PubMed

Related Articles [Metabonomics studies of urine from APP/PS1 mice with early-stage Alzheimer's disease]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2018 Dec 25;47(6):636-642 Authors: Zheng Y, Zhang X, Chen J, Zhou Q, Gao H Abstract OBJECTIVE: To investigate the metabolic profiles of urine from APP/PS1 mice with early-stage Alzheimer's disease (AD). METHODS: Urine samples were collected from 13 APP/PS1 mice of 16 weeks and 15 wild-type mice. 1H-NMR spectroscopy was acquired with a one-dimensional NOESY pulse sequence, and the integral values were imported to SIMCA-P+12.0 software for analysis. RESULTS: The metabonomic analysis showed that the metabolic profiles of the APP/PS1 mice were significantly different from that of age-matched wild-type mice. The levels of 3-hydroxybutyrate, 2-hydroxybutyrate, succinic acid, 2-ketoglutaric acid, citric acid, cis-aconitic acid, fumaric acid decreased, and those of acetic acid, trimethylamine, taurine, creatinine, hippuric acid, formic acid, trigonelline, urea increased (all P<0.05). CONCLUSIONS: Metabolic pathways including glucose metabolism and methylamine metabolism may be involved in the pathogenesis of early AD. PMID: 30900843 [PubMed - indexed for MEDLINE]

Related Articles [Effects of Niaoduqing granule on urine metabolic profile in chronic renal failure rats]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2018 Dec 25;47(6):628-635 Authors: Zhu M, Wu Y, Shou Z Abstract OBJECTIVE: To investigate the effects of Niaoduqing granule on the urine metabolic profile in chronic renal failure (CRF) rats. METHODS: Thirty six male SD rats were divided into the normal control group, the model group, and the Niaoduqing group with 12 rats in each group. The CRF was induced by gavage of 250 mg·kg-1·d-1 adenine for 21 d. UPLC-Q-TOF-MS/MS technique was used in combination with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to analyze the urine metabolic profiles in three groups. The endogenous substances with the variable importance projection (VIP)>1 and P<0.05 were screened as the potential biomarkers for CRF, and enrichment analysis of metabolic pathways was carried out. RESULTS: Compared with the normal control group, the model group had lower body weight, higher kidney coefficient, higher serum creatinine and urea nitrogen levels (all P<0.01), while the above indexes in the Niaoduqing group were ameliorated compared with the model group (all P<0.01). Fifteen potential biomarkers were found in the urine of the model group, which were involved in 9 metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylate and dicarboxylate metabolism, valine, leucine and isoleucine biosynthesis, arachidonic acid metabolism, cysteine and methionine metabolism, tricarboxylic acid cycle, glycerophosphatide metabolism, tryptophan metabolism and tyrosine metabolism. CONCLUSIONS: Niaoduqing granules has therapeutic effect on rats with CRF, which may be related to the regulation of amino acid metabolism, lipid metabolism and energy metabolism. PMID: 30900842 [PubMed - indexed for MEDLINE]

Related Articles NMR and MS urinary metabolic phenotyping in kidney diseases is fit-for-purpose in the presence of a protease inhibitor. Mol Omics. 2019 02 11;15(1):39-49 Authors: Boulangé CL, Rood IM, Posma JM, Lindon JC, Holmes E, Wetzels JFM, Deegens JKJ, Kaluarachchi MR Abstract Nephrotic syndrome with idiopathic membranous nephropathy as a major contributor, is characterized by proteinuria, hypoalbuminemia and oedema. Diagnosis is based on renal biopsy and the condition is treated using immunosuppressive drugs; however nephrotic syndrome treatment efficacy varies among patients. Multi-omic urine analyses can discover new markers of nephrotic syndrome that can be used to develop personalized treatments. For proteomics, a protease inhibitor (PI) is sometimes added at sample collection to conserve proteins but its impact on urine metabolic phenotyping needs to be evaluated. Urine from controls (n = 4) and idiopathic membranous nephropathy (iMN) patients (n = 6) were collected with and without PI addition and analysed using 1H NMR spectroscopy and UPLC-MS. PI-related data features were observed in the 1H NMR spectra but their removal followed by a median fold change normalisation, eliminated the PI contribution. PI-related metabolites in UPLC-MS data had limited effect on metabolic patterns specific to iMN. When using an appropriate data processing pipeline, PI-containing urine samples are appropriate for 1H NMR and MS metabolic profiling of patients with nephrotic syndrome. PMID: 30672550 [PubMed - indexed for MEDLINE]

