PubMed

Alteration in Metabolic Signature and Lipid Metabolism in Patients with Angina Pectoris and Myocardial Infarction. PLoS One. 2015;10(8):e0135228 Authors: Park JY, Lee SH, Shin MJ, Hwang GS Abstract Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD. PMID: 26258408 [PubMed - as supplied by publisher]

Related Articles Coping with drought: stress and adaptive responses in potato and perspectives for improvement. Front Plant Sci. 2015;6:542 Authors: Obidiegwu JE, Bryan GJ, Jones HG, Prashar A Abstract Potato (Solanum tuberosum L.) is often considered as a drought sensitive crop and its sustainable production is threatened due to frequent drought episodes. There has been much research aiming to understand the physiological, biochemical, and genetic basis of drought tolerance in potato as a basis for improving production under drought conditions. The complex phenotypic response of potato plants to drought is conditioned by the interactive effects of the plant's genotypic potential, developmental stage, and environment. Effective crop improvement for drought tolerance will require the pyramiding of many disparate characters, with different combinations being appropriate for different growing environments. An understanding of the interaction between below ground water uptake by the roots and above ground water loss from the shoot system is essential. The development of high throughput precision phenotyping platforms is providing an exciting new tool for precision screening, which, with the incorporation of innovative screening strategies, can aid the selection and pyramiding of drought-related genes appropriate for specific environments. Outcomes from genomics, proteomics, metabolomics, and bioengineering advances will undoubtedly compliment conventional breeding strategies and presents an alternative route toward development of drought tolerant potatoes. This review presents an overview of past research activity, highlighting recent advances with examples from other crops and suggesting future research directions. PMID: 26257752 [PubMed]

Related Articles Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights. Tetrahedron Lett. 2015 Jun 3;56(23):3246-3250 Authors: Li SG, Vilchèze C, Chakraborty S, Wang X, Kim H, Anisetti M, Ekins S, Rhee KY, Jacobs WR, Freundlich JS Abstract The metabolic instability of an antitubercular small molecule CD117 was addressed through iterative alteration of a key sulfide substituent and interrogation of the effect on growth inhibition of cultured Mycobacterium tuberculosis. This process was informed by studies of the intramycobacterial metabolism of CD117 and its inactive carboxylic acid derivative. Isoxazole 4e and thiazole 4m demonstrated significant gains in mouse liver microsomal stability with slight losses in whole-cell activity. This work illustrates the challenges of antitubercular hit evolution, requiring a balance of chemical and biological insights. PMID: 26257441 [PubMed - as supplied by publisher]

Related Articles Metabolomics-proteomics profiles delineate metabolic changes in kidney fibrosis disease. Proteomics. 2015 Aug 10; Authors: Cao H, Zhang A, Sun H, Zhou X, Guan Y, Liu Q, Kong L, Wang X Abstract Kidney fibrosis (KF) is a common process that leads to the progression of various types of kidney disease including kidney-yang deficiency syndrome, however, little is known regarding the underlying biology of this disorder. Fortunately, integrated omics approaches provide the molecule fingerprints related to the disease. In an attempt to address this issue, we integrated metabolomics- proteomics profiles analyzed pathogenic mechanisms of KF based on rat model. A total 37 serum differential metabolites were contributed to KF progress, involved several important metabolic pathways. Using iTRAQ-based quantitative proteomics analysis, 126 differential serum proteins were identified and provide valuable insight into the underlying mechanisms of KF. These proteins appear to be involved in complement and coagulation cascades, regulation of actin cytoskeleton, MAPK signaling pathway, RNA transport, etc. Interestingly, pathway/pathway analysis of integrated proteomics and metabolomics data firstly reveals that these signaling pathways were closely related with KF. It further indicated that most of these proteins play a pivotal role in the regulation of metabolism pathways. This article is protected by copyright. All rights reserved. PMID: 26256572 [PubMed - as supplied by publisher]

