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Related Articles iSCHRUNK - In Silico Approach to Characterization and Reduction of Uncertainty in the Kinetic Models of Genome-scale Metabolic Networks. Metab Eng. 2015 Oct 14; Authors: Andreozzi S, Miskovic L, Hatzimanikatis V Abstract Accurate determination of physiological states of cellular metabolism requires detailed information about metabolic fluxes, metabolite concentrations and distribution of enzyme states. Integration of fluxomics and metabolomics data, and thermodynamics-based metabolic flux analysis contribute to improved understanding of steady-state properties of metabolism. However, knowledge about kinetics and enzyme activities though essential for quantitative understanding of metabolic dynamics remains scarce and involves uncertainty. Here, we present a computational methodology that allow us to determine and quantify the kinetic parameters that correspond to a certain physiology as it is described by a given metabolic flux profile and a given metabolite concentration vector. Though we initially determine kinetic parameters that involve a high degree of uncertainty, through the use of kinetic modeling and machine learning principles we are able to obtain more accurate ranges of kinetic parameters, and hence we are able to reduce the uncertainty in the model analysis. We computed the distribution of kinetic parameters for glucose-fed E. coli producing 1,4-butanediol and we discovered that the observed physiological state corresponds to a narrow range of kinetic parameters of only a few enzymes, whereas the kinetic parameters of other enzymes can vary widely. Furthermore, this analysis suggests which are the enzymes that should be manipulated in order to engineer the reference state of the cell in a desired way. The proposed approach also sets up the foundations of a novel type of approaches for efficient, non-asymptotic, uniform sampling of solution spaces. PMID: 26474788 [PubMed - as supplied by publisher]

Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission. PLoS One. 2015;10(10):e0140716 Authors: Hisamatsu T, Ono N, Imaizumi A, Mori M, Suzuki H, Uo M, Hashimoto M, Naganuma M, Matsuoka K, Mizuno S, Kitazume MT, Yajima T, Ogata H, Iwao Y, Hibi T, Kanai T Abstract Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41-4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease. PMID: 26474176 [PubMed - as supplied by publisher]

Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Metabolic Adaptation and Enables Glucose-Independent Tumor Growth. Mol Cell. 2015 Oct 15;60(2):195-207 Authors: Vincent EE, Sergushichev A, Griss T, Gingras MC, Samborska B, Ntimbane T, Coelho PP, Blagih J, Raissi TC, Choinière L, Bridon G, Loginicheva E, Flynn BR, Thomas EC, Tavaré JM, Avizonis D, Pause A, Elder DJ, Artyomov MN, Jones RG Abstract Cancer cells adapt metabolically to proliferate under nutrient limitation. Here we used combined transcriptional-metabolomic network analysis to identify metabolic pathways that support glucose-independent tumor cell proliferation. We found that glucose deprivation stimulated re-wiring of the tricarboxylic acid (TCA) cycle and early steps of gluconeogenesis to promote glucose-independent cell proliferation. Glucose limitation promoted the production of phosphoenolpyruvate (PEP) from glutamine via the activity of mitochondrial PEP-carboxykinase (PCK2). Under these conditions, glutamine-derived PEP was used to fuel biosynthetic pathways normally sustained by glucose, including serine and purine biosynthesis. PCK2 expression was required to maintain tumor cell proliferation under limited-glucose conditions in vitro and tumor growth in vivo. Elevated PCK2 expression is observed in several human tumor types and enriched in tumor tissue from non-small-cell lung cancer (NSCLC) patients. Our results define a role for PCK2 in cancer cell metabolic reprogramming that promotes glucose-independent cell growth and metabolic stress resistance in human tumors. PMID: 26474064 [PubMed - as supplied by publisher]

