PubMed

Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy. Oncotarget. 2015 Aug 28;6(25):20840-50 Authors: Vacchelli E, Semeraro M, Enot DP, Chaba K, Poirier Colame V, Dartigues P, Perier A, Villa I, Rusakiewicz S, Gronnier C, Goéré D, Mariette C, Zitvogel L, Kroemer G Abstract Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy. PMID: 26369701 [PubMed - in process]

Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants. BMC Plant Biol. 2015;15(1):220 Authors: Hagel JM, Mandal R, Han B, Han J, Dinsmore DR, Borchers CH, Wishart DS, Facchini PJ Abstract BACKGROUND: Recent progress toward the elucidation of benzylisoquinoline alkaloid (BIA) metabolism has focused on a small number of model plant species. Current understanding of BIA metabolism in plants such as opium poppy, which accumulates important pharmacological agents such as codeine and morphine, has relied on a combination of genomics and metabolomics to facilitate gene discovery. Metabolomics studies provide important insight into the primary biochemical networks underpinning specialized metabolism, and serve as a key resource for metabolic engineering, gene discovery, and elucidation of governing regulatory mechanisms. Beyond model plants, few broad-scope metabolomics reports are available for the vast number of plant species known to produce an estimated 2500 structurally diverse BIAs, many of which exhibit promising medicinal properties. RESULTS: We applied a multi-platform approach incorporating four different analytical methods to examine 20 non-model, BIA-accumulating plant species. Plants representing four families in the Ranunculales were chosen based on reported BIA content, taxonomic distribution and importance in modern/traditional medicine. One-dimensional (1)H NMR-based profiling quantified 91 metabolites and revealed significant species- and tissue-specific variation in sugar, amino acid and organic acid content. Mono- and disaccharide sugars were generally lower in roots and rhizomes compared with stems, and a variety of metabolites distinguished callus tissue from intact plant organs. Direct flow infusion tandem mass spectrometry provided a broad survey of 110 lipid derivatives including phosphatidylcholines and acylcarnitines, and high-performance liquid chromatography coupled with UV detection quantified 15 phenolic compounds including flavonoids, benzoic acid derivatives and hydroxycinnamic acids. Ultra-performance liquid chromatography coupled with high-resolution Fourier transform mass spectrometry generated extensive mass lists for all species, which were mined for metabolites putatively corresponding to BIAs. Different alkaloids profiles, including both ubiquitous and potentially rare compounds, were observed. CONCLUSIONS: Extensive metabolite profiling combining multiple analytical platforms enabled a more complete picture of overall metabolism occurring in selected plant species. This study represents the first time a metabolomics approach has been applied to most of these species, despite their importance in modern and traditional medicine. Coupled with genomics data, these metabolomics resources serve as a key resource for the investigation of BIA biosynthesis in non-model plant species. PMID: 26369413 [PubMed - in process]

Related Articles Age-related proteostasis and metabolic alterations in Caspase-2-deficient mice. Cell Death Dis. 2015;6:e1597 Authors: Wilson CH, Shalini S, Filipovska A, Richman TR, Davies S, Martin SD, McGee SL, Puccini J, Nikolic A, Dorstyn L, Kumar S Abstract Ageing is a complex biological process for which underlying biochemical changes are still largely unknown. We performed comparative profiling of the cellular proteome and metabolome to understand the molecular basis of ageing in Caspase-2-deficient (Casp2(-/-)) mice that are a model of premature ageing in the absence of overt disease. Age-related changes were determined in the liver and serum of young (6-9 week) and aged (18-24 month) wild-type and Casp2(-/-) mice. We identified perturbed metabolic pathways, decreased levels of ribosomal and respiratory complex proteins and altered mitochondrial function that contribute to premature ageing in the Casp2(-/-) mice. We show that the metabolic profile changes in the young Casp2(-/-) mice resemble those found in aged wild-type mice. Intriguingly, aged Casp2(-/-) mice were found to have reduced blood glucose and improved glucose tolerance. These results demonstrate an important role for caspase-2 in regulating proteome and metabolome remodelling during ageing. PMID: 25611376 [PubMed - indexed for MEDLINE]

