Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Phthalate exposure and childhood overweight and obesity: Urinary metabolomic evidence.

Thu, 13/09/2018 - 13:04
Phthalate exposure and childhood overweight and obesity: Urinary metabolomic evidence. Environ Int. 2018 Sep 08;121(Pt 1):159-168 Authors: Xia B, Zhu Q, Zhao Y, Ge W, Zhao Y, Song Q, Zhou Y, Shi H, Zhang Y Abstract OBJECTIVE: Metabolomics may unravel global metabolic changes in response to environmental exposures and identify important biological pathways involved in the pathophysiology of childhood obesity. Phthalate has been considered an obesogen and contributing to overweight and obesity in children. The purpose of this study is to evaluate changes in urine metabolites in response to the environmental phthalate exposure among overweight or obese children, and to investigate the metabolic mechanisms involved in the obesogenic effect of phthalate on children at puberty. METHODS: Within the national Puberty Timing and Health Effects in Chinese Children (PTHEC) study, 69 overweight/obese children and 80 normal weight children were selected into the current study according to their puberty timing and WGOC (The Working Group for obesity in China) references. Urinary concentrations of six phthalate monoesters (MMP, MEP, MnBP, MEHP, MEOHP and MEHHP) were measured using API 2000 electrospray triple quadrupole mass spectrometer (ESIMS/MS). Metabolomic profiling of spot urine was performed using gas chromatography-mass spectrometry. Differentially expressed urinary metabolites associated with phthalate monoesters exposure were examined using orthogonal partial least square-discriminant analysis and multiple linear regression models. In addition, the candidate metabolites were regressed to obesity indices with multiple linear regression models and logistic regression models in all subjects. RESULTS: Compared with normal weight children, higher levels of MnBP were detected in urinary samples of children with overweight and obesity. After adjusting for confounders including chronological age, gender, puberty onset, daily energy intake and physical activity and socio-economic level, positive association remained between urinary MnBP concentration and childhood overweight/obesity [OR = 1.586, 95% CI:1.043,2.412]. We observed elevated MnBP concentration was significantly correlated with increased levels of monostearin, 1-monopalmitin, stearic acid, itaconic acid, glycerol 3-phosphate, 5-methoxytryptamine, kyotorphin, 1-methylhydantoin, d-alanyl-d-alanine, pyrrole-2-carboxylic acid, 3,4-Dihydroxyphenylglycol, and butyraldehyde. Meanwhile, increased MnBP concentration was also significantly correlated with decreased levels of lactate, glucose 6-phosphate, d-fructose 6-phosphate, palmitic acid, 4-acetamidobutyric acid, l-glutamic acid, n-acetyl-l-phenylalanine, iminodiacetic acid, hydroxyproline, pipecolinic acid, l-ornithine, n-acetyl-l-glutamic acid, guanosine, cytosin, and (s)-mandelic acid in the normal weight subjects. The observations indicated that MnBP exposure was related to global urine metabolic abnormalities characterized by disrupting arginine and proline metabolism and increasing oxidative stress and fatty acid reesterification. Among the metabolic markers related to MnBP exposure, 1-methylhydantoin, pyrrole-2-carboxylic acid and monostearin were found to be positively correlated with obesity indices, while hydroxyproline, l-ornithine, and lactate were negatively associated with overweight/obesity in children. CONCLUSIONS: Our results suggested that the disrupted arginine and proline metabolism associated with phthalate exposure might contribute to the development of overweight and obesity in school-age children, providing insights into the pathophysiological changes and molecular mechanisms involved in childhood obesity. PMID: 30208345 [PubMed - as supplied by publisher]

Layers of regulation on cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae.

