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 20 min ago

metabolomics; +16 new citations

Tue, 04/09/2018 - 13:50
16 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 2018/09/04PubMed 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.

Optimization of kidney dysfunction prediction in diabetic kidney disease using targeted metabolomics.

Mon, 03/09/2018 - 13:17
Optimization of kidney dysfunction prediction in diabetic kidney disease using targeted metabolomics. Acta Diabetol. 2018 Sep 01;: Authors: Ibarra-González I, Cruz-Bautista I, Bello-Chavolla OY, Vela-Amieva M, Pallares-Méndez R, Ruiz de Santiago Y Nevarez D, Salas-Tapia MF, Rosas-Flota X, González-Acevedo M, Palacios-Peñaloza A, Morales-Esponda M, Aguilar-Salinas CA, Del Bosque-Plata L Abstract AIMS: Metabolomics have been used to evaluate the role of small molecules in human disease. However, the cost and complexity of the methodology and interpretation of findings have limited the transference of knowledge to clinical practice. Here, we apply a targeted metabolomics approach using samples blotted in filter paper to develop clinical-metabolomics models to detect kidney dysfunction in diabetic kidney disease (DKD). METHODS: We included healthy controls and subjects with type 2 diabetes (T2D) with and without DKD and investigated the association between metabolite concentrations in blood and urine with eGFR and albuminuria. We also evaluated performance of clinical, biochemical and metabolomic models to improve kidney dysfunction prediction in DKD. RESULTS: Using clinical-metabolomics models, we identified associations of decreased eGFR with body mass index (BMI), uric acid and C10:2 levels; albuminuria was associated to years of T2D duration, A1C, uric acid, creatinine, protein intake and serum C0, C10:2 and urinary C12:1 levels. DKD was associated with age, A1C, uric acid, BMI, serum C0, C10:2, C8:1 and urinary C12:1. Inclusion of metabolomics increased the predictive and informative capacity of models composed of clinical variables by decreasing Akaike's information criterion, and was replicated both in training and validation datasets. CONCLUSIONS: Targeted metabolomics using blotted samples in filter paper is a simple, low-cost approach to identify outcomes associated with DKD; the inclusion of metabolomics improves predictive capacity of clinical models to identify kidney dysfunction and DKD-related outcomes. PMID: 30173364 [PubMed - as supplied by publisher]

A metabolomics approach to characterize raw, pasteurized, and ultra-high temperature milk using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and multivariate data analysis.

Mon, 03/09/2018 - 13:17
A metabolomics approach to characterize raw, pasteurized, and ultra-high temperature milk using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and multivariate data analysis. J Dairy Sci. 2018 Aug 29;: Authors: Zhang YD, Li P, Zheng N, Jia ZW, Meruva N, Ladak A, Cleland G, Wen F, Li SL, Zhao SG, Wang JQ Abstract We developed a metabolomics workflow using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to determine the effect of thermal treatment on milk composition and metabolites based on multivariate data analysis. We analyzed raw, pasteurized, and UHT milk samples. The samples were first centrifuged to remove the fat layer and mixed with methanol to precipitate proteins. Subsequently, the supernatant was analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in electrospray negative mode. Mass spectral data were acquired in MSE mode, a technique whereby both precursor and fragment mass spectral are simultaneously acquired by alternating between low and high collision energy (CE) during a single analytical run, to enable metabolite identification. Based on multivariate data analysis, these markers were significantly affected by thermal treatment. Among the 8 potential markers, we identified 7 oxylipids (9-hydroxydecanoic acid, 12-hydroxydodecanoic acid, 2-hydroxymyristic acid, 3-hydroxytetradecanoic acid, 5-hydroxyeicosatetraenoic acid, 3-hydroxyhexadecanoic acid, and 10-hydroxyoctadecanoic acid) and 1 phospholipid (LysoPE, hexadecanoyl-lysophosphatidylethanolamine). The oxylipids seemed to be adequate for distinguishing UHT milk from raw and pasteurized milk. The structures of the 8 potential markers were identified and characterized using informatics software. Our metabolomics workflow provides a fast approach for the identification of various types of milk. PMID: 30172390 [PubMed - as supplied by publisher]

A validated multi-matrix platform for metabolomic fingerprinting of human urine, feces and plasma using ultra-high performance liquid-chromatography coupled to hybrid orbitrap high-resolution mass spectrometry.

