PubMed

Related Articles Probiotic supplements prevented oxonic acid-induced hyperuricemia and renal damage. PLoS One. 2018;13(8):e0202901 Authors: García-Arroyo FE, Gonzaga G, Muñoz-Jiménez I, Blas-Marron MG, Silverio O, Tapia E, Soto V, Ranganathan N, Ranganathan P, Vyas U, Irvin A, Ir D, Robertson CE, Frank DN, Johnson RJ, Sánchez-Lozada LG Abstract Hyperuricemia is highly prevalent and especially common in subjects with metabolic, cardiovascular and renal diseases. In chronic kidney disease, hyperuricemia is extremely common, and uric acid (UA) excretion relies on gut uricolysis by gut microbiota. Current therapy for lowering serum UA includes drugs that may produce undesired secondary effects. Therefore, this pilot study was designed to evaluate the potential of two probiotic supplements to reduce systemic uric acid concentrations. Secondary objectives were to assess whether the hypouricemic effect related to a therapeutic benefit on the hyperuricemia-induced renal damage and hypertension. Analysis of fecal microbiota was also performed. Groups of 6 rats each were followed for 5 weeks and allocated in the following treatment groups: C = Control; HU-ND = Oxonic acid-induced hyperuricemia (HU) +regular diet; HU-P = HU+placebo; HU-F1 = HU+ probiotics formula 1 and HU-F2 = HU+ probiotics formula 2. We confirmed that oxonic acid-induced hyperuricemia produced hypertension and renal functional and structural changes, along with modest changes in the overall composition of fecal microbiota. Both probiotic-containing diets prevented HU, elevated UA urinary excretion and intrarenal UA accumulation induced by oxonic acid. The hypouricemic effect conferred by probiotic supplementation also prevented the renal changes and hypertension caused by hyperuricemia. However, probiotic treatment did not restore the fecal microbiota. In conclusion, we demonstrated for the first time the ability of probiotics containing uricolytic bacteria to lower serum uric acid in hyperuricemic animals with beneficial consequences on blood pressure and renal disease. As probiotics supplements are innocuous for human health, we recommend clinical studies to test if probiotic supplements could benefit hyperuricemic individuals. PMID: 30142173 [PubMed - in process]

Related Articles The mechanism of the preventive effect of Shen'an capsule on the calcium oxalate crystal-induced early renal injury based on metabolomics. Biomed Chromatogr. 2018 Aug 23;:e4374 Authors: Fan W, Hou J, Zhu W, Zhang S, Shao K, Quan F, Chen W Abstract Kidney stone disease is a worldwide metabolism associated disorder with a high incidence of renal dysfunction. However, the effective methods to prevent crystalline nephropathy are still lacking with the absence of aetiological research. Shen'an (SA) capsules are prepared from Chinese medicinal compounds and are considered a promising treatment for the prevention of crystal-induced renal injury. In this study, twenty-four mice were randomly divided into 4 groups including the saline, oxalate, SA-treated (via preventive administration) and SA only groups. A metabolomics analysis based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to explore the plasma metabolic profiles among the different groups. As results, the amount of crystal deposition and declined kidney function were significantly alleviated by the prevention of SA capsule. A total of 24 metabolites that showed a reversal trend following SA capsule administration were identified as plasma biomarkerss of the preventive effects of SA capsules on crystal-induced renal injury. Most of these metabolites were involved in the metabolisms of lipid metabolism, energy metabolism, glutathione metabolism and vitamin metabolism. In conclusions, SA capsules exert a preventive effect in mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways. PMID: 30141275 [PubMed - as supplied by publisher]

