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; +18 new citations

Thu, 02/01/2020 - 12:33
18 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 2020/01/02PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +25 new citations

Wed, 01/01/2020 - 15:26
25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/01/01PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +25 new citations

Wed, 01/01/2020 - 12:26
25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/01/01PubMed 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

Tue, 31/12/2019 - 15:21
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 2019/12/31PubMed 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

Tue, 31/12/2019 - 12:19
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 2019/12/31PubMed 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.

Amino acids levels in early pregnancy predict subsequent gestational diabetes.

Sun, 29/12/2019 - 18:00
Related Articles Amino acids levels in early pregnancy predict subsequent gestational diabetes. J Diabetes. 2019 Dec 27;: Authors: Jiang R, Wu S, Fang C, Wang C, Yang Y, Liu C, Hu J, Huang Y Abstract BACKGROUND: We aimed to estimate the performance of amino acids levels in predicting the risk of subsequent gestational diabetes mellitus (GDM). METHODS: 431 women at 12-16 weeks of gestation in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Soochow University were recruited. High performance liquid chromatography electrospray tandem mass spectrometry was used to measure amino acids levels in maternal blood at 12-16 weeks of gestation. At 24-28 weeks of gestation, all participants were administered a 75 g oral glucose tolerance test for the diagnosis of GDM. RESULTS: Alanine, isoleucine and tyrosine levels in early pregnancy were significantly different between women who developed GDM and those who remained normal glucose tolerant (NGT). Logistic regression showed that after adjustments for age, parity, BMI, family history of diabetes, γ-glutamyltranspeptidase, triglycerides, fasting glucose and fasting insulin levels, alanine (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.05-2.04; P=0.027), isoleucine (OR, 1.48; 95% CI, 1.12-1.96; P=0.0062) and tyrosine (OR, 1.46; 95% CI, 1.07-2.03; P=0.020) levels in early pregnancy were independently associated with subsequent GDM. The addition of isoleucine and tyrosine into the conventional model improved area under curve (AUC) from 0.692 to 0.737 (P=0.036) and significantly increased the net reclassification improvement (NRI, +13.7%, P=0.0025). CONCLUSIONS: The present study suggested that elevated isoleucine, tyrosine and alanine levels were independently and significantly associated with subsequent incidence of GDM. New model including conventional risk factors, isoleucine and tyrosine, in early pregnancy might help physicians identify high risk population of GDM. This article is protected by copyright. All rights reserved. PMID: 31883199 [PubMed - as supplied by publisher]

Metabolite, Protein, and Lipid Extraction (MPLEx): A Method that Simultaneously Inactivates Middle East Respiratory Syndrome Coronavirus and Allows Analysis of Multiple Host Cell Components Following Infection.

Sun, 29/12/2019 - 18:00
Related Articles Metabolite, Protein, and Lipid Extraction (MPLEx): A Method that Simultaneously Inactivates Middle East Respiratory Syndrome Coronavirus and Allows Analysis of Multiple Host Cell Components Following Infection. Methods Mol Biol. 2020;2099:173-194 Authors: Nicora CD, Sims AC, Bloodsworth KJ, Kim YM, Moore RJ, Kyle JE, Nakayasu ES, Metz TO Abstract Mass spectrometry (MS)-based, integrated proteomics, metabolomics, and lipidomics (collectively, multi-omics) studies provide a very detailed snapshot of virus-induced changes to the host following infection and can lead to the identification of novel prophylactic and therapeutic targets for preventing or lessening disease severity. Multi-omics studies with Middle East respiratory syndrome coronavirus (MERS-CoV) are challenging as the requirements of biosafety level 3 containment limit the numbers of samples that can be safely managed. To address these issues, the multi-omics sample preparation technique MPLEx (metabolite, protein, and lipid extraction) was developed to partition a single sample into three distinct parts (metabolites, proteins, and lipids) for multi-omics analysis, while simultaneously inactivating MERS-CoV by solubilizing and disrupting the viral envelope and denaturing viral proteins. Here we describe the MPLEx protocol, highlight the step of inactivation, and describe the details of downstream processing, instrumental analysis of the three separate analytes, and their subsequent informatics pipelines. PMID: 31883096 [PubMed - in process]

Testing the limits of FT-Raman spectroscopy for wine authentication: Cultivar, geographical origin, vintage and terroir effect influence.

