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: 35 min 29 sec ago

Proteomics and metabolomics characterizing the pathophysiology of adaptive reactions to the metabolic challenges during the transition from late pregnancy to early lactation in dairy cows.

Mon, 23/10/2017 - 16:17
Proteomics and metabolomics characterizing the pathophysiology of adaptive reactions to the metabolic challenges during the transition from late pregnancy to early lactation in dairy cows. J Proteomics. 2017 Oct 18;: Authors: Ceciliani F, Lecchi C, Urh C, Sauerwein H Abstract The transition from late pregnancy to early lactation is a critical period in a dairy cow's life due to the rapidly increasing drain of nutrients from the maternal organism towards the foetus and into colostrum and milk. In order to cope with the challenges of parturition and lactation, comprehensive adaptive reactions comprising the endocrine and the immune system need to be accomplished. There is high variation in this coping ability and both metabolic and infectious diseases, summarized as "production diseases", such as hypocalcaemia (milk fever), fatty liver syndrome, laminitis and ketosis, may occur and impact welfare, productive lifespan and economic outcomes. Proteomics and metabolomics have emerged as valuable techniques to characterize proteins and metabolite assets from tissue and biological fluids, such as milk, blood and urine. In this review we provide an overview on metabolic status and physiological changes during the transition period and the related production diseases in dairy cows, and summarize the state of art on proteomics and metabolomics of biological fluids and tissues involved in metabolic stress during the peripartum period. We also provide a current and prospective view of the application of the recent achievements generated by omics for biomarker discovery and their potential in diagnosis. BIOLOGICAL SIGNIFICANCE: For high-yielding dairy cows there are several "occupational diseases" that occur mainly during the metabolic challenges related to the transition from pregnancy to lactation. Such diseases and their sequelae form a major concern for dairy production, and often lead to early culling of animals. Beside the economical perspective, metabolic stress may severely influence animal welfare. There is a multitude of studies about the metabolic backgrounds of such so called production diseases like ketosis, fatty liver, or hypocalcaemia, although the investigations aiming to assess the complexity of the pathophysiological reactions are largely focused on gene expression, i.e. transcriptomics. For extending the knowledge towards the proteome and the metabolome, the respective technologies are of increasing importance and can provide an overall view of how dairy cows react to metabolic stress, which is needed for an in-depth understanding of the molecular mechanisms of the related diseases. We herein review the current findings from studies applying proteomics and metabolomics to transition-related diseases, including fatty liver, ketosis, endometritis, hypocalcaemia and laminitis. For each disease, a brief overview of the up to date knowledge about its pathogenesis is provided, followed by an insight into the most recent achievements on the proteome and metabolome of tissues and biological fluids, such as blood serum and urine, highlighting potential biomarkers. We believe that this review would help readers to be become more familiar with the recent progresses of molecular background of transition-related diseases thus encouraging research in this field. PMID: 29055723 [PubMed - as supplied by publisher]

Development of an on-line solid phase extraction ultra performance liquid chromatography technique coupled to tandem mass spectrometry for quantification of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic investigations.

Mon, 23/10/2017 - 16:17
Development of an on-line solid phase extraction ultra performance liquid chromatography technique coupled to tandem mass spectrometry for quantification of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic investigations. J Chromatogr A. 2017 Oct 12;: Authors: Grandin F, Picard-Hagen N, Gayrard V, Puel S, Viguié C, Toutain PL, Debrauwer L, Lacroix MZ Abstract Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as Bisphenol S (BPS), in consumer products. At present, no toxicokinetic investigations have been conducted to assess the factors determining human internal exposure to BPS for subsequent risk assessment. Toxicokinetic studies require reliable analytical methods to measure the plasma concentrations of BPS and its main conjugated metabolite, BPS-glucuronide (BPS-G). An efficient on-line SPE-UPLC-MS/MS method for the simultaneous quantification of BPS and BPS-G in ovine plasma was therefore developed and validated in accordance with the European Medicines Agency guidelines for bioanalytical method validation. This method has a limit of quantification of 3ngmL(-1) for BPS and 10ngmL(-1) for BPS-G, an analytical capacity of 200 samples per day, and is particularly well suited to toxicokinetic studies. Use of this method in toxicokinetic studies in sheep showed that BPS, like BPA, is efficiently metabolized into its glucuronide form. However, the clearances and distributions of BPS and BPS-G were lower than those of the corresponding unconjugated and glucuroconjugated forms of BPA. PMID: 29055528 [PubMed - as supplied by publisher]

The antimicrobial peptide nisin Z induces selective toxicity and apoptotic cell death in cultured melanoma cells.