Related Articles Mass balance and metabolism of the antimalarial pyronaridine in healthy volunteers. Eur J Drug Metab Pharmacokinet. 2015 Mar;40(1):75-86 Authors: Morris CA, Dueker SR, Lohstroh PN, Wang LQ, Fang XP, Jung D, Lopez-Lazaro L, Baker M, Duparc S, Borghini-Fuhrer I, Pokorny R, Shin JS, Fleckenstein L Abstract This was a single dose mass balance and metabolite characterization study of the antimalarial agent pyronaridine. Six healthy male adults were administered a single oral dose of 720 mg pyronaridine tetraphosphate with 800 nCi of radiolabeled (14)C-pyronaridine. Urine and feces were continuously collected through 168 h post-dose, with intermittent 48 h collection periods thereafter through 2064 h post-dose. Drug recovery was computed for analyzed samples and interpolated for intervening time periods in which collection did not occur. Blood samples were obtained to evaluate the pharmacokinetics of total radioactivity and of the parent compound. Total radioactivity in urine, feces, and blood samples was determined by accelerator mass spectrometry (AMS); parent concentrations in blood were determined with LC/MS. Metabolite identification based on blood, urine, and feces samples was conducted using a combination of LC + AMS for identifying radiopeaks, followed by LC/MS/MS for identity confirmation/elucidation. The mean cumulative drug recovery in the urine and feces was 23.7 and 47.8 %, respectively, with an average total recovery of 71.5 %. Total radioactivity was slowly eliminated from blood, with a mean half-life of 33.5 days, substantially longer than the mean parent compound half-life of 5.03 days. Total radioactivity remained detectable in urine and feces collected in the final sampling period, suggesting ongoing elimination. Nine primary and four secondary metabolites of pyronaridine were identified. This study revealed that pyronaridine and its metabolites are eliminated by both the urinary and fecal routes over an extended period of time, and that multiple, varied pathways characterize pyronaridine metabolism. PMID: 24590312 [PubMed - indexed for MEDLINE]

25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2015/09/15PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

A liquid chromatography-tandem mass spectrometry-based investigation of the lamellar interstitial metabolome in healthy horses and during experimental laminitis induction. Vet J. 2015 Aug 4; Authors: Medina-Torres CE, van Eps AW, Nielsen LK, Hodson MP Abstract Lamellar bioenergetic failure is thought to contribute to laminitis pathogenesis but current knowledge of lamellar bioenergetic physiology is limited. Metabolomic analysis (MA) can systematically profile multiple metabolites. Applied to lamellar microdialysis samples (dialysate), lamellar bioenergetic changes during laminitis (the laminitis metabolome) can be characterised. The objectives of this study were to develop a technique for targeted MA of lamellar and skin dialysates in normal horses, and to compare the lamellar and plasma metabolomic profiles of normal horses with those from horses developing experimentally induced laminitis. Archived lamellar and skin dialysates (n = 7) and tissues (n = 6) from normal horses, and lamellar dialysate and plasma from horses given either 10 g/kg oligofructose (treatment group, OFT; n = 4) or sham (control group, CON; n = 4) were analysed. The concentrations of 44 intermediates of central carbon metabolism (CCM) were determined using liquid chromatography-tandem mass spectrometry. Data were analysed using multivariate (MVA) and univariate (UVA) analysis methods. The plasma metabolome appeared to be more variable than the lamellar metabolome by MVA, driven by malate, pyruvate, aconitate and glycolate. In lamellar dialysate, these metabolites decreased in OFT horses at the later time points. Plasma malate was markedly increased after 6 h in OFT horses. Plasma malate concentrations between OFT and CON at this time point were significantly different by UVA. MA of lamellar CCM was capable of differentiating horses developing experimental laminitis from controls. Lamellar malate, pyruvate, aconitate and glycolate, and plasma malate alone were identified as the source of differentiation between OFT and CON groups. These results highlighted clear discriminators between OFT and CON horses, suggesting that changes in energy metabolism occur locally in the lamellar tissue during laminitis development. The biological significance of these alterations requires further investigation. PMID: 26364239 [PubMed - as supplied by publisher]

