PubMed

Related Articles Temporal covariation of epibacterial community and surface metabolome in the Mediterranean seaweed holobiont Taonia atomaria. Environ Microbiol. 2019 Apr 04;: Authors: Paix B, Othmani A, Debroas D, Culioli G, Briand JF Abstract An integrative multi-omics approach allowed monthly variations for a year of the surface metabolome and the epibacterial community of the Mediterranean Phaeophyceae Taonia atomaria to be investigated. The LC-MS-based metabolomics and 16S rDNA metabarcoding datasets were integrated in a multivariate meta-omics analysis (multi-block PLS-DA from the MixOmic DIABLO analysis) showing a strong seasonal co-variation (Mantel test: p < 0.01). A network based on positive and negative correlations between the two datasets revealed two clusters of variables, one relative to the "spring period" and a second to the "summer period". The "spring period" cluster was mainly characterised by dipeptides positively correlated with a single bacterial taxon of the Alteromonadaceae family (BD1-7 clade). Moreover, "summer" dominant epibacterial taxa from the second cluster (including Erythrobacteraceae, Rhodospirillaceae, Oceanospirillaceae and Flammeovirgaceae) showed positive correlations with few metabolites known as macroalgal antifouling defences [e.g. dimethylsulphoniopropionate (DMSP) and proline] which exhibited a key role within the correlation network. Despite a core community that represents a significant part of the total epibacteria, changes in the microbiota structure associated with surface metabolome variations suggested that both environment and algal host shape the bacterial surface microbiota. This article is protected by copyright. All rights reserved. PMID: 30945796 [PubMed - as supplied by publisher]

Related Articles [Effect of moxibustion at "Zusanli"(ST36) on metabolites of gastric tissue in rats with chronic atrophic gastritis based on metabonomics]. Zhen Ci Yan Jiu. 2019 Feb 25;44(2):113-9 Authors: Liu X, She C, Zhong H, Liu T, Cao JN, Zhang C, Liu M, Chang XR Abstract OBJECTIVE: To observe the effect of moxibustion at "Zusanli" (ST36) on metabolites of gastric tissue in chronic atrophic gastritis (CAG) rats, so as to explore the correlation between Yangming Meridian and stomach based on metabolomics. METHODS: Fifty-six SD rats were randomly divided into normal, normal ＋ moxibustion, model and model ＋ moxibustion groups (n＝14 rats/group). The CAG model was established by gavage of N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) solution and irregular diet for 12 weeks. Moxibustion was applied to ST36 and "Zhongwan" (CV12) for 15 min, once daily for two weeks in the normal＋ moxibustion group and model＋moxibustion group. The histopathological changes of the gastric tissue were observed by H．E. staining. 1H nuclear magnetic resonance (1H NMR) spectroscopy was used to detect gastric tissue metabolites and the data were analyzed using the Chenomx NMR Suite software. RESULTS: After modeling, the regional gastric tissue showed pale thinner gastric wall, and reduction of regional glands with necrosis and disordered arrangement, epithelial cell exfoliation, lymphocyte infiltration as well as scattered punctate hemorrhage, which was evidently milder in the model ＋ moxibustion group. The metabolites of lactic acid, glutathione, N-acetylaspartate, uridine diphosphate glucose and muscle sugar in the gastric tissue in the model group were increased compared with those in the normal group (P<0.05), and the metabolites of leucine, betaine, phosphorylcholine, and uracil were decreased (P<0.05). The glutathione, N-acetylaspartate, phosphorylcholine and uracil in the model＋moxibustion group were significantly reversed relevant to the model group (P<0.05). The inositol in gastric tissue were significantly increased (P<0.05), 3-hydroxybutyric acid, serine and uridine diphosphate glucose were significantly decreased (P<0.05) in the normal ＋ moxibustion group than in the normal group. CONCLUSION: Moxibustion has a good efficacy in regulating some metabolic substances such as glutathione, N-acetylaspartic acid, choline phosphate and uracil of CAG rats, suggesting a specific relationship between the Stomach Meridian and the stomach. PMID: 30945487 [PubMed - in process]