Thu, 13/09/2018 - 13:04
Layers of regulation on cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae. Mol Biol Cell. 2018 Sep 12;:mbcE18040255 Authors: Kelliher CM, Foster MW, Motta FC, Deckard A, Soderblom EJ, Moseley MA, Haase SB Abstract In the budding yeast Saccharomyces cerevisiae, transcription factors (TFs) regulate the periodic expression of many genes during the cell cycle, including gene products required for progression through cell-cycle events. Experimental evidence coupled with quantitative models suggest that a network of interconnected TFs is capable of regulating periodic genes over the cell cycle. Importantly, these dynamical models were built on transcriptomics data and assumed that TF protein levels and activity are directly correlated with mRNA abundance. To ask whether TF transcripts match protein expression levels as cells progress through the cell cycle, we applied a multiplexed targeted mass spectrometry approach (parallel reaction monitoring) on synchronized populations of cells. We found that protein expression of many TFs and cell-cycle regulators closely followed their respective mRNA transcript dynamics in cycling wild-type cells. Discordant mRNA/protein expression dynamics were also observed for a subset of cell-cycle TFs and for proteins targeted for degradation by E3 ubiquitin ligase complexes such as SCF (Skp1/Cul1/F-box) and APC/C (anaphase-promoting complex/cyclosome). We further profiled mutant cells lacking B-type cyclin/CDK activity ( clb1-6), where oscillations in ubiquitin ligase activity, cyclin/CDKs, and cell-cycle progression are halted. We found that a number of proteins were no longer periodically degraded in clb1-6 mutants compared to wild type, highlighting the importance of post-transcriptional regulation. Finally, the TF complexes responsible for activating G1/S transcription (SBF and MBF) were more constitutively expressed at the protein level than their periodic mRNA expression levels in both wild-type and mutant cells. This comprehensive investigation of cell-cycle regulators reveals that multiple layers of regulation (transcription, protein stability, and proteasome targeting) affect protein expression dynamics during the cell cycle. PMID: 30207828 [PubMed - as supplied by publisher]

Discovery and validation of potential serum biomarkers for pediatric patients with congenital heart diseases by metabolomics.

Thu, 13/09/2018 - 13:04
Discovery and validation of potential serum biomarkers for pediatric patients with congenital heart diseases by metabolomics. J Proteome Res. 2018 Sep 12;: Authors: Yu M, Sun S, Yu J, Du F, Zhang S, Yang W, Xiao J, Xie B Abstract In order to identify and screen serum biomarkers to determine pediatric patients with congenital heart diseases (PCH) from healthy control children (NC), a total of 614 clinically diagnosed subjects from 3 hospitals, including 491 PCH and 234 NC were enrolled for non-targeted proton nuclear magnetic resonance spectroscopy (1HNMR)-based and targeted ultra-high performance liquid chromatographic tandem mass spectroscopy (UPLC-MS/MS)-based metabolomics studies. 19 serum metabolites distinguishing PCH from NC were identified by 1HNMR-based metabolomic analysis. The amino acid and choline metabolic pathways were considered to be closely related to PCH. The serum levels of 13 metabolites in these two pathways were further determined by UPLC-MS/MS and observed to be altered significantly in PCH. Taurine, glutamine, and glutamate presented considerable diagnostic value for diagnosis of PCH (AUROC > 0.80). Logistic regression analysis showed that a combination of four variables, namely, betaine, taurine, glutamine, and phenylalanine, yields a high diagnostic value (AUROC=0.949) and prediction accuracy (89.1%) for differentiating PCH from the NC, and the sensitivity and specificity were 93.9% and 95.2%, respectively. Further double-blind sample prediction showed that the accuracy of the model was 83.8 % for 80 unknown samples. Our results showed that the serum amino acid and choline metabolite levels in PCH were changed considerably. The combination of four metabolites, namely, betaine, taurine, glutamine, and phenylalanine, can be used as potential serum biomarkers in PCH diagnosis, which contributes to the early PCH screening. PMID: 30207476 [PubMed - as supplied by publisher]

Role of green fluorescent proteins and their variants in development of FRET-based sensors.