Related Articles The effects of disruption in membrane lipid biosynthetic genes on 1-butanol tolerance of Bacillus subtilis. Appl Microbiol Biotechnol. 2018 Aug 23;: Authors: Vinayavekhin N, Vangnai AS Abstract Microbes with enhanced 1-butanol tolerance have the potentials to be utilized in various biotechnological processes. To achieve the rational design of such strains, we previously conducted an untargeted metabolomics analysis of Bacillus subtilis under 1-butanol stress and uncovered a novel type of microbial responses as the alterations in the glycerolipid and phospholipid composition. However, the current knowledge about the relevance of these changes on 1-butanol tolerance remains quite limited. Here, we constructed the B. subtilis mutants with disruption in the pssA, ugtP (U), mprF (M), yfnI, and yfnI/mprF genes in the membrane lipid biosynthetic pathways. The 1-butanol tolerance test indicated markedly increased and decreased 1-butanol resistance in M and U compared to the wild-type strain, respectively, and slight effects in other strains under high stress level. Further examination of the lipid contents of these strains in the presence of 1-butanol by liquid chromatography-mass spectrometry demonstrated an elevated ratio of neutral and anionic to cationic lipids in direct relation with an improved 1-butanol tolerance. Last, cell morphological studies showed the shortening of only the U cells, compared to the wild-type. All strains including U were capable of elongating by 14-24% under 1-butanol stress. Together, the studies indicated the involvement of membrane lipid biosynthetic genes, which regulated glycerolipid and phospholipid composition, on 1-butanol tolerance and allowed for the procurement of M with enhanced 1-butanol tolerance trait, highlighting the usefulness of the overall approaches on discovery of novel biological insights and engineering of microorganisms with desired resistance characteristics. PMID: 30141082 [PubMed - as supplied by publisher]

Related Articles LAESI mass spectrometry imaging as a tool to differentiate the root metabolome of native and range-expanding plant species. Planta. 2018 Aug 23;: Authors: Kulkarni P, Wilschut RA, Verhoeven KJF, van der Putten WH, Garbeva P Abstract MAIN CONCLUSION: LAESI-MSI, an innovative high-throughput technique holds a unique potential for untargeted detection, profiling and spatial localization of metabolites from intact plant samples without need for extraction or extensive sample preparation. Our understanding of chemical diversity in biological samples has greatly improved through recent advances in mass spectrometry (MS). MS-based-imaging (MSI) techniques have further enhanced this by providing spatial information on the distribution of metabolites and their relative abundance. This study aims to employ laser-ablation electrospray ionization (LAESI) MSI as a tool to profile and compare the root metabolome of two pairs of native and range-expanding plant species. It has been proposed that successful range-expanding plant species, like introduced exotic invaders, have a novel, or a more diverse secondary chemistry. Although some tests have been made using aboveground plant materials, tests using root materials are rare. We tested the hypothesis that range-expanding plants possess more diverse root chemistries than native plant species. To examine the root chemistry of the selected plant species, LAESI-MSI was performed in positive ion mode and data were acquired in a mass range of m/z 50-1200 with a spatial resolution of 100 µm. The acquired data were analyzed using in-house scripts, and differences in the spatial profiles were studied for discriminatory mass features. The results revealed clear differences in the metabolite profiles amongst and within both pairs of congeneric plant species, in the form of distinct metabolic fingerprints. The use of ambient conditions and the fact that no sample preparation was required, established LAESI-MSI as an ideal technique for untargeted metabolomics and for direct correlation of the acquired data to the underlying metabolomic complexity present in intact plant samples. PMID: 30140978 [PubMed - as supplied by publisher]

Related Articles Metabolomics-Based Clinical Efficacy and Effect on the Endogenous Metabolites of Tangzhiqing Tablet, a Chinese Patent Medicine for Type 2 Diabetes Mellitus with Hypertriglyceridemia. Evid Based Complement Alternat Med. 2018;2018:5490491 Authors: Liu J, Li Z, Liu H, Wang X, Lv C, Wang R, Zhang D, Li Y, Du X, Li Y, Wang B, Huang Y Abstract Tangzhiqing tablet (TZQ) is derived from Tangzhiqing formula, which has been used to regulate glucose and lipid metabolism in China for hundreds of years. However, as a new Chinese patent medicine, its clinical indication is not clear. To explore the clinical indication and effect on the patients with type 2 diabetes mellitus (T2DM), a pilot clinical trial and metabolomics study were carried out. In the clinical study, T2DM patients were divided into three groups and treated with TZQ, placebo, or acarbose for 12 weeks, respectively. The metabolomic study based on UPLC Q-TOF MS was performed including patients with hypertriglyceridemia in TZQ and placebo groups and healthy volunteers. The clinical results showed that TZQ could reduce glycosylated hemoglobin (HbA1c) and fasting insulin. For patients with hypertriglyceridemia in TZQ group, the levels of HbA1c all decreased and were correlated with the baseline level of triglyceride. Metabonomics data showed a significant difference between patients and healthy volunteers, and 17 biomarkers were identified. After 12-week treatment with TZQ, 11 biomarkers decreased significantly (p<0.05), suggesting that TZQ could improve the metabolomic abnormalities in these participants. In conclusion, the clinical indication of TZQ was T2DM with hypertriglyceridemia, and its target was related to glycerophospholipid metabolism. PMID: 30140295 [PubMed]

