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1
Roos, Martin. "Metabolom gibt Aufschlüsse." Im Focus Onkologie 19, no. 4 (April 2016): 10. http://dx.doi.org/10.1007/s15015-016-2443-z.
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Schütz, Burkhard, Heiko Hofmann, and Ricarda Kuenen. "Intestinales Mikrobiom und humanes Metabolom." Deutsche Zeitschrift für Onkologie 51, no. 04 (December 2019): 165–70. http://dx.doi.org/10.1055/a-1030-2772.
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ZusammenfassungDie mikrobielle Besiedlung des Darmes (intestinales Mikrobiom) beeinflusst die Gesundheit des gesamten Organismus. Je nach Zusammensetzung des Mikrobioms ergeben sich unterschiedliche Stoffwechselprozesse im Darm (Metabolom), die wiederum zu unterschiedlichen Stoffwechselprodukten, den Metaboliten, führen. In Abhängigkeit des intestinalen Mikrobioms und Metaboloms ergibt sich ein bestimmtes Metaboliten-Profil, welches bei der Entstehung und dem Verlauf diverser Erkrankungen eine bedeutende Rolle spielen kann, auch bei onkologischen Erkrankungen. Mit dem Wissen dieser bisher nicht bekannten biochemischen Zusammenhänge eröffnen sich neue und ursachenorientierte therapeutische Möglichkeiten in der Behandlung und Prävention von onkologischen Fällen. In diesem Artikel stellen wir inzwischen gut erforschte Wechselwirkungen zwischen intestinalem Mikrobiom und der humanen Darmmucosa, dem Gallensäuren-Stoffwechsel, der Biotransformation und Ausscheidung von Hormonen, Toxinen und mehr vor. Auch Mikrobiomeinflüsse auf Nahrungsbestandteile (z. B. Lecithin, Carnitin, Cholin u. a.) und Tryptophanmetabolismus werden erörtert.
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Mardin, W. A. "Das Metabolom des kolorektalen Karzinoms." Der Onkologe 20, no. 6 (May 11, 2014): 587–88. http://dx.doi.org/10.1007/s00761-014-2696-0.
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Tillack, J., N. Paczia, S. Leweke, M. Oldiges, W. Wiechert, K. Nöh, and S. Noack. "Modellierung und detaillierte Fehleranalyse der Metabolom-Datenprozessierung." Chemie Ingenieur Technik 82, no. 9 (August 27, 2010): 1556–57. http://dx.doi.org/10.1002/cite.201050353.
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Staiger, Dorothee. "Wie der Mensch das Tomaten-Metabolom verändert." Biologie in unserer Zeit 48, no. 4 (August 2018): 213–14. http://dx.doi.org/10.1002/biuz.201870407.
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MATOUŠEK, Jaroslav. ""Transgenic" metabolome of hop, some aspects of its development and prospects of utilization." Kvasny Prumysl 58, no. 1 (January 1, 2012): 13–19. http://dx.doi.org/10.18832/kp2012003.
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Fritschka, Emanuel. "Gliflozin verbessert Urin-Metabolom auch bei nierengesunden Diabetikern." Info Diabetologie 15, no. 3 (June 2021): 16–17. http://dx.doi.org/10.1007/s15034-021-3701-5.
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Krome, Dr Susanne. "Multiples Myelom." Onkologische Welt 09, no. 05 (December 2018): 218–19. http://dx.doi.org/10.1055/s-0038-1677584.
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Ein Metabolom umfasst die Gesamtheit der Stoffwechseleigenschaften von Zellen. Bislang war wenig über ein spezifisches metabolisches Muster von Myelomzellen bekannt. Die Studie belegt Unterschiede zu gesunden Kontrollen. Die Abgrenzung inner-halb der Myelom-Patientenpopulation war weniger markant.
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Vergara, Daniele, Sara Ravaioli, Eugenio Fonzi, Loredaria Adamo, Marina Damato, Sara Bravaccini, Francesca Pirini, et al. "Carbonic Anhydrase XII Expression Is Modulated during Epithelial Mesenchymal Transition and Regulated through Protein Kinase C Signaling." International Journal of Molecular Sciences 21, no. 3 (January 22, 2020): 715. http://dx.doi.org/10.3390/ijms21030715.
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Members of the carbonic anhydrase family are functionally involved in the regulation of intracellular and extracellular pH in physiological and pathological conditions. Their expression is finely regulated to maintain a strict control on cellular homeostasis, and it is dependent on the activation of extracellular and intracellular signaling pathways. Combining RNA sequencing (RNA-seq), NanoString, and bioinformatics data, we demonstrated that the expression of carbonic anhydrase 12 (CAXII) is significantly different in luminal and triple negative breast cancer (BC) models and patients, and is associated with the activation of an epithelial mesenchymal transition (EMT) program. In BC models, the phorbol ester 12-myristate 13-acetate (PMA)-mediated activation of protein kinase C (PKC) induced a down-regulation of CAXII with a concomitant modulation of other members of the transport metabolon, including CAIX and the sodium bicarbonate cotransporter 3 (NBCn1). This is associated with a remodeling of tumor glycolytic metabolism induced after PKC activation. Overall, this analysis highlights the dynamic nature of transport metabolom and identifies signaling pathways finely regulating this plasticity.
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Nenko, N. I., I. A. Ilina, M. A. Sundyreva, G. K. Kiseleva, and Т. V. Skhalyakho. "Metabolom characteristics of grape plant stability to low temperature stress." Scientific Works of North Caucasian Federal Scientific Center of Horticulture, Viticulture, Wine-making 15 (June 2018): 39–49. http://dx.doi.org/10.30679/2587-9847-2018-15-39-49.
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Thieme, R., R. Stier, N. Kreuser, S. Niebisch, M. Mehdorn, O. Lyros, Y. Moulla, B. Jansen-Winkeln, U. Ceglarek, and I. Gockel. "Metabolom-Analyse bei Patienten mit Barrett-Ösophagus und Barrett-Karzinom." Zeitschrift für Gastroenterologie 56, no. 08 (August 2018): e304-e304. http://dx.doi.org/10.1055/s-0038-1668927.
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Song, Byung Hoo, Su Young Son, Hyun Kyu Kim, Tae Won Ha, Jeong Suk Im, Aeli Ryu, Hyeji Jeon, et al. "Profiling of Metabolic Differences between Hematopoietic Stem Cells and Acute/Chronic Myeloid Leukemia." Metabolites 10, no. 11 (October 26, 2020): 427. http://dx.doi.org/10.3390/metabo10110427.
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Although many studies have been conducted on leukemia, only a few have analyzed the metabolomic profiles of various leukemic cells. In this study, the metabolomes of THP-1, U937, KG-1 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia, CML), and cord blood-derived CD34-positive hematopoietic stem cells (HSC) were analyzed using gas chromatography-mass spectrometry, and specific metabolic alterations were found using multivariate statistical analysis. Compared to HSCs, leukemia cell metabolomes were found to have significant alterations, among which three were related to amino acids, three to sugars, and five to fatty acids. Compared to CML, four metabolomes were observed specifically in AML. Given that overall more metabolites are present in leukemia cells than in HSCs, we observed that the activation of glycolysis and oxidative phosphorylation (OXPHOS) metabolism facilitated the incidence of leukemia and the proliferation of leukemic cells. Analysis of metabolome profiles specifically present in HSCs and leukemia cells greatly increases our basic understanding of cellular metabolic characteristics, which is valuable fundamental knowledge for developing novel anticancer drugs targeting leukemia metabolism.
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Wichter, J., S. Biemüller, T. Schlösser, W. Wiechert, and M. Oldiges. "Metabolom-Analyse eines industrienahen Prozesses zur Bildung von L-Cystein mit Escherichia coli." Chemie Ingenieur Technik 82, no. 9 (August 27, 2010): 1509–10. http://dx.doi.org/10.1002/cite.201050171.
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Diab, J., T. Hansen, R. Goll, H. Stenlund, E. Jensen, T. Moritz, J. Florholmen, and G. Forsdahl. "P003 Metabolomics for improved patient stratification in inflammatory bowel disease: Characterisation of the ulcerative colitis metabolome." Journal of Crohn's and Colitis 14, Supplement_1 (January 2020): S130—S131. http://dx.doi.org/10.1093/ecco-jcc/jjz203.132.