Thu, 13/09/2018 - 13:04
Role of green fluorescent proteins and their variants in development of FRET-based sensors. J Biosci. 2018 Sep;43(4):763-784 Authors: Soleja N, Manzoor O, Khan I, Ahmad A, Mohsin M Abstract Since the last decade, a lot of advancement has been made to understand biological processes involving complex intracellular pathways. The major challenge faced was monitoring and trafficking of metabolites in real time. Although a range of quantitative and imaging techniques have been developed so far, the discovery of green fluorescent proteins (GFPs) has revolutionized the advancement in the field of metabolomics. GFPs and their variants have enabled researchers to 'paint' a wide range of biological molecules. Fluorescence resonance energy transfer (FRET)-based genetically encoded sensors is a promising technology to decipher the real-time monitoring of the cellular events inside living cells. GFPs and their variants, due to their intrinsic fluorescence properties, are extensively being used nowadays in cell-based assays. This review focuses on structure and function of GFP and its derivatives, mechanism emission and their use in the development of FRET-based sensors for metabolites. PMID: 30207321 [PubMed - in process]

Evaluation of metabolic changes induced by polyphenols in the crayfish Astacus leptodactylus by metabolomics using Fourier transformed infrared spectroscopy.

Thu, 13/09/2018 - 13:04
Evaluation of metabolic changes induced by polyphenols in the crayfish Astacus leptodactylus by metabolomics using Fourier transformed infrared spectroscopy. J Biosci. 2018 Sep;43(4):585-596 Authors: Volpe MG, Costantini S, Coccia E, Parrillo L, Paolucci M Abstract In the present study, the effects of polyphenols on the chemical composition of the hepatopancreas of the Astacus leptodactylus, a highly sought farmed crayfish, have been investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The hepatopancreas spectrum was quite complex and contained several peaks arising from the contribution of different functional groups belonging to protein, lipids and carbohydrates. The PCA statistical analysis revealed that there were significant differences between crayfish fed a diet without polyphenols and crayfish fed a diet containing polyphenols. Such differences indicated an increase in lipids and proteins in the hepatopancreas of polyphenol-fed crayfish. In conclusion, the analysis of the infrared spectral profile of the hepatopancreas of Astacus leptodactylus, allowed us to elucidate the changes in different biomolecules in response to polyphenol treatment, and confirms the suitability of ATR-FTIR spectral data to analyze diet-induced metabolic effects. These considerations, coupled with the small amount of sample and no preparation needed, make ATR-FTIR a useful tool for routine analyses where the metabolic impact of substances is investigated, especially with a large number of samples. PMID: 30207306 [PubMed - in process]

Metabolomics in Vitamin Status Assessment.

Thu, 13/09/2018 - 13:04
Metabolomics in Vitamin Status Assessment. Curr Pharm Des. 2018 Sep 12;: Authors: Yurgita RV, Livantsova NE, Ukrainets VI, Kosyura DS, Starodubova VA Abstract The issue of vitamin deficiency persists to be a major health issue worldwide despite the advancements in medicine. At the same time, the effect of marginal vitamin deficiency status on physiological processes is proven. However, general methods such as immune-enzyme and fluorescence analysis, microbiological assays, for example, have limitations in vitamin status assessment and are not able to reliably reflect personal vitamin demand. The potential usefulness of modern metabolomics methods in vitamin status assessment is described in this review. These methods can be used for vitamin metabolites detection as well as for comprehensive metabolic phenotyping that makes them even more valuable. PMID: 30207224 [PubMed - as supplied by publisher]

Metabolic profiling and targeted lipidomics reveals a disturbed lipid profile in mothers and fetuses with intrauterine growth restriction.

Thu, 13/09/2018 - 13:04
Related Articles Metabolic profiling and targeted lipidomics reveals a disturbed lipid profile in mothers and fetuses with intrauterine growth restriction. Sci Rep. 2018 Sep 11;8(1):13614 Authors: Miranda J, Simões RV, Paules C, Cañueto D, Pardo-Cea MA, García-Martín ML, Crovetto F, Fuertes-Martin R, Domenech M, Gómez-Roig MD, Eixarch E, Estruch R, Hansson SR, Amigó N, Cañellas N, Crispi F, Gratacós E Abstract Fetal growth may be impaired by poor placental function or maternal conditions, each of which can influence the transfer of nutrients and oxygen from the mother to the developing fetus. Large-scale studies of metabolites (metabolomics) are key to understand cellular metabolism and pathophysiology of human conditions. Herein, maternal and cord blood plasma samples were used for NMR-based metabolic fingerprinting and profiling, including analysis of the enrichment of circulating lipid classes and subclasses, as well as the number of sub-fraction particles and their size. Changes in phosphatidylcholines and glycoproteins were prominent in growth-restricted fetuses indicating significant alterations in their abundance and biophysical properties. Lipoprotein profiles showed significantly lower plasma concentrations of cholesterol-intermediate density lipoprotein (IDL), triglycerides-IDL and high-density lipoprotein (HDL) in mothers of growth-restricted fetuses compared to controls (p < 0.05). In contrast, growth-restricted fetuses had significantly higher plasma concentrations of cholesterol and triglycerides transporting lipoproteins [LDL, IDL, and VLDL, (p < 0.005; all)], as well as increased VLDL particle types (large, medium and small). Significant changes in plasma concentrations of formate, histidine, isoleucine and citrate in growth-restricted fetuses were also observed. Comprehensive metabolic profiling reveals that both, mother and fetuses of pregnancies complicated with fetal growth restriction have a substantial disruption in lipid metabolism. PMID: 30206284 [PubMed - in process]

