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

metabolomics; +23 new citations

Thu, 30/01/2020 - 14:45
23 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 2020/01/30PubMed 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.

Metabolic Control over mTOR-Dependent Diapause-like State.

Wed, 29/01/2020 - 14:30
Related Articles Metabolic Control over mTOR-Dependent Diapause-like State. Dev Cell. 2020 Jan 27;52(2):236-250.e7 Authors: Hussein AM, Wang Y, Mathieu J, Margaretha L, Song C, Jones DC, Cavanaugh C, Miklas JW, Mahen E, Showalter MR, Ruzzo WL, Fiehn O, Ware CB, Blau CA, Ruohola-Baker H Abstract Regulation of embryonic diapause, dormancy that interrupts the tight connection between developmental stage and time, is still poorly understood. Here, we characterize the transcriptional and metabolite profiles of mouse diapause embryos and identify unique gene expression and metabolic signatures with activated lipolysis, glycolysis, and metabolic pathways regulated by AMPK. Lipolysis is increased due to mTORC2 repression, increasing fatty acids to support cell survival. We further show that starvation in pre-implantation ICM-derived mouse ESCs induces a reversible dormant state, transcriptionally mimicking the in vivo diapause stage. During starvation, Lkb1, an upstream kinase of AMPK, represses mTOR, which induces a reversible glycolytic and epigenetically H4K16Ac-negative, diapause-like state. Diapause furthermore activates expression of glutamine transporters SLC38A1/2. We show by genetic and small molecule inhibitors that glutamine transporters are essential for the H4K16Ac-negative, diapause state. These data suggest that mTORC1/2 inhibition, regulated by amino acid levels, is causal for diapause metabolism and epigenetic state. PMID: 31991105 [PubMed - in process]

Functional and Computational Genomics Reveal Unprecedented Flexibility in Stage-Specific Toxoplasma Metabolism.

Wed, 29/01/2020 - 14:30
Related Articles Functional and Computational Genomics Reveal Unprecedented Flexibility in Stage-Specific Toxoplasma Metabolism. Cell Host Microbe. 2020 Jan 27;: Authors: Krishnan A, Kloehn J, Lunghi M, Chiappino-Pepe A, Waldman BS, Nicolas D, Varesio E, Hehl A, Lourido S, Hatzimanikatis V, Soldati-Favre D Abstract To survive and proliferate in diverse host environments with varying nutrient availability, the obligate intracellular parasite Toxoplasma gondii reprograms its metabolism. We have generated and curated a genome-scale metabolic model (iTgo) for the fast-replicating tachyzoite stage, harmonized with experimentally observed phenotypes. To validate the importance of four metabolic pathways predicted by the model, we have performed in-depth in vitro and in vivo phenotyping of mutant parasites including targeted metabolomics and CRISPR-Cas9 fitness screening of all known metabolic genes. This led to unexpected insights into the remarkable flexibility of the parasite, addressing the dependency on biosynthesis or salvage of fatty acids (FAs), purine nucleotides (AMP and GMP), a vitamin (pyridoxal-5P), and a cofactor (heme) in both the acute and latent stages of infection. Taken together, our experimentally validated metabolic network leads to a deeper understanding of the parasite's biology, opening avenues for the development of therapeutic intervention against apicomplexans. PMID: 31991093 [PubMed - as supplied by publisher]

Proteomic changes in skeletal muscle of aged rats in response to resistance training.

Wed, 29/01/2020 - 14:30
Related Articles Proteomic changes in skeletal muscle of aged rats in response to resistance training. Cell Biochem Funct. 2020 Jan 27;: Authors: de Sousa Neto IV, Carvalho MM, Marqueti RC, Almeida JA, Oliveira KS, Barin FR, Petriz B, de Araújo HSS, Franco OL, Durigan JLQ Abstract Sarcopenia is a multifactorial process defined by loss of strength and skeletal muscle mass, which leads to a reduction in muscle cross-sectional area (CSA). Although resistance training (RT) has been indicated as a tool to counteract sarcopenia, the protein profile associated with skeletal muscle adaptations remains to be determined. We investigated the effects of 12 weeks of RT on the skeletal muscle proteome profile and CSA of young and older rats. Twenty-four animals were divided into four groups: young sedentary or trained and older sedentary or trained (six animals per group). A 12-week RT protocol was performed, which consisted of climbing a vertical ladder. The proteins from the gastrocnemius were analysed by LC-ESI-MS/MS. One-hundred and thirty-one proteins were identified, of which 28 were assessed between the groups. Ageing induced an increase in proteins associated with the glycolytic pathway, transport and stress response, which represent crucial mechanisms for muscle adaptation. RT upregulated metabolic enzymes, anti-oxidant activity and transport proteins, besides increasing hypertrophy, regardless of age, suggesting a beneficial adaptation to mitigate age-related sarcopenia. RT reduced muscle atrophy through the regulation of stress response and by increasing proteins related to energy production and transport, which in turn might protect tissue damage arising from exercise and ageing. SIGNIFICANCE OF THE STUDY: Protein abundance levels related to the metabolic process and stress response were increased in the aged muscle. RT proved to be an important intervention capable of inducing significant effects on muscle proteome regardless of ageing, due to upregulation of glycolytic enzymes, and anti-oxidant and transport proteins. This effect could lead to a beneficial adaptation in muscle structure, cellular function and overall homeostasis maintenance. This study contributes to better understanding of the basic biology of ageing and clarifies more profoundly the molecular networks behind physiological adaptations promoted by exercise training. Therefore, the results open new perspectives and insights for studies based on transcriptomics, metabolomics and functional assays. PMID: 31989681 [PubMed - as supplied by publisher]

