PubMed

Related Articles Germline BAP1 mutations induce a Warburg effect. Cell Death Differ. 2017 10;24(10):1694-1704 Authors: Bononi A, Yang H, Giorgi C, Patergnani S, Pellegrini L, Su M, Xie G, Signorato V, Pastorino S, Morris P, Sakamoto G, Kuchay S, Gaudino G, Pass HI, Napolitano A, Pinton P, Jia W, Carbone M Abstract Carriers of heterozygous germline BAP1 mutations (BAP1+/-) develop cancer. We studied plasma from 16 BAP1+/- individuals from 2 families carrying different germline BAP1 mutations and 30 BAP1 wild-type (BAP1WT) controls from these same families. Plasma samples were analyzed by liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS), ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-TQ-MS), and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found a clear separation in the metabolic profile between BAP1WT and BAP1+/- individuals. We confirmed the specificity of the data in vitro using 12 cell cultures of primary fibroblasts we derived from skin punch biopsies from 12/46 of these same individuals, 6 BAP1+/- carriers and 6 controls from both families. BAP1+/- fibroblasts displayed increased aerobic glycolysis and lactate secretion, and reduced mitochondrial respiration and ATP production compared with BAP1WT. siRNA-mediated downregulation of BAP1 in primary BAP1WT fibroblasts and in primary human mesothelial cells, led to the same reduced mitochondrial respiration and increased aerobic glycolysis as we detected in primary fibroblasts from carriers of BAP1+/- mutations. The plasma and cell culture results were highly reproducible and were specifically and only linked to BAP1 status and not to gender, age or family, or cell type, and required an intact BAP1 catalytic activity. Accordingly, we were able to build a metabolomic model capable of predicting BAP1 status with 100% accuracy using data from human plasma. Our data provide the first experimental evidence supporting the hypothesis that aerobic glycolysis, also known as the 'Warburg effect', does not necessarily occur as an adaptive process that is consequence of carcinogenesis, but rather that it may also predate malignancy by many years and facilitate carcinogenesis. PMID: 28665402 [PubMed - indexed for MEDLINE]

Related Articles Comprehensive metabonomic analysis of heart tissue from isoproterenol-induced myocardial infarction rat based on reversed-phase and hydrophilic interaction chromatography coupled to mass spectrometry. J Sep Sci. 2017 May;40(10):2198-2206 Authors: Sun L, Liu J, Sun M, Lin L, Miao L, Ge Z, Yang B Abstract We aim to describe the metabonomic characteristics of myocardial infarction rats. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was utilized to develop a metabonomic method of the heart homogenates of myocardial infarction rats. Hydrophilic interaction chromatography allows the analysis of high polar metabolites, providing complementary information to reversed-phase liquid chromatography. We combined reversed phase and hydrophilic interaction chromatographic separations to analyze 18 samples, ten from myocardial infarction rat hearts and eight from normal rat hearts. A total of 16 potential biomarkers in rat heart tissue were screened out, primarily related to oxidative stress, nitric oxide damage, taurine, and hypotaurine metabolism and sphingolipid metabolism. This research showed that a comprehensive metabonomic study is a useful tool to reveal the underlying mechanism of myocardial infarction. PMID: 28371309 [PubMed - indexed for MEDLINE]

Related Articles High-throughput ultra high performance liquid chromatography combined with mass spectrometry approach for the rapid analysis and characterization of multiple constituents of the fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms. J Sep Sci. 2017 May;40(10):2178-2187 Authors: Han Y, Zhang A, Sun H, Zhang Y, Meng X, Yan G, Liu L, Wang X Abstract Acanthopanax senticosus (Rupr. et Maxim.) Harms, a traditional Chinese medicine, has been widely used to improve the function of skeleton, heart, spleen and kidney. This fruit is rich in nutrients, but the chemical constituents of Acanthopanax senticosus fruit are still unclear. A rapid method based on ultra high performance liquid chromatography with time-of-flight mass spectrometry was developed for the compound analysis of Acanthopanax senticosus fruit in vitro and in vivo. In this study, the Acanthopanax senticosus fruit could significantly increase the weight of immune organs, promote the proliferation of lymphatic T cells, regulate the lymphatic B cell function, and decrease the ability of natural killer cells. A total of 104 compounds of Acanthopanax senticosus fruit including lignans, flavones, triterpenoidsaponins, phenolic acids, and other constituents were identified. Among them, seven chemical compounds were reported for the first time in the Acanthopanax senticosus fruit. Compared with the serum sample of blank and dosed samples, 24 prototype compositions were characterized. The results of our experiment could be helpful to understand the complex compounds of Acanthopanax senticosus fruit in vitro and in vivo for further pharmacological activity studies. PMID: 28371133 [PubMed - indexed for MEDLINE]