Sun, 29/12/2019 - 18:00
Related Articles Testing the limits of FT-Raman spectroscopy for wine authentication: Cultivar, geographical origin, vintage and terroir effect influence. Sci Rep. 2019 Dec 27;9(1):19954 Authors: Magdas DA, Cozar BI, Feher I, Guyon F, Dehelean A, Cinta Pinzaru S Abstract FT-Raman spectroscopy represents an environmentally friendly technique, suitable for the analysis of high-water content food matrices, like wines, due to its relatively weak water bending mode in the fingerprint region. Based on metabolomics applied to FT-Raman spectra, this study presents the classifications achieved for a sample set comprising 126 wines, originated from Romania and France, with respect to cultivar, geographical origin and vintage. Cultivar recognition was successfully performed among four varieties (Sauvignon, Riesling, Chardonnay, Pinot Gris) while subtle particularities exiting between the Chardonnay wines, coming from the two countries, because of terroir influences were pointed out. The obtained separations of 100% in both initial and cross-validation procedure for geographical differentiation between the two origin countries, as well as, among the three Romanian areas (Transylvania, Muntenia and Moldova) were also discussed. Apart of this, the limitations and the importance of choosing a meaningful data set, in terms of representativity for each classification criterion, are addressed in the present work. PMID: 31882929 [PubMed - in process]

Metabolic GWAS of elite athletes reveals novel genetically-influenced metabolites associated with athletic performance.

Sun, 29/12/2019 - 18:00
Related Articles Metabolic GWAS of elite athletes reveals novel genetically-influenced metabolites associated with athletic performance. Sci Rep. 2019 Dec 27;9(1):19889 Authors: Al-Khelaifi F, Diboun I, Donati F, Botrè F, Abraham D, Hingorani A, Albagha O, Georgakopoulos C, Suhre K, Yousri NA, Elrayess MA Abstract Genetic research of elite athletic performance has been hindered by the complex phenotype and the relatively small effect size of the identified genetic variants. The aims of this study were to identify genetic predisposition to elite athletic performance by investigating genetically-influenced metabolites that discriminate elite athletes from non-elite athletes and to identify those associated with endurance sports. By conducting a genome wide association study with high-resolution metabolomics profiling in 490 elite athletes, common variant metabolic quantitative trait loci (mQTLs) were identified and compared with previously identified mQTLs in non-elite athletes. Among the identified mQTLs, those associated with endurance metabolites were determined. Two novel genetic loci in FOLH1 and VNN1 are reported in association with N-acetyl-aspartyl-glutamate and Linoleoyl ethanolamide, respectively. When focusing on endurance metabolites, one novel mQTL linking androstenediol (3alpha, 17alpha) monosulfate and SULT2A1 was identified. Potential interactions between the novel identified mQTLs and exercise are highlighted. This is the first report of common variant mQTLs linked to elite athletic performance and endurance sports with potential applications in biomarker discovery in elite athletic candidates, non-conventional anti-doping analytical approaches and therapeutic strategies. PMID: 31882771 [PubMed - in process]

Magnetic resonance microscopy and correlative histopathology of the infarcted heart.

Sun, 29/12/2019 - 18:00
Related Articles Magnetic resonance microscopy and correlative histopathology of the infarcted heart. Sci Rep. 2019 Dec 27;9(1):20017 Authors: Perez-Terol I, Rios-Navarro C, de Dios E, Morales JM, Gavara J, Perez-Sole N, Diaz A, Minana G, Segura-Sabater R, Bonanad C, Bayés-Genis A, Husser O, Monmeneu JV, Lopez-Lereu MP, Nunez J, Chorro FJ, Ruiz-Sauri A, Bodi V, Monleon D Abstract Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI. PMID: 31882712 [PubMed - in process]

Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer.