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Abstract Background The onset of ulcerative colitis (UC) is characterised by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host-microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies toward personalised medicine. This study aims to explore the mucosal metabolomic profile in treatment-naïve and deep remission UC patients, and to define the metabolic signature of UC. Methods Treatment-naive UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopy. The UC activity and the state of deep remission were assessed by endoscopy, histology, and by measuring TNF gene expression. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. Results Multivariate data analysis revealed a distinct metabolomic profile in inflamed mucosa taken from treatment- naïve UC patients compared with non-inflamed mucosa taken from UC remission patients and healthy controls. The mucosal metabolome in UC remission patients differed to a lesser extent from the healthy controls. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acylcarnitine, and amino acid profiles. Several metabolic pathways were perturbed, ranging from amino acid metabolism (such as tryptophan metabolism, and alanine, aspartate and glutamate metabolism) to antioxidant defence pathway (glutathione pathway). Furthermore, the pathway analysis revealed a disruption in the long-and short-chain fatty acid (LCFA and SCFA) metabolism, namely linoleic metabolism and butyrate metabolism. Conclusion The mucosal metabolomic profiling revealed a metabolic signature during the onset of UC, and reflected the homeostatic disturbance in the gut. The altered metabolic pathways highlight the importance of system biology approaches to identify key drivers of IBD pathogenesis which prerequisite personalised treatment.
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Volani, Chiara, Johannes Rainer, Vinicius Veri Hernandes, Viviana Meraviglia, Peter Paul Pramstaller, Sigurður Vidir Smárason, Giulio Pompilio, et al. "Metabolic Signature of Arrhythmogenic Cardiomyopathy." Metabolites 11, no. 4 (March 25, 2021): 195. http://dx.doi.org/10.3390/metabo11040195.
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Arrhythmogenic cardiomyopathy (ACM) is a genetic-based cardiac disease accompanied by severe ventricular arrhythmias and a progressive substitution of the myocardium with fibro-fatty tissue. ACM is often associated with sudden cardiac death. Due to the reduced penetrance and variable expressivity, the presence of a genetic defect is not conclusive, thus complicating the diagnosis of ACM. Recent studies on human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) obtained from ACM individuals showed a dysregulated metabolic status, leading to the hypothesis that ACM pathology is characterized by an impairment in the energy metabolism. However, despite efforts having been made for the identification of ACM specific biomarkers, there is still a substantial lack of information regarding the whole metabolomic profile of ACM patients. The aim of the present study was to investigate the metabolic profiles of ACM patients compared to healthy controls (CTRLs). The targeted Biocrates AbsoluteIDQ® p180 assay was used on plasma samples. Our analysis showed that ACM patients have a different metabolome compared to CTRLs, and that the pathways mainly affected include tryptophan metabolism, arginine and proline metabolism and beta oxidation of fatty acids. Altogether, our data indicated that the plasma metabolomes of arrhythmogenic cardiomyopathy patients show signs of endothelium damage and impaired nitric oxide (NO), fat, and energy metabolism.
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Wang, Shufeng, Xin Yang, Feng Liu, Xinzheng Wang, Xuemin Zhang, Kun He, and Hongxia Wang. "Comprehensive Metabolomic Analysis Reveals Dynamic Metabolic Reprogramming in Hep3B Cells with Aflatoxin B1 Exposure." Toxins 13, no. 6 (May 27, 2021): 384. http://dx.doi.org/10.3390/toxins13060384.
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Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 μM and 32 μM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.
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Fahlbusch, T., M. Buchholz, B. Majchrzak-Stiller, C. Braumann, and W. Uhl. "Evaluation eines Metabolom-Tumormarker-Panels bei Patienten mit duktalem Adenokarzinom des Pankreas und chronischer Pankreatitis." Zeitschrift für Gastroenterologie 56, no. 08 (August 2018): e236-e236. http://dx.doi.org/10.1055/s-0038-1668745.
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Patterson, Jeffrey, Xiaojian Shi, William Bresette, Ryan Eghlimi, Sarah Atlas, Kristin Farr, Sonia Vega-López, and Haiwei Gu. "A Metabolomic Analysis of the Sex-Dependent Hispanic Paradox." Metabolites 11, no. 8 (August 20, 2021): 552. http://dx.doi.org/10.3390/metabo11080552.
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In Mexican Americans, metabolic conditions, such as obesity and type 2 diabetes (T2DM), are not necessarily associated with an increase in mortality; this is the so-called Hispanic paradox. In this cross-sectional analysis, we used a metabolomic analysis to look at the mechanisms behind the Hispanic paradox. To do this, we examined dietary intake and body mass index (BMI; kg/m2) in men and women and their effects on serum metabolomic fingerprints in 70 Mexican Americans (26 men, 44 women). Although having different BMI values, the participants had many similar anthropometric and biochemical parameters, such as systolic and diastolic blood pressure, total cholesterol, and LDL cholesterol, which supported the paradox in these subjects. Plasma metabolomic phenotypes were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS). A two-way ANOVA assessing sex, BMI, and the metabolome revealed 23 significant metabolites, such as 2-pyrrolidinone (p = 0.007), TMAO (p = 0.014), 2-aminoadipic acid (p = 0.019), and kynurenine (p = 0.032). Pathway and enrichment analyses discovered several significant metabolic pathways between men and women, including lysine degradation, tyrosine metabolism, and branch-chained amino acid (BCAA) degradation and biosynthesis. A log-transformed OPLS-DA model was employed and demonstrated a difference due to BMI in the metabolomes of both sexes. When stratified for caloric intake (<2200 kcal/d vs. >2200 kcal/d), a separate OPLS-DA model showed clear separation in men, while females remained relatively unchanged. After accounting for caloric intake and BMI status, the female metabolome showed substantial resistance to alteration. Therefore, we provide a better understanding of the Mexican-American metabolome, which may help demonstrate how this population—particularly women—possesses a longer life expectancy despite several comorbidities, and reveal the underlying mechanisms of the Hispanic paradox.
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Baumann, Thomas W. "Some thoughts on the physiology of caffeine in coffee: and a glimpse of metabolite profiling." Brazilian Journal of Plant Physiology 18, no. 1 (March 2006): 243–51. http://dx.doi.org/10.1590/s1677-04202006000100017.
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Human beings enjoy the flavor and stimulating activity of a cup of coffee without knowing that by doing so, they are part of a 'food web' and receive signals coffee plants build to improve their struggle for life. This review is centered in the first part on the purine alkaloid caffeine and its physiological role in the coffee plant's life cycle. Many of the thoughts and ideas presented here are plain speculation, because the real research revealing the secrets of plant physiology such as e.g. the formation of the coffee bean with all its ingredients, has just started. The recent achievements in molecular biology made it possible to tackle and answer new questions regarding the regulation of secondary metabolism in the coffee plant organs at selected stages of their development. Brazilian research groups have much contributed to the recent progress in molecular biology and physiology of coffee. Among them was Maro R. Söndahl, in commemoration of whom this article has been written. Thus, the second part reports on the very first steps Maro and I made together into a very new field of coffee, that is metabolite profiling. The outcome was amazing and gives an idea of the great potential of this technique to map in future the complex network of the coffee metabolom.
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Diab, Joseph, Terkel Hansen, Rasmus Goll, Hans Stenlund, Einar Jensen, Thomas Moritz, Jon Florholmen, and Guro Forsdahl. "Mucosal Metabolomic Profiling and Pathway Analysis Reveal the Metabolic Signature of Ulcerative Colitis." Metabolites 9, no. 12 (November 27, 2019): 291. http://dx.doi.org/10.3390/metabo9120291.
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The onset of ulcerative colitis (UC) is characterized by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host–microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies. This study aims to explore the mucosal metabolomic profile in UC patients, and to define the UC metabolic signature. Treatment- naïve UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopies. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acyl carnitine, and amino acid profiles. Several pathways were found perturbed according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as tryptophan metabolism) to fatty acid metabolism, namely linoleic and butyrate. These metabolic changes during UC reflect the homeostatic disturbance in the gut, and highlight the importance of system biology approaches to identify key drivers of pathogenesis which prerequisite personalized medicine.