Related Articles Diet-Related Metabolic Perturbations of Gut Microbial Shikimate Pathway-Tryptamine-tRNA Aminoacylation-Protein Synthesis in Human Health and Disease. Int J Tryptophan Res. 2019;12:1178646919834550 Authors: Paley EL Abstract Human gut bacterial Na(+)-transporting NADH:ubiquinone reductase (NQR) sequence is associated with Alzheimer disease (AD). Here, Alzheimer disease-associated sequence (ADAS) is further characterized in cultured spore-forming Clostridium sp. Tryptophan and NQR substrate ubiquinone have common precursor chorismate in microbial shikimate pathway. Tryptophan-derived tryptamine presents in human diet and gut microbiome. Tryptamine inhibits tryptophanyl-tRNA synthetase (TrpRS) with consequent neurodegeneration in cell and animal models. Tryptophanyl-tRNA synthetase inhibition causes protein biosynthesis impairment similar to that revealed in AD. Tryptamine-induced TrpRS gene-dose reduction is associated with TrpRS protein deficiency and cell death. In animals, tryptamine treatment results in toxicity, weight gain, and prediabetes-related hypoglycemia. Sequence analysis of gut microbiome database reveals 89% to 100% ADAS nucleotide identity in American Indian (Cheyenne and Arapaho [C&A]) Oklahomans, of which ~93% being overweight or obese and 50% self-reporting type 2 diabetes (T2D). Alzheimer disease-associated sequence occurs in 10.8% of C&A vs 1.3% of healthy American population. This observation is of considerable interest because T2D links to AD and obesity. Alzheimer disease-associated sequence prevails in gut microbiome of colorectal cancer, which linked to AD. Metabolomics revealed that tryptamine, chorismate precursor quinate, and chorismate product 4-hydroxybenzoate (ubiquinone precursor) are significantly higher, while tryptophan-containing dipeptides are lower due to tRNA aminoacylation deficiency in C&A compared with non-native Oklahoman who showed no ADAS. Thus, gut microbial tryptamine overproduction correlates with ADAS occurrence. Antibiotic and diet additives induce ADAS and tryptamine. Mitogenic/cytotoxic tryptamine cause microbial and human cell death, gut dysbiosis, and consequent disruption of host-microbe homeostasis. Present analysis of 1246 participants from 17 human gut metagenomics studies revealed ADAS in cell death diseases. PMID: 30944520 [PubMed]

Related Articles TMK1-mediated auxin signalling regulates differential growth of the apical hook. Nature. 2019 Apr 03;: Authors: Cao M, Chen R, Li P, Yu Y, Zheng R, Ge D, Zheng W, Wang X, Gu Y, Gelová Z, Friml J, Zhang H, Liu R, He J, Xu T Abstract The plant hormone auxin has crucial roles in almost all aspects of plant growth and development. Concentrations of auxin vary across different tissues, mediating distinct developmental outcomes and contributing to the functional diversity of auxin. However, the mechanisms that underlie these activities are poorly understood. Here we identify an auxin signalling mechanism, which acts in parallel to the canonical auxin pathway based on the transport inhibitor response1 (TIR1) and other auxin receptor F-box (AFB) family proteins (TIR1/AFB receptors)1,2, that translates levels of cellular auxin to mediate differential growth during apical-hook development. This signalling mechanism operates at the concave side of the apical hook, and involves auxin-mediated C-terminal cleavage of transmembrane kinase 1 (TMK1). The cytosolic and nucleus-translocated C terminus of TMK1 specifically interacts with and phosphorylates two non-canonical transcriptional repressors of the auxin or indole-3-acetic acid (Aux/IAA) family (IAA32 and IAA34), thereby regulating ARF transcription factors. In contrast to the degradation of Aux/IAA transcriptional repressors in the canonical pathway, the newly identified mechanism stabilizes the non-canonical IAA32 and IAA34 transcriptional repressors to regulate gene expression and ultimately inhibit growth. The auxin-TMK1 signalling pathway originates at the cell surface, is triggered by high levels of auxin and shares a partially overlapping set of transcription factors with the TIR1/AFB signalling pathway. This allows distinct interpretations of different concentrations of cellular auxin, and thus enables this versatile signalling molecule to mediate complex developmental outcomes. PMID: 30944466 [PubMed - as supplied by publisher]