Brain Magnetic Resonance Imaging of Intracerebral Hemorrhagic Rats after Alcohol Consumption.

Thu, 13/09/2018 - 13:04
Related Articles Brain Magnetic Resonance Imaging of Intracerebral Hemorrhagic Rats after Alcohol Consumption. J Stroke Cerebrovasc Dis. 2018 Sep 08;: Authors: Huang LC, Liew HK, Cheng HY, Kuo JS, Hsu WL, Pang CY Abstract BACKGROUND: Alcoholism is one of the risk factors for cerebrovascular diseases. Our previous study demonstrated that acute alcohol intoxication enhances brain injury and neurological impairment in rats suffering from intracerebral hemorrhage (ICH). We plan to investigate the effect of chronic alcohol consumption (CAC) in rats with ICH by magnetic resonance imaging (MRI). METHODS: Sixteen Sprague-Dawley male rats were divided into 2 groups: CAC group (fed with 10% alcohol drinking water for 4 weeks, n = 8), and Control group (plain drinking water, n = 8). ICH was induced by collagenase infusion into the right striata of all rats. Coronal T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, and diffusion-weighted imaging were generated with a 3.0T MRI scanner to investigate the changes of hemorrhagic volume and edema throughout the injury and recovery stages of ICH in rats. RESULTS: T2-weighted imaging is ideal for monitoring hematoma volume in rats. The hematoma volume was larger in the CAC group than in the control group (P < .001), however, did not correlate to post-ICH progressive edema formation (P > .7), and neurological impairment (P > .28) between the 2 groups, respectively. DISCUSSION: Although our findings indicate that CAC induces larger hematoma in rats with ICH, the underlying mechanism should be studied in the future. PMID: 30205999 [PubMed - as supplied by publisher]

Aberrant Sialylation in Cancer Pathology and Metastasis, a Putative Drug Target Candidate.

Thu, 13/09/2018 - 13:04
Related Articles Aberrant Sialylation in Cancer Pathology and Metastasis, a Putative Drug Target Candidate. Anticancer Agents Med Chem. 2018 Sep 10;: Authors: Lu DY, Lu TR, Xu B, Varki A, Huang M, Zhu H, Shen Y, Yarla NS Abstract BACKGROUNDS: Neoplasm metastasis is a multi-step and multi-level pathological feature causing 90% of cancer mortality due to a shortage of effective drugs and clinical therapeutics. To change this scenario, new drug targets and developments are required. METHOD: Aberrant tumor sialylation as a putative drug target candidate has been evolving over the past half century. Some specific agents and clinical events suggested some promising therapeutic potentiality and benefits against neoplasm metastasis in a number of cellular and animal tumor models. RESULTS: Since neoplasm tissues often contain higher levels and diverse sialic acids (sia) analogues and antigens, sia-related tumor biology/pathology are emerging as cancer diagnostic categories and a series of useful agents until now. Previously some compounds enabling to inhibit sia-related pathologic pathways were reported to exhibit therapeutic activity in cellular or animal tumor models. These types of cancer treatment agents can provide excellent therapeutic outcomes by glycome/metabolomics diagnostics first. CONCLUSION: Taking together of these experimental/clinical discoveries, the "central dogma" of glycobiology might be found out via all these principle discoveries. In addition, mathematic- or physics-majored talents might render new therapeutic discoveries by computational analysis of experimental and clinical data. Overall, therapeutic targets/benefits in the clinic should be pursuit with earnest attitude. PMID: 30205804 [PubMed - as supplied by publisher]

Comprehensive Metabolomics Analysis of Mandarins (Citrus reticulata) as A Tool for Variety, Rootstock and Grove Discrimination.