Related Articles Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Metabolism. 2015 Jul 3; Authors: Wojczynski MK, Parnell LD, Pollin TI, Lai CQ, Feitosa MF, O'Connell JR, Frazier-Wood AC, Gibson Q, Aslibekyan S, Ryan KA, Province MA, Tiwari HK, Ordovas JM, Shuldiner AR, Arnett DK, Borecki IB Abstract OBJECTIVE: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a genome-wide association (GWA) study in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). METHODS: The GOLDN GWAS discovery sample consisted of 872 participants within families of European ancestry. Genotypes for 2,543,887 variants were measured or imputed from HapMap. Replication of our top results was performed in the Heredity and Phenotype Intervention (HAPI) Heart Study (n = 843). PPL TG response phenotypes were constructed from plasma TG measured at baseline (fasting, 0 hour), 3.5 and 6 hours after a high-fat meal, using a random coefficient regression model. Association analyses were adjusted for covariates and principal components, as necessary, in a linear mixed model using the kinship matrix; additional models further adjusted for fasting TG were also performed. Meta-analysis of the discovery and replication studies (n = 1715) was performed on the top SNPs from GOLDN. RESULTS: GOLDN revealed 111 suggestive (p < 1E-05) associations, with two SNPs meeting GWA significance level (p < 5E-08). Of the two significant SNPs, rs964184 demonstrated evidence of replication (p = 1.20E-03) in the HAPI Heart Study and in a joint analysis, was GWA significant (p = 1.26E-09). Rs964184 has been associated with fasting lipids (TG and HDL) and is near ZPR1 (formerly ZNF259), close to the APOA1/C3/A4/A5 cluster. This association was attenuated upon additional adjustment for fasting TG. CONCLUSION: This is the first report of a genome-wide significant association with replication for a novel phenotype, namely PPL TG response. Future investigation into response phenotypes is warranted using pathway analyses, or newer genetic technologies such as metabolomics. PMID: 26256467 [PubMed - as supplied by publisher]

Related Articles Implications of microbiota and bile acid in liver injury and regeneration. J Hepatol. 2015 Aug 6; Authors: Liu HX, Keane R, Sheng L, Wan YY Abstract Studies examining the mechanisms by which the liver injures and regenerates usually focus on factors and pathways within the liver, neglecting the signaling derived from the gut-liver axis. The intestinal content is rich in microorganisms as well as metabolites generated from both the host and colonizing bacteria. Via the gut-liver axis, this complex "soup" exerts an immense impact on liver integrity and function. This review article summarizes data published in the past 30 years that have demonstrated the signaling derived from the gut-liver axis in relation to liver injury and regeneration. Despite many correlative findings, the intricate networks of pathways involved along with a scarcity of mechanistic data urgently require nutrigenomic, metabolomics, and microbiota profiling approaches to provide a deep understanding of the interplay between nutrition, bacteria, and host response. Such knowledge would better elucidate the molecular mechanisms that link microbiota alteration to host physiological response and vice-versa. PMID: 26256437 [PubMed - as supplied by publisher]

Related Articles A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis. Hepatobiliary Pancreat Dis Int. 2015 Aug;14(4):413-21 Authors: Lian JS, Liu W, Hao SR, Chen DY, Wang YY, Yang JL, Jia HY, Huang JR Abstract BACKGROUND: Because of the diversity of the clinical and laboratory manifestations, the diagnosis of autoimmune liver disease (AILD) remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), differed between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS: Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and orthogonal partial least squares discrimination analysis. RESULTS: The partial least squares discrimination analysis model (R2Y=0.991, Q2=0.943) was established between the AIH and PBC groups and exhibited both sensitivity and specificity of 100%. Five groups of biomarkers were identified, including bile acids, free fatty acids, phosphatidylcholines, lysolecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy control group. The other biomarkers decreased in the AIH and PBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS: The biomarkers identified revealed the pathophysiological changes in AILD and helped to discriminate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD. PMID: 26256087 [PubMed - in process]