Mon, 03/09/2018 - 13:17
A validated multi-matrix platform for metabolomic fingerprinting of human urine, feces and plasma using ultra-high performance liquid-chromatography coupled to hybrid orbitrap high-resolution mass spectrometry. Anal Chim Acta. 2018 Nov 29;1033:108-118 Authors: De Paepe E, Van Meulebroek L, Rombouts C, Huysman S, Verplanken K, Lapauw B, Wauters J, Hemeryck LY, Vanhaecke L Abstract In recent years, metabolomics has surfaced as an innovative research strategy in human metabolism, whereby selection of the biological matrix and its inherent metabolome is of crucial importance. However, focusing on a single matrix may imply that relevant molecules of complementary physiological pathways, covered by other matrices, are missed. To address this problem, this study presents a unique multi-matrix platform for polar metabolic fingerprinting of feces, plasma and urine, applying ultra-high performance liquid-chromatography coupled to hybrid quadrupole-Orbitrap high-resolution mass spectrometry, that is able to achieve a significantly higher coverage of the system's metabolome and reveal more significant results and interesting correlations in comparison with single-matrix analyses. All three fingerprinting approaches were proven 'fit-for-purpose' through extensive validation in which a number of endogenous metabolites were measured in representative quality control samples. For targeted and untargeted validation of all three matrices, excellent linearity (coefficients of determination R2 ≥ 0.99 or 0.90 respectively), recovery and precision (coefficients of variance ≤ 15% or 30% respectively) were observed. The potential of the platform was demonstrated by subjecting fecal, urine and plasma samples (collected within one day) from ten healthy volunteers to metabolic fingerprinting, yielding respectively 9 672, 9 647, and 6122 components. Orthogonal partial least-squares discriminant analysis provided similar results for feces and plasma to discriminate according to gender (p-value, R2(X), R2(Y) and Q2(Y)), suggesting feces as an excellent alternative biofluid to plasma. Moreover, combining the different matrices improved the model's predictivity, indicating the superiority of multi-matrix platforms for research purposes in biomarker detection or pathway elucidation and in the selection of the most optimal matrix for future clinical purposes. PMID: 30172316 [PubMed - in process]

[Metabolomics Study on the Differences of Endogenous Small Molecule 
between A549/DDP and A549 Cells Based on High Solution UPLC-TOF-MS].

Mon, 03/09/2018 - 13:17
[Metabolomics Study on the Differences of Endogenous Small Molecule 
between A549/DDP and A549 Cells Based on High Solution UPLC-TOF-MS]. Zhongguo Fei Ai Za Zhi. 2018 Aug 20;21(8):571-577 Authors: Hong W, Zhao Y, Cao L, Cao D, Zhao Z, Jin J Abstract BACKGROUND: Cisplatin acquired resistance is a vital problem in the chemotherapy of non-small cell lung cancer, which needs to be further addressed. In recent years, obtaining drug resistant cells from cell cultivation and serving for metabolomics research to find differential metabolites and get potential biomarkers, is a good reference for clinical research and cancer treatment. This study aimed to obtain metabolite information related to cisplatin resistance through metabolomics analysis. METHODS: Metabolites were extracted from A549 cells and cisplatin resistant A549/DDP cells, and ultraperformance liquid chromatography coupled with time of flight mass spectrometry was used to perform metabolomic analysis of endogenous molecules of the two cells and obtain metabolic differences. RESULTS: Through data analysis, 40 metabolites were identified as differential metabolites, mainly involving phospholipids, fatty acids, amino acids and metabolites related to energy metabolism. CONCLUSIONS: The drug resistance of A549/DDP cells may be caused by the changes of cell membrane structure and related metabolic pathways. PMID: 30172262 [PubMed - in process]

Metabolic signature of the aging eye in mice.

