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

Flavin containing monooxygenases for conversion of trimethylamine in salmon protein hydrolysates.

Mon, 28/09/2020 - 13:50
Related Articles Flavin containing monooxygenases for conversion of trimethylamine in salmon protein hydrolysates. Appl Environ Microbiol. 2020 Sep 25;: Authors: Goris M, Puntervoll P, Rojo D, Claussen J, Larsen Ø, Garcia-Moyano A, Almendral D, Barbas C, Ferrer M, Bjerga GEK Abstract Enzymatic processing of fish by-products for recovery of peptides (hydrolysates) is a promising technology to reach food grade ingredients of high nutritional quality. Despite this, their bitter taste and "fish" odor block implementation in food products and limit their economic potential. Trimethylamine (TMA) is a known contributor to malodor in fish. Current strategies to mask or remove the odor are either not effective or give rise to undesirable side effects. As an alternative approach to remediate TMA, we propose a novel enzymatic strategy to convert it into the odorless trimethylamine N-oxide (TMAO) using TMA monooxygenases (Tmms). We identified a diverse set of bacterial Tmms using a sequence similarity network. Purified, recombinant enzymes were assessed for their biocatalytic capacity by monitoring NADPH consumption and TMAO generation. Selected Tmms were subjected to biochemical characterization, and investigated for their ability to oxidize TMA in an industry relevant substrate. From the 45 bacterial Tmm candidates investigated, eight enzymes from four different taxa were selected for their high activity towards TMA. The three most active enzymes were shown to vary in temperature optimum, with the highest being 45 °C. Enzymatic activity dropped at high temperatures, likely due to structural unfolding. The enzymes were all active from pH 6-8.5 with functional stability being lowest around optimal pH. All three Tmms, given sufficient NADPH cofactor, were found to generate TMAO in the TMA rich salmon protein hydrolysate. The Tmms serve as unique starting points for engineering and should be useful for guiding process development for marine biorefineries.Importance Enzyme-based conversion of marine biomass to high quality peptide ingredients leaves a distinct smell of "fish" caused by the presence of trimethylamine, which is limiting their economic potential. We suggest an enzymatic solution for converting trimethylamine to the odorless trimethylamine N-oxide as a novel strategy to improve the smell quality of marine protein hydrolysates. Following a systematic investigation of 45 putative bacterial trimethylamine monooxygenases from several phyla, we expand the repertoire of known active trimethylamine monooxygenases. As a proof-of-concept, we demonstrate that three of these enzymes oxidized trimethylamine in an industry-relevant salmon protein hydrolysate. Our results add new oxidoreductases to the industrial biocatalytic toolbox, and provide a new point of departure for enzyme process developments in marine biorefineries. PMID: 32978141 [PubMed - as supplied by publisher]

Bileome: The bile acid metabolome of rat.

Mon, 28/09/2020 - 13:50
Related Articles Bileome: The bile acid metabolome of rat. Biochem Biophys Res Commun. 2020 Sep 22;: Authors: Gaikwad NW Abstract Bile acids (BA) play a vital physiological role in vivo. They are not only detergent of dietary lipids and nutrients, but also important hormones or nutrient signaling molecules in metabolic regulation process. Recent studies have also shown BA involvement in various cancers and diseases such as Parkinson's and Alzheimer's and liver diseases. However, majority of the reported literature about BA is restricted to enterohepatic circulation. Hitherto, there has been no comprehensive study of the BA profile in all the major tissue and biofluids in rat has been reported. In this first bileomics study, BA profile of 14 different rat biological specimens (liver, serum, kidney, heart, stomach, ovary, mammary, uterus, small intestine, big intestine, spleen, brain, feces and urine) were studied by ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS). Here I report the comprehensive identification and measurements of bile acids, the bileome, in rat. PCA analysis show distinct separate clusters of tissues as well as biofluids based on BA composition profile. Furthermore, we found that BA profiles of the organs that are involved in enterohepatic circulation were different than the other organs. Most of BA in brain, spleen, heart, ovary, urine, feces and uterus were in the unamidated form, and LCA and MOCA are the most abundant BAs in these organs. Whereas, most of BAs in liver, serum, mammary, large intestine, small intestine, stomach and kidney existed in amidated form, and TCA and T-β-MCA are primary BAs. Finally, first time, BAs are found and measured in kidney, heart, stomach, ovary, mammary, uterus, and spleen of rats. PMID: 32977942 [PubMed - as supplied by publisher]

Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile.