Thu, 13/09/2018 - 13:04
Related Articles Comprehensive Metabolomics Analysis of Mandarins (Citrus reticulata) as A Tool for Variety, Rootstock and Grove Discrimination. J Agric Food Chem. 2018 Sep 12;: Authors: Feng S, Niu L, Suh JH, Hung WL, Wang Y Abstract The metabolite profile responsible for the quality of mandarin fruit is influenced by pre-harvest factors including genotype, rootstock, grove location, etc. In this paper, mandarin varieties were discriminated using metabolomics. Additionally, effects on metabolic profiles due to grove location and rootstock differences were also investigated. Results revealed that mandarin varieties could be differentiated using the metabolite profile, while the compositions of flavonoids have the potential for variety differentiation. With regard to fruits of the same variety, grove location might determine the overall profile of metabolites, whereas rootstock possibly affected composition of secondary metabolites. Pathway enrichment analysis demonstrated biosynthesis pathways of terpenoids and steroids involving limonene and linalool, were highly influenced by variety diversity. Moreover, the flavonoid biosynthesis pathway, involving hesperetin, naringenin, eriodictyol and taxifolin, was indicated to have a close relationship with rootstock differentiation. This study provides useful and important information with depth for breeding and optimizing pre-harvest practices. PMID: 30205680 [PubMed - as supplied by publisher]

A variable selection approach in the multivariate linear model: an application to LC-MS metabolomics data.

Thu, 13/09/2018 - 13:04
Related Articles A variable selection approach in the multivariate linear model: an application to LC-MS metabolomics data. Stat Appl Genet Mol Biol. 2018 Sep 08;: Authors: Perrot-Dockès M, Lévy-Leduc C, Chiquet J, Sansonnet L, Brégère M, Étienne MP, Robin S, Genta-Jouve G PMID: 30205662 [PubMed - as supplied by publisher]

Response of Cisplatin Resistant Skov-3 Cells to [Pt(O,O'-Acac)(γ-Acac)(DMS)] Treatment Revealed by a Metabolomic ¹H-NMR Study.

Thu, 13/09/2018 - 13:04
Related Articles Response of Cisplatin Resistant Skov-3 Cells to [Pt(O,O'-Acac)(γ-Acac)(DMS)] Treatment Revealed by a Metabolomic ¹H-NMR Study. Molecules. 2018 Sep 09;23(9): Authors: De Castro F, Benedetti M, Antonaci G, Del Coco L, De Pascali SA, Muscella A, Marsigliante S, Fanizzi FP Abstract The novel [Pt(O,O'-acac)(γ-acac)(DMS)], Ptac2S, Pt(II) complex has recently gained increasing attention as a potential anticancer agent for its pharmacological activity shown in different tumor cell lines, studied both in vitro and in vivo. The mechanism of action of Ptac2S, operating on non-genomic targets, is known to be very different from that of cis-[PtCl₂(NH₃)₂], cisplatin, targeting nucleic acids. In this work, we evaluated the cytotoxicity of Ptac2S on the cisplatin resistant Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells, by the MTT assay. A ¹H-NMR metabolomic approach coupled with multivariate statistical analysis was used for the first time for Ptac2S to figure out the biological mechanisms of action of the complex. The metabolic variations of intracellular metabolites and the composition of the corresponding extracellular culture media were compared to those of cisplatin (cells were treated at the IC50 doses of both drugs). The reported comparative metabolomic analysis revealed a very different metabolic profile between Ptac2S and cisplatin treated samples, thus confirming the different mechanism of action of Ptac2S also in the Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells line. In particular, higher levels of pyruvate were observed in Ptac2S treated, with respect to cisplatin treated, cells (in both aqueous and culture media). In addition, a very different lipid expression resulted after the exposure to the two drugs (Ptac2S and cisplatin). These results suggest a possible explanation for the Ptac2S ability to circumvent cisplatin resistance in SKOV-3 cells. PMID: 30205612 [PubMed - in process]

Potential Metabolomic Linkage in Blood between Parkinson's Disease and Traumatic Brain Injury.

