PubMed

38 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 2019/01/29PubMed 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.

Impaired Pentose Phosphate Pathway in the Spinal Cord of the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis. Mol Neurobiol. 2019 Jan 26;: Authors: Tefera TW, Bartlett K, Tran SS, Hodson MP, Borges K Abstract Impairments in energy metabolism in amyotrophic lateral sclerosis (ALS) have long been known. However, the changes in the energy-producing pathways in ALS are not comprehensively understood. To investigate specific alterations in glucose metabolism in glycolytic, pentose phosphate, and TCA cycle pathways, we injected uniformly labeled [U-13C]glucose to wild-type and hSOD1G93A mice at symptom onset (80 days). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), levels of metabolites were determined in extracts of the cortex and spinal cord. In addition, the activities of several enzymes involved in glucose metabolism were quantified. In the spinal cord, the levels of pentose phosphate pathway (PPP) intermediate ribose 5-phosphate (p = 0.037) were reduced by 37% in hSOD1G93A mice, while the % 13C enrichments in glucose 6-phosphate were increased threefold. The maximal activities of the enzyme glucose 6-phosphate dehydrogenase were decreased by 24% in the spinal cord (p = 0.005), suggesting perturbations in the PPP. The total amount of pyruvate in the cortex (p = 0.039) was reduced by 20% in hSOD1G93A mice. Also, the activities of the glycolytic enzyme pyruvate kinase were reduced in the cortex by 31% (p = 0.002), indicating alterations in glycolysis. No significant differences were seen in the total amounts as well as % 13C enrichments in most TCA cycle intermediates, suggesting largely normal TCA cycle function. On the other hand, oxoglutarate dehydrogenase activity was decreased in the cortex, which may indicate increased oxidative stress. Overall, this study revealed decreased activity of the PPP in the spinal cord and alterations in glycolysis in hSOD1G93A mouse CNS tissues at the early symptomatic stage of disease. PMID: 30685842 [PubMed - as supplied by publisher]

Precision Diabetes is Slowly Becoming a Reality. Med Princ Pract. 2019 Jan 27;: Authors: Mohan V, Radha V Abstract The concept of precision medicine is becoming increasingly popular. The use of big data, genomics and other 'omics' like metabolomics, proteomics and trancriptomics could make the dream of personalized medicine become a reality in the near future. As far as polygenic forms of diabetes like type 2 diabetes (T2DM) and type 1 diabetes (T1DM) are concerned, interesting leads are emerging, but precision diabetes is still in its infancy. However, with regard to monogenic forms of diabetes like Maturity-Onset-diabetes of the young (MODY) and Neonatal Diabetes Mellitus (NDM), rapid strides have been made and precision diabetes has already become part of the clinical tools used at advanced diabetes centres. In patients with some monogenic forms of diabetes, if the appropriate gene defects are identified, insulin injections can be stopped and they can be replaced with oral sulphonylurea (SU) drugs. In the coming years, rapid strides can be expected to be made in the field of precision diabetes, thereby making the control of diabetes more effective and hopefully leading to prevention of its complications and improvement of the quality of life of people afflicted with diabetes. PMID: 30685765 [PubMed - as supplied by publisher]

Exploration of microbiota targets for major depressive disorder and mood related traits. J Psychiatr Res. 2019 Jan 19;111:74-82 Authors: Chung YE, Chen HC, Chou HL, Chen IM, Lee MS, Chuang LC, Liu YW, Lu ML, Chen CH, Wu CH, Huang MC, Liao SC, Ni YH, Lai MS, Shih WL, Kuo PH Abstract Growing evidence suggests the link between gut microbiota and mood regulation. The current study aimed to identify microbiota targets for major depressive disorder (MDD) and mood-related traits in Taiwanese samples, while taking into account the influence of dietary patterns. We recruited 36 MDD patients and 37 healthy controls for 16S rRNA gene sequencing. We assessed nutrient content using food frequency questionnaire, and mood related phenotypes, including depressive severity, anxiety, and perceived stress. Analysis of composition of microbiomes (ANCOM) models were performed to evaluate microbiota compositions between patients and controls, while adjusted for fat intake% and sequencing platforms. We found 23 taxa (4 phyla, 7 families and 12 genera) to be associated with depression and beta diversity was differed between groups. Phylum Actinobacteria and Firmicutes were overrepresented in MDD patients. At genus level, Bifidobacterium (7%) and Blautia (8%) had relatively high abundance among MDD patients, while Prevotella (16%) had high abundance in controls. Holdemania exhibited moderate correlation with anxiety (r = 0.65) and perceived stress level (r = 0.49) mainly in MDD patients but not controls. Pathway analyses revealed that pentose phosphate and starch and sucrose metabolism processes were important pathways for depression via microbiota functions. In conclusion, our results revealed microbiota targets for depression that are independent of fat intake. It is worthwhile to conduct further studies to replicate the current findings and to integrate with biochemistry and metabolomics data to better understand the functions of identified targets. PMID: 30685565 [PubMed - as supplied by publisher]

