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: 55 min 52 sec ago

metabolomics; +92 new citations

Tue, 15/12/2020 - 16:03
92 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 2020/12/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +92 new citations

Tue, 15/12/2020 - 13:02
92 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 2020/12/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +24 new citations

Sat, 12/12/2020 - 15:18
24 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 2020/12/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +24 new citations

Sat, 12/12/2020 - 12:16
24 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 2020/12/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +23 new citations

Fri, 11/12/2020 - 21:09
23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/12/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +42 new citations

Thu, 10/12/2020 - 14:59
42 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 2020/12/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +18 new citations

Wed, 09/12/2020 - 14:52
18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/12/09PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +18 new citations

Tue, 08/12/2020 - 14:45
18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/12/08PubMed 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.

Phytoplankton trigger the production of cryptic metabolites in the marine actinobacterium Salinispora tropica.

Mon, 07/12/2020 - 14:39
Phytoplankton trigger the production of cryptic metabolites in the marine actinobacterium Salinispora tropica. Microb Biotechnol. 2020 Dec 05;: Authors: Chhun A, Sousoni D, Aguiló-Ferretjans MDM, Song L, Corre C, Christie-Oleza JA Abstract Filamentous members of the phylum Actinobacteria are a remarkable source of natural products with pharmaceutical potential. The discovery of novel molecules from these organisms is, however, hindered because most of the biosynthetic gene clusters (BGCs) encoding these secondary metabolites are cryptic or silent and are referred to as orphan BGCs. While co-culture has proven to be a promising approach to unlock the biosynthetic potential of many microorganisms by activating the expression of these orphan BGCs, it still remains an underexplored technique. The marine actinobacterium Salinispora tropica, for instance, produces valuable compounds such as the anti-cancer molecule salinosporamide but half of its putative BGCs are still orphan. Although previous studies have used marine heterotrophs to induce orphan BGCs in Salinispora, its co-culture with marine phototrophs has yet to be investigated. Following the observation of an antimicrobial activity against a range of phytoplankton by S. tropica, we here report that the photosynthate released by photosynthetic primary producers influences its biosynthetic capacities with production of cryptic molecules and the activation of orphan BGCs. Our work, using an approach combining metabolomics and proteomics, pioneers the use of phototrophs as a promising strategy to accelerate the discovery of novel natural products from marine actinobacteria. PMID: 33280260 [PubMed - as supplied by publisher]

Metabolomics of exhaled breath in critically ill COVID-19 patients: A pilot study.

Mon, 07/12/2020 - 14:39
Related Articles Metabolomics of exhaled breath in critically ill COVID-19 patients: A pilot study. EBioMedicine. 2020 Dec 03;63:103154 Authors: Grassin-Delyle S, Roquencourt C, Moine P, Saffroy G, Carn S, Heming N, Fleuriet J, Salvator H, Naline E, Couderc LJ, Devillier P, Thévenot EA, Annane D, Garches COVID-19 Collaborative GroupRECORDS Collaborators and Exhalomics® Collaborators Abstract BACKGROUND: Early diagnosis of coronavirus disease 2019 (COVID-19) is of the utmost importance but remains challenging. The objective of the current study was to characterize exhaled breath from mechanically ventilated adults with COVID-19. METHODS: In this prospective observational study, we used real-time, online, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of expired air from adults undergoing invasive mechanical ventilation in the intensive care unit due to severe COVID-19 or non-COVID-19 acute respiratory distress syndrome (ARDS). FINDINGS: Between March 25th and June 25th, 2020, we included 40 patients with ARDS, of whom 28 had proven COVID-19. In a multivariate analysis, we identified a characteristic breathprint for COVID-19. We could differentiate between COVID-19 and non-COVID-19 ARDS with accuracy of 93% (sensitivity: 90%, specificity: 94%, area under the receiver operating characteristic curve: 0•94-0•98, after cross-validation). The four most prominent volatile compounds in COVID-19 patients were methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal. INTERPRETATION: The real-time, non-invasive detection of methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal in exhaled breath may identify ARDS patients with COVID-19. FUNDING: The study was funded by Agence Nationale de la Recherche (SoftwAiR, ANR-18-CE45-0017 and RHU4 RECORDS, Programme d'Investissements d'Avenir, ANR-18-RHUS-0004), Région Île de France (SESAME 2016), and Fondation Foch. PMID: 33279860 [PubMed - as supplied by publisher]

Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort.

