Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 15 min 54 sec ago

Analyzing omics data by pair-wise feature evaluation with horizontal and vertical comparisons.

Mon, 14/05/2018 - 13:13
Related Articles Analyzing omics data by pair-wise feature evaluation with horizontal and vertical comparisons. J Pharm Biomed Anal. 2018 May 01;157:20-26 Authors: Huang X, Lin X, Zhou L, Su B Abstract Feature relationships are complex and may contain important information. k top scoring pairs (k-TSP) studies feature relationships by the horizontal comparison. This study examines feature relationships and proposes vertical and horizontal k-TSP (VH-k-TSP) to identify the discriminative feature pairs by evaluating feature pairs based on the vertical and horizontal comparisons. Complexity is introduced to compute the discriminative abilities of feature pairs by means of these two comparisons. VH-k-TSP was compared with support vector machine-recursive feature elimination, relative simplicity-support vector machine, k-TSP and M-k-TSP on nine public genomics datasets. For multi-class problems, one-to-one method was used. The experiments showed that VH-k-TSP outperformed the four methods in most cases. Then, VH-k-TSP was applied to a metabolomics data of liver disease. An accuracy rate of 88.11 ± 3.30% in discrimination between cirrhosis and hepatocellular carcinoma was obtained by VH-k-TSP, better than 77.39 ± 4.10% and 79.28 ± 3.73% obtained by k-TSP and M-k-TSP, respectively. Hence combining the vertical and horizontal comparisons could define more discriminative feature pairs. PMID: 29754039 [PubMed - as supplied by publisher]

Nicotinamide phosphoribosyltransferase regulates cocaine reward through Sirtuin 1.

Mon, 14/05/2018 - 13:13
Related Articles Nicotinamide phosphoribosyltransferase regulates cocaine reward through Sirtuin 1. Exp Neurol. 2018 May 10;: Authors: Kong J, Du C, Jiang L, Jiang W, Deng P, Shao X, Zhang B, Li Y, Zhu R, Zhao Q, Fu D, Gu H, Luo L, Long H, Zhao Y, Cen X Abstract Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis in mammals, converts nicotinamide into nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD, a component that is critical for cell energy metabolism and survival. Sirtuin 1 (SIRT1), an NAD-dependent histone deacetylase, plays an important role in mediating memory and synaptic plasticity. Here, we found that NAMPT was significantly upregulated in the ventral tegmental area (VTA) of cocaine-conditioned mice. Intraperitoneal or intra-VTA injection of FK866, a specific inhibitor of NAMPT, significantly attenuated cocaine reward. However, such effects were clearly repressed by intra-VTA expression of NAMPT or supplementation with NMN. Using 1H-nuclear magnetic resonance metabolomic analysis, we found that the content of NAD and NMN were increased in the VTA of cocaine-conditioned mice; moreover, the expression of SIRT1 was also upregulated. Interestingly, the inhibitory effect of FK866 on cocaine reward was significantly weakened in Sirt1 midbrain conditional knockout mice. Our results suggest that NAMPT-mediated NAD biosynthesis may modify cocaine behavioral effects through SIRT1. Moreover, our findings reveal that the interplay between NAD biosynthesis and SIRT1 regulation may comprise a novel regulatory pathway that responds to chronic cocaine stimuli. PMID: 29753648 [PubMed - as supplied by publisher]

Reserve Flux Capacity in the Pentose Phosphate Pathway Enables Escherichia coli's Rapid Response to Oxidative Stress.

Mon, 14/05/2018 - 13:13
Related Articles Reserve Flux Capacity in the Pentose Phosphate Pathway Enables Escherichia coli's Rapid Response to Oxidative Stress. Cell Syst. 2018 May 02;: Authors: Christodoulou D, Link H, Fuhrer T, Kochanowski K, Gerosa L, Sauer U Abstract To counteract oxidative stress and reactive oxygen species (ROS), bacteria evolved various mechanisms, primarily reducing ROS through antioxidant systems that utilize cofactor NADPH. Cells must stabilize NADPH levels by increasing flux through replenishing metabolic pathways like pentose phosphate (PP) pathway. Here, we investigate the mechanism enabling the rapid increase in NADPH supply by exposing Escherichia coli to hydrogen peroxide and quantifying the immediate metabolite dynamics. To systematically infer active regulatory interactions governing this response, we evaluated ensembles of kinetic models of glycolysis and PP pathway, each with different regulation mechanisms. Besides the known inactivation of glyceraldehyde 3-phosphate dehydrogenase by ROS, we reveal the important allosteric inhibition of the first PP pathway enzyme by NADPH. This NADPH feedback inhibition maintains a below maximum-capacity PP pathway flux under non-stress conditions. Relieving this inhibition instantly increases PP pathway flux upon oxidative stress. We demonstrate that reducing cells' capacity to rapidly reroute their flux through the PP pathway increases their oxidative stress sensitivity. PMID: 29753645 [PubMed - as supplied by publisher]