Related Articles NMR-Based Metabolomic Study on Isatis tinctoria: Comparison of Different Accessions, Harvesting Dates, and the Effect of Repeated Harvesting. J Nat Prod. 2015 May 22;78(5):977-86 Authors: Guldbrandsen N, Kostidis S, Schäfer H, De Mieri M, Spraul M, Skaltsounis AL, Mikros E, Hamburger M Abstract Isatis tinctoria is an ancient dye and medicinal plant with potent anti-inflammatory and antiallergic properties. Metabolic differences were investigated by NMR spectroscopy of accessions from different origins that were grown under identical conditions on experimental plots. For these accessions, metabolite profiles at different harvesting dates were analyzed, and single and repeatedly harvested plants were compared. Leaf samples were shock-frozen in liquid N2 immediately after being harvested, freeze-dried, and cryomilled prior to extraction. Extracts were prepared by pressurized liquid extraction with ethyl acetate and 70% aqueous methanol. NMR spectra were analyzed using a combination of different methods of multivariate data analysis such as principal component analysis (PCA), canonical analysis (CA), and k-nearest neighbor concept (k-NN). Accessions and harvesting dates were well separated in the PCA/CA/k-NN analysis in both extracts. Pairwise statistical total correlation spectroscopy (STOCSY) revealed unsaturated fatty acids, porphyrins, carbohydrates, indole derivatives, isoprenoids, phenylpropanoids, and minor aromatic compounds as the cause of these differences. In addition, the metabolite profile was affected by the repeated harvest regime, causing a decrease of 1,5-anhydroglucitol, sucrose, unsaturated fatty acids, porphyrins, isoprenoids, and a flavonoid. PMID: 25946005 [PubMed - indexed for MEDLINE]

Related Articles Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats. Toxicol Appl Pharmacol. 2015 Jul 15;286(2):65-79 Authors: Miller DB, Karoly ED, Jones JC, Ward WO, Vallanat BD, Andrews DL, Schladweiler MC, Snow SJ, Bass VL, Richards JE, Ghio AJ, Cascio WE, Ledbetter AD, Kodavanti UP Abstract Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O3) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O3 at 0.25, 0.50, or 1.0ppm, 6h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0ppm O3, 6h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18h post-exposure. O3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18h-post second exposure. O3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O3. In conclusion, short-term O3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress-response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. PMID: 25838073 [PubMed - indexed for MEDLINE]

Related Articles Structural analysis of an intact monoclonal antibody by online electrochemical reduction of disulfide bonds and Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem. 2014 Jun 3;86(11):5376-82 Authors: Nicolardi S, Deelder AM, Palmblad M, van der Burgt YE Abstract Structural confirmation and quality control of recombinant monoclonal antibodies (mAbs) by top-down mass spectrometry is still challenging due to the size of the proteins, disulfide content, and post-translational modifications such as glycosylation. In this study we have applied electrochemistry (EC) to overcome disulfide bridge complexity in top-down analysis of mAbs. To this end, an electrochemical cell was coupled directly to an electrospray ionization (ESI) source and a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer (MS) equipped with a 15 T magnet. By performing online EC-assisted reduction of interchain disulfide bonds in an intact mAb, the released light chains could be selected for tandem mass spectrometry (MS/MS) analysis without interference from heavy-chain fragments. Moreover, the acquisition of full MS scans under denaturing conditions allowed profiling of all abundant mAb glycoforms. Ultrahigh-resolution FTICR-MS measurements provided fully resolved isotopic distributions of intact mAb and enabled the identification of the most abundant adducts and other interfering species. Furthermore, it was found that reduction of interchain disulfide bonds occurs in the ESI source dependent on capillary voltage and solvent composition. This phenomenon was systematically evaluated and compared with the results obtained from reduction in the electrochemical cell. PMID: 24780057 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic biomarkers in diabetic kidney diseases-A systematic review. J Diabetes Complications. 2015 Jul 9; Authors: Zhang Y, Zhang S, Wang G Abstract Diabetic kidney disease (DKD) is generally characterized by increasing albuminuria in diabetic patients; however, few biomarkers are available to facilitate early diagnosis of this disease. The application of metabolomics has shown promises addressing this need. In this review, we conducted a search about metabolomic biomarkers in DKD patients through MEDLINE, EMBASE, and Cochrane Database up to the end of March, 2015. 12 eligible studies were selected and evaluated subsequently through the use of QUADOMICS, a quality assessment tool. 7 of the 12 included studies were classified as 'high quality'. We also recorded specific study characteristics including participants' characteristics, metabolomic techniques, sample types, and significantly altered metabolites between DKD and control groups. Products of lipid metabolisms including esterified and non-esterified fatty acids, carnitines, phospholipids and metabolites involved in branch-chained amino acids and aromatic amino acids metabolisms were frequently affected biomarkers of DKD. Other differential metabolites were also found, while some of their associations with DKD were unclear. Further more studies are required to test these findings in larger, diverse ethnic populations with elaborate study designs, and finally we could translate them into the benefits of DKD patients. PMID: 26253264 [PubMed - as supplied by publisher]