Rumen fluid metabolomics of beef steers differing in feed efficiency.

Wed, 29/01/2020 - 14:30
Related Articles Rumen fluid metabolomics of beef steers differing in feed efficiency. Metabolomics. 2020 Jan 27;16(2):23 Authors: Clemmons BA, Powers JB, Campagna SR, Seay TB, Embree MM, Myer PR Abstract INTRODUCTION: Beef is the most consumed red meat in the United States, and the US is the largest producer and consumer of beef cattle globally. Feed is one of the largest input costs for the beef cattle industry, accounting for 40-60% of the total input costs. Identifying methods for improving feed efficiency in beef cattle herds could result in decreased cost to both producers and consumers, as well as increased animal protein available for global consumption. METHODS: In this study, rumen fluid was collected from low- (n = 14) and high-RFI (n = 15) steers. Rumen fluid was filtered through a 0.22 µM syringe filter, extracted using 0.1% formic acid in acetonitrile:water:methanol (2:2:1) and injected into the Dionex UltiMate 3000 UHPLC system with an Exactive Plus Orbitrap MS. Peaks were identified using MAVEN and analyzed using MetaboAnalyst 4.0 and SAS. Significance was determined using an α ≤ 0.05. RESULTS: Eight metabolites were greater in low-RFI steers compared to high-RFI steers, including 3,4-dihydroxyphenylacetate, 4-pyridoxate, citraconate, hypoxanthine, succinate/methylmalonate, thymine, uracil, and xylose (P ≤ 0.05). These metabolites were predominantly involved in amino acid and lipid metabolism. CONCLUSIONS: Rumen fluid metabolomes differ in steers of varying feed efficiencies. These metabolites may be used as biomarkers of feed efficiency, and may provide insight as to factors contributing to differences in feed efficiency that may be exploited to improve feed efficiency in beef cattle herds. PMID: 31989305 [PubMed - in process]

Utilization of GC-MS untargeted metabolomics to assess the delayed response of glufosinate treatment of transgenic herbicide resistant (HR) buffalo grasses (Stenotaphrum secundatum L.).

