scholarly journals Metabolomic Profile at Birth, Bronchiolitis and Recurrent Wheezing: A 3-Year Prospective Study

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 825
Author(s):  
Silvia Carraro ◽  
Valentina Agnese Ferraro ◽  
Michela Maretti ◽  
Giuseppe Giordano ◽  
Paola Pirillo ◽  
...  

There is growing interest for studying how early-life influences the development of respiratory diseases. Our aim was to apply metabolomic analysis to urine collected at birth, to evaluate whether there is any early metabolic signatures capable to distinguish children who will develop acute bronchiolitis and/or recurrent wheezing. Urine was collected at birth in healthy term newborns. Children were followed up to the age of 3 years and evaluated for the development of acute bronchiolitis and recurrent wheezing (≥3 episodes). Urine were analyzed through a liquid-chromatography mass-spectrometry based untargeted approach. Metabolomic data were investigated applying univariate and multivariate techniques. 205 children were included: 35 had bronchiolitis, 11 of whom had recurrent wheezing. Moreover, 13 children had recurrent wheezing not preceded by bronchiolitis. Multivariate data analysis didn’t lead to reliable classification models capable to distinguish children with and without bronchiolitis or with recurrent wheezing preceded by bronchiolitis neither by PLS for classification (PLS2C) nor by Random Forest (RF). However, a reliable signature was discovered to distinguish children who later develop recurrent wheezing not preceded by bronchiolitis, from those who do not (MCCoob = 0.45 for PLS2C and MCCoob = 0.48 for RF). In this unselected birth cohort, a well-established untargeted metabolomic approach found no biochemical-metabolic dysregulation at birth associated with the subsequent development of acute bronchiolitis or recurrent wheezing post-bronchiolitis, not supporting the hypothesis of an underlying predisposing background. On the other hand, a metabolic signature was discovered that characterizes children who develop wheezing not preceded by bronchiolitis.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lun Jing ◽  
Jean-Marie Guigonis ◽  
Delphine Borchiellini ◽  
Matthieu Durand ◽  
Thierry Pourcher ◽  
...  

Abstract Renal cell carcinomas (RCC) are classified according to their histological features. Accurate classification of RCC and comprehensive understanding of their metabolic dysregulation are of critical importance. Here we investigate the use of metabolomic analyses to classify the main RCC subtypes and to describe the metabolic variation for each subtype. To this end, we performed metabolomic profiling of 65 RCC frozen samples (40 clear cell, 14 papillary and 11 chromophobe) using liquid chromatography-mass spectrometry. OPLS-DA multivariate analysis based on metabolomic data showed clear discrimination of all three main subtypes of RCC (R2 = 75.0%, Q2 = 59.7%). The prognostic performance was evaluated using an independent cohort and showed an AUROC of 0.924, 0.991 and 1 for clear cell, papillary and chromophobe RCC, respectively. Further pathway analysis using the 21 top metabolites showed significant differences in amino acid and fatty acid metabolism between three RCC subtypes. In conclusion, this study shows that metabolomic profiling could serve as a tool that is complementary to histology for RCC subtype classification. An overview of metabolic dysregulation in RCC subtypes was established giving new insights into the understanding of their clinical behaviour and for the development of targeted therapeutic strategies.


Author(s):  
Michael Ackah ◽  
Yisu Shi ◽  
Mengmeng Wu ◽  
Lei Wang ◽  
Guo Peng ◽  
...  

Mulberry is an economically significant crop for the sericulture industry worldwide. Stresses such as drought exposure have a significant influence on plant survival. Metabolome directly reflects plant physiological status; thus, a way to assess this impact is to perform a global metabolomic analysis. This study investigated the effect of drought stress on mulberry Yu-711 metabolic balance using a liquid chromatography-mass spectrometry (LC-MS) based on an untargeted metabolomic approach. For this objective, Yu-711 leaves were subjected to two weeks of drought stress treatment and control without drought stress. Multivariate and univariate statistical analyses highlighted numerous differentially-accumulated metabolic elements as a function of time and treatment. Drought stress led to a more differentiated metabolites response than the control. We found that the levels of total lipids and galactolipids, and phospholipids (PC, PA, PE) were significantly altered, producing 48% of the total differentially expressed metabolites. Fatty acyls were the most abundant lipids expressed and decreased considerably by 73.6%. Prenol lipids class of lipids increased in drought leaves. Other classes of metabolites, including polyphenols( flavonoids and cinnamic acid), organic acid (amino acids), carbohydrates, benzenoids, and organoheterocyclic, all had a dynamic trend in response to the drought stress. However, their levels under drought stress generally decreased significantly compared to the control. These results provide an overview of the metabolic profile of the mulberry plant through differentially-accumulated compounds and provide a better understanding of global plant metabolic changes in defense mechanisms.


