z, He T, Bo C, Chang J, Li L, He Y, Liu J, Charbonneau D, Li R, Xu J Abstract Plaque-induced gingivitis can be alleviated by various treatment regimens. To probe the impacts of various anti-gingivitis treatments on plaque microflora, here a double blinded, randomized controlled trial of 91 adults with moderate gingivitis was designed with two anti-gingivitis regimens: the brush-alone treatment and the brush-plus-rinse treatment. In the later group, more reduction in both Plaque Index (TMQHI) and Gingival Index (mean MGI) at Day 3, Day 11 and Day 27 was evident, and more dramatic changes were found between baseline and other time points for both supragingival plaque microbiota structure and salivary metabonomic profiles. A comparison of plaque microbiota changes was also performed between these two treatments and a third dataset where 50 subjects received regimen of dental scaling. Only Actinobaculum, TM7 and Leptotrichia were consistently reduced by all the three treatments, whereas the different microbial signatures of the three treatments during gingivitis relieve indicate distinct mechanisms of action. Our study suggests that microbiota based signatures can serve as a valuable approach for understanding and potentially comparing the modes of action for clinical treatments and oral-care products in the future. PMID: 27094556 [PubMed - indexed for MEDLINE]

(1)H NMR-based metabolomics reveals neurochemical alterations in the brain of adolescent rats following acute methylphenidate administration.

Wed, 08/03/2017 - 13:27
Related Articles (1)H NMR-based metabolomics reveals neurochemical alterations in the brain of adolescent rats following acute methylphenidate administration. Neurochem Int. 2017 Mar 04;: Authors: Quansah E, Ruiz-Rodado V, Grootveld M, Probert F, Zetterström TS Abstract The psychostimulant methylphenidate (MPH) is increasingly used in the treatment of attention deficit hyperactivity disorder (ADHD). While there is little evidence for common brain pathology in ADHD, some studies suggest a right hemisphere dysfunction among people diagnosed with the condition. However, in spite of the high usage of MPH in children and adolescents, its mechanism of action is poorly understood. Given that MPH blocks the neuronal transporters for dopamine and noradrenaline, most research into the effects of MPH on the brain has largely focused on these two monoamine neurotransmitter systems. Interestingly, recent studies have demonstrated metabolic changes in the brain of ADHD patients, but the impact of MPH on endogenous brain metabolites remains unclear. In this study, a proton nuclear magnetic resonance ((1)H NMR)-based metabolomics approach was employed to investigate the effects of MPH on brain biomolecules. Adolescent male Sprague Dawley rats were injected intraperitoneally with MPH (5.0 mg/kg) or saline (1.0 ml/kg), and cerebral extracts from the left and right hemispheres were analysed. A total of 22 variables (representing 13 distinct metabolites) were significantly increased in the MPH-treated samples relative to the saline-treated controls. The upregulated metabolites included: amino acid neurotransmitters such as GABA, glutamate and aspartate; large neutral amino acids (LNAA), including the aromatic amino acids (AAA) tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline; and metabolites associated with energy and cell membrane dynamics, such as creatine and myo-inositol. No significant differences in metabolite concentrations were found between the left and right cerebral hemispheres. These findings provide new insights into the mechanisms of action of the anti-ADHD drug MPH. PMID: 28268188 [PubMed - as supplied by publisher]

Key metabolic traits of Pisum sativum maintain cell vitality during Didymella pinodes infection: cultivar resistance and the microsymbionts' influence.

