PubMed

Related Articles Sensitive screening of abused drugs in dried blood samples using ultra-high-performance liquid chromatography-ion booster-quadrupole time-of-flight mass spectrometry (UHPLC-IB-QTOF-MS). J Chromatogr A. 2017 Feb 21;: Authors: Chepyala D, Tsai IL, Liao HW, Chen GY, Chao HC, Kuo CH Abstract An increased rate of drug abuse is a major social problem worldwide. The dried blood spot (DBS) sampling technique offers many advantages over using urine or whole blood sampling techniques. This study developed a simple and efficient ultra-high-performance liquid chromatography-ion booster-quadrupole time-of-flight mass spectrometry (UHPLC-IB-QTOF-MS) method for the analysis of abused drugs and their metabolites using DBS. Fifty-seven compounds covering the most commonly abused drugs, including amphetamines, opioids, cocaine, benzodiazepines, barbiturates, and many other new and emerging abused drugs, were selected as the target analytes of this study. An 80% acetonitrile solvent with a 5-min extraction by Geno grinder was used for sample extraction. A Poroshell column was used to provide efficient separation, and under optimal conditions, the analytical times were 15 and 5min in positive and negative ionization modes, respectively. Ionization parameters of both electrospray ionization source and ion booster (IB) source containing an extra heated zone were optimized to achieve the best ionization efficiency of the investigated abused drugs. In spite of their structural diversity, most of the abused drugs showed an enhanced mass response with the high temperature ionization from an extra heated zone of IB source. Compared to electrospray ionization, the ion booster (IB) greatly improved the detection sensitivity for 86% of the analytes by 1.5-14-fold and allowed the developed method to detect trace amounts of compounds on the DBS cards. The validation results showed that the coefficients of variation of intra-day and inter-day precision in terms of the signal intensity were lower than 19.65%. The extraction recovery of all analytes was between 67.21 and 115.14%. The limits of detection of all analytes were between 0.2 and 35.7ngmL(-1). The stability study indicated that 7% of compounds showed poor stability (below 50%) on the DBS cards after 6 months of storage at room temperature and -80°C. The reported method provides a new direction for abused drug screening using DBS. PMID: 28238428 [PubMed - as supplied by publisher]

Related Articles Antioxidant activity, anti-proliferative activity, and amino acid profiles of ethanolic extracts of edible mushrooms. Genet Mol Res. 2016 Oct 17;15(4): Authors: Panthong S, Boonsathorn N, Chuchawankul S Abstract Biological activities of various mushrooms have recently been discovered, particularly, immunomodulatory and antitumor activities. Herein, three edible mushrooms, Auricularia auricula-judae (AA), Pleurotus abalonus (PA) and Pleurotus sajor-caju (PS) extracted using Soxhlet ethanol extraction were evaluated for their antioxidative, anti-proliferative effects on leukemia cells. Using the Folin-Ciocalteau method and Trolox equivalent antioxidant capacity assay, phenolics and antioxidant activity were found in all sample mushrooms. Additionally, anti-proliferative activity of mushroom extracts against U937 leukemia cells was determined using a viability assay based on mitochondrial activity. PA (0.5 mg/mL) and AA (0.25-0.5 mg/mL) significantly reduced cell viability. Interestingly, PS caused a hormetic-like biphasic dose-response. Low doses (0-0.25 mg/L) of PS promoted cell proliferation up to 140% relative to control, whereas higher doses (0.50 mg/mL) inhibited cell proliferation. Against U937 cells, AA IC50 was 0.28 ± 0.04 mg/mL, which was lower than PS or PA IC50 (0.45 ± 0.01 and 0.49 ± 0.001 mg/mL, respectively). Furthermore, lactate dehydrogenase (LDH) leakage conferred cytotoxicity. PS and PA were not toxic to U937 cells at any tested concentration; AA (0.50 mg/mL) showed high LDH levels and caused 50% cytotoxicity. Additionally, UPLC-HRMS data indicated several phytochemicals known to support functional activities as either antioxidant or anti-proliferative. Glutamic acid was uniquely found in ethanolic extracts of AA, and was considered an anti-cancer amino acid with potent anti-proliferative effects on U937 cells. Collectively, all mushroom extracts exhibited antioxidant effects, but their anti-proliferative effects were dose-dependent. Nevertheless, the AA extract, with highest potency, is a promising candidate for future applications. PMID: 27813595 [PubMed - indexed for MEDLINE]