Related Articles Exploratory metabolomic study to identify blood-based biomarkers as a potential screen for colorectal cancer. Mol Omics. 2019 02 11;15(1):21-29 Authors: Asante I, Pei H, Zhou E, Liu S, Chui D, Yoo E, Conti DV, Louie SG Abstract INTRODUCTION: colorectal cancer (CRC) continues to be difficult to diagnose due to the lack of reliable and predictive biomarkers. OBJECTIVE: to identify blood-based biomarkers that can be used to distinguish CRC cases from controls. METHODS: a workflow for untargeted followed by targeted metabolic profiling was conducted on the plasma samples of 26 CRC cases and ten healthy volunteers (controls) using liquid chromatography-mass spectrometry (LCMS). The data acquired in the untargeted scan was processed and analyzed using MarkerView™ software. The significantly different ions that distinguish CRC cases from the controls were identified using a mass-based human metabolome search. The result was further used to inform the targeted scan workflow. RESULTS: the untargeted scan yielded putative biomarkers some of which were related to the folate-dependent one-carbon metabolism (FOCM). Analysis of the targeted scan found the plasma levels of nine FOCM metabolites to be significantly different between cases and controls. The classification models of the cases and controls, in both the targeted and untargeted approaches, each yielded a 97.2% success rate after cross-validation. CONCLUSION: we have identified plasma metabolites with screening potential to discriminate between CRC cases and controls. PMID: 30515501 [PubMed - indexed for MEDLINE]

Related Articles Vacuolar sucrose cleavage prevents limitation of cytosolic carbohydrate metabolism and stabilizes photosynthesis under abiotic stress. FEBS J. 2018 11;285(21):4082-4098 Authors: Weiszmann J, Fürtauer L, Weckwerth W, Nägele T Abstract Stabilization of central carbohydrate metabolism plays a key role in plant stress response. Carbohydrates are substrate for numerous metabolic and stress-responsive reactions and have been shown to be involved in diverse signalling processes on a whole-plant level. Regulation of enzymatic sucrose synthesis and degradation is well-known to be central to many stress-related processes as it significantly impacts stress tolerance. Leaf sucrose metabolism involves sucrose cleavage by invertases and ATP-consuming resynthesis catalysed by hexokinase and sucrose phosphate synthase. These reactions establish a metabolic cycle. To study the physiological role of sucrose cycling, a kinetic model was developed to simulate dynamics of subcellular sugar concentrations in Arabidopsis thaliana under combined cold and high-light stress. Model simulation revealed that subcellular reprogramming of invertase-driven sucrose cleavage varies substantially between natural accessions of Arabidopsis which differ in their cold tolerance levels. A stress-induced shift of sucrose cleavage from the cytosol into the vacuole could only be observed for the tolerant accession while the susceptible accession increased the cytosolic proportion of sucrose cleavage. Under stress, reduction in vacuolar invertase activity significantly affected maximum quantum yield of photosystem II and CO2 assimilation rates. While wild-type plants circumvented a limitation of sucrose cleavage by increasing vacuolar invertase activity, mutant plants were not able to compensate their deficiency of vacuolar by cytosolic activity. Consequently, the capacity for cytosolic hexose generation was lower than for enzymatic hexose phosphorylation suggesting a role of vacuolar invertase activity in preventing a limitation in cytosolic hexose metabolism under stress. ENZYMES: Invertase, EC 3.2.1.26; Hexokinase, EC 2.7.1.1. PMID: 30216682 [PubMed - indexed for MEDLINE]