Metabolomics of Disease Resistance in Crops. Curr Issues Mol Biol. 2015 Sep 11;19:13-30 Authors: Arbona V, Gómez-Cadenas A Abstract Plants are continuously exposed to the attack of invasive microorganisms, such as fungi or bacteria, and also viruses. To fight these attackers, plants develop different metabolic and genetic responses whose final outcome is the production of either toxic compounds that kill the pathogen or deter its growth, and/or semiotic molecules that alert other individuals from the same plant species. These molecules are derived from the secondary metabolism and their production is induced upon detection of a pathogen-associated molecular pattern (PAMP). These PAMPs are different molecules that are perceived by the host cell triggering defense responses. PAMP-elicited compounds are highly diverse and specific of every plant species and can be divided into preformed metabolites or phytoanticipins that are converted into toxic molecules upon pathogen perception, and toxic metabolites or phytoalexins that are produced only upon pathogen attack. Moreover, plant volatile emissions are also modified in response to pathogen attack to alert neighboring individuals or to make plants less attractive to pathogen vector arthropods. Plant metabolite profiling techniques have allowed the identification of novel antimicrobial molecules that are induced upon elicitation. However, more studies are required to assess the specific function of metabolites or metabolite blends on plant-microbe interactions. PMID: 26364233 [PubMed - as supplied by publisher]

Metabolomic approach to profile functional and metabolic changes in heart failure. J Transl Med. 2015;13(1):297 Authors: Deidda M, Piras C, Dessalvi CC, Locci E, Barberini L, Torri F, Ascedu F, Atzori L, Mercuro G Abstract BACKGROUND: Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction. METHODS: A 500 MHz proton nuclear magnetic resonance ((1)H-NMR)-based analysis was performed on blood samples from three groups of individuals: 9 control subjects (Group A), 9 HF patients with mild to moderate impairment of left ventricle ejection fraction (LVEF: 41.9 ± 4.0 %; Group B), and 15 HF patients with severe LVEF impairment (25.3 ± 10.3 %; Group C). In order to create a descriptive model of HF, a supervised orthogonal projection on latent structures discriminant analysis (OPLS-DA) was applied using speckle tracking-derived longitudinal strain rate as the Y-variable in the multivariate analysis. RESULTS: OPLS-DA identified three metabolic clusters related to the studied groups achieving good values for R(2) [R(2)(X) = 0.64; R(2)(Y) = 0.59] and Q(2) (0.39). The most important metabolites implicated in the clustering were 2-hydroxybutyrate, glycine, methylmalonate, and myo-inositol. CONCLUSIONS: The results demonstrate the suitability of metabolomics in combination with functional evaluation techniques in HF staging. This innovative tool should facilitate investigation of perturbed metabolic pathways in HF and their correlation with the impairment of myocardial function. PMID: 26364058 [PubMed - as supplied by publisher]

OMICS in Plant Disease Resistance. Curr Issues Mol Biol. 2015 Sep 11;19:1-2 Authors: Bhadauria V Abstract The term OMICS, which look into the global profiling and analysis of various cellular molecules, has gained new heights with the advancement of next-generation sequencing and mass spectrometry technologies. It has broader implication in genetic improvement of crops for resistance against various diseases of economic significance. This focus issue entitled OMICS in Plant Disease Resistance highlights the implication of OMICS (genomics, transcriptomics, proteomics and metabolomics) in agricultural research. PMID: 26363815 [PubMed - as supplied by publisher]

Omics Approach to Identify Factors Involved in Brassica Disease Resistance. Curr Issues Mol Biol. 2015 Sep 11;19:31-42 Authors: Francisco M, Soengas P, Velasco P, Bhadauria V, Cartea ME, Rodríguez VM Abstract Understanding plant's defense mechanisms and their response to biotic stresses is of fundamental meaning for the development of resistant crop varieties and more productive agriculture. The Brassica genus involves a large variety of economically important species and cultivars used as vegetable source, oilseeds, forage and ornamental. Damage caused by pathogens attack affects negatively various aspects of plant growth, development, and crop productivity. Over the last few decades, advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to biotic stress conditions. In this regard, various 'omics' technologies enable qualitative and quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. In this review, we have described advances in 'omic' tools (genomics, transcriptomics, proteomics and metabolomics) in the view of conventional and modern approaches being used to elucidate the molecular mechanisms that underlie Brassica disease resistance. PMID: 26363709 [PubMed - as supplied by publisher]