Related Articles Rapid and efficient galactose fermentation by engineered Saccharomyces cerevisiae. J Biotechnol. 2016 Jul 10;229:13-21 Authors: Quarterman J, Skerker JM, Feng X, Liu IY, Zhao H, Arkin AP, Jin YS Abstract In the important industrial yeast Saccharomyces cerevisiae, galactose metabolism requires energy production by respiration; therefore, this yeast cannot metabolize galactose under strict anaerobic conditions. While the respiratory dependence of galactose metabolism provides benefits in terms of cell growth and population stability, it is not advantageous for producing fuels and chemicals since a substantial fraction of consumed galactose is converted to carbon dioxide. In order to force S. cerevisiae to use galactose without respiration, a subunit (COX9) of a respiratory enzyme was deleted, but the resulting deletion mutant (Δcox9) was impaired in terms of galactose assimilation. Interestingly, after serial sub-cultures on galactose, the mutant evolved rapidly and was able to use galactose via fermentation only. The evolved strain (JQ-G1) produced ethanol from galactose with a 94% increase in yield and 6.9-fold improvement in specific productivity as compared to the wild-type strain. (13)C-metabolic flux analysis demonstrated a three-fold reduction in carbon flux through the TCA cycle of the evolved mutant with redirection of flux toward the fermentation pathway. Genome sequencing of the JQ-G1 strain revealed a loss of function mutation in a master negative regulator of the Leloir pathway (Gal80p). The mutation (Glu348*) in Gal80p was found to act synergistically with deletion of COX9 for efficient galactose fermentation, and thus the double deletion mutant Δcox9Δgal80 produced ethanol 2.4 times faster and with 35% higher yield than a single knockout mutant with deletion of GAL80 alone. When we introduced a functional COX9 cassette back into the JQ-G1 strain, the JQ-G1-COX9 strain showed a 33% reduction in specific galactose uptake rate and a 49% reduction in specific ethanol production rate as compared to JQ-G1. The wild-type strain was also subjected to serial sub-cultures on galactose but we failed to isolate a mutant capable of utilizing galactose without respiration. We concluded that the metabolic "death valley" (i.e. no galactose utilization by the Δcox9 mutant) is a necessary intermediate phenotype to facilitate galactose utilization without respiration in yeast. The results in this study demonstrate a promising approach for directing adaptive evolution toward fermentative metabolism and for generating evolved yeast strains with improved phenotypes under anaerobic conditions. PMID: 27140870 [PubMed - indexed for MEDLINE]

Related Articles Recent advancements in diagnostic tools in mitochondrial energy metabolism diseases. Adv Med Sci. 2016 Sep;61(2):244-248 Authors: Khan N Abstract The involvement of mitochondrial energy metabolism in human disease ranges from rare monogenic disease to common diseases and aging with a genetic and/or lifestyle/environmental cause. This wide ranging involvement is due to the central role played by mitochondrion in cellular metabolism, its role in cellular perception of threats and its role in effecting responses to these threats. Investigating mitochondrial function/dysfunction or mitochondria-associated cell-biological responses have thus become a common finding where the pathogenic processes are investigated. Although, such investigations are warranted, it is not always clear if mitochondria can indeed be associated with cause or merely playing a responsive role in disease pathology. As this key question is also essential to disease progression and therapy, it should be recognized in investigative design. We herewith, present an overview of the current approaches and technologies used and the practicalities around these technologies. PMID: 26998934 [PubMed - indexed for MEDLINE]

