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Metabolomics in Plant Stress Physiology. Adv Biochem Eng Biotechnol. 2018 Feb 23;: Authors: Ghatak A, Chaturvedi P, Weckwerth W Abstract Metabolomics is an essential technology for functional genomics and systems biology. It plays a key role in functional annotation of genes and understanding towards cellular and molecular, biotic and abiotic stress responses. Different analytical techniques are used to extend the coverage of a full metabolome. The commonly used techniques are NMR, CE-MS, LC-MS, and GC-MS. The choice of a suitable technique depends on the speed, sensitivity, and accuracy. This chapter provides insight into plant metabolomic techniques, databases used in the analysis, data mining and processing, compound identification, and limitations in metabolomics. It also describes the workflow of measuring metabolites in plants. Metabolomic studies in plant responses to stress are a key research topic in many laboratories worldwide. We summarize different approaches and provide a generic overview of stress responsive metabolite markers and processes compiled from a broad range of different studies. Graphical Abstract. PMID: 29470599 [PubMed - as supplied by publisher]

RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites. Metabolites. 2018 Feb 22;8(1): Authors: Zhang B, Hu S, Baskin E, Patt A, Siddiqui JK, Mathé EA Abstract The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be checked multiple times a year and RaMP will be updated accordingly. PMID: 29470400 [PubMed]

Plant-derived polyphenols in human health: biological activity, metabolites and putative molecular targets. Curr Drug Metab. 2018 Feb 19;: Authors: Olivares-Vicente M, Barrajon-Catalan E, Herranz-Lopez M, Segura-Carretero A, Joven J, Encinar JA, Micol V Abstract Edible plants such as Hibiscus sabdariffa, Lippia citriodora, Rosmarinus officinalis and Olea europaea, are rich in bioactive compounds that represent most of the phenolic compounds families and have exhibited potential benefits in human health. These plants have been commonly used in folk medicine for their potential therapeutic properties in human chronic diseases. Recent evidence on these plants leads to postulate that polyphenols may account for such effects. Nevertheless, the compounds or metabolites that are responsible for reaching the molecular targets are still unknown. Data based on studies that directly use complex extracts on cellular models, without considering metabolic aspects, have limited applicability. In contrast, studies exploring the absorption process, metabolites in the blood circulation and tissues have become essential to identify the intracellular final effectors that are responsible for extracts bioactivity. Once the cellular metabolites are identified, computational molecular docking techniques suppose a unique tool for virtually screening a large number of compounds on selected protein targets in order to elucidate their potential mechanisms. In this review, we provide an updated overview of the in vitro and in vivo studies on the toxicity, absorption, permeability, pharmacokinetics and cellular metabolism of bioactive compounds derived from the abovementioned plants to identify the potential compounds that are responsible for the observed health effects. We also propose the use of in silico studies to virtually screen metabolites on selected protein targets, in combination with targeted metabolomics with high resolution mass spectrometry and using the candidate metabolites in cellular models, as the method of choice for elucidating the molecular mechanisms of these compounds.  . PMID: 29468962 [PubMed - as supplied by publisher]