A volatilomics approach for off-line discrimination of minced beef and pork meat and their admixture using HS-SPME GC/MS in tandem with multivariate data analysis. Meat Sci. 2019 Jan 21;151:43-53 Authors: Pavlidis DE, Mallouchos A, Ercolini D, Panagou EZ, Nychas GE Abstract Beef, pork and mixed (70% beef and 30% pork) minced meat samples were obtained from a meat processing plant in Athens during a two-year survey and analyzed both microbiologically and by headspace solid-phase microextraction in combination with gas chromatography-mass spectrometry (HS-SPME/GC-MS). A validated method for the discrimination of minced meat was developed based on the volatile fingerprints. Unsupervised (PCA) and supervised (PLS-DA) multivariate statistical methods were applied to visualize, group and classify the samples. The data-set was divided 70% for model calibration and 30% for model prediction. During model calibration 99, 100 and 100% of the samples were correctly classified as beef, pork and mixed meat samples, respectively, while for model prediction the respective percentages were 100, 100 and 95% respectively. In both datasets, the overall correct classification rate amounted to 99% on average. Among the volatile compounds identified, heptanal, octanal, butanol, pentanol, hexanol, octanol, 1-penten-3-ol, 2-octen-1-ol, 3-hydroxy-2-butanone, 2-butanone and 2-heptanone were positively correlated with beef samples. Furthermore, pentanal, hexanal, decanal, nonanal, benzaldehyde, trans-2-hexenal, trans-2-heptenal, trans-2-octenal and 1-octen-3-one were positively correlated with pork. Lastly, the alcohols, 2-butanol and 1-octen-3-ol showed positive correlation with mixed samples. The results indicated that the volatilomics approach employed in this study could be used as an alternative method for robust and reliable discrimination and classification of meat samples in an off-line mode. PMID: 30685510 [PubMed - as supplied by publisher]

A scoring approach for multi-platform acquisition in metabolomics. J Chromatogr A. 2019 Jan 10;: Authors: Pezzatti J, González-Ruiz V, Codesido S, Gagnebin Y, Joshi A, Guillarme D, Schappler J, Picard D, Boccard J, Rudaz S Abstract Since the ultimate goal of untargeted metabolomics is the analysis of the broadest possible range of metabolites, some new metrics have to be used by researchers to evaluate and select different analytical strategies when multi-platform analyses are considered. In this context, we aimed at developing a scoring approach allowing to compare the performance of different LC-MS conditions for metabolomics studies. By taking into account both chromatographic and MS attributes of the analytes' peaks (i.e. retention, signal-to-noise ratio, peak intensity and shape), the newly proposed score reflects the potential of a set of LC-MS operating conditions to provide useful analytical information for a given compound. A chemical library containing 597 metabolites was used as a benchmark to apply this approach on two RPLC and three HILIC methods hyphenated to high resolution mass spectrometry (HRMS) in positive and negative ionization modes. The scores not only allowed to evaluate each analytical platform, but also to optimize the number of analytical methods needed for the analysis of metabolomics samples. As a result, the most informative combination of three LC methods and ionization modes was found, leading to a coverage of nearly 95% of the detected compounds. It was therefore demonstrated that the overall performance reached with three selected methods was almost equivalent to the performance reached when five LC-MS conditions were used. PMID: 30685186 [PubMed - as supplied by publisher]