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Jeong, Jin Young, Minseok Kim, Kondreddy Eswar Reddy, Seul Lee, Soohyun Cho, and Hyun-Jeong Lee. "PSXI-12 Comparative metabolomics of blood plasma from Hanwoo beef cattle at different ages and fed diets with different nutritional levels, by using liquid chromatography-mass spectrometry." Journal of Animal Science 97, Supplement_3 (December 2019): 406–7. http://dx.doi.org/10.1093/jas/skz258.806.
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Abstract Blood metabolome can be used to estimate the growth, nutrition, and health status of livestock. The objective of this study is to find the differently expressed metabolome according to ages and nutritional levels in feeds to predict and control cattle performances. We used Hanwoo cattle at different ages that were fed diets with different nutritional levels. One hundred thirty two blood samples were collected from 22 Hanwoo steers at 13, 16, 19, 22, 25, 28 months and compared their blood metabolomes by using liquid chromatography mass spectrometry. The results of our comparative analysis showed clear discriminations in blood metabolomic profiles among the ages but not between nutritional levels. Based on the results of t-test, fold changes, and partial least square discriminant analysis, 19 metabolites showed high sensitivity for ages. Alanine, asparagine, aspartic acid, betaine, carnitine, choline, citrulline, creatine, cysteine, glutamine, glycine, histidine, lactate, leucine, proline, pyruvate, serine, tryptophan, and valine could be directly linked to ages. In particular, three metabolic pathways, ammonia recycling; urea cycle; and glycine and serine metabolism were shown to be enriched with the ages (FDR < 0.05, P < 0.05). Thus, the differently expressed metabolites and their related metabolic pathways in the blood plasma may contribute to the biomarkers which indicate the potential for early growing and fattening of indiviual beef cattle. Our findings may allow for better understanding of the mechanism of cattle growth physiology and metabolism, which is necessary for selecting appropriate feeding strategies to improve beef quality and productivity.
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Duan, Shuyan, Yusen Wu, Ruifeng Fu, Lei Wang, Yujin Chen, Wenping Xu, Caixi Zhang, Chao Ma, Jianxin Shi, and Shiping Wang. "Comparative Metabolic Profiling of Grape Skin Tissue along Grapevine Berry Developmental Stages Reveals Systematic Influences of Root Restriction on Skin Metabolome." International Journal of Molecular Sciences 20, no. 3 (January 28, 2019): 534. http://dx.doi.org/10.3390/ijms20030534.
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This research aimed to comparatively evaluate the influences of root restriction (RR) cultivation and traditional cultivation (RC) on grape berry skin metabolomics using a non-targeted metabolomics method. Two-hundred-and-ninety-one metabolites were annotated and the kinetics analyses showed that berry skin metabolome is stage- and cultivation-dependent. Our results showed that RR influences significantly the metabolomes of berry skin tissues, particularly on secondary metabolism, and that this effect is more obvious at pre-veraison stage, which was evidenced by the early and fast metabolic shift from primary to secondary metabolism. Altogether, this study provided an insight into metabolic adaptation of berry skin to RR stress and expanded general understanding of berry development.
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Martín-Masot, Rafael, Natàlia Mota-Martorell, Mariona Jové, José Maldonado, Reinald Pamplona, and Teresa Nestares. "Alterations in One-Carbon Metabolism in Celiac Disease." Nutrients 12, no. 12 (December 2, 2020): 3723. http://dx.doi.org/10.3390/nu12123723.
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Celiac disease (CD) is an autoimmune enteropathy associated with alterations of metabolism. Metabolomics studies, although limited, showed changes in choline, choline-derived lipids, and methionine concentrations, which could be ascribed to alterations in one-carbon metabolism. To date, no targeted metabolomics analysis investigating differences in the plasma choline/methionine metabolome of CD subjects are reported. This work is a targeted metabolomic study that analyzes 37 metabolites of the one-carbon metabolism in 17 children with CD, treated with a gluten-free diet and 17 healthy control siblings, in order to establish the potential defects in this metabolic network. Our results demonstrate the persistence of defects in the transsulfuration pathway of CD subjects, despite dietary treatment, while choline metabolism, methionine cycle, and folate cycle seem to be reversed and preserved to healthy levels. These findings describe for the first time, a metabolic defect in one-carbon metabolism which could have profound implications in the physiopathology and treatment of CD.
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Skalska, Aleksandra, Elzbieta Wolny, Manfred Beckmann, John H. Doonan, Robert Hasterok, and Luis A. J. Mur. "Allotetraploidization in Brachypodium May Have Led to the Dominance of One Parent’s Metabolome in Germinating Seeds." Cells 10, no. 4 (April 7, 2021): 828. http://dx.doi.org/10.3390/cells10040828.
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Seed germination is a complex process during which a mature seed resumes metabolic activity to prepare for seedling growth. In this study, we performed a comparative metabolomic analysis of the embryo and endosperm using the community standard lines of three annual Brachypodium species, i.e., B. distachyon (Bd) and B. stacei (Bs) and their natural allotetraploid B. hybridum (BdBs) that has wider ecological range than the other two species. We explored how far the metabolomic impact of allotetraploidization would be observable as over-lapping changes at 4, 12, and 24 h after imbibition (HAI) with water when germination was initiated. Metabolic changes during germination were more prominent in Brachypodium embryos than in the endosperm. The embryo and endosperm metabolomes of Bs and BdBs were similar, and those of Bd were distinctive. The Bs and BdBs embryos showed increased levels of sugars and the tricarboxylic acid cycle compared to Bd, which could have been indicative of better nutrient mobilization from the endosperm. Bs and BdBs also showed higher oxalate levels that could aid nutrient transfer through altered cellular events. In Brachypodium endosperm, the thick cell wall, in addition to starch, has been suggested to be a source of nutrients to the embryo. Metabolites indicative of sugar metabolism in the endosperm of all three species were not prominent, suggesting that mobilization mostly occurred prior to 4 HAI. Hydroxycinnamic and monolignol changes in Bs and BdBs were consistent with cell wall remodeling that arose following the release of nutrients to the respective embryos. Amino acid changes in both the embryo and endosperm were broadly consistent across the species. Taking our data together, the formation of BdBs may have maintained much of the Bs metabolome in both the embryo and endosperm during the early stages of germination. In the embryo, this conserved Bs metabolome appeared to include an elevated sugar metabolism that played a vital role in germination. If these observations are confirmed in the future with more Brachypodium accessions, it would substantiate the dominance of the Bs metabolome in BdBs allotetraploidization and the use of metabolomics to suggest important adaptive changes.
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Kiss, Borbála, Edit Mikó, Éva Sebő, Judit Tóth, Gyula Ujlaki, Judit Szabó, Uray Karen, Péter Bai, and Péter Árkosy. "Onkobiózis és mikrobiális metabolikus jelátvitel pancreas-adenocarcinomában." Central European Journal of Gastroenterology and Hepatology 7, no. 2 (2021): 57–65. http://dx.doi.org/10.33570/ceujgh.7.2.57.
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A hasnyálmirigy-adenocarcinoma az egyik legmagasabb halálozású daganat, medián ötéves túlélése 7-8%, korai diagnosztikája, eredményes kezelése kihívást jelent. A daganatos betegségekhez, így a pancreasrákhoz is gyakran társul a mikrobiom összetételének megváltozása (dysbiosis), amelyet onkobiózisnak nevezünk. Maga a pancreas is gyakran kolonizálódik (pl. többek között Helicobacter pylorival és Malassezia-fajokkal). Az onkobiomok összetétele eltér a rövid és hosszú túlélők esetén. Amennyiben pancreas-adenocarcinomás hosszú túlélők mikrobiomját ültetik hasnyálmirigy-adenocarcinoma állatmodellbe, az egerek túlélése meghosszabbodik. Az onkobiom modulálja a daganatos elfajuláshoz vezető gyulladásos folyamatot pancreas-adenocarcinomában. Az összefoglalóban a bakteriális metabolitok (rövid láncú zsírsavak, másodlagos epesavak, poliaminok, indolszármazékok) szerepét mutatjuk be a pancreas-adenocarcinoma patogenezisében, kitérve arra, hogy a betegségben a bakteriális metabolizmus és a bakteriális metabolom szabályozása is felborul. További metabolitok és anyagcsere-útvonalak felfedezése várható a közeljövőben, tovább bővítve ezen patogenetikai útvonal nyújtotta diagnosztikus és terápiás lehetőségeket hasnyálmirigy-adenocarcinomában.