Related Articles Beta-hydroxybutyrate infusion identifies acutely differentially expressed genes related to metabolism and reproduction in the hypothalamus and pituitary of castrated male sheep. Physiol Genomics. 2018 06 01;50(6):468-477 Authors: Cope ER, Voy BH, Whitlock BK, Staton M, Lane T, Davitt J, Mulliniks JT Abstract To identify molecular pathways that couple metabolic imbalances and reproduction, we randomly assigned 10 castrated male sheep to be centrally injected into the lateral ventricle through intracerebroventricular cannulas with 1 ml of β-hydroxybutyric acid sodium salt solution (BHB; 12,800 µmol/l) or saline solution (CON; 0.9% NaCl). Approximately 2 h postinjection, sheep were humanely euthanized, and hypothalamus and pituitary tissues were harvested for transcriptome characterization by RNA sequencing. RNA was extracted from the hypothalamus and pituitary and sequenced at a high depth (hypothalamus: 468,912,732 reads; pituitary: 515,106,092 reads) with the Illumina Hi-Seq 2500 platform and aligned to Bos taurus and Ovis aries genomes. Of the total raw reads, 87% (hypothalamus) and 90.5% (pituitary) mapped to the reference O. aries genome. Within these read sets, ~56% in hypothalamus and 69% in pituitary mapped to either known or putative protein coding genes. Fragments per kilobase of transcripts per million normalized counts were averaged and ranked to identify the transcript expression level. Gene Ontology analysis (DAVID Bioinformatics Resources) was utilized to identify biological process functions related to genes shared between tissues, as well as functional categories with tissue-specific enrichment. Between CON- and BHB-treated sheep, 11 and 44 genes were differentially expressed (adj. P < 0.05) within the pituitary and hypothalamus, respectively. Functional enrichment analyses revealed BHB altered expression of genes in pathways related to stimulus perception, inflammation, and cell cycle control. The set of genes altered by BHB creates a foundation from which to identify the signaling pathways that impact reproduction during metabolic imbalances. PMID: 29625019 [PubMed - indexed for MEDLINE]

Related Articles Transcriptomic analysis reveals inflammatory and metabolic pathways that are regulated by renal perfusion pressure in the outer medulla of Dahl-S rats. Physiol Genomics. 2018 06 01;50(6):440-447 Authors: Evans LC, Dayton A, Yang C, Liu P, Kurth T, Ahn KW, Komas S, Stingo FC, Laud PW, Vannucci M, Liang M, Cowley AW Abstract Studies exploring the development of hypertension have traditionally been unable to distinguish which of the observed changes are underlying causes from those that are a consequence of elevated blood pressure. In this study, a custom-designed servo-control system was utilized to precisely control renal perfusion pressure to the left kidney continuously during the development of hypertension in Dahl salt-sensitive rats. In this way, we maintained the left kidney at control blood pressure while the right kidney was exposed to hypertensive pressures. As each kidney was exposed to the same circulating factors, differences between them represent changes induced by pressure alone. RNA sequencing analysis identified 1,613 differently expressed genes affected by renal perfusion pressure. Three pathway analysis methods were applied, one a novel approach incorporating arterial pressure as an input variable allowing a more direct connection between the expression of genes and pressure. The statistical analysis proposed several novel pathways by which pressure affects renal physiology. We confirmed the effects of pressure on p-Jnk regulation, in which the hypertensive medullas show increased p-Jnk/Jnk ratios relative to the left (0.79 ± 0.11 vs. 0.53 ± 0.10, P < 0.01, n = 8). We also confirmed pathway predictions of mitochondrial function, in which the respiratory control ratio of hypertensive vs. control mitochondria are significantly reduced (7.9 ± 1.2 vs. 10.4 ± 1.8, P < 0.01, n = 6) and metabolomic profile, in which 14 metabolites differed significantly between hypertensive and control medullas ( P < 0.05, n = 5). These findings demonstrate that subtle differences in the transcriptome can be used to predict functional changes of the kidney as a consequence of pressure elevation. PMID: 29602296 [PubMed - indexed for MEDLINE]