Related Articles Urinary Metabolomics Profiles Associated to Bovine Meat Ingestion in Humans. Mol Nutr Food Res. 2018 Feb 22;: Authors: Khodorova NV, Rutledge DN, Oberli M, Mathiron D, Marcelo P, Benamouzig R, Tomé D, Gaudichon C, Pilard S Abstract SCOPE: The impact of meat consumption on human health is widely examined in nutritional epidemiological studies, especially due to the connexion between the consumption of red and processed meat and the risk of colon cancer. Food questionnaires do not assess the exposure to different methods of meat cooking. This study aimed to identify biomarkers of the acute ingestion of bovine meat cooked with 2 different processes. METHODS AND RESULTS: Non-targeted UPLC-MS metabolite profiling was done on urine samples obtained from 24 healthy volunteers before and 8h after the ingestion of a single meal composed of intrinsically 15 N labelled bovine meat, either cooked at 55 °C for 5 min or at 90 °C for 30 min. A Discriminant Analysis extension of Independent Components Analysis was applied to the mass spectral data. After meat ingestion, the urinary excretion of 1-methylhistidine, phenylacetylglutamine and short and medium-chained acylcarnitines was observed. 15 N labelling was detected in these metabolites thus confirming their origin from ingested meat. However, no difference was observed in urinary metabolomic profiles according to the meat cooking process used. CONCLUSION: Meat ingestion led to the excretion of several nitrogen-containing compounds, but although a metabolic signature was detected for meat ingestion, the impact of cooking process was not detectable at the level of urinary metabolic signature in our experimental conditions. This article is protected by copyright. All rights reserved. PMID: 29468821 [PubMed - as supplied by publisher]

Related Articles Evidence for Shikonin acting as an active inhibitor of human carboxylesterases 2: Implications for herb-drug combination. Phytother Res. 2018 Feb 22;: Authors: Li JN, Cao YF, He RR, Ge GB, Guo B, Wu JJ Abstract Shikonin, a natural naphthoquinone compound derived from the herb Lithospermum erythrorhizon, is widely used for its various pharmacological activities. However, its potential interactions with other medications by inhibiting human carboxylesterases 2 (hCE2) remain unknown. In this study, the inhibitory effects of shikonin on the activity of hCE2 in human liver microsomes are investigated by using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN), and CPT-11 as substrates of hCE2. The results demonstrate that shikonin significantly inhibits the activity of hCE2 when FD and NCEN are used as substrates, whereas the half inhibition concentration value of shikonin increased by 5-30 times when CPT-11 was used as the substrate. The inhibition types of shikonin against hCE2 activity reflected by 3 substrates were all best fit to noncompetitive manners. In addition, shikonin was found to distinctly suppress endogenous hCE2 activity, characterized with attenuated fluorescence. Furthermore, for drugs metabolized by hCE2 with the similar binding sites with FD or NCEN, the estimated magnitudes of area under the curve variation were approximately 9-357% in the presence of shikonin. Also, the area under the curve of CPT-11 could be increased by 1-14% following administration of shikonin. These findings have clear clinical implications for the combination of shikonin and hCE2-metabolizing prodrugs. PMID: 29468758 [PubMed - as supplied by publisher]

Related Articles Wheezing preschool children with early-onset asthma reveal a specific metabolomic profile. Pediatr Allergy Immunol. 2018 Feb 22;: Authors: Carraro S, Bozzetto S, Giordano G, El Mazloum D, Stocchero M, Pirillo P, Zanconato S, Baraldi E Abstract BACKGROUND: Many children of preschool age present with recurrent wheezing. Most of them outgrow their symptoms, while some have early-onset asthma. Aim of this prospective preliminary study was to apply a metabolomic approach to see whether biochemical-metabolic urinary profiles can have a role in the early identification of the children with asthma. METHODS: Preschool children with recurrent wheezing were recruited and followed up for 3 years, after which they were classified as cases of transient wheezing or early-onset asthma. A urine sample was collected at recruitment and analyzed using a metabolomic approach based on UPLC-mass spectrometry. RESULTS: Among 34 children aged 4.0±1.1 years recruited, at the end of the 3-year follow up, 16 were classified as having transient wheezing and 16 as cases of early-onset asthma. Through a joint multivariate and univariate statistical analysis we identified a subset of metabolomic variables that enabled the two groups to be clearly distinguished. The model built using the identified variables showed an AUC=0.99, and an AUC=0.88 on seven-fold full cross-validation(p=0.002). CONCLUSIONS: Metabolomic urinary profile can discriminate preschoolers with recurrent wheezing who will outgrow their symptoms from those who have early-onset asthma. These results may pave the way to the characterization of early non-invasive biomarkers capable of predicting asthma development. This article is protected by copyright. All rights reserved. PMID: 29468750 [PubMed - as supplied by publisher]

