Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 16 min 18 sec ago

New Markers for Predicting Fertility of the Male Gametes in the Post Genomic Age.

Thu, 19/04/2018 - 13:44
New Markers for Predicting Fertility of the Male Gametes in the Post Genomic Age. Protein Pept Lett. 2018 Apr 18;: Authors: Dipresa S, De Toni L, Foresta C, Garolla A Abstract A number of test have been proposed to assess male fertility potential, ranging from routine testing by light microscopic method for evaluating semen samples, to screening test for DNA integrity aimed to look at sperm chromatin abnormalities. Spermatozoa are an extremely differentiated cell, they have critical functions for embryo development and heredity, in addiction to delivering a haploid paternal genome to the oocyte. Towards this goal certain requirements must always be met. The ability of spermatozoa to perform its reproductive function taking place in the spermatogenesis, a highly specialized process depending on multiple factors with effect on male fertility. In the past 30 years, large-scale analyses of transcriptomic and genome expression in mammals have generated a large amount of informations on numberless biomolecules involved in spermatogenesis and male germ cell reproductive function. Sperm proteome represents the protein content that spermatozoa needs to survive and work correctly and modifications of sperm proteome play a role in determining functional changes leading to a decrease of reproductive competence into affected spermatozoa. The post-genomic approach consists of different methodologies for concurrently testicular transcriptome studies, protein compositional analysis and metabolomics findings of the spermatozoa in humans. PMID: 29667547 [PubMed - as supplied by publisher]

Exploring the Sea Urchin Neuropeptide Landscape by Mass Spectrometry.

Thu, 19/04/2018 - 13:44
Related Articles Exploring the Sea Urchin Neuropeptide Landscape by Mass Spectrometry. J Am Soc Mass Spectrom. 2018 Apr 17;: Authors: Monroe EB, Annangudi SP, Wadhams AA, Richmond TA, Yang N, Southey BR, Romanova EV, Schoofs L, Baggerman G, Sweedler JV Abstract Neuropeptides are essential cell-to-cell signaling messengers and serve important regulatory roles in animals. Although remarkable progress has been made in peptide identification across the Metazoa, for some phyla such as Echinodermata, limited neuropeptides are known and even fewer have been verified on the protein level. We employed peptidomic approaches using bioinformatics and mass spectrometry (MS) to experimentally confirm 23 prohormones and to characterize a new prohormone in nervous system tissue from Strongylocentrotus purpuratus, the purple sea urchin. Ninety-three distinct peptides from known and novel prohormones were detected with MS from extracts of the radial nerves, many of which are reported or experimentally confirmed here for the first time, representing a large-scale study of neuropeptides from the phylum Echinodermata. Many of the identified peptides and their precursor proteins have low homology to known prohormones from other species/phyla and are unique to the sea urchin. By pairing bioinformatics with MS, the capacity to characterize novel peptides and annotate prohormone genes is enhanced. Graphical Abstract. PMID: 29667164 [PubMed - as supplied by publisher]

Diversity of Neuropeptide Cell-Cell Signaling Molecules Generated by Proteolytic Processing Revealed by Neuropeptidomics Mass Spectrometry.