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Related Articles Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles. Cell Rep. 2019 Jun 04;27(10):3062-3080.e11 Authors: Cianciaruso C, Beltraminelli T, Duval F, Nassiri S, Hamelin R, Mozes A, Gallart-Ayala H, Ceada Torres G, Torchia B, Ries CH, Ivanisevic J, De Palma M Abstract Extracellular vesicles (EVs), including exosomes, modulate multiple aspects of cancer biology. Tumor-associated macrophages (TAMs) secrete EVs, but their molecular features and functions are poorly characterized. Here, we report methodology for the enrichment, quantification, and proteomic and lipidomic analysis of EVs released from mouse TAMs (TAM-EVs). Compared to source TAMs, TAM-EVs present molecular profiles associated with a Th1/M1 polarization signature, enhanced inflammation and immune response, and a more favorable patient prognosis. Accordingly, enriched TAM-EV preparations promote T cell proliferation and activation ex vivo. TAM-EVs also contain bioactive lipids and biosynthetic enzymes, which may alter pro-inflammatory signaling in the cancer cells. Thus, whereas TAMs are largely immunosuppressive, their EVs may have the potential to stimulate, rather than limit, anti-tumor immunity. PMID: 31167148 [PubMed - in process]

Related Articles Application of Ion Chromatography Coupled with Mass Spectrometry for Human Serum and Urine Metabolomics. SLAS Discov. 2019 Jun 05;:2472555219850082 Authors: Sun Y, Saito K, Iiji R, Saito Y Abstract Biomarkers that indicate the presence or severity of organ damage caused by diseases and toxicities are useful diagnostic tools. Metabolomics platforms using chromatography coupled with mass spectrometry (MS) have been widely used for biomarker screening. In this study, we aimed to establish a novel metabolomics platform using ion chromatography coupled with MS (IC-MS) for human biofluids. We found that ethylenediaminetetraacetic acid (EDTA) plasma is not suitable for IC-MS metabolomics platforms because of the desensitization of MS. IC-MS enabled detection of 131 polar metabolites in human serum and urine from healthy volunteers. Pathway analysis demonstrated that the metabolites detectable using our platform were composed of a broad spectrum of organic acids with carboxylic moieties. These metabolites were significantly associated with pathways such as the tricarboxylic acid (TCA) cycle; glyoxylate and dicarboxylate metabolism; alanine, aspartate, and glutamate metabolism; butanoate metabolism; and the pentose phosphate pathway. Moreover, comparison of serum and urine samples showed that four metabolites (4-hydroxybutyric acid, aspartic acid, lactic acid, and γ-glutamyl glutamine) were abundant in serum, whereas 62 metabolites, including phosphoric acid, vanillylmandelic acid, and N-tiglylglycine, were abundant in urine. In addition, allantoin and uric acid were abundant in male serum, whereas no gender-associated differences were found for polar metabolites in urine. Our results demonstrate that the present established IC-MS metabolomics platform can be applied for analysis of human serum and urine as well as detection of a broad spectrum of polar metabolites in human biofluids. PMID: 31166806 [PubMed - as supplied by publisher]