Wed, 29/01/2020 - 14:30
Related Articles Utilization of GC-MS untargeted metabolomics to assess the delayed response of glufosinate treatment of transgenic herbicide resistant (HR) buffalo grasses (Stenotaphrum secundatum L.). Metabolomics. 2020 Jan 27;16(2):22 Authors: Boonchaisri S, Stevenson T, Dias DA Abstract INTRODUCTION: Herbicide resistant (HR) buffalo grasses were genetically engineered to resist the non-selective herbicide, glufosinate in order to facilitate a modern, 'weeding program' which is highly effective in terms of minimizing costs and labor. The resistant trait was conferred by an insertion of the pat gene to allow for the production of the enzyme phosphinothricin acetyltransferase (PAT) to detoxify the glufosinate inhibitive effect. To date, there are only a few reports using metabolomics as well as molecular characterizations published for glufosinate-resistant crops with no reports on HR turfgrass. Therefore, for the first time, this study examines the metabolome of glufosinate-resistant buffalo grasses which not only will be useful to future growers but also the scientific community. OBJECTIVE: A major aim of this present work is to characterize and evaluate the metabolic alterations which may arise from a genetic transformation of HR buffalo grasses by comprehensively using gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics. METHODS: Eight-week old plants of 4 HR buffalo grasses, (93-1A, 93-2B, 93-3C and 93-5A) and 3 wild type varieties (WT 8-4A, WT 9-1B and WT 9-1B) were selected for physiological, molecular and metabolomics experiments. Plants were either sprayed with 1, 5, 10 and 15% v/v of glufosinate to evaluate the visual injuries or submerged in 5% v/v of glufosinate 3 days prior to a GC-MS based untargeted metabolomics analysis. In contrast, the control group was treated with distilled water. Leaves were extracted in 1:1 methanol:water and then analysed, using an in-house GC-MS untargeted workflow. RESULTS: Results identified 199 metabolites with only 6 of them (cis-aconitic acid, allantoin, cellobiose, glyceric acid, maltose and octadecanoic acid) found to be statistically significant (p < 0.05) between the HR and wild type buffalo grass varieties compared to the control experiment. Among these metabolites, unusual accumulation of allantoin was prominent and was an unanticipated effect of the pat gene insertion. As expected, glufosinate treatment caused significant metabolic alterations in the sensitive wild type, with the up-regulation of several amino acids (e.g. phenylalanine and isoleucine) which was likely due to glufosinate-induced senescence. The aminoacyl-tRNA biosynthetic pathway was identified as the most significant enriched pathway as a result of glufosinate effects because a number of its intermediates were amino acids. CONCLUSION: HR buffalo grasses were very similar to its wild type comparator based on a comprehensive GC-MS based untargeted metabolomics and therefore, should guarantee the safe use of these HR buffalo grasses. The current metabolomics analyses not only confirmed the effects of glufosinate to up-regulate free amino acid pools in the sensitive wild type but also several alterations in sugar, sugar phosphate and organic acid metabolism have been reported. PMID: 31989303 [PubMed - in process]

Design and baseline data of a population-based metabonomics study of eye diseases in eastern China: the Yueqing Ocular Diseases Investigation.

Wed, 29/01/2020 - 14:30
Related Articles Design and baseline data of a population-based metabonomics study of eye diseases in eastern China: the Yueqing Ocular Diseases Investigation. Eye Vis (Lond). 2020;7:8 Authors: Deng Y, Liang Y, Lin S, Wen L, Li J, Zhou Y, Shen M, Zheng J, Feng K, Sun Y, Robert KW, Qu J, Lu F Abstract Background: China is undergoing a massive transition toward an urban and industrial economy. These changes will restructure the demographics and economy which will eventually influence the future patterns of disease. The risk factors of vision-impairing eye diseases remain ambiguous and poorly understood. Metabolomics is an ideal tool to understand and shed light on the ocular disease mechanisms for earlier treatment. This article aims to describe the design, methodology and baseline data of the Yueqing Ocular Diseases Investigation (YODI), a developed county population-based study to determine the prevalence and primary causes of visual impairment; also with metabonomics analysis we aimed to identify, predict and suggest some preventive biomarkers that cause blindness. Methods: A population-based, cross-sectional study. Randomized clustering sampling was used to identify adults aged 50 years and older in Xiangyang Town, Yueqing county-level City. The interviews covered demographic, behavioral, ocular risk factors and mental health state. The ocular examination included visual acuity, autorefraction, intraocular pressure, anterior and posterior segment examinations, fundus photography, retinal tomography and angiography, and visual field testing. Anthropometric measurements included height and weight, waist and hip circumference, blood pressure, pulse rate, electrocardiogram, and abdominal ultrasound scan. A venous blood sample was collected for laboratory tests and metabonomics studies. Results: Of the 5319 individuals recruited for the YODI, 4769 (89.7%) subjects were enrolled for analyses. The median age was 62.0 years, and 45.6% were male. The educational level of illiteracy or semi-illiteracy, primary, middle and high school or above was 29.8%, 45.5%, 20.1%, and 3.3%, respectively. Majority of the participants were female, younger, and less educated when compared with nonparticipants. The average body mass index and waist-hip ratios were 24.4 ± 3.4 kg/m2 and 0.9 ± 0.1 respectively. Blood sample collection reached a sample size of 1909 (479 from subjects with self-reported diabetes and 1430 from one-third of the 4290 subjects without self-reported diabetes). Conclusions: The YODI provides population-based data with a high response rate (89.7%) on the prevalence and primary causes of major vision-impairing eye diseases in developed county areas in eastern China. Metabonomics analysis from YODI will provide further association of metabolic characteristics with the visual impairment eye diseases. The risk prediction model could be created and has the potential to be generalized to developed eastern areas in China for prevention. PMID: 31988968 [PubMed]

Residual feed intake divergence during the preweaning period is associated with unique hindgut microbiome and metabolome profiles in neonatal Holstein heifer calves.