Mon, 07/12/2020 - 14:39
Related Articles Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort. Clin Gastroenterol Hepatol. 2020 Dec 03;: Authors: Rothwell JA, Murphy N, Bešević J, Kliemann N, Jenab M, Ferrari P, Achaintre D, Gicquiau A, Vozar B, Scalbert A, Huybrechts I, Freisling H, Prehn C, Adamski J, Cross AJ, Pala VM, Boutron-Ruault MC, Dahm CC, Overvad K, Gram IT, Sandanger TM, Skeie G, Jakszyn P, Tsilidis KK, Aleksandrova K, Schulze MB, Hughes DJ, van Guelpen B, Bodén S, Sánchez MJ, Schmidt JA, Katzke V, Kühn T, Colorado-Yohar S, Tumino R, Bueno-de-Mesquita B, Vineis P, Masala G, Panico S, Eriksen AK, Tjønneland A, Aune D, Weiderpass E, Severi G, Chajès V, Gunter MJ Abstract BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer (EPIC) cohort. METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5,738 cancer-free EPIC participants with metabolomics data. Partial least squares regression was used to derive fatty acid and endogenous metabolite signatures of WCRF/AICR score in this group. In an independent set of 1,608 colorectal cancer cases and matched controls, odds ratios (OR) and 95% confidence intervals (CI) were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of elevated odd-chain fatty acids, serine, glycine and specific phosphatidylcholines. Signatures were more strongly inversely associated with colorectal cancer risk (fatty acids: OR 0.51 per unit increase, 95% CI 0.29-0.90; endogenous metabolites: OR 0.62 per unit change, 95% CI 0.50-0.78) than the WCRF/AICR score (OR 0.93 per unit change, 95% CI 0.86-1.00) overall. Signature associations were stronger in male compared to female participants. CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer. PMID: 33279777 [PubMed - as supplied by publisher]

Disorders of flavin adenine dinucleotide metabolism: MADD and related deficiencies.

Mon, 07/12/2020 - 14:39
Related Articles Disorders of flavin adenine dinucleotide metabolism: MADD and related deficiencies. Int J Biochem Cell Biol. 2020 Dec 03;:105899 Authors: Mereis M, Wanders RJA, Schoonen M, Dercksen M, Smuts I, van der Westhuizen FH Abstract Multiple acyl-coenzyme A dehydrogenase deficiency (MADD), or glutaric aciduria type II (GAII), is a group of clinically heterogeneous disorders caused by mutations in electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETFQO) - the two enzymes responsible for the re-oxidation of enzyme-bound flavin adenine dinucleotide (FADH2) via electron transfer to the respiratory chain at the level of coenzyme Q10. Over the past decade, an increasing body of evidence has further coupled mutations in FAD metabolism (including intercellular riboflavin transport, FAD biosynthesis and FAD transport) to MADD-like phenotypes. In this review we provide a detailed description of the overarching and specific metabolic pathways involved in MADD. We examine the eight associated genes (ETFA, ETFB, ETFDH, FLAD1, SLC25A32 and SLC52A1-3) and clinical phenotypes, and report ∼437 causative mutations following a systematic literature review. Finally, we focus attention on the value and shortcomings of current diagnostic approaches, as well as current and future therapeutic options for MADD and its phenotypic disorders. PMID: 33279678 [PubMed - as supplied by publisher]

Maneb alters central carbon metabolism and thiol redox status in a toxicant model of Parkinson's disease.