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Michel, Miriam, Karl-Otto Dubowy, Manuela Zlamy, Daniela Karall, Mark Gordian Adam, Andreas Entenmann, Markus Andreas Keller, et al. "Targeted metabolomic analysis of serum phospholipid and acylcarnitine in the adult Fontan patient with a dominant left ventricle." Therapeutic Advances in Chronic Disease 11 (January 2020): 204062232091603. http://dx.doi.org/10.1177/2040622320916031.
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Background: Patients with a Fontan circulation have altered cholesterol and lipoprotein values. We analysed small organic molecules in extended phopsholipid and acylcarnitine metabolic pathways (‘metabolomes’) in adult Fontan patients with a dominant left ventricle, seeking differences between profiles in baseline and Fontan circulations. Methods: In an observational matched cross-sectional study, we compared phosphatidylcholine (PC), sphingomyelin (SM), and acylcarnitine metabolomes (105 analytes; AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) in 20 adult Fontan patients having a dominant left ventricle with those in 20 age- and sex-matched healthy controls. Results: Serum levels of total PC ( q-value 0.01), total SM ( q-value 0.0002) were significantly lower, and total acylcarnitines ( q-value 0.02) were significantly higher in patients than in controls. After normalisation of data, serum levels of 12 PC and 1 SM Fontan patients were significantly lower ( q-values <0.05), and concentrations of 3 acylcarnitines were significantly higher than those in controls ( q-values <0.05). Conclusion: Metabolomic profiling can use small specimens to identify biomarker patterns that track derangement in multiple metabolic pathways. The striking alterations in the phospholipid and acylcarnitine metabolome that we found in Fontan patients may reflect altered cell signalling and metabolism as found in heart failure in biventricular patients, chronic low-level inflammation, and alteration of functional or structural properties of lymphatic or blood vessels. Trial registration number: ClinicalTrials.gov Identifier NCT03886935
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Martín-Masot, Rafael, Jose Daniel Galo-Licona, Natàlia Mota-Martorell, Joaquim Sol, Mariona Jové, José Maldonado, Reinald Pamplona, and Teresa Nestares. "Up-Regulation of Specific Bioactive Lipids in Celiac Disease." Nutrients 13, no. 7 (June 30, 2021): 2271. http://dx.doi.org/10.3390/nu13072271.
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Celiac disease (CD) is an autoimmune enteropathy linked to alterations of metabolism. Currently, limited untargeted metabolomic studies evaluating differences in the plasma metabolome of CD subjects have been documented. We engage in a metabolomic study that analyzes plasma metabolome in 17 children with CD treated with a gluten-free diet and 17 healthy control siblings in order to recognize potential changes in metabolic networks. Our data demonstrates the persistence of metabolic defects in CD subjects in spite of the dietary treatment, affecting a minor but significant fraction (around 4%, 209 out of 4893 molecular features) of the analyzed plasma metabolome. The affected molecular species are mainly, but not exclusively, lipid species with a particular affectation of steroids and derivatives (indicating an adrenal gland affectation), glycerophospholipids (to highlight phosphatidic acid), glycerolipids (with a special affectation of diacylglycerols), and fatty acyls (eicosanoids). Our findings are suggestive of an activation of the diacylglycerol-phosphatidic acid signaling pathway in CD that may potentially have detrimental effects via activation of several targets including protein kinases such as mTOR, which could be the basis of the morbidity and mortality connected with untreated CD. However, more studies are necessary to validate this idea regarding CD.
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Hakimi, A. Ari, Chung-Han Lee, Justin R. Cross, Zhen Li, Yang Chen, Bruce Neri, Victor E. Reuter, Robert John Motzer, Paul Russo, and James Hsieh. "Global metabolic profiling of clear cell renal cell carcinoma." Journal of Clinical Oncology 31, no. 6_suppl (February 20, 2013): 379. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.379.
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379 Background: Recent data has suggested that metabolomic profiling in various cancer states may lead to novel biomarkers and innovative therapeutic strategies. We profiled the metabolome of 140 clear cell renal cell carcinomas (ccRCC) and matched normal tissue of various clinical stages. Methods: In collaboration with Metabolon, Inc., 140 clinically annotated tumors were subject to three global metabolic profiling mass spectroscopy platforms. Demographic, clinical, and pathologic data were recorded and patients were grouped into local, locally advanced and metastatic categories using clinical and pathologic criteria. Welch’s paired two sample t tests were used to identify biochemicals that differed significantly between the tumor and normal tissue groups (p value ≤0.001). Supervised clustering using random forest analysis was performed to identify metabolites that differentiated tumors and normals, as well as those associated with tumor progression. Results: A total of 877 biochemicals (including 300 unnamed metabolites) were identified. Several known cancer metabolic pathways were found to be altered consistent with the Warburg effect including accelerated glycolysis and pentose phosphate pathway (PPP), increased lipogenesis, elevated polyamine production, altered nitrogen handling, cell membrane metabolism, inflammation, and oxidative stress. Interestingly, several novel unexpected pathways were found to be altered and associated with disease progression including alterations in the 2-hydroxyglutarate pathway (2HG). 2HG levels were increased over 6 fold in tumors compared to normal and increased further with respect to disease progression (p = 0.019, q = 0.055). Several promising biomarker candidates were identified as well. Conclusions: We provide the first report of large scale metabolomic analysis of ccRCC, revealing several known and novel alterations to cancer-specific metabolic pathways. Investigation of novel pathway biology and biomarker validation in blood and urine samples is currently underway.
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Bagheri, Minoo, Rachana D. Shah, Jonathan D. Mosley, and Jane F. Ferguson. "Healthy Eating Index, Genomics and Metabolomics; Insights into the Mechanisms Driving Dietary Pattern to Metabolic Disorders." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 506. http://dx.doi.org/10.1093/cdn/nzaa046_006.
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Abstract Objectives Higher diet quality measured by healthy eating index (HEI) is associated with improved metabolic function, however the molecular basis remains unclear. We assessed associations between HEI and the metabolome in plasma and stool and explored interaction between genotype and HEI on circulating and gut metabolites. Methods We analyzed data from heathy individuals recruited to a single cross-sectional study visit (ABO Study, N = 75). HEI score was calculated from food frequency questionnaire. Metabolites in plasma (n = 800) and stool (n = 767) were measured at Metabolon Inc. Genotyping was performed by Exome chip (Illumina, CoreExome, N > 540,000 variants). Multivariable linear regression was used to assess the association of HEI score with metabolites adjusting for age, sex and body mass index. Plasma associations were replicated in the Fish oils and Adipose Inflammation Reduction (FAIR) study (N = 29). Metaboanalyst 4.0 was used to determine metabolic pathways. The interaction of single nucleotide polymorphisms (SNPs) and HEI on metabolites was tested using Plink. Results Metabolites in plasma (n = 74) and stool (n = 77) were associated with the HEI index (P < 0.05). One metabolite (N-acetyl-beta-alanine) overlapped between plasma (B = 0.003, P = 0.035) and stool (B = 0.008, P = 0.02). Glycine replicated between ABO (B = −0.001, P = 0.02) and FAIR studies (B = −0.01, P = 0.02). In plasma there was significant pathway enrichment in glycerophospholipid metabolism, glycine, serine-threonine metabolism and caffeine metabolism. In stool, histidine and caffeine metabolism pathways were significantly enriched. Significant (Pinteraction <5 × 10−8) interactions were observed between HEI and multiple independent SNPs for metabolites including circulating Valylleucine and gut Sedoheptulose-7-phosphate. Conclusions Diet quality, measured by HEI, is associated with differences in plasma and stool metabolites. The observed associations might aid understanding the link between food patterns and metabolic health outcomes. Further, our data support gene-nutrient interactions between HEI and SNPs contributing to plasma and gut metabolomic profiles. Future work will explore the relationship between HEI and gut microbiome composition. Funding Sources This project was supported by the National Institutes of Health.