Omics Approaches for the Engineering of Pathogen Resistant Plants. Curr Issues Mol Biol. 2015 Sep 11;19:89-98 Authors: Gomez-Casati DF, Pagani MA, Busi MV, Bhadauria V Abstract The attack of different pathogens, such as bacteria, fungi and viruses has a negative impact on crop production. In counter such attacks, plants have developed different strategies involving the modification of gene expression, activation of several metabolic pathways and post-translational modification of proteins, which culminate into the accumulation of primary and secondary metabolites implicated in plant defense responses. The recent advancement in omics techniques allows the increase coverage of plants transcriptomes, proteomes and metabolomes during pathogen attack, and the modulation of the response after the infection. Omics techniques also allow us to learn more about the biological cycle of the pathogens in addition to the identification of novel virulence factors in pathogens and their host targets. Both approaches become important to decipher the mechanism underlying pathogen attacks and to develop strategies for improving disease-resistant plants. In this review, we summarize some of the contribution of genomics, transcriptomics, proteomics, metabolomics and metallomics in devising the strategies to obtain plants with increased resistance to pathogens. These approaches constitute important research tools in the development of new technologies for the protection against diseases and increase plant production. PMID: 26363625 [PubMed - as supplied by publisher]

Related Articles [¹H NMR metabonomics study of pancreatic extracts from insulin-resistant rats induced by fructose feeding]. Nan Fang Yi Ke Da Xue Xue Bao. 2014 Aug;34(9):1301-4 Authors: Wang L, Zheng L, Zhang L, Chen A, Qiu C, Xu J, Yang Y Abstract OBJECTIVE: To study the metabolic changes of pancreatic extracts from insulin-resistant rats induced by fructose feeding using nuclear magnetic resonance ¹H spectroscopy (¹H NMR). METHODS: Sixteen Wistar rats were divided equally into control group and model group and given water and 10% fructose water for 8 weeks, respectively. The pancreatic tissues were then obtained for H NMR spectra analysis and principal component analysis (PCA). RESULTS: Compared with the control rats, the rats in the model group showed significantly increased creatine, betaine/TMAO, taurine, glycine and myo-inositol and decreased levels of lipids, lactate, glutamate, choline and GPC/PC. CONCLUSION: ¹H NMR and pattern recognition can define the metabolic characteristics of the pancreatic tissue extracts from insulin-resistant rats and provide reliable metabolic evidence for studying the mechanisms of insulin resistance at the molecular level. PMID: 25263363 [PubMed - indexed for MEDLINE]

Related Articles [Determination of serum carbamazepine concentration and metabonomic analysis in rats]. Nan Fang Yi Ke Da Xue Xue Bao. 2014 Jun;34(7):1025-9 Authors: Cai Z, Mo LQ, Guan SY, Liu CY, Liu Y, Guo D Abstract OBJECTIVE: To study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magnetic resonance (NMR) spectroscopy. METHODS: Twenty-four healthy male Wistar rats were randomized into 4 groups (n=6) for daily intragastric administration of high-, medium- or low-dose carbamazepine or distilled water (control) for 7 days. Blood samples were collected from the abdominal aortic under anesthesia after the treatment to determine serum carbamazepine concentration using high-performance liquid chromatography. ¹H nuclear magnetic resonance (¹H NMR) spectra were acquired for pattern recognition analysis. Histopathological changes of the renal and liver tissues of the rats were also examined. RESULTS: Steady-state blood concentration of carbamazepine in high-, medium- and low-dose groups were 14.64 ± 1.41, 8.54 ± 1.19, and 4.56 ± 0.64 µg/ml, respectively. Slight liver swelling was found in high-dose group, but none of the groups showed renal pathologies. Compared with the control group, the high-dose carbamazepine group showed lowered serum concentrations of 1,3-diaminopropane, deoxycorticosterone, 7-dehydrocholesterol, betaine, beta-alanine, L-cystathionine, 4-methyl-2-oxovaleric acid, and creatine with increased levels of saccharides, lactate, succinic acid, acetyl phosphate, and adipic acid. Principal component analysis revealed significant differences of the metabolites between carbamazepine-treated groups and the control group. The metabolic profiles showed no differences in the kinds of metabolites although the concentrations of the metabolites varied between the carbamazepine groups. CONCLUSIONS: Carbamazepine significantly affects metabolism in normal rats. This finding provides evidence for clinical drug monitoring and drug safety of carbamazepine. NMR technique has important values for pharmacodynamic and toxicological evaluation of drugs. PMID: 25057077 [PubMed - indexed for MEDLINE]