Wed, 29/01/2020 - 14:30
Related Articles Residual feed intake divergence during the preweaning period is associated with unique hindgut microbiome and metabolome profiles in neonatal Holstein heifer calves. J Anim Sci Biotechnol. 2020;11:13 Authors: Elolimy A, Alharthi A, Zeineldin M, Parys C, Loor JJ Abstract Background: Recent studies underscored that divergence in residual feed intake (RFI) in mature beef and dairy cattle is associated with changes in ruminal microbiome and metabolome profiles which may contribute, at least in part, to better feed efficiency. Because the rumen in neonatal calves during the preweaning period is underdeveloped until close to weaning, they rely on hindgut microbial fermentation to breakdown undigested diet components. This leads to production of key metabolites such as volatile fatty acids (VFA), amino acids, and vitamins that could potentially be absorbed in the hind-gut and help drive growth and development. Whether RFI divergence in neonatal calves is associated with changes in hindgut microbial communities and metabolites is largely unknown. Therefore, the objective of the current study was to determine differences in hindgut microbiome and metabolome in neonatal Holstein heifer calves retrospectively-grouped based on feed efficiency as most-efficient (M-eff) or least-efficient (L-eff) calves using RFI divergence during the preweaning period. Methods: Twenty-six Holstein heifer calves received 3.8 L of first-milking colostrum from their respective dams within 6 h after birth. Calves were housed in individual outdoor hutches bedded with straw, fed twice daily with a milk replacer, and had ad libitum access to a starter grain mix from birth to weaning at 42 d of age. Calves were classified into M-eff [n = 13; RFI coefficient = - 5.72 ± 0.94 kg DMI (milk replacer + starter grain)/d] and L-eff [n = 13; RFI coefficient = 5.61 ± 0.94 kg DMI (milk replacer + starter grain)/d] based on a linear regression model including the combined starter grain mix and milk replacer DMI, average daily gain (ADG), and metabolic body weight (MBW). A deep sterile rectal swab exposed only to the rectum was collected immediately at birth before colostrum feeding (i.e., d 0), and fecal samples at d 14, 28, and 42 (prior to weaning) for microbiome and untargeted metabolome analyses using 16S rRNA gene sequencing and LC-MS. Microbiome data were analyzed with the QIIME 2 platform and metabolome data with the MetaboAnalyst 4.0 pipeline. Results: No differences (P > 0.05) in body measurements including body weight (BW), body length (BL), hip height (HH), hip width (HW), and wither height (WH) were detected between M-eff and L-eff calves at birth and during preweaning. Although milk replacer intake did not differ between groups, compared with L-eff, M-eff heifers had lower starter intake (P < 0.01) between d 18 to 42 of age, whereas no differences (P > 0.05) for ADG, cumulative BWG, or body measurements were observed between RFI groups during the preweaning period. Microbiome and metabolome profiles through the first 42 d of age indicated greater hindgut capacity for the production of energy-generating substrates (butyrate and propionate) and essential nutrients (vitamins and amino acids) in heifers with greater estimated feed efficiency. Conclusion: Despite consuming approximately 54.6% less solid feed (cumulative intake, 10.90 vs. 19.98 ± 1.66 kg) from birth to weaning, the microbiome-metabolome changes in the hindgut of most-efficient heifers might have helped them maintain the same level of growth as the least-efficient heifers. PMID: 31988748 [PubMed]

Metabolite profile comparisons between ascending and descending colon tissue in healthy adults.

Wed, 29/01/2020 - 14:30
Related Articles Metabolite profile comparisons between ascending and descending colon tissue in healthy adults. World J Gastroenterol. 2020 Jan 21;26(3):335-352 Authors: Baxter BA, Parker KD, Nosler MJ, Rao S, Craig R, Seiler C, Ryan EP Abstract BACKGROUND: Obesity is a risk factor for colorectal cancer, yet metabolic distinctions between healthy right and left colon tissue, before cancer is diagnosed, remains largely unknown. This study compared right-ascending and left-descending colon tissue metabolomes to identify differences from the stool metabolome in normal weight, overweight, and obese adults. AIM: To examine right and left colon tissue metabolites according to body mass index that may serve as mechanistic targets for interventions and biomarkers for colon cancer risk. METHODS: Global, non-targeted metabolomics was applied to assess right-ascending and left-descending colon tissue collected from healthy adults undergoing screening colonoscopies to test the hypothesis that BMI differentially impacts colon tissue metabolite profiles. The colon tissue and stool metabolome of healthy adults (n = 24) was analyzed for metabolite signatures and metabolic pathway networks implicated in progression of colorectal cancer. RESULTS: Ascending and descending colon contained 504 host, food, and microbiota-derived metabolites from normal weight, overweight and obese adults grouped according to body mass index. Amino acids, lipids, and nucleotides were among the chemical types that further differentiated from the stool metabolite profiles. Normal weight adults had 46 significantly different metabolites between ascending and descending colon tissue locations, whereas there were 37 metabolite differences in overweight and 28 metabolite differences for obese adults (P < 0.05). Obese adults had trimethylamine N-oxide, endocannabinoids and monoacylglycerols with different relative abundances identified between ascending and descending colon. Primary and secondary bile acids, vitamins, and fatty acids also showed marked relative abundance differences in colon tissue from overweight/obese adults. CONCLUSION: There were metabolite profile differences between right-ascending and left-descending colon tissue in healthy adults. Colon lipids and other metabolites in obese and overweight adults were distinguished from normal weight participants and associated with gut inflammation, nutrient absorption, and products of microbiota metabolism. PMID: 31988593 [PubMed - in process]

