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; +22 new citations

Wed, 22/01/2020 - 16:02
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 2020/01/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +22 new citations

Wed, 22/01/2020 - 13:02
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 2020/01/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +17 new citations

Tue, 21/01/2020 - 15:50
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/01/21PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +17 new citations

Tue, 21/01/2020 - 12:49
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/01/21PubMed 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.

Nutritional ketosis improves exercise metabolism in patients with very long-chain acyl-CoA dehydrogenase deficiency.

Mon, 20/01/2020 - 12:39
Nutritional ketosis improves exercise metabolism in patients with very long-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2020 Jan 18;: Authors: Bleeker JC, Visser G, Clarke K, Ferdinandusse S, de Haan FH, Houtkooper RH, IJlst L, Kok IL, Langeveld M, van der Pol WL, de Sain-van der Velden MGM, Sibeijn-Kuiper A, Takken T, Wanders RJA, van Weeghel M, Wijburg FA, van der Woude LH, Wüst RCI, Cox PJ, Jeneson JAL Abstract BACKGROUND: A maladaptive shift from fat to carbohydrate (CHO) oxidation during exercise is thought to underlie myopathy and exercise-induced rhabdomyolysis in patients with fatty acid oxidation (FAO) disorders. We hypothesized that ingestion of a ketone ester (KE) drink prior to exercise could serve as an alternative oxidative substrate supply to boost muscular ATP homeostasis. To establish a rational basis for therapeutic use of KE supplementation in FAO, we tested this hypothesis in patients deficient in Very Long-Chain acyl-CoA Dehydrogenase (VLCAD). METHODS: Five patients (range 17-45 y; 4M/1F) patients were included in an investigator-initiated, randomized, blinded, placebo-controlled, 2-way cross-over study. Patients drank either a KE+CHO mix or an isocaloric CHO equivalent and performed 35 min upright cycling followed by 10 minutes supine cycling inside a Magnetic Resonance scanner at individual maximal FAO work rate (fatmax; ~40% VO2 max). The protocol was repeated after a one-week interval with the alternate drink. Primary outcome measures were quadriceps phosphocreatine (PCr), Pi and pH dynamics during exercise and recovery assayed by in vivo 31 P-MR spectroscopy. Secondary outcomes included plasma and muscle metabolites and respiratory gas exchange recordings. RESULTS: Ingestion of KE rapidly induced mild ketosis and increased muscle BHB content. During exercise at FATMAX, VLCADD-specific plasma acylcarnitine levels, quadriceps glycolytic intermediate levels and in vivo Pi/PCr ratio were all lower in KE+CHO than CHO. CONCLUSION: These results provide a rational basis for future clinical trials of synthetic ketone ester supplementation therapy in patients with FAO disorders. This article is protected by copyright. All rights reserved. PMID: 31955429 [PubMed - as supplied by publisher]

Metabolomics, sleepiness, and sleep duration in sleep apnea.

Mon, 20/01/2020 - 12:39
Metabolomics, sleepiness, and sleep duration in sleep apnea. Sleep Breath. 2020 Jan 18;: Authors: Diallo I, Pak VM Abstract PURPOSE: Although the mechanism is unclear, daytime sleepiness, a common sequela of obstructive sleep apnea (OSA), has been found to be correlated with a adverse cardiovascular outcomes. Reviewing metabolomics mechanisms of sleep disturbances and cardiovascular disease may help to explain this correlation. METHODS: This review examines the current literature on the relationships between sleepiness, sleep duration, and metabolites in sleep apnea. RESULTS: Although there is a lack of comprehensive literature in this emerging area, existing studies point to a variety of metabolites in different pathways that are associated with sleepiness and sleep duration. CONCLUSION: Advancing metabolomics research in sleep apnea will guide symptom research and provide alternate and novel opportunities for effective treatment for patients with OSA. PMID: 31955318 [PubMed - as supplied by publisher]

Canine metabolomics advances.