Metabolomics ◽  
2021 ◽  
Vol 17 (10) ◽  
Author(s):  
Thomas M. O’Connell ◽  
David L. Logsdon ◽  
Gloria Mitscher ◽  
R. Mark Payne

Abstract Background Children and young adults with single ventricle (SV) heart disease frequently develop heart failure (HF) that is intractable and difficult to treat. Our understanding of the molecular and biochemical reasons underlying this is imperfect. Thus, there is an urgent need for biomarkers that predict outcome and provide a rational basis for treatment, and advance our understanding of the basis of HF. Objective We sought to determine if a metabolomic approach would provide biochemical signatures of HF in SV children and young adults. If significant, these analytes might serve as biomarkers to predict outcome and inform on the biological mechanism(s) of HF. Methods We applied a multi-platform metabolomics approach composed of mass spectrometry (MS) and nuclear magnetic resonance (NMR) which yielded 495 and 26 metabolite measurements respectively. The plasma samples came from a cross-sectional set of young SV subjects, ages 2–19 years with ten control (Con) subjects and 16 SV subjects. Of the SV subjects, nine were diagnosed as congestive HF (SVHF), and 7 were not in HF. Metabolomic data were correlated with clinical status to determine if there was a signature associated with HF. Results There were no differences in age, height, weight or sex between the 3 cohorts. However, statistical analysis of the metabolomic profiles using ANOVA revealed 44 metabolites with significant differences between cohorts including 41 profiled by MS and 3 by NMR. These metabolites included acylcarnitines, amino acids, and bile acids, which distinguished Con from all SV subjects. Furthermore, metabolite profiles could distinguish between SV and SVHF subjects. Conclusion These are the first data to demonstrate a clear metabolomic signature associated with HF in children and young adults with SV. Larger studies are warranted to determine if these findings are predictive of progression to HF in time to provide intervention.


2020 ◽  
Author(s):  
Zhaoyu Ren ◽  
Ghulam Muhae-Ud-Din ◽  
Jianjian Liu ◽  
Taiguo Liu ◽  
Wanquan Chen ◽  
...  

Abstract Dwarf bunt caused by the pathogen Tilletia controversa Kühn is one of the most serious quarantine disease of winter wheat. Metabolomics studies provide detailed information about biochemical changes at the cell and tissue level of the plants. In the present study, liquid chromatography/mass spectrometry (LC/MS) metabolomic approach was used to investigate the changes in the grains metabolomics of T. controversa infected and non-infected samples. PCA analysis suggested that T. controversa infected and non-infected samples scattered separately during the interaction. LC/MS analysis showed that 62 different metabolites were recorded in the grains, among them total of 34 metabolites were up-regulated and 28 metabolite were down-regulated. The prostaglandins (PGs) and 9-hydroxyoctadecaenoic acids (9-HODEs) are fungal toxin related substances and their expression significantly increased in T. controversa infected grains. Additionally, the concentration of cucurbic acid and octadecatrienoic acid were changed significantly after pathogen infection, which has great role in plant defense. The eight different metabolic pathways activated during the T. controversa and wheat plants interactions including phenylalanine metabolism, isoquinoline alkaloid biosynthesis, starch and sucrose metabolism, tyrosine metabolism, sphingolipid metabolism, arginine and proline metabolism, alanine, aspartate, glutamate metabolism, and tryptophan metabolism.


Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1636
Author(s):  
Michael Ackah ◽  
Yisu Shi ◽  
Mengmeng Wu ◽  
Lei Wang ◽  
Peng Guo ◽  
...  

Mulberry is an economically significant crop for the sericulture industry worldwide. Stresses such as drought exposure have a significant influence on plant survival. Because metabolome directly reflects plant physiological condition, performing a global metabolomic analysis is one technique to examine this influence. Using a liquid chromatography-mass spectrometry (LC-MS) technique based on an untargeted metabolomic approach, the effect of drought stress on mulberry Yu-711 metabolic balance was examined. For this objective, Yu-711 leaves were subjected to two weeks of drought stress treatment and control without drought stress. Numerous differentially accumulated metabolic components in response to drought stress treatment were revealed by multivariate and univariate statistical analysis. Drought stress treatment (EG) revealed a more differentiated metabolite response than the control (CK). We found that the levels of total lipids, galactolipids, and phospholipids (PC, PA, PE) were significantly altered, producing 48% of the total differentially expressed metabolites. Fatty acyls components were the most abundant lipids expressed and decreased considerably by 73.6%. On the other hand, the prenol lipids class of lipids increased in drought leaves. Other classes of metabolites, including polyphenols (flavonoids and cinnamic acid), organic acid (amino acids), carbohydrates, benzenoids, and organoheterocyclic, had a dynamic trend in response to the drought stress. However, their levels under drought stress decreased significantly compared to the control. These findings give an overview for the understanding of global plant metabolic changes in defense mechanisms by revealing the mulberry plant metabolic profile through differentially accumulated compounds.