Sun, 22/10/2017 - 12:51
Related Articles The antimicrobial peptide nisin Z induces selective toxicity and apoptotic cell death in cultured melanoma cells. Biochimie. 2017 Oct 17;: Authors: Lewies A, Wentzel JF, van Dyk H, Du Plessis LH Abstract Reprogramming of cellular metabolism is now considered one of the hallmarks of cancer. Most malignant cells Reprogramming of cellular metabolism is now considered one of the hallmarks of cancer. Most malignant cells present with altered energy metabolism which is associated with elevated reactive oxygen species (ROS) generation. This is also evident for melanoma, the leading cause of skin cancer related deaths. Altered mechanisms affecting mitochondrial bioenergetics pose attractive targets for novel anti-cancer therapies. Antimicrobial peptides have been shown to exhibit selective anti-cancer activities. In this study, the anti-melanoma potential of the antimicrobial peptide, nisin Z, was evaluated in vitro. Nisin Z was shown to induce selective toxicity in melanoma cells compared to non-malignant keratinocytes. Furthermore, nisin Z was shown to negatively affect the energy metabolism (glycolysis and mitochondrial respiration) of melanoma cells, increase reactive oxygen species generation and cause apoptosis. Results also indicate that nisin Z can decrease the invasion and proliferation of melanoma cells demonstrating its potential use against metastasis associated with melanoma. As nisin Z seems to place a considerable extra burden on the energy metabolism of melanoma cells, combination therapies with known anti-melanoma agents may be effective treatment options. PMID: 29054798 [PubMed - as supplied by publisher]

Fluvial biofilms exposed to desiccation and pharmaceutical pollution: New insights using metabolomics.

Sun, 22/10/2017 - 12:51
Related Articles Fluvial biofilms exposed to desiccation and pharmaceutical pollution: New insights using metabolomics. Sci Total Environ. 2017 Oct 17;: Authors: Serra-Compte A, Corcoll N, Huerta B, Rodríguez-Mozaz S, Sabater S, Barceló D, Álvarez-Muñoz D Abstract In many arid and semi-arid systems, biological communities in river ecosystems are submitted to flow interruption and desiccation, as well as to the impact of urban wastewaters. In this work, we studied (using a LC-LTQ-Orbitrap) the metabolomic response of biofilm communities exposed to both hydrological and chemical stressors. Fluvial biofilms were exposed to a mixture of 9 pharmaceuticals at a total concentration of 5000ng/L (mimicking concentrations and compounds found in polluted aquatic environments) and/or to seven days of desiccation, under laboratory conditions. The biosynthesis of fatty acids was the main metabolic pathway disrupted in biofilms. Endogenous biofilm's metabolites (metabolome) altered due to these stressors were identified. The metabolites that significantly changed only due to one of the stressors could be proposed as potential specific biomarkers. A biomarker of pharmaceutical exposure was the lysophosphatidic acid, which decreased a 160%, while for desiccation stearidonic acid (increased 160%), 16-Oxohexadecanoic acid (increased 340%) and palmitoleic acid (decreased 290%) were the biomarkers proposed. Besides, other metabolites showed different responses depending on the treatment, such as palmitic acid, linolenic acid, behenic acid, lignoceric acid and azelaic acid. The Carbon:Phosphorus (C:P) molar ratio increased due to all stress factors, whereas the algal community composition changed mainly due to desiccation. A possible relationship between those changes observed in structural parameters and the metabolome of biofilms was explored. Overall, our findings support the use of metabolomics to unravel at molecular level the effects from chemical and physical stressors on complex microbial communities, such as biofilms, and pinpoint biomarkers of exposure. PMID: 29054673 [PubMed - as supplied by publisher]

Enhanced MS/MS coverage for metabolite identification in LC-MS-based untargeted metabolomics by target-directed data dependent acquisition with time-staggered precursor ion list.

