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Related Articles An apolar Pistacia lentiscus L. leaf extract: GC-MS metabolic profiling and evaluation of cytotoxicity and apoptosis inducing effects on SH-SY5Y and SK-N-BE(2)C cell lines. Food Chem Toxicol. 2016 Sep;95:64-74 Authors: Piccolella S, Nocera P, Carillo P, Woodrow P, Greco V, Manti L, Fiorentino A, Pacifico S Abstract In the course of a cytotoxicity screening of Mediterranean plants vs. neuroblastoma cells, Pistacia lentiscus was of interest. Pl-C extract, prepared from dried leaves by ultrasound assisted maceration (UAM) in chloroform, was profiled through using GC-MS techniques. To evaluate Pl-C cytotoxicity towards SH-SY5Y and SK-N-BE(2)-C cell lines, MTT, SRB and LDH assays were performed. The caspase-3 activation, DNA fragmentation, as well as micronucleation, were also evaluated. The Pl-C oxidant/antioxidant ability was estimated using different methods. The extract, rich in pentacyclic triterpenes, inhibited mitochondrial redox activity and cell viability of the tested cell lines. LDH assay established that Pl-C did not affect the cell membrane integrity. Indeed, it was able to activate caspase-3 and to cause a ladder pattern of DNA. Western blotting analysis showed that Pl-C processed caspase-3 providing two cleavage products of approximately 20 and 17-kDa, whose densitometric evaluation highlighted that Pl-C was more effective than vinblastine by 3-fold. The pro-apoptotic effect could be related to a disturbance in cell redox balance. In fact, it increased intracellular ROS production, GSSG/GSH ratio and the formation of lipoperoxidation products. The data obtained prompted to further investigate and assess the in vivo efficacy of Pl-C to prevent and/or treat neuroblastoma. PMID: 27375189 [PubMed - indexed for MEDLINE]

24 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 2017/03/23PubMed comprises more than millions of 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.

23 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 2017/03/21PubMed comprises more than millions of 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.

Related Articles A metabolomic approach shows sphingosine 1-phosphate and lysophospholipids as mediators of the therapeutic effect of liver growth factor in emphysema. J Pharm Biomed Anal. 2017 Feb 27;139:238-246 Authors: Navarrete A, Rupérez FJ, Mendes TO, Pérez-Rial S, Girón-Martínez A, Terrón-Expósito R, Díaz-Gil JJ, Peces-Barba G, Barbas C, García A Abstract Tobacco smoke exposure is the principal cause of lung tissue destruction, which in turn results in emphysema that leads into shortness of breath. Liver growth factor (LGF, a cell and tissue regenerating factor with therapeutic activity in several organs) has antifibrotic and antioxidant properties that could be useful to promote lung tissue regenerating capacity in damaged lungs. The current study has examined differences in metabolite profiles (fingerprints) of plasma from mice (strain C57BL/6J, susceptible to develop emphysema) exposed to tobacco smoke during six months. One group of mice received a treatment with Liver Growth Factor (LGF) after emphysema was established, whereas the other group did not receive the treatment. Age and sex-matched mice not exposed to smoke were also maintained with or without treatment as controls. Metabolic fingerprints (untargeted analysis) of plasma after protein precipitation were obtained by LC-QTOF-MS. The signals were processed and a large number of possible metabolites were found (23944). Multivariate data analysis provided models that highlighted the differences between control and smoke exposed mice in both conditions. Accurate masses of features (possible compounds) representing significant differences were searched using online public databases. Lipid mediators, related to intracellular signaling in inflammation, were found among the metabolites putatively identified as markers of the different conditions and among them, sphingosine, sphingosine 1-phosphate and lysophospholipids point at the relevance of such metabolites in the regulation of the processes related to tissue regeneration mediated by LGF. These results also suggest that metabolomic fingerprinting could potentially guide the characterization of relevant metabolites leading the regeneration of lungs in emphysema disease. PMID: 28314215 [PubMed - as supplied by publisher]

