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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 48 min 2 sec ago

Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies.

Thu, 12/07/2018 - 14:37
Related Articles Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies. Ann Oncol. 2018 Jul 09;: Authors: Dong X, Ma G, Chen F PMID: 29992296 [PubMed - as supplied by publisher]

Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects.

Thu, 12/07/2018 - 14:37
Related Articles Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects. Biomed Res Int. 2018;2018:6852857 Authors: Dinis-Oliveira RJ Abstract Propofol is an intravenous short-acting anesthetic widely used to induce and maintain general anesthesia and to provide procedural sedation. The potential for propofol dependency and abuse has been recognized, and several cases of accidental overdose and suicide have emerged, mostly among the health professionals. Different studies have demonstrated an unpredictable interindividual variability of propofol pharmacokinetics and pharmacodynamics with forensic and clinical adverse relevant outcomes (e.g., pronounced respiratory and cardiac depression), namely, due to polymorphisms in the UDP-glucuronosyltransferase and cytochrome P450 isoforms and drugs administered concurrently. In this work the pharmacokinetics of propofol and fospropofol with particular focus on metabolic pathways is fully reviewed. It is concluded that knowing the metabolism of propofol may lead to the development of new clues to help further toxicological and clinical interpretations and to reduce serious adverse reactions such as respiratory failure, metabolic acidosis, rhabdomyolysis, cardiac bradyarrhythmias, hypotension and myocardial failure, anaphylaxis, hypertriglyceridemia, renal failure, hepatomegaly, hepatic steatosis, acute pancreatitis, abuse, and death. Particularly, further studies aiming to characterize polymorphic enzymes involved in the metabolic pathway, the development of additional routine forensic toxicological analysis, and the relatively new field of ''omics" technology, namely, metabolomics, can offer more in explaining the unpredictable interindividual variability. PMID: 29992157 [PubMed - in process]

Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study.

Thu, 12/07/2018 - 14:37
Related Articles Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study. Transl Psychiatry. 2018 Jul 10;8(1):130 Authors: Pan JX, Xia JJ, Deng FL, Liang WW, Wu J, Yin BM, Dong MX, Chen JJ, Ye F, Wang HY, Zheng P, Xie P Abstract Major depressive disorder (MDD) is a debilitating psychiatric illness. However, there is currently no objective laboratory-based diagnostic tests for this disorder. Although, perturbations in multiple neurotransmitter systems have been implicated in MDD, the biochemical changes underlying the disorder remain unclear, and a comprehensive global evaluation of neurotransmitters in MDD has not yet been performed. Here, using a GC-MS coupled with LC-MS/MS-based targeted metabolomics approach, we simultaneously quantified the levels of 19 plasma metabolites involved in GABAergic, catecholaminergic, and serotonergic neurotransmitter systems in 50 first-episode, antidepressant drug-naïve MDD subjects and 50 healthy controls to identify potential metabolite biomarkers for MDD (training set). Moreover, an independent sample cohort comprising 49 MDD patients, 30 bipolar disorder (BD) patients and 40 healthy controls (testing set) was further used to validate diagnostic generalizability and specificity of these candidate biomarkers. Among the 19 plasma neurotransmitter metabolites examined, nine were significantly changed in MDD subjects. These metabolites were mainly involved in GABAergic, catecholaminergic and serotonergic systems. The GABAergic and catecholaminergic had better diagnostic value than serotonergic pathway. A panel of four candidate plasma metabolite biomarkers (GABA, dopamine, tyramine, kynurenine) could distinguish MDD subjects from health controls with an AUC of 0.968 and 0.953 in the training and testing set, respectively. Furthermore, this panel distinguished MDD subjects from BD subjects with high accuracy. This study is the first to globally evaluate multiple neurotransmitters in MDD plasma. The altered plasma neurotransmitter metabolite profile has potential differential diagnostic value for MDD. PMID: 29991685 [PubMed - in process]

Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism.