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Pradas, Irene, Mariona Jové, Rosanna Cabré, Victoria Ayala, Natalia Mota-Martorell, and Reinald Pamplona. "Effects of Aging and Methionine Restriction on Rat Kidney Metabolome." Metabolites 9, no. 11 (November 14, 2019): 280. http://dx.doi.org/10.3390/metabo9110280.
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Methionine restriction (MetR) in animal models extends maximum longevity and seems to promote renoprotection by attenuating kidney injury. MetR has also been proven to affect several metabolic pathways including lipid metabolism. However, there is a lack of studies about the effect of MetR at old age on the kidney metabolome. In view of this, a mass spectrometry-based high-throughput metabolomic and lipidomic profiling was undertaken of renal cortex samples of three groups of male rats—An 8-month-old Adult group, a 26-month-old Aged group, and a MetR group that also comprised of 26-month-old rats but were subjected to an 80% MetR diet for 7 weeks. Additionally, markers of mitochondrial stress and protein oxidative damage were analyzed by mass spectrometry. Our results showed minor changes during aging in the renal cortex metabolome, with less than 59 differential metabolites between the Adult and Aged groups, which represents about 4% of changes in the kidney metabolome. Among the compounds identified are glycerolipids and lipid species derived from arachidonic acid metabolism. MetR at old age preferentially induces lipid changes affecting glycerophospholipids, docosanoids, and eicosanoids. No significant differences were observed between the experimental groups in the markers of mitochondrial stress and tissue protein damage. More than rejuvenation, MetR seems to induce a metabolic reprogramming.
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Shigematsu, Mei, Ryosuke Nakagawa, Shozo Tomonaga, Masayuki Funaba, and Tohru Matsui. "Fluctuations in metabolite content in the liver of magnesium-deficient rats." British Journal of Nutrition 116, no. 10 (November 9, 2016): 1694–99. http://dx.doi.org/10.1017/s0007114516003676.
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AbstractMg deficiency induces various metabolic disturbances including glucose metabolism in the liver. However, no comprehensive information is currently available on the metabolic pathways affected by Mg deficiency. The present study examined metabolite content in the liver of Mg-deficient rats using a metabolomic analysis. In this study, 4-week-old, male Sprague–Dawley rats were fed a control diet or a Mg-deficient diet for 8 weeks. The metabolomic analysis identified 105 metabolites in the liver, and significant differences were observed in the hepatic contents for thirty-three metabolites between the two groups. An analysis by MetaboAnalyst, a web-based metabolome data analysis tool, indicated that the Mg deficiency affected taurine/hypotaurine metabolism, methionine metabolism and glycine/serine/threonine metabolism; taurine, hypotaurine, glycine, serine and threonine contents were increased by Mg deficiency, whereas the amounts of 2-ketobutyric acid (a metabolite produced by the catabolism of cystathionine or threonine) and 5'-methylthioadenosine (a metabolite involved in spermidine synthesis) were decreased. The amount of glucose 6-phosphate, a hub metabolite of glycolysis/gluconeogenesis and the pentose phosphate pathway, was significantly decreased in Mg-deficient rats. Mg deficiency also decreased metabolite contents from the citric acid cycle, including citric acid, fumaric acid and malic acid. Aberrant metabolism may be related to the allosteric regulation of enzymes; the mRNA levels of enzymes were generally similar between the two groups. The present study suggests that the Mg deficiency-mediated modulation of hepatic metabolism is as yet uncharacterised.
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Patt, Andrew, Bryce Demoret, Colin Stets, Kate-Lynn Bill, Philip Smith, Anitha Vijay, Andrew Patterson, et al. "MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models." Cancers 12, no. 8 (August 4, 2020): 2157. http://dx.doi.org/10.3390/cancers12082157.
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Dedifferentiated liposarcoma (DDLPS) is an aggressive mesenchymal cancer marked by amplification of MDM2, an inhibitor of the tumor suppressor TP53. DDLPS patients with higher MDM2 amplification have lower chemotherapy sensitivity and worse outcome than patients with lower MDM2 amplification. We hypothesized that MDM2 amplification levels may be associated with changes in DDLPS metabolism. Six patient-derived DDLPS cell line models were subject to comprehensive metabolomic (Metabolon) and lipidomic (SCIEX 5600 TripleTOF-MS) profiling to assess associations with MDM2 amplification and their responses to metabolic perturbations. Comparing metabolomic profiles between MDM2 higher and lower amplification cells yielded a total of 17 differentially abundant metabolites across both panels (FDR < 0.05, log2 fold change < 0.75), including ceramides, glycosylated ceramides, and sphingomyelins. Disruption of lipid metabolism through statin administration resulted in a chemo-sensitive phenotype in MDM2 lower cell lines only, suggesting that lipid metabolism may be a large contributor to the more aggressive nature of MDM2 higher DDLPS tumors. This study is the first to provide comprehensive metabolomic and lipidomic characterization of DDLPS cell lines and provides evidence for MDM2-dependent differential molecular mechanisms that are critical factors in chemoresistance and could thus affect patient outcome.
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Lazcano-Ramírez, Hugo Gerardo, Roberto Gamboa-Becerra, Irving J. García-López, Ricardo A. Chávez Montes, David Díaz-Ramírez, Octavio Martínez de la Vega, José Juan Ordaz-Ortíz, et al. "Effects of the Developmental Regulator BOLITA on the Plant Metabolome." Genes 12, no. 7 (June 29, 2021): 995. http://dx.doi.org/10.3390/genes12070995.
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Transcription factors are important regulators of gene expression. They can orchestrate the activation or repression of hundreds or thousands of genes and control diverse processes in a coordinated way. This work explores the effect of a master regulator of plant development, BOLITA (BOL), in plant metabolism, with a special focus on specialized metabolism. For this, we used an Arabidopsis thaliana line in which the transcription factor activity can be induced. Fingerprinting metabolomic analyses of whole plantlets were performed at different times after induction. After 96 h, all induced replicas clustered as a single group, in contrast with all controls which did not cluster. Metabolomic analyses of shoot and root tissues enabled the putative identification of differentially accumulated metabolites in each tissue. Finally, the analysis of global gene expression in induced vs. non-induced root samples, together with enrichment analyses, allowed the identification of enriched metabolic pathways among the differentially expressed genes and accumulated metabolites after the induction. We concluded that the induction of BOL activity can modify the Arabidopsis metabolome. Future work should investigate whether its action is direct or indirect, and the implications of the metabolic changes for development regulation and bioprospection.
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Du, YanDan, ZhiHui Mi, YaPing Xie, DeSheng Lu, HaiJun Zheng, Hui Sun, Meng Zhang, and YiQing Niu. "Insights into the molecular basis of tick-borne encephalitis from multiplatform metabolomics." PLOS Neglected Tropical Diseases 15, no. 3 (March 10, 2021): e0009172. http://dx.doi.org/10.1371/journal.pntd.0009172.