Related Articles NMR-based plasma metabolomic discrimination for male fertility assessment of rats treated with Eurycoma longifolia extracts. Syst Biol Reprod Med. 2017 Mar 17;:1-13 Authors: Ebrahimi F, Ibrahim B, Teh CH, Murugaiyah V, Chan KL Abstract Male infertility is one of the leading causes of infertility which affects many couples worldwide. Semen analysis is a routine examination of male fertility status which is usually performed on semen samples obtained through masturbation that may be inconvenient to patients. Eurycoma longifolia (Tongkat Ali, TA), native to Malaysia, has been traditionally used as a remedy to boost male fertility. In our recent studies in rats, upon the administration of high-quassinoid content extracts of TA including TA water (TAW), quassinoid-rich TA (TAQR) extracts, and a low-quassinoid content extract including quassinoid-poor TA (TAQP) extract, sperm count (SC) increased in TAW- and TAQR-treated rats when compared to the TAQP-treated and control groups. Consequently, the rats were divided into normal- (control and TAQP-treated) and high- (TAW- and TAQR-treated) SC groups [Ebrahimi et al. 2016]. Post-treatment rat plasma was collected. An optimized plasma sample preparation method was developed with respect to the internal standards sodium 3- (trimethylsilyl) propionate- 2,2,3,3- d4 (TSP) and deuterated 4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA). Carr-Purcell-Meibum-Gill (CPMG) experiments combined with orthogonal partial least squares discriminant analysis (OPLS-DA) was employed to evaluate plasma metabolomic changes in normal- and high-SC rats. The potential biomarkers associated with SC increase were investigated to assess fertility by capturing the metabolomic profile of plasma. DSA was selected as the optimized internal standard for plasma analysis due to its significantly smaller half-height line width (W h/2) compared to that of TSP. The validated OPLS-DA model clearly discriminated the CPMG profiles in regard to the SC level. Plasma profiles of the high-SC group contained higher levels of alanine, lactate, and histidine, while ethanol concentration was significantly higher in the normal-SC group. This approach might be a new alternative applicable to the fertility assessment in humans through the quantitative metabolomic analysis of plasma without requiring semen. ABBREVIATIONS: TA: Tongkat Ali; LOD: limit of detection; LOQ: limit of quantification; HPLC-UV: high performance liquid chromatography-ultrviolet; PDA: photodiode array; NMR: nuclear magnetic resonance; FID: free induction decay; LC-MS: liquid chromatography-mass spectrometry; GC-MS: gas chromatography-mass spectrometry; HSQC: heteronuclear single quantum coherence; CPMG: Carr-Purcell-Meibum-Gill; VLDL: very low density lipoprotein; HDL: high density lipoprotein; EDTA: ethylenediaminetetraacetic acid; ANOVA: analysis of variance; AMIX: analysis of mixtures; SIMCA: soft independent modeling of class analogy; PCA: principal components analysis; OPLS-DA: orthogonal partial least-squares discriminant analysis; VIP: variable importance plot; AUROC: area under the receiver operating characteristic; TSP: sodium 3-(trimethylsilyl) propionate- 2,2,3,3- d4; DSA: deuterated 4-dimethyl-4-silapentane-1-ammonium trifluoroacetate; ESI: electrospray ionization; TCA: trichloroacetic acid; ACN: acetonitrile; dd H2O: distilled deionized water; FSH: follicle-stimulating hormone; LH: luteinizing hormone; OECD: Organisation for Economic Co-operation and Development. PMID: 28306342 [PubMed - as supplied by publisher]