Fatty acid metabolism in the progression and resolution of CNS disorders.

Wed, 29/01/2020 - 14:30
Related Articles Fatty acid metabolism in the progression and resolution of CNS disorders. Adv Drug Deliv Rev. 2020 Jan 24;: Authors: Bogie JFJ, Haidar M, Kooij G, Hendriks JJA Abstract Recent advances in lipidomics and metabolomics have unveiled the complexity of fatty acid metabolism and the fatty acid lipidome in health and disease. A growing body of evidence indicates that imbalances in the metabolism and level of fatty acids drive the initiation and progression of central nervous system (CNS) disorders such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. Here, we provide an in-depth overview on the impact of the β-oxidation, synthesis, desaturation, elongation, and peroxidation of fatty acids on the pathophysiology of these and other neurological disorders. Furthermore, we discuss the impact of individual fatty acids species, acquired through the diet or endogenously synthesized in mammals, on neuroinflammation, neurodegeneration, and CNS repair. The findings discussed in this review highlight the therapeutic potential of modulators of fatty acid metabolism and the fatty acid lipidome in CNS disorders, and underscore the diagnostic value of lipidome signatures in these diseases. PMID: 31987838 [PubMed - as supplied by publisher]

The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor?

Wed, 29/01/2020 - 14:30
Related Articles The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor? Ann Oncol. 2019 Oct;30(10):1572-1579 Authors: Elkrief A, Derosa L, Kroemer G, Zitvogel L, Routy B Abstract Immune-checkpoint inhibitors (ICI) now represent the standard of care for several cancer types. In pre-clinical models, absence of an intact gut microbiome negatively impacted ICI efficacy and these findings permitted to unravel the importance of the commensal microbiota in immuno-oncology. Recently, multiple clinical studies including more than 1800 patients in aggregate demonstrated the negative predictive impact of treatments with broad-spectrum antibiotics (ATB) on cancer patients receiving ICI. Altogether, these results have led to the hypothesis that ATB-induced dysbiosis might influence the clinical response through the modulation of the gut microbiome. Controversy still remains, as ATB treatment might simply constitute a surrogate marker of unfit or immunodeficient patients. In this review, we summarize recent publications addressing the impact of the gut microbiome on ICI efficacy, discuss currently available data on the effect of ATB administered in different time-frames respect to ICI initiation, and finally, evoke the therapeutic implications of these findings. PMID: 31987448 [PubMed - in process]

Metabolomic analysis of serum reveals the potential effective ingredients and pathways of Danggui Buxue Tang in promoting erythropoiesis.

Wed, 29/01/2020 - 14:30
Related Articles Metabolomic analysis of serum reveals the potential effective ingredients and pathways of Danggui Buxue Tang in promoting erythropoiesis. Complement Ther Med. 2020 Jan;48:102247 Authors: Wang X, Bei H, Du R, Chen Q, Wu F, Chen J, Bo H Abstract Danggui Buxue Tang has been used for menopausal women in China for more than 800 years. However, the potential effective ingredients and pathways require further investigation. The main objective of this work was to explore the potential effective ingredients and pathways. The optimal administration time was optimized by detecting the changes of reticulocytes in peripheral blood. Drug-containing serum (DCS) was taken every 30 min after last administration. Because of the different concentration of effective ingredients absorbed into blood at different time, the pharmacodynamic effect is different. Therefore, bone marrow stromal cells as a member of hematopoietic microenvironment were used to evaluate the pharmacodynamics of DCS. Metabolomics was used to detect changes of metabolites (DBT and endogenous metabolites). The correlation of the metabolites and pharmacodynamics was used to identify the metabolites associated with erythropoiesis. After 14 days, the number of reticulocytes in peripheral blood, erythroid-related cells and erythroid progenitor cells in bone marrow in the DBT group were significantly increased. In vitro experiments showed that DCS at different time had different proliferation effects on BMSCs. Metabolomic analysis showed that the concentration of metabolites in DCS at different time was significantly different. The correlation analysis identified 7 DBT metabolites and 15 endogenous metabolites related to erythropoiesis. 15 endogenous metabolites were finally connected to different pathways. Glutamate is a node molecule. 7 potential effective ingredients of DBT were found. DBT promoted erythropoiesis via promoting the metabolism of glutamate and further affect other pathways. PMID: 31987250 [PubMed - in process]

