LC–MS-Based Urinary Metabolite Signatures in Idiopathic Parkinson’s Disease

Increasing evidence has shown that abnormal metabolic phenotypes in body fluids reflect the pathogenesis and pathophysiology of Parkinson’s disease (PD). These body fluids include urine; however, the relationship between, specifically, urinary metabolic phenotypes and PD is not fully understood. In this study, urinary metabolites from a total of 401 clinical urine samples collected from 106 idiopathic PD patients and 104 normal control subjects were profiled by using high-performance liquid chromatography coupled to high-resolution mass spectrometry. Our study revealed significant correlation between clinical phenotype and urinary metabolite profile. Metabolic profiles of idiopathic PD patients differed significantly and consistently from normal controls, with related metabolic pathway variations observed in steroidogenesis, fatty acid beta-oxidation, histidine metabolism, phenylalanine metabolism, tryptophan metabolism, nucleotide metabolism, and tyrosine metabolism. In the fruit fly <i>Drosophila melanogaster</i>, the alteration of the kynurenine pathway in tryptophan metabolism corresponded with pathogenic changes in the alpha-synuclein overexpressed <i>Drosophila</i> model of PD. The results suggest that LC–MS-based urinary metabolomic profiling can reveal the metabolite signatures and related variations in metabolic pathways that characterize PD. Consistent PD-related changes across species may provide the basis for understanding metabolic regulation of PD at the molecular level

Pregnancy-Induced Metabolic Phenotype Variations in Maternal Plasma

Metabolic variations occur during normal pregnancy to provide the growing fetus with a supply of nutrients required for its development and to ensure the health of the woman during gestation. Mass spectrometry-based metabolomics was employed to study the metabolic phenotype variations in the maternal plasma that are induced by pregnancy in each of its three trimesters. Nontargeted metabolomics analysis showed that pregnancy significantly altered the profile of metabolites in maternal plasma. The levels of six metabolites were found to change significantly throughout pregnancy, with related metabolic pathway variations observed in biopterin metabolism, phospholipid metabolism, amino acid derivatives, and fatty acid oxidation. In particular, there was a pronounced elevation of dihydrobiopterin (BH₂), a compound produced in the synthesis of dopa, dopamine, norepinephrine, and epinephrine, in the second trimester, whereas it was markedly decreased in the third trimester. The turnover of BH₂ and tryptophan catabolites indicated that the fluctuations of neurotransmitters throughout pregnancy might reveal the metabolic adaption in the maternal body for the growth of the fetus. Furthermore, 11 lipid classes and 41 carnitine species were also determined and this showed variations in the presence of long-chain acylcarnitines and lysophospholipids in later pregnancy, suggesting changes of acylcarnitines and lysophospholipids to meet the energy demands in pregnant women. To our knowledge, this work is the first report of dynamic metabolic signatures and proposed related metabolic pathways in the maternal plasma for normal pregnancies and provided the basis for time-dependent metabolic trajectory against which disease-related disorders may be contrasted

Principal component analysis of transcriptome profiling in <i>D. radiodurans</i> R1.

<p>A, the plot of the principal component 1 (PC1) versus principal component 2 (PC2) was presented. B, Loadings plot of PC1. C, Hierarchical clustering analyses of the selected genes that have a high correlation with PC1. D, Loadings plot of PC2. E, Hierarchical clustering analyses of the selected genes that have a high correlation with PC2.</p

Expression patterns of selected genes for DNA repair pathway system (* <i>padj</i><0.1).

<p>A, base excision repair. B, nucleotide excision repair. C, homologous recombination. D. mismatch repair.</p

Strand-Specific RNA-seq analysis of the genes from <i>D. radiodurans</i> R1.

<p>Strand-specific coverage plot is shown. (Orange indicates the chromosome 1; violet, chromosome 2; green, plasmid 1; red, plasmid 2).</p

The differentially expressed TCA cycle genes during <i>D. radiodurans</i> R1 irradiation and recovery.

<p>The significant level (<i>padj</i>-value <0.1) of genes are indicated by the asterisks.</p

Overview of network components including genes and antioxidants in <i>D. radiodurans</i> that prevent cell damage from extreme irradiation.

<p>Red arrows and green arrows indicate the up-regulation and down-regulation, respectively. The representative <i>D.radiodurans</i> gene name is shown. The response of the DNA repair system activated in different stages of irradiation is listed. DC: wild type before radiation. D1: wild type with 1000 Gy radiation; D3: wild type with 3000 Gy radiation. DR: wild type one hour after 3000 Gy radiation.</p

Gene expression patterns in stages of <i>D. radiodurans</i> R1 irradiation and recovery.

<p>A, The differentially expressed genes in stages of <i>D. radiodurans</i> R1 irradiation and recovery. B, The expression pattern of annotated CDS and ncRNA reads. DC: wild type before radiation. D1: wild type with 1000 Gy radiation; D3: wild type with 3000 Gy radiation. DR: wild type one hour after 3000 Gy radiation.</p