Profiling and comparison of toxicant metabolites in hair and urine using a mass spectrometry-based metabolomic data processing method. Anal Chim Acta. 2019 Apr 04;1052:84-95 Authors: Shih CL, Wu HY, Liao PM, Hsu JY, Tsao CY, Zgoda VG, Liao PC Abstract Urine and hair are used for assessing human exposure to toxicants. Urine tests can show acute toxicant exposure. Hair analysis can be used to determine chronic toxicant exposure after months to years; however, compared to urine, hair analysis in exposure assessments is much less frequently investigated. Urine and hair are different matrices, and their mechanisms of toxicant metabolite incorporation are different. The toxicant metabolites present in urine and hair may also be different. To clarify this issue, a procedure was developed to identify toxicant metabolites in rat samples using a mass spectrometry-based metabolomic data processing method. Di-(2-propylheptyl) phthalate (DPHP), an industrial plasticizer, was used as the model toxicant. The developed procedure identified not only known DPHP metabolites (mono-(propyl-6-oxo-heptyl) phthalate, mono-(propyl-6-hydroxyheptyl) phthalate, and mono-(propyl-6-carboxyhexyl) phthalate) but also novel metabolites that were structurally related to DPHP in the rat samples, indicating that the developed procedure successfully identified toxicant metabolites in in vivo samples. Among the 62 tentative metabolites identified from the 7th-day urine and the 28th-day hair samples, 33 were detected in only the urine samples, 19 were detected in only the hair samples, and 10 were identified in both the urine and hair samples. A total of 15 out of the 62 metabolites were confirmed as DPHP structure-related metabolites based on MS/MS analysis. Among the 15 DPHP structure-related metabolites, only 2 metabolites were present in both the urine and hair samples. These results suggested that the metabolites identified in urine could not be applied to exposure assessments based on hair analysis. PMID: 30685045 [PubMed - in process]

Fingerprinting of traditionally produced red wines using liquid chromatography combined with drift tube ion mobility-mass spectrometry. Anal Chim Acta. 2019 Apr 04;1052:179-189 Authors: Causon TJ, Ivanova-Petropulos V, Petrusheva D, Bogeva E, Hann S Abstract The characterization of wine via MS-based metabolic fingerprinting techniques remains a challenging undertaking due to the large number of phenolic compounds that cannot be confidently annotated and identified within analytical workflows. The combination of high performance liquid chromatography with low-field drift tube ion mobility time-of-flight mass spectrometry (HPLC × IMS-TOFMS) offers potential for the confident characterization and fingerprinting of wine using a metabolomics-type workflow. In particular, the use of collision cross section values from low-field drift tube IMS using nitrogen as drift gas (DTCCSN2) in addition to retention time and a high resolution mass spectrum for putative compounds allows rugged statistical assessment and identity confirmation using CCS libraries (<0.5% error) to be performed. In the present work, an HPLC × IMS-TOFMS platform has been utilized for the fingerprinting of 42 traditionally produced red wines emanating from the Republic of Macedonia. After establishing the reliability of DTCCSN2 as an identification point for wine metabolomics in both ionization modes, fingerprinting of wines according to grape variety was undertaken and a full dataset containing retention, accurate mass and DTCCSN2 values used to derive lists of compounds found to be statistically characteristic for each variety. Putative compounds were further assessed by assignment of in-source and post-drift mass fragments aligned according to retention time, drift time, and accurate mass providing up to seven identification points for a single compound when data from both positive and negative mode measurements are combined. PMID: 30685037 [PubMed - in process]

27 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 2019/01/27PubMed 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.