A network pharmacology-integrated metabolomics strategy for clarifying the difference between effective compounds of raw and processed Farfarae flos by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry.

Sun, 13/05/2018 - 12:49
Related Articles A network pharmacology-integrated metabolomics strategy for clarifying the difference between effective compounds of raw and processed Farfarae flos by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry. J Pharm Biomed Anal. 2018 May 04;156:349-357 Authors: Ding M, Li Z, Yu XA, Zhang D, Li J, Wang H, He J, Gao XM, Chang YX Abstract This study aimed to clarify the difference between the effective compounds of raw and processed Farfarae flos using a network pharmacology-integrated metabolomics strategy. First, metabolomics data were obtained by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS). Then, metabolomics analysis was developed to screen for the influential compounds that were different between raw and processed Farfarae flos. Finally, a network pharmacology approach was applied to verify the activity of the screened compounds. As a result, 4 compounds (chlorogenic acid, caffeic acid, rutin and isoquercitrin) were successfully screened, identified, quantified and verified as the most influential effective compounds. They may synergistically inhibit the p38, JNK and ERK-mediated pathways, which would induce the inhibition of the expression of the IFA virus. The results revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful tool for discovering the effective compounds that were responsible for the difference between raw and processed Chinese herbs. PMID: 29753281 [PubMed - as supplied by publisher]

Identification and efficacy of glycine, serine and threonine metabolism in potentiating kanamycin-mediated killing of Edwardsiella piscicida.

Sun, 13/05/2018 - 12:49
Related Articles Identification and efficacy of glycine, serine and threonine metabolism in potentiating kanamycin-mediated killing of Edwardsiella piscicida. J Proteomics. 2018 May 09;: Authors: Ye JZ, Lin XM, Cheng ZX, Su YB, Li WX, Ali FM, Zheng J, Peng B Abstract We previously showed that glucose potentiated kanamycin to kill multidrug-resistant Edwardsiella piscicida through activation of the TCA cycle. However, whether other regulatory mechanism is involved requires further investigation. By quantitative proteomics technology, iTRAQ, we systematically mapped the altered proteins in the presence of glucose and identified 94 differentially expressed proteins. The analysis of the altered proteins by pathways, amino acid biosynthesis and metabolism were enriched. And the most significantly altered eight amino acids tyrosine, phenylalanine, valine, leucine, isoleucine, glycine, serine and threonine were investigated for their potentiation of kanamycin to kill EIB202, where glycine, serine and threonine showed the strongest efficacy than the others. The combinations of glycine and serine or glucose with glycine, serine or threonine had the best effects. Moreover, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and succinate dehydrogenase activities were increased as well as the proton motive force (PMF) and intracellular kanamycin. Finally, inhibitors that disrupt PMF production abolished the potentiation. These results shed light on the mechanism of how glucose promoting the amino acids biosynthesis and metabolism to potentiate kanamycin to kill antibiotic-resistant bacteria. More importantly, our results suggested that adjusting amino acid biosynthesis and metabolism might be a strategy to become phenotypic resistance to antibiotics in bacteria. SIGNIFICANCE: Tackling antibiotic resistance is an emerging issue in current years. Despite the efforts made toward developing new antibiotics, the progress is still lagged behind expectation. Novel strategies are required. The use of metabolite to revert antibiotic resistant is highly appreciated in recent years due to the less toxicity, more economic and high efficacy. As a continued study of our previous report on glucose potentiating kanamycin to kill antibiotic-resistant bacteria. The current study further expands the previous discovery on the mechanism of how glucose potentiate this effect. This result provides more basis on the action of glucose in reverting antibiotic resistance. And more importantly, we may derive more metabolites other than glucose to manage antibiotic resistance. PMID: 29753025 [PubMed - as supplied by publisher]

Metabolomic Analysis of Overactive Bladder in Male Patients: Identification of Potential Metabolite Biomarkers.