Thu, 19/04/2018 - 13:44
Related Articles Diversity of Neuropeptide Cell-Cell Signaling Molecules Generated by Proteolytic Processing Revealed by Neuropeptidomics Mass Spectrometry. J Am Soc Mass Spectrom. 2018 Apr 17;: Authors: Hook V, Lietz CB, Podvin S, Cajka T, Fiehn O Abstract Neuropeptides are short peptides in the range of 3-40 residues that are secreted for cell-cell communication in neuroendocrine systems. In the nervous system, neuropeptides comprise the largest group of neurotransmitters. In the endocrine system, neuropeptides function as peptide hormones to coordinate intercellular signaling among target physiological systems. The diversity of neuropeptide functions is defined by their distinct primary sequences, peptide lengths, proteolytic processing of pro-neuropeptide precursors, and covalent modifications. Global, untargeted neuropeptidomics mass spectrometry is advantageous for defining the structural features of the thousands to tens of thousands of neuropeptides present in biological systems. Defining neuropeptide structures is the basis for defining the proteolytic processing pathways that convert pro-neuropeptides into active peptides. Neuropeptidomics has revealed that processing of pro-neuropeptides occurs at paired basic residues sites, and at non-basic residue sites. Processing results in neuropeptides with known functions and generates novel peptides representing intervening peptide domains flanked by dibasic residue processing sites, identified by neuropeptidomics. While very short peptide products of 2-4 residues are predicted from pro-neuropeptide dibasic processing sites, such peptides have not been readily identified; therefore, it will be logical to utilize metabolomics to identify very short peptides with neuropeptidomics in future studies. Proteolytic processing is accompanied by covalent post-translational modifications (PTMs) of neuropeptides comprising C-terminal amidation, N-terminal pyroglutamate, disulfide bonds, phosphorylation, sulfation, acetylation, glycosylation, and others. Neuropeptidomics can define PTM features of neuropeptides. In summary, neuropeptidomics for untargeted, global analyses of neuropeptides is essential for elucidation of proteases that generate diverse neuropeptides for cell-cell signaling. Graphical Abstract ᅟ. PMID: 29667161 [PubMed - as supplied by publisher]

Drought delays development of the sorghum root microbiome and enriches for monoderm bacteria.

Thu, 19/04/2018 - 13:44
Related Articles Drought delays development of the sorghum root microbiome and enriches for monoderm bacteria. Proc Natl Acad Sci U S A. 2018 Apr 16;: Authors: Xu L, Naylor D, Dong Z, Simmons T, Pierroz G, Hixson KK, Kim YM, Zink EM, Engbrecht KM, Wang Y, Gao C, DeGraaf S, Madera MA, Sievert JA, Hollingsworth J, Birdseye D, Scheller HV, Hutmacher R, Dahlberg J, Jansson C, Taylor JW, Lemaux PG, Coleman-Derr D Abstract Drought stress is a major obstacle to crop productivity, and the severity and frequency of drought are expected to increase in the coming century. Certain root-associated bacteria have been shown to mitigate the negative effects of drought stress on plant growth, and manipulation of the crop microbiome is an emerging strategy for overcoming drought stress in agricultural systems, yet the effect of drought on the development of the root microbiome is poorly understood. Through 16S rRNA amplicon and metatranscriptome sequencing, as well as root metabolomics, we demonstrate that drought delays the development of the early sorghum root microbiome and causes increased abundance and activity of monoderm bacteria, which lack an outer cell membrane and contain thick cell walls. Our data suggest that altered plant metabolism and increased activity of bacterial ATP-binding cassette (ABC) transporter genes are correlated with these shifts in community composition. Finally, inoculation experiments with monoderm isolates indicate that increased colonization of the root during drought can positively impact plant growth. Collectively, these results demonstrate the role that drought plays in restructuring the root microbiome and highlight the importance of temporal sampling when studying plant-associated microbiomes. PMID: 29666229 [PubMed - as supplied by publisher]

Synergistic anti-proliferative effect of mTOR inhibitor (rad001) plus gemcitabine on cholangiocarcinoma by decreasing choline kinase activity.