A surface-enhanced Raman spectroscopy database of 63 metabolites.

Wed, 29/01/2020 - 14:30
Related Articles A surface-enhanced Raman spectroscopy database of 63 metabolites. Talanta. 2020 Apr 01;210:120645 Authors: Sherman LM, Petrov AP, Karger LFP, Tetrick MG, Dovichi NJ, Camden JP Abstract Metabolomics, the study of metabolic profiles in a biological sample, has seen rapid growth due to advances in measurement technologies such as mass spectrometry (MS). While MS metabolite reference libraries have been generated for metabolomics applications, mass spectra alone are unable to unambiguously identify many metabolites in a sample; these unidentified compounds are typically annotated as "features". Surface-enhanced Raman spectroscopy (SERS) is an interesting technology for metabolite identification based on vibrational spectra. However, no reports have been published that present SERS metabolite spectra from chemical libraries. In this paper, we demonstrate that an untargeted approach utilizing citrate-capped silver nanoparticles yields SERS spectra for 20% of 80 compounds chosen randomly from a commercial metabolite library. Furthermore, prescreening of the metabolites according to chemical functionality allowed for the efficient identification of samples within the library that yield distinctive SERS spectra under our experimental conditions. Last, we present a reference database of 63 metabolite SERS spectra for use as an identification tool in metabolomics studies; this set includes 30 metabolites that have not had previously published SERS spectra. PMID: 31987216 [PubMed - in process]

Targeted metabolomics: Liquid chromatography coupled to mass spectrometry method development and validation for the identification and quantitation of modified nucleosides as putative cancer biomarkers.

Wed, 29/01/2020 - 14:30
Related Articles Targeted metabolomics: Liquid chromatography coupled to mass spectrometry method development and validation for the identification and quantitation of modified nucleosides as putative cancer biomarkers. Talanta. 2020 Apr 01;210:120640 Authors: Godoy AT, Eberlin MN, Simionato AVC Abstract A notable change in the body fluids nucleosides of cancer patients has been actively highlighted in searches for new biomarkers to early cancer detection. For this reason, improvements of bioanalytical methods for these compounds focused on a noninvasive sampling trend are of great importance. Therefore, this work aimed firstly to develop efficient methods for nucleoside analysis in urine and serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS), applying different strategies to quantify nine nucleosides, and further identify other untargeted nucleosides. Sample preparation was based on protein precipitation and affinity-solid phase extraction (SPE), whereas quantification was performed using a triple quadrupole (QqQ) mass analyzer operating in the selected reaction monitoring (SRM) mode. Surrogates matrices were proposed as an alternative to standard addition calibration. Specifically, to quantitate creatinine, a simple LC-MS/MS method was validated and used for normalization of urinary metabolites quantitation. To identify the other nucleosides, LC methods using different MS scans modes were evaluated on a quadrupole-time of flight (Q-TOF) or a hybrid triple quadrupole linear ion trap (Q-trap). Validation was performed for nucleosides quantification using the synthetic matrices of urine and serum, and selectivity, linearity, accuracy, reproducibility, matrix effect, LOD's and LOQ's were accessed, providing trustworthy results for bioanalysis purposes. Both LC-Q-Trap/MS and LC-Q-TOF/MS methods showed proper sensitivity for structural characterization on assays with urine and serum samples from healthy volunteers and could also be used in the identification of untargeted nucleosides. The investigated approaches delivered in-depth results and seem promising for future applications on urine and serum samples analyses aiming to validate nucleosides as cancer biomarkers. PMID: 31987192 [PubMed - in process]

Plasma lipidomic profiling in murine mutants of Hermansky-Pudlak syndrome reveals differential changes in pro- and anti-atherosclerotic lipids.