Related Articles What about the herb? A new metabolomics approach for synthetic cannabinoid drug testing. Anal Bioanal Chem. 2018 Jun 16;: Authors: Bijlsma L, Gil-Solsona R, Hernández F, Sancho JV Abstract Synthetic cannabinoids (SCs) are consumed as legal alternative to cannabis and often allow passing drug-screening tests. Their rapid transience on the drug scene, combined with their mostly unknown metabolic profiles, creates a scenario with constantly moving analytical targets, making their monitoring and identification challenging. The development of fast screening strategies for SCs, not directly focused on their chemical structure, as an alternative to the commonly applied target acquisition methods, would be highly appreciated in forensic and public health laboratories. An innovative untargeted metabolomics approach, focused on herbal components commonly used for 'spice' products, was applied. Saliva samples of healthy volunteers were collected at pre-dose and after smoking herbal components and analysed by high-resolution mass spectrometry. The data obtained, combined with appropriate statistical analysis, allowed to highlight and elucidate two markers (scopoletin and N,N-bis(2-hydroxyethyl)dodecylamine), which ratio permitted to differentiate herbal smokers from non-smokers. The proposed strategy will allow discriminating potential positives, on the basis of the analysis of two markers identified in the herbal blends. This work is presented as a step forward in SC drug testing, promoting a smart first-line screening approach, which will allow reducing the number of samples to be further investigated by more sophisticated HRMS methods. Graphical abstract The development of an alternative, generic screening methods of synthetic cannabinoids, not directly based on the chemical structure, in order to provide fast response on its potential consumption. PMID: 29909458 [PubMed - as supplied by publisher]

Related Articles Thrombospondin-1 interactions regulate eicosanoid metabolism and signaling in cancer-related inflammation. Cancer Metastasis Rev. 2018 Jun 16;: Authors: Ramirez MU, Stirling ER, Emenaker NJ, Roberts DD, Soto-Pantoja DR Abstract The metabolism of arachidonic acid and other polyunsaturated fatty acids produces eicosanoids, a family of biologically active lipids that are implicated in homeostasis and in several pathologies that involve inflammation. Inflammatory processes mediated by eicosanoids promote carcinogenesis by exerting direct effects on cancer cells and by affecting the tumor microenvironment. Therefore, understanding how eicosanoids mediate cancer progression may lead to better approaches and chemopreventive strategies for the treatment of cancer. The matricellular protein thrombospondin-1 is involved in processes that profoundly regulate inflammatory pathways that contribute to carcinogenesis and metastatic spread. This review focuses on interactions of thrombospondin-1 and eicosanoids in the microenvironment that promote carcinogenesis and how the microenvironment can be targeted for cancer prevention to increase curative responses of cancer patients. PMID: 29909440 [PubMed - as supplied by publisher]