Mon, 07/12/2020 - 14:39
Related Articles Maneb alters central carbon metabolism and thiol redox status in a toxicant model of Parkinson's disease. Free Radic Biol Med. 2020 Dec 03;: Authors: Anderson CC, Marentette JO, Rauniyar AK, Prutton K, Khatri M, Matheson C, Reisz JA, Reigan P, D'Alessandro A, Roede JR Abstract The dithiocarbamate fungicide maneb (MB) has attracted interest due to increasing concern of the negative health effects of pesticides, as well as its association with Parkinson's disease (PD). Our laboratory has previously reported distinct phenotypic changes of neuroblastoma cells exposed to acute, sub-toxic levels of MB, including decreased mitochondrial respiration, altered lactate dynamics, and metabolic stress. In this study, we aimed to further define the specific molecular mechanisms of MB toxicity through the comparison of several thiol-containing compounds and their effects on cellular energy metabolism and thiol redox nodes. Extracellular flux analyses and stable isotope labeled tracer metabolomics were employed to evaluate alterations in energy metabolism of SK-N-AS human neuroblastoma cells after acute exposure of an array of compounds, including dithiocarbamates (maneb, nabam, zineb) and other thiol-containing small molecules (glutathione, N-acetylcysteine). These studies revealed MB and its methylated form (MeDTC) as unique toxicants with significant alterations to mitochondrial respiration, proliferation, and glycolysis. We observed MB to significantly impact cellular thiol redox status by oxidizing cellular glutathione and altering the thiol redox status of peroxiredoxin 3 (Prx3, mitochondrial) after acute exposure. Redox Western blotting revealed a MB-specific modification of cellular Prx3, strengthening the argument that MB can preferentially target mitochondrial enzymes containing reactive cysteine thiols. Further, stable isotope tracer metabolomics confirmed our energetics assessments, and demonstrated that MB exposure results in acute derangement of central carbon metabolism. Specifically, we observed shunting of cellular glucose into the pentose-phosphate pathway and reduction of TCA intermediates derived from glucose and glutamine. Also, we report novel lactate utilization for TCA enrichment and glutathione synthesis after MB exposure. In summary, our results further confirm that MB exerts its toxic effects via thiol modification, and significantly transforms central carbon metabolism. PMID: 33279619 [PubMed - as supplied by publisher]

Postprandial Dried Blood Spot-Based Nutritional Metabolomic Analysis Discriminates a High-Fat, High-Protein Meat-Based Diet from a High Carbohydrate Vegan Diet: A Randomized Controlled Crossover Trial.

Mon, 07/12/2020 - 14:39
Related Articles Postprandial Dried Blood Spot-Based Nutritional Metabolomic Analysis Discriminates a High-Fat, High-Protein Meat-Based Diet from a High Carbohydrate Vegan Diet: A Randomized Controlled Crossover Trial. J Acad Nutr Diet. 2020 Dec 03;: Authors: McNairn M, Brito A, Dillard K, Heath H, Pantaleon M, Fanter R, Pilolla K, Amin S, La Frano MR Abstract BACKGROUND: Due to the challenges associated with accurate monitoring of dietary intake in humans, nutritional metabolomics (including food intake biomarkers) analysis as a complementary tool to traditional dietary assessment methods has been explored. Food intake biomarker assessment using postprandial dried blood spot (DBS) collection can be a convenient and accurate means of monitoring dietary intake vs 24-hour urine collection. OBJECTIVE: The objective of this study was to use nutritional metabolomics analysis to differentiate a high-fat, high-protein meat (HFPM) diet from a high-carbohydrate vegan (HCV) diet in postprandial DBS and 24-hour urine. DESIGN: This was a randomized controlled crossover feeding trial. PARTICIPANTS/SETTING: Participants were healthy young adult volunteers (n = 8) in California. The study was completed in August 2019. INTERVENTION: The standardized isocaloric diet interventions included an HFPM and an HCV diet. Participants attended 2 intervention days, separated by a 2-week washout. MAIN OUTCOME MEASURES: During each intervention day, a finger-prick blood sample was collected in the fasting state, 3 hours post breakfast, and 3 hours post lunch. Participants also collected their urine for 24 hours. DBS and urine samples were analyzed by ultra-performance liquid chromatography mass spectrometry to identify potential food intake biomarkers. STATISTICAL ANALYSES PERFORMED: Principal component analysis for discriminatory analysis and univariate analysis using paired t tests were performed. RESULTS: Principal component analysis found no discrimination of baseline DBS samples. In both the postprandial DBS and 24-hour urine, post-HFPM consumption had higher (P < 0.05) levels of acylcarnitines, creatine, and cis-trans hydroxyproline, and the HCV diet was associated with elevated sorbitol (P < 0.05). The HFPM diet had higher concentrations of triacylglycerols with fewer than 54 total carbons in DBS, and 24-hour urine had higher nucleoside mono- and di-phosphates (P < 0.05). CONCLUSIONS: Nutritional metabolomics profiles of postprandial DBS and 24-hour urine collections were capable of differentiating the HFPM and HCV diets. The potential use of postprandial DBS-based metabolomic analysis deserves further investigation for dietary intake monitoring. PMID: 33279463 [PubMed - as supplied by publisher]