Mon, 20/01/2020 - 12:39
Canine metabolomics advances. Metabolomics. 2020 Jan 18;16(2):16 Authors: Carlos G, Dos Santos FP, Fröehlich PE Abstract INTRODUCTION: Canis lupus familiaris is a domestic dog and many owners consider their pets as a family member. Medical bills with dogs are overcame only by the health care received by humans. Medical care is constantly progressing, and so is veterinary care. Metabolomics is the ''omic" technique aimed to the study of metabolome, low-molecular weight molecules, through biofluids or tissue samples. And it also allows to evaluate disease diagnosis and prognosis, therapeutic evaluation and toxicological studies. OBJECTIVES: The goal of this paper is to review the current and potential applications of metabolomics in domestic dogs. METHOD: ScienceDirect, Scopus, Reaxys and PubMed were searched for papers that performed canine metabolomics in any research area. RESULTS: We analysed 38 papers, published until April 2019 in canine metabolomics approach. Metabolomic research in dogs so far can be divided into three areas: (a) Metabolomics studies in veterinary science, such as improving pet dogs health and welfare. (b) Diet, breeds and species discrimination. (c) Use of dogs as animal model in different diseases and drug development (evaluation toxicity and effect). CONCLUSIONS: The results of this review showed that interest in metabolomics is growing in veterinary research. Several canine diseases have been evaluated with some promise for potential biomarker and/or disease mechanism discovery. Because canine metabolomics is a relatively new area, the researches spread across different research areas and with few studies in each area. PMID: 31955274 [PubMed - in process]

Untargeted and targeted metabolomics strategy for the classification of strong aroma-type baijiu (liquor) according to geographical origin using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry.

Mon, 20/01/2020 - 12:39
Untargeted and targeted metabolomics strategy for the classification of strong aroma-type baijiu (liquor) according to geographical origin using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry. Food Chem. 2019 Dec 30;314:126098 Authors: Song X, Jing S, Zhu L, Ma C, Song T, Wu J, Zhao Q, Zheng F, Zhao M, Chen F Abstract A metabolomics strategy was developed to differentiate strong aroma-type baijiu (SAB) (distilled liquor) from the Sichuan basin (SCB) and Yangtze-Huaihe River Basin (YHRB) through liquid-liquid extraction coupled with GC×GC-TOFMS. PCA effectively separated the samples from these two regions. The PLS-DA training model was excellent, with explained variation and predictive capability values of 0.988 and 0.982, respectively. As a result, the model demonstrated its ability to perfectly differentiate all the unknown SAB samples. Twenty-nine potential markers were located by variable importance in projection values, and twenty-four of them were identified and quantitated. Discrimination ability is closely correlated to the characteristic flavor compounds, such as acid, esters, furans, alcohols, sulfides and pyrazine. Most of the marker compounds were less abundant in the SCB samples than in the YHRB samples. The quantitated markers were further processed using hierarchical cluster analysis for targeted analysis, indicating that the markers had great discrimination power to differentiate the SAB samples. PMID: 31954940 [PubMed - as supplied by publisher]

The Galactose Index measured in fibroblasts of GALT deficient patients distinguishes variant patients detected by newborn screening from patients with classical phenotypes.

Mon, 20/01/2020 - 12:39
The Galactose Index measured in fibroblasts of GALT deficient patients distinguishes variant patients detected by newborn screening from patients with classical phenotypes. Mol Genet Metab. 2020 Jan 09;: Authors: Welsink-Karssies MM, van Weeghel M, Hollak CEM, Elfrink HL, Janssen MCH, Lai K, Langendonk JG, Oussoren E, Ruiter JPN, Treacy EP, de Vries M, Ferdinandusse S, Bosch AM Abstract BACKGROUND: The high variability in clinical outcome of patients with Classical Galactosemia (CG) is poorly understood and underlines the importance of prognostic biomarkers, which are currently lacking. The aim of this study was to investigate if residual galactose metabolism capacity is associated with clinical and biochemical outcomes in CG patients with varying geno- and phenotypes. METHODS: Galactose Metabolite Profiling (GMP) was used to determine residual galactose metabolism in fibroblasts of CG patients. The association between the galactose index (GI) defined as the ratio of the measured metabolites [U13C]Gal-1-P/ [13C6]UDP-galactose, and both intellectual and neurological outcome and galactose-1-phosphate (Gal-1-P) levels was investigated. RESULTS: GMP was performed in fibroblasts of 28 patients and 3 control subjects. The GI of the classical phenotype patients (n = 22) was significantly higher than the GI of four variant patients detected by newborn screening (NBS) (p = .002), two homozygous p.Ser135Leu patients (p = .022) and three controls (p = .006). In the classical phenotype patients, 13/18 (72%) had a poor intellectual outcome (IQ < 85) and 6/12 (50%) had a movement disorder. All the NBS detected variant patients (n = 4) had a normal intellectual outcome (IQ ≥ 85) and none of them has a movement disorder. In the classical phenotype patients, there was no significant difference in GI between patients with a poor and normal clinical outcome. The NBS detected variant patients had significantly lower GI levels and thus higher residual galactose metabolism than patients with classical phenotypes. There was a clear correlation between Gal-1-P levels in erythrocytes and the GI (p = .001). CONCLUSIONS: The GI was able to distinguish CG patients with varying geno- and phenotypes and correlated with Gal-1-P. The data of the NBS detected variant patients demonstrated that a higher residual galactose metabolism may result in a more favourable clinical outcome. Further research is needed to enable individual prognostication and treatment in all CG patients. PMID: 31954591 [PubMed - as supplied by publisher]