Related Articles Metabolomics analysis reveals the association between lipid abnormalities and oxidative stress, inflammation, fibrosis, and Nrf2 dysfunction in aristolochic acid-induced nephropathy. Sci Rep. 2015;5:12936 Authors: Zhao YY, Wang HL, Cheng XL, Wei F, Bai X, Lin RC, Vaziri ND Abstract Alternative medicines are commonly used for the disease prevention and treatment worldwide. Aristolochic acid (AAI) nephropathy (AAN) is a common and rapidly progressive interstitial nephropathy caused by ingestion of Aristolochia herbal medications. Available data on pathophysiology and molecular mechanisms of AAN are limited and were explored here. SD rats were randomized to AAN and control groups. AAN group was treated with AAI by oral gavage for 12 weeks and observed for additional 12 weeks. Kidneys were processed for histological evaluation, Western blotting, and metabolomics analyses using UPLC-QTOF/HDMS. The concentrations of two phosphatidylcholines, two diglycerides and two acyl-carnitines were significantly altered in AAI treated rats at week 4 when renal function and histology were unchanged. Data obtained on weeks 8 to 24 revealed progressive tubulointerstitial fibrosis, inflammation, renal dysfunction, activation of NF-κB, TGF-β, and oxidative pathways, impaired Nrf2 system, and profound changes in lipid metabolites including numerous PC, lysoPC, PE, lysoPE, ceramides and triglycerides. In conclusion, exposure to AAI results in dynamic changes in kidney tissue fatty acid, phospholipid, and glycerolipid metabolisms prior to and after the onset of detectable changes in renal function or histology. These findings point to participation of altered tissue lipid metabolism in the pathogenesis of AAN. PMID: 26251179 [PubMed - in process]

Related Articles The role of vitamin D in reducing gastrointestinal disease risk and assessment of individual dietary intake needs: focus on genetic and genomic technologies. Mol Nutr Food Res. 2015 Aug 7; Authors: Ferguson LR, Laing B, Marlow G, Bishop K Abstract With the endogenous formation of vitamin D being significantly curtailed because of public awareness of skin cancer dangers, attention is turning to dietary sources. Cumulative evidence has implicated vitamin D deficiency in increasing susceptibility to various gastrointestinal disorders, including colorectal cancer, inflammatory bowel diseases, diverticulitis and irritable bowel syndrome. There is also reason to suggest adjunct vitamin D therapy for such diseases. Although there is justification for increasing vitamin D intake overall, optimal intakes will vary among individuals. Genomic technologies have revealed several hundreds of genes associated with vitamin D actions. The nature of these genes emphasizes the potentially negative implications of modulating vitamin D intakes in the absence of complementary human genetic and genomic data, including information on the gut microbiome. However, we are not yet in a position to apply this information. Genomic data (transcriptomics, metabolomics, proteomics and metagenomics) could provide evidence that vitamin D sufficiency has been achieved. We suggest that there is an increasingly strong case for considering the more widespread use of vitamin D fortified foods and/and dietary supplements to benefit gastrointestinal health. However, intake levels might beneficially be informed by personalized genetic and genomic information, for optimal disease prevention and maintenance of remission. This article is protected by copyright. All rights reserved. PMID: 26251177 [PubMed - as supplied by publisher]