Thu, 13/09/2018 - 13:04
Related Articles Potential Metabolomic Linkage in Blood between Parkinson's Disease and Traumatic Brain Injury. Metabolites. 2018 Sep 07;8(3): Authors: Fiandaca MS, Gross TJ, Johnson TM, Hu MT, Evetts S, Wade-Martins R, Merchant-Borna K, Bazarian J, Cheema AK, Mapstone M, Federoff HJ Abstract The etiologic basis for sporadic forms of neurodegenerative diseases has been elusive but likely represents the product of genetic predisposition and various environmental factors. Specific gene-environment interactions have become more salient owing, in part, to the elucidation of epigenetic mechanisms and their impact on health and disease. The linkage between traumatic brain injury (TBI) and Parkinson's disease (PD) is one such association that currently lacks a mechanistic basis. Herein, we present preliminary blood-based metabolomic evidence in support of potential association between TBI and PD. Using untargeted and targeted high-performance liquid chromatography-mass spectrometry we identified metabolomic biomarker profiles in a cohort of symptomatic mild TBI (mTBI) subjects (n = 75) 3⁻12 months following injury (subacute) and TBI controls (n = 20), and a PD cohort with known PD (n = 20) or PD dementia (PDD) (n = 20) and PD controls (n = 20). Surprisingly, blood glutamic acid levels in both the subacute mTBI (increased) and PD/PDD (decreased) groups were notably altered from control levels. The observed changes in blood glutamic acid levels in mTBI and PD/PDD are discussed in relation to other metabolite profiling studies. Should our preliminary results be replicated in comparable metabolomic investigations of TBI and PD cohorts, they may contribute to an "excitotoxic" linkage between TBI and PD/PDD. PMID: 30205491 [PubMed]

Sepsis: Personalized Medicine Utilizing 'Omic' Technologies-A Paradigm Shift?

Thu, 13/09/2018 - 13:04
Related Articles Sepsis: Personalized Medicine Utilizing 'Omic' Technologies-A Paradigm Shift? Healthcare (Basel). 2018 Sep 07;6(3): Authors: Itenov TS, Murray DD, Jensen JUS Abstract Sepsis has over the years proven a considerable challenge to physicians and researchers. Numerous pharmacological and non-pharmacological interventions have been tested in trials, but have unfortunately failed to improve the general prognosis. This has led to the speculation that the sepsis population may be too heterogeneous to be targeted with the traditional one treatment suits all' approach. Recent advances in genetic and biochemical analyses now allow genotyping and biochemical characterisation of large groups of patients via the 'omics' technologies. These new opportunities could lead to a paradigm shift in the approach to sepsis towards personalised treatments with interventions targeted towards specific pathophysiological mechanisms activated in the patient. In this article, we review the potentials and pitfalls of using new advanced technologies to deepen our understanding of the clinical syndrome of sepsis. PMID: 30205441 [PubMed]

A sensitive and efficient procedure for the high-throughput determination of nine urinary metabolites of pyrethroids by GC-MS/MS and its application in a sample of Japanese children.

