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; +17 new citations

Sat, 28/04/2018 - 14:49
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 2018/04/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +22 new citations

Fri, 27/04/2018 - 14:18
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 2018/04/27PubMed 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.

Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages.

Thu, 26/04/2018 - 14:04
Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages. Cell Rep. 2018 Apr 24;23(4):1099-1111 Authors: Krishnan S, Ding Y, Saedi N, Choi M, Sridharan GV, Sherr DH, Yarmush ML, Alaniz RC, Jayaraman A, Lee K Abstract The gut microbiota plays a significant role in the progression of fatty liver disease; however, the mediators and their mechanisms remain to be elucidated. Comparing metabolite profile differences between germ-free and conventionally raised mice against differences between mice fed a low- and high-fat diet (HFD), we identified tryptamine and indole-3-acetate (I3A) as metabolites that depend on the microbiota and are depleted under a HFD. Both metabolites reduced fatty-acid- and LPS-stimulated production of pro-inflammatory cytokines in macrophages and inhibited the migration of cells toward a chemokine, with I3A exhibiting greater potency. In hepatocytes, I3A attenuated inflammatory responses under lipid loading and reduced the expression of fatty acid synthase and sterol regulatory element-binding protein-1c. These effects were abrogated in the presence of an aryl-hydrocarbon receptor (AhR) antagonist, indicating that the effects are AhR dependent. Our results suggest that gut microbiota could influence inflammatory responses in the liver through metabolites engaging host receptors. PMID: 29694888 [PubMed - in process]

Correction to ADAP-GC 3.0: Improved Peak Detection and Deconvolution of Co-eluting Metabolites from GC/TOF-MS Data for Metabolomics Studies.

Thu, 26/04/2018 - 14:04
Correction to ADAP-GC 3.0: Improved Peak Detection and Deconvolution of Co-eluting Metabolites from GC/TOF-MS Data for Metabolomics Studies. Anal Chem. 2018 Apr 25;: Authors: Ni Y, Su M, Qiu Y, Jia W, Du X PMID: 29694022 [PubMed - as supplied by publisher]

Metabolic characterization of serum from mice challenged with Orientia tsutsugamushi-infected mites.

Thu, 26/04/2018 - 14:04
Metabolic characterization of serum from mice challenged with Orientia tsutsugamushi-infected mites. New Microbes New Infect. 2018 May;23:70-76 Authors: Chao CC, Ingram BO, Lurchachaiwong W, Ching WM Abstract Scrub typhus is an acute zoonosis caused by the obligate intracellular Gram-negative bacterium Orientia tsutsugamushi. To better understand the host response elicited by natural infection by chigger feeding, ICR mice were infected by Leptotrombidium chiangraiensis (Lc1) chiggers, and the metabolic profiles of their serum were examined over several time points after initiation of feeding. ICR mice were infected by either naive Lc1 chiggers (i.e. not infected by O. tsutsugamushi, NLc1) or O. tsutsugamushi-infected Lc1 chiggers (OLc1). Serum was collected from both groups of mice at 6 hours and 10 days after initiation of feeding. Metabolites were extracted from the serum and analysed by ultra performance liquid chromatography-tandem mass spectrometry. The resulting ion/chromatographic features were matched to a library of chemical standards for identification and quantification. Biochemicals that differed significantly between the experimental groups were identified using Welch's two-sample t tests; p ≤ 0.05 was considered statistically significant. A number of biochemicals linked to immune function were found to be significantly altered between mice infected by the NLc1 and OLc1 chiggers, including itaconate, kynurenine and histamine. Several metabolites linked to energy production were also found to be altered in the animals. In addition lipid and carbohydrate metabolism, bile acid and phospholipid homeostasis, and nucleotide metabolism were also found to be different in these two groups of mice. Markers of stress and food intake were also significantly altered. Global untargeted metabolomic characterization revealed significant differences in the biochemical profiles of mice infected by the NLc1 versus OLc1 chiggers. These findings provide an important platform for further investigation of the host responses associated with chigger-borne O. tsutsugamushi infections. PMID: 29692908 [PubMed]

Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities.