Related Articles Polyamines: Bio-Molecules with Diverse Functions in Plant and Human Health and Disease. Front Chem. 2018;6:10 Authors: Handa AK, Fatima T, Mattoo AK Abstract Biogenic amines-polyamines (PAs), particularly putrescine, spermidine and spermine are ubiquitous in all living cells. Their indispensable roles in many biochemical and physiological processes are becoming commonly known, including promoters of plant life and differential roles in human health and disease. PAs positively impact cellular functions in plants-exemplified by increasing longevity, reviving physiological memory, enhancing carbon and nitrogen resource allocation/signaling, as well as in plant development and responses to extreme environments. Thus, one or more PAs are commonly found in genomic and metabolomics studies using plants, particulary during different abiotic stresses. In humans, a general decline in PA levels with aging occurs parallel with some human health disorders. Also, high PA dose is detrimental to patients suffering from cancer, aging, innate immunity and cognitive impairment during Alzheimer and Parkinson diseases. A dichotomy exists in that while PAs may increase longevity and reduce some age-associated cardiovascular diseases, in disease conditions involving higher cellular proliferation, their intake has negative consequences. Thus, it is essential that PA levels be rigorously quantified in edible plant sources as well as in dietary meats. Such a database can be a guide for medical experts in order to recommend which foods/meats a patient may consume and which ones to avoid. Accordingly, designing both high and low polyamine diets for human consumption are in vogue, particularly in medical conditions where PA intake may be detrimental, for instance, cancer patients. In this review, literature data has been collated for the levels of the three main PAs, putrescine, spermidine and spermine, in different edible sources-vegetables, fruits, cereals, nuts, meat, sea food, cheese, milk, and eggs. Based on our analysis of vast literature, the effects of PAs in human/animal health fall into two broad, Yang and Yin, categories: beneficial for the physiological processes in healthy cells and detrimental under pathological conditions. PMID: 29468148 [PubMed]

Related Articles Antioxidant Phytochemicals in Fresh Produce: Exploitation of Genotype Variation and Advancements in Analytical Protocols. Front Chem. 2017;5:95 Authors: Manganaris GA, Goulas V, Mellidou I, Drogoudi P Abstract Horticultural commodities (fruit and vegetables) are the major dietary source of several bioactive compounds of high nutraceutical value for humans, including polyphenols, carotenoids and vitamins. The aim of the current review was dual. Firstly, toward the eventual enhancement of horticultural crops with bio-functional compounds, the natural genetic variation in antioxidants found in different species and cultivars/genotypes is underlined. Notably, some landraces and/or traditional cultivars have been characterized by substantially higher phytochemical content, i.e., small tomato of Santorini island (cv. "Tomataki Santorinis") possesses appreciably high amounts of ascorbic acid (AsA). The systematic screening of key bioactive compounds in a wide range of germplasm for the identification of promising genotypes and the restoration of key gene fractions from wild species and landraces may help in reducing the loss of agro-biodiversity, creating a healthier "gene pool" as the basis of future adaptation. Toward this direction, large scale comparative studies in different cultivars/genotypes of a given species provide useful insights about the ones of higher nutritional value. Secondly, the advancements in the employment of analytical techniques to determine the antioxidant potential through a convenient, easy and fast way are outlined. Such analytical techniques include electron paramagnetic resonance (EPR) and infrared (IR) spectroscopy, electrochemical, and chemometric methods, flow injection analysis (FIA), optical sensors, and high resolution screening (HRS). Taking into consideration that fruits and vegetables are complex mixtures of water- and lipid-soluble antioxidants, the exploitation of chemometrics to develop "omics" platforms (i.e., metabolomics, foodomics) is a promising tool for researchers to decode and/or predict antioxidant activity of fresh produce. For industry, the use of optical sensors and IR spectroscopy is recommended to estimate the antioxidant activity rapidly and at low cost, although legislation does not allow its correlation with health claims. PMID: 29468146 [PubMed]