Related Articles Metabolome analysis of multi-connected biparental chromosome segment substitution line populations. Plant Physiol. 2018 Aug 23;: Authors: Chen J, Wang J, Chen W, Sun W, Peng M, Yuan Z, Shen S, Xie K, Jin C, Sun Y, Liu X, Fernie AR, Yu S, Luo J Abstract Metabolomic analysis coupled with advanced genetic populations represents a powerful tool to investigate the plant metabolome. However, genetic analyses of the rice (Oryza sativa) metabolome have been conducted mainly using natural accessions or a single biparental population. Here, the flag leaves from three inter-connected chromosome segment substitution line (CSSL) populations with a common recurrent genetic background were used to dissect rice metabolic diversity. We effectively used multiple inter-connected biparental populations, constructed by introducing genomic segments into Zhenshan 97 from ACC10 (A/Z), Minghui 63 (M/Z), and Nipponbare (N/Z), to map metabolic quantitative trait loci (mQTL). A total of 1,587 mQTL were generated, of which 684, 479, and 722 were obtained from the A/Z, M/Z, and N/Z CSSL populations, respectively, and we designated 99 candidate genes for 367 mQTL. In addition, 1,001 mQTL were specifically generated from joint linkage analysis with 25 candidate genes assigned. Several of these candidates were validated, such as LOC_Os07g01020 for the in vivo content of pyridoxine and its derivative, and LOC_Os04g25980 for cis-zeatin glucosyltransferase activity. We propose a novel biosynthetic pathway for O-methylapigenin C-pentoside, and demonstrated that LOC_Os04g11970 encodes a component of this pathway through fine mapping. We postulate that the methylated apigenin may confer plant disease resistance. This study demonstrates the power of using multiple inter-connected populations to generate a large number of veritable mQTL. The combined results are discussed in the context of functional metabolomics and possible features of assigned candidates underlying respective metabolites. PMID: 30139795 [PubMed - as supplied by publisher]

Related Articles Mutations of the glycine cleavage system genes possibly affect the negative symptoms of schizophrenia through metabolomic profile changes. Psychiatry Clin Neurosci. 2018 Mar;72(3):168-179 Authors: Yoshikawa A, Nishimura F, Inai A, Eriguchi Y, Nishioka M, Takaya A, Tochigi M, Kawamura Y, Umekage T, Kato K, Sasaki T, Ohashi Y, Iwamoto K, Kasai K, Kakiuchi C Abstract AIM: Hypofunction of N-methyl-D-aspartate receptors (NMDAR) may contribute to the pathophysiology of schizophrenia (SCZ). Recently, the glycine cleavage system (GCS) was shown to affect NMDAR function in the brain. GCS functional defects cause nonketotic hyperglycinemia, the atypical phenotype of which presents psychiatric symptoms similar to SCZ. Here, we examined the involvement of GCS in SCZ. METHODS: First, to identify the rare variants and the exonic deletions, we resequenced all the coding exons and the splice sites of four GCS genes (GLDC, AMT, GCSH, and DLD) in 474 patients with SCZ and 475 controls and performed multiplex ligation-dependent probe amplification analysis in SCZ. Next, we performed metabolome analysis using plasma of patients harboring GCS variants (n = 5) and controls (n = 5) by capillary electrophoresis time-of-flight mass spectrometry. The correlation between plasma metabolites and Positive and Negative Syndrome Scale score was further examined. RESULTS: Possibly damaging variants were observed in SCZ: A203V, S801N in GLDC, near the atypical nonketotic hyperglycinemia causative mutations (A202V, A802V); G825D in GLDC, a potential neural tube defect causative mutation; and R253X in AMT. Marked elevation of plasma 5-oxoproline (pyroglutamic acid), aspartate, and glutamate, which might affect NMDAR function, was observed in patients harboring GCS variants. The aspartate level inversely correlated with negative symptoms (r = -0.942, P = 0.0166). CONCLUSION: These results suggest that GCS rare variants possibly contribute to the pathophysiology of SCZ by affecting the negative symptoms through elevation of aspartate. PMID: 29232014 [PubMed - indexed for MEDLINE]