Sun, 02/09/2018 - 12:32
Metabolic signature of the aging eye in mice. Neurobiol Aging. 2018 Aug 07;71:223-233 Authors: Wang Y, Grenell A, Zhong F, Yam M, Hauer A, Gregor E, Zhu S, Lohner D, Zhu J, Du J Abstract Aging is a major risk factor for age-related ocular diseases including age-related macular degeneration in the retina and retinal pigment epithelium (RPE), cataracts in the lens, glaucoma in the optic nerve, and dry eye syndrome in the cornea. We used targeted metabolomics to analyze metabolites from young (6 weeks) and old (73 weeks) eyes in C57 BL6/J mice. Old mice had diminished electroretinogram responses and decreased number of photoreceptors in their retinas. Among the 297 detected metabolites, 45-114 metabolites are significantly altered in aged eye tissues, mostly in the neuronal tissues (retina and optic nerve) and less in cornea, RPE/choroid, and lens. We noted that changes of metabolites in mitochondrial metabolism and glucose metabolism are common features in the aged retina, RPE/choroid, and optic nerve. The aging retina, cornea, and optic nerve also share similar changes in Nicotinamide adenine dinucleotide (NAD), 1-methylnicotinamides, 3-methylhistidine, and other methylated metabolites. Metabolites in taurine metabolism are strikingly influenced by aging in the cornea and lens. In conclusion, the aging eye has both common and tissue-specific metabolic signatures. These changes may be attributed to dysregulated mitochondrial metabolism, reprogrammed glucose metabolism and impaired methylation in the aging eye. Our findings provide biochemical insights into the mechanisms of age-related ocular changes. PMID: 30172221 [PubMed - as supplied by publisher]

Physiological and metabolome changes during anther development in wheat (Triticum aestivum L.).

Sun, 02/09/2018 - 12:32
Physiological and metabolome changes during anther development in wheat (Triticum aestivum L.). Plant Physiol Biochem. 2018 Aug 23;132:18-32 Authors: Tang H, Song Y, Guo J, Wang J, Zhang L, Niu N, Ma S, Zhang G, Zhao H Abstract This study used cytology, cytochemistry, and non-targeted metabolomics to investigate the distribution characteristic of polysaccharides, lipids, and all the metabolites present during five wheat (Triticum aestivum L.) anther developmental stages to provide insights into wheat anther development. Anthers were collected from the tetrad through trinucleate stages, and 1.5% (w/v) acetocarmine and 4',6-diamidino-2-phenylindole staining were used to confirm the developmental stage and visualize the nuclei, respectively. Polysaccharides and lipids were detected by staining with periodic acid-Schiff and Sudan Black B, respectively. The integrated optical density of the tapetum and microspores were calculated using IPP6.0 software. Furthermore, the metabolites were identified by gas chromatograph system coupled with a Pegasus HT time-of-flight mass spectrometer (GC-TOF-MS). The results indicated that the interior and exterior surface cells of anthers are orderly. Pollen was rich in numerous nutrient substances (e.g., lipids, insoluble carbohydrates, and others), and formed a normal sperm cell that contained three nuclei, i.e., one vegetative nuclei and two reproductive nuclei in the mature pollen. Semi-thin sectioning indicated that the tapetum cells degraded progressively from the tetrad to late uninucleate stage and disappeared from the bi-to trinucleate stages. Moreover, nutrient substances (lipids and insoluble carbohydrates) accumulated, were synthesized in the pollen, and gradually increased from the tetrad to trinucleate stages. Finally, the metabolomics results identified that 146 metabolites were present throughout the wheat anther developmental stages. Principal component analysis, hierarchical cluster analysis, and metabolite-metabolite correlation revealed distinct dynamic changes in metabolites. The metabolism of organic acids, amino acids, sugars, fatty acids, amines, polyols, and nucleotides were interrelated and involved in the tricarboxylic acid (TCA) cycle and glycolysis. Furthermore, their interactions were revealed using an integrated metabolic map, which indicated that the TCA cycle and glycolysis were very active during anther development to provide the required energy for anther and pollen development. Our study provides valuable insights into the mechanisms of substance metabolism in wheat anthers and can be used for possible application by metabolic engineers for the improvement of cell characteristics or creating new compounds and molecular breeders in improving pollen fertility or creating the ideal male sterile line, to improve wheat yield per unit area to address global food security. PMID: 30172190 [PubMed - as supplied by publisher]

Metabolomic Analysis Identifies Lactate as One Important Pathogenic Factor in Diabetes-associated Cognitive Decline Rats.