Assessment of the effect of methyl-triclosan and its mixture with triclosan on developing zebrafish (Danio rerio) embryos using mass spectrometry-based metabolomics. J Hazard Mater. 2019 Jan 11;368:186-196 Authors: Fu J, Gong Z, Bae S Abstract Methyl-triclosan (MTCS), as a biodegradation product from antibacterial triclosan (TCS), has been detected in water catchments, and it has also been verified to accumulate in biota due to its hydrophobicity. There is a lack, however, of toxicity studies on MTCS and its effects on organisms in conjunction with TCS. In this study, exposure experiments were conducted to assess the toxicity to embryonic zebrafish of selected concentrations of MTCS (from 1 ng/L to 400 μg/L) and MTCS/TCS mixtures (from 1 μg/L TCS and 100 ng/L MTCS to 300 μg/L TCS and 30 μg/L MTCS). Specimens were extracted using acetonitrile: isopropanol: water (3:3:2; v/v/v) and then analyzed using Gas chromatography-mass spectrometry (GC-MS) to identify the metabolites based on the Fiehn library database. The results showed that MTCS exposure led to the alterations of the metabolomes of the zebrafish embryos, including level changes of l-valine, d-mannose, d-glucose, and other metabolites. Multivariate analysis (PCA, PLS-DA, sPLS-DA) and univariate analysis (one-way ANOVA) indicated differences between the control and exposure groups of the metabolites, indicating that biological pathways, such as amino acid synthesis, pentose phosphate pathway (PPP), starch and sucrose metabolism were influenced. Moreover, when the embryos were exposed to a mix of TCS and MTCS, TCS dominated the mixture's effect on biological pathways because the concentration ratio within the mixture, which mimics environmental ratio of 10 TCS : 1 MTCS, leads to high bioavailability of TCS. PMID: 30677650 [PubMed - as supplied by publisher]

Metabolic Profiling of Different Parts of Acer truncatum from the Mongolian Plateau Using UPLC-QTOF-MS with Comparative Bioactivity Assays. J Agric Food Chem. 2019 Jan 24;: Authors: Gu R, Rybalov L, Negrin A, Morcol T, Long W, Myers AK, Isaac G, Yuk J, Kennelly EJ, Long C Abstract Acer truncatum is an important ornamental, edible, and medicinal plant resource in China. Previous phytochemical research has focused on the leaf (AL) due to its long history as a tea for health. Other parts such as the branch (ABr), bark (ABa), fruit (AF), and root (AR) have drawn little attention regarding their metabolites and bioactivities. The strategy of an in-house chemical library combined with Progenesis QI informatics platform was applied to characterize the metabolites. A total of 98 compounds were characterized or tentatively identified, including 63 compounds reported from this species for the first time. Principal component analysis showed the close clustering of ABr, ABa, and AR, indicating that they share similar chemical components, while AL and AF clustered more distantly. By multiple orthogonal partial least-squares discriminant analyses (OPLS-DA), 52 compounds were identified as potential marker compounds differentiating these different plant parts. The variable influence on projection score from OPLS-DA revealed that catechin, procyanidins B2 or B3, and procyanidins C1 or C2 are the significant metabolites in ABa extracts, which likely contribute to its antioxidant and cytotoxic activities. PMID: 30675777 [PubMed - as supplied by publisher]

Discovery and evaluation of inhibitor of LARP6 as specific antifibrotic compound. Sci Rep. 2019 Jan 23;9(1):326 Authors: Stefanovic B, Manojlovic Z, Vied C, Badger CD, Stefanovic L Abstract Fibrosis is characterized by excessive production of type I collagen. Biosynthesis of type I collagen in fibrosis is augmented by binding of protein LARP6 to the 5' stem-loop structure (5'SL), which is found exclusively in type I collagen mRNAs. A high throughput screen was performed to discover inhibitors of LARP6 binding to 5'SL, as potential antifibrotic drugs. The screen yielded one compound (C9) which was able to dissociate LARP6 from 5' SL RNA in vitro and to inactivate the binding of endogenous LARP6 in cells. Treatment of hepatic stellate cells (liver cells responsible for fibrosis) with nM concentrations of C9 reduced secretion of type I collagen. In precision cut liver slices, as an ex vivo model of hepatic fibrosis, C9 attenuated the profibrotic response at 1 μM. In prophylactic and therapeutic animal models of hepatic fibrosis C9 prevented development of fibrosis or hindered the progression of ongoing fibrosis when administered at 1 mg/kg. Toxicogenetics analysis revealed that only 42 liver genes changed expression after administration of C9 for 4 weeks, suggesting minimal off target effects. Based on these results, C9 represents the first LARP6 inhibitor with significant antifibrotic activity. PMID: 30674965 [PubMed - in process]