Related Articles Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study. Sci Rep. 2019 Apr 03;9(1):5582 Authors: Ravacci GR, Ishida R, Torrinhas RS, Sala P, Machado NM, Fonseca DC, André Baptista Canuto G, Pinto E, Nascimento V, Franco Maggi Tavares M, Sakai P, Faintuch J, Santo MA, Moura EGH, Neto RA, Logullo AF, Waitzberg DL Abstract We evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (≥4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB. PMID: 30944407 [PubMed - in process]

Related Articles Metabolic reaction network-based recursive metabolite annotation for untargeted metabolomics. Nat Commun. 2019 Apr 03;10(1):1516 Authors: Shen X, Wang R, Xiong X, Yin Y, Cai Y, Ma Z, Liu N, Zhu ZJ Abstract Large-scale metabolite annotation is a challenge in liquid chromatogram-mass spectrometry (LC-MS)-based untargeted metabolomics. Here, we develop a metabolic reaction network (MRN)-based recursive algorithm (MetDNA) that expands metabolite annotations without the need for a comprehensive standard spectral library. MetDNA is based on the rationale that seed metabolites and their reaction-paired neighbors tend to share structural similarities resulting in similar MS2 spectra. MetDNA characterizes initial seed metabolites using a small library of MS2 spectra, and utilizes their experimental MS2 spectra as surrogate spectra to annotate their reaction-paired neighbor metabolites, which subsequently serve as the basis for recursive analysis. Using different LC-MS platforms, data acquisition methods, and biological samples, we showcase the utility and versatility of MetDNA and demonstrate that about 2000 metabolites can cumulatively be annotated from one experiment. Our results demonstrate that MetDNA substantially expands metabolite annotation, enabling quantitative assessment of metabolic pathways and facilitating integrative multi-omics analysis. PMID: 30944337 [PubMed - in process]

Related Articles Author Correction: Squaramide-based synthetic chloride transporters activate TFEB but block autophagic flux. Cell Death Dis. 2019 Apr 03;10(4):301 Authors: Zhang S, Wang Y, Xie W, Howe ENW, Busschaert N, Sauvat A, Leduc M, Gomes-da-Silva LC, Chen G, Martins I, Deng X, Maiuri L, Kepp O, Soussi T, Gale PA, Zamzami N, Kroemer G Abstract In the version of this article originally submitted, it was stated that the first three authors (Shaoyi_ Than, Yan Wang, Wei Xie) had contributed equally. However, in the published version this information was missing. PMID: 30944306 [PubMed - in process]

Related Articles Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine. Neurology. 2019 Apr 03;: Authors: Onderwater GLJ, Ligthart L, Bot M, Demirkan A, Fu J, van der Kallen CJH, Vijfhuizen LS, Pool R, Liu J, Vanmolkot FHM, Beekman M, Wen KX, Amin N, Thesing CS, Pijpers JA, Kies DA, Zielman R, de Boer I, van Greevenbroek MMJ, Arts ICW, Milaneschi Y, Schram MT, Dagnelie PC, Franke L, Ikram MA, Ferrari MD, Goeman JJ, Slagboom PE, Wijmenga C, Stehouwer CDA, Boomsma DI, van Duijn CM, Penninx BW, 't Hoen PAC, Terwindt GM, van den Maagdenberg AMJM, BBMRI Metabolomics Consortium Abstract OBJECTIVE: To identify a plasma metabolomic biomarker signature for migraine. METHODS: Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses. RESULTS: Decreases in the level of apolipoprotein A1 (β -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (β -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (β -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status. CONCLUSIONS: Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs. PMID: 30944236 [PubMed - as supplied by publisher]

