PubMed

Metabolic changes in mice cardiac tissue after low-dose irradiation revealed by 1H NMR spectroscopy. J Radiat Res. 2019 Dec 16;: Authors: Gramatyka M, Boguszewicz ᴌ, Ciszek M, Gabryś D, Kulik R, Sokół M Abstract Ionizing radiation may cause cardiotoxicity not only at high, but even at low (considered as harmless) doses, yet the molecular mechanisms of the heart's response to low doses are not clear. In this work, we used high-resolution nuclear magnetic resonance (NMR) spectroscopy to detect the early and late effects of radiation on the metabolism of murine hearts. The hearts of C57Bl/6NCrl female mice were irradiated in vivo with single 0.2 Gy or 2 Gy doses using 6 MV photons, then tissues were collected 48 h and 20 weeks after exposure. The most distinct changes in the profile of polar metabolites were detected 48 h after irradiation with 2 Gy, and included increased levels of pantothenate and glutamate as well as decreased levels of alanine, malonate, acetylcarnitine, glycine and adenosine. Significant effects of the 2 Gy dose were also observed 20 weeks after irradiation and included decreased levels of glutamine and acetylcarnitine when compared with age-matched controls. Moreover, several differences were observed between hearts irradiated with 2 Gy and analyzed either 48 h or 20 weeks after the exposure, which included changes in levels of acetylcarnitine, alanine, glycine, glutamate, glutamine, formate, myo-inositol and trimethylamine. No statistically significant effects induced by the 0.2 Gy dose were observed 20 weeks after irradiation. In general, radiation-affected compounds were associated with energy metabolism, fatty acid beta-oxidation, oxidative stress and damage to cell structures. At the same time, radiation-related effects were not detected at the level of tissue histology, which indicated a higher sensitivity of metabolomics-based tests for cardiac tissue response to radiation. PMID: 31840756 [PubMed - as supplied by publisher]

Related Articles Metabolic compounds within the porcine uterine environment are unique to the type of conceptus present during the early stages of blastocyst elongation. Mol Reprod Dev. 2019 Dec 16;: Authors: Walsh SC, Miles JR, Yao L, Broeckling CD, Rempel LA, Wright-Johnson EC, Pannier AK Abstract The objective of this study was to identify metabolites within the porcine uterine milieu during the early stages of blastocyst elongation. At Days 9, 10, or 11 of gestation, reproductive tracts of White cross-bred gilts (n = 38) were collected immediately following harvest and flushed with Roswell Park Memorial Institute-1640 medium. Conceptus morphologies were assessed from each pregnancy and corresponding uterine flushings were assigned to one of five treatment groups based on these morphologies: (a) uniform spherical (n = 8); (b) heterogeneous spherical and ovoid (n = 8); (c) uniform ovoid (n = 8); (d) heterogeneous ovoid and tubular (n = 8); and (e) uniform tubular (n = 6). Uterine flushings from these pregnancies were submitted for nontargeted profiling by gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography (UPLC)-MS techniques. Unsupervised multivariate principal component analysis (PCA) was performed using pcaMethods and univariate analysis of variance was performed in R with false discovery rate (FDR) adjustment. PCA analysis of the GC-MS and UPLC-MS data identified 153 and 104 metabolites, respectively. After FDR adjustment of the GC-MS and UPLC-MS data, 38 and 59 metabolites, respectively, differed (p < .05) in uterine flushings from pregnancies across the five conceptus stages. Some metabolites were greater (p  < .05) in abundance for uterine flushings containing earlier stage conceptuses (i.e., spherical), such as uric acid, tryptophan, and tyrosine. In contrast, some metabolites were greater (p < .05) in abundance for uterine flushings containing later stage conceptuses (i.e., tubular), such as creatinine, serine, and urea. These data illustrate several putative metabolites that change within the uterine milieu during early porcine blastocyst elongation. PMID: 31840336 [PubMed - as supplied by publisher]