Related Articles CREB mediates glucagon action to upregulate hepatic MPC1: inhibitory effect of ginsenoside Rb1 on hepatic gluconeogenesis. Br J Pharmacol. 2019 Jun 05;: Authors: Lou MD, Li J, Cheng Y, Xiao N, Ma G, Li P, Liu B, Liu Q, Qi LW Abstract BACKGROUND AND PURPOSE: Hepatic mitochondrial pyruvate carrier (MPC) transports pyruvate into mitochondria. This study investigated the involvement of MPC1 in hepatic glucagon response, with the aim of finding a potential for pharmacological intervention. EXPERIMENTAL APPROACH: The correlation between hepatic glucagon response and MPC1 induction was investigated in fasted mice and primary hepatocytes. The effects of ginsenoside Rb1 on MPC1 function were observed. KEY RESULTS: Glucagon challenge raised blood glucose with hepatic MPC1 induction and inhibition of MPC induction coincided with a reduced rise in blood glucose. Cyclic AMP-responsive element-binding protein (CREB) knockdown abrogated glucagon-induced MPC1 expression, while CREB overexpression increased MPC1 expression. Luciferase reporter, ChIP assay and promoter mutation confirmed that CREB increased MPC1 transcription through gene promoter induction. CRTC2 nuclear translocation was also required for CREB to promote MPC1 induction. Glucagon shifted mitochondrial pyruvate towards carboxylation for gluconeogenesis via the opposite regulation of pyruvate dehydrogenase and carboxylase with respect to MPC1 induction. MPC1 induction was necessary for glucagon to promote pyruvate-driven HGP, while glucagon failed to influence HGP from other gluconeogenic substrates that are routed into the TCA cycle independent of MPC. Rb1 blocked cAMP signaling by inhibition of adenyl cyclase activity and deactivated CREB by dephosphorylation, likely contributing to inhibiting MPC1 induction to reduce HGP. CONCLUSIONS AND IMPLICATIONS: CREB transcriptionally upregulates MPC1 to ensure pyruvate availability for gluconeogenesis. Rb1 reduced cAMP formation which consequently reduced CREB-mediated MPC1 induction, and thereby might contribute to limiting pyruvate-dependent HGP. These results suggest a therapeutic strategy to reduce hyperglycemia in diabetes. PMID: 31166615 [PubMed - as supplied by publisher]

Related Articles Association of Dimethylguanidino Valeric Acid With Partial Resistance to Metabolic Health Benefits of Regular Exercise. JAMA Cardiol. 2019 Jun 05;: Authors: Robbins JM, Herzig M, Morningstar J, Sarzynski MA, Cruz DE, Wang TJ, Gao Y, Wilson JG, Bouchard C, Rankinen T, Gerszten RE Abstract Importance: Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual's responsiveness to exercise interventions. Objective: To investigate the association between a novel circulating biomarker of hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits before and after 20 weeks of endurance exercise training. Design, Setting, and Participants: This study involved cross-sectional and longitudinal analyses of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a 20-week, single-arm endurance exercise clinical trial performed in multiple centers between 1993 and 1997. White participants with sedentary lifestyles who were free of cardiometabolic disease were included. Metabolomic tests were performed using a liquid chromatography, tandem mass spectrometry method on plasma samples collected before and after exercise training in the HERITAGE study. Metabolomics and data analysis were performed from August 2017 to May 2018. Exposures: Plasma DMGV levels. Main Outcome and Measures: The association between DMGV levels and measures of body composition, plasma lipids, insulin, and glucose homeostasis before and after exercise training. Results: Among the 439 participants included in analyses from HERITAGE, the mean (SD) age was 36 (15) years, 228 (51.9%) were female, and the median (interquartile range) body mass index was 25 (22-28). Baseline levels of DMGV were positively associated with body fat percentage, abdominal visceral fat, very low-density lipoprotein cholesterol, and triglycerides, and inversely associated with insulin sensitivity, low-density lipoprotein cholesterol, high-density lipoprotein size, and high-density lipoprotein cholesterol (range of β coefficients, 0.17-0.46 [SEs, 0.026-0.050]; all P < .001, after adjusting for age and sex). After adjusting for age, sex, and baseline traits, baseline DMGV levels were positively associated with changes in small high-density lipoprotein particles (β, 0.14 [95% CI, 0.05-0.23]) and inversely associated with changes in medium and total high-density lipoprotein particles (β, -0.15 [95% CI, -0.24 to -0.05] and -0.19 [95% CI, -0.28 to -0.10], respectively), apolipoprotein A1 (β, -0.14 [95% CI, -0.23 to -0.05]), and insulin sensitivity (β, -0.13; P = 3.0 × 10-3) after exercise training. Conclusions and Relevance: Dimethylguanidino valeric acid is an early marker of cardiometabolic dysfunction that is associated with attenuated improvements in lipid traits and insulin sensitivity after exercise training. Levels of DMGV may identify individuals who require additional therapies beyond guideline-directed exercise to improve their metabolic health. PMID: 31166569 [PubMed - as supplied by publisher]