Thu, 19/04/2018 - 13:44
Related Articles Synergistic anti-proliferative effect of mTOR inhibitor (rad001) plus gemcitabine on cholangiocarcinoma by decreasing choline kinase activity. Dis Model Mech. 2018 Apr 12;: Authors: Lin G, Lin KJ, Wang F, Chen TC, Yen TC, Yeh TS Abstract Although gemcitabine plus cisplatin is the gold standard chemotherapy regimen for advanced cholangiocarcinoma, the response rate has been disappointing. This study aims to investigate a novel therapeutic regimen (gemcitabine plus rad001, an mTOR inhibitor) for cholangiocarcinoma. Gemcitabine, oxaliplatin, cetuximab, and rad001 in various combinations were first evaluated in vitro using six cholangiocarcinoma cell lines. In vivo therapeutic efficacies of gemcitabine, rad001 alone and combination were further evaluated using a xenograft mouse model and a chemically induced orthotopic cholangiocarcinoma rat model. In the in vitro study, gemcitabine plus rad001 exhibited a synergistic therapeutic effect on the cholangiocarcinoma cells irrespective of the k-ras status. In the xenograft study, gemcitabine plus rad001 showed the best therapeutic effect on tumor volume change, which was associated with an increased caspase-3 expression, a decreased eIF4E expression, as well as overexpression of both death receptor and mitochondrial apoptotic pathway-related genes. In a chemically-induced cholangiocarcinoma-afflicted rat model, the gemcitabine plus rad001 treatment suppressed tumor glycolysis as measured by 18F FDG micro-PET (positron emission tomography). Also, an increased intra-tumoral free choline, a decreased glycerophosphocholine and nearly undetectable phosphocholine levels were demonstrated by proton NMR (nuclear magnetic resonance), supported by a decreased choline kinase expression on Western blotting. We concluded that gemcitabine plus rad001 has a synergistic anti-proliferative effect on the cholangiocarcinoma irrespective of the k-ras status. The antitumor effect is associated with the flare-ups of both death receptor and mitochondrial pathways, as well as the down-regulation of the choline kinase activity, resulting in a characteristic change of choline metabolism. PMID: 29666220 [PubMed - as supplied by publisher]

Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review.

Thu, 19/04/2018 - 13:44
Related Articles Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review. Biochem Soc Trans. 2018 Apr 17;: Authors: Tomas C, Newton J Abstract Chronic fatigue syndrome (CFS), commonly known as myalgic encephalomyelitis (ME), is a debilitating disease of unknown etiology. CFS/ME is a heterogeneous disease associated with a myriad of symptoms but with severe, prolonged fatigue as the core symptom associated with the disease. There are currently no known biomarkers for the disease, largely due to the lack of knowledge surrounding the eitopathogenesis of CFS/ME. Numerous studies have been conducted in an attempt to identify potential biomarkers for the disease. This mini-review offers a brief summary of current research into the identification of metabolic abnormalities in CFS/ME which may represent potential biomarkers for the disease. The progress of research into key areas including immune dysregulation, mitochondrial dysfunction, 5'-adenosine monophosphate-activated protein kinase activation, skeletal muscle cell acidosis, and metabolomics are presented here. Studies outlined in this mini-review show many potential causes for the pathogenesis of CFS/ME and identify many potential metabolic biomarkers for the disease from the aforementioned research areas. The future of CFS/ME research should focus on building on the potential biomarkers for the disease using multi-disciplinary techniques at multiple research sites in order to produce robust data sets. Whether the metabolic changes identified in this mini-review occur as a cause or a consequence of the disease must also be established. PMID: 29666214 [PubMed - as supplied by publisher]

A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells.

Thu, 19/04/2018 - 13:44
Related Articles A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells. J Exp Med. 2018 Apr 17;: Authors: Luimstra JJ, Garstka MA, Roex MCJ, Redeker A, Janssen GMC, van Veelen PA, Arens R, Falkenburg JHF, Neefjes J, Ovaa H Abstract Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. We designed conditional peptides for HLA-A*02:01 and H-2Kb that form stable peptide-MHC I complexes at low temperatures, but dissociate when exposed to a defined elevated temperature. The resulting conditional MHC I complexes, either alone or prepared as ready-to-use multimers, can swiftly be loaded with peptides of choice without additional handling and within a short time frame. We demonstrate the ease and flexibility of this approach by monitoring the antiviral immune constitution in an allogeneic stem cell transplant recipient and by analyzing CD8+ T cell responses to viral epitopes in mice infected with lymphocytic choriomeningitis virus or cytomegalovirus. PMID: 29666167 [PubMed - as supplied by publisher]

Prevention and Treatment of Type 2 Diabetes: A Pathophysiological-Based Approach.