Related Articles Matrix-assisted laser desorption/ionization mass spectrometry imaging to uncover protein alterations associated with the progression of IgA nephropathy. Virchows Arch. 2019 Dec 14;: Authors: Ivanova M, Dyadyk O, Ivanov D, Clerici F, Smith A, Magni F Abstract IgA nephropathy (IgAN) is one of the most diffuse glomerulonephrites worldwide, and many issues still remain regarding our understanding of its pathogenesis. The disease is diagnosed by renal biopsy examination, but potential pitfalls still persist with regard to discriminating its primary origin and, as a result, determining patient outcome remains challenging. In this pilot study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) was performed on renal biopsies obtained from patients with IgAN (n = 11) and other mesangioproliferative glomerulonephrites (MesPGN, n = 6) in order to enlighten proteomic alterations that may be associated with the progression of IgAN. Differences in the proteomic profiles of IgAN and MesPGN tissue could clearly be detected using this approach and, furthermore, 14 signals (AUC ≥ 0.8) were observed to have an altered intensity among the different CKD stages within the IgAN group. In particular, large increases in the intensity of these signals could be observed at CKD stages II and above. These signals primarily corresponded to proteins involved in either inflammatory and healing pathways and their increased intensity was localized within regions of tissue with large amounts of inflammatory cells or sclerosis. Despite much work in recent years, our molecular understanding of IgAN progression remains incomplete. This pilot study represents a promising starting point in the search for novel protein markers that can assist clinicians in better understanding the pathogenesis of IgAN and highlighting those patients who may progress to end-stage renal disease. PMID: 31838587 [PubMed - as supplied by publisher]

Implications of gut microbiota dysbiosis and metabolic changes in prion disease. Neurobiol Dis. 2019 Dec 11;:104704 Authors: Yang D, Zhao D, Shah SZA, Wu W, Lai M, Zhang X, Li J, Guan Z, Zhao H, Li W, Gao H, Zhou X, Yang L Abstract Evidence of the gut microbiota influencing neurodegenerative diseases has been reported for several neural diseases. However, there is little insight regarding the relationship between the gut microbiota and prion disease. Here, using fecal samples of 12 prion-infected mice and 25 healthy controls, we analyzed the structure of the gut microbiota and metabolic changes by 16S rRNA sequencing and LC-MS-based metabolomics respectively as multi-omic analyses. Additionally, SCFAs and common amino acids were detected by GC-MS and UPLC respectively. Enteric changes induced by prion disease affected both structure and abundances of the gut microbiota. The gut microbiota of infected mice displayed greater numbers of Proteobacteria and less Saccharibacteria at the phylum level and more Lactobacillaceae and Helicobacteraceae and less Prevotellaceae and Ruminococcaceae at the family level. A total of 145 fecal metabolites were found to be significantly different in prion infection, and most (114) of these were lipid metabolites. Using KEGG pathway enrichment analysis, we found that 3 phosphatidylcholine (PC) compounds significantly decreased and 4 hydrophobic bile acids significantly increased. Decreases of 8 types of short-chain acids (SCFAs) and increases of Cys and Tyr and decreases of His, Trp, and Arg were observed in prion infection. Correlation analysis indicated that the gut microbiota changes observed in our study may have been the shared outcome of prion disease. These findings suggest that prion disease can cause significant shifts in the gut microbiota. Certain bacterial taxa can then respond to the resulting change to the enteric environment by causing dramatic shifts in metabolite levels. Our data highlight the health impact of the gut microbiota and related metabolites in prion disease. PMID: 31837420 [PubMed - as supplied by publisher]

Related Articles Gut microbiome and cardiometabolic risk. Rev Endocr Metab Disord. 2019 Dec 14;: Authors: Kappel BA, Federici M Abstract The last decade has been characterized by an intense research on the composition of the gut microbiome and the links with human health. While previous work was focused on the effects of prebiotics and probiotics, nowadays several laboratories are describing the gut microbiome and its metabolic functions. Gut microbiome interaction with nutrients allows the gut microbiome to survive and at the same time determines the production of metabolites that are either adsorbed by intestinal cell in a mutual relationship or promote detrimental effect. Metabolomics, a new method to approach identification of biomarkers has been used to identify small metabolites in blood and other biofluids. The study of metabolome revealed several microbial derived metabolites that are circulating in blood and potentially affect human health. In this review we describe the links between regulation of metabolism and microbial derived metabolites. PMID: 31836950 [PubMed - as supplied by publisher]