Effects of Repeated Sublethal External Exposure to Deep Water Horizon Oil on the Avian Metabolome. Sci Rep. 2019 Jan 23;9(1):371 Authors: Dorr BS, Hanson-Dorr KC, Assadi-Porter FM, Selen ES, Healy KA, Horak KE Abstract We assessed adverse effects of external sublethal exposure of Deepwater Horizon, Mississippi Canyon 252 oil on plasma and liver metabolome profiles of the double-crested cormorant (Phalacrocorax auritus), a large (1.5 to 3.0 kg) diving waterbird common in the Gulf of Mexico. Metabolomics analysis of avian plasma showed significant negative effects on avian metabolic profiles, in some cases after only two external exposures (26 g cumulative) to oil. We observed significant (p < 0.05) changes in intermediate metabolites of energy metabolism and fatty acid and amino acid metabolic pathways in cormorants after repeated exposure to oil. Exposure to oil increased several metabolites (glycine, betaine, serine and methionine) that are essential to the one-carbon metabolism pathway. Lipid metabolism was affected, causing an increase in production of ketone bodies, suggesting lipids were used as an alternative energy source for energy production in oil exposed birds. In addition, metabolites associated with hepatic bile acid metabolism were affected by oil exposure which was correlated with changes observed in bile acids in exposed birds. These changes at the most basic level of phenotypic expression caused by sublethal exposure to oil can have effects that would be detrimental to reproduction, migration, and survival in avian species. PMID: 30674908 [PubMed - in process]

In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation. Nat Commun. 2019 Jan 23;10(1):386 Authors: Spence EF, Dube S, Uezu A, Locke M, Soderblom EJ, Soderling SH Abstract Excitatory synapse formation during development involves the complex orchestration of both structural and functional alterations at the postsynapse. However, the molecular mechanisms that underlie excitatory synaptogenesis are only partially resolved, in part because the internal machinery of developing synapses is largely unknown. To address this, we apply a chemicogenetic approach, in vivo biotin identification (iBioID), to discover aspects of the proteome of nascent synapses. This approach uncovered sixty proteins, including a previously uncharacterized protein, CARMIL3, which interacts in vivo with the synaptic cytoskeletal regulator proteins SrGAP3 (or WRP) and actin capping protein. Using new CRISPR-based approaches, we validate that endogenous CARMIL3 is localized to developing synapses where it facilitates the recruitment of capping protein and is required for spine structural maturation and AMPAR recruitment associated with synapse unsilencing. Together these proteomic and functional studies reveal a previously unknown mechanism important for excitatory synapse development in the developing perinatal brain. PMID: 30674877 [PubMed - in process]

PPARα and PPARγ activation attenuates total free fatty acid and triglyceride accumulation in macrophages via the inhibition of Fatp1 expression. Cell Death Dis. 2019 Jan 15;10(2):39 Authors: Ye G, Gao H, Wang Z, Lin Y, Liao X, Zhang H, Chi Y, Zhu H, Dong S Abstract Lipid accumulation in macrophages interacts with microenvironment signals and accelerates diabetic atherosclerosis. However, the molecular mechanisms by which macrophage metabolism interacts with microenvironment signals during lipid accumulation are not clearly understood. Accordingly, an untargeted metabolomics approach was employed to characterize the metabolic reprogramming, and to identify potential regulatory targets related to lipid accumulation in macrophages treated with oleate, an important nutrient. The metabolomics approach revealed that multiple metabolic pathways were significantly disturbed in oleate-treated macrophages. We discovered that amino acids, nucleosides, lactate, monoacylglycerols, total free fatty acids (FFAs), and triglycerides (TGs) accumulated in oleate-treated macrophages, but these effects were effectively attenuated or even abolished by resveratrol. Notably, 1-monooleoylglycerol and 2-monooleoylglycerol showed the largest fold changes in the levels among the differential metabolites. Subsequently, we found that oleate triggered total FFA and TG accumulation in macrophages by accelerating FFA influx through the activation of Fatp1 expression, but this effect was attenuated by resveratrol via the activation of PPARα and PPARγ signaling. We verified that the activation of PPARα and PPARγ by WY14643 and pioglitazone, respectively, attenuated oleate triggered total FFA and TG accumulation in macrophages by repressing FFA import via the suppression of Fatp1 expression. Furthermore, the inhibition of Fatp1 by tumor necrosis factor α alleviated oleate-induced total FFA and TG accumulation in macrophages. This study provided the first demonstration that accumulation of amino acids, nucleosides, lactate, monoacylglycerols, total FFAs, and TGs in oleate-treated macrophages is effectively attenuated or even abolished by resveratrol, and that the activation of PPARα and PPARγ attenuates oleate-induced total FFA and TG accumulation via suppression of Fatp1 expression in macrophages. Therapeutic strategies aim to activate PPAR signaling, and to repress FFA import and triglyceride synthesis are promising approaches to reduce the risk of obesity, diabetes and atherosclerosis. PMID: 30674874 [PubMed - in process]