Mon, 28/09/2020 - 13:50
Related Articles Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile. Nutrients. 2020 Sep 23;12(10): Authors: Mecocci S, Gevi F, Pietrucci D, Cavinato L, Luly FR, Pascucci L, Petrini S, Ascenzioni F, Zolla L, Chillemi G, Cappelli K Abstract In recent years, extracellular vesicles (EVs), cell-derived micro and nano-sized structures enclosed in a double-layer membrane, have been in the spotlight for their high potential in diagnostic and therapeutic applications. Indeed, they act as signal mediators between cells and/or tissues through different mechanisms involving their complex cargo and exert a number of biological effects depending upon EVs subtype and cell source. Being produced by almost all cell types, they are found in every biological fluid including milk. Milk EVs (MEVs) can enter the intestinal cells by endocytosis and protect their labile cargos against harsh conditions in the intestinal tract. In this study, we performed a metabolomic analysis of MEVs, from three different species (i.e., bovine, goat and donkey) by mass spectroscopy (MS) coupled with Ultrahigh-performance liquid chromatography (UHPLC). Metabolites, both common or specific of a species, were identified and enriched metabolic pathways were investigated, with the final aim to evaluate their anti-inflammatory and immunomodulatory properties in view of prospective applications as a nutraceutical in inflammatory conditions. In particular, metabolites transported by MEVs are involved in common pathways among the three species. These metabolites, such as arginine, asparagine, glutathione and lysine, show immunomodulating effects. Moreover, MEVs in goat milk showed a greater number of enriched metabolic pathways as compared to the other kinds of milk. PMID: 32977543 [PubMed - as supplied by publisher]

Urine Untargeted Metabolomic Profiling Is Associated with the Dietary Pattern of Successful Aging among Malaysian Elderly.

Mon, 28/09/2020 - 13:50
Related Articles Urine Untargeted Metabolomic Profiling Is Associated with the Dietary Pattern of Successful Aging among Malaysian Elderly. Nutrients. 2020 Sep 23;12(10): Authors: Nik Mohd Fakhruddin NNI, Shahar S, Ismail IS, Ahmad Azam A, Rajab NF Abstract Food intake biomarkers (FIBs) can reflect the intake of specific foods or dietary patterns (DP). DP for successful aging (SA) has been widely studied. However, the relationship between SA and DP characterized by FIBs still needs further exploration as the candidate markers are scarce. Thus, 1H-nuclear magnetic resonance (1H-NMR)-based urine metabolomics profiling was conducted to identify potential metabolites which can act as specific markers representing DP for SA. Urine sample of nine subjects from each three aging groups, SA, usual aging (UA), and mild cognitive impairment (MCI), were analyzed using the 1H-NMR metabolomic approach. Principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were applied. The association between SA urinary metabolites and its DP was assessed using the Pearson's correlation analysis. The urine of SA subjects was characterized by the greater excretion of citrate, taurine, hypotaurine, serotonin, and melatonin as compared to UA and MCI. These urinary metabolites were associated with alteration in "taurine and hypotaurine metabolism" and "tryptophan metabolism" in SA elderly. Urinary serotonin (r = 0.48, p < 0.05) and melatonin (r = 0.47, p < 0.05) were associated with oat intake. These findings demonstrate that a metabolomic approach may be useful for correlating DP with SA urinary metabolites and for further understanding of SA development. PMID: 32977370 [PubMed - as supplied by publisher]

metabolomics; +35 new citations

Sat, 26/09/2020 - 13:25
35 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 2020/09/26PubMed 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; +20 new citations

Fri, 25/09/2020 - 13:12
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 2020/09/25PubMed 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; +27 new citations

Thu, 24/09/2020 - 16:07
27 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 2020/09/24PubMed 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; +27 new citations

Thu, 24/09/2020 - 13:06
27 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 2020/09/24PubMed 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; +19 new citations

Wed, 23/09/2020 - 16:03
19 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 2020/09/23PubMed 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; +19 new citations

Wed, 23/09/2020 - 13:00
19 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 2020/09/23PubMed 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; +34 new citations

Tue, 22/09/2020 - 15:47
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 2020/09/22PubMed 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; +34 new citations

Tue, 22/09/2020 - 12:47
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 2020/09/22PubMed 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.