Sun, 13/05/2018 - 12:49
Related Articles Metabolomic Analysis of Overactive Bladder in Male Patients: Identification of Potential Metabolite Biomarkers. Urology. 2018 May 09;: Authors: Shimura H, Mitsui T, Kira S, Ihara T, Sawada N, Nakagomi H, Miyamoto T, Tsuchiya S, Kanda M, Takeda M Abstract OBJECTIVES: To identify metabolites that are associated with an overactive bladder (OAB) using metabolomics. PATIENTS AND METHODS: A total of 58 males without apparent neurological disease completed 24-hr bladder diaries of their micturition behavior and International Prostate Symptom Score (IPSS) for the assessment of micturition behavior and lower urinary tract symptoms. Urgency was defined as an IPSS urgency score of ≥2 (OAB group), and patients with IPSS urgency scores of ≤1 belonged to the control group. A comprehensive study of plasma metabolites was also conducted using capillary electrophoresis time-of-flight mass spectrometry. Metabolite levels were compared between the control and OAB groups using the Mann-Whitney U test. Potential metabolite biomarkers were selected using multivariate logistic regression analysis. RESULTS: Of the 58 subjects, the control and OAB groups consisted of 32 and 26 males, respectively. Nocturnal urinary volume, 24-hr micturition frequency, nocturnal micturition frequency, and the nocturia index were significantly higher in the OAB group. Metabolomic analysis revealed 60 metabolites in the subjects' plasma. The levels of 11 metabolites differed between and the control and OAB groups. Multivariate analysis showed that an increased glutamate level and reduced arginine, glutamine, and inosine monophosphate levels are significantly associated with OAB in males. Reduced levels of asparagine and hydroxyproline could also be associated with OAB. CONCLUSIONS: Urgency is associated with abnormal metabolism. Analyses of amino acid profiles might aid the search for new treatment targets for OAB. PMID: 29752971 [PubMed - as supplied by publisher]

Metabolomic comparison between wild Ophiocordyceps Sinensis and artificial cultured Cordyceps militaris.

Sun, 13/05/2018 - 12:49
Related Articles Metabolomic comparison between wild Ophiocordyceps Sinensis and artificial cultured Cordyceps militaris. Biomed Chromatogr. 2018 May 11;:e4279 Authors: Chen L, Liu Y, Guo Q, Zheng Q, Zhang W Abstract In this study, a systematic research on the metabolome differences between wild Ophiocordyceps sinensis (O. sinensis) and artificial cultured Cordyceps militaris (C. militaris) was conducted using liquid chromatography-mass spectrometry. Principal components analysis (PCA) and Orthogonal projection on latent structure-discriminant analysis (OPLS-DA) results showed that C. militaris grown on solid rice medium (R-CM) and C. militaris grown on tussah pupa (T-CM) evidently separated and individually separated from wild O. sinensis, indicating the metabolome difference among wild O. sinensis, R-CM and T-CM. The metabolome differences between R-CM and T-CM indicated that C. militaris could accommodate to culture medium by different metabolic regulation. Hierarchical clustering analysis (HCA) was further performed to cluster the differential metabolites and samples based on their metabolic similarity. The higher content of amino acids (pyroglutamic acid, glutamic acid, histidine, phenylalanine and arginine), unsaturated fatty acid (linolenic acid and linoleic acid), peptides, mannitol, adenosine and succinoadenosine in O. sinensis make it as an excellent choice as traditional Chinese medicine for invigoration or nutritional supplementation. Similar compositions with O. sinensis and easy cultivation make artificial cultured C. militaris possible as alternatives as O. sinensis. PMID: 29752731 [PubMed - as supplied by publisher]

NMR metabolomic study of blood plasma in ischemic and ischemically preconditioned rats: an increased level of ketone bodies and decreased content of glycolytic products 24 h after global cerebral ischemia.