Wed, 08/03/2017 - 13:27
Related Articles Key metabolic traits of Pisum sativum maintain cell vitality during Didymella pinodes infection: cultivar resistance and the microsymbionts' influence. J Proteomics. 2017 Mar 04;: Authors: Turetschek R, Desalegn G, Epple T, Kaul HP, Wienkoop S Abstract Ascochyta blight causes severe losses in field pea production and the search for resistance traits towards the causal agent Didymella pinodes is of particular importance for farmers. Various microsymbionts were reported to shape the plants' immune response. However, regardless their contribution to resistance, they are hardly included in experimental designs. Here, we first delineate the bi-directional effect of the symbionts' (rhizobia, mycorrhiza) and the leaf proteome/metabolome of two field pea cultivars with varying resistance levels towards D. pinodes. The pathogen infection showed higher influence on the interaction with the microsymbionts in the susceptible cultivar which was reflected in decreased nodule weight and root mycorrhiza colonisation. Vice versa, symbionts induced variation in the pathogen infection response, which, however, appeared to be overruled by the genotypic characteristics such as maintenance of photosynthesis and provision of sugars and carbon back bones to fuel secondary metabolism. An active sulphur metabolism, functionality of the glutathione-ascorbate hub and fine adjustment of hormone synthesis to suppress induced cell death appeared to support resistance. Thus, we conclude that sustainment of cell vitality through these complex metabolic traits is substantial for a more efficient infection response of the tolerant cultivar. SIGNIFICANCE: The infection response of two Pisum sativum cultivars with varying resistance levels towards Didymella pinodes was analysed most comprehensively at a proteomic and metabolomic level. Enhanced tolerance was linked to newly discovered cultivar specific metabolic traits such as hormone synthesis and presumably suppression of cell death. PMID: 28268116 [PubMed - as supplied by publisher]

NMR-based metabolomics for the environmental assessment of Kaohsiung Harbor sediments exemplified by a marine amphipod (Hyalella azteca).

Wed, 08/03/2017 - 13:27
Related Articles NMR-based metabolomics for the environmental assessment of Kaohsiung Harbor sediments exemplified by a marine amphipod (Hyalella azteca). Mar Pollut Bull. 2017 Mar 03;: Authors: Chiu KH, Dong CD, Chen CF, Tsai ML, Ju YR, Chen TM, Chen CW Abstract Inflow of wastewater from upstream causes a large flux of pollutants to enter Kaohsiung Harbor in Taiwan daily. To reveal the ecological risk posed by Kaohsiung Harbor sediments, an ecological metabolomic approach was employed to investigate environmental factors pertinent to the physiological regulation of the marine amphipod Hyalella azteca. The amphipods were exposed to sediments collected from different stream inlets of the Love River (LR), Canon River (CR), Jen-Gen River (JR), and Salt River (SR). Harbor entrance 1 (E1) was selected as a reference site. After 10-day exposure, metabolomic analysis of the Hyalella azteca revealed differences between two groups: {E1, LR, CR} and {JR, SR}. The metabolic pathways identified in the two groups of amphipods were significantly different. The results demonstrated that NMR-based metabolomics can be effectively used to characterize metabolic response related to sediment from polluted areas. PMID: 28267993 [PubMed - as supplied by publisher]

In vivo microsampling to capture the elusive exposome.

Wed, 08/03/2017 - 13:27
Related Articles In vivo microsampling to capture the elusive exposome. Sci Rep. 2017 Mar 07;7:44038 Authors: Bessonneau V, Ings J, McMaster M, Smith R, Bragg L, Servos M, Pawliszyn J Abstract Loss and/or degradation of small molecules during sampling, sample transportation and storage can adversely impact biological interpretation of metabolomics data. In this study, we performed in vivo sampling using solid-phase microextraction (SPME) in combination with non-targeted liquid chromatography and high-resolution tandem mass spectrometry (LC-MS/MS) to capture the fish tissue exposome using molecular networking analysis, and the results were contrasted with molecular differences obtained with ex vivo SPME sampling. Based on 494 MS/MS spectra comparisons, we demonstrated that in vivo SPME sampling provided better extraction and stabilization of highly reactive molecules, such as 1-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoleoyl-glycero-3-phosphocholine, from fish tissue samples. This sampling approach, that minimizes sample handling and preparation, offers the opportunity to perform longitudinal monitoring of the exposome in biological systems and improve the reliability of exposure-measurement in exposome-wide association studies. PMID: 28266605 [PubMed - in process]

Metabolic mechanism for L-leucine-induced metabolome to eliminate Streptococcus iniae.