Targeted and untargeted metabolomics provide insight into the consequences of glycine-N-methyltransferase deficiency including the novel finding of defective immune function.

Mon, 21/09/2020 - 12:32
Targeted and untargeted metabolomics provide insight into the consequences of glycine-N-methyltransferase deficiency including the novel finding of defective immune function. Physiol Rep. 2020 Sep;8(18):e14576 Authors: Eudy BJ, McDermott CE, Liu X, da Silva RP Abstract Fatty liver disease is increasing along with the prevalence of obesity and type-2 diabetes. Hepatic fibrosis is a major health complication for which there are no efficacious treatment options available. A better understanding of the fundamental mechanisms that contribute to the accumulation of fibrosis is needed. Glycine-N-methyltransferase (GNMT) is a critical enzyme in one-carbon metabolism that serves to regulate methylation and remethylation reactions. GNMT knockout (GNMT-/- ) mice display spontaneous hepatic fibrosis and later develop hepatocellular carcinoma. Previous literature supports the idea that hypermethylation as a consequence of GNMT deletion contributes to the hepatic phenotype observed. However, limited metabolomic information is available and the underlying mechanisms that contribute to hepatic fibrogenesis in GNMT-/- mice are still incomplete. Therefore, our goals were to use dietary intervention to determine whether increased lipid load exacerbates steatosis and hepatic fibrosis in this model and to employ both targeted and untargeted metabolomics to further understand the metabolic consequences of GNMT deletion. We find that GNMT mice fed high-fat diet do not accumulate more lipid or fibrosis in the liver and are in fact resistant to weight gain. Metabolomics analysis confirmed that pan-hypermethylation occurs in GNMT mice resulting in a depletion of nicotinamide intermediate metabolites. Further, there is a disruption in tryptophan catabolism that prevents adequate immune cell activation in the liver. The chronic cellular damage cannot be appropriately cleared due to a lack of immune checkpoint activation. This mouse model is an excellent example of how a disruption in small molecule metabolism can significantly impact immune function. PMID: 32951289 [PubMed - as supplied by publisher]

Urbanization in China is associated with pronounced perturbation of plasma metabolites.

Mon, 21/09/2020 - 12:32
Urbanization in China is associated with pronounced perturbation of plasma metabolites. Metabolomics. 2020 Sep 19;16(10):103 Authors: Wang Y, Sha W, Wang H, Howard AG, Tsilimigras MCB, Zhang J, Su C, Wang Z, Zhang B, Fodor AA, Gordon-Larsen P Abstract INTRODUCTION: Urbanization is associated with major changes in environmental and lifestyle exposures that may influence metabolic signatures. OBJECTIVES: We investigated cross-sectional urban and rural differences in plasma metabolome analyzed by liquid chromatography/mass spectrometry platform in 500 Chinese adults aged 25-68 years from two neighboring southern Chinese provinces. METHODS: We first examined the overall metabolome differences by urban and rural residential location, using Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) and random forest classification. We then tested the association between urbanization status and individual metabolites using a linear regression adjusting for age, sex, and province and conducted pathway analysis (Fisher's exact test) to identify metabolic pathways differed by urbanization status. RESULTS: We observed distinct overall metabolome by urbanization status in OPLS-DA and random forest classification. Using linear regression, out of a total of 1108 unique metabolite features identified in this sample, we found that 266 metabolites were differed by urbanization status (positive false discovery rate-adjusted p-value, q-value < 0.05). For example, the following metabolites were positively associated with urbanization status: caffeine metabolites from xanthine metabolism, hazardous pollutants like 4-hydroxychlorothalonil and perfluorooctanesulfonate, and metabolites implicated in cardiometabolic diseases, such as branched-chain amino acids. In pathway analysis, we found that xanthine metabolism pathways differed by urbanization status (q-value = 1.64E-04). CONCLUSION: We detected profound differences in host metabolites by urbanization status. Urban residents were characterized by metabolites signaling caffeine metabolism and toxic pollutants and metabolites on known pathways to cardiometabolic disease risks, compared to their rural counterparts. Our findings highlight the importance of considering urbanization in metabolomics analysis. PMID: 32951074 [PubMed - as supplied by publisher]