Related Articles Regulation of ascorbate biosynthesis in green algae has evolved to enable rapid stress-induced response via the VTC2 gene encoding GDP-l-galactose phosphorylase. New Phytol. 2017 Apr;214(2):668-681 Authors: Vidal-Meireles A, Neupert J, Zsigmond L, Rosado-Souza L, Kovács L, Nagy V, Galambos A, Fernie AR, Bock R, Tóth SZ Abstract Ascorbate (vitamin C) plays essential roles in stress resistance, development, signaling, hormone biosynthesis and regulation of gene expression; however, little is known about its biosynthesis in algae. In order to provide experimental proof for the operation of the Smirnoff-Wheeler pathway described for higher plants and to gain more information on the regulation of ascorbate biosynthesis in Chlamydomonas reinhardtii, we targeted the VTC2 gene encoding GDP-l-galactose phosphorylase using artificial microRNAs. Ascorbate concentrations in VTC2 amiRNA lines were reduced to 10% showing that GDP-l-galactose phosphorylase plays a pivotal role in ascorbate biosynthesis. The VTC2 amiRNA lines also grow more slowly, have lower chlorophyll content, and are more susceptible to stress than the control strains. We also demonstrate that: expression of the VTC2 gene is rapidly induced by H2 O2 and 1 O2 resulting in a manifold increase in ascorbate content; in contrast to plants, there is no circadian regulation of ascorbate biosynthesis; photosynthesis is not required per se for ascorbate biosynthesis; and Chlamydomonas VTC2 lacks negative feedback regulation by ascorbate in the physiological concentration range. Our work demonstrates that ascorbate biosynthesis is also highly regulated in Chlamydomonas albeit via mechanisms distinct from those previously described in land plants. PMID: 28112386 [PubMed - indexed for MEDLINE]

17 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 2018/02/22PubMed 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.

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 2018/02/21PubMed 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 Circulating bile acids in healthy adults respond differently to a dietary pattern characterized by whole grains, legumes and fruits and vegetables compared to a diet high in refined grains and added sugars: a randomized, controlled, crossover feeding study. Metabolism. 2018 Feb 16;: Authors: Ginos BNR, Navarro SL, Schwarz Y, Gu H, Wang D, Randolph TW, Shojaie A, Hullar MAJ, Lampe PD, Kratz M, Neuhouser ML, Raftery D, Lampe JW Abstract OBJECTIVE: The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively. However, the effects of diets high in whole versus refined grains on circulating bile acids, which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied. MATERIALS AND METHODS: We conducted a secondary analysis from a randomized controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40 women/40 men, age 18-45 years) from the greater Seattle Area, half of which were normal weight (BMI 18.5-25.0 kg/m2) and half overweight to obese (BMI 28.0-39.9 kg/m2). Participants consumed two four-week controlled diets in randomized order: 1) a whole grain diet (WG diet), designed to be low in glycemic load (GL), high in whole grains, legumes, and fruits and vegetables, and 2) a refined grain diet (RG diet), designed to be high GL, high in refined grains and added sugars, separated by a four-week washout period. Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography tandem mass spectrometry. Concentrations of glucose, insulin, and CRP were measured in fasting serum. Linear mixed models were used to test the effects of diet on bile acid concentrations, and determine the association between plasma bile acid concentrations and HOMA-IR and CRP. Benjamini-Hochberg false discovery rate (FDR) < 0.05 was used to control for multiple testing. RESULTS: A total of 29 plasma bile acids were reliably detected and retained for analysis. Taurolithocholic acid (TLCA), taurocholic acid (TCA) and glycocholic acid (GCA) were statistically significantly higher after the WG compared to the RG diet (FDR < 0.05). There were no significant differences by BMI or sex. When evaluating the association of bile acids and HOMA-IR, GCA, taurochenodeoxycholic acid, ursodeoxycholic acid (UDCA), 5β-cholanic acid-3β,12α-diol, 5-cholanic acid-3β-ol, and glycodeoxycholic acid (GDCA) were statistically significantly positively associated with HOMA-IR individually, and as a group, total, 12α-hydroxylated, primary and secondary bile acids were also significant (FDR < 0.05). When stratifying by BMI, chenodeoxycholic acid (CDCA), cholic acid (CA), UDCA, 5β-cholanic acid-3β, deoxycholic acid, and total, 12α-hydroxylated, primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals (FDR <0.05). When stratifying by sex, GCA, CDCA, TCA, CA, UDCA, GDCA, glycolithocholic acid (GLCA), total, primary, 12α-hydroxylated, and glycine-conjugated bile acids were significantly associated with HOMA-IR among women, and CDCA, GDCA, and GLCA were significantly associated among men (FDR < 0.05). There were no significant associations between bile acids and CRP. CONCLUSIONS: Diets with comparable macronutrient and energy composition, but differing in carbohydrate source, affected fasting plasma bile acids differently. Specifically, a diet characterized by whole grains, legumes, and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA, TCA and GCA, ligands for FXR and TGR5, which may have beneficial effects on glucose homeostasis. PMID: 29458053 [PubMed - as supplied by publisher]