Wed, 08/03/2017 - 13:27
Related Articles Metabolic mechanism for L-leucine-induced metabolome to eliminate Streptococcus iniae. J Proteome Res. 2017 Mar 07;: Authors: Du CC, Yang M, Li MY, Yang J, Peng B, Li H, Peng XX Abstract Crucial metabolites that modulate hosts' metabolome to eliminate bacterial pathogens have been documented, but the metabolic mechanisms are largely unknown. The present study explores the metabolic mechanism for L-leucine-induced metabolome to eliminate Streptococcus iniae in tilapia. GC-MS based metabolomics was used to investigate tilapia liver metabolic profile in the presence of exogenous L-leucine. Thirty-seven metabolites of differential abundance were determined, and eleven metabolic pathways were enriched. Pattern recognition analysis identified serine and proline as crucial metabolites, which are the two metabolites identified in survived tilapias during S. iniae infection, suggesting the two metabolites play crucial roles in L-leucine-induced elimination of the pathogen by the host. Exogenous L-serine reduces mortality of tilapias infected by S. iniae, providing a robust proof for supporting the conclusion. Furthermore, exogenous serine elevates expression of genes Il-1β and Il-8 in tilapia spleen, but not TNFα, CXCR4 and Mx, suggesting the metabolite promotes a phagocytosis role of macrophages, which is consistent with the finding that L-leucine promotes macrophages to kill both Gram-positive and negative bacterial pathogens. Therefore, the ability of phagocytosis enhanced by exogenous L-leucine is partly attributed to elevation of serine. These results demonstrate a metabolic mechanism by which exogenous L-leucine modulates tilapias' metabolome to enhance innate immunity and eliminate pathogens. PMID: 28266220 [PubMed - as supplied by publisher]

Quality control of Hypericum perforatum L. analytical challenges and recent progress.

Wed, 08/03/2017 - 13:27
Related Articles Quality control of Hypericum perforatum L. analytical challenges and recent progress. J Pharm Pharmacol. 2017 Mar 07;: Authors: Agapouda A, Booker A, Kiss T, Hohmann J, Heinrich M, Csupor D Abstract OBJECTIVES: The most widely applied qualitative and quantitative analytical methods in the quality control of Hypericum perforatum extracts will be reviewed, including routine analytical tools and most modern approaches. KEY FINDINGS: Biologically active components of H. perforatum are chemically diverse; therefore, different chromatographic and detection methods are required for the comprehensive analysis of St. John's wort extracts. Naphthodianthrones, phloroglucinols and flavonoids are the most widely analysed metabolites of this plant. For routine quality control, detection of major compounds belonging to these groups seems to be sufficient; however, closer characterization requires the detection of minor compounds as well. CONCLUSIONS: TLC and HPTLC are basic methods in the routine analysis, whereas HPLC-DAD is the most widely applied method for quantitative analysis due to its versatility. LC-MS is gaining importance in pharmacokinetic studies due to its sensitivity. Modern approaches, such as DNA barcoding, NIRS and NMR metabolomics, may offer new possibilities for the more detailed characterization of secondary metabolite profile of H. perforatum extracts. PMID: 28266019 [PubMed - as supplied by publisher]

Expanding Lipidome Coverage Using LC-MS/MS Data-Dependent Acquisition with Automated Exclusion List Generation.

Wed, 08/03/2017 - 13:27
Related Articles Expanding Lipidome Coverage Using LC-MS/MS Data-Dependent Acquisition with Automated Exclusion List Generation. J Am Soc Mass Spectrom. 2017 Mar 06;: Authors: Koelmel JP, Kroeger NM, Gill EL, Ulmer CZ, Bowden JA, Patterson RE, Yost RA, Garrett TJ Abstract Untargeted omics analyses aim to comprehensively characterize biomolecules within a biological system. Changes in the presence or quantity of these biomolecules can indicate important biological perturbations, such as those caused by disease. With current technological advancements, the entire genome can now be sequenced; however, in the burgeoning fields of lipidomics, only a subset of lipids can be identified. The recent emergence of high resolution tandem mass spectrometry (HR-MS/MS), in combination with ultra-high performance liquid chromatography, has resulted in an increased coverage of the lipidome. Nevertheless, identifications from MS/MS are generally limited by the number of precursors that can be selected for fragmentation during chromatographic elution. Therefore, we developed the software IE-Omics to automate iterative exclusion (IE), where selected precursors using data-dependent topN analyses are excluded in sequential injections. In each sequential injection, unique precursors are fragmented until HR-MS/MS spectra of all ions above a user-defined intensity threshold are acquired. IE-Omics was applied to lipidomic analyses in Red Cross plasma and substantia nigra tissue. Coverage of the lipidome was drastically improved using IE. When applying IE-Omics to Red Cross plasma and substantia nigra lipid extracts in positive ion mode, 69% and 40% more molecular identifications were obtained, respectively. In addition, applying IE-Omics to a lipidomics workflow increased the coverage of trace species, including odd-chained and short-chained diacylglycerides and oxidized lipid species. By increasing the coverage of the lipidome, applying IE to a lipidomics workflow increases the probability of finding biomarkers and provides additional information for determining etiology of disease. Graphical Abstract ᅟ. PMID: 28265968 [PubMed - as supplied by publisher]