Thu, 19/04/2018 - 13:44
Related Articles Prevention and Treatment of Type 2 Diabetes: A Pathophysiological-Based Approach. Trends Endocrinol Metab. 2018 Apr 14;: Authors: Samocha-Bonet D, Debs S, Greenfield JR Abstract Prediabetes affects approximately 40% of American adults. Randomized trials report that a proportion of individuals with prediabetes develop diabetes despite caloric restriction, physical activity, and/or when treated with metformin, the first-line medication for patients with type 2 diabetes mellitus (T2DM). Currently, there are no valid predictors of the effectiveness of these measures in determining who will and who will not progress to the T2DM state. Few studies have examined the clinical and phenotypic predictors of better and worse glycemic response to lifestyle interventions and metformin in prediabetes and diabetes. Further studies incorporating 'omic' approaches to discover novel markers of phenotypes and treatment effectiveness may pave the way to personalizing the treatment of prediabetes and diabetes. PMID: 29665986 [PubMed - as supplied by publisher]

Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy.

Thu, 19/04/2018 - 13:44
Related Articles Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy. Nutrients. 2017 Jun 28;9(7): Authors: Aitoro R, Paparo L, Amoroso A, Di Costanzo M, Cosenza L, Granata V, Di Scala C, Nocerino R, Trinchese G, Montella M, Ercolini D, Berni Canani R Abstract The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms. Short-chain fatty acids are crucial metabolic products of gut microbiota responsible for many protective effects against food allergy. These compounds are involved in epigenetic regulation of the immune system. These evidences provide a foundation for developing innovative strategies to prevent and treat food allergy. Here, we present an overview on the potential role of gut microbiota as the target of intervention against food allergy. PMID: 28657607 [PubMed - indexed for MEDLINE]

Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development.

Wed, 18/04/2018 - 13:28
Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development. Mol Nutr Food Res. 2018 Apr 17;:e1700942 Authors: Hoving LR, Katiraei S, Heijink M, Pronk A, van der Wee-Pals L, Streefland T, Giera M, van Dijk KW, van Harmelen V Abstract SCOPE: Mannan oligosaccharides (MOS) have proven effective at improving growth performance, while also reducing hyperlipidemia and inflammation. As atherosclerosis is accelerated both by hyperlipidemia and inflammation, we aimed to determine the effect of dietary MOS on atherosclerosis development in hyperlipidemic ApoE*3-Leiden.CETP (E3L.CETP) mice, a well-established model for human-like lipoprotein metabolism. METHODS AND RESULTS: Female E3L.CETP mice were fed a high cholesterol diet, with or without 1% MOS for 14 weeks. MOS substantially decreased atherosclerotic lesions up to 54% as assessed in the valve area of the aortic root. In blood, IL-1RA, monocyte subtypes, lipids and bile acids (BAs) were not affected by MOS. Gut microbiota composition was determined using 16S rRNA gene sequencing and MOS increased the abundance of cecal Bacteroides Ovatus. MOS did not affect fecal excretion of cholesterol, but increased fecal BAs as well as butyrate in cecum as determined by gas-chromatography-mass-spectrometry. CONCLUSION: MOS decreased the onset of atherosclerosis development, via lowering of plasma cholesterol levels. These effects were accompanied by increased cecal butyrate and fecal excretion of BAs, presumably mediated via interactions of MOS with the gut microbiota. This article is protected by copyright. All rights reserved. PMID: 29665623 [PubMed - as supplied by publisher]

Lipidomic insight into cardiovascular diseases.