Related Articles The multilevel antibiotic-induced perturbations to biological systems: Early-life exposure induces long-lasting damages to muscle structure and mitochondrial metabolism in flies. Environ Pollut. 2018 Jun 07;241:821-833 Authors: Renault D, Yousef H, Mohamed AA Abstract Antibiotics have been increasingly used over the past decades for human medicine, food-animal agriculture, aquaculture, and plant production. A significant part of the active molecules of antibiotics can be released into the environment, in turn affecting ecosystem functioning and biogeochemical processes. At lower organizational scales, these substances affect bacterial symbionts of insects, with negative consequences on growth and development of juveniles, and population dynamics. Yet, the multiple alterations of cellular physiology and metabolic processes have remained insufficiently explored in insects. We evaluated the effects of five antibiotics with different mode of action, i.e. ampicillin, cefradine, chloramphenicol, cycloheximide, and tetracycline, on the survival and ultrastructural organization of the flight muscles of newly emerged blow flies Chrysomya albiceps. Then, we examined the effects of different concentrations of antibiotics on mitochondrial protein content, efficiency of oxidative phosphorylation, and activity of transaminases (Glutamate oxaloacetate transaminase and glutamate pyruvate transaminase) and described the cellular metabolic perturbations of flies treated with antibiotics. All antibiotics affected the survival of the insects and decreased the total mitochondrial protein content in a dose-dependent manner. Ultrastructural organization of flight muscles in treated flies differs dramatically compared to the control groups and severe pathological damages/structures disorganization of mitochondria appeared. The activities of mitochondrial transaminases significantly increased with increased antibiotic concentrations. The oxidation rate of pyruvate + proline from isolated mitochondria of the flight muscles of 1-day-old flies was significantly reduced at high doses of antibiotics. In parallel, the level of several metabolites, including TCA cycle intermediates, was reduced in antibiotics-treated flies. Overall, antibiotics provoked a system-wide alteration of the structure and physiology of flight muscles of the blow fly Ch. albiceps, and may have fitness consequences at the organism level. Environmental antibiotic pollution is likely to have unwanted cascading ecological effects of insect population dynamics and community structure. PMID: 29909308 [PubMed - as supplied by publisher]

Related Articles Evidence that microplastics aggravate the toxicity of organophosphorus flame retardants in mice (Mus musculus). J Hazard Mater. 2018 Jun 08;357:348-354 Authors: Deng Y, Zhang Y, Qiao R, Bonilla MM, Yang X, Ren H, Lemos B Abstract This study was performed to reveal the health risks of co-exposure to organophosphorus flame retardants (OPFRs) and microplastics (MPs). We exposed mice to polyethylene (PE) and polystyrene (PS) MPs and OPFRs [tris (2-chloroethy) phosphate (TCEP) and tris (1,3-dichloro-2-propyl) phosphate (TDCPP)] for 90 days. Biochemical markers and metabolomics were used to determine whether MPs could enhance the toxicity of OPFRs. Superoxide dismutase (SOD) and catalase (CAT) increased (p < 0.05) by 21% and 26% respectively in 10 μg/L TDCPP + PE group compared to TDCPP group. Lactate dehydrogenase (LDH) in TDCPP + MPs groups were higher (18%-30%) than that in TDCPP groups (p < 0.05). Acetylcholinesterase (AChE) in TCEP + PE groups were lower (10%-19%) than those in TCEP groups (p < 0.05). These results suggested that OPFR co-exposure with MPs induced more toxicity than OPFR exposure alone. Finally, in comparison to controls we observed that 29, 41, 41, 26, 40 and 37 metabolites changed significantly (p < 0.05; fold-change > 1.2) in TCEP, TCEP + PS, TCEP + PE, TDCPP, TDCPP + PS and TDCPP + PE groups, respectively. Most of these metabolites are related to pathways of amino acid and energy metabolism. Our results indicate that MPs aggravate the toxicity of OPFRs and highlight the health risks of MP co-exposure with other pollutants. PMID: 29908513 [PubMed - as supplied by publisher]

Related Articles Stereoselective effects of ibuprofen in adult zebrafish (Danio rerio) using UPLC-TOF/MS-based metabolomics. Environ Pollut. 2018 Jun 09;241:730-739 Authors: Song Y, Chai T, Yin Z, Zhang X, Zhang W, Qian Y, Qiu J Abstract Ibuprofen (IBU), as a commonly used non-steroidal anti-inflammatory drug (NSAID) and pharmaceutical and personal care product (PPCP), is frequently prescribed by doctors to relieve pain. It is widely released into environmental water and soil in the form of chiral enantiomers by the urination and defecation of humans or animals and by sewage discharge from wastewater treatment plants. This study focused on the alteration of metabolism in the adult zebrafish (Danio rerio) brain after exposure to R-(-)-/S-(+)-/rac-IBU at 5 μg L-1 for 28 days. A total of 45 potential biomarkers and related pathways, including amino acids and their derivatives, purine and its derivatives, nucleotides and other metabolites, were observed with untargeted metabolomics. To validate the metabolic disorders induced by IBU, 22 amino acids and 3 antioxidant enzymes were selected to be quantitated and determined using targeted metabolomics and enzyme assay. Stereoselective changes were observed in the 45 identified biomarkers from the untargeted metabolomics analysis. The 22 amino acids quantitated in targeted metabolomics and 3 antioxidant enzymes determined in enzyme assay also showed stereoselective changes after R-(-)-/S-(+)-/rac-IBU exposure. Results showed that even at a low concentration of R-(-)-/S-(+)-/rac-IBU, disorders in metabolism and antioxidant defense systems were still induced with stereoselectivity. Our study may enable a better understanding of the risks of chiral PPCPs in aquatic organisms in the environment. PMID: 29908497 [PubMed - as supplied by publisher]