Related Articles Metabolism-Guided Bowel Resection: Potential Role and Accuracy of Instant Capillary Lactates to Identify the Optimal Resection Site. Surg Innov. 2015 Aug 5; Authors: Diana M, Noll E, Diemunsch P, Moussallieh FM, Namer IJ, Charles AL, Lindner V, Agnus V, Geny B, Marescaux J Abstract BACKGROUND: Strip-based handheld devices can measure lactatemia on capillary blood obtained by needle puncturing. We aimed to assess the kinetic of bowel capillary lactates, metabolomics profiling, and mitochondria respiratory rate in a prolonged model of bowel hypoperfusion. MATERIALS AND METHODS: In 6 pigs, a 3- to 4-cm ischemic segment was created in 6 small bowel loops (total = 36 loops) by clamping the vascular supply, for a duration of 1 to 6 hours. Hourly, 5 blood samples were obtained by puncturing the serosa, and lactates were measured using a handheld analyzer. Samples were made at the following regions of interest (ROIs): center of the ischemic area (1), proximal and distal clinical margins of resection (2a-2b), and vascularized zones (3a-3b). Every hour, surgical biopsies of ROIs were sampled. Activity of bowel mitochondria complexes was measured after 1, 3, and 5 hours of ischemia. Quantification of metabolites was performed on all samples (total N = 180). RESULTS: Capillary lactates were significantly higher at ROI 1 versus ROI 3ab at all time points. After 1 hour lactates at the margins were significantly higher than those at vascularized areas (P = .0095), showing a mismatch between visual assessment and actual perfusion status. From 2 to 6 hours, there was no difference in lactates between ROIs 2a-2b and 3a-3b. Maximal tissue respiration decreased significantly after 1 hour (ROI 1 vs ROI 3ab). Seven metabolites (lactate, glucose, aspartate, choline, creatine, taurine, and tyrosine) expressed significantly different evolutions between ROIs. CONCLUSIONS: Capillary lactates could help precisely estimate local bowel perfusion status. PMID: 26250483 [PubMed - as supplied by publisher]

Related Articles Metabolomics of cocaine: implications in toxicity. Toxicol Mech Methods. 2015 Aug 7;:1-7 Authors: Dinis-Oliveira RJ Abstract Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects. PMID: 26249365 [PubMed - as supplied by publisher]

Related Articles Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview. Cell Death Dis. 2015;6:e1846 Authors: Nardacci R, Perfettini JL, Grieco L, Thieffry D, Kroemer G, Piacentini M Abstract Infection by human immunodeficiency virus-1 (HIV-1) is associated with a progressive decrease in CD4 T-cell numbers and the consequent collapse of host immune defenses. The major pathogenic mechanism of AIDS is the massive apoptotic destruction of the immunocompetent cells, including uninfected cells. The latter process, also known as by-stander killing, operates by various mechanisms one of which involves the formation of syncytia which undergo cell death by following a complex pathway. We present here a detailed and curated map of the syncytial apoptosis signaling network, aimed at simplifying the whole mechanism that we have characterized at the molecular level in the last 15 years. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner software and encompasses 36 components (proteins/genes) and 54 interactions. The simplification of this complex network paves the way for the development of novel therapeutic strategies to eradicate HIV-1 infection. Agents that induce the selective death of HIV-1-elicited syncytia might lead to the elimination of viral reservoirs and hence constitute an important complement to current antiretroviral therapies. PMID: 26247731 [PubMed - in process]