Gill damage and neurotoxicity of ammonia nitrogen on the clam Ruditapes philippinarum. Ecotoxicology. 2017 Feb 25;: Authors: Cong M, Wu H, Yang H, Zhao J, Lv J Abstract Ammonia nitrogen has been a potential menace to aquatic animals along the coastline of China. Presently, the toxicological effects of ammonia nitrogen were mainly concentrated on fishes, while little attention has been paid to molluscs. In this study, the clam Ruditapes philippinarum was used as the target animal to investigate the toxic effects of ammonia nitrogen. Our results showed that ammonia exposure could significantly reduce the integrity of lysosomes in a dose-dependent manner. Metabolite analysis revealed that exposure doses and duration time of ammonia nitrogen could affect the variation profiles of gill metabolites. In detail, branched chain amino acids, glutamate, choline and phosphocholine were significantly decreased after a one-day exposure. Inosine and phenylalanine were found significantly increased and ATP was decreased after a three-day exposure. The changes of metabolites implied that metabolisms of muscle element, neurotransmission and cell apoptosis of gill tissues would be affected by ammonia exposure. Such inferences were supported by the diminished muscle element, decreased concentrations of catecholamines and increased apoptosis rates, respectively. Therefore, we take advantage of metabolomics integrated with conventional biological assays to find out that ammonia exposure could cause lysosome instability, metabolic disturbance, aberrant gill structures and changes to neurotransmitters, and would result in mollusk gill dysfunction in feeding, respiration and immunity. PMID: 28238072 [PubMed - as supplied by publisher]

Metabolic responses of the growing Daphnia similis to chronic AgNPs exposure as revealed by GC-Q-TOF/MS and LC-Q-TOF/MS. Water Res. 2017 Feb 20;114:135-143 Authors: Zhang B, Zhang H, Du C, Ng QX, Hu C, He Y, Ong CN Abstract Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. Their fast-growing utilization has increased the occurrence of AgNPs in the environment, posing potential health and ecological risks. In this study, we conducted chronic toxicity tests and investigated the metabolic changes of the growing Daphna similis with exposure to 0, 0.02, and 1 ppb AgNPs, using non-targeted mass spectrometry-based metabolomics. To the best of our knowledge, this study is the first to report the baseline metabolite change of a common aquatic organism Daphnia crustacean through its life-cycle. The results show a dynamic kinetic pattern of the growing Daphnia's metabolome underwent a cycle from day 0 to day 21, with the level of metabolites gradually increasing from day 0 to day 13, before falling back to the baseline level of day 0 on day 21. As for the samples exposed to environmental concentrations of AgNPs, although without morphological or structural changes, numerous metabolite changes occurred abruptly during the first 10 days, and these changes reached steady state by day 13. The significant changes in certain metabolites, such as amino acids (serine, threonine and tyrosine), sugars (d-allose) and fatty acids (arachidonic acid) revealed new insights into how these metabolites in Daphnia respond to chronic AgNPs stress. These findings highlight the capability of metabolomics to discover early metabolic responses to environmental silver nanoparticles. PMID: 28237781 [PubMed - as supplied by publisher]

Identification of urine tauro-β-muricholic acid as a promising biomarker in Polygoni Multiflori Radix-induced hepatotoxicity by targeted metabolomics of bile acids. Food Chem Toxicol. 2017 Feb 22;: Authors: Zhao DS, Jiang LL, Fan YX, Dong LC, Ma J, Dong X, Xu XJ, Li P, Li HJ Abstract Polygoni Multiflori Radix (PMR) has been widely used as a tonic for centuries. However, hepatotoxicity cases linked to PMR have been frequently reported and appropriate biomarkers for clinical diagnosis are currently lacking. Here, an approach using UPLC-QqQ/MS-based targeted metabolomics of bile acids (BAs) complemented with biochemistry and histopathology was applied to characterize the development and recovery processes of PMR-induced hepatotoxicity in rats and to identify biomarkers. The expression of bile salt export pump (Bsep) and sodium taurocholate cotransporting polypeptide (Ntcp) were evaluated to investigate the underlying mechanism. Steatosis and inflammatory cell infiltration were observed in PMR-treated rats, which were accompanied by the elevation of serum biochemistry. The metabolic profiles of BAs were analyzed by Principal Component Analysis, hyodeoxycholic acid (HDCA) in serum and tauro-β-muricholic acid (TβMCA) in urine were identified as potential biomarkers for PMR-induced hepatotoxicity. The elevated expression of Bsep and decreased expression of Ntcp in the liver of PMRtreated rats indicated that hepatotoxicity was related to the disorders of BAs metabolism. Our study demonstrated that BAs may be used for clinical diagnosis of PMR-induced hepatotoxicity. Urine TβMCA was identified as a promising biomarker to facilitate the clinical monitoring of PMR-induced hepatotoxicity and may serve as potential therapeutic target. PMID: 28237774 [PubMed - as supplied by publisher]