Comparative phytochemical profile of the elephant garlic (Allium ampeloprasum var. holmense) and the common garlic (Allium sativum) from the Val di Chiana area (Tuscany, Italy) before and after in vitro gastrointestinal digestion.

Sun, 20/09/2020 - 12:22
Comparative phytochemical profile of the elephant garlic (Allium ampeloprasum var. holmense) and the common garlic (Allium sativum) from the Val di Chiana area (Tuscany, Italy) before and after in vitro gastrointestinal digestion. Food Chem. 2020 Sep 13;338:128011 Authors: Ceccanti C, Rocchetti G, Lucini L, Giuberti G, Landi M, Biagiotti S, Guidi L Abstract This study is aimed to comparatively investigate the phytochemical profiles, focusing on the nutritional and phytochemical properties of common garlic (Allium sativum L.; CG) and elephant garlic (EG) (Allium ampeloprasum var. holmense) collected from the Val di Chiana area (Tuscany, Italy). The results showed a lower amount of fibers, demonstrating a higher digestibility of the bulb, and sulfur-containing compounds in EG rather than in CG. Untargeted metabolomic profiling followed by supervised and unsupervised statistics allowed understanding the differences in phytochemical composition among the two bulbs, both as raw bulbs, processed following the in vitro gastrointestinal digestion process. Typical sulfur-containing compounds, such as alliin and N-gamma-glutamyl-S-allyl cysteine, could notably be detected in lower amounts in EG. EG maintains a distinct phytochemical signature during in vitro gastrointestinal digestion. Our findings support the distinct sensorial attributes of the bulbs. PMID: 32950006 [PubMed - as supplied by publisher]

Potential causal role of l-glutamine in sickle cell disease painful crises: A Mendelian randomization analysis.

Sun, 20/09/2020 - 12:22
Potential causal role of l-glutamine in sickle cell disease painful crises: A Mendelian randomization analysis. Blood Cells Mol Dis. 2020 Sep 10;86:102504 Authors: Iboudo Y, Garrett ME, Bartolucci P, Brugnara C, Clish CB, Hirschhorn JN, Galactéros F, Ashley-Koch AE, Telen MJ, Lettre G Abstract In a recent clinical trial, the metabolite l-glutamine was shown to reduce painful crises in sickle cell disease (SCD) patients. To support this observation and identify other metabolites implicated in SCD clinical heterogeneity, we profiled 129 metabolites in the plasma of 705 SCD patients. We tested correlations between metabolite levels and six SCD-related complications (painful crises, cholecystectomy, retinopathy, leg ulcer, priapism, aseptic necrosis) or estimated glomerular filtration rate (eGFR), and used Mendelian randomization (MR) to assess causality. We found a potential causal relationship between l-glutamine levels and painful crises (N = 1278, odds ratio (OR) [95% confidence interval] = 0.68 [0.52-0.89], P = 0.0048). In two smaller SCD cohorts (N = 299 and 406), the protective effect of l-glutamine was observed (OR = 0.82 [0.50-1.34]), although the MR result was not significant (P = 0.44). We identified 66 significant correlations between the levels of other metabolites and SCD-related complications or eGFR. We tested these correlations for causality using MR analyses and found no significant causal relationship. The baseline levels of quinolinic acid were associated with prospectively ascertained survival in SCD patients, and this effect was dependent on eGFR. Metabolomics provide a promising approach to prioritize small molecules that may serve as biomarkers or drug targets in SCD. PMID: 32949984 [PubMed - as supplied by publisher]

Comprehensive analysis of metabolic alterations in Schizochytrium sp. strains with different DHA content.