Related Articles Application of Omics and Bioinformatics Tools in Streptococcus Research. Curr Issues Mol Biol. 2019 Jun 05;32:327-376 Authors: Liao M, Tong T, Zong Y, Zhou X, Cheng L, Huang R, Ren B, Alterovitz G Abstract Researchers used to focus on analyzing single gene or protein expression of the microbes. But recently, genome, transcriptome, proteome and metabolome have gained more and more attention. Based on technologies of omics, including genomics, transcriptomics and metabolomics, a large quantity of information about cells, microbes and human, such as the information about phylogeny, virulence, antibiotic resistance and other aspects, has been revealed. Genus Streptococcus is one of the most invasive groups of bacteria that cause both human and animal diseases, threatening public health. In this review, we summarize the application of omics to analyze this genus-Streptococcus. PMID: 31166175 [PubMed - as supplied by publisher]

Related Articles Parahydrogen induced hyperpolarization provides a tool for NMR metabolomics at nanomolar concentrations. Chem Commun (Camb). 2019 Jun 05;: Authors: Sellies L, Reile I, Aspers RLEG, Feiters MC, Rutjes FPJT, Tessari M Abstract An NMR approach based on parahydrogen hyperpolarization is presented to detect and resolve specific classes of metabolites in complex biomixtures at down to nanomolar concentrations. We demonstrate our method on solid phase extracts of urine, by simultaneously observing hundreds of metabolites well below the limits of detection of thermal NMR. PMID: 31165813 [PubMed - as supplied by publisher]

Related Articles Metabolomic signatures of asthma-COPD overlap (ACO) are different from asthma and COPD. Metabolomics. 2019 Jun 04;15(6):87 Authors: Ghosh N, Choudhury P, Subramani E, Saha D, Sengupta S, Joshi M, Banerjee R, Roychowdhury S, Bhattacharyya P, Chaudhury K Abstract INTRODUCTION: Asthma-chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease without any clear diagnostic or therapeutic guidelines. The pathophysiology of the disease, its characteristic features, and existence as a unique disease entity remains unclear. Individuals with ACO have a faster lung function decline, more frequent exacerbations, and worse quality of life than those with COPD or asthma alone. OBJECTIVES: The present study aims to determine whether ACO has a distinct metabolic profile in comparison to asthma and COPD. METHODS: Two different groups of patients were recruited as discovery (D) and validation (V) cohorts. Serum samples obtained from moderate and severe asthma patients diagnosed as per GINA guidelines [n = 34(D); n = 32(V)], moderate and severe COPD cases identified by GOLD guidelines [n = 30(D); 32(V)], ACO patients diagnosed by joint GOLD and GINA guidelines [n = 35(D); 40(V)] and healthy controls [n = 33(D)] were characterized using nuclear magnetic resonance (NMR) spectrometry. RESULTS: Multivariate and univariate analysis indicated that 12 metabolites [lipid, isoleucine, N-acetylglycoproteins (NAG), valine, glutamate, citric acid, glucose, L-leucine, lysine, asparagine, phenylalanine and histidine] were dysregulated in ACO patients when compared with both asthma and COPD. These metabolites were further validated in a fresh cohort of patients, which again exhibited a similar expression pattern. CONCLUSIONS: Our findings suggest that ACO has an enhanced energy and metabolic burden associated with it as compared to asthma and COPD. It is anticipated that our results will stimulate researchers to further explore ACO and unravel the pathophysiological complexities associated with the disease. PMID: 31165288 [PubMed - in process]