Related Articles A Multi-Omics Analysis of Glycine max Leaves Reveals Alteration in Flavonoid and Isoflavonoid Metabolism upon Ethylene and Abscisic acid Treatment. Proteomics. 2018 Feb 19;: Authors: Gupta R, Min CW, Kramer K, Agrawal GK, Rakwal R, Park KH, Wang Y, Finkemeier I, Kim ST Abstract Phytohormones are central to the plant growth and development. Despite the advancement in our knowledge of hormone signaling, downstream targets and their interactions upon hormones action remain largely fragmented, especially at the protein and metabolite levels. With an aim to get new insight into the effects of two hormones, ethylene (ET) and abscisic acid (ABA), this study utilizes an integrated proteomics and metabolomics approach to investigate their individual and combined (ABA+ET) signaling in soybean leaves. Targeting low-abundance proteins, our previously established protamine sulfate precipitation method was applied, followed by label-free quantification of identified proteins. A total of 4129 unique protein groups including 1083 differentially modulated in one (individual) or other (combined) treatments were discerned. Functional annotation of the identified proteins showed an increased abundance of proteins related to the flavonoid and isoflavonoids biosynthesis and MAPK-signaling pathway in response to ET treatment. HPLC analysis showed an accumulation of isoflavones (genistin, daidzein, and genistein) upon ET treatment, in agreement with the proteomics results. A metabolome analysis assigned 79 metabolites and further confirmed the accumulation of flavonoids and isoflavonoids in response to ET. A potential cross-talk between ET and MAPK-signaling, leading to the accumulation of flavonoids and isoflavonoids in soybean leaves is suggested. This article is protected by copyright. All rights reserved. PMID: 29457974 [PubMed - as supplied by publisher]