Thu, 12/07/2018 - 14:37
Related Articles Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. Proc Natl Acad Sci U S A. 2018 Jul 10;: Authors: Skene DJ, Skornyakov E, Chowdhury NR, Gajula RP, Middleton B, Satterfield BC, Porter KI, Van Dongen HPA, Gaddameedhi S Abstract Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is essential to assess whether and how peripheral clocks are disturbed during shift work and to what extent this is linked to the central suprachiasmatic nuclei (SCN) pacemaker and/or misaligned behavioral time cues. Investigating rhythms in circulating metabolites as biomarkers of peripheral clock disturbances may offer new insights. We evaluated the impact of misaligned sleep/wake and feeding/fasting cycles on circulating metabolites using a targeted metabolomics approach. Sequential plasma samples obtained during a 24-h constant routine that followed a 3-d simulated night-shift schedule, compared with a simulated day-shift schedule, were analyzed for 132 circulating metabolites. Nearly half of these metabolites showed a 24-h rhythmicity under constant routine following either or both simulated shift schedules. However, while traditional markers of the circadian clock in the SCN-melatonin, cortisol, and PER3 expression-maintained a stable phase alignment after both schedules, only a few metabolites did the same. Many showed reversed rhythms, lost their rhythms, or showed rhythmicity only under constant routine following the night-shift schedule. Here, 95% of the metabolites with a 24-h rhythmicity showed rhythms that were driven by behavioral time cues externally imposed during the preceding simulated shift schedule rather than being driven by the central SCN circadian clock. Characterization of these metabolite rhythms will provide insight into the underlying mechanisms linking shift work and metabolic disorders. PMID: 29991600 [PubMed - as supplied by publisher]

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

Thu, 12/07/2018 - 14:37
Related Articles Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward? Mol Diagn Ther. 2017 Oct;21(5):525-537 Authors: Langley RJ, Wong HR Abstract Sepsis remains one of the leading causes of death in the USA and it is expected to get worse as the population ages. Moreover, the standard of care, which recommends aggressive treatment with appropriate antibiotics, has led to an increase in multiple drug-resistant organisms. There is a dire need for the development of new antibiotics, improved antibiotic stewardship, and therapies that treat the host response. Development of new sepsis therapeutics has been a disappointment as no drugs are currently approved to treat the various complications from sepsis. Much of the failure has been blamed on animal models that do not accurately reflect the course of the disease. However, recent improvements in metabolomic, transcriptomic, genomic, and proteomic platforms have allowed for a broad-spectrum look at molecular changes in the host response using clinical samples. Integration of these multi-omic datasets allows researchers to perform systems biology approaches to identify novel pathophysiology of the disease. In this review, we highlight what is currently known about sepsis and how integrative omics has identified new diagnostic and predictive models of sepsis as well as novel mechanisms. These changes may improve patient care as well as guide future preclinical analysis of sepsis. PMID: 28624903 [PubMed - indexed for MEDLINE]

metabolomics; +22 new citations

Wed, 11/07/2018 - 17:18
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 2018/07/11PubMed 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.

metabolomics; +22 new citations

Wed, 11/07/2018 - 14:15
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 2018/07/11PubMed 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.

metabolomics; +17 new citations

Tue, 10/07/2018 - 13:41
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/07/10PubMed 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.

Proteome profiling in the hippocampus, medial prefrontal cortex, and striatum of aging rat.

Sun, 08/07/2018 - 12:50
Proteome profiling in the hippocampus, medial prefrontal cortex, and striatum of aging rat. Exp Gerontol. 2018 Jul 04;: Authors: Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Bellier JP, Makpol S, Ngah WZW, Damanhuri HA, Tooyama I Abstract Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein S100B and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging. PMID: 29981398 [PubMed - as supplied by publisher]

Predictors of Treatment Response in Rheumatoid Arthritis.