Related Articles Decelerating ageing and biological clocks by autophagy. Nat Rev Mol Cell Biol. 2019 Jun 04;: Authors: Lopez-Otín C, Kroemer G PMID: 31164727 [PubMed - as supplied by publisher]

Related Articles MYC-driven small cell lung cancer is metabolically distinct and vulnerable to arginine depletion. Clin Cancer Res. 2019 Jun 04;: Authors: Chalishazar MD, Wait SJ, Huang F, Ireland AS, Mukhopadhyay A, Lee Y, Schuman S, Guthrie MR, Berrett K, Vahrenkamp J, Hu Z, Kudla M, Modzelewska K, Wang G, Ingolia NT, Gertz J, Lum DH, Cosulich SC, Bomalaski JS, DeBerardinis RJ, Oliver TG Abstract PURPOSE: Small cell lung cancer (SCLC) has been treated clinically as a homogeneous disease, but recent discoveries suggest that SCLC is heterogeneous. Whether metabolic differences exist among SCLC subtypes is largely unexplored. In this study, we aimed to determine whether metabolic vulnerabilities exist between SCLC subtypes that can be therapeutically exploited. EXPERIMENTAL DESIGN: We performed steady state metabolomics on tumors isolated from distinct GEMMs representing the MYC and MYCL-driven subtypes of SCLC. Using genetic and pharmacological approaches, we validated our findings in chemo-naive and resistant human SCLC cell lines, multiple GEMMs, four human cell line xenografts, and four newly-derived PDX models. RESULTS: We discover that SCLC subtypes driven by different MYC family members have distinct metabolic profiles. MYC-driven SCLC preferentially depends on arginine-regulated pathways including polyamine biosynthesis and mTOR pathway activation. Chemo-resistant SCLC cells exhibit increased MYC expression and similar metabolic liabilities as chemo-naive MYC-driven cells. Arginine depletion with pegylated arginine deiminase (ADI-PEG 20) dramatically suppresses tumor growth and promotes survival of mice specifically with MYC-driven tumors, including in GEMMs, human cell line xenografts, and a PDX from a relapsed patient. Finally, ADI-PEG 20 is significantly more effective than the standard of care chemotherapy. CONCLUSIONS: These data identify metabolic heterogeneity within SCLC and suggest arginine deprivation as a subtype-specific therapeutic vulnerability for MYC-driven SCLC. PMID: 31164374 [PubMed - as supplied by publisher]

Related Articles Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort. Cancer Epidemiol Biomarkers Prev. 2019 Jun 04;: Authors: Lécuyer L, Dalle C, Lyan B, Demidem A, Rossary A, Vasson MP, Petera M, Lagree M, Ferreira T, Centeno D, Galan P, Hercberg S, Deschasaux M, Partula V, Srour B, Latino-Martel P, Kesse-Guyot E, Druesne-Pecollo N, Durand S, Pujos-Guillot E, Touvier M Abstract BACKGROUND: Breast cancer is a major cause of death in occidental women. The role of metabolism in breast cancer etiology remains unclear. Metabolomics may help to elucidate novel biological pathways and identify new biomarkers in order to predict breast cancer long before symptoms appear. The aim of this study was to investigate whether untargeted metabolomic signatures from blood draws of healthy women could contribute to better understand and predict the long-term risk of developing breast cancer. METHODS: A nested case-control study was conducted within the SU.VI.MAX prospective cohort (13 years of follow-up) to analyze baseline plasma samples of 211 incident breast cancer cases and 211 matched controls by LC-MS mass spectrometry. Multivariable conditional logistic regression models were computed. RESULTS: 3565 ions were detected and 1221 were retained for statistical analysis. 73 ions were associated with breast cancer risk (p<0.01, FDR≤0.2). Notably, we observed that a lower plasma level of O-succinyl-homoserine (0.70[0.55-0.89]) and higher plasma levels of valine/norvaline (1.45[1.15-1.83]), glutamine/isoglutamine (1.33[1.07-1.66]), 5-aminovaleric acid (1.46[1.14-1.87]), phenylalanine (1.43[1.14-1.78]), tryptophan (1.40[1.10-1.79]), γ-glutamyl-threonine (1.39[1.09-1.77]), ATBC (1.41[1.10-1.79]) and pregnene-triol sulfate (1.38[1.08-1.77]) were associated with an increased risk of developing breast cancer during follow-up. CONCLUSIONS: Several pre-diagnostic plasmatic metabolites were associated with long-term breast cancer risk and suggested a role of microbiota metabolism and environmental exposure. IMPACT: After confirmation in other independent cohort studies, these results could help to identify healthy women at higher risk of developing breast cancer in the subsequent decade and to propose a better understanding of the complex mechanisms involved in its etiology. PMID: 31164347 [PubMed - as supplied by publisher]