Related Articles Metabolomic Profiles of Bovine Mammary Epithelial Cells Stimulated by Lipopolysaccharide. Sci Rep. 2019 Dec 13;9(1):19131 Authors: Huang Y, Shen L, Jiang J, Xu Q, Luo Z, Luo Q, Yu S, Yao X, Ren Z, Hu Y, Yang Y, Cao S Abstract Bovine mammary epithelial cells (bMECs) are the main cells of the dairy cow mammary gland. In addition to their role in milk production, they are effector cells of mammary immunity. However, there is little information about changes in metabolites of bMECs when stimulated by lipopolysaccharide (LPS). This study describes a metabolomics analysis of the LPS-stimulated bMECs to provide a basis for the identification of potential diagnostic screening biomarkers and possible treatments for bovine mammary gland inflammation. In the present study, bMECs were challenged with 500 ng/mL LPS and samples were taken at 0 h, 12 h and 24 h post stimulation. Metabolic changes were investigated using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS) with univariate and multivariate statistical analyses. Clustering and metabolic pathway changes were established by MetaboAnalyst. Sixty-three differential metabolites were identified, including glycerophosphocholine, glycerol-3-phosphate, L-carnitine, L-aspartate, glutathione, prostaglandin G2, α-linolenic acid and linoleic acid. They were mainly involved in eight pathways, including D-glutamine and D-glutamic acid metabolism; linoleic acid metabolism; α-linolenic metabolism; and phospholipid metabolism. The results suggest that bMECs are able to regulate pro-inflammatory, anti-inflammatory, antioxidation and energy-producing related metabolites through lipid, antioxidation and energy metabolism in response to inflammatory stimuli. PMID: 31836784 [PubMed - in process]

Related Articles Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites. Nat Commun. 2019 Dec 13;10(1):5695 Authors: Michonneau D, Latis E, Curis E, Dubouchet L, Ramamoorthy S, Ingram B, de Latour RP, Robin M, de Fontbrune FS, Chevret S, Rogge L, Socié G Abstract Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of genotypically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity. PMID: 31836702 [PubMed - in process]

Related Articles Multi-omic characterisation of the mode of action of a potent new antimalarial compound, JPC-3210, against Plasmodium falciparum. Mol Cell Proteomics. 2019 Dec 13;: Authors: Birrell GW, Challis MP, De Paoli A, Anderson D, Devine SM, Heffernan GD, Jacobus DP, Edstein MD, Siddiqui G, Creek DJ Abstract The increasing incidence of antimalarial drug resistance to the first-line artemisinin combination therapies underpins an urgent need for new antimalarial drugs, ideally with a novel mode of action. The recently developed 2-aminomethylphenol, JPC-3210, (MMV 892646) is an erythrocytic schizonticide with potent in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, low cytotoxicity, potent in vivo efficacy against murine malaria, and favourable preclinical pharmacokinetics including a lengthy plasma elimination half-life. To investigate the impact of JPC-3210 on biochemical pathways within P. falciparum-infected red blood cells, we have applied a "multi-omics" workflow based on high resolution orbitrap mass spectrometry combined with biochemical approaches. Metabolomics, peptidomics and hemoglobin fractionation analyses revealed a perturbation in hemoglobin metabolism following JPC-3210 exposure. The metabolomics data demonstrated a specific depletion of short hemoglobin-derived peptides, peptidomics analysis revealed a depletion of longer hemoglobin-derived peptides, and the hemoglobin fractionation assay demonstrated decreases in hemoglobin, heme and hemozoin levels. In order to further elucidate the mechanism responsible for inhibition of hemoglobin metabolism, we used in vitro β-hematin polymerisation assays and showed JPC-3210 to be an intermediate inhibitor of β-hematin polymerisation, about 10-fold less potent then the quinoline antimalarials, such as chloroquine and mefloquine. Furthermore, quantitative proteomics analysis showed that JPC-3210 treatment results in a distinct proteomic signature in comparison to other known antimalarials. Whilst JPC-3210 clustered closely with mefloquine in the metabolomics and proteomics analyses, a key differentiating signature for JPC-3210 was the significant enrichment of parasite proteins involved in regulation of translation. These studies revealed that the mode of action for JPC-3210 involves inhibition of the hemoglobin digestion pathway and elevation of regulators of protein translation. Importantly, JPC-3210 demonstrated rapid parasite killing kinetics compared to other quinolones, suggesting that JPC-3210 warrants further investigation as a potentially long acting partner drug for malaria treatment. PMID: 31836637 [PubMed - as supplied by publisher]