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Background Tick-borne encephalitis virus (TBEV) is the most prevalent arbovirus, with a tentative estimate of 10,000 to 10,500 infections occurring in Europe and Asia every year. Endemic in Northeast China, tick-borne encephalitis (TBE) is emerging as a major threat to public health, local economies and tourism. The complicated array of host physiological changes has hampered elucidation of the molecular mechanisms underlying the pathogenesis of this disease. Methodology/Principle findings System-level characterization of the serum metabolome and lipidome of adult TBEV patients and a healthy control group was performed using liquid chromatography tandem mass spectrometry. By tracking metabolic and lipid changes during disease progression, crucial physiological changes that coincided with disease stages could be identified. Twenty-eight metabolites were significantly altered in the sera of TBE patients in our metabolomic analysis, and 14 lipids were significantly altered in our lipidomics study. Among these metabolites, alpha-linolenic acid, azelaic acid, D-glutamine, glucose-1-phosphate, L-glutamic acid, and mannose-6-phosphate were altered compared to the control group, and PC(38:7), PC(28:3;1), TAG(52:6), etc. were altered based on lipidomics. Major perturbed metabolic pathways included amino acid metabolism, lipid and oxidative stress metabolism (lipoprotein biosynthesis, arachidonic acid biosynthesis, leukotriene biosynthesis and sphingolipid metabolism), phospholipid metabolism and triglyceride metabolism. These metabolites were significantly perturbed during disease progression, implying their latent utility as prognostic markers. Conclusions/Significance TBEV infection causes distinct temporal changes in the serum metabolome and lipidome, and many metabolites are potentially involved in the acute inflammatory response and immune regulation. Our global analysis revealed anti- and pro-inflammatory processes in the host and changes to the entire metabolic profile. Relationships between metabolites and pathologies were established. This study provides important insight into the pathology of TBE, including its pathology, and lays the foundation for further research into putative markers of TBE disease.
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Vizioli, Carlotta, Rosario B. Jaime-Lara, Alexis T. Franks, Rodrigo Ortiz, and Paule V. Joseph. "Untargeted Metabolomic Approach Shows No Differences in Subcutaneous Adipose Tissue of Diabetic and Non-Diabetic Subjects Undergoing Bariatric Surgery: An Exploratory Study." Biological Research For Nursing 23, no. 1 (August 7, 2020): 109–18. http://dx.doi.org/10.1177/1099800420942900.
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Background: Obesity plays a major role in the development of insulin resistance (IR) and diabetes (T2DM). Increased adipose tissue (AT) is particularly of interest because it activates a chronic inflammatory response in adipocytes and other tissues. AT plays key endocrine and metabolic functions, acting in the regulation of insulin sensitivity and energy homeostasis. Additionally, it can be easily collected during bariatric surgery. The purpose of this pilot study was to explore the potential differences in AT metabolism, through comparing the untargeted metabolomic profiles of diabetic and non-diabetic obese patients undergoing bariatric surgery. Methods: For this exploratory study, samples were collected from 17 subjects. Subcutaneous AT (SAT) samples from obese-diabetic (n = 8) and Obese-non-Diabetic (n = 9) subjects were obtained from the Human Metabolic Tissue Bank. Untargeted metabolomic profiling was performed by Metabolon® Inc. Statistical analysis was performed using the MetaboAnalyst 4.0 platform. Results: Among the 421 metabolites identified and analyzed there were no significant differences between the Obese-Diabetics and the Obese-non-Diabetics. Small changes were observed by fold change analysis mainly in lipid (n = 12; e.g. NEFAs) and amino acid (n = 8; e.g. BCAAs) metabolic pathways. Dysregulation of these metabolites has been associated with IR and other T2DM-related pathophysiological processes. Conclusion: Obesity may influence SAT metabolism masking T2DM-dependent dysregulation. Better understanding the metabolic differences within SAT in diabetic populations may help identify potential biomarkers for diagnosis and monitoring of T2DM in patients undergoing bariatric surgery.
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Putluri, N., Y. Zhang, V. Putluri, S. Vareed, V. T. Vasu, S. M. Fischer, C. Chad, and A. Sreekumar. "Androgen-regulated metabolome in prostate cancer." Journal of Clinical Oncology 29, no. 7_suppl (March 1, 2011): 25. http://dx.doi.org/10.1200/jco.2011.29.7_suppl.25.
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25 Background: Prostate cancer (PC) is the second most prevalent cancer among American men which is primarily treated by androgen ablation therapy. Although a number of patients respond to this regimen, a significant subset fail and the tumor invariably progresses into a hormone refractory metastatic state, which is lethal. Earlier we had reported the first unbiased metabolomic signature for localized and metastatic prostate cancer tissues. Advancing further, we attempt to delineate the subset of metabolome in prostate cancer which is regulated by androgen-action. Methods: Androgen responsive (R22V1, LnCap and VCAP) and independent (PC3, DU145) PC cells and benign prostate epithelial cells (RWPE) were profiled for their metabolomic alterations using mass spectrometry. Extracted metabolome from these cells were profiles using a combination quadrupole-time-of-flight (Q-TOF) and triple quadrupole (QQQ) mass spectrometers coupled to reverse phase and aqueous normal phase chromatography. The metabolomic profiles were analyzed to delineate class-specific signatures which were interrogated for altered bioprocesses using Oncomine Concept Map (OCM, www.oncomine.org ). The androgen receptor (AR) regulated metabolome was verified using treatment of PC cells with synthetic androgen, R1881. Results: A total of 3,092 metabolites (113 named) were detected across the 4 cells lines, of which 869 compounds were significantly (ANOVA P<0.01) different between androgen responsive and non-responsive cells. The differential compendia included 28 named metabolites, including sarcosine which was earlier shown to be elevated during PC development and progression. Bioprocess mapping of AR-regulated metabolome revealed enrichment of amino acid metabolism and methylation potential, both of which were earlier defined to be the hallmarks of PC development and progression. Conclusions: The study defines AR-regulated metabolic signature which portrays enrichment of amino acid metabolism and methylation potential that are hallmarks of PC development and progression. No significant financial relationships to disclose.
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Gisevius, Barbara, Aiden Haghikia, and Sarah Hirschberg. "Impact of Diet and the Gut Microbiome on Neurodegeneration and Regeneration in Neurological Disorders." Neuroforum 25, no. 1 (February 7, 2019): 39–47. http://dx.doi.org/10.1515/nf-2018-0013.
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Zusammenfassung Aktuelle Forschungsergebnisse im Bereich neurodegenerativer Erkrankungen deuten vermehrt darauf hin, dass die Ernährung und damit assoziiert die Zusammensetzung des Darm-Mikrobioms einen entscheidenden Einfluss auf die Entstehung und den Verlauf verschiedenster Krankheiten haben. Die sogenannte Darm-Hirn Achse, oder präziser die Darm-Mikrobiom-Hirn Achse hat dadurch deutlich an Aufmerksamkeit gewonnen. Dabei kann der Darm das zentrale Nervensystem auf unterschiedliche Weisen beeinflussen, I) direkt durch bakterielle Bestandteile und Metaboliten von Bakterien, II) durch Manipulation der im Körper zirkulierenden Immunzellen, oder III) durch direkten Kontakt, z. B. über den N. vagus. Fortschritte auf dem Gebiet der Molekularbiologie, wie das Next Generation Sequencing ermöglichen aufgrund ihres hohen Auflösungsvermögens die genaue Identifikation von Bakterien und die Kompositionen ganzer Mikrobiome. Dadurch ist es möglich, die Interaktionen zwischen dem intestinalen Mikrobiom, dem Metabolom und dem Darm- assoziierten Immunsystem detailliert zu erforschen. In dieser Arbeit diskutieren wir den Einfluss des Mikrobioms, der Ernährung und den damit verbundenen Gesundheitszustand auf die Neuroregeneration. Der Fokus liegt dabei auf der Möglichkeit, wie dieses Wissen in Zukunft für therapeutische Zwecke genutzt werden kann.
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Darghouth, Dhouha, Bérengère Koehl, Geoffrey Madalinski, Jean-François Heilier, Petra Bovee, Ying Xu, Marie-Françoise Olivier, et al. "Pathophysiology of sickle cell disease is mirrored by the red blood cell metabolome." Blood 117, no. 6 (February 10, 2011): e57-e66. http://dx.doi.org/10.1182/blood-2010-07-299636.