Related Articles Automated High-Throughput Permethylation for Glycosylation Analysis of Biologics Using MALDI-TOF-MS. Anal Chem. 2016 09 06;88(17):8562-9 Authors: Shubhakar A, Kozak RP, Reiding KR, Royle L, Spencer DI, Fernandes DL, Wuhrer M Abstract Monitoring glycoprotein therapeutics for changes in glycosylation throughout the drug's life cycle is vital, as glycans significantly modulate the stability, biological activity, serum half-life, safety, and immunogenicity. Biopharma companies are increasingly adopting Quality by Design (QbD) frameworks for measuring, optimizing, and controlling drug glycosylation. Permethylation of glycans prior to analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is a valuable tool for glycan characterization and for screening of large numbers of samples in QbD drug realization. However, the existing protocols for manual permethylation and liquid-liquid extraction (LLE) steps are labor intensive and are thus not practical for high-throughput (HT) studies. Here we present a glycan permethylation protocol, based on 96-well microplates, that has been developed into a kit suitable for HT work. The workflow is largely automated using a liquid handling robot and includes N-glycan release, enrichment of N-glycans, permethylation, and LLE. The kit has been validated according to industry analytical performance guidelines and applied to characterize biopharmaceutical samples, including IgG4 monoclonal antibodies (mAbs) and recombinant human erythropoietin (rhEPO). The HT permethylation enabled glycan characterization and relative quantitation with minimal side reactions: the MALDI-TOF-MS profiles obtained were in good agreement with hydrophilic liquid interaction chromatography (HILIC) and ultrahigh performance liquid chromatography (UHPLC) data. Automated permethylation and extraction of 96 glycan samples was achieved in less than 5 h and automated data acquisition on MALDI-TOF-MS took on average less than 1 min per sample. This automated and HT glycan preparation and permethylation showed to be convenient, fast, and reliable and can be applied for drug glycan profiling and clinical glycan biomarker studies. PMID: 27479043 [PubMed - indexed for MEDLINE]

Related Articles Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies. Anal Chem. 2016 06 07;88(11):5742-51 Authors: Gray N, Adesina-Georgiadis K, Chekmeneva E, Plumb RS, Wilson ID, Nicholson JK Abstract A rapid gradient microbore ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) method has been developed to provide a high-throughput analytical platform for the metabolic phenotyping of urine from large sample cohorts. The rapid microbore metabolic profiling (RAMMP) approach was based on scaling a conventional reversed-phase UPLC-MS method for urinary profiling from 2.1 mm × 100 mm columns to 1 mm × 50 mm columns, increasing the linear velocity of the solvent, and decreasing the gradient time to provide an analysis time of 2.5 min/sample. Comparison showed that conventional UPLC-MS and rapid gradient approaches provided peak capacities of 150 and 50, respectively, with the conventional method detecting approximately 19 000 features compared to the ∼6 000 found using the rapid gradient method. Similar levels of repeatability were seen for both methods. Despite the reduced peak capacity and the reduction in ions detected, the RAMMP method was able to achieve similar levels of group discrimination as conventional UPLC-MS when applied to rat urine samples obtained from investigative studies on the effects of acute 2-bromophenol and chronic acetaminophen administration. When compared to a direct infusion MS method of similar analysis time the RAMMP method provided superior selectivity. The RAMMP approach provides a robust and sensitive method that is well suited to high-throughput metabonomic analysis of complex mixtures such as urine combined with a 5-fold reduction in analysis time compared with the conventional UPLC-MS method. PMID: 27116471 [PubMed - indexed for MEDLINE]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/24PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Early mechanical leaf removal in Merlot (Vitis vinifera L.) enhances fruit technological maturity and alters the flavonoid metabolomic profile. J Agric Food Chem. 2018 Aug 21;: Authors: VanderWeide J, Medina-Meza IG, Frioni T, Sivilotti P, Falchi R, Sabbatini P Abstract Removal of basal leaves near bloom inevitably affects grapevine balance and cluster microclimate conditions, improving fruit quality. Mechanization of this practice allows growers to save time and resources, but, to our knowledge, has not yet been compared with manual application in a cool climate region where seasonal temperature accumulation frequently limits fruit technological maturity and phenolic ripening in red Vitis vinifera cultivars. In our research, berry sugar concentration was highest in the pre-bloom mechanical treatment (PB-ME). Furthermore, metabolomics analysis revealed that PB-ME favored the accumulation of significantly more di-substituted anthocyanins and flavonols and OH-substituted anthocyanins compared to the manual application. Given that vine balance was similar between treatments, increased ripening in PB-ME is likely due to enhanced microclimate conditions, and higher carbon partitioning through a younger canopy containing basal leaf fragments proximal to fruit. This information provides an important strategy to consistently ripen red Vitis vinifera cultivars in cool climates. PMID: 30130400 [PubMed - as supplied by publisher]