Wed, 18/04/2018 - 13:28
Lipidomic insight into cardiovascular diseases. Biochem Biophys Res Commun. 2018 Apr 14;: Authors: Kohno S, Keenan AL, Ntambi JM, Miyazaki M Abstract Cardiovascular disease is a primary cause of mortality worldwide. Therefore, it is of major interest to identify sensitive molecular markers that predict cardiovascular events and point to therapeutic strategies that will increase lifespans. Dysregulated lipid metabolism is recognized as an established risk factor in cardiovascular diseases. However, it is still largely unknown which specific lipid molecular species reflect cardiovascular risk. In addition, understanding the whole lipidome signature in vascular pathophysiology is challenging. Recent advancements of mass-spectrometry allow researchers to detect each individual lipid species from unbiased small samples. In this review, we update the current research on lipidomic approaches in cardiovascular diseases. PMID: 29665359 [PubMed - as supplied by publisher]

Sepsis Diagnostics in the Era of "Omics" Technologies.

Wed, 18/04/2018 - 13:28
Sepsis Diagnostics in the Era of "Omics" Technologies. Prague Med Rep. 2018;119(1):9-29 Authors: Průcha M, Zazula R, Russwurm S Abstract Sepsis is a multifactorial clinical syndrome with an extremely dynamic clinical course and with high diverse clinical phenotype. Early diagnosis is crucial for the final clinical outcome. Previous studies have not identified a biomarker for the diagnosis of sepsis which would have sufficient sensitivity and specificity. Identification of the infectious agents or the use of molecular biology, next gene sequencing, has not brought significant benefit for the patient in terms of early diagnosis. Therefore, we are currently searching for biomarkers, through "omics" technologies with sufficient diagnostic specificity and sensitivity, able to predict the clinical course of the disease and the patient response to therapy. Current progress in the use of systems biology technologies brings us hope that by using big data from clinical trials such biomarkers will be found. PMID: 29665344 [PubMed - in process]

A prototypic small molecule database for bronchoalveolar lavage-based metabolomics.

Wed, 18/04/2018 - 13:28
A prototypic small molecule database for bronchoalveolar lavage-based metabolomics. Sci Data. 2018 Apr 17;5:180060 Authors: Walmsley S, Cruickshank-Quinn C, Quinn K, Zhang X, Petrache I, Bowler RP, Reisdorph R, Reisdorph N Abstract The analysis of bronchoalveolar lavage fluid (BALF) using mass spectrometry-based metabolomics can provide insight into lung diseases, such as asthma. However, the important step of compound identification is hindered by the lack of a small molecule database that is specific for BALF. Here we describe prototypic, small molecule databases derived from human BALF samples (n=117). Human BALF was extracted into lipid and aqueous fractions and analyzed using liquid chromatography mass spectrometry. Following filtering to reduce contaminants and artifacts, the resulting BALF databases (BALF-DBs) contain 11,736 lipid and 658 aqueous compounds. Over 10% of these were found in 100% of samples. Testing the BALF-DBs using nested test sets produced a 99% match rate for lipids and 47% match rate for aqueous molecules. Searching an independent dataset resulted in 45% matching to the lipid BALF-DB compared to<25% when general databases are searched. The BALF-DBs are available for download from MetaboLights. Overall, the BALF-DBs can reduce false positives and improve confidence in compound identification compared to when general databases are used. PMID: 29664467 [PubMed - in process]

PPARα mediates the hepatoprotective effects of nutmeg.