Sun, 02/09/2018 - 12:32
Related Articles Metabolomic Analysis Identifies Lactate as One Important Pathogenic Factor in Diabetes-associated Cognitive Decline Rats. Mol Cell Proteomics. 2018 Aug 31;: Authors: Zhao L, Dong M, Ren M, Li C, Zheng H, Gao H Abstract Diabetes mellitus causes brain structure changes and cognitive decline, and it has been estimated that diabetes doubles the risk for dementia. Until now, the pathogenic mechanism of diabetes-associated cognitive decline (DACD) has remained unclear. Using metabolomics, we show that lactate levels increased over time in the hippocampus of rats with streptozotocin-induced diabetes, as compared to age-matched control rats. Additionally, mRNA levels, protein levels, and enzymatic activity of lactate dehydrogenase-A (LDH-A) were significantly up-regulated, suggesting increased glycolysis activity. Importantly, by specifically blocking the glycolysis pathway through an LDH-A inhibitor, chronic diabetes-induced memory impairment was prevented. Analyzing the underlying mechanism, we show that the expression levels of cAMP-dependent protein kinase and of phosphorylated transcription factor cAMP response element-binding proteins were decreased in 12-week diabetic rats. We suggest that G protein-coupled receptor 81 mediates cognitive decline in the diabetic rat. In this study, we report that progressively increasing lactate levels is an important pathogenic factor in DACD, directly linking diabetes to cognitive dysfunction. LDH-A may be considered as a potential target for alleviating or treating DACD in the future. PMID: 30171160 [PubMed - as supplied by publisher]

Supplementation with Qter® and Creatine improves functional performance in COPD patients on long term oxygen therapy.

Sun, 02/09/2018 - 12:32
Related Articles Supplementation with Qter® and Creatine improves functional performance in COPD patients on long term oxygen therapy. Respir Med. 2018 Sep;142:86-93 Authors: De Benedetto F, Pastorelli R, Ferrario M, de Blasio F, Marinari S, Brunelli L, Wouters EFM, Polverino F, Celli BR, Interdisciplinary Association for Research in Lung Disease (AIMAR) Study Group Abstract BACKGROUND: Skeletal muscle dysfunction and poor functional capacity are important extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD), especially in COPD patients on long-term O2 therapy (LTOT). Beside the role of pulmonary rehabilitation, the effect of nutritional interventions is still controversial, and there are knowledge gaps on the effective role of nutraceutical supplementation on hard endpoints. The aim of this study was to investigate the effects of nutritional supplementation with Coenzyme Q10 (QTer®) - a powerful antioxidant with the potential to reduce oxidative stress and improve mitochondrial function - and Creatine on functional, nutritional, and metabolomic profile in COPD patients on long-term O2 therapy. METHODS: One-hundred and eight patients with COPD from 9 Italian hospitals were enrolled in this double-blinded randomized placebo-controlled clinical study. At baseline and after 2 months of therapy, the patients underwent spirometry, 6-minute walk test (6MWT), bioelectrical impedance analysis, and activities of daily living questionnaire (ADL). Also, dyspnea scores and BODE index were calculated. At both time points, plasma concentration of CoQ10 and metabolomic profiling were measured. FINDINGS: Ninety patients, who randomly received supplementation with QTer® and Creatine or placebo, completed the study. Compared with placebo, supplemented patients showed improvements in 6MWT (51 ± 69 versus 15 ± 91 m, p < 0.05), body cell mass and phase angle, sodium/potassium ratio, dyspnea indices and ADL score. The CoQ10 plasma concentration increased in the supplementation group whereas it did not change in the placebo group. The metabolomics profile also differed between groups. Adverse events were similar in both groups. INTERPRETATION: These results show that in patients with COPD, dietary supplementation with CoQ10 and Creatine improves functional performance, body composition and perception of dyspnea. A systemic increase in some anti-inflammatory metabolites supports a pathobiological mechanism as a reason for these benefits. Further trials should help clarifying the role of QTer® and Creatine supplementation in patients with COPD. PMID: 30170808 [PubMed - in process]

Sensitive targeted methods for brain metabolomic studies in microdialysis samples.