Mathematical models of amino acid panel for assisting diagnosis of children acute leukemia. J Transl Med. 2019 Jan 23;17(1):38 Authors: Liu Z, Zhou T, Han X, Lang T, Liu S, Zhang P, Liu H, Wan K, Yu J, Zhang L, Chen L, Beuerman RW, Peng B, Zhou L, Zou L Abstract BACKGROUND: The altered concentrations of amino acids were found in the bone marrow or blood of leukemia patients. Metabolomics technology combining mathematical model of biomarkers could be used for assisting the diagnosis of pediatric acute leukemia (AL). METHODS: The concentrations of 17 amino acids was measured by targeted liquid chromatograph-tandem mass spectrometry in periphery blood collected using dried blood spots. After evaluation, the mathematical models were further evaluated by prospective clinical validation cohort for AL diagnosis. RESULTS: The concentrations of 13 in 17 amino acids were statistically different between the periphery blood dried serum dots measured by targeted LC-MS/MS. The receiver operating characteristic analysis for the models of amino acid panel showed that the area under curve for AL diagnosis were 0.848, 0.834 and 0.856 by SVM, RF and XGBoost. The Kappa values in further prospectively evaluated clinical cohort were 0.697, 0.703 and 0.789 (p > 0.05) respectively, and the accuracies for the models were 84.86%, 85.20% and 89.46% respectively with further clinical validation. CONCLUSIONS: The established mathematical model is a faster, cheaper and more convenient way than conventional methods, and no significant difference on the effect of diagnosis comparing with conventional methods. The mathematical model can be clinically useful for assisting pediatric AL diagnosis. PMID: 30674317 [PubMed - in process]

Related Articles 1H NMR toxicometabolomics following cisplatin-induced nephrotoxicity in male rats. J Toxicol Sci. 2019;44(1):57-71 Authors: Ryu SH, Lee JD, Kim JW, Kim S, Kim S, Kim KB Abstract Cisplatin (CP) is an anti-cancer drug used for treatment of solid tumors, but the major adverse effect is drug-induced nephrotoxicity. The current study aimed to determine biomarkers that might predict nephrotoxicity induced by CP using serum or urinary proton nuclear magnetic resonance (1H NMR) spectral data in male Sprague-Dawley (S-D) rats. CP (0, 0.5 or 5 mg/kg) was intraperitoneally (i.p.) administered for single dose. Animals were sacrificed 2 days (D2) or 8 days (D8) after administration of CP in order to perform analysis of serum biochemistries and histopathologic examination. Urine samples were collected every 24 hr from pre-treatment to sacrifice. Serum and urinary 1H NMR spectral data revealed apparent differential clustering between control and CP-treated groups as evidenced by principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) in global and targeted profiling. The concentrations of endogenous serum metabolites, alanine, betaine, glucose, glutamine, lactate, and leucine were significantly increased on D2. Urinary concentrations of alanine, glucose, glycine, guanidinoacetate, acetate, and lactate were significantly elevated on D2 or D8, whereas concentrations of urinary metabolites, citrate and hippurate were significantly decreased on D2 or D8. The correlation of serum and urinary 1H NMR OPLS-DA with serum biochemistry and renal histopathologic changes suggests that 1H NMR urinalysis may be used to reliably predict or screen CP-induced nephrotoxicity. Data suggest that these altered endogenous metabolites might serve as specific biomarkers for CP-induced nephrotoxicity. PMID: 30626780 [PubMed - indexed for MEDLINE]