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Abstract Emerging metabolomic tools can now be used to establish metabolic signatures of specialized circulating hematopoietic cells in physiologic or pathologic conditions and in human hematologic diseases. To determine metabolomes of normal and sickle cell erythrocytes, we used an extraction method of erythrocytes metabolites coupled with a liquid chromatography-mass spectrometry–based metabolite profiling method. Comparison of these 2 metabolomes identified major changes in metabolites produced by (1) endogenous glycolysis characterized by accumulation of many glycolytic intermediates; (2) endogenous glutathione and ascorbate metabolisms characterized by accumulation of ascorbate metabolism intermediates, such as diketogulonic acid and decreased levels of both glutathione and glutathione disulfide; (3) membrane turnover, such as carnitine, or membrane transport characteristics, such as amino acids; and (4) exogenous arginine and NO metabolisms, such as spermine, spermidine, or citrulline. Finally, metabolomic analysis of young and old normal red blood cells indicates metabolites whose levels are directly related to sickle cell disease. These results show the relevance of metabolic profiling for the follow-up of sickle cell patients or other red blood cell diseases and pinpoint the importance of metabolomics to further depict the pathophysiology of human hematologic diseases.
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Zeng, Su-Ling, Shang-Zhen Li, Ping-Ting Xiao, Yuan-Yuan Cai, Chu Chu, Bai-Zhong Chen, Ping Li, Jing Li, and E.-Hu Liu. "Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism." Science Advances 6, no. 1 (January 2020): eaax6208. http://dx.doi.org/10.1126/sciadv.aax6208.
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Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)–induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.
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Araújo, Ana Margarida, Maria Enea, Félix Carvalho, Maria de Lourdes Bastos, Márcia Carvalho, and Paula Guedes de Pinho. "Hepatic Metabolic Derangements Triggered by Hyperthermia: An In Vitro Metabolomic Study." Metabolites 9, no. 10 (October 15, 2019): 228. http://dx.doi.org/10.3390/metabo9100228.
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Background and aims: Liver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the in vitro metabolic response of primary mouse hepatocytes (PMH, n = 10) to a heat stress stimulus, i.e., after 24 h exposure to 40.5 °C. Metabolomic profiling of both intracellular metabolites and volatile metabolites in the extracellular medium of PMH was performed. Results: Multivariate analysis showed alterations in levels of 22 intra- and 59 extracellular metabolites, unveiling the capability of the metabolic pattern to discriminate cells exposed to heat stress from cells incubated at normothermic conditions (37 °C). Hyperthermia caused a considerable loss of cell viability that was accompanied by significant alterations in the tricarboxylic acid cycle, amino acids metabolism, urea cycle, glutamate metabolism, pentose phosphate pathway, and in the volatile signature associated with the lipid peroxidation process. Conclusion: These results provide novel insights into the mechanisms underlying hyperthermia-induced hepatocellular damage.
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Schepkens, Dallons, Dehairs, Talebi, Jeandriens, Drossart, Auquier, Tagliatti, Swinnen, and Colet. "A New Classification Method of Metastatic Cancers Using a 1H-NMR-Based Approach: A Study Case of Melanoma, Breast, and Prostate Cancer Cell Lines." Metabolites 9, no. 11 (November 17, 2019): 281. http://dx.doi.org/10.3390/metabo9110281.
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In this study, metastatic melanoma, breast, and prostate cancer cell lines were analyzed using a 1H-NMR-based approach in order to investigate common features and differences of aggressive cancers metabolomes. For that purpose, 1H-NMR spectra of both cellular extracts and culture media were combined with multivariate data analysis, bringing to light no less than 20 discriminant metabolites able to separate the metastatic metabolomes. The supervised approach succeeded in classifying the metastatic cell lines depending on their glucose metabolism, more glycolysis-oriented in the BRAF proto-oncogene mutated cell lines compared to the others. Other adaptive metabolic features also contributed to the classification, such as the increased total choline content (tCho), UDP-GlcNAc detection, and various changes in the glucose-related metabolites tree, giving additional information about the metastatic metabolome status and direction. Finally, common metabolic features detected via 1H-NMR in the studied cancer cell lines are discussed, identifying the glycolytic pathway, Kennedy’s pathway, and the glutaminolysis as potential and common targets in metastasis, opening up new avenues to cure cancer.
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Xu, Puzhi, Ping Liu, Changming Zhou, Yan Shi, Qingpeng Wu, Yitian Yang, Guyue Li, Guoliang Hu, and Xiaoquan Guo. "A Multi-Omics Study of Chicken Infected by Nephropathogenic Infectious Bronchitis Virus." Viruses 11, no. 11 (November 16, 2019): 1070. http://dx.doi.org/10.3390/v11111070.
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Chicken gout resulting from nephropathogenic infectious bronchitis virus (NIBV) has become a serious kidney disease problem in chicken worldwide with alterations of the metabolic phenotypes in multiple metabolic pathways. To investigate the mechanisms in chicken responding to NIBV infection, we examined the global transcriptomic and metabolomic profiles of the chicken’s kidney using RNA-seq and GC–TOF/MS, respectively. Furthermore, we analyzed the alterations in cecal microorganism composition in chickens using 16S rRNA-seq. Integrated analysis of these three phenotypic datasets further managed to create correlations between the altered kidney transcriptomes and metabolome, and between kidney metabolome and gut microbiome. We found that 2868 genes and 160 metabolites were deferentially expressed or accumulated in the kidney during NIBV infection processes. These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. In addition, the comprehensive correlations between the kidney metabolome and cecal microbial community showed contributions of gut microbiota in the progression of NIBV-infection. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout.
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Del Coco, Laura, Daniele Vergara, Serena De Matteis, Emanuela Mensà, Jacopo Sabbatinelli, Francesco Prattichizzo, Anna Rita Bonfigli, et al. "NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus." Journal of Clinical Medicine 8, no. 5 (May 21, 2019): 720. http://dx.doi.org/10.3390/jcm8050720.
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Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naïve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort.
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Zhu, Chenglin, Cheng Li, Yaning Wang, and Luca Laghi. "Characterization of Yak Common Biofluids Metabolome by Means of Proton Nuclear Magnetic Resonance Spectroscopy." Metabolites 9, no. 3 (March 2, 2019): 41. http://dx.doi.org/10.3390/metabo9030041.
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The aim of this study was to evaluate the metabolic profiles of yak (Bos grunniens) serum, feces, and urine by using proton nuclear magnetic resonance (1H-NMR), to serve as a reference guide for the healthy yak milieu. A total of 108 metabolites, giving information about diet, protein digestion, and energy generation or gut-microbial co-metabolism, were assigned across the three biological matrices. A core metabolome of 15 metabolites was ubiquitous across all biofluids. Lactate, acetate, and creatinine could be regarded as the most abundant metabolites in the metabolome of serum, feces, and urine, respectively. Metabolic pathway analysis showed that the molecules identified could be able to give thorough information about four main metabolic pathways, namely valine, leucine, and isoleucine biosynthesis; phenylalanine, tyrosine, and tryptophan biosynthesis; glutamine and glutamate metabolism; and taurine and hypotaurine metabolism.
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Caterino, Marianna, Michele Costanzo, Roberta Fedele, Armando Cevenini, Monica Gelzo, Alessandro Di Minno, Immacolata Andolfo, et al. "The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism." International Journal of Molecular Sciences 22, no. 17 (September 2, 2021): 9548. http://dx.doi.org/10.3390/ijms22179548.
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COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.
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Yu, Elaine A., Tianwei Yu, Dean P. Jones, Reynaldo Martorell, Manuel Ramirez-Zea, and Aryeh D. Stein. "Macronutrient, Energy, and Bile Acid Metabolism Pathways Altered Following a Physiological Meal Challenge, Relative to Fasting, among Guatemalan Adults." Journal of Nutrition 150, no. 8 (June 29, 2020): 2031–40. http://dx.doi.org/10.1093/jn/nxaa169.