Related Articles Development of Chemical Isotope Labeling LC-MS for Milk Metabolomics: Comprehensive and Quantitative Profiling of the Amine/Phenol Submetabolome. Anal Chem. 2017 Mar 17;: Authors: Mung D, Li L Abstract Milk is a complex sample containing a variety of proteins, lipids and metabolites. Studying the milk metabolome represents an important application of metabolomics in the general area of nutritional research. However, comprehensive and quantitative analysis of milk metabolites is a challenging task due to the wide range of variations in chemical/physical properties and concentrations of these metabolites. We report an analytical workflow for in-depth profiling of the milk metabolome based on chemical isotope labeling (CIL) and liquid chromatography mass spectrometry (LC-MS) with a focus of using dansylation labeling to target the amine/phenol submetabolome. An optimal sample preparation method including the use of methanol at a 3:1 ratio of solvent to milk for protein precipitation and dichloromethane for lipid removal was developed to detect and quantify as many metabolites as possible. This workflow was found to be generally applicable to profile milk metabolomes of different species (cow, goat and human) and types. Results from experimental replicate analysis (n=5) of 1:1, 2:1 and 1:2 (12)C-/(13)C-labeled cow milk samples showed that 95.7%, 94.3% and 93.2% of peak pairs, respectively, had ratio values within ±50% accuracy range and 90.7%, 92.6% and 90.8% peak pairs had RSD values of less than 20%. In the metabolomic analysis of 36 samples from different categories of cow milk (brands, batches and fat percentages) with experimental triplicates, a total of 7104 peak pairs or metabolites could be detected with an average of 4573±505 (n=108) pairs detected per LC-MS run. Among them, 3820 peak pairs were consistently detected in over 80% of the samples with 70 metabolites positively identified by mass and retention time matches to the dansyl standard library and 2988 pairs with their masses matched to the human metabolome libraries. This unprecedentedly high coverage of the amine/phenol submetabolome illustrates the complexity of the milk metabolome. Since milk and milk products are consumed in large quantities on a daily basis, the intake of these milk metabolites even at low concentrations can be cumulatively high. The high-coverage analysis of the milk metabolome using CIL LC-MS should be very useful in future research involving the study of the effects of these metabolites on human health. It should also be useful in the dairy industry in areas such as improving milk production, developing new processing technologies, developing improved nutritional products, quality control, and milk product authentication. PMID: 28306241 [PubMed - as supplied by publisher]

Related Articles Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles. Sci Rep. 2017 Mar 17;7:44541 Authors: Lopes-Rodrigues V, Di Luca A, Mleczko J, Meleady P, Henry M, Pesic M, Cabrera D, van Liempd S, Lima RT, O'Connor R, Falcon-Perez JM, Vasconcelos MH Abstract Multidrug resistance (MDR) is a serious obstacle to efficient cancer treatment. Overexpression of P-glycoprotein (P-gp) plays a significant role in MDR. Recent studies proved that targeting cellular metabolism could sensitize MDR cells. In addition, metabolic alterations could affect the extracellular vesicles (EVs) cargo and release. This study aimed to: i) identify metabolic alterations in P-gp overexpressing cells that could be involved in the development of MDR and, ii) identify a potential role for the EVs in the acquisition of the MDR. Two different pairs of MDR and their drug-sensitive counterpart cancer cell lines were used. Our results showed that MDR (P-gp overexpressing) cells have a different metabolic profile from their drug-sensitive counterparts, demonstrating decreases in the pentose phosphate pathway and oxidative phosphorylation rate; increases in glutathione metabolism and glycolysis; and alterations in the methionine/S-adenosylmethionine pathway. Remarkably, EVs from MDR cells were capable of stimulating a metabolic switch in the drug-sensitive cancer cells, towards a MDR phenotype. In conclusion, obtained results contribute to the growing knowledge about metabolic alterations in MDR cells and the role of EVs in the intercellular transfer of MDR. The specific metabolic alterations identified in this study may be further developed as targets for overcoming MDR. PMID: 28303926 [PubMed - in process]

Related Articles Alterations in Cytosolic and Mitochondrial [U-(13)C]Glucose Metabolism in a Chronic Epilepsy Mouse Model. eNeuro. 2017 Jan-Feb;4(1): Authors: McDonald TS, Carrasco-Pozo C, Hodson MP, Borges K Abstract Temporal lobe epilepsy is a common form of adult epilepsy and shows high resistance to treatment. Increasing evidence has suggested that metabolic dysfunction contributes to the development of seizures, with previous studies indicating impairments in brain glucose metabolism. Here we aim to elucidate which pathways involved in glucose metabolism are impaired, by tracing the hippocampal metabolism of injected [U-(13)C]glucose (i.p.) during the chronic stage of the pilocarpine-status epilepticus mouse model of epilepsy. The enrichment of (13)C in the intermediates of glycolysis and the TCA cycle were quantified in hippocampal extracts using liquid chromatography-tandem mass spectroscopy, along with the measurement of the activities of enzymes in each pathway. We show that there is reduced incorporation of (13)C in the intermediates of glycolysis, with the percentage enrichment of all downstream intermediates being highly correlated with those of glucose 6-phosphate. Furthermore, the activities of all enzymes in this pathway including hexokinase and phosphofructokinase were unaltered, suggesting that glucose uptake is reduced in this model without further impairments in glycolysis itself. The key findings were 33% and 55% losses in the activities of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase, respectively, along with reduced (13)C enrichment in TCA cycle intermediates. This lower (13)C enrichment is best explained in part by the reduced enrichment in glycolytic intermediates, whereas the reduction of key TCA cycle enzyme activity indicates that TCA cycling is also impaired in the hippocampal formation. Together, these data suggest that multitarget approaches may be necessary to restore metabolism in the epileptic brain. PMID: 28303258 [PubMed - in process]