Sun, 13/05/2018 - 12:49
Related Articles NMR metabolomic study of blood plasma in ischemic and ischemically preconditioned rats: an increased level of ketone bodies and decreased content of glycolytic products 24 h after global cerebral ischemia. J Physiol Biochem. 2018 May 11;: Authors: Baranovicova E, Grendar M, Kalenska D, Tomascova A, Cierny D, Lehotsky J Abstract Cardiac arrest is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia at global level is essential for the prevention and ischemic patient's treatment. In this study, we used a global cerebral ischemia induced by four-vessel occlusion as an established animal model for ischemic stroke to investigate metabolic changes after 24 h reperfusion, when transitions occur due to the onset of delayed neuronal death. We also focused on the endogenous phenomenon known as ischemic tolerance by the pre-ischemic treatment. The experiments were carried out on blood plasma samples as easily available and metabolically reflecting the overall changes in injured organism. Our results imply that disturbed glycolysis pathway, as a consequence of ischemic injury, leads to the increased level of ketone bodies (acetone, acetoacetate and β-hydroxybutyrate) along with increased utilization of triacylglycerols in plasma of ischemic and ischemically preconditioned rats. Complementary to, a decreased level of glycolytic intermediates (lactate, pyruvate, acetate) with increased level of glucose was found in ischemic and preconditioned animals. The protective effect of ischemic preconditioning on metabolome recovery was demonstrated by significantly increased level of creatine compared to ischemic, non-preconditioned rats. We also document that acetoacetate, pyruvate, lactate, and leucine have the best discriminatory power between ischemic and control plasma. Conclusively, our results provide evidence that NMR spectra analysis can identify specific group of metabolites present in plasma with the capability for discrimination between individual groups of animals. In addition, an excellent feasibility for the statistical discrimination among ischemic, preconditioned, and control rats can be applied regardless of native or deproteinated plasma and also regardless of noesy or cpmg NMR acquisition. PMID: 29752707 [PubMed - as supplied by publisher]

Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models.

Sun, 13/05/2018 - 12:49
Related Articles Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models. Chin J Integr Med. 2018 May;24(5):390-398 Authors: Liu L, Wang LP, He S, Ma Y Abstract Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of IgE antibodies by B cells and a decrease of the interferon-γ/interleukin-4 (Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine (CM) research on the mechanisms and effificacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the PubMed and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specifific immunoglobulin E, inflflammatory cell infifiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM. PMID: 29752613 [PubMed - in process]

TG2 regulates the heat-shock response by the post-translational modification of HSF1.

Sun, 13/05/2018 - 12:49
Related Articles TG2 regulates the heat-shock response by the post-translational modification of HSF1. EMBO Rep. 2018 May 11;: Authors: Rossin F, Villella VR, D'Eletto M, Farrace MG, Esposito S, Ferrari E, Monzani R, Occhigrossi L, Pagliarini V, Sette C, Cozza G, Barlev NA, Falasca L, Fimia GM, Kroemer G, Raia V, Maiuri L, Piacentini M Abstract Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter. We show that the inhibition of TG2 restores the unbalance in HSF1-HSP70 pathway in cystic fibrosis (CF), a human disorder characterized by deregulation of proteostasis. The absence of TG2 leads to an increase of about 40% in CFTR function in a new experimental CF mouse model lacking TG2. Altogether, these results indicate that TG2 plays a key role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat-shock response. PMID: 29752334 [PubMed - as supplied by publisher]

Mass Spectrometric Identification of Urinary Biomarkers of Pulmonary Tuberculosis.