Related Articles Mus musculus deficient for secretory antibodies show delayed growth with an altered urinary metabolome. Mol Med. 2019 Apr 03;25(1):12 Authors: Simpfendorfer KR, Wang N, Tull DL, De Souza DP, Nahid A, Mu A, Hocking DM, Pedersen JS, Wijburg OLC, McConville MJ, Strugnell RA Abstract BACKGROUND: The polymeric immunoglobulin receptor (pIgR) maintains the integrity of epithelial barriers by transporting polymeric antibodies and antigens through the epithelial mucosa into the lumen. In this study, we examined the role of pIgR in maintaining gut barrier integrity, which is important for the normal development in mice. METHODS: Cohorts of pIgR-/- mice and their wildtype controls were housed under Specific Pathogen Free (SPF) conditions and monitored for weight gain as an indicator of development over time. The general physiology of the gastrointestinal tract was analysed using immunohistochemistry in young (8-12 weeks of age) and aged mice (up to 18 months of age), and the observed immunopathology in pIgR-/- mice was further characterised using flow cytometry. Urinary metabolites were analysed using gas chromatography-mass spectrometry (GC-MS), which revealed changes in metabolites that correlated with age-related increase in gut permeability in pIgR-/- mice. RESULTS: We observed that pIgR-/- mice exhibited delayed growth, and this phenomenon is associated with low-grade gut inflammation that increased with ageing. The gross intraepithelial lymphocytic (IEL) infiltration characteristic of pIgR-/- mice was redefined as CD8α+αβ+ T cells, the majority of which expressed high levels of CD103 and CD69 consistent with tissue resident memory T cells (TRM). Comparison of the urinary metabolome between pIgR-/- and wild-type mice revealed key changes in urinary biomarkers fucose, glycine and Vitamin B5, suggestive of altered mucosal permeability. A significant increase in gut permeability was confirmed by analysing the site-specific uptake of sugar probes in different parts of the intestine. CONCLUSION: Our data show that loss of the secretory antibody system in mice results in enhanced accumulation of inflammatory IELs in the gut, which likely reflects ongoing inflammation in reaction to gut microbiota or food antigens, leading to delayed growth in pIgR-/- mice. We demonstrate that this leads to the presence of a unique urinary metabolome profile, which may provide a biomarker for altered gut permeability. PMID: 30943912 [PubMed - in process]

Related Articles A post-translational modification of human Norovirus capsid protein attenuates glycan binding. Nat Commun. 2019 03 21;10(1):1320 Authors: Mallagaray A, Creutznacher R, Dülfer J, Mayer PHO, Grimm LL, Orduña JM, Trabjerg E, Stehle T, Rand KD, Blaum BS, Uetrecht C, Peters T Abstract Attachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains. PMID: 30899001 [PubMed - indexed for MEDLINE]

Related Articles Development of an adaptable headspace sampling method for metabolic profiling of the fungal volatome. Analyst. 2018 Aug 20;143(17):4155-4162 Authors: Ahmed WM, Geranios P, White IR, Lawal O, Nijsen TM, Bromley MJ, Goodacre R, Read ND, Fowler SJ Abstract Pulmonary aspergillosis can cause serious complications in people with a suppressed immune system. Volatile metabolites emitted by Aspergillus spp. have shown promise for early detection of pathogenicity. However, volatile profiles require further research, as effective headspace analysis methods are required for extended chemical coverage of the volatome; in terms of both very volatile and semi-volatile compounds. In this study, we describe a novel adaptable sampling method in which fungal headspace samples can be sampled continuously throughout a defined time period using both active (pumped) and passive (diffusive) methods, with the capability for samples to be stored for later off-line analysis. For this method we utilise thermal desorption-gas chromatography-mass spectrometry to generate volatile metabolic profiles using Aspergillus fumigatus as the model organism. Several known fungal-specific volatiles associated with secondary metabolite biosynthesis (including α-pinene, camphene, limonene, and several sesquiterpenes) were identified. A comparison between the wild-type A. fumigatus with a phosphopantetheinyl transferase null mutant strain (ΔpptA) that is compromised in secondary metabolite synthesis, revealed reduced production of sesquiterpenes. We also showed the lack of terpene compounds production during the early growth phase, whilst pyrazines were identified in both early and late growth phases. We have demonstrated that the fungal volatome is dynamic and it is therefore critically necessary to sample the headspace across several time periods using a combination of active and passive sampling techniques to analyse and understand this dynamism. PMID: 30069568 [PubMed - indexed for MEDLINE]