Sun, 08/07/2018 - 12:50
Predictors of Treatment Response in Rheumatoid Arthritis. Joint Bone Spine. 2018 Jul 04;: Authors: Lequerré T, Rottenberg P, Derambure C, Cosette P, Vittecoq O Abstract The expanding array of drugs available for treating rheumatoid arthritis is creating challenges in drug selection for the individual patient. The identification of biomarkers that predict the treatment response prior to drug exposure is therefore a current priority. This new approach, known as theranostics, is a component of personalized medicine, which involves selecting the management strategies that are most effective for a given patient at a given point in time. Antibodies to citrullinated peptides, rheumatoid factor, and the interferon signature are the most robust and best validated biomarkers identified to date. Matrices containing clinical or laboratory parameters of diagnostic or prognostic relevance may help to select the best treatment for the individual patient. Furthermore, the development of large-scale approaches requiring no a priori knowledge, such as functional genomics and metabolomics, hold considerable promise, despite persistent difficulties in replicating findings. The complexity of the treatment response in a given patient and substantial variability across patients suggest that biomarkers may be more helpful in combination than singly. The objectives of this review article are to discuss the approaches used to identify theranostic biomarkers and to present an overview of currently available biomarkers and of their performance in everyday clinical practice. However, the range of biomarkers suitable for use in daily practice remains extremely narrow. PMID: 29981377 [PubMed - as supplied by publisher]

Metabolomic Profiling of rats'Urine After Oral Administration of the Prescription Antipyretic Hao Jia Xu Re Qing Granules by UPLC/Q-TOF-MS.

Sun, 08/07/2018 - 12:50
Metabolomic Profiling of rats'Urine After Oral Administration of the Prescription Antipyretic Hao Jia Xu Re Qing Granules by UPLC/Q-TOF-MS. Biomed Chromatogr. 2018 Jul 07;:e4332 Authors: Yu CQ, Chen JP, Zhong YM, Zhong XL, Tang CP, Yang Y, Lin HQ Abstract Hao Jia Xu Re Qing Granules (HJ), is an effective clinically used antipyretic based on Traditional Chinese Medicine (TCM). Although its antipyretic therapeutic effectiveness is obvious, its therapeutic mechanism has not been comprehensively explored yet. In this research, we first identified potential biomarkers which may be relevant for the antipyretic effect of HJ based on urine metabolomics using Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A rat model of fever was established using the yeast-induced febrile response. Total-ion-current metabolic profiles of different groups were acquired and the data were processed by multivariate statistical analysis-partial least-squares discriminant analysis (PLSDA). As envisioned, the results revealed changes of urine metabolites related to the antipyretic effect. fourteen potential biomarkers were selected from the urine samples based on the results of Student's t-test, "shrinkaget", variable importance in projection (VIP), and PLSDA. N-acetylleucine, kynurenic acid, indole-3-ethanol, nicotinuric acid, pantothenic acid, and tryptophan were the most significant biomarkers found in the urine samples, and may be crucially related to the antipyretic effect of HJ. Consequently, we propose the hypothesis that the significant antipyretic effect the HJ may be related to the inhibition of tryptophan metabolism. This research thus provides strong theoretical support and further direction to explain the antipyretic mechanism of HJ, laying the foundation for future studies. PMID: 29981286 [PubMed - as supplied by publisher]

Transformed Root Culture: From Genetic Transformation to NMR-Based Metabolomics.