metabolomics; +34 new citations

Sun, 19/01/2020 - 15:22
34 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 2020/01/19PubMed 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.

metabolomics; +34 new citations

Sun, 19/01/2020 - 12:19
34 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 2020/01/19PubMed 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.

Perinatal exposure to 2-Ethylhexyl Diphenyl Phosphate (EHDPHP) affected the metabolic homeostasis of male mouse offspring: Unexpected findings help to explain dose- and diet- specific phenomena.

Sat, 18/01/2020 - 12:03
Perinatal exposure to 2-Ethylhexyl Diphenyl Phosphate (EHDPHP) affected the metabolic homeostasis of male mouse offspring: Unexpected findings help to explain dose- and diet- specific phenomena. J Hazard Mater. 2020 Jan 10;388:122034 Authors: Yan S, Wang D, Teng M, Meng Z, Yan J, Li R, Jia M, Tian S, Zhou Z, Zhu W Abstract The environmental health risks of a new type of organophosphate flame retardant, 2-ethylhexyl diphenyl phosphate (EHDPHP), which is present in large quantities in various Nordic foods, have attracted the attention of scientists recently. In this study, the metabolic homeostasis of low-fat diet (LFD) and high-fat diet (HFD) fed male mice offspring was assessed after perinatal exposure to two doses (30 μg/kg bw/day and 300 μg/kg bw/day) of EHDPHP. Perinatal exposure to EHDPHP resulted in weight changes in male mice offspring, altered glucose tolerance and induced liver damage, and surprisingly these changes were dose- and diet- specific. Then the 1H NMR-based metabolomics, 16S rRNA sequencing, and qRT-PCR techniques were used to explore the mechanisms of these specific changes. The results indicate that the increase in short-chain fatty acids and the increase in Clostridium in the high-dose group may be responsible for the dose-specificity, while the attenuation of the purine metabolic pathway and the decrease in glutamine levels in the HFD group are accountable for the diet-specificity. In addition, down-regulation of PPARG (peroxisome proliferator-activated receptor gamma) gene expression levels might have caused the decrease in body weight in the H + HFD (high dose exposure with HFD feeding) group. Over all, these results elucidated the effects of dosage and diet on the toxicology of EHDPHP. PMID: 31951990 [PubMed - as supplied by publisher]

Perspectives on Data Analysis in Metabolomics: Points of Agreement and Disagreement from the 2018 ASMS Fall Workshop.

Sat, 18/01/2020 - 12:03
Perspectives on Data Analysis in Metabolomics: Points of Agreement and Disagreement from the 2018 ASMS Fall Workshop. J Am Soc Mass Spectrom. 2019 Oct 01;30(10):2031-2036 Authors: Baker ES, Patti GJ Abstract In November 2018, the American Society for Mass Spectrometry hosted the Annual Fall Workshop on informatic methods in metabolomics. The Workshop included sixteen lectures presented by twelve invited speakers. The focus of the talks was untargeted metabolomics performed with liquid chromatography/mass spectrometry. In this review, we highlight five recurring topics that were covered by multiple presenters: (i) data sharing, (ii) artifacts and contaminants, (iii) feature degeneracy, (iv) database organization, and (v) requirements for metabolite identification. Our objective here is to present viewpoints that were widely shared among participants, as well as those in which varying opinions were articulated. We note that most of the presenting speakers employed different data processing software, which underscores the diversity of informatic programs currently being used in metabolomics. We conclude with our thoughts on the potential role of reference datasets as a step towards standardizing data processing methods in metabolomics. PMID: 31951742 [PubMed - in process]

Exposure to the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine causes compensatory changes to macronutrient utilization and energy metabolism in placental HTR-8/SVneo cells.