Related Articles Reactive oxygen species detection-approaches in plants: insights into genetically encoded FRET-based sensors. J Biotechnol. 2019 Dec 10;: Authors: Anjum NA, Amreen, Tantray AY, Khan NA, Ahmad A Abstract The generation of reactive oxygen species (ROS) (and their reaction products) in abiotic stressed plants can be simultaneous. Hence, it is very difficult to establish individual roles of ROS (and their reaction products) in plants particularly under abiotic stress conditions. It is highly imperative to detect ROS (and their reaction products) and ascertain their role in vivo and also to point their optimal level in order to unveil exact relation of ROS (and their reaction products) with the major components of ROS-controlling systems. Förster Resonance Energy Transfer (FRET) technology enables us with high potential for monitoring and quantification of ROS and redox variations, avoiding some of the obstacles presented by small-molecule fluorescent dyes. This paper aims to: (i) introduce ROS and overview ROS-chemistry and ROS-accrued major damages to major biomolecules; (ii) highlight invasive and non-invasive approaches for the detection of ROS (and their reaction products); (iii) appraise literature available on genetically encoded ROS (and their reaction products)-sensors based on FRET technology, and (iv) enlighten so far unexplored aspects in the current context. The studies integrating the outcomes of the FRET-based ROS-detection approaches with the OMICS (genetics, genomics, proteomics, and metabolomics) would enlighten insights into real-time ROS and redox dynamics, and their signaling at cellular and subcellular levels in living cells. PMID: 31836526 [PubMed - as supplied by publisher]

Related Articles Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach. Molecules. 2019 Dec 11;24(24): Authors: Phakeovilay C, Bourgeade-Delmas S, Perio P, Valentin A, Chassagne F, Deharo E, Reybier K, Marti G Abstract With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. The aim of this study was to obtain potential antileishmanial natural products from Psidium guajava leaves using a metabolomic workflow. Several crude extracts from P. guajava leaves harvested from different locations in the Lao People's Democratic Republic (Lao PDR) were profiled by liquid chromatography coupled to high-resolution mass spectrometry, and subsequently evaluated for their antileishmanial activities. The putative active compounds were highlighted by multivariate correlation analysis between the antileishmanial response and chromatographic profiles of P. guajava mixtures. The results showed that the pooled apolar fractions from P. guajava were the most active (IC50 = 1.96 ± 0.47 µg/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC50 = 1.318 ± 0.59 µg/mL) and corosolic acid (IC50 = 1.01 ± 0.06 µg/mL). Our approach allowed the identification of antileishmanial compounds from the crude extracts in only a small number of steps and can be easily adapted for use in the discovery workflows of several other natural products. PMID: 31835791 [PubMed - in process]

Related Articles Multi-Omics Integration Reveals Short and Long-Term Effects of Gestational Hypoxia on the Heart Development. Cells. 2019 Dec 11;8(12): Authors: Gao Y, Dasgupta C, Huang L, Song R, Zhang Z, Zhang L Abstract Antenatal hypoxia caused epigenetic reprogramming of methylome and transcriptome in the developing heart and increased the risk of heart disease later in life. Herein, we investigated the impact of gestational hypoxia in proteome and metabolome in the hearts of fetus and adult offspring. Pregnant rats were treated with normoxia or hypoxia (10.5% O2) from day 15 to 21 of gestation. Hearts were isolated from near-term fetuses and 5 month-old offspring, and proteomics and metabolomics profiling was determined. The data demonstrated that antenatal hypoxia altered proteomics and metabolomics profiling in the heart, impacting energy metabolism, lipid metabolism, oxidative stress, and inflammation-related pathways in a developmental and sex dependent manner. Of importance, integrating multi-omics data of transcriptomics, proteomics, and metabolomics profiling revealed reprogramming of the mitochondrion, especially in two clusters: (a) the cluster associated with "mitochondrial translation"/"aminoacyl t-RNA biosynthesis"/"one-carbon pool of folate"/"DNA methylation"; and (b) the cluster with "mitochondrion"/"TCA cycle and respiratory electron transfer"/"acyl-CoA dehydrogenase"/"oxidative phosphorylation"/"complex I"/"troponin myosin cardiac complex". Our study provides a powerful means of multi-omics data integration and reveals new insights into phenotypic reprogramming of the mitochondrion in the developing heart by fetal hypoxia, contributing to an increase in the heart vulnerability to disease later in life. PMID: 31835778 [PubMed - in process]