Related Articles Comprehensive Tandem-Mass-Spectrometry Coverage of Complex Samples Enabled by Data-Set-Dependent Acquisition. Anal Chem. 2018 07 03;90(13):8020-8027 Authors: Broeckling CD, Hoyes E, Richardson K, Brown JM, Prenni JE Abstract Tandem mass spectrometry (MS/MS) is an invaluable experimental tool for providing analytical data supporting the identification of small molecules and peptides in mass-spectrometry-based "omics" experiments. Data-dependent MS/MS (DDA) is a real-time MS/MS-acquisition strategy that is responsive to the signals detected in a given sample. However, in analysis of even moderately complex samples with state-of-the-art instrumentation, the speed of MS/MS acquisition is insufficient to offer comprehensive MS/MS coverage of all detected molecules. Data-independent approaches (DIA) offer greater MS/MS coverage, typically at the expense of selectivity or sensitivity. This report describes data-set-dependent MS/MS (DsDA), a novel integration of MS1-data processing and target prioritization to enable comprehensive MS/MS sampling during the initial MS-level experiment. This approach is guided by the premise that in omics experiments, individual injections are typically made as part of a larger set of samples, and feedback between data processing and data acquisition can allow approximately real-time optimization of MS/MS-acquisition parameters and nearly complete MS/MS-sampling coverage. Using a combination of R, Proteowizard, XCMS, and WRENS software, this concept was implemented on a liquid-chromatograph-coupled quadrupole time-of-flight mass spectrometer. The results illustrate comprehensive MS/MS coverage for a set of complex small-molecule samples and demonstrate a strong improvement on traditional DDA. PMID: 29846054 [PubMed - indexed for MEDLINE]

Related Articles Nano-LC/NSI MS Refines Lipidomics by Enhancing Lipid Coverage, Measurement Sensitivity, and Linear Dynamic Range. Anal Chem. 2018 07 03;90(13):8093-8101 Authors: Danne-Rasche N, Coman C, Ahrends R Abstract Nano-liquid chromatography (nLC)-nanoelectrospray (NSI) is one of the cornerstones of mass-spectrometry-based bioanalytics. Nevertheless, the application of nLC is not yet prevalent in lipid analyses. In this study, we established a reproducible nLC separation for global lipidomics and describe the merits of using such a miniaturized system for lipid analyses. In order to enable comprehensive lipid analyses that is not restricted to specific lipid classes, we particularly optimized sample preparation conditions and reversed-phase separation parameters. We further benchmarked the developed nLC system to a commonly used high flow HPLC/ESI MS system in terms of lipidome coverage and sensitivity. The comparison revealed an intensity gain between 2 and 3 orders of magnitude for individual lipid classes and an increase in the linear dynamic range of up to 2 orders of magnitude. Furthermore, the analysis of the yeast lipidome using nLC/NSI resulted in more than a 3-fold gain in lipid identifications. All in all, we identified 447 lipids from the core phospholipid lipid classes (PA, PE, PC, PS, PG, and PI) in Saccharomyces cerevisiae. PMID: 29792796 [PubMed - indexed for MEDLINE]