Sat, 01/09/2018 - 14:57
Related Articles Sensitive targeted methods for brain metabolomic studies in microdialysis samples. J Pharm Biomed Anal. 2018 Aug 23;161:192-205 Authors: Bongaerts J, De Bundel D, Mangelings D, Smolders I, Vander Heyden Y, Van Eeckhaut A Abstract In vivo determination of brain mediators plays an important role in providing insight in how the brain functions. For this purpose, targeted metabolomics can be a very useful tool. Targeted metabolomics detects and measures certain known low-molecular-weight biomolecules involved in signaling pathways and biochemical processes in the central nervous system. Microdialysis is a powerful technique to sample brain mediators in the central nervous system. Several analytical techniques that can possibly be coupled to microdialysis are available. However, selection of an appropriate technique should be considered carefully, since sensitivity and specificity are critical when measuring these mediators in volume-restricted microdialysis samples. This review outlines some of the commonly applied sampling methods and analytical techniques and discusses some of the challenges encountered during the in vivo determination of central nervous system mediators. PMID: 30170201 [PubMed - as supplied by publisher]

Influence of 6-aminonicotinamide (6AN) on Leishmania promastigotes evaluated by metabolomics: Beyond the pentose phosphate pathway.

Sat, 01/09/2018 - 14:57
Related Articles Influence of 6-aminonicotinamide (6AN) on Leishmania promastigotes evaluated by metabolomics: Beyond the pentose phosphate pathway. Chem Biol Interact. 2018 Aug 28;: Authors: Almugadam SH, Trentini A, Maritati M, Contini C, Rugna G, Bellini T, Manfrinato MC, Dallocchio F, Hanau S Abstract 6-Aminonicotinamide (6AN) is an antimetabolite used to inhibit the NADPH-producing pentose phosphate pathway (PPP) in many cellular systems, making them more susceptible to oxidative stress. It is converted by a NAD(P)+ glycohydrolase to 6-aminoNAD and 6-aminoNADP, causing the accumulation of PPP intermediates, due to their inability to participate in redox reactions. Some parasites like Plasmodium falciparum and Coccidia are highly sensitive but not all cell types showed a strong responsiveness to 6AN, probably due to the different targeted pathway. For instance, in bacteria the main target is the Preiss-Handler salvage pathway for NAD+ biosynthesis. We were interested in testing 6AN on the kinetoplastid protozoan Leishmania as another model to clarify the mechanisms of action of 6AN, by using metabolomics. Leishmania promastigotes, the life-cycle stage residing in the sandfly, demonstrated a three order of magnitude higher EC50 (mM) compared to P. falciparum and mammalian cells (μM), although pre-treatment with 100 μM 6AN prior to sub-lethal oxidative challenge induced a supra-additive cell kill in L. infantum. By metabolomics, we did not detect 6ANAD/P suggesting that NAD+ glycohydrolases in Leishmania may not be highly efficient in catalysing transglycosidation as happens in other microorganisms. Contrariwise to the reported effect on 6AN-treated cancer cells, we did not detect 6-phosphogluconate (6 PG) accumulation, indicating that 6ANADP cannot bind with high affinity to the PPP enzyme 6 PG dehydrogenase. By contrast, 6AN caused a profound phosphoribosylpyrophosphate (PRPP) decrease and nucleobases accumulation confirming that PPP is somehow affected. More importantly, we found a decrease in nicotinate production, evidencing the interference with the Preiss-Handler salvage pathway for NAD+ biosynthesis, most probably by inhibiting the reaction catalysed by nicotinamidase. Therefore, our combined data from Leishmania strains, though confirming the interference with PPP, also showed that 6AN impairs the Preiss-Handler pathway, underlining the importance to develop compounds targeting this last route. PMID: 30170107 [PubMed - as supplied by publisher]

Pharmacometabolomics Informs About Pharmacokinetic Profile of Methylphenidate.