Related Articles Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism. Int J Mol Sci. 2019 Dec 11;20(24): Authors: Muxel SM, Mamani-Huanca M, Aoki JI, Zampieri RA, Floeter-Winter LM, López-Gonzálvez Á, Barbas C Abstract BACKGROUND: Leishmaniases are neglected tropical diseases that are caused by Leishmania, being endemic worldwide. L-arginine is an essential amino acid that is required for polyamines production on mammal cells. During Leishmania infection of macrophages, L-arginine is used by host and parasite arginase to produce polyamines, leading to parasite survival; or, by nitric oxide synthase 2 to produce nitric oxide leading to parasite killing. Here, we determined the metabolomic profile of BALB/c macrophages that were infected with L. amazonensis wild type or with L. amazonensis arginase knockout, correlating the regulation of L-arginine metabolism from both host and parasite. METHODS: The metabolites of infected macrophages were analyzed by capillary electrophoresis coupled with mass spectrometry (CE-MS). The metabolic fingerprints analysis provided the dual profile from the host and parasite. RESULTS: We observed increased levels of proline, glutamic acid, glutamine, L-arginine, ornithine, and putrescine in infected-L. amazonensis wild type macrophages, which indicated that this infection induces the polyamine production. Despite this, we observed reduced levels of ornithine, proline, and trypanothione in infected-L. amazonensis arginase knockout macrophages, indicating that this infection reduces the polyamine production. CONCLUSIONS: The metabolome fingerprint indicated that Leishmania infection alters the L-arginine/polyamines/trypanothione metabolism inside the host cell and the parasite arginase impacts on L-arginine metabolism and polyamine production, defining the infection fate. PMID: 31835767 [PubMed - in process]

Related Articles Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases. Metabolites. 2019 Dec 11;9(12): Authors: Imperiale A, Poncet G, Addeo P, Ruhland E, Roche C, Battini S, Cicek AE, Chenard MP, Hervieu V, Goichot B, Bachellier P, Walter T, Namer IJ Abstract To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution. PMID: 31835679 [PubMed]

Related Articles Chemical Profiling and Biological Properties of Extracts from Different Parts of Colchicum Szovitsii Subsp. Szovitsii. Antioxidants (Basel). 2019 Dec 11;8(12): Authors: Rocchetti G, Senizza B, Zengin G, Okur MA, Montesano D, Yildiztugay E, Lobine D, Mahomoodally MF, Lucini L Abstract Like other members of the Colchicum genus, C. szovitsii subsp. szovitsii is also of medicinal importance in Turkish traditional medicine. However, its biological properties have not been fully investigated. Herein, we focused on the evaluation of the in vitro antioxidant and enzyme inhibitory effects of flower, root and leaf extracts, obtained using different extraction methods. In addition, a comprehensive (poly)-phenolic and alkaloid profiling of the different extracts was undertaken. In this regard, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) allowed us to putatively annotate 195 polyphenols and 87 alkaloids. The most abundant polyphenols were flavonoids (83 compounds), whilst colchicine and 2-demethylcolchicine were some of the most widespread alkaloids in each extract analyzed. However, our findings showed that C. szovitsii leaf extracts were a superior source of both total polyphenols and total alkaloids (being, on average 24.00 and 2.50 mg/g, respectively). Overall, methanolic leaf extracts showed the highest (p < 0.05) ferric reducing antioxidant power (FRAP) reducing power (on average 109.52 mgTE/g) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging (on average 90.98 mgTE/g). Interestingly, each C. szovitsii methanolic extract was more active than the water extracts when considering enzymatic inhibition such as against tyrosinase, glucosidase, and acetylcholinesterase (AChE). Strong correlations (p < 0.01) were also observed between polyphenols/alkaloids and the biological activities determined. Multivariate statistics based on supervised orthogonal projections to latent structures discriminant analysis (OPLS-DA) allowed for the detection of those compounds most affected by the different extraction methods. Therefore, this is the first detailed evidence showing that C. szovitsii subsp. szovitsii might provide beneficial effects against oxidative stress and the associated chronic diseases. Nevertheless, the detailed mechanisms of action need to be further investigated. PMID: 31835669 [PubMed]