Sun, 29/12/2019 - 18:00
Related Articles Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer. Sci Rep. 2019 Dec 27;9(1):20198 Authors: Martín-Blázquez A, Díaz C, González-Flores E, Franco-Rivas D, Jiménez-Luna C, Melguizo C, Prados J, Genilloud O, Vicente F, Caba O, Pérez Del Palacio J Abstract Colorectal cancer is one of the main causes of cancer death worldwide, and novel biomarkers are urgently needed for its early diagnosis and treatment. The utilization of metabolomics to identify and quantify metabolites in body fluids may allow the detection of changes in their concentrations that could serve as diagnostic markers for colorectal cancer and may also represent new therapeutic targets. Metabolomics generates a pathophysiological 'fingerprint' that is unique to each individual. The purpose of our study was to identify a differential metabolomic signature for metastatic colorectal cancer. Serum samples from 60 healthy controls and 65 patients with metastatic colorectal cancer were studied by liquid chromatography coupled to high-resolution mass spectrometry in an untargeted metabolomic approach. Multivariate analysis revealed a separation between patients with metastatic colorectal cancer and healthy controls, who significantly differed in serum concentrations of one endocannabinoid, two glycerophospholipids, and two sphingolipids. These findings demonstrate that metabolomics using liquid-chromatography coupled to high-resolution mass spectrometry offers a potent diagnostic tool for metastatic colorectal cancer. PMID: 31882610 [PubMed - in process]

Untargeted UPLC-MS metabolomics reveals multiple changes of urine composition in healthy adult volunteers after consumption of curcuma longa L. extract.

Sun, 29/12/2019 - 18:00
Related Articles Untargeted UPLC-MS metabolomics reveals multiple changes of urine composition in healthy adult volunteers after consumption of curcuma longa L. extract. Food Res Int. 2020 Jan;127:108730 Authors: Peron G, Sut S, Dal Ben S, Voinovich D, Dall'Acqua S Abstract Curcuma longa L. is used as food supplement to prevent diseases, although limited studies have been performed on healthy subjects up to now. In the present work, an untargeted UPLC-MS metabolomics approach was applied to study the changes of 24-hours urinary composition on healthy volunteers due to a 28-days daily consumption of a dried C. longa extract containing a standardized amount of curcuminoids. Changes in the excretion of different metabolites were observed after supplementation. Curcumin and two metabolic derivatives (hexahydrocurcumin and dihydrocurcumin) were detected in urine, indicating the absorption of the main curcuminoid from the extract and its further metabolism by liver and gut microbiota. For the first time ar-turmerone, the main apolar constituent of curcuma, was detected in urine in intact form, and its presence was confirmed by a targeted GC-MS analysis. The increase of tetranor-PGJM and tetranor-PGDM, two prostaglandin-D2 metabolites, was observed, being related to the anti-inflammatory effect exerted by curcuma. The variation of the amounts of HPAG, PAG, proline-betaine and hydroxyphenyllactic acid indicate that the supplementation induced changes to the activity of gut microbiota. Finally, the reduced excretion of niacin metabolites (nicotinuric acid, trigonelline and 2PY) and medium- and short-chain acylcarnitines suggests that curcuma could induce the mitochondrial β-oxidation of fatty acids for energy production in healthy subjects. Overall, the results indicate that a prolonged daily consumption of a dried curcuma extract exerts multiple effects on healthy subjects, furthermore they show the opportunity offered by untargeted metabolomics for the study of the bioactivity of natural extracts in healthy human volunteers. PMID: 31882111 [PubMed - in process]

Phenolic profiling and in vitro bioactivity of Moringa oleifera leaves as affected by different extraction solvents.

Sun, 29/12/2019 - 18:00
Related Articles Phenolic profiling and in vitro bioactivity of Moringa oleifera leaves as affected by different extraction solvents. Food Res Int. 2020 Jan;127:108712 Authors: Rocchetti G, Pagnossa JP, Blasi F, Cossignani L, Hilsdorf Piccoli R, Zengin G, Montesano D, Cocconcelli PS, Lucini L Abstract In this work the (poly)-phenolic profile of Moringa oleifera leaves was comprehensively investigated through untargeted metabolomics, following a homogenizer-assisted extraction (HAE) using three solvent systems, i.e. methanol (HAE-1), methanol-water 50:50 v/v (HAE-2) and ethyl acetate (HAE-3). This approach allowed to putatively annotate 291 compounds, recording mainly flavonoids and phenolic acids. Thereafter, antioxidant capacity, antimicrobial activity and enzyme inhibition were assayed in the different extracts. HAE-1 extract showed the highest total phenolic content (31.84 mg/g), followed by HAE-2 (26.95 mg/g) and HAE-3 (14.71 mg/g). In addition, HAE-1 and HAE-2 extracts exhibited an expressive activity against Bacillus cereus and Listeria innocua. The HAE-2 leaf extract was characterized by the highest DPPH and ABTS values (being 49.55 and 45.26 mgTE/g), while ferric reducing antioxidant power was found to be higher in HAE-1 (58.26 mgTE/g). Finally, the enzyme inhibitory effects of M. oleifera leaf extracts were investigated against five enzymes, namely acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase. All of the tested extracts exhibited inhibitory effects on AChE and BChE with a higher activity for HAE-3 and HAE-1, whilst HAE-1 showed the higher impact on tyrosinase, glucosidase and amylase activities. Taken together, these findings suggest that M. oleifera leaf extracts are a good source of bioactive polyphenols with a potential use in food and pharma industries. PMID: 31882101 [PubMed - in process]