Sat, 01/09/2018 - 14:57
Related Articles Pharmacometabolomics Informs About Pharmacokinetic Profile of Methylphenidate. CPT Pharmacometrics Syst Pharmacol. 2018 Aug;7(8):525-533 Authors: Kaddurah-Daouk R, Hankemeier T, Scholl EH, Baillie R, Harms A, Stage C, Dalhoff KP, Jűrgens G, Taboureau O, Nzabonimpa GS, Motsinger-Reif AA, Thomsen R, Linnet K, Rasmussen HB, INDICES Consortium, Pharmacometabolomics Research Network Abstract Carboxylesterase 1 (CES1) metabolizes methylphenidate and other drugs. CES1 gene variation only partially explains pharmacokinetic (PK) variability. Biomarkers predicting the PKs of drugs metabolized by CES1 are needed. We identified lipids in plasma from 44 healthy subjects that correlated with CES1 activity as determined by PK parameters of methylphenidate including a ceramide (q value = 0.001) and a phosphatidylcholine (q value = 0.005). Carriers of the CES1 143E allele had decreased methylphenidate metabolism and altered concentration of this phosphatidylcholine (q value = 0.040) and several high polyunsaturated fatty acid lipids (PUFAs). The half-maximal inhibitory concentration (IC50 ) values of chenodeoxycholate and taurocholate were 13.55 and 19.51 μM, respectively, consistent with a physiological significance. In silico analysis suggested that bile acid inhibition of CES1 involved both binding to the active and superficial sites of the enzyme. We initiated identification of metabolites predicting PKs of drugs metabolized by CES1 and suggest lipids to regulate or be regulated by this enzyme. PMID: 30169917 [PubMed - in process]

Pluripotent Stem Cells in Developmental Toxicity Testing: A Review of Methodological Advances.

Sat, 01/09/2018 - 14:57
Related Articles Pluripotent Stem Cells in Developmental Toxicity Testing: A Review of Methodological Advances. Toxicol Sci. 2018 Sep 01;165(1):31-39 Authors: Luz AL, Tokar EJ Abstract Millions of children are born each year with a birth defect. Many of these defects are caused by environmental factors, although the underlying etiology is often unknown. In vivo mammalian models are frequently used to determine if a chemical poses a risk to the developing fetus. However, there are over 80 000 chemicals registered for use in the United States, many of which have undergone little safety testing, necessitating the need for higher-throughput methods to assess developmental toxicity. Pluripotent stem cells (PSCs) are an ideal in vitro model to investigate developmental toxicity as they possess the capacity to differentiate into nearly any cell type in the human body. Indeed, a burst of research has occurred in the field of stem cell toxicology over the past decade, which has resulted in numerous methodological advances that utilize both mouse and human PSCs, as well as cutting-edge technology in the fields of metabolomics, transcriptomics, transgenics, and high-throughput imaging. Here, we review the wide array of approaches used to detect developmental toxicants, suggest areas for further research, and highlight critical aspects of stem cell biology that should be considered when utilizing PSCs in developmental toxicity testing. PMID: 30169765 [PubMed - in process]

Application of NMR metabolomics to search for human disease biomarkers in blood.

Sat, 01/09/2018 - 14:57
Related Articles Application of NMR metabolomics to search for human disease biomarkers in blood. Clin Chem Lab Med. 2018 Aug 31;: Authors: Song Z, Wang H, Yin X, Deng P, Jiang W PMID: 30169327 [PubMed - as supplied by publisher]

Untargeted metabolomics-like screening approach for chemical characterization and differentiation of canopic jar and mummy samples from Ancient Egypt using GC-high resolution MS.

Sat, 01/09/2018 - 14:57
Related Articles Untargeted metabolomics-like screening approach for chemical characterization and differentiation of canopic jar and mummy samples from Ancient Egypt using GC-high resolution MS. Analyst. 2018 Aug 31;: Authors: Brockbals L, Habicht M, Hajdas I, Galassi FM, Rühli FJ, Kraemer T Abstract In Ancient Egypt it was common practice to embalm corpses and specific internal organs to ensure eternal life. The exact nature of the employed embalming fluids, particularly for organ preservation within the canopic jars, is debated. Therefore, the aim of the current study, was to chemically characterize and differentiate canopic jars (n = 28) and mummies (n = 6) using gas chromatography - high resolution mass spectrometry (GC-HR MS) with a new untargeted metabolomics-like screening approach; as part of a larger minimal-invasive transdisciplinary study on Ancient Egyptian human tissues. Post-analytical data processing included deconvolution, screening against the NIST 14 spectral database as well as a high resolution metabolomics library, and positive peak evaluation. In the majority of samples the presence of a coniferous resin was indicated by the detection of longiborneol in combination with abietadiene acid derivatives and guajacol. Beeswax, proposedly used for symbolic reasons and/or as a binding agent, was detected in 10 samples. Previously not mentioned in the literature, but identified in the current sample set, were medical-related substances like aniseed constituents, salicylic acid, chamazulene and jacobine. By applying an untargeted metabolomics-like approach to archaeological samples for the first time, extensive statistical analysis was made possible (using both identified and non-identified features; adding up to 4381 features), which showed significant differences in the overall chemical composition of canopic jar and mummy samples using principle component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). This emphasizes the necessity for more extensive canopic jar studies in the future in order to interpret findings correctly. PMID: 30168542 [PubMed - as supplied by publisher]

Metabolomics of tracheal wash samples and exhaled breath condensates in healthy horses and horses affected by equine asthma.