A direct ionization mass spectrometry-based approach for differentiation of medicinal Ephedra species. J Pharm Biomed Anal. 2015 Oct 3;117:492-498 Authors: Xin GZ, Hu B, Shi ZQ, Zheng JY, Wang L, Chang WQ, Li P, Yao Z, Liu LF Abstract Herein, rapid and efficient identification of species of medicinal Ephedrae Herba was performed using DI-MS (direct ionization-mass spectrometry)-based metabolomics analysis. As a direct ionization technique, DI-MS can provide rapid analysis of samples without sample preparation, so it has been advantageously applied to high-throughput metabolomics analysis. In this flow chart, the MS fingerprints of Ephedrae Herba samples obtained by DI-MS method were firstly pretreated by background subtracts, smooth and center procedures to extract MS features. Then, these MS features were aligned using in a house program written in MATLAB to produce MS dataset. After that, PCA and PLS-DA analysis were performed based on the obtained MS dataset. Finally, the parameter VIP (Variable importance in the Projection) was employed to screen the valuable MS features for discrimination. Using such an approach, three medicinal species of Ephedrae Herba, Ephedra sinica, Ephedra intermedia, and Ephedra equisetina., had been successfully differentiated. Additionally, this method has also been applied to identify the changes in components of Ephedrae Herba after honey treated. In present study, DI-MS in combination with metabolomics was shown to be an efficient and accurate way to identify the sources of herbs. PMID: 26473988 [PubMed - as supplied by publisher]

Effects of ceftiofur treatment on the susceptibility of commensal porcine E.coli - comparison between treated and untreated animals housed in the same stable. BMC Vet Res. 2015;11(1):265 Authors: Beyer A, Baumann S, Scherz G, Stahl J, von Bergen M, Friese A, Roesler U, Kietzmann M, Honscha W Abstract BACKGROUND: Healthy farm animals have been found to act as a reservoir of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli). Therefore, the objective of the study was to determine the input of antimicrobial active ceftiofur metabolites in the stable via faeces and urine after intramuscular administration of the drug to pigs and the elucidation of the Escherichia coli ESBL resistance pattern of treated and untreated pigs housed in the same barn during therapy. METHODS: For determination of the minimal inhibitory concentration (MIC) the method of microdilutionaccording to the recommended procedure of the Clinical and Laboratory Standards Institute was used. Inaddition to that, a qualitative determination was performed by agar dilution. Unsusceptible E. coli speciesselected via agar dilution with cefotaxime were confirmed by MALDI-TOF and ESBL encoding genes wereidentified by PCR. The amounts of ceftiofur measured as desfuroylceftiofur (DFC) in the different probes (plasma, urine, faeces and dust) were analysed by UPLC-MS/MS. RESULTS: In a first experiment two groups of pigs (6 animals per group) were housed in the same barn in two separated boxes. One group (group B) were treated with ceftiofur according to the licence (3 mg/kg administered intramuscularly (i.m.) on three consecutive days, day 1-3). During a second treatment period (day 29-31) an increased rate of ESBL resistant E. coli was detectable in these treated pigs and in the air of the stable. Moreover, the second group of animals (group A) formerly untreated but housed for the whole period in the same stable as the treated animals revealed increased resistance rates during their first treatment (day 45-47) with ceftiofur. In order to investigate the environmental input of ceftiofur during therapy and to simulate oral uptake of ceftiofur residues from the air of the stable a second set of experiments were performed. Pigs (6 animals) were treated with an interval of 2 weeks for 3 days with different doses of ceftiofur (3 mg/kg, 1 mg/kg and 0.3 mg/kg i.m.) as well as with 3 mg/kg per os) and the renal and biliary excretion of ceftiofur as its active metabolite were measured in comparison to the plasma levels. In addition to that, probes of the sedimentation dust and the air of the stable were analysed for drug residues. CONCLUSION: The present study shows that treatment of several animals in a stable with ceftiofur influences the resistance pattern of intestinal Escherichia coli of the treated as well as untreated animals housed in the same stable. During therapy with the drug which was administered by injection according to the licence we detected nameable amounts of ceftiofur and its active metabolites in the dust and air of the stable. PMID: 26472561 [PubMed - in process]