Hepatotoxicity and the role of the gut-liver axis in rats after oral administration of titanium dioxide nanoparticles.

Sun, 29/12/2019 - 18:00
Related Articles Hepatotoxicity and the role of the gut-liver axis in rats after oral administration of titanium dioxide nanoparticles. Part Fibre Toxicol. 2019 Dec 27;16(1):48 Authors: Chen Z, Zhou D, Han S, Zhou S, Jia G Abstract BACKGROUND: Due to its excellent physicochemical properties and wide applications in consumer goods, titanium dioxide nanoparticles (TiO2 NPs) have been increasingly exposed to the environment and the public. However, the health effects of oral exposure of TiO2 NPs are still controversial. This study aimed to illustrate the hepatotoxicity induced by TiO2 NPs and the underlying mechanisms. Rats were administered with TiO2 NPs (29 nm) orally at exposure doses of 0, 2, 10, 50 mg/kg daily for 90 days. Changes in the gut microbiota and hepatic metabolomics were analyzed to explore the role of the gut-liver axis in the hepatotoxicity induced by TiO2 NPs. RESULTS: TiO2 NPs caused slight hepatotoxicity, including clear mitochondrial swelling, after subchronic oral exposure at 50 mg/kg. Liver metabolomics analysis showed that 29 metabolites and two metabolic pathways changed significantly in exposed rats. Glutamate, glutamine, and glutathione were the key metabolites leading the generation of energy-related metabolic disorders and imbalance of oxidation/antioxidation. 16S rDNA sequencing analysis showed that the diversity of gut microbiota in rats increased in a dose-dependent manner. The abundance of Lactobacillus_reuteri increased and the abundance of Romboutsia decreased significantly in feces of TiO2 NPs-exposed rats, leading to changes of metabolic function of gut microbiota. Lipopolysaccharides (LPS) produced by gut microbiota increased significantly, which may be a key factor in the subsequent liver effects. CONCLUSIONS: TiO2 NPs could induce slight hepatotoxicity at dose of 50 mg/kg after long-term oral exposure. The indirect pathway of the gut-liver axis, linking liver metabolism and gut microbiota, played an important role in the underlying mechanisms. PMID: 31881974 [PubMed - in process]

Green and White Asparagus (Asparagus officinalis): A Source of Developmental, Chemical and Urinary Intrigue.

Sun, 29/12/2019 - 18:00
Related Articles Green and White Asparagus (Asparagus officinalis): A Source of Developmental, Chemical and Urinary Intrigue. Metabolites. 2019 Dec 25;10(1): Authors: Pegiou E, Mumm R, Acharya P, de Vos RCH, Hall RD Abstract Asparagus (Asparagus officinalis) is one of the world's top 20 vegetable crops. Both green and white shoots (spears) are produced; the latter being harvested before becoming exposed to light. The crop is grown in nearly all areas of the world, with the largest production regions being China, Western Europe, North America and Peru. Successful production demands high farmer input and specific environmental conditions and cultivation practices. Asparagus materials have also been used for centuries as herbal medicine. Despite this widespread cultivation and consumption, we still know relatively little about the biochemistry of this crop and how this relates to the nutritional, flavour, and neutra-pharmaceutical properties of the materials used. To date, no-one has directly compared the contrasting compositions of the green and white crops. In this short review, we have summarised most of the literature to illustrate the chemical richness of the crop and how this might relate to key quality parameters. Asparagus has excellent nutritional properties and its flavour/fragrance is attributed to a set of volatile components including pyrazines and sulphur-containing compounds. More detailed research, however, is needed and we propose that (untargeted) metabolomics should have a more prominent role to play in these investigations. PMID: 31881716 [PubMed]

metabolomics; +19 new citations

Sat, 28/12/2019 - 14:54
19 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 2019/12/28PubMed 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.