Metabolic profiling of stages of healthy pregnancy in Hu sheep using nuclear magnetic resonance (NMR). Theriogenology. 2017 Apr 01;92:121-128 Authors: Sun L, Guo Y, Fan Y, Nie H, Wang R, Wang F Abstract Nutrition is one of the most important factors affecting the reproductive performance of animals. Changes in the ovine maternal metabolism during pregnancy are critical to fetal development. To understand the differences in ovine metabolic changes that occur during normal pregnancy, pregnant ewes carrying twin fetuses (n = 8) were selected at 35 days of gestation (dG). All ewes received 100% of National Research Council (NRC) requirements of all nutrients and energy during this experiment. At 50, 70, 90, and 110 dG, maternal plasma samples were collected and designated as one of four corresponding time points (T1, T2, T3, and T4, respectively). Maternal plasma samples were analyzed using (1)H nuclear magnetic resonance spectroscopy to compare their metabolomic profiles among time points. We used multivariate pattern recognition to screen for different metabolites in the plasma of the ewes. The body weight and food intake of the ewes were significantly (P < 0.05) different at the four time points, and increased with the passage of pregnancy time. The principal component analysis model results showed that the metabolic states at time points T2 and T3 moved gradually further away from that at T1 and were furthest away from that at T1 at time point T4. Among the different time points, there were thirteen significantly differential metabolites in the maternal plasma (P < 0.05). These metabolites were closely related to amino acid metabolism and lipid metabolism, which might occur at different time points in pregnant ewes. In particular, newly observed changes in 1-methylhistidine and malonate were the first such changes found in maternal plasma. These results demonstrate that the metabolomics approach has value for evaluating metabolism in pregnancy with advancing gestation. In conclusion, during normal pregnancy in Hu sheep, related metabolites play an important role in amino acid and lipid metabolism for meeting the nutritional demands of pregnant ewes. PMID: 28237326 [PubMed - in process]

Preface. Methods Enzymol. 2017;588:xxv-xxxi Authors: Galluzzi L, Bravo-San Pedro JM, Kroemer G PMID: 28237121 [PubMed - in process]

Automated Analysis of Fluorescence Colocalization: Application to Mitophagy. Methods Enzymol. 2017;588:219-230 Authors: Sauvat A, Zhou H, Leduc M, Gomes-da-Silva LC, Bezu L, Müller K, Forveille S, Liu P, Zhao L, Kroemer G, Kepp O Abstract Mitophagy is a peculiar form of organelle-specific autophagy that targets mitochondria. This process ensures cellular homeostasis, as it fosters the disposal of aged and damaged mitochondria that otherwise would be prone to produce reactive oxygen species and hence endanger genomic stability. Similarly, autophagic clearance of depolarized mitochondria plays a fundamental role in organismal homeostasis as exemplified by the link between Parkinson disease and impaired function of the mitophagy-mediating proteins PINK1 and Parkin. Here, we detail an image-based approach for the quantification of mitochondrial Parkin translocation, which is mechanistically important for the initiation of mitophagy. PMID: 28237103 [PubMed - in process]