Physiological conditions can be reflected in human urine proteome and metabolome. Expert Rev Proteomics. 2015 Oct 15;:1-14 Authors: Wu J, Gao Y Abstract Biomarkers are the measurable changes associated with physiological or pathophysiological processes. Urine, unlike blood, lacks mechanisms for maintaining homeostasis: it is therefore an ideal source of biomarkers that can reflect systemic changes. Urinary proteome and metabolome have been studied for their diagnostic capabilities, ability to monitor disease and prognostic utility. In this review, the effects of common physiological conditions such as gender, age, diet, daily rhythms, exercise, hormone status, lifestyle and extreme environments on human urine are discussed. These effects should be considered when biomarker studies of diseases are conducted. More importantly, if physiological changes can be reflected in urine, we have reason to expect that urine will become widely used to detect small and early changes in pathological and/or pharmacological conditions. PMID: 26472227 [PubMed - as supplied by publisher]

Analysis of urinary metabolomic profiling for unstable angina pectoris disease based on nuclear magnetic resonance spectroscopy. Mol Biosyst. 2015 Oct 16; Authors: Li Z, Liu X, Wang J, Gao J, Guo S, Gao K, Man H, Wang Y, Chen J, Wang W Abstract (1)H NMR-based urinary metabolic profiling is used for investigating the unstable angina pectoris (UAP) metabolic signatures, in order to find out candidate biomarkers to facilitate medical diagnosis. In this work, 27 urine samples from UAP patients and 20 healthy controls were used. The metabolic profiles of the samples were analyzed by multivariate statistics analysis, including PCA, PLS-DA and OPLS-DA. The PCA analysis exhibited slight separation with R(2)X of 0.681 and Q(2) of 0.251, while the PLS-DA (R(2)X = 0.121, R(2)Y = 0.931, and Q(2) = 0.661) and the OPLS-DA (R(2)X = 0.121, R(2)Y = 0.931, Q(2) = 0.653) demonstrated that the model showed good performance. By OPLS-DA, 20 metabolites were identified. A diagnostic model was further constructed using the receiver-operator characteristic (ROC) curves (AUC = 0.953), which exhibited a satisfying sensitivity of 92.6%, specificity of 90% and accuracy of 89.1%. The results demonstrated that the NMR-based metabolomics approach showed good performance in identifying diagnostic urinary biomarkers, providing new insights into the metabolic process related to UAP. PMID: 26471262 [PubMed - as supplied by publisher]

Metabolic dysfunction is restricted to the sciatic nerve in experimental diabetic neuropathy. Diabetes. 2015 Oct 15; Authors: Freeman OJ, Unwin RD, Dowsey AW, Begley P, Ali S, Hollywood KA, Rustogi N, Petersen RS, Dunn WB, Cooper GJ, Gardiner NJ Abstract High glucose levels in the peripheral nervous system (PNS) have been implicated in the pathogenesis of diabetic neuropathy (DN). However our understanding of the molecular mechanisms which cause the marked distal pathology is incomplete. Here we performed a comprehensive, system-wide analysis of the PNS of a rodent model of DN. We integrated proteomics and metabolomics from the sciatic nerve (SN), the lumbar 4/5 dorsal root ganglia (DRG) and the trigeminal ganglia (TG) of streptozotocin-diabetic and healthy control rats. Even though all tissues showed a dramatic increase in glucose and polyol pathway intermediates in diabetes, there was a striking upregulation of mitochondrial oxidative phosphorylation and perturbation of lipid metabolism in the distal SN that was not present in the corresponding cell bodies of the DRG or the cranial TG. This suggests that the most severe molecular consequences of diabetes in the nervous system present in the SN, the region most affected by neuropathy. Such spatial metabolic dysfunction suggests a failure of energy homeostasis and/or oxidative stress specifically in the distal axon/Schwann cell-rich SN. These data provide a detailed molecular description of the distinct compartmental effects of diabetes on the PNS which could underlie the distal-proximal distribution of pathology. PMID: 26470786 [PubMed - as supplied by publisher]

Related Articles Temperament type specific metabolite profiles of the prefrontal cortex and serum in cattle. PLoS One. 2015;10(4):e0125044 Authors: Brand B, Hadlich F, Brandt B, Schauer N, Graunke KL, Langbein J, Repsilber D, Ponsuksili S, Schwerin M Abstract In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response. PMID: 25927228 [PubMed - indexed for MEDLINE]