Metabolomics analysis of microbiota-gut-brain axis in neurodegenerative and psychiatric diseases.

Mon, 07/12/2020 - 14:39
Related Articles Metabolomics analysis of microbiota-gut-brain axis in neurodegenerative and psychiatric diseases. J Pharm Biomed Anal. 2020 Nov 21;:113681 Authors: Konjevod M, Nikolac Perkovic M, Sáiz J, Svob Strac D, Barbas C, Rojo D Abstract Gut microbiota represents a complex physiological ecosystem that influences the host health. Alterations in the microbiome metabolism affect the body homeostasis and they have been associated with the development of different human neurodegenerative and neuropsychiatric disorders, such as Alzheimer's disease, autism spectrum disorder, bipolar disorder, depression, Huntington's disease, Parkinson's disease, posttraumatic stress disorder and schizophrenia. The development of these complex diseases is influenced by various factors, including genetic predisposition and environmental triggers. Gut microbiota has recently emerged as an important actor in their physiopathology that has been shown to play a role in inflammation, oxidative stress, and gut permeability. Therefore, targeting the metabolites that are produced by or associated with the gut microbiota may help us understand how imbalance in the gut-brain axis affects human health. This review offers a comprehensive overview of the literature on this matter, offering the readers an insight in the state-of-art metabolic measurements of the gut-brain axis in various brain-related diseases. PMID: 33279302 [PubMed - as supplied by publisher]

Development of mass spectrometry-based relatively quantitative targeted method for amino acids and neurotransmitters: Applications in the diagnosis of major depression.

Mon, 07/12/2020 - 14:39
Related Articles Development of mass spectrometry-based relatively quantitative targeted method for amino acids and neurotransmitters: Applications in the diagnosis of major depression. J Pharm Biomed Anal. 2020 Nov 20;:113773 Authors: Chen H, Xie H, Huang S, Xiao T, Wang Z, Ni X, Deng S, Lu H, Hu J, Li L, Wen Y, Shang D Abstract Targeted metabolomics analysis based on triple quadrupole (QQQ) MS coupled with multiple reaction monitoring mode (MRM) is the gold standard for metabolite quantification and it is widely applied in metabolomics. However, standard compounds for each metabolite and the corresponding analogs are necessary for quantitative measurements. To identify the differentially present metabolites in various groups, determining the relative concentration of metabolites would be more efficient than accurate quantification. In this study, a relatively quantitative targeted method was established for metabonomics research, on the basis of hydrophilic interaction liquid chromatography (HILIC)/QQQ MS operated in MRM mode. The quality control-base random forest signal correction algorithm (QC-RFSC algorithm) was applied for quality control instead of the internal standard method. High quality relative quantification was achieved without internal standards, and integrated peak areas were successfully used for statistical and pathway analyses. Amino acids and neurotransmitters (dopamine, kynurenic acid, urocanic acid, tryptophan, kynurenine, tyrosine, valine, threonine, serine, alanine, glycine, glutamine, citrulline, GABA, glutamate, aspartate, arginine, ornithine and histidine) in serum samples were simultaneously determined with the newly developed method. To demonstrate the applicability of this method in large-scale analyses, we analyzed the above metabolites in serum from patients with major depression. The serum levels of glutamate, aspartate, threonine, glycine and alanine were significantly higher, and those of citrulline, kynurenic acid and urocanic acid were significantly lower, in patients with major depression than in controls. This is the first report of the difference in urocanic acid, a compound reported to improve glutamate biosynthesis and release in the central nervous system, between healthy controls and patients with major depression. PMID: 33279298 [PubMed - as supplied by publisher]