Related Articles Bax Inhibitor-1 protects from Non-Alcoholic Steatohepatitis by limiting IRE1α signaling. Hepatology. 2018 Feb 19;: Authors: Lebeaupin C, Vallée D, Rousseau D, Patouraux S, Bonnafous S, Adam G, Luciano F, Luci C, Anty R, Iannelli A, Marchetti S, Kroemer G, Lacas-Gervais S, Tran A, Gual P, Bailly-Maitre B Abstract Endoplasmic reticulum (ER) stress is activated in non-alcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation and cell death underlie the transition from steatosis to steatohepatitis (NASH). Bax inhibitor-1 (BI-1), a negative regulator of the ER stress sensor IRE1α, has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH due to unrestrained IRE1α signaling. ER stress was induced in wild-type and BI-1-/- mice acutely by tunicamycin injection (1 mg/kg) or chronically by high-fat diet (HFD) feeding to determine the NAFLD phenotype. Livers of tunicamycin-treated BI-1-/- mice showed IRE1α-dependent NLRP3 inflammasome activation, hepatocyte death, fibrosis and dysregulated lipid homeostasis that led to liver failure within a week. The analysis of human NAFLD liver biopsies revealed BI-1 downregulation parallel to the upregulation of IRE1α endoribonuclease (RNase) signaling. In HFD-fed BI-1-/- mice that presented NASH and type-2 diabetes, exaggerated hepatic IRE1α, XBP1 and CHOP expression was linked to activated NLRP3 inflammasome and caspase-1/-11. Rises in IL-1β, IL-6, MCP1, CXCL1 and ALT/AST levels revealed significant inflammation and injury, respectively. The pharmacological inhibition of IRE1α RNase activity with the small molecules STF-083010 or 4µ8c was evaluated in HFD-induced NAFLD. In BI-1-/- mice, either treatment effectively counteracted IRE1α RNase activity, improving glucose tolerance and rescuing from NASH. The hepatocyte-specific role of IRE1α RNase activity in mediating NLRP3 inflammasome activation and cell death was confirmed in primary mouse hepatocytes by IRE1α axis knockdown or its inhibition with STF-083010 or 4µ8c. CONCLUSION: Targeting IRE1α-dependent NLRP3 inflammasome signaling with pharmacological agents or via BI-1 may represent a tangible therapeutic strategy for NASH. This article is protected by copyright. All rights reserved. PMID: 29457838 [PubMed - as supplied by publisher]

Related Articles Urinary metabolomic study of the antagonistic effect of P. ginseng in rats with estrogen decline using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Food Funct. 2018 Feb 19;: Authors: Lin H, Liu Z, Pi Z, Men L, Chen W, Liu Z Abstract Estrogens are biologically active steroid hormones mainly released from the ovary by ovarian secretion of estrogen into the circulating blood to regulate or function at the distal target. Estrogens play an important role in the central nervous system, cardiovascular system and immune system, especially for post-menopausal women. Panax ginseng Mayer has been reported to relieve women's menopausal symptoms and affect estrogen activities. However, the mechanism of its estrogen regulation has not yet been clearly investigated. In this work, ovariectomized rats were administered a P. ginseng decoction intragastrically for 8 weeks. Urine samples were analyzed by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to identify metabolites. The estrous cycle, body weight, uterine weight index and serum hormone levels were measured. The results showed that P. ginseng significantly prolonged the estrus stage, decreased the body weight and serum luteinizing hormone (LH) levels and increased the uterine weight index and serum estradiol (E2) levels of ovariectomized rats. A total of twelve potential biomarkers for which levels changed markedly upon treatment have been identified based on metabolomics. A systematic network analysis of their corresponding pathways indicates that the antagonistic effect of P. ginseng on ovariectomized rats occurs mainly through regulating steroid hormone metabolism, fatty acid biosynthesis, the citric acid cycle and tryptophan metabolism. In conclusion, this study validated the antagonistic effect of P. ginseng in rats with estrogen decline and explored the metabolic and biochemical mechanisms involved. PMID: 29457805 [PubMed - as supplied by publisher]