Wed, 29/01/2020 - 14:30
Related Articles Plasma lipidomic profiling in murine mutants of Hermansky-Pudlak syndrome reveals differential changes in pro- and anti-atherosclerotic lipids. Biosci Rep. 2019 02 28;39(2): Authors: Ma J, Wang R, Lam SM, Zhang C, Shui G, Li W Abstract Atherosclerosis is characterized by the accumulation of lipid-rich plaques in the arterial wall. Its pathogenesis is very complicated and has not yet been fully elucidated. It is known that dyslipidemia is a major factor in atherosclerosis. Several different Hermansky-Pudlak syndrome (HPS) mutant mice have been shown either anti-atherosclerotic or atherogenic phenotypes, which may be mainly attributed to corresponding lipid perturbation. To explore the effects of different HPS proteins on lipid metabolism and plasma lipid composition, we analyzed the plasma lipid profiles of three HPS mutant mice, pa (Hps9 -/-), ru (Hps6 -/-), ep (Hps1 -/-), and wild-type (WT) mice. In pa and ru mice, some pro-atherosclerotic lipids, e.g. ceramide (Cer) and diacylglycerol (DAG), were down-regulated whereas triacylglycerol (TAG) containing docosahexaenoic acid (DHA) (22:6) fatty acyl was up-regulated when compared with WT mice. Several pro-atherosclerotic lipids including phosphatidic acid (PA), lysophosphatidylserine (LPS), sphingomyelin (SM), and cholesterol (Cho) were up-regulated in ep mice compared with WT mice. The lipid droplets in hepatocytes showed corresponding changes in these mutants. Our data suggest that the pa mutant resembles the ru mutant in its anti-atherosclerotic effects, but the ep mutant has an atherogenic effect. Our findings may provide clues to explain why different HPS mutant mice exhibit distinct anti-atherosclerotic or atherogenic effects after being exposed to high-cholesterol diets. PMID: 30710063 [PubMed - indexed for MEDLINE]

metabolomics; +20 new citations

Tue, 28/01/2020 - 14:20
20 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 2020/01/28PubMed 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.

Orchids and their mycorrhizal fungi: an insufficiently explored relationship.

Mon, 27/01/2020 - 14:12
Related Articles Orchids and their mycorrhizal fungi: an insufficiently explored relationship. Mycorrhiza. 2020 Jan 25;: Authors: Favre-Godal Q, Gourguillon L, Lordel-Madeleine S, Gindro K, Choisy P Abstract Orchids are associated with diverse fungal taxa, including nonmycorrhizal endophytic fungi as well as mycorrhizal fungi. The orchid mycorrhizal (OM) symbiosis is an excellent model for investigating the biological interactions between plants and fungi due to their high dependency on these symbionts for growth and survival. To capture the complexity of OM interactions, significant genomic, numerous transcriptomic, and proteomic studies have been performed, unraveling partly the role of each partner. On the other hand, several papers studied the bioactive metabolites from each partner but rarely interpreted their significance in this symbiotic relationship. In this review, we focus from a biochemical viewpoint on the OM dynamics and its molecular interactions. The ecological functions of OM in plant development and stress resistance are described first, summarizing recent literature. Secondly, because only few studies have specifically looked on OM molecular interactions, the signaling pathways and compounds allowing the establishment/maintenance of mycorrhizal association involved in arbuscular mycorrhiza (AM) are discussed in parallel with OM. Based on mechanistic similarities between OM and AM, and recent findings on orchids' endophytes, a putative model representing the different molecular strategies that OM fungi might employ to establish this association is proposed. It is hypothesized here that (i) orchids would excrete plant molecule signals such as strigolactones and flavonoids but also other secondary metabolites; (ii) in response, OM fungi would secrete mycorrhizal factors (Myc factors) or similar compounds to activate the common symbiosis genes (CSGs); (iii) overcome the defense mechanism by evasion of the pathogen-associated molecular patterns (PAMPs)-triggered immunity and by secretion of effectors such as small inhibitor proteins; and (iv) finally, secrete phytohormones to help the colonization or disrupt the crosstalk of plant defense phytohormones. To challenge this putative model, targeted and untargeted metabolomics studies with special attention to each partner's contribution are finally encouraged and some technical approaches are proposed. PMID: 31982950 [PubMed - as supplied by publisher]

The potential role of nutritional components in improving brain function among patients with Alzheimers disease: a meta-analysis of RCT studies.