Sun, 20/09/2020 - 12:22
Comprehensive analysis of metabolic alterations in Schizochytrium sp. strains with different DHA content. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 May 26;1160:122193 Authors: Yang J, Song X, Wang L, Cui Q Abstract Along with the daily growth of the market requirements for docosahexaenoic acid (DHA) algae oil, a large DHA ingredients are needed to ensure worldwide supply. Undoubtedly a high-productive strain would be the prerequisite for high quality and yield. A comprehensive understanding of the processes of DHA synthesis from glycolysis to the lipid accumulation would be benefit to achieve the final optimization of DHA production. In this study, we comprehensively characterized the metabolic profiles of a Schizochytrium sp. strain, which has higher DHA content and different biomass amino acid composition compared with the wild type to explore the affected pathways and underlying mechanism. Combined with the multivariate statistical analysis, twenty-two differential metabolites were screened as relevant to the discrepancy between two strains. The results showed relatively downregulated glycolysis and saturated fatty acids (SFA) synthesis, and upregulated TCA cycle, amino acids and polyunsaturated fatty acids (PUFA) synthesis in DHA high yield strain. The current study provide a terminal picture of gene regulation from downstream metabolism and demonstrate the advantage of metabolomics in characterizing metabolic status which in turn could provide effective information for the metabolic engineering. PMID: 32949924 [PubMed - as supplied by publisher]

Multi-omics analysis reveals that co-exposure to phthalates and metals disturbs urea cycle and choline metabolism.

Sun, 20/09/2020 - 12:22
Multi-omics analysis reveals that co-exposure to phthalates and metals disturbs urea cycle and choline metabolism. Environ Res. 2020 Sep 16;:110041 Authors: Papaioannou N, Distel E, de Oliveira E, Gabriel C, Frydas IS, Anesti O, Attignon EA, Odena A, Díaz R, Aggerbeck Μ, Horvat M, Barouki R, Karakitsios S, Sarigiannis DA Abstract This study aimed to evaluate the response of HepaRG cells after co-exposure to phthalates and heavy metals, using a high-dimensional biology paradigm (HDB). Liver is the main metabolism site for the majority of xenobiotics. For this reason, the HepaRG cell line was used as an in vitro model, and cells were exposed to two characteristic mixtures of phthalates and heavy metals containing phthalates (DEHP, DiNP, BBzP) and metals (lead, methylmercury, total mercury) in a concentration-dependent manner. The applied chemical mixtures were selected as the most abundant pollutants in the REPRO_PL and PHIME cohorts, which were studied using the exposome-wide approach in the frame of the EU project HEALS. These studies investigated the environmental causation of neurodevelopmental disorders in neonates and across Europe. The INTEGRA computational platform was used for the calculation of the effective concentrations of the chemicals in the liver through extrapolation from human biomonitoring data and this dose (and a ten-times higher one) was applied to the hepatocyte model. Multi-omics analysis was performed to reveal the genes, proteins, and metabolites affected by the exposure to these chemical mixtures.By extension, we could detect the perturbed metabolic pathways. The generated data were analyzed using advanced bioinformatic tools following the HEALS connectivity paradigm for multi-omics pathway analysis. Co-mapped transcriptomics and proteomics data showed that co-exposure to phthalates and heavy metals leads to perturbations of the urea cycle due to differential expression levels of arginase-1 and -2, argininosuccinate synthase, carbamoyl-phosphate synthase, ornithine carbamoyltransferase, and argininosuccinate lyase. Joint pathway analysis of proteomics and metabolomics data revealed that the detected proteins and metabolites, choline phosphate cytidylyltransferase A, phospholipase D3, group XIIA secretory phospholipase A2, α-phosphatidylcholine, and the a 1,2-diacyl-sn-glycero-3-phosphocholine, are responsible for the homeostasis of the metabolic pathways phosphatidylcholine biosynthesis I, and phospholipases metabolism. The urea, phosphatidylcholine biosynthesis I and phospholipase metabolic pathways are of particular interest since they have been identified also in human samples from the REPRO_PL and PHIME cohorts using untargeted metabolomics analysis and have been associated with impaired psychomotor development in children at the age of two. In conclusion, this study provides the mechanistic evidence that co-exposure to phthalates and metals disturb biochemical processes related to mitochondrial respiration during critical developmental stages, which are clinically linked to neurodevelopmental perturbations. PMID: 32949613 [PubMed - as supplied by publisher]

On sample preparation methods for fermented beverage VOCs profiling by GCxGC-TOFMS.