Related Articles MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function. Sci Rep. 2015;5:9073 Authors: Caicedo A, Fritz V, Brondello JM, Ayala M, Dennemont I, Abdellaoui N, de Fraipont F, Moisan A, Prouteau CA, Boukhaddaoui H, Jorgensen C, Vignais ML Abstract Mitochondrial activity is central to tissue homeostasis. Mitochondria dysfunction constitutes a hallmark of many genetic diseases and plays a key role in tumor progression. The essential role of mitochondria, added to their recently documented capacity to transfer from cell to cell, obviously contributes to their current interest. However, determining the proper role of mitochondria in defined biological contexts was hampered by the lack of suitable experimental tools. We designed a protocol (MitoCeption) to directly and quantitatively transfer mitochondria, isolated from cell type A, to recipient cell type B. We validated and quantified the effective mitochondria transfer by imaging, fluorescence-activated cell sorting (FACS) and mitochondrial DNA analysis. We show that the transfer of minute amounts of mesenchymal stem/stromal cell (MSC) mitochondria to cancer cells, a process otherwise occurring naturally in coculture, results in cancer cell enhanced oxidative phosphorylation (OXPHOS) activity and favors cancer cell proliferation and invasion. The MitoCeption technique, which can be applied to different cell systems, will therefore be a method of choice to analyze the metabolic modifications induced by exogenous mitochondria in host cells. PMID: 25766410 [PubMed - indexed for MEDLINE]

Related Articles Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers. Sci Rep. 2015;5:9114 Authors: Kwan HY, Niu X, Dai W, Tong T, Chao X, Su T, Chan CL, Lee KC, Fu X, Yi H, Yu H, Li T, Tse AK, Fong WF, Pan SY, Lu A, Yu ZL Abstract Schisandrin B (SchB) is one of the most abundant bioactive dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis. Here, we investigated the potential therapeutic effects of SchB on non-alcoholic fatty-liver disease (NAFLD). In lipidomic study, ingenuity pathway analysis highlighted palmitate biosynthesis metabolic pathway in the liver samples of SchB-treated high-fat-diet-fed mice. Further experiments showed that the SchB treatment reduced expression and activity of fatty acid synthase, expressions of hepatic mature sterol regulatory element binding protein-1 and tumor necrosis factor-α, and hepatic level of palmitic acid which is known to promote progression of steatosis to steatohepatitis. Furthermore, the treatment also reduced hepatic fibrosis, activated nuclear factor-erythroid-2-related factor-2 which is known to attenuate the progression of NASH-related fibrosis. Interestingly, in fasting mice, a single high-dose SchB induced transient lipolysis and increased the expressions of adipose triglyceride lipase and phospho-hormone sensitive lipase. The treatment also increased plasma cholesterol levels and 3-hydroxy-3-methylglutaryl-CoA reductase activity, reduced the hepatic low-density-lipoprotein receptor expression in these mice. Our data not only suggest SchB is a potential therapeutic agent for NAFLD, but also provided important information for a safe consumption of SchB because SchB overdosed under fasting condition will have adverse effects on lipid metabolism. PMID: 25766252 [PubMed - indexed for MEDLINE]

Related Articles Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation. Sci Rep. 2013;3:3432 Authors: Quinn KP, Sridharan GV, Hayden RS, Kaplan DL, Lee K, Georgakoudi I Abstract The non-invasive high-resolution spatial mapping of cell metabolism within tissues could provide substantial advancements in assessing the efficacy of stem cell therapy and understanding tissue development. Here, using two-photon excited fluorescence microscopy, we elucidate the relationships among endogenous cell fluorescence, cell redox state, and the differentiation of human mesenchymal stem cells into adipogenic and osteoblastic lineages. Using liquid chromatography/mass spectrometry and quantitative PCR, we evaluate the sensitivity of an optical redox ratio of FAD/(NADH + FAD) to metabolic changes associated with stem cell differentiation. Furthermore, we probe the underlying physiological mechanisms, which relate a decrease in the redox ratio to the onset of differentiation. Because traditional assessments of stem cells and engineered tissues are destructive, time consuming, and logistically intensive, the development and validation of a non-invasive, label-free approach to defining the spatiotemporal patterns of cell differentiation can offer a powerful tool for rapid, high-content characterization of cell and tissue cultures. PMID: 24305550 [PubMed - indexed for MEDLINE]

19 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 2015/10/16PubMed 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.