Sun, 08/07/2018 - 12:50
Related Articles Transformed Root Culture: From Genetic Transformation to NMR-Based Metabolomics. Methods Mol Biol. 2018;1815:457-474 Authors: Marchev AS, Yordanova ZP, Georgiev MI Abstract Hairy root (HR) culture is considered as "green factory" for mass production of bioactive molecules with pharmaceutical relevance. As such, HR culture has an immense potential as a valuable platform to elucidate biosynthetic pathways and physiological processes, generate recombinant therapeutic proteins, assist molecular breeding, and enhance phytoremediation efforts. However, some plant species appear recalcitrant to the classical Agrobacterium rhizogenes transformation techniques. Sonication-assisted Agrobacterium-mediated transformation (SAArT) is a highly effective method to deliver bacteria to target plant tissues that includes exposure of the explants to short periods of ultrasound in the presence of the bacteria.Nuclear magnetic resonance (NMR)-based metabolomics is one of the most powerful and suitable platforms for identifying and obtaining structural information on a wide range of compounds with a high analytical precision. In terms of plant science, NMR metabolomics is used to determine the phytochemical variations of medicinal plants or commercial cultivars in certain environments and conditions, including biotic stress and plant biotic interaction, structural determination of natural products, quality control of herbal drugs or dietary supplements, and comparison of metabolite differences between plants and their respective in vitro cultures.In this chapter, we attempt to summarize our knowledge and expertise in induction of hairy roots from rare and recalcitrant plant species by SAArT technique and further methodology for extraction of secondary metabolites of moderate to high polarity and their identification by using NMR-based metabolomics. PMID: 29981142 [PubMed - in process]

Analysis of Terpenoid Indole Alkaloids, Carotenoids, Phytosterols, and NMR-Based Metabolomics for Catharanthus roseus Cell Suspension Cultures.

Sun, 08/07/2018 - 12:50
Related Articles Analysis of Terpenoid Indole Alkaloids, Carotenoids, Phytosterols, and NMR-Based Metabolomics for Catharanthus roseus Cell Suspension Cultures. Methods Mol Biol. 2018;1815:437-455 Authors: Saiman MZ, Mustafa NR, Verpoorte R Abstract The plant Catharanthus roseus is a rich source of terpenoid indole alkaloids (TIA). Some of the TIA are important as antihypertensive (ajmalicine) and anticancer (vinblastine and vincristine) drugs. However, production of the latter is very low in the plant. Therefore, in vitro plant cell cultures have been considered as a potential supply of these chemicals or their precursors. Some monomeric alkaloids can be produced by plant cell cultures, but not on a level feasible for commercialization, despite extensive studies on this plant that deepened the understanding of the TIA biosynthesis and its regulation. In order to analyze the metabolites in C. roseus cell cultures, this chapter presents the method of TIA, carotenoids, and phytosterols analyses. Furthermore, an NMR-based metabolomics approach to study C. roseus cell culture is described. PMID: 29981141 [PubMed - in process]

An Introduction to Plant Tissue Culture: Advances and Perspectives.

Sun, 08/07/2018 - 12:50
Related Articles An Introduction to Plant Tissue Culture: Advances and Perspectives. Methods Mol Biol. 2018;1815:3-13 Authors: Loyola-Vargas VM, Ochoa-Alejo N Abstract Plant tissue culture techniques are the most frequently used biotechnological tools for basic and applied purposes ranging from investigation on plant developmental processes, functional gene studies, commercial plant micropropagation, generation of transgenic plants with specific industrial and agronomical traits, plant breeding and crop improvement, virus elimination from infected materials to render high-quality healthy plant material, preservation and conservation of germplasm of vegetative propagated plant crops, and rescue of threatened or endangered plant species. Additionally, plant cell and organ cultures are of interest for the production of secondary metabolites of industrial and pharmaceutical interest. New technologies, such as the genome editing ones combined with tissue culture and Agrobacterium tumefaciens infection, are currently promising alternatives for the highly specific genetic manipulation of interesting agronomical or industrial traits in crop plants. Application of omics (genomics, transcriptomics, and proteomics) to plant tissue culture will certainly help to unravel complex developmental processes such as organogenesis and somatic embryogenesis, which will probably enable to improve the efficiency of regeneration protocols for recalcitrant species. Additionally, metabolomics applied to tissue culture will facilitate the extraction and characterization of complex mixtures of natural plant products of industrial interest. General and specific aspects and applications of plant tissue culture and the advances and perspectives are described in this edition. PMID: 29981111 [PubMed - in process]

The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics.