Related Articles Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells. Front Oncol. 2018;8:13 Authors: Sant'Anna-Silva ACB, Santos GC, Campos SPC, Oliveira Gomes AM, Pérez-Valencia JA, Rumjanek FD Abstract Tumor cells are subjected to a broad range of selective pressures. As a result of the imposed stress, subpopulations of surviving cells exhibit individual biochemical phenotypes that reflect metabolic reprograming. The present work aimed at investigating metabolic parameters of cells displaying increasing degrees of metastatic potential. The metabolites present in cell extracts fraction of tongue fibroblasts and of cell lines derived from human tongue squamous cell carcinoma lineages displaying increasing metastatic potential (SCC9 ZsG, LN1 and LN2) were analyzed by 1H NMR (nuclear magnetic resonance) spectroscopy. Living, intact cells were also examined by the non-invasive method of fluorescence lifetime imaging microscopy (FLIM) based on the auto fluorescence of endogenous NADH. The cell lines reproducibly exhibited distinct metabolic profiles confirmed by Partial Least-Square Discriminant Analysis (PLS-DA) of the spectra. Measurement of endogenous free and bound NAD(P)H relative concentrations in the intact cell lines showed that ZsG and LN1 cells displayed high heterogeneity in the energy metabolism, indicating that the cells would oscillate between glycolysis and oxidative metabolism depending on the microenvironment's composition. However, LN2 cells appeared to have more contributions to the oxidative status, displaying a lower NAD(P)H free/bound ratio. Functional experiments of energy metabolism, mitochondrial physiology, and proliferation assays revealed that all lineages exhibited similar energy features, although resorting to different bioenergetics strategies to face metabolic demands. These differentiated functions may also promote metastasis. We propose that lipid metabolism is related to the increased invasiveness as a result of the accumulation of malonate, methyl malonic acid, n-acetyl and unsaturated fatty acids (CH2)n in parallel with the metastatic potential progression, thus suggesting that the NAD(P)H reflected the lipid catabolic/anabolic pathways. PMID: 29456966 [PubMed]

Related Articles Growth and lipid accumulation by different nutrients in the microalga Chlamydomonas reinhardtii. Biotechnol Biofuels. 2018;11:40 Authors: Yang L, Chen J, Qin S, Zeng M, Jiang Y, Hu L, Xiao P, Hao W, Hu Z, Lei A, Wang J Abstract Background: Individual nutrient depletion is widely used to induce lipid accumulation in microalgae, which also causes cell growth inhibition and decreases the total biomass. Thus, improving the lipid accumulation without biomass loss in the nutrient deficiency cells becomes a potential cost-effective treatment for cheaper biofuels. Methods: In this study, the effects of different nutritional conditions on the growth and contents of lipids in Chlamydomonas reinhardtii were compared, and the metabolic profiles under different nutritional conditions were also investigated. Results: We showed that similar to other microalgae, nitrogen or phosphorus deficiency inhibited the growth of Chlamydomonas and combined nutrition deficiency reduced biomass by up to 31.7%, though lipid contents in cells (g/g dry weight [DW]) were significantly increased. The addition of sodium acetate countered this growth inhibition that resulted from nitrogen and phosphorus deficiency, with significantly increased biomass. Furthermore, the combination of 4 g/L sodium acetate supplementation with nitrogen and phosphorous deficiency increased total fatty acid yield (mg/L) by 93.0 and 150.1% compared to nutrient-depleted and normal culture conditions, respectively. Metabolite content was affected by the different nutritional conditions, especially metabolites that are involved in lipid metabolism, amino acid metabolism and metabolism of external substances. Conclusion: Further research into these metabolites could shed light onto the relationship between cell growth inhibition and fatty acid accumulation in Chlamydomonas. PMID: 29456627 [PubMed]

Related Articles The relevance of tyrosine kinase inhibitors for global metabolic pathways in cancer. Mol Cancer. 2018 Feb 19;17(1):27 Authors: Poliaková M, Aebersold DM, Zimmer Y, Medová M Abstract Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyrosine kinases (TKs) involved in proliferation, metastasis and growth count for several years to promising anti-cancer approaches. In this respect, small molecule inhibitors are the most widely used clinically relevant means for targeted therapy, with a rising number of approvals for TKs inhibitors. In this review, we discuss recent observations related to TKs-associated metabolism and to metabolic feedback that is initialized as cellular response to particular TK-targeted therapies. These observations provide collective evidence that therapeutic responses are primarily linked to such pathways as regulation of lipid and amino acid metabolism, TCA cycle and glycolysis, advocating therefore the development of further effective targeted therapies against a broader spectrum of TKs to treat patients whose tumors display deregulated signalling driven by these proteins. PMID: 29455660 [PubMed - in process]