Comparison of Fc N-Glycosylation of Pharmaceutical Products of Intravenous Immunoglobulin G. PLoS One. 2015;10(10):e0139828 Authors: Fokkink WJ, Falck D, Santbergen TC, Huizinga R, Wuhrer M, Jacobs BC Abstract Intravenous immunoglobulin (IVIg) products from different pharmaceutical companies vary in composition, in part because of the selected blood donors and production process. N-glycosylation of the Fc-portion of IgG varies between blood donors and may influence both the side-effects and therapeutic effectiveness of IVIg. At present, the variation in Fc N-glycosylation between IVIg products has not been defined. Utilizing mass spectrometry, we performed relative quantitation of the Fc N-glycosylation of IgG, assessing a total of 154 unique lot numbers of IVIg. Seven products showed comparable Fc N-glycosylation, with only one product differing from the others in all glycosylation features (galactosylation, sialylation, fucosylation and bisecting N-acetylglucosamine). However, the mean difference did not exceed 3%. Within product variation was present to a minor degree, but largely indistinguishable from analytical variation. In conclusion, we expect that the minor variation in Fc N-glycosylation between IVIg products has a small effect, if any, on the biological activity. PMID: 26457892 [PubMed - as supplied by publisher]

Influence of Different Drying Treatments and Extraction Solvents on the Metabolite Profile and Nitric Oxide Inhibitory Activity of Ajwa Dates. J Food Sci. 2015 Oct 12; Authors: Abdul-Hamid NA, Abas F, Ismail IS, Shaari K, Lajis NH Abstract This study aimed to examine the variation in the metabolite profiles and nitric oxide (NO) inhibitory activity of Ajwa dates that were subjected to 2 drying treatments and different extraction solvents. (1) H NMR coupled with multivariate data analysis was employed. A Griess assay was used to determine the inhibition of the production of NO in RAW 264.7 cells treated with LPS and interferon-γ. The oven dried (OD) samples demonstrated the absence of asparagine and ascorbic acid as compared to the freeze dried (FD) dates. The principal component analysis showed distinct clusters between the OD and FD dates by the second principal component. In respect of extraction solvents, chloroform extracts can be distinguished by the absence of arginine, glycine and asparagine compared to the methanol and 50% methanol extracts. The chloroform extracts can be clearly distinguished from the methanol and 50% methanol extracts by first principal component. Meanwhile, the loading score plot of partial least squares analysis suggested that beta glucose, alpha glucose, choline, ascorbic acid and glycine were among the metabolites that were contributing to higher biological activity displayed by FD and methanol extracts of Ajwa. The results highlight an alternative method of metabolomics approach for determination of the metabolites that contribute to NO inhibitory activity. PMID: 26457883 [PubMed - as supplied by publisher]

Bioanalytical derivatization: is there still room for development? Bioanalysis. 2015 Oct 12; Authors: Giera M PMID: 26457481 [PubMed - as supplied by publisher]