Sun, 08/07/2018 - 12:50
Related Articles The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics. Alzheimers Res Ther. 2018 Jul 06;10(1):64 Authors: Bos I, Vos S, Vandenberghe R, Scheltens P, Engelborghs S, Frisoni G, Molinuevo JL, Wallin A, Lleó A, Popp J, Martinez-Lage P, Baird A, Dobson R, Legido-Quigley C, Sleegers K, Van Broeckhoven C, Bertram L, Ten Kate M, Barkhof F, Zetterberg H, Lovestone S, Streffer J, Visser PJ Abstract BACKGROUND: There is an urgent need for novel, noninvasive biomarkers to diagnose Alzheimer's disease (AD) in the predementia stages and to predict the rate of decline. Therefore, we set up the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. In this report we describe the design of the study, the methods used and the characteristics of the participants. METHODS: Participants were selected from existing prospective multicenter and single-center European studies. Inclusion criteria were having normal cognition (NC) or a diagnosis of mild cognitive impairment (MCI) or AD-type dementia at baseline, age above 50 years, known amyloid-beta (Aβ) status, availability of cognitive test results and at least two of the following materials: plasma, DNA, magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF). Targeted and untargeted metabolomic and proteomic analyses were performed in plasma, and targeted and untargeted proteomics were performed in CSF. Genome-wide SNP genotyping, next-generation sequencing and methylation profiling were conducted in DNA. Visual rating and volumetric measures were assessed on MRI. Baseline characteristics were analyzed using ANOVA or chi-square, rate of decline analyzed by linear mixed modeling. RESULTS: We included 1221 individuals (NC n = 492, MCI n = 527, AD-type dementia n = 202) with a mean age of 67.9 (SD 8.3) years. The percentage Aβ+ was 26% in the NC, 58% in the MCI, and 87% in the AD-type dementia groups. Plasma samples were available for 1189 (97%) subjects, DNA samples for 929 (76%) subjects, MRI scans for 862 (71%) subjects and CSF samples for 767 (63%) subjects. For 759 (62%) individuals, clinical follow-up data were available. In each diagnostic group, the APOE ε4 allele was more frequent amongst Aβ+ individuals (p < 0.001). Only in MCI was there a difference in baseline Mini Mental State Examination (MMSE) score between the A groups (p < 0.001). Aβ+ had a faster rate of decline on the MMSE during follow-up in the NC (p < 0.001) and MCI (p < 0.001) groups. CONCLUSIONS: The characteristics of this large cohort of elderly subjects at various cognitive stages confirm the central roles of Aβ and APOE ε4 in AD pathogenesis. The results of the multimodal analyses will provide new insights into underlying mechanisms and facilitate the discovery of new diagnostic and prognostic AD biomarkers. All researchers can apply for access to the EMIF-AD MBD data by submitting a research proposal via the EMIF-AD Catalog. PMID: 29980228 [PubMed - in process]

Analysis of pharmaceuticals and small molecules in aqueous humor.

Sat, 07/07/2018 - 12:15
Analysis of pharmaceuticals and small molecules in aqueous humor. J Pharm Biomed Anal. 2018 Jun 25;159:23-36 Authors: Pietrowska K, Dmuchowska DA, Krasnicki P, Mariak Z, Kretowski A, Ciborowski M Abstract Aqueous humor (AH) is a transparent fluid found in the anterior chamber of the eye. The circulating AH nourishes the cornea and lens and removes the metabolic waste moving through the ocular chambers and drains from the eye to the venous blood. Analysis of drugs in AH is necessary to evaluate their pharmacokinetics parameters, which may be crucial to avoid potential adverse effects. Analysis of endogenous components of AH may help to understand its physiology as well as changes evoked by pathological situation. This review describes analytical methods used for determination of pharmaceuticals and small endogenous molecules in AH, focusing on sample preparation procedures and analytical techniques. Studies on human and animal samples are included. After inspection and filtering of records found in PubMed about 100 research papers were selected to review. In these articles AH samples of human and rabbit origin were studied most often. Sample evaporation and reconstitution in smaller solvent volume was the most popular method for analyte pre-concentration. Acetonitrile, methanol or mixture of both solvents were used most often for protein precipitation. PMID: 29980016 [PubMed - as supplied by publisher]

Effects of lobeglitazone on insulin resistance and hepatic steatosis in high-fat diet-fed mice.