Sat, 18/01/2020 - 12:03
Exposure to the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine causes compensatory changes to macronutrient utilization and energy metabolism in placental HTR-8/SVneo cells. Chem Res Toxicol. 2020 Jan 17;: Authors: Elkin ER, Bridges D, Harris SM, Loch-Caruso RK Abstract Trichloroethylene (TCE) is a widespread environmental contaminant following decades of use as an industrial solvent, improper disposal and remediation challenges. Consequently, TCE exposure continues to constitute a risk to human health. Despite epidemiological evidence associating exposure with adverse birth outcomes, the effects of TCE and its metabolite S-(1, 2-dichlorovinyl)-L-cysteine (DCVC) on the placenta remain undetermined. Flexible and efficient macronutrient and energy metabolism pathway utilization is essential for placental cell physiological adaptability. Because DCVC is known to compromise cellular energy status and disrupt energy metabolism in renal proximal tubular cells, this study investigated the effects of DCVC on cellular energy status and energy metabolism pathways in placental cells. Human extravillous trophoblast cells, HTR-8/SVneo, were exposed to 5-20 µM DCVC for 6 or 12 h. After establishing concentration and exposure duration thresholds for DCVC-induced cytotoxicity, targeted metabolomics was used to evaluate overall energy status and metabolite concentrations from energy metabolism pathways. The data revealed glucose metabolism perturbations including a time-dependent accumulation of glucose-6-phosphate+frutose-6-phosphate (G6P+F6P) as well as independent shunting of glucose intermediates that diminished with time, with modest energy status decline but in the absence of significant changes in ATP concentrations. Furthermore, metabolic profiling suggested that DCVC stimulated compensatory utilization of glycerol, lipid and amino acid metabolism to provide intermediate substrates entering downstream in the glycolytic pathway or the tricarboxylic acid cycle. Lastly, amino acid deprivation increased susceptibility to DCVC-induced cytotoxicity. Taken together, these results suggest that DCVC caused metabolic perturbations necessitating adaptations in macronutrient and energy metabolism pathway utilization in order to maintain adequate ATP levels. PMID: 31951115 [PubMed - as supplied by publisher]

Targeted Realignment of LC-MS Profiles by Neighbor-wise Compound-specific Graphical Time Warping with Misalignment Detection.

Sat, 18/01/2020 - 12:03
Targeted Realignment of LC-MS Profiles by Neighbor-wise Compound-specific Graphical Time Warping with Misalignment Detection. Bioinformatics. 2020 Jan 17;: Authors: Wu CT, Wang Y, Wang Y, Ebbels T, Karaman I, Graça G, Pinto R, Herrington DM, Wang Y, Yu G Abstract MOTIVATION: Liquid chromatography - mass spectrometry (LC-MS) is a standard method for proteomics and metabolomics analysis of biological samples. Unfortunately, it suffers from various changes in the retention times (RT) of the same compound in different samples, and these must be subsequently corrected (aligned) during data processing. Classic alignment methods such as in the popular XCMS package often assume a single time-warping function for each sample. Thus, the potentially varying RT drift for compounds with different masses in a sample is neglected in these methods. Moreover, the systematic change in RT drift across run order is often not considered by alignment algorithms. Therefore, these methods cannot effectively correct all misalignments. For a large-scale experiment involving many samples, the existence of misalignment becomes inevitable and concerning. RESULTS: Here we describe an integrated reference-free profile alignment method, neighbor-wise compound-specific Graphical Time Warping (ncGTW), that can detect misaligned features and align profiles by leveraging expected RT drift structures and compound-specific warping functions. Specifically, ncGTW uses individualized warping functions for different compounds and assigns constraint edges on warping functions of neighboring samples. Validated with both realistic synthetic data and internal quality control samples, ncGTW applied to two large-scale metabolomics LC-MS datasets identifies many misaligned features and successfully realigns them. These features would otherwise be discarded or uncorrected using existing methods. The ncGTW software tool is developed currently as a plug-in to detect and realign misaligned features present in standard XCMS output. AVAILABILITY AND IMPLEMENTATION: An R package of ncGTW is freely available at Bioconductor and https://github.com/ChiungTingWu/ncGTW. A detailed user's manual and a vignette are provided within the package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID: 31950989 [PubMed - as supplied by publisher]