Related Articles Omics Studies Revealed the Factors Involved in the Formation of Colony Boundary in Myxococcus xanthus. Cells. 2019 Jun 03;8(6): Authors: Anwar MN, Li ZF, Gong Y, Singh RP, Li YZ Abstract Two unrecognizable strains of the same bacterial species form a distinct colony boundary. During growth as colonies, Myxococcus xanthus uses multiple factors to establish cooperation between recognized strains and prevent interactions with unrecognized strains of the same species. Here, ΔMXAN_0049 is a mutant strain deficient in immunity for the paired nuclease gene, MXAN_0050, that has a function in the colony-merger incompatibility of Myxococcus xanthus DK1622. With the aim to investigate the factors involved in boundary formation, a proteome and metabolome study was employed. Visualization of the boundary between DK1622 and ΔMXAN_0049 was done scanning electron microscope (SEM), which displayed the presence of many damaged cells in the boundary. Proteome analysis of the DK1622- boundary disclosed many possible proteins, such as cold shock proteins, cell shape-determining protein MreC, along with a few pathways, such as RNA degradation, phenylalanine, tyrosine and tryptophan biosynthesis, and Type VI secretion system (T6SS), which may play major roles in the boundary formation. Metabolomics studies revealed various secondary metabolites that were significantly produced during boundary formation. Overall, the results concluded that multiple factors participated in the boundary formation in M. xanthus, leading to cellular damage that is helpful in solving the mystery of the boundary formation mechanism. PMID: 31163575 [PubMed]

Related Articles A review on remediation of cyanide containing industrial wastes using biological systems with special reference to enzymatic degradation. World J Microbiol Biotechnol. 2019 Apr 22;35(5):70 Authors: Sharma M, Akhter Y, Chatterjee S Abstract Cyanide is a nitrile which is used extensively in many industries like jewelry, mining, electroplating, plastics, dyes, paints, pharmaceuticals, food processing, and coal coking. Cyanides pose a serious health hazard due to their high affinity towards metals and cause malfunction of cellular respiration by inhibition of cytochrome c oxidase. This inhibition ultimately leads to histotoxic hypoxia, increased acidosis, reduced the functioning of the central nervous system and myocardial activity. Different physicochemical processes including oxidation by hydrogen peroxide, alkaline chlorination, and ozonization have been used to reduce cyanide waste from the environment. Microbial cyanide degradation which is considered as one the most successful techniques is used to take place through different biochemical/metabolic pathways involving reductive, oxidative, hydrolytic or substitution/transfer reactions. Groups of enzymes involved in microbial degradation are cyanidase, cyanide hydratase, formamidase, nitrilase, nitrile hydratase, cyanide dioxygenase, cyanide monooxygenase, cyanase and nitrogenase. In the future, more advancement of omics technologies and protein engineering will help us to recoup the environment from cyanide effluent. In this review, we have discussed the origin and environmental distribution of cyanide waste along with different bioremediation pathways and enzymes involved therein. PMID: 31011828 [PubMed - indexed for MEDLINE]