Synergistic effect of Aconiti Lateralis Radix Praeparata water-soluble alkaloids and Ginseng Radix et Rhizoma total ginsenosides compatibility on acute heart failure rats.

Fri, 27/12/2019 - 14:49
Related Articles Synergistic effect of Aconiti Lateralis Radix Praeparata water-soluble alkaloids and Ginseng Radix et Rhizoma total ginsenosides compatibility on acute heart failure rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Dec 09;1137:121935 Authors: Liu M, Li Y, Tang Y, Zheng L, Peng C Abstract The aim of this study was to investigate the synergistic effect and underlying mechanism of compatibility of Aconiti Lateralis Radix Praeparata water-soluble alkaloids (FWA) and Ginseng Radix et Rhizoma total ginsenosides (RTG) on propafenone hydrochloride induced acute heart failure (AHF) rats. Firstly, hemodynamics and serum biochemical indexes were measured to observe the therapeutic effect of FWA, RTG and their compatibility on AHF rats. Non-target serum metabolomics and multicomponent pharmacokinetic experiments were then performed to reveal the mechanism from the two aspects of body reaction and drug behavior in vivo. Data showed the haemodynamics indexes (maximum change rate of left ventricular pressure, heart rate) and neuroendocrine cytokines (TNF-α and Nt-proBNP) levels in rats treated by compatibility of FWA and RTG were improved more significantly than that treated by single drug. Through metabolomics analysis, six metabolites, including L-pipecolic acid, L-arginine, uric acid, N-benzoylglycine, sphingosine-1-phosphate and phosphatidylinositol lyso 16:0, were selected and identified as the potential biomarkers of the synergistic effect. Furthermore, lysine degradation, arginine and proline metabolism, purine metabolism, sphingolipid metabolism, etc. were the differential pathways involved. The results of pharmacokinetics showed Cmax, AUClast and t1/2 of the four components (uracil, salsolinol, guanosine, higenamine) of FWA in compatibility group were obviously higher than that in single drug group, which indicated the absorption and bioavailability of these alkaloids were increased, and the residence time was prolonged after FWA combined with RTG. In conclusion, the therapeutic effect of FWA-RTG on AHF rats was enhanced and that might because the compatibility of FWA-RTG affected the process of some metabolites in AHF rats, and pharmacokinetic behavior of components in FWA was obviously influenced after co-administered with RTG. PMID: 31877430 [PubMed - as supplied by publisher]

Perspective: Cell Danger Response Biology-The New Science that Connects Environmental Health with Mitochondria and the Rising Tide of Chronic Illness.

Fri, 27/12/2019 - 14:49
Related Articles Perspective: Cell Danger Response Biology-The New Science that Connects Environmental Health with Mitochondria and the Rising Tide of Chronic Illness. Mitochondrion. 2019 Dec 23;: Authors: Naviaux RK Abstract This paper is written for non-specialists in mitochondrial biology to provide access to an important area of science that has broad implications for all people. The cell danger response (CDR) is a universal response to environmental threat or injury. Once triggered, healing cannot be completed until the choreographed stages of the CDR are returned to an updated state of readiness. Although the CDR is a cellular response, it has the power to change human thought and behavior, child development, physical fitness and resilience, fertility, and the susceptibility of entire populations to disease. Mitochondria regulate the CDR by monitoring and responding to the physical, chemical, and microbial conditions within and around the cell. In this way, mitochondria connect cellular health to environmental health. Over 7,000 chemicals are now made or imported to the US for industrial, agricultural, and personal care use in amounts ranging from 25,000 to over 1 million pounds each year, and plastic waste now exceeds 83 billion pounds/year. This chemical load creates a rising tide of manmade pollutants in the oceans, air, water, and food chain. Fewer than 5% of these chemicals have been tested for developmental toxicity. In the 1980s, 5-10% of children lived with a chronic illness. As of 2018, 40% of children, 50% of teens, 60% of adults under age 65, and 90% of adults over 65 live with chronic illness. Several studies now report the presence of dozens to hundreds of manmade chemicals and pollutants in placenta, umbilical cord blood, and newborn blood spots. New methods in metabolomics and exposomics allow scientists to measure thousands of chemicals in blood, air, water, soil, and the food chain. Systematic measurements of environmental chemicals can now be correlated with annual and regional patterns of childhood illness. These data can be used to prepare a prioritized list of molecules for congressional action, ranked according to their impact on human health. "When a deep injury is done to us, we never heal until we forgive." --Nelson Mandela (1918-2013). PMID: 31877376 [PubMed - as supplied by publisher]

Metabolites in a mouse cancer model enhance venous thrombogenicity through the aryl hydrocarbon receptor-tissue factor axis.