Sun, 22/10/2017 - 12:51
Related Articles Enhanced MS/MS coverage for metabolite identification in LC-MS-based untargeted metabolomics by target-directed data dependent acquisition with time-staggered precursor ion list. Anal Chim Acta. 2017 Nov 01;992:67-75 Authors: Wang Y, Feng R, Wang R, Yang F, Li P, Wan JB Abstract Metabolite identification is one of the major bottlenecks in liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics owing to the difficulty of acquiring MS/MS information of most metabolites detected. Data dependent acquisition (DDA) has been currently used to acquire MS/MS data in untargeted metabolomics. When dealing with the complex biological samples, top-n-based DDA method selects only a small fraction of the ions for fragmentation, leading to low MS/MS coverage of metabolites in untargeted metabolomics. In this study, we proposed a novel DDA method to improve the performance of MS/MS acquisition in LC-MS-based untargeted metabolomics using target-directed DDA (t-DDA) with time-staggered precursor ion lists (ts-DDA). Full scan-based untargeted analysis was applied to extract the target ions. After peak alignment, ion filtration, and ion fusion, the target precursor ion list was generated for subsequent t-DDA and ts-DDA. Compared to the conventional DDA, the ts-DDA exhibits the better MS/MS coverage of metabolomes in a plasma sample, especially for the low abundant metabolites. Even in high co-elution zones, the ts-DDA also showed the superiority in acquiring MS/MS information of co-eluting ions, as evidenced by better MS/MS coverage and MS/MS efficiency, which was mainly attributed to the pre-selection of precursor ion and the reduced number of concurrent ions. The newly developed method might provide more informative MS/MS data of metabolites, which will be helpful to increase the confidence of metabolite identification in untargeted metabolomics. PMID: 29054151 [PubMed - in process]

Subacute oral toxicity assessment of benalaxyl in mice based on metabolomics methods.

Sat, 21/10/2017 - 12:38
Subacute oral toxicity assessment of benalaxyl in mice based on metabolomics methods. Chemosphere. 2017 Oct 15;191:373-380 Authors: Wang X, Wang D, Zhou Z, Zhu W Abstract In this study, the metabolic responses of mice after 30 days of exposure to benalaxyl were assessed using NMR-based untargeted metabolomics and LC-MS-based targeted profiling of 20 amino acids. Urinary (1)H NMR analyses revealed alterations in energy metabolism, lipid metabolism, vitamin B metabolism, the urea cycle and amino acid metabolism, and targeted analyses indicated that the serum levels of asparagine, histidine, lysine and aspartic acid were significantly altered. Additionally, significant oxidative stress was observed in the liver and kidney, although no apparent histopathological injury was observed. The tissue distribution indicated a significant stereoselectivity in the brain, where (-)-R-benalaxyl was enriched. These data provide a comprehensive picture of the subacute toxic effects of benalaxyl in mice. The results of this study suggested that, for a toxicity evaluation, metabolomics analysis is much more sensitive than traditional toxicological methods. The results also highlight the combined use of untargeted and targeted metabolomics approaches in evaluating the health risks of xenobiotics. PMID: 29054078 [PubMed - as supplied by publisher]

Resolution of inflammation and sepsis survival are improved by dietary Ω-3 fatty acids.