Related Articles Anemone medicinal plants: ethnopharmacology, phytochemistry and biology. Acta Pharm Sin B. 2017 Mar;7(2):146-158 Authors: Hao DC, Gu X, Xiao P Abstract The Ranunculaceae genus Anemone (order Ranunculales), comprising more than 150 species, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine. Various medicinal compounds have been found in Anemone plants, especially triterpenoid saponins, some of which have shown anti-cancer activities. Some Anemone compounds and extracts display immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial activities. More than 50 species have ethnopharmacological uses, which provide clues for modern drug discovery. Anemone compounds exert anticancer and other bioactivities via multiple pathways. However, a comprehensive review of the Anemone medicinal resources is lacking. We here summarize the ethnomedical knowledge and recent progress on the chemical and pharmacological diversity of Anemone medicinal plants, as well as the emerging molecular mechanisms and functions of these medicinal compounds. The phylogenetic relationships of Anemone species were reconstructed based on nuclear ITS and chloroplast markers. The molecular phylogeny is largely congruent with the morphology-based classification. Commonly used medicinal herbs are distributed in each subgenus and section, and chemical and biological studies of more unexplored taxa are warranted. Gene expression profiling and relevant "omics" platforms could reveal differential effects of phytometabolites. Genomics, transcriptomics, proteomics, and metabolomics should be highlighted in deciphering novel therapeutic mechanisms and utilities of Anemone phytometabolites. PMID: 28303220 [PubMed]

Related Articles Urinary metabolites along with common and rare genetic variations are associated with incident chronic kidney disease. Kidney Int. 2017 Mar 14;: Authors: McMahon GM, Hwang SJ, Clish CB, Tin A, Yang Q, Larson MG, Rhee EP, Li M, CKDGen Consortium, Levy D, O'Donnell CJ, Coresh J, Young JH, Gerszten RE, Fox CS Abstract We assessed the association between urinary metabolites, genetic variants, and incident chronic kidney disease (CKD) in the Framingham Offspring cohort. Among the participants, 193 individuals developed CKD (estimated glomerular filtration rate under 60 ml/min/1.73m(2)) between cohort examinations 6 (1995-1998) and 8 (2005-2008, mean follow-up 9.7 years). They were age- and sex-matched to 193 control individuals free of CKD. A total of 154 urinary metabolites were measured using mass spectrometry, and the association between metabolites and CKD was examined using logistic regression. Next, we tested the genetic associations of each metabolite with an Illumina exome chip. Urinary glycine and histidine were associated with a lower risk of incident CKD with an odds ratio of 0.59 (95% confidence interval [CI] 0.43-0.80) and 0.65 (0.50-0.85) respectively, per one standard deviation increase in metabolite concentration. Follow-up in the Atherosclerosis Risk in Communities cohort confirmed the association of urinary glycine with CKD. In exome chip analyses, 36 single nucleotide polymorphisms at 30 loci were significantly associated with 31 metabolites. We surveyed exome chip findings for associations with known renal function loci such as rs8101881 in SLC7A9 coding for an amino acid transporter, which has been associated with a lower risk of CKD. We found this polymorphism was significantly associated with higher levels of lysine and NG-monomethyl-L-arginine (NMMA). Increased urinary lysine and NMMA were associated with a lower risk of CKD (0.73 [0.50-0.90] and 0.66 [0.53-0.83], respectively) in the univariate model. Thus, low urinary glycine and histidine are associated with incident CKD. Furthermore, genomic association of urinary metabolomics identified lysine and NMMA as being linked with CKD and provided additional evidence for the association of SLC7A9 with kidney disease. PMID: 28302371 [PubMed - as supplied by publisher]