Related Articles Metabolite assignment of Ultra-Filtered Synovial Fluid extracted from knee joints of Reactive Arthritis patients using High Resolution NMR spectroscopy. Magn Reson Chem. 2018 Jun 15;: Authors: Dubey D, Chaurasia S, Guleria A, Kumar S, Modi DR, Misra R, Kumar D Abstract Currently, there are no reliable clinical biomarkers available that can aid early differential diagnosis of reactive arthritis (ReA) from other inflammatory joint diseases. Metabolic profiling of synovial fluid (SF) -obtained from joints affected in ReA- holds great promise in this regard and will further aid monitoring treatment and improving our understanding about disease mechanism. As a first step in this direction, we report here the metabolite specific assignment of 1 H and 13 C resonances detected in the NMR spectra of SF samples extracted from human patients with established ReA. The metabolite characterization has been carried out on both normal as well as on ultra-filtered (deproteinized) SF samples of eight ReA patients (n=8) using high resolution (800 MHz) 1 H and 1 H-13 C NMR spectroscopy methods such as one-dimensional (1D) 1 H CPMG and two-dimensional (2D) J-resolved1 H NMR and homonuclear 1 H-1 H TOCSY and heteronuclear1 H-13 C HSQC correlation spectra. Compared to normal SF samples, several distinctive 1 H NMR signals were identified and assigned to metabolites in the 1 H NMR spectra of ultra-filtered SF samples. Overall, we assigned 53 metabolites in normal filtered SF and 64 metabolites in filtered pooled SF sample compared to non-filtered SF samples for which only 48 metabolites (including lipid/membrane metabolites as well) have been identified. The established NMR characterization of SF metabolites will serve to guide future metabolomics studies aiming to identify/evaluate the SF based metabolic biomarkers of diagnostic/prognostic potential or seeking biochemical insights into disease mechanisms in a clinical perspective. PMID: 29907975 [PubMed - as supplied by publisher]

Related Articles Analysis of human C24 bile acids metabolome in serum and urine based on enzyme digestion of conjugated bile acids and LC-MS determination of unconjugated bile acids. Anal Bioanal Chem. 2018 Jun 16;: Authors: Zhu P, Zhang J, Chen Y, Yin S, Su M, Xie G, Brouwer KLR, Liu C, Lan K, Jia W Abstract Host-gut microbiota metabolic interactions are closely associated with health and disease. A manifestation of such co-metabolism is the vast structural diversity of bile acids (BAs) involving both oxidative stereochemistry and conjugation. Herein, we describe the development and validation of a LC-MS-based method for the analysis of human C24 BA metabolome in serum and urine. The method has high throughput covering the discrimination of oxidative stereochemistry of unconjugated species in a 15-min analytical cycle. The validated quantitative performance provided an indirect way to ascertain the conjugation patterns of BAs via enzyme-digestion protocols that incorporated the enzymes, sulfatase, β-glucuronidase, and choloylglycine hydrolase. Application of the method has led to the detection of at least 70 unconjugated BAs including 27 known species and 43 newly found species in the post-prandial serum and urine samples from 7 nonalcoholic steatohepatitis patients and 13 healthy volunteers. Newly identified unconjugated BAs included 3α, 12β-dihydroxy-5β-cholan-24-oic acid, 12α-hydroxy-3-oxo-5β-cholan-24-oic acid, and 3α, 7α, 12β-trihydroxy-5β-cholan-24-oic acid. High-definition negative fragment spectra of the other major unknown species were acquired to facilitate future identification endeavors. An extensive conjugation pattern is the major reason for the "invisibility" of the newly found BAs to other common analytical methods. Metabolomic analysis of the total unconjugated BA profile in combination with analysis of their conjugation patterns and urinary excretion tendencies have provided substantial insights into the interconnected roles of host and gut microbiota in maintaining BA homeostasis. It was proposed that the urinary total BA profile may serve as an ideal footprint for the functional status of the host-gut microbial BA co-metabolism. In summary, this work provided a powerful tool for human C24 BA metabolome analysis that bridges the gap between GC-MS techniques in the past age and LC-MS techniques currently prevailing in biomedical researches. Further applications of the present method in clinical, translational research, and other biomedical explorations will continue to boost the construction of a host-gut microbial co-metabolism network of BAs and thus facilitate the decryption of BA-mediated host-gut microbiota crosstalk in health and diseases. Graphical abstract ᅟ. PMID: 29907951 [PubMed - as supplied by publisher]