Sat, 01/09/2018 - 14:57
Related Articles Metabolomics of tracheal wash samples and exhaled breath condensates in healthy horses and horses affected by equine asthma. J Breath Res. 2018 Aug 31;: Authors: Bazzano M, Laghi L, Zhu C, Magi GE, Serri E, Spaterna A, Tesei B, Laus F Abstract The present work characterized the metabolomic profile of tracheal wash (TW) and exhaled breath condensate (EBC) in healthy horses and horses with respiratory disease. Six asthma-affected horses (Group A) and six healthy controls (Group H) underwent clinical, endoscopic and cytologic examinations of upper airways to confirm the active phase of asthma. TW and EBC samples were collected from each animal and investigated by Proton Nuclear magnetic resonance (1H-NMR) metabolomic analysis. A total of 10 out of 38 metabolites found in TW were significantly different between groups (p&lt; 0.05). Higher concentrations of histamine and oxidant agents like glutamate, valine, leucine and isoleucine, as well as lower levels of ascorbate, methylamine, dimethylamine and O-phosphocholine were found in Group A compared to Group H. Eight metabolites were found in equine EBC, namely methanol, ethanol, formate, trimethylamine, acetone, acetate, lactate and butanone, previously observed also in human EBC. Despite this was a pilot study, the results showed that metabolomic analysis of TW and EBC has the potentiality to serve as a basis for diagnostic tools in horses with asthma. PMID: 30168442 [PubMed - as supplied by publisher]

Vasculitis research: Current trends and future perspectives.

Sat, 01/09/2018 - 14:57
Related Articles Vasculitis research: Current trends and future perspectives. Int J Rheum Dis. 2018 Aug 30;: Authors: Misra DP, Naidu GSRSNK, Agarwal V, Sharma A Abstract We discuss recent and prospective research in small and large vessel vasculitis. Large cohorts of Takayasu arteritis (TA) have been recently published from across the world, clarifying our understanding of this uncommon disease. Novel open-ended approaches like large-scale genotyping, proteomics and metabolomics have helped gain novel insights into TA, giant cell arteritis (GCA) and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Recent advances in the imaging of TA and GCA offer promise for earlier diagnosis and better monitoring of response to therapy. Although two randomized controlled trials of abatacept and tocilizumab failed to meet their primary end-points, successful large-scale studies of abatacept and tocilizumab in GCA hold promise for better disease control. While cyclophosphamide has revolutionized the management of AAV, increasing use of rituximab as an alternative induction regimen, as well as use of novel approaches involving reduced or no corticosteroid use for AAV and alternative agents such as avacopan (a complement 5a receptor antagonist) hold promise for lesser toxic induction regimens in the future. Increasingly, the risk of cardiovascular events and comorbidities such as osteoporosis are being recognized as factors affecting long-term prospects of patients with vasculitis. There is a shift in emphasis to utilize patient-reported outcomes to more accurately gauge the impact of vasculitides and their treatment. PMID: 30168260 [PubMed - as supplied by publisher]

From genomics to metabolomics: emerging metastatic biomarkers in osteosarcoma.

Sat, 01/09/2018 - 14:57
Related Articles From genomics to metabolomics: emerging metastatic biomarkers in osteosarcoma. Cancer Metastasis Rev. 2018 Aug 31;: Authors: Dean DC, Shen S, Hornicek FJ, Duan Z Abstract Although the investigation into biomarkers specific for pulmonary metastasis within osteosarcoma (OS) has recently expanded, their usage within the clinic remains sparse. The current screening protocol after any OS diagnosis includes a chest CT scan; however, metastatic lung nodules frequently go undetected and remain the primary cause of death in OS. Recently, screening technologies such as liquid biopsy and next-generation sequencing have revealed a promising array of biomarkers with predictive and diagnostic value for the pulmonary metastasis associated with OS. These biomarkers draw from genomics, transcriptomics, epigenetics, and metabolomics. When assessed in concert, their utility is most promising as OS is a highly heterogeneous cancer. Accordingly, there has been an expansion of clinical trials not only aimed at further demonstrating the significance of these individual biomarkers but to also reveal which therapies resolve the pulmonary metastasis once detected. This review will focus on the recently discovered and novel metastatic biomarkers within OS, their molecular and cellular mechanisms, the expansion of humanized OS mouse models amenable to their testing, and the associated clinical trials aimed at managing the metastatic phase of OS. PMID: 30167827 [PubMed - as supplied by publisher]