Related Articles Clinically proven mtDNA mutations are not common in those with chronic fatigue syndrome. BMC Med Genet. 2017 Mar 16;18(1):29 Authors: Schoeman EM, Van Der Westhuizen FH, Erasmus E, van Dyk E, Knowles CV, Al-Ali S, Ng WF, Taylor RW, Newton JL, Elson JL Abstract BACKGROUND: Chronic Fatigue Syndrome (CFS) is a prevalent debilitating condition that affects approximately 250,000 people in the UK. There is growing interest in the role of mitochondrial function and mitochondrial DNA (mtDNA) variation in CFS. It is now known that fatigue is common and often severe in patients with mitochondrial disease irrespective of their age, gender or mtDNA genotype. More recently, it has been suggested that some CFS patients harbour clinically proven mtDNA mutations. METHODS: MtDNA sequencing of 93 CFS patients from the United Kingdom (UK) and South Africa (RSA) was performed using an Ion Torrent Personal Genome Machine. The sequence data was examined for any evidence of clinically proven mutations, currently; more than 200 clinically proven mtDNA mutations point mutations have been identified. RESULTS: We report the complete mtDNA sequence of 93 CFS patients from the UK and RSA, without finding evidence of clinically proven mtDNA mutations. This finding demonstrates that clinically proven mtDNA mutations are not a common element in the aetiology of disease in CFS patients. That is patients having a clinically proven mtDNA mutation and subsequently being misdiagnosed with CFS are likely to be rare. CONCLUSION: The work supports the assertion that CFS should not be considered to fall within the spectrum of mtDNA disease. However, the current study cannot exclude a role for nuclear genes with a mitochondrial function, nor a role of mtDNA population variants in susceptibility to disease. This study highlights the need for more to be done to understand the pathophysiology of CFS. PMID: 28302057 [PubMed - in process]

Related Articles Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools. Curr Drug Metab. 2017 Mar 15;: Authors: Issa NT, Wathieu H, Ojo A, Byers SW, Dakshanamurthy S Abstract Increased R & D spending and high failure rates exist in drug development, due in part to inadequate prediction of drug metabolism and its consequences in the human body. Hence, there is a need for computational methods to supplement and complement current biological assessment strategies. In this review, we provide an overview of drug metabolism in pharmacology, and discuss the current in vitro and in vivo strategies for assessing drug metabolism in preclinical drug development. We highlight computational tools available to the scientific community for the in silico prediction of drug metabolism, and examine how these tools have been implemented to produce drug-target signatures relevant to metabolic routes. Computational workflows that assess drug metabolism and its toxicological and pharmacokinetic effects, such as by applying the adverse outcome pathway framework for risk assessment, may improve the efficiency and speed of preclinical drug development. PMID: 28302026 [PubMed - as supplied by publisher]

20 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 2017/03/17PubMed comprises more than millions of 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.

30 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 2017/03/16PubMed comprises more than millions of 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.

Related Articles Metabolomics of the tick-Borrelia interaction during the nymphal tick blood meal. Sci Rep. 2017 Mar 13;7:44394 Authors: Hoxmeier JC, Fleshman AC, Broeckling CD, Prenni JE, Dolan MC, Gage KL, Eisen L Abstract The causal agents of Lyme disease in North America, Borrelia burgdorferi and Borrelia mayonii, are transmitted primarily by Ixodes scapularis ticks. Due to their limited metabolic capacity, spirochetes rely on the tick blood meal for nutrients and metabolic intermediates while residing in the tick vector, competing with the tick for nutrients in the blood meal. Metabolomics is an effective methodology to explore dynamics of spirochete survival and multiplication in tick vectors before transmission to a vertebrate host via tick saliva. Using gas chromatography coupled to mass spectrometry, we identified statistically significant differences in the metabolic profile among uninfected I. scapularis nymphal ticks, B. burgdorferi-infected nymphal ticks and B. mayonii-infected nymphal ticks by measuring metabolism every 24 hours over the course of their up to 96 hour blood meals. Specifically, differences in the abundance of purines, amino acids, carbohydrates, and fatty acids during the blood meal among the three groups of nymphal ticks suggest that B. mayonii and B. burgdorferi may have different metabolic capabilities, especially during later stages of nymphal feeding. Understanding mechanisms underlying variable metabolic requirements of different Lyme disease spirochetes within tick vectors could potentially aid development of novel methods to control spirochete transmission. PMID: 28287618 [PubMed - in process]