HR-MAS NMR-based metabolomics reveals metabolic changes in lung of mice infected with P. aeruginosa consistent with the degree of disease severity, and is a powerful evaluation tool for new treatment. J Proteome Res. 2018 Aug 21;: Authors: Le Gouellec A, Moyne O, Meynet E, Toussaint B, Fauvelle F Abstract Pseudomonas aeruginosa is a critical pathogen for human health, due to increased resistances to antibiotics and to nosocomial infections. There is an urgent need for tools allowing to better understand mechanisms underlying the disease processes and to evaluate new therapeutic strategies with animal models. Here, we used a novel approach, applying high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HRMAS NMR) directly to lung biopsies of mice to better understand the impact of infection on the tissue at a molecular level. Mice were infected with two P. aeruginosa strains of different virulence levels. Statistical analysis applied to HRMAS NMR data allowed us to build a multivariate discriminant model to distinguish the lungs' metabolic profiles of mice infected or not. Moreover, a second model was built to appreciate the degree of severity of infection, demonstrating sufficient sensitivity of HRMAS NMR based metabolomics to investigate this type of infection. The metabolic features that discriminate infection statuses are dominated by some key differentially expressed metabolites which are related respectively to bacterial carbon metabolism (glycerophosphocholine) and to septic hypoxic stress response of host (succinate). Finally, in order to get closer to clinical and diagnosis issues, we proposed to build simple logistic regression models to predict the infection status on the basis of only one metabolite intensity. Thus, we have demonstrated that Succinate intensity could discriminate the infected/non-infected status infection with a sensibility of 89% and a specificity of 95%, and leucine/isoleucine intensity could predict the severe/not severe status of infection with a sensibility of 100% and a specificity of 95%. We also looked for the interest of this model in order to predict the efficacy of anti-P. aeruginosa treatment. By HRMAS metabolomics analysis of lungs infected with P. aeruginosa after vaccination, we demonstrated that this model could be an useful tool to predict the efficacy of new anti-P. aeruginosa drugs. This metabolomics approach could therefore be useful both for the definition of biomarkers of severity of infection and for an earlier characterization of therapeutic efficacy. PMID: 30129763 [PubMed - as supplied by publisher]

Related Articles Trends in herbgenomics. Sci China Life Sci. 2018 Aug 14;: Authors: Xin T, Zhang Y, Pu X, Gao R, Xu Z, Song J Abstract From Shen Nong's Herbal Classic (Shennong Bencao Jing) to the Compendium of Materia Medica (Bencao Gangmu) and the first scientific Nobel Prize for the mainland of China, each milestone in the historical process of the development of traditional Chinese medicine (TCM) involves screening, testing and integrating. After thousands of years of inheritance and development, herbgenomics (bencaogenomics) has bridged the gap between TCM and international advanced omics studies, promoting the application of frontier technologies in TCM. It is a discipline that uncovers the genetic information and regulatory networks of herbs to clarify their molecular mechanism in the prevention and treatment of human diseases. The main theoretical system includes genomics, functional genomics, proteomics, transcriptomics, metabolomics, epigenomics, metagenomics, synthetic biology, pharmacogenomics of TCM, and bioinformatics, among other fields. Herbgenomics is mainly applicable to the study of medicinal model plants, genomic-assisted breeding, herbal synthetic biology, protection and utilization of gene resources, TCM quality evaluation and control, and TCM drug development. Such studies will accelerate the application of cutting-edge technologies, revitalize herbal research, and strongly promote the development and modernization of TCM. PMID: 30128965 [PubMed - as supplied by publisher]