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Related Articles Multi-Omics Approach: New Potential Key Mechanisms Implicated in Cardiorenal Syndromes. Cardiorenal Med. 2019 Apr 02;9(4):201-211 Authors: Virzì GM, Clementi A, Battaglia GG, Ronco C Abstract Cardiorenal syndromes (CRS) include a scenario of clinical interactions characterized by the heart and kidney dysfunction. The crosstalk between cardiac and renal systems is clearly evidenced but not completely understood. Multi-factorial mechanisms leading to CRS do not involve only hemodynamic parameters. In fact, in recent works on organ crosstalk endothelial injury, the alteration of normal immunologic balance, cell death, inflammatory cascades, cell adhesion molecules, cytokine and chemokine overexpression, neutrophil migration, leukocyte trafficking, caspase-mediated induction of apoptotic mechanisms and oxidative stress has been demonstrated to induce distant organ dysfunction. Furthermore, new alternative mechanisms using the multi-omics approach may be implicated in the pathogenesis of cardiorenal crosstalk. The study of "omics" modifications in the setting of cardiovascular and renal disease represents an emerging area of research. Over the last years, indeed, many studies have elucidated the exact mechanisms involved in gene expression and regulation, cellular communication and organ crosstalk. In this review, we analyze epigenetics, gene expression, small non-coding RNAs, extracellular vesicles, proteomics, and metabolomics in the setting of CRS. PMID: 30939477 [PubMed - as supplied by publisher]

Related Articles Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis. FASEB J. 2019 Apr 02;:fj201802457RR Authors: Gumucio JP, Qasawa AH, Ferrara PJ, Malik AN, Funai K, McDonagh B, Mendias CL Abstract Myosteatosis is the pathologic accumulation of lipid that can occur in conjunction with atrophy and fibrosis following skeletal muscle injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many clinical studies have demonstrated that the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our objective was to determine the pathologic changes that result in lipid accumulation in injured muscle fibers. We used a rat model of rotator cuff injury in this study because the rotator cuff muscle group is particularly prone to the development of myosteatosis after injury. Muscles were collected from uninjured controls or 10, 30, or 60 d after injury and analyzed using a combination of muscle fiber contractility assessments, RNA sequencing, and undirected metabolomics, lipidomics, and proteomics, along with bioinformatics techniques to identify potential pathways and cellular processes that are dysregulated after rotator cuff tear. Bioinformatics analyses indicated that mitochondrial function was likely disrupted after injury. Based on these findings and given the role that mitochondria play in lipid metabolism, we then performed targeted biochemical and imaging studies and determined that mitochondrial dysfunction and reduced fatty acid oxidation likely leads to the accumulation of lipid in myosteatosis.-Gumucio, J. P., Qasawa, A. H., Ferrara, P. J., Malik, A. N., Funai, K., McDonagh, B., Mendias, C. L. Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis. PMID: 30939247 [PubMed - as supplied by publisher]

Related Articles Loss of the glucocorticoid receptor in zebrafish improves muscle glucose availability and increases growth. Am J Physiol Endocrinol Metab. 2019 Apr 02;: Authors: Faught E, Vijayan MM Abstract Chronic stress and the associated elevation in corticosteroid levels increase muscle protein catabolism. We hypothesized that the GR-regulated restriction of muscle glucose availability may play a role in the increased protein catabolism during chronic stress. To test this, we generated a ubiquitous GR knockout (GRKO) zebrafish to determine the physiological consequence of glucocorticoid stimulation on muscle metabolism and growth. Adult GRKO zebrafish had higher body mass, and this corresponded with an increased protein and lipid, but not carbohydrate content. GRKO fish were hypercortisolemic, but they elicited a higher cortisol response to an acute stressor. However, the stressor-induced increase in plasma glucose level observed in the wildtype was completely abolished in the GRKO fish. Also, the muscle, but not liver, capacity for glucose uptake was enhanced in the GRKO fish, and this corresponded with a higher hexokinase activity in the mutants. Zebrafish lacking GR also showed a higher capacity for protein synthesis, including increased phosphorylation of eIF4B, higher expression of heat shock protein cognate 70, and total protein content. A chronic fasting stressor reduced body mass and muscle protein content in adult zebrafish, but this decrease was attenuated in the GRKO compared to the wildtype fish. Metabolomics analysis revealed that the free pool of amino acid substrates used for oxidation and gluconeogenesis were lower in the fasted GRKO fish muscle compared to the wildtype. Altogether, chronic stressor-mediated GR signalling limits muscle glucose uptake, and this may play a role in protein catabolism, leading to the growth suppression in fish. PMID: 30939052 [PubMed - as supplied by publisher]