Assessment of Glycolytic Flux and Mitochondrial Respiration in the Course of Autophagic Responses. Methods Enzymol. 2017;588:155-170 Authors: Sica V, Bravo-San Pedro JM, Pietrocola F, Izzo V, Maiuri MC, Kroemer G, Galluzzi L Abstract Autophagy is an evolutionarily conserved process that mediates prominent homeostatic functions, both at the cellular and organismal level. Indeed, baseline autophagy not only ensures the disposal of cytoplasmic entities that may become cytotoxic upon accumulation, but also contributes to the maintenance of metabolic fitness in physiological conditions. Likewise, autophagy plays a fundamental role in the cellular and organismal adaptation to homeostatic perturbations of metabolic, physical, or chemical nature. Thus, the molecular machinery for autophagy is functionally regulated by a broad panel of sensors that detect indicators of metabolic homeostasis. Moreover, increases in autophagic flux have a direct impact on core metabolic circuitries including (but not limited to) glycolysis and mitochondrial respiration. Here, we detail a simple methodological approach to monitor these two processes in cultured cancer cells that mount a proficient autophagic response to stress. PMID: 28237099 [PubMed - in process]

Identification and Profiling of Specialized Pro-Resolving Mediators in Human Tears by Lipid Mediator Metabolomics. Prostaglandins Leukot Essent Fatty Acids. 2017 Feb;117:17-27 Authors: English JT, Norris PC, Hodges RR, Dartt DA, Serhan CN Abstract Specialized pro-resolving mediators (SPM), e.g. Resolvin D1, Protectin D1, Lipoxin A₄, and Resolvin E1 have each shown to be active in ocular models reducing inflammation. In general, SPMs have specific agonist functions that stimulate resolution of infection and inflammation in animal disease models. The presence and quantity of SPM in human emotional tears is of interest. Here, utilizing a targeted LC-MS-MS metabololipidomics based approach we document the identification of pro-inflammatory (Prostaglandins and Leukotriene B₄) and pro-resolving lipid mediators (D-series Resolvins, Protectin D1, and Lipoxin A₄) in human emotional tears from 12 healthy individuals. SPMs from the Maresin family (Maresin 1 and Maresin 2) were not present in these samples. Principal Component Analysis (PCA) revealed gender differences in the production of specific mediators within these tear samples as the SPMs were essentially absent in these female donors. These results indicate that specific SPM signatures are present in human emotional tears at concentrations known to be bioactive. Moreover, they will help to further appreciate the mechanisms of production and action of SPMs in the eye, as well as their physiologic roles in human ocular disease resolution. PMID: 28237084 [PubMed - in process]

Related Articles Oxidative stress, metabolomics profiling, and mechanism of local anesthetic induced cell death in yeast. Redox Biol. 2017 Feb 03;12:139-149 Authors: Boone CH, Grove RA, Adamcova D, Seravalli J, Adamec J Abstract The World Health Organization designates lidocaine as an essential medicine in healthcare, greatly increasing the probability of human exposure. Its use has been associated with ROS generation and neurotoxicity. Physiological and metabolomic alterations, and genetics leading to the clinically observed adverse effects have not been temporally characterized. To study alterations that may lead to these undesirable effects, Saccharomyces cerevisiae grown on aerobic carbon sources to stationary phase was assessed over 6h. Exposure of an LC50 dose of lidocaine, increased mitochondrial depolarization and ROS/RNS generation assessed using JC-1, ROS/RNS specific probes, and FACS. Intracellular calcium also increased, assessed by ICP-MS. Measurement of the relative ATP and ADP concentrations indicates an initial 3-fold depletion of ATP suggesting an alteration in the ATP:ADP ratio. At the 6h time point the lidocaine exposed population contained ATP concentrations roughly 85% that of the negative control suggesting the surviving population adapted its metabolic pathways to, at least partially restore cellular bioenergetics. Metabolite analysis indicates an increase of intermediates in the pentose phosphate pathway, the preparatory phase of glycolysis, and NADPH. Oxidative stress produced by lidocaine exposure targets aconitase decreasing its activity with an observed decrease in isocitrate and an increase citrate. Similarly, increases in α-ketoglutarate, malate, and oxaloacetate imply activation of anaplerotic reactions. Antioxidant molecule glutathione and its precursor amino acids, cysteine and glutamate were greatly increased at later time points. Phosphatidylserine externalization suggestive of early phase apoptosis was also observed. Genetic studies using metacaspase null strains showed resistance to lidocaine induced cell death. These data suggest lidocaine induces perpetual mitochondrial depolarization, ROS/RNS generation along with increased glutathione to combat the oxidative cellular environment, glycolytic to PPP cycling of carbon generating NADPH, obstruction of carbon flow through the TCA cycle, decreased ATP generation, and metacaspase dependent apoptotic cell death. PMID: 28236766 [PubMed - as supplied by publisher]