Toxicological effects of benzo(a)pyrene, DDT and their mixture on the green mussel Perna viridis revealed by proteomic and metabolomic approaches. Chemosphere. 2015 Sep 9;144:214-224 Authors: Song Q, Chen H, Li Y, Zhou H, Han Q, Diao X Abstract Benzo(a)pyrene (BaP) and dichlorodiphenyltrichloroethane (DDT) are persistent organic pollutants and environmental estrogens (EEs) with known toxicity towards the green mussel, Perna viridis. In this study, the toxic effects of BaP (10 μg/L) and DDT (10 μg/L) and their mixture were assessed in green mussel gills with proteomic and metabolomic approaches. Metabolic responses indicated that BaP mainly caused disturbance in osmotic regulation by significantly decrease in branched chain amino acids, dimethylamine and dimethylglycine in gills of male green mussels after exposure for 7 days. DDT mainly caused disturbance in osmotic regulation and energy metabolism by differential alteration of betaine, dimethylamine, dimethylglycine, amino acids, and succinate in gills of male green mussels. However, the mixture of BaP and DDT didn't show obvious metabolite changes. Proteomic analysis showed different protein expression profiles between different treatment groups, which demonstrated that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced cell apoptosis, disturbance in protein digestion and energy metabolism in gills of green mussels, whereas DDT exposure altered proteins that were associated with oxidative stress, cytoskeleton and cell structure, protein digestion and energy metabolism. However, the mixture of BaP and DDT affected proteins related to the oxidative stress, cytoskeleton and cell structure, protein biosynthesis and modification, energy metabolism, growth and apoptosis. PMID: 26363323 [PubMed - as supplied by publisher]

Biomarkers of An Autoimmune Skin Disease - Psoriasis. Genomics Proteomics Bioinformatics. 2015 Sep 8; Authors: Jiang S, Hinchliffe TE, Wu T Abstract Psoriasis is one of the most prevalent autoimmune skin diseases. However, its etiology and pathogenesis is still unclear. Over the last decade, omics-based technologies have been extensively utilized for biomarker discovery. As a result, some promising markers for psoriasis have been identified at the genome, transcriptome, proteome, and metabolome level. These discoveries have provided new insights into the underlying molecular mechanisms and signaling pathways in psoriasis pathogenesis. More importantly, some of these markers may prove useful in the diagnosis of psoriasis and in the prediction of disease progression once they have been validated. In this review, we summarize the most recent findings in psoriasis biomarker discovery. In addition, we will discuss several emerging technologies and their potential for novel biomarker discovery and diagnostics for psoriasis. PMID: 26362816 [PubMed - as supplied by publisher]

Metabolomics in rheumatology. Rheumatology (Oxford). 2015 Sep 11; Authors: Kapoor SR, McGrath CM, Fitzpatrick MA, Young SP PMID: 26361880 [PubMed - as supplied by publisher]

Related Articles (1)H NMR metabolomics to study the effects of diazepam on anisatin induced convulsive seizures. J Pharm Biomed Anal. 2015 Sep 1;117:184-194 Authors: Li P, Wei DD, Wang JS, Yang MH, Kong LY Abstract The anticonvulsive properties of diazepam have been extensively studied, mainly focusing on the γ-amino butyrate (GABA) system. The aim of this investigation was to integrally analyze the metabolic events related to neuroprotection of diazepam on anisatin-induced convulsive seizures by a NMR-based metabolomic approach combined with histopathological examination and behavior examination. Multivariate analysis on metabolic profiles of the piriform cortex and cerebellum of mice revealed that diazepam could relieve mice suffering from the convulsive seizures by recovering destructed neurotransmitter and neuromodulator metabolism, ameliorating oxidative stress, alleviating the disturbance in energy, amino acid and nucleic acid metabolism in anisatin intoxicated mice. This integrated metabolomics study provided a powerful and highly effective approach to elucidate therapeutic effects and assessed the safety of diazepam. This study should be helpful for our understanding of convulsive seizures, and provide a holistic view of the treatment effects of benzodiazepine on convulsive seizures. PMID: 26361344 [PubMed - as supplied by publisher]