Sex-related differences in urinary immune-related metabolic profiling of alopecia areata patients.

Sat, 18/01/2020 - 12:03
Related Articles Sex-related differences in urinary immune-related metabolic profiling of alopecia areata patients. Metabolomics. 2020 Jan 16;16(2):15 Authors: Lee YR, Kim H, Lew BL, Sim WY, Lee J, Oh HB, Hong J, Chung BC Abstract INTRODUCTION: Alopecia areata is a well-known autoimmune disease affecting humans. Polyamines are closely associated with proliferation and inflammation, and steroid hormones are involved in immune responses. Additionally, bile acids play roles in immune homeostasis by activating various signaling pathways; however, the roles of these substances and their metabolites in alopecia areata remain unclear. OBJECTIVES: In this study, we aimed to identify differences in metabolite levels in urine samples from patients with alopecia areata and healthy controls. METHODS: To assess polyamine, androgen, and bile acid concentrations, we performed high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Our results showed that spermine and dehydroepiandrosterone levels differed significantly between male patients and controls, whereas ursodeoxycholic acid levels were significantly higher in female patients with alopecia areata than in controls. CONCLUSION: Our findings suggested different urinary polyamine, androgen, and bile acid concentrations between alopecia areata patients and normal controls. Additionally, levels of endogenous substances varied according to sex, and this should be considered when developing appropriate treatments and diagnostic techniques. Our findings improve our understanding of polyamine, androgen, and bile acid profiles in patients with alopecia areata and highlight the need to consider sex-related differences. PMID: 31950279 [PubMed - in process]

Metabolomics Reveals that Cysteine Metabolism Plays a Role in Celastrol-Induced Mitochondrial Apoptosis in HL-60 and NB-4 Cells.

Sat, 18/01/2020 - 12:03
Related Articles Metabolomics Reveals that Cysteine Metabolism Plays a Role in Celastrol-Induced Mitochondrial Apoptosis in HL-60 and NB-4 Cells. Sci Rep. 2020 Jan 16;10(1):471 Authors: Chen M, Yang J, Li L, Hu Y, Lu X, Sun R, Wang Y, Wang X, Zhang X Abstract Recently, celastrol has shown great potential for inducing apoptosis in acute myeloid leukemia cells, especially acute promyelocytic leukaemia cells. However, the mechanism is poorly understood. Metabolomics provides an overall understanding of metabolic mechanisms to illustrate celastrol's mechanism of action. We treated both nude mice bearing HL-60 cell xenografts in vivo and HL-60 cells as well as NB-4 cells in vitro with celastrol. Ultra-performance liquid chromatography coupled with mass spectrometry was used for metabolomics analysis of HL-60 cells in vivo and for targeted L-cysteine analysis in HL-60 and NB-4 cells in vitro. Flow cytometric analysis was performed to assess mitochondrial membrane potential, reactive oxygen species and apoptosis. Western blotting was conducted to detect the p53, Bax, cleaved caspase 9 and cleaved caspase 3 proteins. Celastrol inhibited tumour growth, induced apoptosis, and upregulated pro-apoptotic proteins in the xenograft tumour mouse model. Metabolomics showed that cysteine metabolism was the key metabolic alteration after celastrol treatment in HL-60 cells in vivo. Celastrol decreased L-cysteine in HL-60 cells. Acetylcysteine supplementation reversed reactive oxygen species accumulation and apoptosis induced by celastrol and reversed the dramatic decrease in the mitochondrial membrane potential and upregulation of pro-apoptotic proteins in HL-60 cells. In NB-4 cells, celastrol decreased L-cysteine, and acetylcysteine reversed celastrol-induced reactive oxygen species accumulation and apoptosis. We are the first to identify the involvement of a cysteine metabolism/reactive oxygen species/p53/Bax/caspase 9/caspase 3 pathway in celastrol-triggered mitochondrial apoptosis in HL-60 and NB-4 cells, providing a novel underlying mechanism through which celastrol could be used to treat acute myeloid leukaemia, especially acute promyelocytic leukaemia. PMID: 31949255 [PubMed - in process]

A Feedback Circuitry between Polycomb Signaling and Fructose-1, 6-bisphosphatase Enables Hepatic and Renal Tumorigenesis.