Wed, 18/04/2018 - 13:28
PPARα mediates the hepatoprotective effects of nutmeg. J Proteome Res. 2018 Apr 17;: Authors: Yang XN, Liu XM, Fang JH, Zhu X, Yang XW, Xiao XR, Huang JF, Gonzalez FJ, Li F Abstract Nutmeg is a traditional Chinese medicine used to treat gastrointestinal diseases. Some reports indicated that nutmeg has hepatoprotective activity. In this study, a thioacetamide (TAA)-induced acute liver injury model in mice was used to explore the mechanism of the protective effects of nutmeg extract (NME), including its major bioactive component myrislignan. The results indicated that NME could effectively protect TAA-induced liver damage as assessed by recovery of increased serum liver transaminases, decrease hepatic oxidative stress and lower hepatic inflammation. Metabolomics analysis further revealed that treatment with NME led to the recovery of a series of lipids including lysophosphatidylcholines that were decreased, and a lowering of acylcarnitines that were increased, in mouse plasma and liver after TAA exposure. Gene expression analysis demonstrated the hepatoprotective effect of NME was achieved by activation of the peroxisome proliferator-activated receptor alpha (PPARα), as well as the decrease of oxidative stress. NME could not protect from TAA-induced liver injury in Ppara-null mice, suggesting that its protective effect was dependent on PPARα. Myrislignan, a representative neolignan in nutmeg, showed potent protective activity against TAA-induced liver toxicity. These data demonstrate that nutmeg alleviates TAA-induced liver injury through the modulation of PPARα, and that the lignan compounds in nutmeg such as myrislignan partly contributed to this action. PMID: 29664296 [PubMed - as supplied by publisher]

Physiology, gene expression and metabolome of two wheat cultivars with contrasting submergence tolerance.

Wed, 18/04/2018 - 13:28
Physiology, gene expression and metabolome of two wheat cultivars with contrasting submergence tolerance. Plant Cell Environ. 2018 Apr 17;: Authors: Herzog M, Fukao T, Winkel A, Konnerup D, Lamichhane S, Alpuerto JB, Hasler-Sheetal H, Pedersen O PMID: 29664146 [PubMed - as supplied by publisher]

Identification of Potential Biomarkers for Urine Metabolomics of Polycystic Ovary Syndrome Based on Gas Chromatography-Mass Spectrometry.

Wed, 18/04/2018 - 13:28
Identification of Potential Biomarkers for Urine Metabolomics of Polycystic Ovary Syndrome Based on Gas Chromatography-Mass Spectrometry. Chin Med J (Engl). 2018 Apr 20;131(8):945-949 Authors: Zou Y, Zhu FF, Fang CY, Xiong XY, Li HY Abstract Background: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and it's diagnosis is difficult. The aim of this study was to investigate the metabolic profiles of PCOS patients by analyzing urine samples and identify useful biomarkers for diagnosis of PCOS. Methods: This study was carried out in the Department of Obstetrics and Gynecology of the Maternal and Child Health Hospital of Hunan Province from December 2014 to July 2016. In this study, the urine samples of 21 women with PCOS and 16 healthy controls were assessed through gas chromatography-mass spectrometry to investigate the urine metabolite characteristics of PCOS and identify useful biomarkers for the diagnosis of this disorder. The Student's t-test and rank sum test were applied to validate the statistical significance of the between the two groups. Results: In total, 35 urine metabolites were found to be significantly different between the PCOS patients and the controls. In particular, a significant increase in the levels of lactose (10.01 [0,13.99] mmol/mol creatinine vs. 2.35 [0.16, 3.26] mmol/mol creatinine, P = 0.042), stearic acid (2.35 [1.47, 3.14] mmol/mol creatinine vs. 0.05 [0, 0.14] mmol/mol creatinine, P < 0.001), and palmitic acid (2.13 [1.07, 2.79] mmol/mol creatinine vs. 0 [0, 0] mmol/mol creatinine, P < 0.001) and a decrease in the levels of succinic acid (0 [0, 0] mmol/mol creatinine vs. 38.94 [4.16, 51.30] mmol/mol creatinine, P < 0.001) were found in the PCOS patients compared with the controls. It was possible to cluster the PCOS patients and the healthy controls into two distinct regions based on a principal component analysis model. Of the differentially expressed metabolites, four compounds, including stearic acid, palmitic acid, benzoylglycine, and threonine, were selected as potential biomarkers. Conclusions: This study offers new insight into the pathogenesis of PCOS, and the discriminating urine metabolites may provide a prospect for the diagnosis of PCOS. PMID: 29664055 [PubMed - in process]

Hepatocellular Carcinoma-associated Protein TD26 Interacts and Enhances SREBP1 Activity to Promote Tumor Cell Proliferation and Growth.