Related Articles Cardioprotective mechanism of omega-3 polyunsaturated fatty acids. J Cardiol. 2015 Sep 7; Authors: Endo J, Arita M Abstract Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid and docosahexaenoic acid, are widely regarded as cardioprotective. Several large-scale, randomized clinical trials have shown that dietary intake of omega-3 PUFAs improves the prognosis of patients with symptomatic heart failure or recent myocardial infarction. Therefore, dietary consumption of omega-3 PUFA is recommended in international guidelines for the general population to prevent the occurrence of cardiovascular diseases (CVDs). However, the precise mechanisms underlying the cardioprotective effects of omega-3 PUFAs are not fully understood. Omega-3 PUFAs can be incorporated into the phospholipid bilayer of cell membranes and can affect membrane fluidity, lipid microdomain formation, and signaling across membranes. Omega-3 PUFAs also modulate the function of membrane ion channels, such as Na and L-type Ca channels, to prevent lethal arrhythmias. Moreover, omega-3 PUFAs also prevent the conversion of arachidonic acid into pro-inflammatory eicosanoids by serving as an alternative substrate for cyclooxygenase or lipoxygenase, resulting in the production of less potent products. In addition, a number of enzymatically oxygenated metabolites derived from omega-3 PUFAs were recently identified as anti-inflammatory mediators. These omega-3 metabolites may contribute to the beneficial effects against CVDs that are attributed to omega-3 PUFAs. PMID: 26359712 [PubMed - as supplied by publisher]

Related Articles Using the matrix-induced ion suppression method for concentration normalization in cellular metabolomics studies. Anal Chem. 2015 Sep 10; Authors: Chen GY, Liao HW, Tsai IL, Tseng YJ, Kuo CH Abstract Studies of the cell metabolome greatly improve our understanding of cell biology. Currently, most cellular metabolomics studies control only cell numbers or protein content without adjusting the total metabolite concentration, mainly because of the lack of an effective concentration normalization method for cell metabolites. This study proposed a matrix-induced ion suppression method (MIIS) to measure the total amount of cellular metabolites by utilizing flow injection analysis coupled with electrospray ionization mass spectrometry (FIA-ESI-MS). We used series dilutions of HL-60 cell extracts to establish the relationship between cellular metabolite concentration and the degree of ion suppression of the ion suppression indicator, and a good correlation was obtained between 2- to 12-fold dilutions of cell extracts (R2 = 0.999). Two lung cancer cells, CL1-0 and CL1-5, were selected as the model cell lines to evaluate the efficacy of the MIIS method and the importance of metabolite concentration normalization. Through MIIS analysis, CL1-0 cells were found to contain metabolites at a concentration 2.1 times higher than in CL1-5, and the metastatic properties of CL1-5 could only be observed after 2.1-fold dilution of CL1-0 before metabolomic analysis. Our results demonstrated that the MIIS method is an effective approach for metabolite concentration normalization and that controlling metabolite concentrations can improve data integrity in cellular metabolomics studies. PMID: 26359637 [PubMed - as supplied by publisher]

Related Articles [Application and research advances of metabolomics in the field of orthopedics]. Zhonghua Wai Ke Za Zhi. 2015 Jun;53(6):476-80 Authors: Sun Z, Qiu G, Zhao Y Abstract Metabolomics is a subject of systematic, qualitative and quantitative analysis of all metabolites in all organisms, which is applied to finding biomarkers and studying pathogenesis of diseases. Study procedures of metabolomics include data acquisition by spectroscopic/spectrometric techniques, multivariate statistical analysis and projection of the acquired metabolomic information. In recent years, metabolomics have gained popularity in orthopedic field. Metabolomic study of osteoarthritis was firstly conducted and widely developed. Metabolite profiles of different samples, including serum/plasma, urine, synovial fluid and synovial tissue, were studied and dozens of differential metabolites and several disturbed metabolic pathways were found. In addition, metabolomic studies of osteoporosis, ankylosing spondylitis and bone tumors were also conducted, which identified many potential biomarkers and made further understanding of pathogenesis of corresponding disease. However, metabolomic studies in orthopedic field just begin. More orthopedic diseases will be researched thank to the satisfactory results of previous reports. PMID: 26359065 [PubMed - in process]