Fri, 27/12/2019 - 14:49
Related Articles Metabolites in a mouse cancer model enhance venous thrombogenicity through the aryl hydrocarbon receptor-tissue factor axis. Blood. 2019 Dec 26;134(26):2399-2413 Authors: Belghasem M, Roth D, Richards S, Napolene MA, Walker J, Yin W, Arinze N, Lyle C, Spencer C, Francis JM, Thompson C, Andry C, Whelan SA, Lee N, Ravid K, Chitalia VC Abstract Patients with malignancy are at 4- to 7-fold higher risk of venous thromboembolism (VTE), a potentially fatal, yet preventable complication. Although general mechanisms of thrombosis are enhanced in these patients, malignancy-specific triggers and their therapeutic implication remain poorly understood. Here we examined a colon cancer-specific VTE model and probed a set of metabolites with prothrombotic propensity in the inferior vena cava (IVC) ligation model. Athymic mice injected with human colon adenocarcinoma cells exhibited significantly higher IVC clot weights, a biological readout of venous thrombogenicity, compared with the control mice. Targeted metabolomics analysis of plasma of mice revealed an increase in the blood levels of kynurenine and indoxyl sulfate (tryptophan metabolites) in xenograft-bearing mice, which correlated positively with the increase in the IVC clot size. These metabolites are ligands of aryl hydrocarbon receptor (AHR) signaling. Accordingly, plasma from the xenograft-bearing mice activated the AHR pathway and augmented tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) levels in venous endothelial cells in an AHR-dependent manner. Consistent with these findings, the endothelium from the IVC of xenograft-bearing animals revealed nuclear AHR and upregulated TF and PAI-1 expression, telltale signs of an activated AHR-TF/PAI-1 axis. Importantly, pharmacological inhibition of AHR activity suppressed TF and PAI-1 expression in endothelial cells of the IVC and reduced clot weights in both kynurenine-injected and xenograft-bearing mice. Together, these data show dysregulated tryptophan metabolites in a mouse cancer model, and they reveal a novel link between these metabolites and the control of the AHR-TF/PAI-1 axis and VTE in cancer. PMID: 31877217 [PubMed - in process]

Dried blood spot N-glycome analysis by MALDI mass spectrometry.

Fri, 27/12/2019 - 14:49
Related Articles Dried blood spot N-glycome analysis by MALDI mass spectrometry. Talanta. 2019 Dec 01;205:120104 Authors: Vreeker GCM, Bladergroen MR, Nicolardi S, Mesker WE, Tollenaar RAEM, van der Burgt YEM, Wuhrer M Abstract Body fluid N-glycome analysis as well as glyco-proteoform profiling of existing protein biomarkers potentially provides a stratification layer additional to quantitative, diagnostic protein levels. For clinical omics applications, the collection of a dried blood spot (DBS) is increasingly pursued as an alternative to sampling milliliters of peripheral blood. Here we evaluate DBS cards as a blood collection strategy for protein N-glycosylation analysis aiming for high-throughput clinical applications. A protocol for facile N-glycosylation profiling from DBS is developed that includes sialic acid linkage differentiation. This protocol is based on a previously established total plasma N-glycome mass spectrometry (MS) method, with adjustments for the analysis of DBS specimens. After DBS-punching and protein solubilization N-glycans are released, followed by chemical derivatization of sialic acids and MS-measurement of N-glycan profiles. With this method, more than 80 different glycan structures are identified from a DBS, with RSDs below 10% for the ten most abundant glycans. N-glycan profiles of finger-tip blood and venous blood are compared and short-term stability of DBS is demonstrated. This method for fast N-glycosylation profiling of DBS provides a minimally invasive alternative to conventional serum and plasma protein N-glycosylation workflows. With simplified blood sampling this DBS approach has vast potential for clinical glycomics applications. PMID: 31450448 [PubMed - indexed for MEDLINE]

Pages