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ABSTRACT Background The healthy human metabolome, including its physiological responses after meal consumption, remains incompletely understood. One major research gap is the limited literature assessing how human metabolomic profiles differ between fasting and postprandial states after physiological challenges. Objectives Our study objective was to evaluate alterations in high-resolution metabolomic profiles following a standardized meal challenge, relative to fasting, in Guatemalan adults. Methods We studied 123 Guatemalan adults without obesity, hypertension, diabetes, metabolic syndrome, or comorbidities. Every participant received a standardized meal challenge (520 kcal, 67.4 g carbohydrates, 24.3 g fat, 8.0 g protein) and provided blood samples while fasting and at 2 h postprandial. Plasma samples were assayed by high-resolution metabolomics with dual-column LC [C18 (negative electrospray ionization), hydrophilic interaction LC (HILIC, positive electrospray ionization)] coupled to ultra-high-resolution MS. Associations between metabolomic features and the meal challenge timepoint were assessed in feature-by-feature multivariable linear mixed regression models. Two algorithms (mummichog, gene set enrichment analysis) were used for pathway analysis, and P values were combined by the Fisher method. Results Among participants (62.6% male, median age 43.0 y), 1130 features (C18: 777; HILIC: 353) differed between fasting and postprandial states (all false discovery rate–adjusted q < 0.05). Based on differing C18 features, top pathways included: tricarboxylic acid cycle (TCA), primary bile acid biosynthesis, and linoleic acid metabolism (all Pcombined < 0.05). Mass spectral features included: taurine and cholic acid in primary bile acid biosynthesis; and fumaric acid, malic acid, and citric acid in the TCA. HILIC features that differed in the meal challenge reflected linoleic acid metabolism (Pcombined < 0.05). Conclusions Energy, macronutrient, and bile acid metabolism pathways were responsive to a standardized meal challenge in adults without cardiometabolic diseases. Our findings reflect metabolic flexibility in disease-free individuals.
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Mateus, Tiago, Idália Almeida, Adriana Costa, Diana Viegas, Sandra Magalhães, Filipa Martins, Maria Teresa Herdeiro, et al. "Fourier-Transform Infrared Spectroscopy as a Discriminatory Tool for Myotonic Dystrophy Type 1 Metabolism: A Pilot Study." International Journal of Environmental Research and Public Health 18, no. 7 (April 6, 2021): 3800. http://dx.doi.org/10.3390/ijerph18073800.
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Myotonic dystrophy type 1 (DM1) is a hereditary disease characterized by progressive distal muscle weakness and myotonia. Patients with DM1 have abnormal lipid metabolism and a high propensity to develop a metabolic syndrome in comparison to the general population. It follows that metabolome evaluation in these patients is crucial and may contribute to a better characterization and discrimination between DM1 disease phenotypes and severities. Several experimental approaches are possible to carry out such an analysis; among them is Fourier-transform infrared spectroscopy (FTIR) which evaluates metabolic profiles by categorizing samples through their biochemical composition. In this study, FTIR spectra were acquired and analyzed using multivariate analysis (Principal Component Analysis) using skin DM1 patient-derived fibroblasts and controls. The results obtained showed a clear discrimination between both DM1-derived fibroblasts with different CTG repeat length and with the age of disease onset; this was evident given the distinct metabolic profiles obtained for the two groups. Discrimination could be attributed mainly to the altered lipid metabolism and proteins in the 1800–1500 cm−1 region. These results suggest that FTIR spectroscopy is a valuable tool to discriminate both DM1-derived fibroblasts with different CTG length and age of onset and to study the metabolomic profile of patients with DM1.
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Heresi, Gustavo A., Jacob T. Mey, John R. Bartholomew, Ihab S. Haddadin, Adriano R. Tonelli, Raed A. Dweik, John P. Kirwan, and Satish C. Kalhan. "Plasma metabolomic profile in chronic thromboembolic pulmonary hypertension." Pulmonary Circulation 10, no. 1 (January 2020): 204589401989055. http://dx.doi.org/10.1177/2045894019890553.
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We aimed to characterize the plasma metabolome of chronic thromboembolic pulmonary hypertension patients using a high-throughput unbiased omics approach. We collected fasting plasma from a peripheral vein in 33 operable chronic thromboembolic pulmonary hypertension patients, 31 healthy controls, and 21 idiopathic pulmonary arterial hypertension patients matched for age, gender, and body mass index. Metabolomic analysis was performed using an untargeted approach (Metabolon Inc. Durham, NC). Of the total of 862 metabolites identified, 362 were different in chronic thromboembolic pulmonary hypertension compared to controls: 178 were higher and 184 were lower. Compared to idiopathic pulmonary arterial hypertension, 147 metabolites were different in chronic thromboembolic pulmonary hypertension: 45 were higher and 102 were lower. The plasma metabolome allowed us to distinguish subjects with chronic thromboembolic pulmonary hypertension and healthy controls with a predictive accuracy of 89%, and chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension with 80% accuracy. Compared to idiopathic pulmonary arterial hypertension and healthy controls, chronic thromboembolic pulmonary hypertension patients had higher fatty acids and glycerol; while acyl cholines and lysophospholipids were lower. Compared to healthy controls, both idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients had increased acyl carnitines, beta-hydroxybutyrate, amino sugars and modified amino acids and nucleosides. The plasma global metabolomic profile of chronic thromboembolic pulmonary hypertension suggests aberrant lipid metabolism characterized by increased lipolysis, fatty acid oxidation, and ketogenesis, concomitant with reduced acyl choline and phospholipid moieties. Future research should investigate the pathogenetic and therapeutic potential of modulating lipid metabolism in chronic thromboembolic pulmonary hypertension.
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Garayburu-Caruso, Vanessa A., Robert E. Danczak, James C. Stegen, Lupita Renteria, Marcy Mccall, Amy E. Goldman, Rosalie K. Chu, et al. "Using Community Science to Reveal the Global Chemogeography of River Metabolomes." Metabolites 10, no. 12 (December 20, 2020): 518. http://dx.doi.org/10.3390/metabo10120518.
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River corridor metabolomes reflect organic matter (OM) processing that drives aquatic biogeochemical cycles. Recent work highlights the power of ultrahigh-resolution mass spectrometry for understanding metabolome composition and river corridor metabolism. However, there have been no studies on the global chemogeography of surface water and sediment metabolomes using ultrahigh-resolution techniques. Here, we describe a community science effort from the Worldwide Hydrobiogeochemistry Observation Network for Dynamic River Systems (WHONDRS) consortium to characterize global metabolomes in surface water and sediment that span multiple stream orders and biomes. We describe the distribution of key aspects of metabolomes including elemental groups, chemical classes, indices, and inferred biochemical transformations. We show that metabolomes significantly differ across surface water and sediment and that surface water metabolomes are more rich and variable. We also use inferred biochemical transformations to identify core metabolic processes shared among surface water and sediment. Finally, we observe significant spatial variation in sediment metabolites between rivers in the eastern and western portions of the contiguous United States. Our work not only provides a basis for understanding global patterns in river corridor biogeochemical cycles but also demonstrates that community science endeavors can enable global research projects that are unfeasible with traditional research models.
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Mao, Qingqing, Juer Liu, Justin R. Wiertzema, Dongjie Chen, Paul Chen, David J. Baumler, Roger Ruan, and Chi Chen. "Identification of Quinone Degradation as a Triggering Event for Intense Pulsed Light-Elicited Metabolic Changes in Escherichia coli by Metabolomic Fingerprinting." Metabolites 11, no. 2 (February 10, 2021): 102. http://dx.doi.org/10.3390/metabo11020102.
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Intense pulsed light (IPL) is becoming a new technical platform for disinfecting food against pathogenic bacteria. Metabolic changes are deemed to occur in bacteria as either the causes or the consequences of IPL-elicited bactericidal and bacteriostatic effects. However, little is known about the influences of IPL on bacterial metabolome. In this study, the IPL treatment was applied to E. coli K-12 for 0–20 s, leading to time- and dose-dependent reductions in colony-forming units (CFU) and morphological changes. Both membrane lipids and cytoplasmic metabolites of the control and IPL-treated E. coli were examined by the liquid chromatography-mass spectrometry (LC-MS)-based metabolomic fingerprinting. The results from multivariate modeling and marker identification indicate that the metabolites in electron transport chain (ETC), redox response, glycolysis, amino acid, and nucleotide metabolism were selectively affected by the IPL treatments. The time courses and scales of these metabolic changes, together with the biochemical connections among them, revealed a cascade of events that might be initiated by the degradation of quinone electron carriers and then followed by oxidative stress, disruption of intermediary metabolism, nucleotide degradation, and morphological changes. Therefore, the degradations of membrane quinones, especially the rapid depletion of menaquinone-8 (MK-8), can be considered as a triggering event in the IPL-elicited metabolic changes in E. coli.