Related Articles Sortilin 1 knockout alters basal adipose glucose metabolism but not diet-induced obesity in mice. FEBS Lett. 2017 Feb 25;: Authors: Li J, Matye DJ, Wang Y, Li T Abstract Sortilin 1 (Sort1) is a trafficking receptor that has been implicated in the regulation of plasma cholesterol in humans and mice. Here, we use metabolomics and hyperinsulinemic-euglycemic clamp approaches to obtain further understanding of the in vivo effects of Sort1 deletion on diet-induced obesity as well as on adipose lipid and glucose metabolism. Results show that Sort1 knockout does not affect Western diet-induced obesity or adipose fatty acid and ceramide concentrations. Under the basal fasting state, chow-fed Sort1 knockout mice have decreased adipose glycolytic metabolites, but Sort1 deletion does not affect insulin-stimulated tissue glucose uptake during the insulin clamp. These results suggest that Sort1 loss-of-function in vivo does not affect obesity development, but differentially modulates adipose glucose metabolism under fasting and insulin-stimulated states. This article is protected by copyright. All rights reserved. PMID: 28236654 [PubMed - as supplied by publisher]

Related Articles The Role of Genomics in Common Variable Immunodeficiency Disorders. Clin Exp Immunol. 2017 Feb 25;: Authors: Kienzler AK, Hargreaves CE, Patel SY Abstract The advent of next generation sequencing (NGS) and 'omic' technologies has revolutionised the field of genetics and its implementation in healthcare has the potential to realise precision medicine. Primary immunodeficiencies (PID) are a group of rare diseases which have benefitted from NGS, with a massive increase in causative genes identified in the past few years. Common Variable Immunodeficiency Disorders (CVID) are a heterogeneous form of PID and the most common form of antibody failure in children and adults. While a monogenic cause of disease has been identified in a small subset of CVID patients, a genome wide association study and whole genome sequencing have found a polygenic cause is likely in the majority. Other NGS technologies such as RNA sequencing and epigenetic studies have further contributed to our understanding of the contribution of altered gene expression in CVID pathogenesis. We believe that to further unravel the complexities of CVID, a multi-omic approach, combining DNA sequencing with gene expression, methylation, proteomic and metabolomics data, will be essential to identify novel disease-associated pathways and therapeutic targets. This article is protected by copyright. All rights reserved. PMID: 28236292 [PubMed - as supplied by publisher]

Related Articles Multivalent Small-Molecule Pan-RAS Inhibitors. Cell. 2017 Feb 23;168(5):878-889.e29 Authors: Welsch ME, Kaplan A, Chambers JM, Stokes ME, Bos PH, Zask A, Zhang Y, Sanchez-Martin M, Badgley MA, Huang CS, Tran TH, Akkiraju H, Brown LM, Nandakumar R, Cremers S, Yang WS, Tong L, Olive KP, Ferrando A, Stockwell BR Abstract Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, may provide chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small-molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy, and isothermal titration calorimetry and to exhibit lethality in cells partially dependent on expression of RAS proteins. This compound was metabolically stable in liver microsomes and displayed anti-tumor activity in xenograft mouse cancer models. These findings suggest that pan-RAS inhibition may be an effective therapeutic strategy for some cancers and that structure-based design of small molecules targeting multiple adjacent sites to create multivalent inhibitors may be effective for some proteins. PMID: 28235199 [PubMed - in process]

Related Articles Correction: Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment. PLoS One. 2017;12(2):e0173164 Authors: Scarpellini B, Zanoni M, Sucupira MC, Truong HM, Janini LM, da Silva ID, Diaz RS Abstract [This corrects the article DOI: 10.1371/journal.pone.0161920.]. PMID: 28235085 [PubMed - in process]