Sat, 21/10/2017 - 12:38
Resolution of inflammation and sepsis survival are improved by dietary Ω-3 fatty acids. Cell Death Differ. 2017 Oct 20;: Authors: Körner A, Schlegel M, Theurer J, Frohnmeyer H, Adolph M, Heijink M, Giera M, Rosenberger P, Mirakaj V Abstract Critical conditions such as sepsis following infection or traumatic injury disturb the complex state of homeostasis that may lead to uncontrolled inflammation resulting in organ failure, shock and death. They are associated with endogenous mediators that control the onset of acute inflammatory response, but the central problem remains the complete resolution of inflammation. Omega-3 enriched lipid emulsions (Ω-3(+) LEs) were used in experimental studies and clinical trials to establish homeostasis, yet with little understanding about their role on the resolution of inflammation and tissue regeneration. Here, we demonstrate that Ω-3 lipid emulsions (LEs) orchestrate inflammation-resolution/regeneration mechanism during sterile peritonitis and murine polymicrobial sepsis. Ω-3(+) LEs recessed neutrophil infiltration, reduced pro-inflammatory mediators, reduced the classical monocyte and enhanced the non-classical monocytes/macrophages recruitment and finally increased the efferocytosis in sepsis. The actions of Ω-3(+) LE were 5-lipoxygenase (5-LOX) and 12/15-lipoxygenase (12/15-LOX) dependent. Ω-3(+) LEs shortened the resolution interval by 56%, stimulated the endogenous biosynthesis of resolution mediators lipoxin A4, protectin DX and maresin 1 and contributed to tissue regeneration. Ω-3(+) LEs protected against hypothermia and weight loss and enhanced survival in murine polymicrobial sepsis. We highlighted a role of Ω-3(+) LEs in regulating key mechanisms within the resolution terrain during murine sepsis. This might form the basis for a rational design of sepsis specific clinical nutrition.Cell Death and Differentiation advance online publication, 20 October 2017; doi:10.1038/cdd.2017.177. PMID: 29053142 [PubMed - as supplied by publisher]

Metabolic shift in density-dependent stem cell differentiation.

Sat, 21/10/2017 - 12:38
Metabolic shift in density-dependent stem cell differentiation. Cell Commun Signal. 2017 Oct 20;15(1):44 Authors: Singh SJ, Turner W, Glaser DE, McCloskey KE, Filipp FV Abstract BACKGROUND: Vascular progenitor cells (VPCs) derived from embryonic stem cells (ESCs) are a valuable source for cell- and tissue-based therapeutic strategies. During the optimization of endothelial cell (EC) inductions from mouse ESCs using our staged and chemically-defined induction methods, we found that cell seeding density but not VEGF treatment between 10 ng/mL and 40 ng/mL was a significant variable directing ESCs into FLK1(+) VPCs during stage 1 induction. Here, we examine potential contributions from cell-to-cell signaling or cellular metabolism in the production of VPCs from ESCs seeded at different cell densities. METHODS: Using 1D (1)H-NMR spectroscopy, transcriptomic arrays, and flow cytometry, we observed that the density-dependent differentiation of ESCs into FLK1(+) VPCs positively correlated with a shift in metabolism and cellular growth. RESULTS: Specifically, cell differentiation correlated with an earlier plateauing of exhaustive glycolysis, decreased lactate production, lower metabolite consumption, decreased cellular proliferation and an increase in cell size. In contrast, cells seeded at a lower density of 1,000 cells/cm(2) exhibited increased rates of glycolysis, lactate secretion, metabolite utilization, and proliferation over the same induction period. Gene expression analysis indicated that high cell seeding density correlated with up-regulation of several genes including cell adhesion molecules of the notch family (NOTCH1 and NOTCH4) and cadherin family (CDH5) related to vascular development. CONCLUSIONS: These results confirm that a distinct metabolic phenotype correlates with cell differentiation of VPCs. PMID: 29052507 [PubMed - in process]

[Serum metabonomics in mice infected with mycoplasma pneumoniae by UPLC-Q-TOF-MS].