Related Articles Purine Catabolism Shows a Dampened Circadian Rhythmicity in a High-fat Diet-Induced Mouse Model of Obesity. Molecules. 2019 Dec 10;24(24): Authors: Sun R, Huang J, Yang N, He J, Yu X, Feng S, Xie Y, Wang G, Ye H, Aa J Abstract High-calorie diet, circadian rhythms and metabolic features are intimately linked. However, the mediator(s) between nutritional status, circadian rhythms and metabolism remain largely unknown. This article aims to clarify the key metabolic pathways bridging nutritional status and circadian rhythms based on a combination of metabolomics and molecular biological techniques. A mouse model of high-fat diet-induced obesity was established and serum samples were collected in obese and normal mice at different zeitgeber times. Gas chromatography/mass spectrometry, multivariate/univariate data analyses and metabolic pathway analysis were used to reveal changes in metabolism. Metabolites involved in the metabolism of purines, carbohydrates, fatty acids and amino acids were markedly perturbed in accordance with circadian related variations, among which purine catabolism showed a typical oscillation. What's more, the rhythmicity of purine catabolism dampened in the high-fat diet group. The expressions of clock genes and metabolic enzymes in the liver were measured. The mRNA expression of Xanthine oxidase (Xor) was highly correlated with the rhythmicity of Clock, Rev-erbα and Bmal1, as well as the metabolites involved in purine catabolism. These data showed that a high-fat diet altered the circadian rhythm of metabolic pathways, especially purine catabolism. It had an obvious circadian oscillation and a high-fat diet dampened its circadian rhythmicity. It was suggested that circadian rhythmicity of purine catabolism is related to circadian oscillations of expression of Xor, Uox and corresponding clock genes. PMID: 31835615 [PubMed - in process]

Applications of metabolomics in the research of soybean plant under abiotic stress. Food Chem. 2019 Dec 02;310:125914 Authors: Feng Z, Ding C, Li W, Wang D, Cui D Abstract Qualitative and quantitative metabolomics analysis of all small-molecule metabolites in organisms is an emerging omics technology alongside genomics and proteomics. Plant metabolites are extremely diverse both within species and in terms of their physiological function. Plant metabolomics studies use mainly liquid/gas chromatography-mass spectrometry (LC/GC-MS) and nuclear magnetic resonance (NMR) techniques combined with chemometrics and multivariate statistical analysis to analyze plant metabolites, and metabolomics plays a key role in agricultural and food science research. In this review, we discuss the status of metabolomics in soybean in response to abiotic stresses such as drought, heat, salinity, flooding, chilling and heavy metal stresses and analyze the challenges and opportunities. Furthermore, the notable metabolites detected in response to different stresses are summarized to provide a reference for applications of metabolomics in soybean research. PMID: 31835223 [PubMed - as supplied by publisher]

Stage-specific metabolomic changes in equine oviductal fluid: New insights into the equine fertilization environment. Theriogenology. 2019 Nov 30;143:35-43 Authors: González-Fernández L, Sánchez-Calabuig MJ, Calle-Guisado V, García-Marín LJ, Bragado MJ, Fernández-Hernández P, Gutiérrez-Adán A, Macías-García B Abstract A repeatable protocol for equine in vitro fertilization (IVF) has remained elusive. This is likely, in part, due to suboptimal composition of capacitation or IVF media that are currently in use. Hence, we aimed to analyse the metabolome of equine oviductal fluid (OF) at the pre- (PRE) and immediate post-ovulatory (PST) stages using proton magnetic resonance spectroscopy (1H NMR). Oviductal fluid from eight PRE and six PST mares were used to prepare a total of five samples per group. A total of 18 metabolites were identified. The five metabolites with the highest concentrations in the OF samples were lactate, myoinositol, creatine, alanine and carnitine. Only fumarate and glycine showed significant differences in their concentrations between PRE and PST OF samples, with higher concentrations in the PST samples. In a preliminary study, stallion spermatozoa (n = 3 ejaculates) were incubated with different concentrations of PST OF from one mare (0, 0.0625, 0.125, 0.25, 0.5 or 1%; v:v). After 4 h of sperm incubation, protein tyrosine phosphorylation (PY) by western blotting, sperm motility, and acrosomal status were evaluated. An increase of PY was observed in sperm from two stallions when treated with 0.0625% and 0.125% of OF; however no change in PY was noted in the other stallion. There were no effects of OF on spermatozoa motility or acrosome status. These results provide the first information on the metabolomics of equine OF at different stages of the estrus cycle, and present the possibility that OF may affect PY in stallion spermatozoa. PMID: 31835098 [PubMed - as supplied by publisher]