Wed, 18/04/2018 - 13:28
Related Articles Hepatocellular Carcinoma-associated Protein TD26 Interacts and Enhances SREBP1 Activity to Promote Tumor Cell Proliferation and Growth. Hepatology. 2018 Apr 16;: Authors: Wang C, Tong Y, Wen Y, Cai J, Guo H, Huang L, Xu M, Feng M, Chen X, Zhang J, Wu H, Kong X, Xia Q Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Increased lipogenesis has been reported to play a critical role in HCC progression. However, the underlying mechanism contributing to lipogenesis increase in HCC remains elusive. Here, we show that hepatocellular carcinoma-associated protein TD26 (TD26) was highly expressed in HCC tumor tissues compared to matched normal tissues. From the clinicopathologic analyses of two independent HCC cohorts, we demonstrate that TD26 expression was positively correlated with tumor size and was an independent predictor of overall survival (OS) and recurrence free survival (RFS) in HCC patients. Our metabolomics assays demonstrate that TD26 had no effect on glycometabolism but significantly increased lipogenesis in HCC cells. In addition, our functional assays indicate that TD26 promoted HCC cell proliferation and tumor growth. We further demonstrate that TD26-mediated increase in lipogenesis and tumor cell proliferation was SREBP1-dependent. Mechanistically, we demonstrate that, through its C-terminus (amino acids from 121 to 198), TD26 interacted with the truncated nuclear SREBP1 form (nSREBP1) but not the SREBP1 full-length (flSREBP1) to block AMPK-mediated inhibition on SREBP1 activity, resulting in increased lipogenesis, elevated tumor cell proliferation and enhanced tumor progression. Therefore, we propose that TD26 is a novel positive regulator on SREBP1 transactivity and the interaction between TD26 and SREBP1 can serve as a potential therapeutic target for HCC treatment. This article is protected by copyright. All rights reserved. PMID: 29663480 [PubMed - as supplied by publisher]

The role of the Human Metabolome Database in inborn errors of metabolism.

Wed, 18/04/2018 - 13:28
Related Articles The role of the Human Metabolome Database in inborn errors of metabolism. J Inherit Metab Dis. 2018 Apr 16;: Authors: Mandal R, Chamot D, Wishart DS Abstract Metabolomics holds considerable promise to advance our understanding of human disease, including our understanding of inborn errors of metabolism (IEM). The application of metabolomics in IEM research has already led to the discovery of several novel IEMs and the identification of novel IEM biomarkers. However, with hundreds of known IEMs and more than 700 associated IEM metabolites, it is becoming increasingly challenging for clinical researchers to keep track of IEMs, their associated metabolites, and their corresponding metabolic mechanisms. Furthermore, when using metabolomics to assist in IEM biomarker discovery or even in IEM diagnosis, it is becoming much more difficult to properly identify metabolites from the complex NMR and MS spectra collected from IEM patients. To that end, comprehensive, open access metabolite databases that provide up-to-date referential information about metabolites, metabolic pathways, normal/abnormal metabolite concentrations, and reference NMR or MS spectra for compound identification are essential. Over the last few years, a number of compound databases, including the Human Metabolome Database (HMDB), have been developed to address these challenges. First described in 2007, the HMDB is now the world's largest and most comprehensive metabolomic resource for human metabolic studies. The latest release of the HMDB contains 114,100 metabolite entries (with 247 being relevant to IEMs), thousands of metabolite concentrations (with 600 being relevant to IEMs), and ~33,000 metabolic and disease-associated pathways (with 202 being relevant to IEMs). Here we provide a summary of the HMDB and offer some guidance on how it can be used in metabolomic studies of IEMs. PMID: 29663269 [PubMed - as supplied by publisher]

Comparative Analysis of the Microbiota Between Sheep Rumen and Rabbit Cecum Provides New Insight Into Their Differential Methane Production.