Sat, 21/10/2017 - 12:38
Related Articles [Serum metabonomics in mice infected with mycoplasma pneumoniae by UPLC-Q-TOF-MS]. Zhongguo Zhong Yao Za Zhi. 2017 Apr;42(7):1382-1389 Authors: Wei WF, Chu YT, Liu Y, Huo JH, Wang WM Abstract Ultra high performance liquid chromatography coupled with tandem quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) was applied to metabonomics study in BALB/c mice infected with mycoplasma pneumoniae(MP) to analyze the changes in serum endogenous metabolites, identify potential biomarkers associated with mycoplasma pneumoniae pneumonia(MPP), analyze the metabolic pathway and explore the pathogenic mechanism of MPP. The BALB/c mice were inoculated with MP by repeated intranasal infectious routes to establish MPP models, and the results of the lung tissue biopsy, IgM and mycoplasma nucleic acid content determination showed that the models of MP in BALB/c mice were successfully established. UPLC-Q-TOF-MS was used to analyze the serum metabolic profiling of BALB/c mice infected with MP, and then principal component analysis(PCA) was combined with orthogonal partial least squares discriminant analysis(OPLS-DA) for data processing. The results showed that there were significant differences in serum metabolic profile between the MP infected mice and the normal mice. Forty-seven potential biomarkers such as ornithine, cortisol, vitamin A and tryptophan were screened out by database searching and MS information matching. These potential biomarkers related to 17 metabolic pathways including retinol metabolism, arginine and proline metabolism, steroid hormone synthesis and so on. The metabonomic research method for serum of mice infected with mycoplasma pneumoniae based on UPLC-Q-TOF-MS was established in this study. The metabolic changes of endogenous small molecules in mice infected with MP were reflected in the overall level, laying the foundation for the selection and evaluation of MPP drugs. PMID: 29052403 [PubMed - in process]

[Research progress of serum pharmacochemistry of traditional Chinese medicine].

Sat, 21/10/2017 - 12:38
Related Articles [Research progress of serum pharmacochemistry of traditional Chinese medicine]. Zhongguo Zhong Yao Za Zhi. 2017 Apr;42(7):1265-1270 Authors: Ma FX, Xue PF, Wang YY, Wang YN, Xue SY Abstract Serum pharmacochemistry of traditional Chinese medicine(TCM) is an effective method to rapidly screen the effective substances and reveal the compatibility law of compound by identification and analysis of constituents migrating to blood after oral administration. In the last two decades, it has been universally accepted and widely applied in the field. With the cross-fusion with other disciplines, such as serum pharmacology, pharmacokinetics, metabolomics, network pharmacology and systems biology, serum pharmacochemistry shows comprehensive superiority in explaining drug changes in vivo and in vitro, interactions between drugs, interactions between drug and body, which coincides with the complexity of TCM compatibility, multi-components, multi-targets and multi-mechanisms. Based on the references related with the serum pharmacochemistry from CNKI scholar and Pubmed in 2013-2016, the research results of serum pharmacochemistry were statistically analyzed, and the key technical problems during the study of serum pharmacochemistry, for example, preparation of test sample, selection of experimental animal, determination of drug delivery scheme, method and time of the adoption blood, preparation and pretreatment of blood sample, as well as analysis of constituents migrating to blood, and the solving ways were empirically introduced. In addition, the development and comprehensive application of serum pharmacochemistry in TCM were summarized in this paper, hoping to lay a foundation for the further application of this method in TCM research. PMID: 29052384 [PubMed - in process]

Control of biotin biosynthesis in mycobacteria by a pyruvate carboxylase dependent metabolic signal.

Sat, 21/10/2017 - 12:38
Related Articles Control of biotin biosynthesis in mycobacteria by a pyruvate carboxylase dependent metabolic signal. Mol Microbiol. 2017 Oct 20;: Authors: Lazar N, Fay A, Nandakumar M, Boyle KE, Xavier J, Rhee K, Glickman MS Abstract Biotin is an essential cofactor utilized by all domains of life, but only synthesized by bacteria, fungi and plants, making biotin biosynthesis a target for antimicrobial development. To understand biotin biosynthesis in mycobacteria, we executed a genetic screen in Mycobacterium smegmatis for biotin auxotrophs and identified pyruvate carboxylase (Pyc) as required for biotin biosynthesis. The biotin auxotrophy of the pyc::tn strain is due to failure to transcriptionally induce late stage biotin biosynthetic genes in low biotin conditions. Loss of bioQ, the repressor of biotin biosynthesis, in the pyc::tn strain reverted biotin auxotrophy, as did reconstituting the last step of the pathway through heterologous expression of BioB and provision of its substrate DTB. The role of Pyc in biotin regulation required its catalytic activities and could be supported by M. tuberculosis Pyc. Quantitation of the kinetics of depletion of biotinylated proteins after biotin withdrawal revealed that Pyc is the most rapidly depleted biotinylated protein and metabolomics revealed a broad metabolic shift in wild type cells upon biotin withdrawal which was blunted in cell lacking Pyc. Our data indicate that mycobacterial cells monitor biotin sufficiency through a metabolic signal generated by dysfunction of a biotinylated protein of central metabolism. This article is protected by copyright. All rights reserved. PMID: 29052269 [PubMed - as supplied by publisher]