Mon, 27/01/2020 - 14:12
Related Articles The potential role of nutritional components in improving brain function among patients with Alzheimers disease: a meta-analysis of RCT studies. Neurosciences (Riyadh). 2020 Jan;25(1):4-17 Authors: Albrahim T Abstract OBJECTIVE: To find out the potential role of nutritional components in improving brain function among patients with Alzheimer`s disease (AD). METHODS: The correlation between nutrition and cerebral function in cases of AD has been the focus of 19 prospective randomised controlled trials (RCTs) with a combined research sample of 2297 patients. These RCTs are subject to systematic review and meta-analysis in the current paper RESULTS: Findings showed that chain-free secondary saturated fatty acids (SFA) and trans fatty acids (TFA) occurred in higher concentrations in AD patients` brains than in controls. Furthermore, neuroinflammation was caused by remodelling of the lipid membrane and AD patients` cognitive function was impacted by alterations in tyrosine, tryptophan, purine, and tocopherol pathway metabolomics. Moreover, in cases of mild-to-moderate AD, reduction in functionality was induced by administration of alpha-tocopherol for more than 12 months. Consumption of Souvenaid helps in synaptic synthesis, which enhances functional connectivity. Furthermore, consumption of the B vitamins folate, cobalamin and pyridoxine at dosages of 0.8 mg, 0.5 mg and 20 mg per day, respectively, over a period of one year resulted in lower plasma tHcy levels and brain atrophy. CONCLUSION: Chain-free SFA and TFA occur in greater amounts in the brains of individuals with AD than in those without AD. PMID: 31982903 [PubMed - in process]

Hot water pretreatment-induced significant metabolite changes in the sea cucumber Apostichopus japonicus.

Mon, 27/01/2020 - 14:12
Related Articles Hot water pretreatment-induced significant metabolite changes in the sea cucumber Apostichopus japonicus. Food Chem. 2020 Jan 16;314:126211 Authors: Yin P, Jia A, Heimann K, Zhang M, Liu X, Zhang W, Liu C Abstract Hot water pretreatment of sea cucumbers potentially changes nutritional benefits. This study aimed to quantify hot water pretreatment-induced changes in metabolite profiles of sea cucumber body walls. ICP-OES, GC-MS, and LC-MS analyses of untreated- (UT-BW), hot water-treated body walls (HW-BW) of Apostichopus japonicus, and the hot water extract (HW-E) determined significant losses of minerals (25-50% w/w), protein (~11% w/w), carbohydrate (33% w/w), saponins (~41% w/w), and spermidine (100%), a potential antipsychotic from hot water-treated samples. Multivariate comparisons of HW-BW with UT-BW and HW-BW with HW-E showed increases in amino acids and fatty acids, suggesting hot water-induced degradation or transformation or easier extraction of protein, lipid or other components. Presence of 80 to 88.5% of compounds in the HW-E and lower DHA, EPA and glycerophospholipids levels in HW-BW suggested extraction of these metabolites. These data indicate that novel processing technologies are required to preserve the full nutritional benefits of sea cucumbers. PMID: 31982856 [PubMed - as supplied by publisher]

Metabolomics analysis of urine from healthy wild type mice exposed to ambient PM2.5.

Mon, 27/01/2020 - 14:12
Related Articles Metabolomics analysis of urine from healthy wild type mice exposed to ambient PM2.5. Sci Total Environ. 2020 Jan 18;714:136790 Authors: Du X, Zeng X, Pan K, Zhang J, Song L, Zhou J, Chen R, Xie Y, Sun Q, Zhao J, Kan H Abstract BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been linked with various adverse health outcomes. However, the urine metabolomics changes impacted by PM2.5 have not been well elucidated. METHODS: The normal healthy C57BL/6 mice were exposed to concentrated ambient PM2.5 (PM) or filtered air (FA) for four weeks using "Shanghai-METAS". The urinary metabolome was quantified using liquid/gas chromatography coupled with mass spectrometry. RESULTS: There were 2213 metabolites identified in total and 163 of them were significantly different between FA- and PM-exposed mice. The KEGG pathway analysis suggested that there were nine perturbed metabolic pathways related to amino acid metabolism. The amino acid metabolism what mainly impacted by PM2.5 were beta-alanine, arginine, proline, alanine, aspartate, glutamate, phenylalanine, glycine, serine, threonine and tyrosine metabolism. Meanwhile, nineteen differential metabolites related to lipid metabolism and seven differential metabolites related to glucose homeostasis were different between FA and PM mice. Furthermore, the glucose and its metabolites were significantly increased in the PM mice compared with the FA mice. CONCLUSION: The current study provided a critical information on evaluating the systemic toxicity of PM2.5. The results demonstrated that there were significant alterations in urine metabolome by short-term exposure to PM, including amino acid metabolism, lipid metabolism and glucose metabolism. The metabolomics approach might be an effective tool to evaluate the potential mechanism of PM2.5 in inducing adverse health outcomes. PMID: 31982767 [PubMed - as supplied by publisher]

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