Metabolic profiling study of shikonin's cytotoxic activity in the Huh7 human hepatoma cell line.

Wed, 08/03/2017 - 13:27
Related Articles Metabolic profiling study of shikonin's cytotoxic activity in the Huh7 human hepatoma cell line. Mol Biosyst. 2017 Mar 07;: Authors: Spyrelli ED, Kyriazou AV, Virgiliou C, Nakas A, Deda O, Papageorgiou VP, Assimopoulou AN, Gika HG Abstract Shikonin and its enantiomer alkannin, which are natural products, have been extensively studied in vitro and in vivo for, among others, their antitumor activity. The investigation of the molecular pathways involved in their action is of interest, since they are not yet clearly defined. Metabolic profiling in cells can provide a picture of a cell's phenotype upon intervention, assisting in the elucidation of the mechanism of action. In this study, the cytotoxic effect of shikonin on a human hepatocarcinoma cell line was studied. Huh7 cells were treated with shikonin at 5 μM, and it was found that shikonin markedly inhibited cell growth. Metabolic profiling indicated alterations in the metabolic content of the cells and the culture media upon treatment, detecting the metabolic response of the cells. This study demonstrates the potential of metabolomics to improve knowledge on the mechanisms involved in shikonin's antitumor action. PMID: 28265634 [PubMed - as supplied by publisher]

Perspective on precision medicine in paediatric heart failure.

Wed, 08/03/2017 - 13:27
Related Articles Perspective on precision medicine in paediatric heart failure. Clin Sci (Lond). 2017 Mar 01;131(6):439-448 Authors: Fridman MD, Mital S Abstract In 2015, President Obama launched the Precision Medicine Initiative (PMI), which introduced new funding to a method of research with the potential to study rare and complex diseases. Paediatric heart failure, a heterogeneous syndrome affecting approximately 1 in 100000 children, is one such condition in which precision medicine techniques may be applied with great benefit. Current heart failure therapies target downstream effects of heart failure rather than the underlying cause of heart failure. As such, they are often ineffective in paediatric heart failure, which is typically of primary (e.g. genetic) rather than secondary (e.g. acquired) aetiology. It is, therefore, important to develop therapies that can target the causes of heart failure in children with greater specificity thereby decreasing morbidity, mortality and burden of illness on both patients and their families. The benefits of co-ordinated research in genomics, proteomics, metabolomics, transcriptomics and phenomics along with dietary, lifestyle and social factors have led to novel therapeutic and prognostic applications in other fields such as oncology. Applying such co-ordinated research efforts to heart failure constitutes an important step in advancing care and improving the lives of those affected. PMID: 28265035 [PubMed - in process]

Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics.

Wed, 08/03/2017 - 13:27
Related Articles Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics. FASEB J. 2017 Mar 06;: Authors: Vorrink SU, Ullah S, Schmidt S, Nandania J, Velagapudi V, Beck O, Ingelman-Sundberg M, Lauschke VM Abstract Adverse reactions or lack of response to medications are important concerns for drug development programs. However, faithful predictions of drug metabolism and toxicity are difficult because animal models show only limited translatability to humans. Furthermore, current in vitro systems, such as hepatic cell lines or primary human hepatocyte (PHH) 2-dimensional (2D) monolayer cultures, can be used only for acute toxicity tests because of their immature phenotypes and inherent instability. Therefore, the migration to novel phenotypically stable models is of prime importance for the pharmaceutical industry. Novel 3-dimensional (3D) culture systems have been shown to accurately mimic in vivo hepatic phenotypes on transcriptomic and proteomic level, but information about their metabolic stability is lacking. Using a combination of targeted and untargeted high-resolution mass spectrometry, we found that PHHs in 3D spheroid cultures remained metabolically stable for multiple weeks, whereas metabolic patterns of PHHs from the same donors cultured as conventional 2D monolayers rapidly deteriorated. Furthermore, pharmacokinetic differences between donors were maintained in 3D spheroid cultures, enabling studies of interindividual variability in drug metabolism and toxicity. We conclude that the 3D spheroid system is metabolically stable and constitutes a suitable model for in vitro studies of long-term drug metabolism and pharmacokinetics.-Vorrink, S. U., Ullah, S., Schmid, S., Nandania, J., Velagapudi, V., Beck, O., Ingelman-Sundberg, M., Lauschke, V. M. Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics. PMID: 28264975 [PubMed - as supplied by publisher]