Chemometric Analysis of Cannabinoids: Chemotaxonomy and Domestication Syndrome.

Sat, 01/09/2018 - 14:57
Related Articles Chemometric Analysis of Cannabinoids: Chemotaxonomy and Domestication Syndrome. Sci Rep. 2018 Aug 30;8(1):13090 Authors: Mudge EM, Murch SJ, Brown PN Abstract Cannabis is an interesting domesticated crop with a long history of cultivation and use. Strains have been selected through informal breeding programs with undisclosed parentage and criteria. The term "strain" refers to minor morphological differences and grower branding rather than distinct cultivated varieties. We hypothesized that strains sold by different licensed producers are chemotaxonomically indistinguishable and that the commercial practice of identifying strains by the ratio of total THC and CBD is insufficient to account for the reported human health outcomes. We used targeted metabolomics to analyze 11 known cannabinoids and an untargeted metabolomics approach to identify 21 unknown cannabinoids. Five clusters of chemotaxonomically indistinguishable strains were identified from the 33 commercial products. Only 3 of the clusters produce CBDA in significant quantities while the other 2 clusters redirect metabolic resources toward the THCA production pathways. Six unknown metabolites were unique to CBD-rich strains and/or correlated to CBDA and 3 unknowns were found only in THC-rich strains. Together, these data indicate the domestication of the cannabis germplasm has resulted in a loss of the CBDA pathway in some strains and reallocation of resources between CBDA and THCA pathways in others. The impact of domestication is a lack of chemical diversity and loss of biodiversity in modern cannabis strains. PMID: 30166613 [PubMed - in process]

Characterization of bacteria and yeasts isolated from traditional fermentation starter (Fen-Daqu) through a 1H NMR-based metabolomics approach.

Sat, 01/09/2018 - 14:57
Related Articles Characterization of bacteria and yeasts isolated from traditional fermentation starter (Fen-Daqu) through a 1H NMR-based metabolomics approach. Food Microbiol. 2018 Dec;76:11-20 Authors: Li RY, Zheng XW, Zhang X, Yan Z, Wang XY, Han BZ Abstract Daqu is a traditional fermentation starter for the production of baijiu and vinegar. It is an important saccharifying and fermenting agent associated with alcoholic fermentation and also a determining factor for the flavour development of these products. Bacterial and yeast isolates from a traditional fermentation starter (Fen-Daqu) were examined for their amylolytic activity, ethanol tolerance and metabolite production during sorghum-based laboratory-scale alcoholic fermentation. The selected strains (Bacillus licheniformis, Pediococcus pentosaceus, Lactobacillus plantarum, Pichia kudriavzevii, Wickerhamomyces anomalus, Saccharomyces cerevisiae, and Saccharomycopsis fibuligera) were blended in different combinations, omitting one particular strain in each mixture. 1H nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical analysis was used to investigate the influence of the selected strains on the metabolic changes observed under the different laboratory-controlled fermentation conditions. Principal component analysis showed differences in the metabolites produced by different mixtures of pure cultures. S. cerevisiae was found to be superior to other species with respect to ethanol production. S. fibuligera and B. licheniformis converted starch or polysaccharides to soluble sugars. Lactic acid bacteria had high amylolytic and proteolytic activities, thereby contributing to increased saccharification and protein degradation. W. anomalus was found to have a positive effect on the flavour of the Daqu-derived product. This study highlights the specific functions of S. cerevisiae, S. fibuligera, B. licheniformis, W. anomalus and lactic acid bacteria in the production of light-flavour baijiu (fen-jiu). Our results show that all investigated species deliver an important contribution to the functionality of the fermentation starter Daqu. PMID: 30166130 [PubMed - in process]

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