Thu, 13/09/2018 - 13:04
Related Articles A sensitive and efficient procedure for the high-throughput determination of nine urinary metabolites of pyrethroids by GC-MS/MS and its application in a sample of Japanese children. Anal Bioanal Chem. 2018 Sep;410(24):6207-6217 Authors: Ueda Y, Oda M, Saito I, Hamada R, Kondo T, Kamijima M, Ueyama J Abstract Four pyrethroids (PYRs), metofluthrin, profluthrin, tefluthrin, and transfluthrin, which were newly developed and have relatively high vapor activity at ambient temperature, are now playing a key role in safely controlling insects in our daily lives. We developed a sensitive and high-throughput determination method for urinary metabolites derived from the newly developed PYR, e.g., 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al), 2,3,5,6-tetrafluorobenzyl alcohol (FB-Al), and other PYR metabolites such as trans-chrysanthemumdicarboxylic acid (trans-CDCA) and 3-phenoxybenzoic acid (3PBA). After high temperature acid hydrolysis of 2 mL urine sample in 24-deep well plate, the PYR metabolites were extracted by semi-automated liquid-liquid extraction with tert-butyl methyl ether. N,O-Bis (trimethylsilyl) trifluoroacetamide containing 1% trimethylchlorosilane or 1,1,1,3,3,3-hexafluoroisopropanol were used for the derivatization of PYR metabolites, and the derivatized metabolites were analyzed separately by GC-MS/MS equipped with dual injector system (DB-5MS and mid- to high-polarity phase Rtx-65 columns). The derivatization and evaporation conditions were mainly optimized for improving sensitivity and reproducibility. The mean within-run day precisions were less than 18.4% (relative standard deviation, %RSD) with low detection limits ranging from 0.01 μg/L for HOCH2-FB-Al to 0.06 μg/L for trans-CDCA. This method was successfully applied to urine samples obtained from 50 3-year-old children with high detection frequencies (e.g., 82% for HOCH2-FB-Al and 84% for FB-Al). This method may be a pivotal tool for developing risk assessment from PYR exposure in the general population. PMID: 30046868 [PubMed - indexed for MEDLINE]

metabolomics; +25 new citations

Wed, 12/09/2018 - 15:20
25 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 2018/09/12PubMed 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.

metabolomics; +25 new citations

Wed, 12/09/2018 - 12:10
25 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 2018/09/12PubMed 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.

metabolomics; +22 new citations

Tue, 11/09/2018 - 14:13
22 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 2018/09/11PubMed 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.

Analytical Platforms and Techniques to Study Stem Cell Metabolism.

Mon, 10/09/2018 - 13:42
Related Articles Analytical Platforms and Techniques to Study Stem Cell Metabolism. Methods Mol Biol. 2018;1842:265-281 Authors: Tang C, Chen K, Bajic A, Choi WT, Baluya DL, Maletic-Savatic M Abstract Over the past decade, advances in systems biology or 'omics techniques have enabled unprecedented insights into the biological processes that occur in cells, tissues, and on the organism level. One of these technologies is the metabolomics, which examines the whole content of the metabolites in a given sample. In a biological system, a stem cell for instance, there are thousands of single components, such as genes, RNA, proteins, and metabolites. These multiple molecular species interact with each other and these interactions may change over the life-time of a cell or in response to specific stimuli, adding to the complexity of the system. Using metabolomics, we can obtain an instantaneous snapshot of the biological status of a cell, tissue, or organism and gain insights on the pattern(s) of numerous analytes, both known and unknown, that result because of a given biological condition. Here, we outline the main methods to study the metabolism of stem cells, including a relatively recent technology of mass spectrometry imaging. Given the abundant and increasing interest in stem cell metabolism in both physiological and pathological conditions, we hope that this chapter will provide incentives for more research in these areas to ultimately reach wide network of applications in biomedical, pharmaceutical, and nutritional research and clinical medicine. PMID: 30196417 [PubMed - in process]

Ganoderma Lucidum Polysaccharide Peptide Alleviates Hepatoteatosis via Modulating Bile Acid Metabolism Dependent on FXR-SHP/FGF.

Mon, 10/09/2018 - 13:42
Related Articles Ganoderma Lucidum Polysaccharide Peptide Alleviates Hepatoteatosis via Modulating Bile Acid Metabolism Dependent on FXR-SHP/FGF. Cell Physiol Biochem. 2018 Sep 07;49(3):1163-1179 Authors: Zhong D, Xie Z, Huang B, Zhu S, Wang G, Zhou H, Lin S, Lin Z, Yang B Abstract BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) encompasses a series of pathologic changes ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma. The purpose of this study was to determine whether ganoderma lucidum polysaccharide peptide (GLPP) has therapeutic effect on NAFLD. METHODS: Ob/ ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blot. Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. RESULTS: GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1, CYP8B1, FXR, SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid. CONCLUSION: GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis, indicating that GLPP might be developed as a therapeutic drug for NAFLD. PMID: 30196282 [PubMed - as supplied by publisher]

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