The Impacts of Genistein and Daidzein on Estrogen Conjugations in Human Breast Cancer Cells: A Targeted Metabolomics Approach.

Sat, 21/10/2017 - 12:38
Related Articles The Impacts of Genistein and Daidzein on Estrogen Conjugations in Human Breast Cancer Cells: A Targeted Metabolomics Approach. Front Pharmacol. 2017;8:699 Authors: Poschner S, Maier-Salamon A, Zehl M, Wackerlig J, Dobusch D, Pachmann B, Sterlini KL, Jäger W Abstract The beneficial effect of dietary soy food intake, especially for women diagnosed with breast cancer, is controversial, as in vitro data has shown that the soy isoflavones genistein and daidzein may even stimulate the proliferation of estrogen-receptor alpha positive (ERα+) breast cancer cells at low concentrations. As genistein and daidzein are known to inhibit key enzymes in the steroid metabolism pathway, and thus may influence levels of active estrogens, we investigated the impacts of genistein and daidzein on the formation of estrogen metabolites, namely 17β-estradiol (E2), 17β-estradiol-3-(β-D-glucuronide) (E2-G), 17β-estradiol-3-sulfate (E2-S) and estrone-3-sulfate (E1-S) in estrogen-dependent ERα+ MCF-7 cells. We found that both isoflavones were potent inhibitors of E1 and E2 sulfation (85-95% inhibition at 10 μM), but impeded E2 glucuronidation to a lesser extent (55-60% inhibition at 10 μM). The stronger inhibition of E1 and E2 sulfation compared with E2 glucuronidation was more evident for genistein, as indicated by significantly lower inhibition constants for genistein [Kis: E2-S (0.32 μM) < E1-S (0.76 μM) < E2-G (6.01 μM)] when compared with those for daidzein [Kis: E2-S (0.48 μM) < E1-S (1.64 μM) < E2-G (7.31 μM)]. Concomitant with the suppression of E1 and E2 conjugation, we observed a minor but statistically significant increase in E2 concentration of approximately 20%. As the content of genistein and daidzein in soy food is relatively low, an increased risk of breast cancer development and progression in women may only be observed following consumption of high-dose isoflavone supplements. Further long-term human studies monitoring free estrogens and their conjugates are therefore highly warranted to evaluate the potential side effects of high-dose genistein and daidzein, especially in patients diagnosed with ERα+ breast cancer. PMID: 29051735 [PubMed]

Myocardial metabolic alterations in mice with diet-induced atherosclerosis: linking sulfur amino acid and lipid metabolism.

Sat, 21/10/2017 - 12:38
Related Articles Myocardial metabolic alterations in mice with diet-induced atherosclerosis: linking sulfur amino acid and lipid metabolism. Sci Rep. 2017 Oct 19;7(1):13597 Authors: Lee J, Jung S, Kim N, Shin MJ, Ryu DH, Hwang GS Abstract Atherosclerosis is a leading cause of cardiovascular disease (CVD), but the effect of diet on the atherosclerotic heart's metabolism is unclear. We used an integrated metabolomics and lipidomics approach to evaluate metabolic perturbations in heart and serum from mice fed an atherogenic diet (AD) for 8, 16, and 25 weeks. Nuclear magnetic resonance (NMR)-based metabolomics revealed significant changes in sulfur amino acid (SAA) and lipid metabolism in heart from AD mice compared with heart from normal diet mice. Higher SAA levels in AD mice were quantitatively verified using liquid chromatography-mass spectrometry (LC/MS). Lipidomic profiling revealed that fatty acid and triglyceride (TG) levels in the AD group were altered depending on the degree of unsaturation. Additionally, levels of SCD1, SREBP-1, and PPARγ were reduced in AD mice after 25 weeks, while levels of reactive oxygen species were elevated. The results suggest that a long-term AD leads to SAA metabolism dysregulation and increased oxidative stress in the heart, causing SCD1 activity suppression and accumulation of toxic TGs with a low degree of unsaturation. These findings demonstrate that the SAA metabolic pathway is a promising therapeutic target for CVD treatment and that metabolomics can be used to investigate the metabolic signature of atherosclerosis. PMID: 29051579 [PubMed - in process]