Related Articles Bladder cancer recurrence surveillance by urine metabolomics analysis. Sci Rep. 2018 Jun 15;8(1):9172 Authors: Loras A, Trassierra M, Sanjuan-Herráez D, Martínez-Bisbal MC, Castell JV, Quintás G, Ruiz-Cerdá JL Abstract Non Muscle Invasive Bladder Cancer (NMIBC) is among the most frequent malignant cancers worldwide. NMIBC is treated by transurethral resection of the bladder tumor (TURBT) and intravesical therapies, and has the highest recurrence rate among solid tumors. It requires a lifelong patient monitoring based on repeated cystoscopy and urinary cytology, both having drawbacks that include lack of sensitivity and specificity, invasiveness and care costs. We conducted an investigative clinical study to examine changes in the urinary metabolome of NMBIC patients before and after TURBT, as well during the subsequent surveillance period. Adjusting by prior probability of recurrence per risk, discriminant analysis of UPLC-MS metabolic profiles, displayed negative predictive values for low, low-intermediate, high-intermediate and high risk patient groups of 96.5%, 94.0%, 92.9% and 76.1% respectively. Detailed analysis of the metabolome revealed several candidate metabolites and perturbed phenylalanine, arginine, proline and tryptophan metabolisms as putative biomarkers. A pilot retrospective analysis of longitudinal trajectories of a BC metabolic biomarkers during post TURBT surveillance was carried out and the results give strong support for the clinical use of metabolomic profiling in assessing NMIBC recurrence. PMID: 29907864 [PubMed - in process]

Related Articles Plasma metabolites reveal distinct profiles associating with different metabolic risk factors in monozygotic twin pairs. Int J Obes (Lond). 2018 Jun 15;: Authors: Muniandy M, Velagapudi V, Hakkarainen A, Lundbom J, Lundbom N, Rissanen A, Kaprio J, Pietiläinen KH, Ollikainen M Abstract BACKGROUND: Obesity is related to a myriad of cardiometabolic outcomes, each of which may have a specific metabolomic signature and a genetic basis. We identified plasma metabolites associating with different cardiometabolic risk factors (adiposity, cholesterol, insulin resistance, and inflammation) in monozygotic (MZ) twins. Additionally, we assessed if metabolite profiling can identify subgroups differing by cardiometabolic risk factors. METHODS: We quantified 111 plasma metabolites (Acquity UPLC-triple quadrupole mass spectrometry), and measured blood lipids, HOMA index, CRP, and adiposity (BMI, %bodyfat by DEXA, fat distribution by MRI) in 40 MZ twin pairs (mean BMI 27.9 kg/m2, age 30.7). We determined associations among individuals (via linear regression) between metabolites and clinical phenotypes, and assessed, with within-twin pair analysis, if these associations were free from genetic confounding. We also performed cluster analysis to identify distinct subgroups based on subjects' metabolite profiles. RESULTS: We identified 42 metabolite-phenotype associations (FDR < 0.05), 19 remained significant after controlling for shared factors within the twin pairs. Aspartate, propionylcarnitine, tyrosine hexanoylcarnitine, and deoxycytidine associated positively with two or more adiposity measures. HDL cholesterol (HDL-C) associated negatively and BMI positively with the most numbers of metabolites; 12 were unique for HDL-C and 3 for BMI. Metabolites associating with HDL-C had the strongest effect size. Metabolite profiling revealed two distinct subgroups of individuals, differing by 32 metabolites (p < 0.05), and by total and LDL cholesterol (LDL-C). Forty-two metabolites predicted subgroup membership in correlation with total cholesterol and 45 metabolites predicted subgroup membership in correlation with LDL-C. CONCLUSIONS: Different fat depots share metabolites associating with general adiposity. BMI and HDL-C associated with the most pronounced and specific metabolomic signature. Metabolomics profiling can be used to identify distinct subgroups of individuals that differ by cholesterol measures. Most of the observed metabolite-phenotype associations are free of confounding by genetics and environmental factors shared by the co-twins. PMID: 29907843 [PubMed - as supplied by publisher]