Related Articles Differentiation of Rums Produced from Sugar Cane Juice (Rhum Agricole) from Rums Manufactured from Sugar Cane Molasses by a Metabolomics Approach. J Agric Food Chem. 2018 Feb 17;: Authors: Franitza L, Nicolotti L, Granvogl M, Schieberle P Abstract A large set of volatiles (a metabolome) was isolated by SAFE distillation from twenty-five high priced rums prepared from sugar cane juice (SCJ) and twenty-six high priced rums manufactured from sugar cane molasses (SCM). The volatile fractions were first analyzed by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF-MS) and the 'comprehensive template matching fingerprinting' was used to extract the entire features present in the respective set of volatile compounds. After raw data pre-treatment, chemometrics was used to locate marker compounds. Following, a sparse-partial-least-squares discriminant analysis (sPLS-DA) and a partial-least-squares discriminant analysis (PLS-DA) was applied to a training data set for creating a model. The model was validated using leave-one-out cross validation and tested over an independent data set to evaluate its predictive power. The characteristic fingerprint resulted in a 100% correct classification of sugar cane juice rums, thus achieving the first aim of locating markers for these higher quality rums. Then, past-processing identification within the discriminant features was done to characterize 12 significant marker compounds as 1-decanol, γ-dodecalactone, ethyl 3-methylbutanoate, ethyl nonanoate, 3-furancarboxaldehyde, 1-hexanol, β-ionone, 2- and 3-methylbutanol, methyl decanoate, 3-octanol, and 2-undecanone. Quantitation of eight selected markers by stable isotope dilution assays confirmed higher concentrations in SCJ compared to SCM and served as the final proof to differentiate both types of spirits. PMID: 29455529 [PubMed - as supplied by publisher]

Related Articles Nano-sized TiO2 (nTiO2) induces metabolic perturbations in Physarum polycephalum macroplasmodium to counter oxidative stress under dark conditions. Ecotoxicol Environ Saf. 2018 Feb 15;154:108-117 Authors: Zhang Z, Liang ZC, Zhang JH, Tian SL, Le Qu J, Tang JN, De Liu S Abstract Nano-sized TiO2 (nTiO2) exerts an oxidative effect on cells upon exposure to solar or UV irradiation and ecotoxicity of the nTiO2 is an urgent concern. Little information is available regarding the effect of TiO2 on cells under dark conditions. Metabolomics is a unique approach to the discovery of biomarkers of nTiO2 cytotoxicity, and leads to the identification of perturbed metabolic pathways and the mechanism underlying nTiO2 toxicity. In the present study, gas chromatography mass spectrometry (GC/MS)-based metabolomics was performed to investigate the effect of nTiO2 on sensitive cells (P. polycephalum macroplasmodium) under dark conditions. According to the multivariate pattern recognition analysis, at least 60 potential metabolic biomarkers related to sugar metabolism, amino acid metabolism, nucleotide metabolism, polyamine biosynthesis, and secondary metabolites pathways were significantly perturbed by nTiO2. Notably, many metabolic biomarkers and pathways were related to anti-oxidant mechanisms in the living organism, suggesting that nTiO2 may induce oxidative stress, even under dark conditions. This speculation was further validated by the biochemical levels of reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine (8-OHdG), and total soluble phenols (TSP). We inferred that the oxidative stress might be related to nTiO2-induced imbalance of cellular ROS. To the best of our knowledge, the present study is the first to investigate the nTiO2-induced metabolic perturbations in slime mold, provide a new perspective of the mechanism underlying nTiO2 toxicity under dark conditions, and show that metabolomics can be employed as a rapid, reliable and powerful tool to investigate the interaction among organisms, the environment, and nanomaterials. PMID: 29454986 [PubMed - as supplied by publisher]