Related Articles Metabolomics analysis of Pseudomonas chlororaphis JK12 algicidal activity under aerobic and micro-aerobic culture condition. AMB Express. 2018 Aug 20;8(1):131 Authors: Kim J, Lyu XM, Lee JJL, Zhao G, Chin SF, Yang L, Chen WN Abstract Utilization of algicidal bacteria as a biological agent have been receiving significant interest for controlling harmful algal blooms. While various algicidal bacterial strains have been identified, limited studies have explored the influence of bacterial culture conditions on its algicidal activity. Here, the effect of oxygen on the algicidal activity of a novel bacterium JK12, against a model diatom, Phaeodactylum tricornutum (P. tricornutum) was studied. Strain JK12 showed high algicidal activity against P. tricornutum and was identified as Pseudomonas chlororaphis (P. chlororaphis) by 16S ribosomal RNA gene analysis. JK12 culture supernatant exhibited strong algicidal activity while washed JK12 cells showed no obvious activity, indicating that JK12 indirectly attacks algae by secreting extracellular algicidal metabolites. Micro-aerobic culture condition dramatically enhanced the algicidal activity of JK12 by 50%, compared to that cultured under aerobic condition in 24 h. Extracellular metabolomic profiling of JK12 using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analysis revealed significantly higher amounts of allantoic acid, urocanic acid, cytidine 2',3'-cyclic phosphate, uridine 2',3'-cyclic phosphate, and chlorinated tryptophan in the micro-aerobic culture. This is the first report to demonstrate the important role of oxygen on the algicidal activity of a non-pathogenic strain P. chlororaphis. In addition, the metabolomics analysis provided insights into the algicidal mechanism of P. chlororaphis. PMID: 30128639 [PubMed]

Related Articles De novo NAD+ biosynthetic impairment in acute kidney injury in humans. Nat Med. 2018 Aug 20;: Authors: Poyan Mehr A, Tran MT, Ralto KM, Leaf DE, Washco V, Messmer J, Lerner A, Kher A, Kim SH, Khoury CC, Herzig SJ, Trovato ME, Simon-Tillaux N, Lynch MR, Thadhani RI, Clish CB, Khabbaz KR, Rhee EP, Waikar SS, Berg AH, Parikh SM Abstract Nicotinamide adenine dinucleotide (NAD+) extends longevity in experimental organisms, raising interest in its impact on human health. De novo NAD+ biosynthesis from tryptophan is evolutionarily conserved yet considered supplanted among higher species by biosynthesis from nicotinamide (NAM). Here we show that a bottleneck enzyme in de novo biosynthesis, quinolinate phosphoribosyltransferase (QPRT), defends renal NAD+ and mediates resistance to acute kidney injury (AKI). Following murine AKI, renal NAD+ fell, quinolinate rose, and QPRT declined. QPRT+/- mice exhibited higher quinolinate, lower NAD+, and higher AKI susceptibility. Metabolomics suggested an elevated urinary quinolinate/tryptophan ratio (uQ/T) as an indicator of reduced QPRT. Elevated uQ/T predicted AKI and other adverse outcomes in critically ill patients. A phase 1 placebo-controlled study of oral NAM demonstrated a dose-related increase in circulating NAD+ metabolites. NAM was well tolerated and was associated with less AKI. Therefore, impaired NAD+ biosynthesis may be a feature of high-risk hospitalizations for which NAD+ augmentation could be beneficial. PMID: 30127395 [PubMed - as supplied by publisher]

Related Articles Metabolic profiles of cysteine, methionine, glutamate, glutamine, arginine, aspartate, asparagine, alanine and glutathione in Streptococcus thermophilus during pH-controlled batch fermentations. Sci Rep. 2018 Aug 20;8(1):12441 Authors: Qiao Y, Liu G, Leng C, Zhang Y, Lv X, Chen H, Sun J, Feng Z Abstract Elucidating the amino acid (AA) metabolism patterns of Streptococcus thermophilus has important effects on the precise design of nitrogen sources for high-cell-density culture. Transcriptomics and metabolomics were combined to reveal the cysteine, methionine, glutamate, glutamine, arginine, aspartate, asparagine and alanine metabolic pathways in S. thermophilus MN-ZLW-002, including glutathione. The changes in the synthesis, consumption and concentration of AAs and their metabolites, as well as regulatory genes with time were revealed. The metabolism of L-cysteine, L-glutamate, L-aspartate and L-alanine generated some potential functional metabolites. The metabolism of methionine and glutamate generated potential harmful metabolites. S. thermophilus MN-ZLW-002 can synthesize glutathione. Some potential functional metabolites have similar biological functions, indicating that S. thermophilus can resist environmental stresses through multiple mechanisms. The expression of some key genes in synthesis pathway of AA indicated that cysteine, methionine, asparagine, aspartate, arginine and lysine were insufficient or imbalance between nutrient components. The accumulation of large amounts of AA metabolites might be the primary cause of the overconsumption of AAs and influence the growth of S. thermophilus. The present study revealed the metabolic profiles of abovementioned AAs as well as those of regulatory genes and metabolites. These results were beneficial to the precise design of nitrogen sources and regulation of functional metabolites for the high-cell-density culture of S. thermophilus. PMID: 30127376 [PubMed - in process]