Sat, 07/07/2018 - 12:15
Effects of lobeglitazone on insulin resistance and hepatic steatosis in high-fat diet-fed mice. PLoS One. 2018;13(7):e0200336 Authors: Choi BH, Jin Z, Yi CO, Oh J, Jeong EA, Lee JY, Park KA, Kim KE, Lee JE, Kim HJ, Hahm JR, Roh GS Abstract Lobeglitazone (Lobe) is a novel thiazolidinedione antidiabetic drug that reduces insulin resistance by activating peroxisome proliferator-activated receptor-gamma (PPARγ). However, the exact mechanisms of antidiabetic effects of Lobe have not been established in an animal model. The aim of this study was to evaluate the hypoglycemic effects of Lobe and investigate possible factors involved in Lobe-enhanced hepatic steatosis in high-fat diet (HFD)-fed mice. Mice were fed an HFD for 15 weeks. Lobe was administrated orally during the last 9 weeks. Lobe treatment significantly reduced insulin resistance and increased expression of hepatic glucose transporter 4 (GLUT4) and PPARs in HFD-fed mice. However, increased body weight and hepatic steatosis were not reduced by Lobe in these mice. Metabolomics fingerprinting showed that several lipogenesis-related hepatic and serum metabolites in HFD-fed mice had positive or negative correlations with Lobe administration. In particular, increased leptin levels during HFD were further increased by Lobe. HFD-induced signaling transducer and activator of transcription 3 (STAT3) phosphorylation in the hypothalamus was increased by Lobe. In addition, immunohistochemical analysis showed more proopiomelanocortin (POMC)-positive neurons in the hypothalamus of HFD-fed mice (with or without Lobe) compared with normal diet-fed mice. Despite improving leptin signaling in the hypothalamus and enhancing insulin sensitivity in HFD-fed mice, Lobe increased body weight and steatosis. Further research is necessary regarding other factors affecting Lobe-enhanced hepatic steatosis and hyperphagia. PMID: 29979770 [PubMed - in process]

HappyTools: A software for high-throughput HPLC data processing and quantitation.

Sat, 07/07/2018 - 12:15
HappyTools: A software for high-throughput HPLC data processing and quantitation. PLoS One. 2018;13(7):e0200280 Authors: Jansen BC, Hafkenscheid L, Bondt A, Gardner RA, Hendel JL, Wuhrer M, Spencer DIR Abstract High-performance liquid chromatography (HPLC) is widely used for absolute quantitation. The advent of new columns and HPLC technology has enabled higher sample throughput, and hence, larger scale studies that perform quantitation on different sample types (e.g. healthy controls vs. patients with rheumatoid arthritis) using HPLC are becoming feasible. However, there remains a lack of methods that can analyse the increased number of HPLC samples. To address this in part, the modular toolkit HappyTools has been developed for the high-throughput targeted quantitation of HPLC measurements. HappyTools enables the user to create an automated workflow that includes retention time (tr) calibration, data extraction and the calculation of several quality criteria for data curation. HappyTools has been tested on a biopharmaceutical standard and previously published clinical samples. The results show comparable accuracy between HappyTools, Waters Empower and ThermoFisher Chromeleon. However, HappyTools offered superior precision and throughput when compared with Waters Empower and ThermoFisher Chromeleon. HappyTools is released under the Apache 2.0 license, both the source code and a Windows binary can be freely downloaded from https://github.com/Tarskin/HappyTools. PMID: 29979768 [PubMed - in process]

Plant galactolipid dLGG suppresses lung metastasis of melanoma through deregulating TNF-α-mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice.