Related Articles Characterization of metabolic profile of intact non-tumor and tumor breast cells by HR-MAS NMR spectroscopy. Anal Biochem. 2015 Aug 3; Authors: Maria RM, Altei WF, Andricopulo AD, Becceneri AB, Cominetti MR, Venâncio T, Colnago LA Abstract (1)H high-resolution magic angle spinning NMR ((1)H HR-MAS NMR) spectroscopy was used to analyze the metabolic profile of intact non-tumor breast cell line (MCF-10A) and intact breast tumor cell lines (MCF-7 and MDA-MB-231). In the spectra of MCF-10A cells six metabolites were assigned, with glucose and ethanol in higher concentration. Fifteen metabolites were assigned in MCF-7 and MDA-MB-231 (1)H HR-MAS NMR spectra. They did not show glucose and ethanol and the major component in both tumor cells was phosphocholine (higher in MDA-MB-231 than in MCF-7), which can be consider as a tumor biomarker of breast cancer malignant transformation. These tumor cells also show acetone signal that was higher in MDA-MB-231 than in MCF-7 cells. The high acetone level may be an indication of high demand for energy in MDA-MB-231 to maintain cell proliferation. The higher acetone and phosphocholine levels in MDA-MB-231cells, indicates the higher malignance of the cell line. Therefore, HR-MAS is a rapid, reproducible method to study the metabolic profile of intact breast cells, with minimal sample preparation and contamination, which are critical in the analyses of slow growth cells. PMID: 26247715 [PubMed - as supplied by publisher]

Related Articles MET-XAlign: A Metabolite Cross-alignment Tool for LC/MS-based Comparative Metabolomics. Anal Chem. 2015 Aug 6; Authors: Zhang W, Lei Z, Huhman D, Sumner LW, Zhao PX Abstract Liquid chromatography-mass spectrometry (LC/MS) metabolite profiling has been widely used in comparative metabolomics studies; however, LC/MS-based comparative metabolomics currently faces several critical challenges. One of the greatest challenges is how to effectively align metabolites across different LC/MS profiles; a single metabolite can give rise to multiple peak features, and the grouped peak features that can be used to construct a spectrum pattern of single metabolite can vary greatly between biochemical experiments and even between instrument runs. Another major challenge is that the observed retention time for a single metabolite can also be significantly affected by experimental conditions. To overcome these two key challenges, we present a novel metabolite-based alignment approach entitled MET-XAlign to align metabolites across LC/MS metabolomics profiles. MET-XAlign takes the deduced molecular mass and estimated compound retention time information that can be extracted by our previously published tool, MET-COFEA, and aligns metabolites based on this information. We demonstrate that MET-XAlign is able to cross-align metabolite compounds, either known or unknown, in LC/MS profiles not only across different samples, but also across different biological experiments, and different electrospray ionization modes. Therefore, our proposed metabolite-based cross-alignment approach is a great step forward and its implementation, MET-XAlign, is a very useful tool in LC/MS-based comparative metabolomics. MET-XAlign has been successfully implemented with core algorithm coding in C++, making it very efficient, and visualization interface coding in the Microsoft .NET Framework. The MET-XAlign software along with demonstrative data is freely available at http://bioinfo.noble.org/manuscript-support/met-xalign/. PMID: 26247233 [PubMed - as supplied by publisher]