Sun, 13/05/2018 - 12:49
Related Articles Mass Spectrometric Identification of Urinary Biomarkers of Pulmonary Tuberculosis. EBioMedicine. 2018 Apr 22;: Authors: Isa F, Collins S, Lee MH, Decome D, Dorvil N, Joseph P, Smith L, Salerno S, Wells MT, Fischer S, Bean JM, Pape JW, Johnson WD, Fitzgerald DW, Rhee KY Abstract BACKGROUND: Tuberculosis (TB) is the leading infectious cause of death worldwide. A major barrier to control of the pandemic is a lack of clinical biomarkers with the ability to distinguish active TB from healthy and sick controls and potential for development into point-of-care diagnostics. METHODS: We conducted a prospective case control study to identify candidate urine-based diagnostic biomarkers of active pulmonary TB (discovery cohort) and obtained a separate blinded "validation" cohort of confirmed cases of active pulmonary TB and controls with non-tuberculous pulmonary disease for validation. Clean-catch urine samples were collected and analyzed using high performance liquid chromatography-coupled time-of-flight mass spectrometry. RESULTS: We discovered ten molecules from the discovery cohort with receiver-operator characteristic (ROC) area-under-the-curve (AUC) values >85%. These 10 molecules also significantly decreased after 60 days of treatment in a subset of 20 participants followed over time. Of these, a specific combination of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine exhibited ROC AUCs >80% in a blinded validation cohort of participants with active TB and non-tuberculous pulmonary disease. CONCLUSION: Urinary levels of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine distinguished patients with tuberculosis from healthy controls and patients with non-tuberculous pulmonary diseases, providing a potential noninvasive biosignature of active TB. FUNDING: This study was funded by Weill Cornell Medicine, the National Institute of Allergy and Infectious Diseases, the Clinical and Translational Science Center at Weill Cornell, the NIH Fogarty International Center grants, and the NIH Tuberculosis Research Unit (Tri-I TBRU). PMID: 29752217 [PubMed - as supplied by publisher]

Blood biomarkers in Alzheimer's disease.

Sun, 13/05/2018 - 12:49
Related Articles Blood biomarkers in Alzheimer's disease. Neurologia. 2018 May 08;: Authors: Altuna-Azkargorta M, Mendioroz-Iriarte M Abstract INTRODUCTION: The early diagnosis of Alzheimer's disease (AD) via the use of biomarkers could facilitate the implementation and monitoring of early therapeutic interventions with the potential capacity to significantly modify the course of the disease. DEVELOPMENT: Classic cerebrospinal fluid biomarkers and approved structural and functional neuroimaging have a limited clinical application given their invasive nature and/or high cost. The identification of more accessible and less costly biomarkers, such as blood biomarkers, would facilitate application in clinical practice. We present a literature review of the main blood biochemical biomarkers with potential use for diagnosing Alzheimer's disease. CONCLUSIONS: Blood biomarkers are cost and time effective with regard to cerebrospinal fluid biomarkers. However, the immediate applicability of blood biochemical biomarkers in clinical practice is not very likely. The main limitations come from the difficulties in measuring and standardising thresholds between different laboratories and in failures to replicate results. Among all the molecules studied, apoptosis and neurodegeneration biomarkers and the biomarker panels obtained through omics approaches, such as isolated or combined metabolomics, offer the most promising results. PMID: 29752036 [PubMed - as supplied by publisher]

NMR-based metabolic study of fruits of Physalis peruviana L. grown in eight different Peruvian ecosystems.

Sun, 13/05/2018 - 12:49
Related Articles NMR-based metabolic study of fruits of Physalis peruviana L. grown in eight different Peruvian ecosystems. Food Chem. 2018 Oct 01;262:94-101 Authors: Maruenda H, Cabrera R, Cañari-Chumpitaz C, Lopez JM, Toubiana D Abstract The berry of Physalis peruviana L. (Solanaceae) represents an important socio-economical commodity for Latin America. The absence of a clear phenotype renders it difficult to trace its place of origin. In this study, Cape gooseberries from eight different regions within the Peruvian Andes were profiled for their metabolism implementing a NMR platform. Twenty-four compounds could be unequivocally identified and sixteen quantified. One-way ANOVA and post-hoc Tukey test revealed that all of the quantified metabolites changed significantly among regions: Bambamarca I showed the most accumulated significant differences. The coefficient of variation demonstrated high phenotypic plasticity for amino acids, while sugars displayed low phenotypic plasticity. Correlation analysis highlighted the closely coordinated behavior of the amino acid profile. Finally, PLS-DA revealed a clear separation among the regions based on their metabolic profiles, accentuating the discriminatory capacity of NMR in establishing significant phytochemical differences between producing regions of the fruit of P. peruviana L. PMID: 29751927 [PubMed - in process]

Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline.