Cassava Metabolomics and Starch Quality. Curr Protoc Plant Biol. 2019 Dec;4(4):e20102 Authors: Rosado-Souza L, David LC, Drapal M, Fraser PD, Hofmann J, Klemens PAW, Ludewig F, Neuhaus HE, Obata T, Perez-Fons L, Schlereth A, Sonnewald U, Stitt M, Zeeman SC, Zierer W, Fernie AR Abstract Cassava plays an important role as a staple food for more than 800 million people in the world due to its ability to maintain relatively high productivity even in nutrient-depleted soils. Even though cassava has been the focus of several breeding programs and has become a strong focus of research in the last few years, relatively little is currently known about its metabolism and metabolic composition in different tissues. In this article, the absolute content of sugars, organic acids, amino acids, phosphorylated intermediates, minerals, starch, carotenoids, chlorophylls, tocopherols, and total protein as well as starch quality is described based on multiple analytical techniques, with protocols specifically adjusted for material from different cassava tissues. Moreover, quantification of secondary metabolites relative to internal standards is presented using both non-targeted and targeted metabolomics approaches. The protocols have also been adjusted to apply to freeze-dried material in order to allow processing of field harvest samples that typically will require long-distance transport. © 2019 The Authors. Basic Protocol 1: Metabolic profiling by gas chromatography-mass spectrometry (GC-MS) Support Protocol 1: Preparation of freeze-dried cassava material Support Protocol 2: Preparation of standard compound mixtures for absolute quantification of metabolites by GC-MS Support Protocol 3: Preparation of retention-time standard mixture Basic Protocol 2: Determination of organic acids and phosphorylated intermediates by ion chromatography-mass spectrometry (IC-MS) Support Protocol 4: Preparation of standards and recovery experimental procedure Basic Protocol 3: Determination of soluble sugars, starch, and free amino acids Alternate Protocol: Determination of soluble sugars and starch Basic Protocol 4: Determination of anions Basic Protocol 5: Determination of elements Basic Protocol 6: Determination of total protein Basic Protocol 7: Determination of non-targeted and targeted secondary metabolites Basic Protocol 8: Determination of carotenoids, chlorophylls, and tocopherol Basic Protocol 9: Determination of starch quality. PMID: 31834991 [PubMed - in process]

Metabolomics Horizon Scanning for 2020: Three Actionable Challenges. OMICS. 2019 Dec 13;: Authors: Kilk K PMID: 31834853 [PubMed - as supplied by publisher]

Linking 24-h urines to clinical phenotypes: what alternatives does the future bring? Curr Opin Urol. 2019 Dec 12;: Authors: Sui W, Hsi RS Abstract PURPOSE OF REVIEW: The 24-h urine test is recommended as part of the metabolic evaluation for patients with nephrolithiasis to guide preventive interventions. However, this test may be challenging to interpret and has limits in its predictive ability. In this review, we summarize and discuss the most recent research on the opportunities and challenges for utilizing urinary biomarkers for kidney stone prevention. RECENT FINDINGS: Contemporary studies utilizing the 24-h urine test have improved our understanding of how to better administer testing and interpret test results. Beyond the standard panel of 24-h urine parameters, recent applications of proteomics and metabolomics have identified protein and metabolic profiles of stone formers. These profiles can be assayed in future studies as potential biomarkers for risk stratification and prediction. Broad collaborative efforts to create large datasets and biobanks from kidney stone formers will be invaluable for kidney stone research. SUMMARY: Recent advances in our understanding of kidney stone risk have opened opportunities to improve metabolic testing for kidney stone formers. These strategies do not appear to be mutually exclusive of 24-h urine testing but instead complementary in their approach. Finally, large clinical datasets hold promise to be leveraged to identify new avenues for stone prevention. PMID: 31834081 [PubMed - as supplied by publisher]