Related Articles The Effect of Chinese Herbal Medicine Formula mKG on Allergic Asthma by Regulating Lung and Plasma Metabolic Alternations. Int J Mol Sci. 2017 Mar 10;18(3): Authors: Yu M, Jia HM, Cui FX, Yang Y, Zhao Y, Yang MH, Zou ZM Abstract Asthma is a chronic inflammatory disorder of the airway and is characterized by airway remodeling, hyperresponsiveness, and shortness of breath. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to have good therapeutic effects on experimental allergic asthma. However, its anti-asthma mechanism remains currently unknown. In the present work, metabolomics studies of biochemical changes in the lung tissue and plasma of ovalbumin (OVA)-induced allergic asthma mice with mKG treatment were performed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation induced by OVA was reduced after mKG treatment. A total of twenty-four metabolites involved in seven metabolic pathways were identified as potential biomarkers in the development of allergic asthma. Among them, myristic acid (L3 or P2), sphinganine (L6 or P4), and lysoPC(15:0) (L12 or P16) were detected both in lung tissue and plasma. Additionally, l-acetylcarnitine (L1), thromboxane B2 (L2), 10-HDoHE (L10), and 5-HETE (L11) were first reported to be potential biomarkers associated with allergic asthma. The treatment of mKG mediated all of those potential biomarkers except lysoPC(15:0) (P16). The anti-asthma mechanism of mKG can be achieved through the comprehensive regulation of multiple perturbed biomarkers and metabolic pathways. PMID: 28287417 [PubMed - in process]

Related Articles Metabolic map of osthole and its effect on lipids. Xenobiotica. 2017 Mar 13;:1-38 Authors: Zhao Q, Li XM, Liu HN, Gonzalez FJ, Li F Abstract 1. Osthole, a coumarin compound from plants, is a promising agent for the treatment of metabolic diseases, including hyperglycemia, fatty liver, and cancers. Studies indicate that the peroxisome proliferator-activated receptors (PPAR) α and γ are involved in the pharmacological effects of osthole. The in vitro and in vivo metabolism of osthole, and its biological activity are not completely understood. 2. In this study, UPLC-ESI-QTOFMS-based metabolomics was used to determine the metabolic pathway of osthole and its influence on the levels of endogenous metabolites. Forty-one osthole metabolites, including twenty-three novel metabolites, were identified and structurally elucidated from its metabolism in vitro and in vivo. Recombinant cytochrome P450s (CYPs) screening showed that CYP3A4 and CYP3A5 were the primary enzymes contributing to osthole metabolism. 3. More importantly, osthole was able to decrease the levels of lysophosphatidylethanolamine and lysophosphatidylcholine in the plasma, which explains in part its modulatory effects on metabolic diseases. 4. This study gives the insights about the metabolic pathways of osthole in vivo, including hydroxylation, glucuronidation, and sulfation. Furthermore, the levels of the lipids regulated by osthole indicated its potential effects on adipogenesis. These data contribute to the understanding of the disposition and pharmacological activity of osthole in vivo. PMID: 28287022 [PubMed - as supplied by publisher]