Diet-derived fruit and vegetable metabolites show sex-specific inverse relationships to osteoporosis status.

Sun, 06/12/2020 - 14:30
Related Articles Diet-derived fruit and vegetable metabolites show sex-specific inverse relationships to osteoporosis status. Bone. 2020 Dec 02;:115780 Authors: Mangano KM, Noel SE, Lai CQ, Christensen JJ, Ordovas JM, Dawson-Hughes B, Tucker KL, Parnell LD Abstract BACKGROUND: The impact of nutrition on the metabolic profile of osteoporosis (OS) is unknown. OBJECTIVE: Identify biochemical factors driving the association of fruit and vegetable (FV) intakes with OS prevalence using an untargeted metabolomics approach. DESIGN: Cross-sectional dietary, anthropometric and plasma metabolite data were examined from the Boston Puerto Rican Osteoporosis Study, n = 600 (46-79 yr). METHODS: Bone mineral density was assessed by DXA. OS was defined by clinical standards. A culturally adapted FFQ assessed usual dietary intake. Principal components analysis (PCA) of 42 FV items created 6 factors. Metabolomic profiles derived from plasma samples were assessed on a commercial platform. Differences in levels of 525 plasma metabolites between disease groups (OS vs no-OS) were compared using logistic regression; and associations with FV intakes by multivariable linear regression, adjusted for covariates. Metabolites significantly associated with OS status or with total FV intake were analyzed for enrichment in various biological pathways using Mbrole 2.0, MetaboAnalyst, and Reactome, using FDR correction of P-values. Correlation coefficients were calculated as Spearman's rho rank correlations, followed by hierarchical clustering of the resulting correlation coefficients using PCA FV factors and sex-specific sets of OS-associated metabolites. RESULTS: High FV intake was inversely related to OS prevalence (Odds Ratio = 0.73; 95% CI = 0.57, 0.94; P = 0.01). Several biological processes affiliated with the FV-associating metabolites, including caffeine metabolism, carnitines and fatty acids, and glycerophospholipids. Important processes identified with OS-associated metabolites were steroid hormone biosynthesis in women and branched-chain amino acid metabolism in men. Factors derived from PCA were correlated with the OS-associated metabolites, with high intake of dark leafy greens and berries/melons appearing protective in both sexes. CONCLUSIONS: These data warrant investigation into whether increasing intakes of dark leafy greens, berries and melons causally affect bone turnover and BMD among middle-aged and older adults at risk for osteoporosis via sex-specific metabolic pathways, and how gene-diet interactions alter these sex-specific metabolomic-osteoporosis links. PMID: 33278656 [PubMed - as supplied by publisher]

Systems biology approaches to study lipidomes in health and disease.

Sun, 06/12/2020 - 14:30
Related Articles Systems biology approaches to study lipidomes in health and disease. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Dec 02;:158857 Authors: Alves MA, Lamichhane S, Dickens A, McGlinchey A, Ribeiro HC, Sen P, Wei F, Hyötyläinen T, Orešič M Abstract Lipids have many important biological roles, such as energy storage sources, structural components of plasma membranes and as intermediates in metabolic and signaling pathways. Lipid metabolism is under tight homeostatic control, exhibiting spatial and dynamic complexity at multiple levels. Consequently, lipid-related disturbances play important roles in the pathogenesis of most of the common diseases. Lipidomics, defined as the study of lipidomes in biological systems, has emerged as a rapidly-growing field. Due to the chemical and functional diversity of lipids, the application of a systems biology approach is essential if one is to address lipid functionality at different physiological levels. In parallel with analytical advances to measure lipids in biological matrices, the field of computational lipidomics has been rapidly advancing, enabling modeling of lipidomes in their pathway, spatial and dynamic contexts. This review focuses on recent progress in systems biology approaches to study lipids in health and disease, with specific emphasis on methodological advances and biomedical applications. PMID: 33278596 [PubMed - as supplied by publisher]