Related Articles One Way to Achieve Germination: Common Molecular Mechanism Induced by Ethylene and After-Ripening in Sunflower Seeds. Int J Mol Sci. 2018 Aug 20;19(8): Authors: Xia Q, Saux M, Ponnaiah M, Gilard F, Perreau F, Huguet S, Balzergue S, Langlade N, Bailly C, Meimoun P, Corbineau F, El-Maarouf-Bouteau H Abstract Dormancy is an adaptive trait that blocks seed germination until the environmental conditions become favorable for subsequent vegetative plant growth. Seed dormancy is defined as the inability to germinate in favorable conditions. Dormancy is alleviated during after-ripening, a dry storage period, during which dormant (D) seeds unable to germinate become non-dormant (ND), able to germinate in a wide range of environmental conditions. The treatment of dormant seeds with ethylene (D/ET) promotes seed germination, and abscisic acid (ABA) treatment reduces non-dormant (ND/ABA) seed germination in sunflowers (Helianthus annuus). Metabolomic and transcriptomic studies have been performed during imbibition to compare germinating seeds (ND and D/ET) and low-germinating seeds (D and ND/ABA). A PCA analysis of the metabolites content showed that imbibition did not trigger a significant change during the first hours (3 and 15 h). The metabolic changes associated with germination capacity occurred at 24 h and were related to hexoses, as their content was higher in ND and D/ET and was reduced by ABA treatment. At the transcriptional level, a large number of genes were altered oppositely in germinating, compared to the low-germinating seeds. The metabolomic and transcriptomic results were integrated in the interpretation of the processes involved in germination. Our results show that ethylene treatment triggers molecular changes comparable to that of after-ripening treatment, concerning sugar metabolism and ABA signaling inhibition. PMID: 30127315 [PubMed - in process]

Related Articles A Comparative Metabolomics Analysis Reveals the Tissue-Specific Phenolic Profiling in Two Acanthopanax Species. Molecules. 2018 Aug 20;23(8): Authors: Wu KX, Liu J, Liu Y, Guo XR, Mu LQ, Hu XH, Tang ZH Abstract Acanthopanax senticosus (Rupr. Maxim.) Harms (ASH) and Acanthopanax sessiliflorus (Rupr. Maxim.) Seem (ASS), are members of the Araliaceae family, and both are used in Asian countries. These herbals have drawn much attention in recent years due to their strong biological activity, with innocuity and little side effects. However, the common and distinct mode of compound profiles between ASH and ASS is still unclear. In this study, a high performance liquid chromatograph-mass spectrometry (HPLC-MS) method was developed to simultaneously quantify the seven major active compounds, including protocatechuate, eleutheroside B, eleutheroside E, isofraxidin, hyperoside, kaempferol and oleanolic acid. Then the targeted metabolomics were conducted to identify 19 phenolic compounds, with tight relation to the above mentioned active compounds, including nine C6C3C6-type, six C6C3-type and four C6C1-type in the two Acanthopanax species studied here. The results showed that the seven active compounds presented a similar trend of changes in different tissues, with more abundant accumulation in roots and stems for both plants. From the view of plant species, the ASH plants possess higher abundance of compounds, especially in the tissues of roots and stems. For phenolics, the 19 phenols detected here could be clearly grouped into five main clusters based on their tissue-specific accumulation patterns. Roots are the tissue for the most abundance of their accumulations. C6C3C6-type compounds are the most widely existing type in both plants. In conclusion, the tissue- and species-specificity in accumulation of seven active compounds and phenolics were revealed in two Acanthopanax species. PMID: 30127238 [PubMed - in process]