Sun, 20/09/2020 - 12:22
Related Articles On sample preparation methods for fermented beverage VOCs profiling by GCxGC-TOFMS. Metabolomics. 2020 Sep 19;16(10):102 Authors: Zhang P, Carlin S, Lotti C, Mattivi F, Vrhovsek U Abstract INTRODUCTION: Aromas and tastes have crucial influences on the quality of fermented beverages. The determination of aromatic compounds requires global non-targeted profiling of the volatile organic compounds (VOCs) in the beverages. However, experimental VOC profiling result depends on the chosen VOC collection method. OBJECTIVES: This study aims to observe the impact of using different sample preparation techniques [dynamic headspace (DHS), vortex-assisted liquid-liquid microextraction (VALLME), multiple stir bar sorptive extraction (mSBSE), solid phase extraction (SPE), and solid phase micro-extraction (SPME)] to figure out the most suitable sample preparation protocol for profiling the VOCs from fermented beverages. METHODS: Five common sample preparation methods were studied with beer, cider, red wine, and white wine samples. After the sample preparation, collected VOCs were analyzed by two-dimensional gas chromatography coupled with time of flight mass spectrometry (GCxGC-TOFMS). RESULTS: GCxGC oven parameters can be optimized with the Box-Behnken surface response model and response measure on peak dispersion. Due to the unavoidable column and detector saturation during metabolomic analysis, errors may happen during mass spectrum construction. Profiling results obtained with different sample preparation methods show considerable variance. Common findings occupy a small fraction of total annotated VOCs. For known fermentative aromas, best coverage can be reached by using SPME together with SPE for beer, and VALLME for wine and cider. CONCLUSIONS: GCxGC-TOFMS is a promising tool for non-targeted profiling on VOCs from fermented beverages. However, a proper data processing protocol is lacking for metabolomic analysis. Each sample preparation method has a specific profiling spectrum on VOC profiling. The coverage of the VOC metabolome can be improved by combining complementary methods. PMID: 32949264 [PubMed - as supplied by publisher]

The free amino acid profiles and metabolic biomarkers of predicting the chemotherapeutic response in advanced sarcoma patients.

Sun, 20/09/2020 - 12:22
Related Articles The free amino acid profiles and metabolic biomarkers of predicting the chemotherapeutic response in advanced sarcoma patients. Clin Transl Oncol. 2020 Sep 18;: Authors: Jia B, Wang W, Lin S, Shi L, Li Y, Gu Y, Gao F, Qin Y Abstract PURPOSE: Metabolomics is an emerging field in cancer research. Plasma free amino acid profiles (PFAAs) have shown different features in various cancers, but the characteristic in advanced sarcoma remains unclear. We aimed to uncover the specific PFAAs in advanced sarcoma and to find the relationship between the altering of PFAAs and response to chemotherapy. PATIENTS AND METHODS: We analyzed the differences in PFAAs between 23 sarcoma patients and 30 healthy subjects basing on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, we compared the dynamics of PFAAs after chemotherapy between improvement group and deterioration group. RESULTS: We identified seven biological differential amino acids and four pathways which were perturbed in the sarcoma patients compared with healthy subjects. After one cycle chemotherapy, the levels of γ-aminobutyric acid (GABA) and carnosine (Car) decreased significantly in the improvement group but not in deterioration group. The levels of α-aminobutyric acid (Abu) increased significantly in the deterioration group but not in the improvement group. CONCLUSION: Our study suggests the potential specific PFAAs in sarcoma patients. The unusual amino acids and metabolic pathways may provide ideas for clinical drugs targeting therapy. Three amino acids including Car, GABA and Abu may be metabolic biomarkers playing a role in dynamic monitoring of the therapeutic effect. PMID: 32948983 [PubMed - as supplied by publisher]

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