Related Articles [Precision medicine and omic sciences: promises and facts]. Assist Inferm Ric. 2018 Jan-Mar;37(1):52-55 Authors: Collecchia G Abstract . Precision Medicine refers to the tailoring of medical treatment to the individual characteristics of each patient. It aims at classifying individuals into subpopulations that differ in their susceptibility to a disease, in the biology or prognosis, or in their response to a specific treatment. In this paper a general overview of precision medicine is offered, focusing on promises and limitations, and stressing its importance also for the nursing profession. PMID: 29658542 [PubMed - indexed for MEDLINE]

Related Articles Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial. Diabet Med. 2018 07;35(7):944-953 Authors: Safai N, Suvitaival T, Ali A, Spégel P, Al-Majdoub M, Carstensen B, Vestergaard H, Ridderstråle M, CIMT Trial Group Abstract AIM: Metformin is the first-line treatment for Type 2 diabetes. However, not all people benefit from this drug. Our aim was to investigate the effects of metformin on the plasma metabolome and whether the pretreatment metabolite profile can predict HbA1c outcome. METHODS: Post hoc analysis of the Copenhagen Insulin and Metformin Therapy (CIMT) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non-target method to analyse 87 plasma metabolites in participants with Type 2 diabetes (n = 370) who were randomized in a 1 : 1 ratio to 18 months of metformin or placebo treatment. Metabolites were measured by liquid chromatography-mass spectrometry at baseline and at 18-month follow-up and the data were analysed using a linear mixed-effect model. RESULTS: At baseline, participants who were on metformin before the trial (n = 312) had higher levels of leucine/isoleucine and five lysophosphatidylethanolamines (LPEs), and lower levels of carnitine and valine compared with metformin-naïve participants (n = 58). At follow-up, participants randomized to metformin (n = 188) had elevated levels of leucine/isoleucine and reduced carnitine, tyrosine and valine compared with placebo (n = 182). At baseline, participants on metformin treatment with the highest levels of carnitine C10:1 and leucine/isoleucine had the lowest HbA1c (P-interaction = 0.02 and 0.03, respectively). This association was not significant with HbA1c at follow-up. CONCLUSIONS: Metformin treatment is associated with decreased levels of valine, tyrosine and carnitine, and increased levels of leucine/isoleucine. None of the identified metabolites can predict the HbA1c -lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted. PMID: 29633349 [PubMed - indexed for MEDLINE]

Related Articles Reconstruction of HMBC Correlation Networks: A Novel NMR-Based Contribution to Metabolite Mixture Analysis. J Chem Inf Model. 2018 02 26;58(2):262-270 Authors: Bakiri A, Hubert J, Reynaud R, Lambert C, Martinez A, Renault JH, Nuzillard JM Abstract A new in silico method is introduced for the dereplication of natural metabolite mixtures based on HMBC and HSQC spectra that inform about short-range and long-range H-C correlations occurring in the carbon skeleton of individual chemical entities. Starting from the HMBC spectrum of a metabolite mixture, an algorithm was developed in order to recover individualized HMBC footprints of the mixture constituents. The collected H-C correlations are represented by a network of NMR peaks connected to each other when sharing either a 1H or 13C chemical shift value. The network obtained is then divided into clusters using a community detection algorithm, and finally each cluster is tentatively assigned to a molecular structure by means of a NMR chemical shift database containing the theoretical HMBC and HSQC correlation data of a range of natural metabolites. The proof of principle of this method is demonstrated on a model mixture of 3 known natural compounds and then on a real-life bark extract obtained from the common spruce (Picea abies L.). PMID: 29320182 [PubMed - indexed for MEDLINE]