Metabolites ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 270 ◽  
Author(s):  
Daniel W. Bearden ◽  
David A. Sheen ◽  
Yamil Simón-Manso ◽  
Bruce A. Benner ◽  
Werickson F. C. Rocha ◽  
...  

There is a lack of experimental reference materials and standards for metabolomics measurements, such as urine, plasma, and other human fluid samples. Reasons include difficulties with supply, distribution, and dissemination of information about the materials. Additionally, there is a long lead time because reference materials need their compositions to be fully characterized with uncertainty, a labor-intensive process for material containing thousands of relevant compounds. Furthermore, data analysis can be hampered by different methods using different software by different vendors. In this work, we propose an alternative implementation of reference materials. Instead of characterizing biological materials based on their composition, we propose using untargeted metabolomic data such as nuclear magnetic resonance (NMR) or gas and liquid chromatography-mass spectrometry (GC-MS and LC-MS) profiles. The profiles are then distributed with the material accompanying the certificate, so that researchers can compare their own metabolomic measurements with the reference profiles. To demonstrate this approach, we conducted an interlaboratory study (ILS) in which seven National Institute of Standards and Technology (NIST) urine Standard Reference Material®s (SRM®s) were distributed to participants, who then returned the metabolomic data to us. We then implemented chemometric methods to analyze the data together to estimate the uncertainties in the current measurement techniques. The participants identified similar patterns in the profiles that distinguished the seven samples. Even when the number of spectral features is substantially different between platforms, a collective analysis still shows significant overlap that allows reliable comparison between participants. Our results show that a urine suite such as that used in this ILS could be employed for testing and harmonization among different platforms. A limited quantity of test materials will be made available for researchers who are willing to repeat the protocols presented here and contribute their data.


2020 ◽  
Vol 25 (1) ◽  
pp. 89-101
Author(s):  
Emily D. Lette ◽  
Nathan G. Lawler ◽  
Quinton F. Burnham ◽  
Mary C. Boyce ◽  
Rodney Duffy ◽  
...  

Abstract Hairy marron (Cherax tenuimanus Smith) are critically endangered freshwater crayfish found only in a single river in south-west Australia. Conservation efforts have included a captive breeding program, which has been largely unsuccessful, despite the closely related smooth marron (Cherax cainii Austin) being successfully bred for aquaculture. Using an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic approach we created a profile of the metabolites in the haemolymph for males and females of the two species of marron. A non-lethal method was used to collect haemolymph and 84 reproducible annotated metabolites were identified. Variation in the levels of some metabolites were detected between species and between sexes within species. Multivariate analyses clearly differentiated the congeneric species and univariate analyses identified differences between species, sex and for some metabolite interactions between species and sex. This study created a baseline metabolome dataset for the two species and began to investigate the biological significance of metabolites that varied between species. We have shown metabolomics could be used for targeted studies to potentially assist reproductive success. This approach will be beneficial for conservation and aquaculture practices with potential applications for other aquatic taxa worldwide.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Juryun Kim ◽  
Sunyoung Christina Kang ◽  
Na Eun Yoon ◽  
Yena Kim ◽  
Jinhyeok Choi ◽  
...  

Abstract Background Metabolomics is the systemic study of the unique fingerprints of metabolites involved in cellular processes and biochemical reactions. The metabolomic approach is useful in diagnosing and predicting the development of rheumatoid arthritis (RA) and osteoarthritis (OA) and is emerging as a useful tool for identifying disease biomarkers. The aim of this study was to compare the metabolic blueprint of fibroblast-like synoviocyte (FLS) cells and induced pluripotent stem cells (iPSCs) derived from RA and OA patients. Methods Somatic cells of RA patients (n = 3) and OA patients (n = 3) were isolated, transduced with a lentiviral plasmid, and reprogrammed into iPSCs displaying pluripotency. Metabolic profiling of RA and OA patient–derived FLS cells and iPSCs was performed using liquid chromatography/mass spectrometry and statistical analysis. After normalization by the sum of the peak intensities through LC/MS, 37 metabolites were detected across RA and OA patients. Results The metabolites of RA and OA were distinguishable according to the PLS-DA analysis. LysoPC (20:4), 4-methoxychalcone, phosphorylcholine, and nicotinamide (NAM) were significantly higher in RA iPSCs than in OA iPSCs (p < 0.05). The NMNAT-3 enzyme, which catalyzes an important step in the biosynthesis of NAD+ from adenosine triphosphate, was also upregulated in RA iPSCs. Interestingly, the proliferation of RA iPSCs was significantly greater than OA iPSC proliferation (p < 0.05). NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. When iPSCs were treated with 100 nM of the NAM inhibitor tannic acid (TA), the proliferation of RA iPSCs was significantly reduced (p < 0.001). Conclusions The metabolites of RA and OA FLS cells and RA and OA iPSCs were all clearly distinguishable from each other. NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. TA effectively inhibited the expression of NAM in RA iPSCs and is a possible effective treatment for RA patients.


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