CE-MS-based metabolomics reveals the metabolic profile of maitake mushroom (Grifola frondosa) strains with different cultivation characteristics.

Sat, 21/10/2017 - 12:38
Related Articles CE-MS-based metabolomics reveals the metabolic profile of maitake mushroom (Grifola frondosa) strains with different cultivation characteristics. Biosci Biotechnol Biochem. 2017 Oct 20;:1-9 Authors: Sato M, Miyagi A, Yoneyama S, Gisusi S, Tokuji Y, Kawai-Yamada M Abstract Maitake mushroom (Grifola frondosa [Dicks.] Gray) is generally cultured using the sawdust of broadleaf trees. The maitake strain Gf433 has high production efficiency, with high-quality of fruiting bodies even when 30% of the birch sawdust on the basal substrate is replaced with conifer sawdust. We performed metabolome analysis to investigate the effect of different cultivation components on the metabolism of Gf433 and Mori52 by performing CE-MS on their fruiting bodies in different cultivation conditions to quantify the levels of amino acids, organic acids, and phosphorylated organic acids. We found that amino acid and organic acid content in Gf433 were not affected by the kind of sawdust. However, Gf433 contained more organic acids and less amino acids than Mori52, and Gf433 also contained more chitin compared with Mori52. We believe that these differences in the metabolome contents of the two strains are related to the high production efficiency of Gf433. PMID: 29050513 [PubMed - as supplied by publisher]

A prospective study of serum metabolites and glioma risk.

Sat, 21/10/2017 - 12:38
Related Articles A prospective study of serum metabolites and glioma risk. Oncotarget. 2017 Sep 19;8(41):70366-70377 Authors: Huang J, Weinstein SJ, Kitahara CM, Karoly ED, Sampson JN, Albanes D Abstract Malignant glioma is one of the most lethal adult cancers, yet its etiology remains largely unknown. We conducted a prospective serum metabolomic analysis of glioma based on 64 cases and 64 matched controls selected from Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Median time from collection of baseline fasting serum to diagnosis was nine years (inter-decile range 3-20 years). LC/MS-MS identified 730 known metabolites, and conditional logistic regression models estimated odds ratios for one-standard deviation differences in log-metabolite signals. Forty-three metabolites were associated with glioma at P<0.05. 2-Oxoarginine, cysteine, alpha-ketoglutarate, chenodeoxycholate and argininate yielded the strongest metabolite signals and were inversely related to overall glioma risk (0.0065≤P<0.0083). Also, seven xanthine metabolites related to caffeine metabolism were higher in cases than in controls (0.017≤P<0.042). Findings were mostly similar in high-grade glioma cases, although prominent inversely associated metabolites included the secondary bile acids glycocholenate sulfate and 3β-hydroxy-5-cholenoic acid, xenobiotic methyl 4-hydroxybenzoate sulfate, sex steroid 5alpha-pregnan-3beta, 20beta-diol-monosulfate, and cofactor/vitamin oxalate (0.0091≤P<0.021). A serum metabolomic profile of glioma identified years in advance of clinical diagnoses is characterized by altered signals in arginine/proline, antioxidant, and coffee-related metabolites. The observed pattern provides new potential leads regarding the molecular basis relevant to etiologic or sub-clinical biomarkers for glioma. PMID: 29050286 [PubMed]

Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease.