Sat, 07/07/2018 - 12:15
Related Articles Plant galactolipid dLGG suppresses lung metastasis of melanoma through deregulating TNF-α-mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice. Int J Cancer. 2018 Jul 06;: Authors: Yang CC, Chang CK, Chang MT, Shyur LF Abstract This study demonstrates the bioefficacy and gives mechanistic insights into a plant galactolipid 1,2-di-O-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) against metastatic melanoma using a syngeneic mouse model implanted with B16COX-2/Luc melanoma. dLGG-20 (p.o. dLGG 20 mg/kg) and anti-cancer drug CP-2 (i.p. cisplatin 2 mg/kg) treatment significantly inhibited lung metastasis of melanoma in mice 91% and 57%, respectively, as determined by bioluminescence intensity. Moreover, dLGG-20 and CP-2 treatment prolonged mouse mean survival time. dLGG-20 treatment significantly inhibited the expression levels of several molecular markers, i.e., PCNA, MMP2, COX-2, VEGF, vimentin, snail, TGF-β, β-catenin, TNF-α, PD-1 and PD-L1 in mouse lung tissues compared to tumor control mice. Significant inhibition of macrophage and neutrophil infiltration and promotion of CD8+Tc cell recruitment in the lung microenvironment was observed in dLGG-20-treated mice. A LC/MS-based comparative oxylipin metabolomics study showed that dLGG-20 treatment significantly induced (5.0- to 12.8-fold) the 12/15-LOX catalyzed oxylipin products in mouse serum including 17-HDHA from DHA, 15-HEPE from EPA, 8- and 12-HETEs from AA, and CYP450-derived 20-HETE from AA. CP-2 treatment increased 12/15-LOX derived 8-, 11- and 12-HETEs from AA, and CYP450 derived 11(12)-EET from AA and 9,10-DHOME from LA by 5.3- to 8.1-fold. Of note, dLGG and 17-HDHA were more effective than CP in preventing B16 melanoma cell-induced pulmonary vascular permeability in mice through inhibition of TNF-α production, up-regulation of tight junction proteins claudin1 and ZO-2, and deregulation of Src activation. In conclusion, this study shows the novel therapeutic effect of phytoagent dLGG and suggests its potential as a therapeutic agent for metastatic melanoma. This article is protected by copyright. All rights reserved. PMID: 29978476 [PubMed - as supplied by publisher]

The use of Metabolomics to Elucidate Resistance Markers Against Damson-Hop Aphid.

Sat, 07/07/2018 - 12:15
Related Articles The use of Metabolomics to Elucidate Resistance Markers Against Damson-Hop Aphid. J Chem Ecol. 2018 Jul 06;: Authors: Undas AK, Weihrauch F, Lutz A, van Tol R, Delatte T, Verstappen F, Bouwmeester H Abstract Phorodon humuli (Damson-hop aphid) is one of the major pests of hops in the northern hemisphere. It causes significant yield losses and reduces hop quality and economic value. Damson-hop aphid is currently controlled with insecticides, but the number of approved pesticides is steadily decreasing. In addition, the use of insecticides almost inevitably results in the development of resistant aphid genotypes. An integrated approach to pest management in hop cultivation is therefore badly needed in order to break this cycle and to prevent the selection of strains resistant to the few remaining registered insecticides. The backbone of such an integrated strategy is the breeding of hop cultivars that are resistant to Damson-hop aphid. However, up to date mechanisms of hops resistance towards Damson-hop aphids have not yet been unraveled. In the experiments presented here, we used metabolite profiling followed by multivariate analysis and show that metabolites responsible for hop aroma and flavor (sesquiterpenes) in the cones can also be found in the leaves, long before the hop cones develop, and may play a role in resistance against aphids. In addition, aphid feeding induced a change in the metabolome of all hop genotypes particularly an increase in a number of oxidized compounds, which suggests this may be part of a resistance mechanism. PMID: 29978430 [PubMed - as supplied by publisher]

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