Related Articles Altered maternal and placental lipid metabolism and fetal fat development in obesity: Current knowledge and advances in non-invasive assessment. Placenta. 2018 May 26;: Authors: Delhaes F, Giza SA, Koreman T, Eastabrook G, McKenzie CA, Bedell S, Regnault TRH, de Vrijer B Abstract Abnormal maternal lipid profiles, a hallmark of increased maternal adiposity, are associated with pregnancy complications such as preeclampsia and gestational diabetes, and offspring long-term metabolic health is impacted as the consequence of altered fetal growth, physiology and often iatrogenic prematurity. The metabolic changes associated with maternal obesity and/or the consumption of a high-fat diet effecting maternal lipid profiles and metabolism have also been documented to specifically affect placental function and may underlie changes in fetal development and life course disease risk. The placenta plays a critical role in mediating nutritional signals between the fetus and the mother. As obesity rates in women of reproductive age continue to increase, it is becoming evident that inclusion of new technologies that allow for a better understanding of early changes in placental lipid transport and metabolism, non-invasively in maternal circulation, maternal tissues, placenta, fetal circulation and fetal tissues are needed to aid timely clinical diagnosis and treatment for obesity-associated diseases. This review describes pregnancy lipid homeostasis, with specific reference to changes arising from altered maternal body composition on placental and fetal lipid transport and metabolism. Current technologies for lipid assessments, such as metabolomics and lipidomics may be impacted by labour or mode of delivery and are only reflective of a single time point. This review further addresses how established and novel technologies for assessing lipids and their metabolism non-invasively and during the course of pregnancy may guide future research into the effect of maternal metabolic health on pregnancy outcome, placenta and fetus. PMID: 29907450 [PubMed - as supplied by publisher]

Related Articles Comprehensive evaluation of untargeted metabolomics data processing software in feature detection, quantification and discriminating marker selection. Anal Chim Acta. 2018 Oct 31;1029:50-57 Authors: Li Z, Lu Y, Guo Y, Cao H, Wang Q, Shui W Abstract Data analysis represents a key challenge for untargeted metabolomics studies and it commonly requires extensive processing of more than thousands of metabolite peaks included in raw high-resolution MS data. Although a number of software packages have been developed to facilitate untargeted data processing, they have not been comprehensively scrutinized in the capability of feature detection, quantification and marker selection using a well-defined benchmark sample set. In this study, we acquired a benchmark dataset from standard mixtures consisting of 1100 compounds with specified concentration ratios including 130 compounds with significant variation of concentrations. Five software evaluated here (MS-Dial, MZmine 2, XCMS, MarkerView, and Compound Discoverer) showed similar performance in detection of true features derived from compounds in the mixtures. However, significant differences between untargeted metabolomics software were observed in relative quantification of true features in the benchmark dataset. MZmine 2 outperformed the other software in terms of quantification accuracy and it reported the most true discriminating markers together with the fewest false markers. Furthermore, we assessed selection of discriminating markers by different software using both the benchmark dataset and a real-case metabolomics dataset to propose combined usage of two software for increasing confidence of biomarker identification. Our findings from comprehensive evaluation of untargeted metabolomics software would help guide future improvements of these widely used bioinformatics tools and enable users to properly interpret their metabolomics results. PMID: 29907290 [PubMed - in process]