Wed, 18/04/2018 - 13:28
Related Articles Comparative Analysis of the Microbiota Between Sheep Rumen and Rabbit Cecum Provides New Insight Into Their Differential Methane Production. Front Microbiol. 2018;9:575 Authors: Mi L, Yang B, Hu X, Luo Y, Liu J, Yu Z, Wang J Abstract The rumen and the hindgut represent two different fermentation organs in herbivorous mammals, with the former producing much more methane than the latter. The objective of this study was to elucidate the microbial underpinning of such differential methane outputs between these two digestive organs. Methane production was measured from 5 adult sheep and 15 adult rabbits, both of which were placed in open-circuit respiratory chambers and fed the same diet (alfalfa hay). The sheep produced more methane than the rabbits per unit of metabolic body weight, digestible neutral detergent fiber, and acid detergent fiber. pH in the sheep rumen was more than 1 unit higher than that in the rabbit cecum. The acetate to propionate ratio in the rabbit cecum was more than threefold greater than that in the sheep rumen. Comparative analysis of 16S rRNA gene amplicon libraries revealed distinct microbiota between the rumen of sheep and the cecum of rabbits. Hydrogen-producing fibrolytic bacteria, especially Butyrivibrio, Succiniclastium, Mogibacterium, Prevotella, and Christensenellaceae, were more predominant in the sheep rumen, whereas non-hydrogen producing fibrolytic bacteria, such as Bacteroides, were more predominant in the rabbit cecum. The rabbit cecum had a greater predominance of acetogens, such as those in the genus Blautia, order Clostridiales, and family Ruminococcaceae. The differences in the occurrence of hydrogen-metabolizing bacteria probably explain much of the differential methane outputs from the rumen and the cecum. Future research using metatranscriptomics and metabolomics shall help confirm this premise and understand the factors that shape the differential microbiota between the two digestive organs. Furthermore, our present study strongly suggests the presence of new fibrolytic bacteria in the rabbit cecum, which may explain the stronger fibrolytic activities therein. PMID: 29662480 [PubMed]

Initial Metabolic Profiles Are Associated with 7-Day Survival among Infants Born at 22-25 Weeks of Gestation.

Wed, 18/04/2018 - 13:28
Related Articles Initial Metabolic Profiles Are Associated with 7-Day Survival among Infants Born at 22-25 Weeks of Gestation. J Pediatr. 2018 Apr 13;: Authors: Oltman SP, Rogers EE, Baer RJ, Anderson JG, Steurer MA, Pantell MS, Partridge JC, Rand L, Ryckman KK, Jelliffe-Pawlowski LL Abstract OBJECTIVE: To evaluate the association between early metabolic profiles combined with infant characteristics and survival past 7 days of age in infants born at 22-25 weeks of gestation. STUDY DESIGN: This nested case-control consisted of 465 singleton live births in California from 2005 to 2011 at 22-25 weeks of gestation. All infants had newborn metabolic screening data available. Data included linked birth certificate and mother and infant hospital discharge records. Mortality was derived from linked death certificates and death discharge information. Each death within 7 days was matched to 4 surviving controls by gestational age and birth weight z score category, leaving 93 cases and 372 controls. The association between explanatory variables and 7-day survival was modeled via stepwise logistic regression. Infant characteristics, 42 metabolites, and 12 metabolite ratios were considered for model inclusion. Model performance was assessed via area under the curve. RESULTS: The final model included 1 characteristic and 11 metabolites. The model demonstrated a strong association between metabolic patterns and infant survival (area under the curve [AUC] 0.885, 95% CI 0.851-0.920). Furthermore, a model with just the selected metabolites performed better (AUC 0.879, 95% CI 0.841-0.916) than a model with multiple clinical characteristics (AUC 0.685, 95% CI 0.627-0.742). CONCLUSIONS: Use of metabolomics significantly strengthens the association with 7-day survival in infants born extremely premature. Physicians may be able to use metabolic profiles at birth to refine mortality risks and inform postnatal counseling for infants born at <26 weeks of gestation. PMID: 29661562 [PubMed - as supplied by publisher]

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