Metabolic markers for diagnosis and risk-prediction of multiple myeloma.

Sun, 06/12/2020 - 14:30
Related Articles Metabolic markers for diagnosis and risk-prediction of multiple myeloma. Life Sci. 2020 Dec 02;:118852 Authors: Fei F, Ma T, Zhou X, Zheng M, Cao B, Li J Abstract AIMS: To discriminate metabolic biomarkers for diagnosis and risk prediction of multiple myeloma (MM) on a basis of metabolic characteristics in systemic circulation and local pathogenic niche. MAIN METHODS: A gas chromatography mass spectrometry-based untargeted metabolomics analysis was performed within the bone marrow (BM) supernatants and peripheral plasma from healthy donors and patients with MM. KEY FINDINGS: Distinct metabolic features between MM patients and healthy volunteers were profiled in both BM and plasma. Metabolic profiles of subgroups in which MM patients undergo high/medium/low risk displayed risk-dependent metabolic shift especially in BM. In MM patients, up-regulated glutamate level and down-regulated glutamine level in BM indicated enhanced glutamate metabolism which provided NH4+ for ammonia utilization. This resulted in increased level of urea and creatinine produced from urea cycle, arginine and proline metabolism in both BM and plasma collected from MM patients. The disorders of tricarboxylic acid cycle and carnitine synthesis were unique in BM of MM patients. Receiver operating characteristic curve analysis indicated that aspartate was a candidate plasma biomarker for diagnosis with the highest sensitivity and specificity in both BM and plasma. Threonine was identified as a preferential plasma biomarker for risk prediction due to significant relation with various risk indexes of MM in both BM and plasma. SIGNIFICANCE: The perturbed glutamate metabolism and carnitine synthesis in BM of MM patients provided a new sight on pathogenesis of MM. The plasma level of aspartate and threonine may become a preferential metabolic marker for diagnosis and risk prediction of MM, respectively. PMID: 33278388 [PubMed - as supplied by publisher]

Ex vivo thyroid fine needle aspirations as an alternative for MALDI-MSI proteomic investigation: intra-patient comparison.

Sun, 06/12/2020 - 14:30
Related Articles Ex vivo thyroid fine needle aspirations as an alternative for MALDI-MSI proteomic investigation: intra-patient comparison. Anal Bioanal Chem. 2020 Dec 05;: Authors: Piga I, Capitoli G, Clerici F, Mahajneh A, Brambilla V, Smith A, Leni D, L'Imperio V, Galimberti S, Pagni F, Magni F Abstract Fine needle aspiration (FNA) is the reference standard for the diagnosis of thyroid nodules. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been successfully used to discriminate the proteomic profiles of benign and malignant thyroid FNAs within the scope of providing support to pathologists for the classification of morphologically borderline cases. However, real FNAs provide a limited amount of material due to sample collection restrictions. Ex vivo FNAs could represent a valuable alternative, increasing sample size and the power of statistical conclusions. In this study, we compared the real and ex vivo MALDI-MSI proteomic profiles, extracted from thyrocyte containing regions of interest, of 13 patients in order to verify their similarity. Statistical analysis demonstrated the mass spectra similarity of the proteomic profiles by performing intra-patient comparison, using statistical similarity systems. In conclusion, these results show that post-surgical FNAs represent a possible alternative source of material for MALDI-MSI proteomic investigations in instances where pre-surgical samples are unavailable or the number of cells is scarce. PMID: 33277997 [PubMed - as supplied by publisher]

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