Rice-gall midge interactions: battle for survival. J Insect Physiol. 2015 Oct 8; Authors: Bentur JS, Rawat N, Divya D, Sinha DK, Agarrwal R, Atray I, Nair S Abstract Gall midges are insects specialized in maneuvering plant growth, metabolic and defense pathways for their benefit. The Asian rice gall midge and rice share such an intimate relationship that there is a constant battle for survival by either partner. Diverse responses by the rice host against the midge include necrotic hypersensitive resistance reaction, non-hypersensitive resistance reaction and gall-forming compatible interaction. Genetic studies have revealed that major R (resistance) genes confer resistance to gall midge in rice. Eleven gall midge R genes have been characterized so far in different rice varieties in India. In addition, no single R gene confers resistance against all the seven biotypes of the Asian rice gall midge, and none of the biotypes is virulent against all the resistance genes. Further, the interaction of the plant resistance gene with the insect avirulence gene is on a gene-for-gene basis. Our recent investigations involving suppressive subtraction hybridization cDNA libraries, microarray analyses, gene expression assays and metabolic profiling have revealed several molecular mechanisms, metabolite markers and pathways that are induced, down-regulated or altered in the rice host during incompatible or compatible interactions with the pest. This is also true for some of the pathways studied in the gall midge. Next generation sequencing technology, gene expression studies and conventional screening of gall midge cDNA libraries highlighted molecular approaches adopted by the insect to feed, survive and reproduce. This constant struggle by the midge to overcome the host defenses and the host to resist the pest has provided us with an opportunity to observe this battle for survival at the molecular level. PMID: 26455891 [PubMed - as supplied by publisher]

Related Articles A metabolomic study using HPLC-TOF/MS coupled with ingenuity pathway analysis: Intervention effects of Rhizoma Alismatis on spontaneous hypertensive rats. J Pharm Biomed Anal. 2015 Sep 25;117:446-452 Authors: Chu Y, Jiang H, Ju J, Li Y, Gong L, Wang X, Yang W, Deng Y Abstract Rhizoma Alismatis, an important crude herb component in traditional Chinese medicine, has been commonly used for treating hypertension, but its mechanism has not been clarified in level of metabolic. Therefore, in the present work, metabolomics study coupled with ingenuity pathway analysis (IPA) have been performed to explore the potential mechanism in anti-hypertensive effect of Rhizoma Alismatis. Serum samples from SHRs and WKYs were analyzed with the use of high performance liquid chromatography coupled with time of flight mass spectrometry detection (HPLC-TOF/MS) in positive polarity. The obtained data sets were statistically analyzed using univariate and multivariate statistical analyses including the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) for pattern recognition and selection of significant metabolites. 12 potential biomarkers in rat serum were screened out from HMDB, METLIN and KEGG databases. Furthermore, IPA was introduced and Glycerophospholipid metabolism and Purine metabolism were filtered out as potential target pathways. This metabolomic approach coupled with IPA provided a feasible way to understand the therapeutic mechanism of Rhizoma Alismatis on spontaneous hypertensive rats. PMID: 26454337 [PubMed - as supplied by publisher]

Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice. Biochem Biophys Res Commun. 2015 Oct 7; Authors: Geiger A, Walker A, Nissen E Abstract Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. PMID: 26454169 [PubMed - as supplied by publisher]

Altered histamine neurotransmission in HPRT-deficient mice. Neurosci Lett. 2015 Oct 7; Authors: Tschirner SK, Gutzki F, Kaever V, Seifert R, Schneider EH Abstract Lesch-Nyhan syndrome (LNS) is an X-chromosomal disorder with congenital deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) as underlying defect. We determined the concentrations of dopamine, histamine and their metabolites in brains of HPRT knockout mice, which serve as an animal model for LNS, and compared the results to those obtained from wild-type controls. Analyses were performed by high performance liquid chromatography (HPLC)-coupled tandem mass spectrometry (MS/MS). Besides a decrease of dopamine and 3-methoxytyramine (3-MT) concentrations in the cerebral hemisphere, HPRT-deficient mice also exhibited significantly reduced 1-methyl histamine (1-MH) and 1-methylimidazole-4-acetic acid (1-MI4AA) concentrations in the brain hemisphere and medulla. Moreover, the amount of 1-MI4AA was significantly decreased in the cerebellum. Our findings show that neuronal perturbations caused by HPRT deficiency are not restricted to the dopamine system but also affect histaminergic neurotransmission. These new insights into the brain metabolism of an LNS mouse model may help to find new therapeutic strategies to improve the quality of life of LNS patients. PMID: 26453761 [PubMed - as supplied by publisher]