Related Articles Emerging role of lipid metabolism alterations in Cancer stem cells. J Exp Clin Cancer Res. 2018 Jun 15;37(1):118 Authors: Yi M, Li J, Chen S, Cai J, Ban Y, Peng Q, Zhou Y, Zeng Z, Peng S, Li X, Xiong W, Li G, Xiang B Abstract BACKGROUND: Cancer stem cells (CSCs) or tumor-initiating cells (TICs) represent a small population of cancer cells with self-renewal and tumor-initiating properties. Unlike the bulk of tumor cells, CSCs or TICs are refractory to traditional therapy and are responsible for relapse or disease recurrence in cancer patients. Stem cells have distinct metabolic properties compared to differentiated cells, and metabolic rewiring contributes to self-renewal and stemness maintenance in CSCs. MAIN BODY: Recent advances in metabolomic detection, particularly in hyperspectral-stimulated raman scattering microscopy, have expanded our knowledge of the contribution of lipid metabolism to the generation and maintenance of CSCs. Alterations in lipid uptake, de novo lipogenesis, lipid droplets, lipid desaturation, and fatty acid oxidation are all clearly implicated in CSCs regulation. Alterations on lipid metabolism not only satisfies the energy demands and biomass production of CSCs, but also contributes to the activation of several important oncogenic signaling pathways, including Wnt/β-catenin and Hippo/YAP signaling. In this review, we summarize the current progress in this attractive field and describe some recent therapeutic agents specifically targeting CSCs based on their modulation of lipid metabolism. CONCLUSION: Increased reliance on lipid metabolism makes it a promising therapeutic strategy to eliminate CSCs. Targeting key players of fatty acids metabolism shows promising to anti-CSCs and tumor prevention effects. PMID: 29907133 [PubMed - in process]

Reducing impacts of organism variability in metabolomics via time trajectory in vivo NMR. Magn Reson Chem. 2018 Jun 15;: Authors: Anaraki MT, Simpson MJ, Simpson AJ PMID: 29906816 [PubMed - as supplied by publisher]

Simultaneous measurement of folate cycle intermediates in different biological matrices using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jun 05;1092:168-178 Authors: Nandania J, Kokkonen M, Euro L, Velagapudi V Abstract The folate cycle is an essential metabolic pathway in the cell, involved in nucleotide synthesis, maintenance of the redox balance in the cell, methionine metabolism and re-methylation reactions. Standardised methods for the measurement of folate cycle intermediates in different biological matrices are in great demand. Here we describe a rapid, sensitive, precise and accurate liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method with a wide calibration curve range and a short run time for the simultaneous determination of folate cycle metabolites, including tetrahydrofolic acid (THF), 5‑methyl THF, 5‑formyl THF, 5,10‑methenyl THF, 5,10‑methylene THF, dihydrofolic acid (DHF) and folic acid in different biological matrices. Extraction of folate derivatives from soft and hard tissue samples as well as from adherent cells was achieved using homogenisation in buffer, while extraction from the whole blood and plasma relied on the anion exchange solid-phase extraction (SPE) method. Chromatographic separation was completed using a Waters Atlantis dC18 2.0 × 100 mm, 3-μ column with a gradient elution using formic acid in water (0.1% v/v) and acetonitrile as the mobile phases. LC gradient started with 95% of the aqueous phase which was gradually changed to 95% of the organic phase during 2.70 min in order to separate the selected metabolites. The analytes were separated with a run time of 5 min at a flow rate of 0.300 mL/min and detected using a Waters Xevo-TQS triple quadrupole mass spectrometer in the multiple reaction monitoring mode (MRM) at positive polarity. The instrument response was linear over a calibration range of 0.5 to 2500 ng/mL (r2 > 0.980). The developed bioanalytical method was thoroughly validated in terms of accuracy, precision, linearity, recovery, sensitivity and stability for tissue and blood samples. The matrix effect was compensated by using structurally similar isotope labelled internal standard (IS), 13C5‑methyl THF, for all folate metabolites. However, not all folate metabolites can be accurately quantified using this method due to their high interconversion rates especially at low pH. This applies to 5,10‑methylene THF which interconverts into THF, and 5,10‑methenyl‑THF interconverting into 5‑formyl‑THF. Using this method, we measured folate cycle intermediates in mouse bone marrow cells and plasma, in human whole blood; in mouse muscle, liver, heart and brain samples. PMID: 29906678 [PubMed - as supplied by publisher]