Sun, 13/05/2018 - 12:49
Related Articles Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline. Respir Res. 2018 May 11;19(1):94 Authors: Zheng HK, Zhao JH, Yan Y, Lian TY, Ye J, Wang XJ, Wang Z, Jing ZC, He YY, Yang P Abstract BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. METHOD: A single subcutaneous injection of monocrotaline (MCT) (60 mg kg- 1) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. RESULTS: Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. CONCLUSION: The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile. PMID: 29751839 [PubMed - in process]

Xanthones Content in Swertia multicaulis D. Don from Nepal.

Sun, 13/05/2018 - 12:49
Related Articles Xanthones Content in Swertia multicaulis D. Don from Nepal. Molecules. 2018 May 03;23(5): Authors: Timsina B, Kindlmann P, Rokaya MB, Vrchotová N, Tříska J, Horník Š, Sýkora J Abstract The medicinal plant Swertia multicaulis D. Don was collected in Rasuwa District (Nepal) and the xanthone content of its ethyl acetate extracts was studied. The total amount of xanthones in S. multicaulis determined by HPLC reaches almost 13 g of xanthones per 1 kg of dry matter. The identification of xanthones in S. multicaulis was achieved by a combination of HPLC, LC⁻MS and LC⁻NMR. The final assignment of the individual chemical structures was provided by NMR, supported by preparative HPLC. In eight chromatographic peaks, four major xanthones were identified—1,3-dihydroxy-5,8-dimethoxyxanthone, 1-hydroxy-3,5,8-trimethoxyxanthone, bellidifolin (1,5,8-tri-hydroxy-3-methoxyxanthone), and decussatin (1-hydroxy-3,7,8-trimethoxyxanthone). PMID: 29751500 [PubMed - in process]

Procyanidin B2 protects against d-galactose-induced mimetic aging in mice: Metabolites and microbiome analysis.

Sat, 12/05/2018 - 12:28
Related Articles Procyanidin B2 protects against d-galactose-induced mimetic aging in mice: Metabolites and microbiome analysis. Food Chem Toxicol. 2018 May 08;: Authors: Xiao Y, Dong J, Yin Z, Wu Q, Zhou Y, Zhou X Abstract To elucidate the possible mechanisms for the preventive effect of procyanidin B2 on aging, a combined analysis of metabolic profile and gut microbiome was carried out in the present study. The mimetic aged mice induced by d-galactose injection (500 mg/kg, sc daily), and the preventive group was fed with the diet plus 0.2% procyanidin B2. After 7 weeks of treatment, the spatial memory was assayed using the Morris water maze test. Procyanidin B2 significantly ameliorated the impaired memory and antioxidant abilities induced by d-galactose. Furthermore, metabolomics analysis of plasma based on LC/Q-TOF-MS demonstrated that phosphatidyl cholines, oleic acid, linoleic acid, carnitine, pantothenic acid, and taurocholic acid were significantly increased in the mice treated with procyanidin B2, and pyruvic acid, hydroxybutyric acid, hippuric acid, and cholic acid were decreased significantly. Together, gut microbiome analysis using Illumina sequencing showed that there were significant differences in the Firmicutes/Bacteroidetes ratio and abundance of Roseburia, Lachnospiraceae, and Bifidobacterium between the aging and supplemental procyanidin B2 groups. In summary, procyanidin B2 possessed potential prevention of the cognitive and oxidative impairment via the metabolic pathway regulation related to glycolysis, fatty acid, and bile acid in the aged mice, accompanied by remodeling the gut flora. PMID: 29751077 [PubMed - as supplied by publisher]

Metabolomics analysis of the potential anticancer mechanism of annonaceous acetogenins on a multidrug resistant mammary adenocarcinoma cell.

Sat, 12/05/2018 - 12:28
Related Articles Metabolomics analysis of the potential anticancer mechanism of annonaceous acetogenins on a multidrug resistant mammary adenocarcinoma cell. Anal Biochem. 2018 May 08;: Authors: Ma C, Li Y, Wu H, Ji J, Sun Q, Song Y, Wang S, Li X, Chen Y, Chen J Abstract Although annonaceous acetogenins (ACGs) have been reported to have antitumor activity for over three decades, and many of the underlying mechanism of ACGs on cancer have been clarified, there are still outstanding issues. In particular, the changes of small metabolite in cancer cells, caused by ACGs intake, have been reported rarely. Recent research has showed that cellular metabolic profiling coupled with ultra-flow liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UFLC-Q-TOF-MS) and multivariable statistical analysis enables a good understanding of ACGs' effects on multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells. As a result, 23 potential biomarkers (p < 0.05, VIP >1) were identified, and 5 pathways (impact-value > 0.10) identified. The differential metabolites suggested that ACGs affected metabolomics pathways, including arginine and proline metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism and D-Glutamine and D-glutamate metabolism. PMID: 29750943 [PubMed - as supplied by publisher]

Saliva in the "Omics" era: a promising tool in Paediatrics.