Related Articles Metabolic Consequences of LDHA inhibition by Epigallocatechin Gallate and Oxamate in MIA PaCa-2 Pancreatic Cancer Cells. Metabolomics. 2015 Feb;11(1):71-80 Authors: Lu QY, Zhang L, Yee JK, Go VW, Lee WN Abstract Lactate dehydrogenase A (LDHA) is the enzyme that converts pyruvate to lactate and oxidizes the reduced form of nicotinamide adenine dinucleotide (NADH) to NAD(+). Several human cancers including the pancreas display elevated expression of LDHA. Because of its essential role in cancer metabolism, LDHA has been considered to be a potential target for cancer therapy. Recently, we have shown that a green tea extract significantly down-regulated LDHA in HPAF-II pancreatic cancer cells using global proteomics profiling. The present study is to investigate how EGCG, a major biological active constituent of green tea, targets the metabolism of human pancreatic adenocarcinoma MIA PaCa-2 cells. We compared the effect of EGCG to that of oxamate, an inhibitor of LDHA, on the multiple metabolic pathways as measured by extracellular lactate production, glucose consumption, as well as intracellular aspartate and glutamate production, fatty acid synthesis, acetyl-CoA, RNA ribose and deoxyribose. Specific metabolic pathways were studied using [1, 2-(13)C2]-d-glucose as the single precursor metabolic tracer. Isotope incorporations in metabolites were analyzed using gas chromatography/mass spectrometry (GC/MS) and stable isotope-based dynamic metabolic profiling (SiDMAP). We found that the EGCG treatment of MIA PaCa-2 cells significantly reduced lactate production, anaerobic glycolysis, glucose consumption and glycolytic rate that are comparable to the inhibition of LDHA by oxamate treatment. Significant changes in intracellular glucose carbon re-distribution among major glucose-utilizing macromolecule biosynthesis pathways in response to EGCG and oxamate treatment were observed. The inhibition of LDHA by EGCG or oxamate impacts on various pathways of the cellular metabolic network and significantly modifies the cancer metabolic phenotype. These results suggest that phytochemical EGCG and LDHA inhibitor oxamate confer their anti-cancer activities by disrupting the balance of flux throughout the cellular metabolic network. PMID: 26246802 [PubMed - as supplied by publisher]

Related Articles Metabolic fingerprinting to understand therapeutic effects and mechanisms of silybin on acute liver damage in rat. Pharmacogn Mag. 2015 Jul-Sep;11(43):586-93 Authors: Liang Q, Wang C, Li B, Zhang AH Abstract BACKGROUND: Metabolic fingerprinting is a rapid and noninvasive analysis, representing a powerful approach for the characterization of phenotypes and the distinction of specific metabolic states due to environmental alterations. It has become a valuable analytical approach for the characterization of phenotypes and is the rapidly evolving field of the comprehensive measurement of ideally all endogenous metabolites in bio-samples. Silybin has displayed bright prospects in the prevention and therapy of liver injury, and we had conducted a preliminary exploration on the molecular mechanism of the hepatoprotective effects of silybin. Because the knowledge on the metabolic responses of an acute liver damage rat to the silybin is still scarce, metabolic fingerprinting can provide relevant information on the intrinsic metabolic adjustments. MATERIALS AND METHODS: Here, the physiological and metabolic changes in the acute liver damage rat were investigated by performing a metabolic analysis. The phenotypic response was assessed by liquid chromatography/mass spectrometry (LC/MS) combined with pattern recognition approaches such as principal components analysis and partial least squares projection to supervised latent structures and discriminant analysis. Multivariate analysis of the data showed trends in scores plots that were related to the concentration of the silybin. RESULTS: Results indicate 10 ions (7 upregulated and 3 downregulated) as differentiating metabolites. Key observations include perturbations of metabolic pathways linked to glutathione metabolism, tryptophan metabolism, cysteine and methionine metabolism, etc., Overall, this investigation illustrates the power of the LC/MS combined with the pattern recognition methods that can engender new insights into silybin affecting on metabolism pathways of an acute liver damage rat. CONCLUSION: The present study demonstrates that the combination of metabolic fingerprinting with appropriate chemometric analysis is a valuable approach for studying cellular responses to silybin drug and can provide additional insight into the mechanisms. PMID: 26246736 [PubMed]