Related Articles Diagnosis of a malignant adrenal mass: the role of urinary steroid metabolite profiling. Curr Opin Endocrinol Diabetes Obes. 2017 Feb 23;: Authors: Bancos I, Arlt W Abstract PURPOSE OF REVIEW: Adrenal masses are highly prevalent, found in 5% of the population. Differentiation of benign adrenocortical adenoma from adrenocortical carcinoma is currently hampered by the poor specificity and limited evidence base of imaging tests. This review summarizes the results of studies published to date on urine steroid metabolite profiling for distinguishing benign from malignant adrenal masses. RECENT FINDINGS: Three studies have described cohorts of at least 100 patients with adrenal tumors showing significant differences between urinary steroid metabolite excretions according to the nature of the underlying lesion, suggesting significant value of steroid metabolite profiling as a highly accurate diagnostic test. SUMMARY: Steroid profiling is emerging as a powerful novel diagnostic tool with a significant potential for improving the management for patients with adrenal tumors. Although the current studies use gas chromatography-mass spectrometry for proof of concept, widespread use of the method in routine clinical care will depend on transferring the approach to high-throughput tandem mass spectrometry platforms. The use of computational data analysis in conjunction with urine steroid metabolite profiling, that is, steroid metabolomics, adds accuracy and precision. PMID: 28234802 [PubMed - as supplied by publisher]

Related Articles Metabolite profiling of ascidian Styela plicata using LC-MS with multivariate statistical analysis and their antitumor activity. J Enzyme Inhib Med Chem. 2017 Dec;32(1):614-623 Authors: Palanisamy SK, Trisciuoglio D, Zwergel C, Del Bufalo D, Mai A Abstract To identify the metabolite distribution in ascidian, we have applied an integrated liquid chromatography- tandem mass spectrometry (LC-MS) metabolomics approach to explore and identify patterns in chemical diversity of invasive ascidian Styela plicata. A total of 71 metabolites were reported among these alkaloids, fatty acids and lipids are the most dominant chemical group. Multivariate statistical analysis, principal component analysis (PCA) showed a clear separation according to chemical diversity and taxonomic groups. PCA and partial least square discriminant analysis were applied to discriminate the chemical group of S. plicata crude compounds and classify the compounds with unknown biological activities. In this study, we reported for the first time that a partially purified methanol extract prepared from the ascidian S. plicata and Ascidia mentula possess antitumor activity against four tumor cell lines with different tumor histotype, such as HeLa (cervical carcinoma), HT29 (colon carcinoma), MCF-7 (breast carcinoma) and M14 (melanoma). S. plicata fraction SP-50 showed strong inhibition of cell proliferation and induced apoptosis in HeLa and HT29 cells, thus indicating S. plicata fraction SP-50 a potential lead compound for anticancer therapy. The molecular mechanism of action and chemotherapeutic potential of these ascidian unknown biomolecules need further research. PMID: 28234548 [PubMed - in process]

Related Articles Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites and Metabolic Pathways. Chem Res Toxicol. 2017 Feb 24;: Authors: Gao B, Chi L, Mahbub R, Bian X, Tu P, Ru H, Lu K Abstract Lead exposure remains as a global public health issue and recent Flint water crisis has again raised concern about lead toxicity in the public. The toxicity of lead has been well established in a variety of systems and organs. It has been increasingly appreciated that gut microbiome is highly involved in many critical physiological processes, such as food digestion, immune system development, and metabolic homeostasis, etc. However, despite the key role of gut microbiome in human health, the functional impact of lead exposure on gut microbiome has not been studied yet. This study aims at defining gut microbiome toxicity induced by lead exposure in C57BL/6 mice by multi-omics approaches including 16S rRNA sequencing, whole genome metagenomics sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics profiling. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E and bile acids, nitrogen metabolism, energy metabolism, oxidative stress and defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications in lead toxicity in the host. Taken together, we have demonstrated that lead exposure not only alters the gut microbiome community structures/diversity, but also largely affects its metabolic functions, leading to gut microbiome toxicity. PMID: 28234468 [PubMed - as supplied by publisher]