Sat, 18/01/2020 - 12:03
Related Articles A Feedback Circuitry between Polycomb Signaling and Fructose-1, 6-bisphosphatase Enables Hepatic and Renal Tumorigenesis. Cancer Res. 2020 Jan 16;: Authors: Liao K, Deng S, Xu L, Pan W, Yang S, Zheng F, Wu X, Hu H, Liu Z, Luo J, Zhang R, Kuang DM, Dong J, Wu Y, Zhang H, Zhou P, Bei JX, Xu Y, Ji Y, Wang P, Ju HQ, Xu RH, Li B Abstract Suppression of gluconeogenesis elevates glycolysis and is commonly observed in tumors derived from gluconeogenic tissues including liver and kidney, yet the definitive regulatory mechanism remains elusive. Here we screened an array of transcription regulators and identified the enhancer of zeste homolog 2 (EZH2) as a key factor that inhibits gluconeogenesis in cancer cells. Specifically, EZH2 repressed the expression of a rate-limiting gluconeogenic enzyme fructose-1, 6-bisphosphatase 1 (FBP1), and promoted tumor growth primarily through FBP1 suppression. Furthermore, EZH2 was upregulated by genotoxins that commonly induce hepatic and renal tumorigenesis. Genotoxin treatments augmented EZH2 acetylation, leading to reduced association between EZH2 and its E3 ubiquitin ligase SMURF2. Consequently, EZH2 became less ubiquitinated and more stabilized, promoting FBP1 attenuation and tumor formation. Intriguingly, FBP1 physically interacted with EZH2, competed for EZH2 binding, and dissembled the polycomb complex. Therefore, FBP1 suppresses polycomb-initiated transcriptional responses, and constitutes a double-negative feedback loop indispensable for EZH2-promoted tumorigenesis. Finally, EZH2 and FBP1 levels were inversely correlated in tumor tissues and accurately predicted patient survival. This work reveals an unexpected crosstalk between epigenetic and metabolic events, and identifies a new feedback circuitry that highlights EZH2 inhibitors as liver and kidney cancer therapeutics. PMID: 31948940 [PubMed - as supplied by publisher]

Real-Time Volatilomics: A Novel Approach for Analyzing Biological Samples.

Sat, 18/01/2020 - 12:03
Related Articles Real-Time Volatilomics: A Novel Approach for Analyzing Biological Samples. Trends Plant Sci. 2020 Jan 13;: Authors: Majchrzak T, Wojnowski W, Rutkowska M, Wasik A Abstract The use of the 'omics techniques in environmental research has become common-place. The most widely implemented of these include metabolomics, proteomics, genomics, and transcriptomics. In recent years, a similar approach has also been taken with the analysis of volatiles from biological samples, giving rise to the so-called 'volatilomics' in plant analysis. Developments in direct infusion mass spectrometry (DI-MS) techniques have made it possible to monitor the changes in the composition of volatile flux from parts of plants, single specimens, and entire ecosystems in real-time. The application of these techniques enables a unique insight into the dynamic metabolic processes that occur in plants. Here, we provide an overview of the use of DI-MS in real-time volatilomics research involving plants. PMID: 31948793 [PubMed - as supplied by publisher]

Lp(a)'s Odyssey: Should We Measure Lp(a) Post-ACS and What Should We Do With the Results?

Sat, 18/01/2020 - 12:03
Related Articles Lp(a)'s Odyssey: Should We Measure Lp(a) Post-ACS and What Should We Do With the Results? J Am Coll Cardiol. 2020 Jan 21;75(2):145-147 Authors: Mora S PMID: 31948642 [PubMed - in process]

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