Genomics and Biochemistry of Saccharomyces cerevisiae Wine Yeast Strains.

Wed, 08/03/2017 - 13:27
Related Articles Genomics and Biochemistry of Saccharomyces cerevisiae Wine Yeast Strains. Biochemistry (Mosc). 2016 Dec;81(13):1650-1668 Authors: Eldarov MA, Kishkovskaia SA, Tanaschuk TN, Mardanov AV Abstract Saccharomyces yeasts have been used for millennia for the production of beer, wine, bread, and other fermented products. Long-term "unconscious" selection and domestication led to the selection of hundreds of strains with desired production traits having significant phenotypic and genetic differences from their wild ancestors. This review summarizes the results of recent research in deciphering the genomes of wine Saccharomyces strains, the use of comparative genomics methods to study the mechanisms of yeast genome evolution under conditions of artificial selection, and the use of genomic and postgenomic approaches to identify the molecular nature of the important characteristics of commercial wine strains of Saccharomyces. Succinctly, data concerning metagenomics of microbial communities of grapes and wine and the dynamics of yeast and bacterial flora in the course of winemaking is provided. A separate section is devoted to an overview of the physiological, genetic, and biochemical features of sherry yeast strains used to produce biologically aged wines. The goal of the review is to convince the reader of the efficacy of new genomic and postgenomic technologies as tools for developing strategies for targeted selection and creation of new strains using "classical" and modern techniques for improving winemaking technology. PMID: 28260488 [PubMed - indexed for MEDLINE]

(1)H NMR-based metabonomic study on the effects of Epimedium on glucocorticoid-induced osteoporosis.

Wed, 08/03/2017 - 13:27
Related Articles (1)H NMR-based metabonomic study on the effects of Epimedium on glucocorticoid-induced osteoporosis. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Dec 01;1038:118-126 Authors: Pan S, Chen A, Han Z, Wang Y, Lu X, Yang Y Abstract Glucocorticoids are widely used in clinical practice for the treatment of many immune-mediated and inflammatory diseases, and glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. Epimedium is one of the most commonly used traditional Chinese medicines for treating osteoporosis. In the present study, we systematically analysed the metabonomic characteristics of GIO model rats and elucidated the therapeutic effect of Epimedium by using a (1)H NMR-based metabonomic approach in conjunction with multivariate data analysis. Rats in treatment and model groups were injected with dexamethasone (0.1mg/kg/day) for 5 weeks. Simultaneously, two treatment groups were orally administered Epimedium (10g/kg/day) or Alendronate (1.2mg/kg/day) for 5 weeks. In GIO model rats, lipid and lactate levels in serum were increased, while creatine/creatinine, PC/GPC, taurine, glycine and β-glucose levels were decreased. In urine, GIO rats had higher levels of phenylacetylglycine but lower levels of 2-oxoglutarate, citrate, creatine/creatinine, taurine, PC/GPC and hippurate than controls. Epimedium reversed the aforementioned metabolic alterations in multiple metabolic pathways involved in energy, lipid, amino acid and phospholipid metabolism and gut microbiota derangement. Our results indicated that Epimedium had significant effects in the prevention and treatment of osteoporosis. It is concluded that (1)H NMR metabonomics is a useful method for studying the metabolic effects of traditional Chinese medicine from a systematic and holistic view. PMID: 27810280 [PubMed - indexed for MEDLINE]

metabolomics; +20 new citations

Tue, 07/03/2017 - 13:05
20 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 2017/03/07PubMed 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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