Related Articles Pharmacomicrobiomics: The holy grail to variability in drug response? Clin Pharmacol Ther. 2019 Apr 02;: Authors: Sharma A, Buschmann MM, Gilbert JA Abstract The human body, with 3.0×1013 cells and more than 3.8×1013 microorganisms, has nearly a one-to-one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents i.e. pharamacomicrobiomics has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics and chemotherapeutic-agents to human disease and treatment outcomes. We also discuss the significance of studying diet-gene-drug interactions and further address the key challenges associated with pharamacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other omics data, and provide approaches to elucidate microbiome-drug interactions to improve future translation to personalized medicine. This article is protected by copyright. All rights reserved. PMID: 30937887 [PubMed - as supplied by publisher]

Related Articles Advances in metabolomics of thyroid cancer diagnosis and metabolic regulation. Endocrine. 2019 Apr 01;: Authors: Abooshahab R, Gholami M, Sanoie M, Azizi F, Hedayati M Abstract Thyroid cancers (TCs) are the most frequent endocrine malignancy with an unpredictable fast-growing incidence, especially in females all over the world. Fine-needle aspiration biopsy (FNAB) analysis is an accurate diagnostic method for detecting thyroid nodules and classification of TC. Though simplicity, safety, and accuracy of FNAB, 15-30% of cases are indeterminate, and it is not possible to determine the exact cytology of the specimen. This demands the need for innovative methods capable to find crucial biomarkers with adequate sensitivity for diagnosis and prediction in TC researches. Cancer-based metabolomics is a vast emerging field focused on the detection of a large set of metabolites extracted from biofluids or tissues. Using analytical chemistry procedures allows for the potential recognition of cancer-based metabolites for the purposes of advancing the era of personalized medicine. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) coupled with separation techniques e.g., gas chromatography (GC) and liquid chromatography (LC) are the main approaches for metabolic studies in cancers. The immense metabolite profiling has provided a chance to discover novel biomarkers for early detection of thyroid cancer and reduce unnecessary aggressive surgery. In this review, we recapitulate the recent advances and developed methods of diverse metabolomics tools and metabolic phenotypes of thyroid cancer, following a brief discussion of recent challenges in the thyroid cancer diagnosis. PMID: 30937722 [PubMed - as supplied by publisher]

Related Articles Disturbed energy and amino acid metabolism with their diagnostic potential in mitral valve disease revealed by untargeted plasma metabolic profiling. Metabolomics. 2019 Apr 01;15(4):57 Authors: Jiang L, Wang J, Li R, Fang ZM, Zhu XH, Yi X, Lan H, Wei X, Jiang DS Abstract INTRODUCTION: Mitral valve disease (MVD), including mitral valve regurgitation (MR) and mitral valve stenosis (MS), is a chronic and progressive cardiac malady. However, the metabolic alterations in MVD is not well-understood till now. The current gold standard diagnostic test, transthoracic echocardiography, has limitations on high-throughput measurement and lacks molecular information for early diagnosis of the disease. OBJECTIVE: The present study aimed to investigate the biochemical alterations and to explore their diagnostic potential for MVD. METHODS: Plasma metabolic profile derangements and their diagnostic potential were non-invasively explored in 34 MR and 20 MS patients against their corresponding controls, using high-throughput NMR-based untargeted metabolomics. RESULTS: Eighteen differential metabolites were identified for MR and MS patients respectively, on the basis of multivariate and univariate data analysis, which were mainly involved in energy metabolism, amino acid metabolism, calcium metabolism and inflammation. These differential metabolites, notably the significantly down-regulated formate and lactate, showed high diagnostic potential for MVD by using Spearman's rank-order correlation analysis and ROC analysis. CONCLUSIONS: To the best of our knowledge, the present study is the first one that explores the metabolic derangements and their diagnostic values in MVD patients using metabolomics. The findings indicated that metabolic disturbance occurred in MVD patients, with plasma formate and lactate emerged as important candidate biomarkers for MVD. PMID: 30937548 [PubMed - in process]