Related Articles Systems analysis of ethanol production in the genetically engineered cyanobacterium Synechococcus sp. PCC 7002. Biotechnol Biofuels. 2017;10:56 Authors: Kopka J, Schmidt S, Dethloff F, Pade N, Berendt S, Schottkowski M, Martin N, Dühring U, Kuchmina E, Enke H, Kramer D, Wilde A, Hagemann M, Friedrich A Abstract BACKGROUND: Future sustainable energy production can be achieved using mass cultures of photoautotrophic microorganisms, which are engineered to synthesize valuable products directly from CO2 and sunlight. As cyanobacteria can be cultivated in large scale on non-arable land, these phototrophic bacteria have become attractive organisms for production of biofuels. Synechococcus sp. PCC 7002, one of the cyanobacterial model organisms, provides many attractive properties for biofuel production such as tolerance of seawater and high light intensities. RESULTS: Here, we performed a systems analysis of an engineered ethanol-producing strain of the cyanobacterium Synechococcus sp. PCC 7002, which was grown in artificial seawater medium over 30 days applying a 12:12 h day-night cycle. Biosynthesis of ethanol resulted in a final accumulation of 0.25% (v/v) ethanol, including ethanol lost due to evaporation. The cultivation experiment revealed three production phases. The highest production rate was observed in the initial phase when cells were actively growing. In phase II growth of the producer strain stopped, but ethanol production rate was still high. Phase III was characterized by a decrease of both ethanol production and optical density of the culture. Metabolomics revealed that the carbon drain due to ethanol diffusion from the cell resulted in the expected reduction of pyruvate-based intermediates. Carbon-saving strategies successfully compensated the decrease of central intermediates of carbon metabolism during the first phase of fermentation. However, during long-term ethanol production the producer strain showed clear indications of intracellular carbon limitation. Despite the decreased levels of glycolytic and tricarboxylic acid cycle intermediates, soluble sugars and even glycogen accumulated in the producer strain. The changes in carbon assimilation patterns are partly supported by proteome analysis, which detected decreased levels of many enzymes and also revealed the stress phenotype of ethanol-producing cells. Strategies towards improved ethanol production are discussed. CONCLUSIONS: Systems analysis of ethanol production in Synechococcus sp. PCC 7002 revealed initial compensation followed by increasing metabolic limitation due to excessive carbon drain from primary metabolism. PMID: 28286551 [PubMed]

Related Articles Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria. Metabolomics. 2017;13(4):41 Authors: Orikiiriza J, Surowiec I, Lindquist E, Bonde M, Magambo J, Muhinda C, Bergström S, Trygg J, Normark J Abstract INTRODUCTION: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection. METHODS: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5-6 years. Lipids from patient's plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method. RESULTS: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia. CONCLUSIONS: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses. PMID: 28286460 [PubMed - in process]

Related Articles Earwax: A neglected body secretion or a step ahead in clinical diagnosis? A pilot study. J Proteomics. 2017 Mar 09;: Authors: Shokry E, de Oliveira AE, Avelino MA, de Deus MM, Filho NR Abstract This work combines the advantages of volatile metabolites profiling as a young growing research field with a non-invasive sampling technique using earwax "a neglected body secretion" for detection and monitoring of biomarkers for diabetes mellitus (types 1 and 2). Earwax samples were collected from 26 diabetic patients of both types, analyzed by headspace gas chromatography mass spectrometry and confronted to the volatile earwax composition of 33 healthy individuals. Data mining analysis was conducted using different models to discriminate the healthy individuals from the diabetic patients and to discriminate between both types of diabetes as well. The model with the best discriminating ability was found to be partial least squares discriminant analysis (PLS-DA) after variable selection. The 6 most important biomarkers were ethanol, acetone, methoxyacetone, hydroxyurea, isobutyraldehyde, and acetic acid. The multivariate model constructed was validated using a test data set and was able to correctly predict all the samples. The receiver operating characteristic (ROC) curves were built for the 6 variables for diabetes types 1 and 2 diagnoses. Among the 6 variables selected, methoxyacetone was the only biomarker able solely to perfectly discriminate between diabetes types 1 and 2. The method is simple, non-invasive, accurate, and highly accepted by patients. SIGNIFICANCE: Our method involves a volatolomic approach by headspace gas chromatography coupled with mass spectrometry as a single analytical technique combined with multivariate data analysis to detect biomarkers of diabetes in earwax samples. Our method was able to discriminate with high accuracy between 33 healthy controls and 26 diabetic patients as well as its types (1 and 2). Our method employing earwax, a "neglected biological matrix" not only has the advantage of non-invasive sampling but also overcomes the limitations of the applied procedures in other biological samples, involving no or minimum sample pretreatment, no external contamination and utilizing a simple sample collection technique. PMID: 28286320 [PubMed - as supplied by publisher]