Sat, 21/10/2017 - 12:38
Related Articles Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease. J Transl Med. 2016 Sep 15;14:266 Authors: Chang X, Wang Z, Zhang J, Yan H, Bian H, Xia M, Lin H, Jiang J, Gao X Abstract BACKGROUND: We recently demonstrated a positive effect of berberine on nonalcoholic fatty liver disease patients after 16 weeks of treatment by comparing mere lifestyle intervention in type 2 diabetes patients with berberine treatment, which decreased the content of hepatic fat. However, the potential mechanisms of the clinical effects are unclear. We used a lipidomic approach to characterize the state of lipid metabolism as reflected in the circulation of subjects with nonalcoholic fatty liver disease (NAFLD) before and after berberine treatment. METHODS: Liquid chromatography-mass spectrometry evaluated the various lipid metabolites in serum samples obtained from the participants (41 patients in the berberine group and 39 patients in the mere lifestyle intervention group) before and after treatment. RESULTS: A total of 256 serum lipid molecular species were identified and quantified. Both treatments regulated various types of lipids in metabolic pathways, such as free fatty acids, phosphoglycerides and glycerides, in metabolic pathways, but berberine induced a substantially greater change in serum lipid species compared with mere lifestyle intervention after treatment. Berberine also caused obvious differences on ceramides. Berberine treatment markedly decreased serum levels of ceramide and ceramide-1-phosphate. CONCLUSIONS: Berberine altered circulating ceramides, which may underlie the improvement in fatty liver disease. ClinicalTrials.gov NCT00633282, Registered March 3, 2008. PMID: 27629750 [PubMed - indexed for MEDLINE]

Synergistic Cysteamine Delivery Nanowafer as an Efficacious Treatment Modality for Corneal Cystinosis.

Sat, 21/10/2017 - 12:38
Related Articles Synergistic Cysteamine Delivery Nanowafer as an Efficacious Treatment Modality for Corneal Cystinosis. Mol Pharm. 2016 Oct 03;13(10):3468-3477 Authors: Marcano DC, Shin CS, Lee B, Isenhart LC, Liu X, Li F, Jester JV, Pflugfelder SC, Simpson J, Acharya G Abstract A synergy between the polymer biomaterial and drug plays an important role in enhancing the therapeutic efficacy, improving the drug stability, and minimizing the local immune responses in the development of drug delivery systems. Particularly, in the case of ocular drug delivery, the need for the development of synergistic drug delivery system becomes more pronounced because of the wet ocular mucosal surface and highly innervated cornea, which elicit a strong inflammatory response to the instilled drug formulations. This article presents the development of a synergistic cysteamine delivery nanowafer to treat corneal cystinosis. Corneal cystinosis is a rare metabolic disease that causes the accumulation of cystine crystals in the cornea resulting in corneal opacity and loss of vision. It is treated with topical cysteamine (Cys) eye drops that need to be instilled 6-12 times a day throughout the patient's life, which causes side effects such as eye pain, redness, and ocular inflammation. As a result, compliance and treatment outcomes are severely compromised. To surmount these issues, we have developed a clinically translatable Cys nanowafer (Cys-NW) that can be simply applied on the eye with a fingertip. During the course of the drug release, Cys-NW slowly dissolves and fades away. The in vivo studies in cystinosin knockout mice demonstrated twice the therapeutic efficacy of Cys-NW containing 10 μg of Cys administered once a day, compared to 44 μg of Cys as topical eye drops administered twice a day. Furthermore, Cys-NW stabilizes Cys for up to four months at room temperature compared to topical Cys eye drops that need to be frozen or refrigerated and still remain active for only 1 week. The Cys-NW, because of its enhanced therapeutic efficacy, safety profile, and extended drug stability at room temperature, can be rapidly translated to the clinic for human trials. PMID: 27571217 [PubMed - indexed for MEDLINE]

metabolomics; +22 new citations

Fri, 20/10/2017 - 15:09
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 2017/10/20PubMed 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

Fri, 20/10/2017 - 12:02
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 2017/10/20PubMed 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; +27 new citations

Thu, 19/10/2017 - 14:41
27 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 2017/10/19PubMed 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.

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