Recombinant Newcastle disease viruses with targets for PCR diagnostics for rinderpest and peste des petits ruminants. J Virol Methods. 2018 Jun 12;: Authors: van Rijn PA, Boonstra J, van Gennip HGP Abstract Since February 1st 2011, rinderpest (RP) has been officially declared eradicated worldwide. National authorities have been requested to destroy all their RP related materials. Nonetheless, their national reference laboratories performing real time reverse transcription polymerase chain reaction assays (PCR diagnostics) need RP positive control samples, since some countries still prefer to maintain diagnostic capability for RP for several reasons. In the future, a similar situation will arise for peste des petits ruminants (PPR) as the ambition has been expressed to eradicate PPR. Anticipating on this, we intended to perform qualified PCR diagnostics without use of infectious RPV or PPRV. Therefore, Newcastle disease virus (NDV) with small RNA inserts based on RPV or PPRV sequences were generated and used as positive control material. Recombinant NDVs (recNDVs) were differentially detected by previously established PCR diagnostics for RPV or PPRV. Both recNDVs contain a second PCR target showing that additional targets in NDV are feasible and would increase the diagnostic sensitivity by use of two PCR assays. RecNDV with small PCR targets is not classified as RPV or PPRV containing material, and can be used to mimic RPV or PPRV. Using these recNDVs as virus positive material contributes to the ambition of worldwide eradication, while qualified PCR diagnostics for these OIE-listed diseases remains operational. PMID: 29906491 [PubMed - as supplied by publisher]

Liver Metabolomics in a Mouse Model of Erythropoietic Protoporphyria. Biochem Pharmacol. 2018 Jun 12;: Authors: Wang P, Sachar M, Guo GL, Shehu AI, Lu J, Zhong XB, Ma X Abstract Erythropoietic protoporphyria (EPP) is a genetic disease that results from the defective mutation in the gene encoding ferrochelatase (FECH), the enzyme that converts protoporphyrin IX (PPIX) to heme. Liver injury and even liver failure can occur in EPP patients because of PPIX accumulation in the liver. The current study profiled the liver metabolome in an EPP mouse model caused by a Fech mutation (Fech-mut). As expected, we observed the accumulation of PPIX in the liver of Fech-mut mice. In addition, our metabolomic analysis revealed the accumulation of bile acids and ceramide (Cer) in the liver of Fech-mut mice. High levels of bile acids and Cer are toxic to the liver. Furthermore, we found that the major phosphatidylcholines (PC) in the liver and the ratio of total PC to PPIX in the bile were decreased in Fech-mut mice compared to wild type mice. A decrease of the ratio of PC to PPIX in the bile can potentiate the accumulation of PPIX in the liver because PC increases PPIX solubility and excretion. These metabolomic findings suggest that the accumulation of PPIX, together with the disruption of the homeostasis of bile acids, Cer, and PC, contributes to EPP-associated liver injury. PMID: 29906468 [PubMed - as supplied by publisher]

Mass spectrometry is a multifaceted weapon to be used in the battle against Alzheimer's disease: Amyloid beta peptides and beyond. Mass Spectrom Rev. 2018 Jun 15;: Authors: Grasso G Abstract Amyloid-β peptide (Aβ) accumulation and aggregation have been considered for many years the main cause of Alzheimer's disease (AD), and therefore have been the principal target of investigation as well as of the proposed therapeutic approaches (Grasso [2011] Mass Spectrom Rev. 30: 347-365). However, the amyloid cascade hypothesis, which considers Aβ accumulation the only causative agent of the disease, has proven to be incomplete if not wrong. In recent years, actors such as metal ions, oxidative stress, and other cofactors have been proposed as possible co-agents or, in some cases, main causative factors of AD. In this scenario, MS investigation has proven to be fundamental to design possible diagnostic strategies of this elusive disease, as well as to understand the biomolecular mechanisms involved, in the attempt to find a possible therapeutic solution. We review the current applications of MS in the search for possible Aβ biomarkers of AD to help the diagnosis of the disease. Recent examples of the important contributions that MS has given to prove or build theories on the molecular pathways involved with such terrible disease are also reviewed. PMID: 29905953 [PubMed - as supplied by publisher]