Sat, 12/05/2018 - 12:28
Related Articles Saliva in the "Omics" era: a promising tool in Paediatrics. Oral Dis. 2018 May 11;: Authors: Pappa E, Kousvelari E, Vastardis H Abstract In vulnerable populations, such as infants and children, saliva makes the perfect diagnostic medium because of its non-invasive collection, easy handling and storage of samples. Its unique biomarker profiles help tremendously in the diagnosis of many diseases and conditions. In fact, saliva genomics, proteomics, transcriptomics, metabolomics and microbiome-based discoveries have led to complementary and powerful diagnostic information. In children and neonates, saliva is the preferred medium not only for diagnosis of caries and aggressive periodontitis but also for a number of systemic conditions, metabolic diseases, cognitive functions, stress assessment and evaluation of immunological and inflammatory responses to vaccination. In this review, we provide an overview of current and future applications of saliva diagnostics to various diseases and conditions and highlight studies in paediatrics across the "omic" spectrum. Emerging frontiers in salivary diagnostics research that may significantly advance the field are also highlighted. This article is protected by copyright. All rights reserved. PMID: 29750386 [PubMed - as supplied by publisher]

Gut microbial diversity is associated with lower arterial stiffness in women.

Sat, 12/05/2018 - 12:28
Related Articles Gut microbial diversity is associated with lower arterial stiffness in women. Eur Heart J. 2018 May 09;: Authors: Menni C, Lin C, Cecelja M, Mangino M, Matey-Hernandez ML, Keehn L, Mohney RP, Steves CJ, Spector TD, Kuo CF, Chowienczyk P, Valdes AM Abstract Aims: The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness. Methods and results: We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= -0.25(0.07), P = 1 × 10-4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing-two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3-12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions: Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing. PMID: 29750272 [PubMed - as supplied by publisher]

Metabolomics study of the therapeutic mechanism of Schisandra chinensis lignans on aging rats induced by d-galactose.

Sat, 12/05/2018 - 12:28
Related Articles Metabolomics study of the therapeutic mechanism of Schisandra chinensis lignans on aging rats induced by d-galactose. Clin Interv Aging. 2018;13:829-841 Authors: Sun J, Jing S, Jiang R, Wang C, Zhang C, Chen J, Li H Abstract Objective: The aim of this study was to evaluate the antiaging effect of Schisandra chinensis lignans (SCL) by analyzing the characteristics in the serum of d-galactose (d-gal)-induced rats. Methods: Forty male Wistar rats were randomly divided into control group, d-gal model group, low-dose SCL group (50 mg/kg/d), medium-dose SCL group (100 mg/kg/d), and high-dose SCL group (200 mg/kg/d). A serum metabolomics analysis method based on rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry was carried out to study the characteristics of d-gal-induced aging rats and evaluate the antiaging effects of SCL, and multivariate statistical analysis was performed for pattern recognition and characteristic metabolites identification. The relative levels of p19, p53, and p21 genes in the brain tissue were measured by quantitative real-time polymerase chain reaction for investigating the underlying mechanism. Results: Metabolomics analysis showed that 15 biomarkers were identified and 13 of them recovered to the normal levels after the administration of SCL. Based on the pathway analysis, the antiaging mechanisms of SCL might be involved in the following metabolic pathways: energy, amino acid, lipid, and phospholipid metabolism. Furthermore, SCL significantly inhibited the mRNA expression level of p19, p53, and p21 in the brain of aging rats induced by d-gal. Conclusion: These results suggest that SCL can delay rat aging induced by d-gal through multiple pathways. PMID: 29750025 [PubMed - in process]

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