Thu, 26/04/2018 - 14:04
Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities. Cancer Metab. 2018;6:4 Authors: Garrett M, Sperry J, Braas D, Yan W, Le TM, Mottahedeh J, Ludwig K, Eskin A, Qin Y, Levy R, Breunig JJ, Pajonk F, Graeber TG, Radu CG, Christofk H, Prins RM, Lai A, Liau LM, Coppola G, Kornblum HI Abstract Background: There is considerable interest in defining the metabolic abnormalities of IDH mutant tumors to exploit for therapy. While most studies have attempted to discern function by using cell lines transduced with exogenous IDH mutant enzyme, in this study, we perform unbiased metabolomics to discover metabolic differences between a cohort of patient-derived IDH1 mutant and IDH wildtype gliomaspheres. Methods: Using both our own microarray and the TCGA datasets, we performed KEGG analysis to define pathways differentially enriched in IDH1 mutant and IDH wildtype cells and tumors. Liquid chromatography coupled to mass spectrometry analysis with labeled glucose and deoxycytidine tracers was used to determine differences in overall cellular metabolism and nucleotide synthesis. Radiation-induced DNA damage and repair capacity was assessed using a comet assay. Differences between endogenous IDH1 mutant metabolism and that of IDH wildtype cells transduced with the IDH1 (R132H) mutation were also investigated. Results: Our KEGG analysis revealed that IDH wildtype cells were enriched for pathways involved in de novo nucleotide synthesis, while IDH1 mutant cells were enriched for pathways involved in DNA repair. LC-MS analysis with fully labeled 13C-glucose revealed distinct labeling patterns between IDH1 mutant and wildtype cells. Additional LC-MS tracing experiments confirmed increased de novo nucleotide synthesis in IDH wildtype cells relative to IDH1 mutant cells. Endogenous IDH1 mutant cultures incurred less DNA damage than IDH wildtype cultures and sustained better overall growth following X-ray radiation. Overexpression of mutant IDH1 in a wildtype line did not reproduce the range of metabolic differences observed in lines expressing endogenous mutations, but resulted in depletion of glutamine and TCA cycle intermediates, an increase in DNA damage following radiation, and a rise in intracellular ROS. Conclusions: These results demonstrate that IDH1 mutant and IDH wildtype cells are easily distinguishable metabolically by analyzing expression profiles and glucose consumption. Our results also highlight important differences in nucleotide synthesis utilization and DNA repair capacity that could be exploited for therapy. Altogether, this study demonstrates that IDH1 mutant gliomas are a distinct subclass of glioma with a less malignant, but also therapy-resistant, metabolic profile that will likely require distinct modes of therapy. PMID: 29692895 [PubMed]

A Vegetal Biopolymer-Based Biostimulant Promoted Root Growth in Melon While Triggering Brassinosteroids and Stress-Related Compounds.

Thu, 26/04/2018 - 14:04
A Vegetal Biopolymer-Based Biostimulant Promoted Root Growth in Melon While Triggering Brassinosteroids and Stress-Related Compounds. Front Plant Sci. 2018;9:472 Authors: Lucini L, Rouphael Y, Cardarelli M, Bonini P, Baffi C, Colla G Abstract Plant biostimulants are receiving great interest for boosting root growth during the first phenological stages of vegetable crops. The present study aimed at elucidating the morphological, physiological, and metabolomic changes occurring in greenhouse melon treated with the biopolymer-based biostimulant Quik-link, containing lateral root promoting peptides, and lignosulphonates. The vegetal-based biopolymer was applied at five rates (0, 0.06, 0.12, 0.24, or 0.48 mL plant-1) as substrate drench. The application of biopolymer-based biostimulant at 0.12 and 0.24 mL plant-1 enhanced dry weight of melon leaves and total biomass by 30.5 and 27.7%, respectively, compared to biopolymer applications at 0.06 mL plant-1 and untreated plants. The root dry biomass, total root length, and surface in biostimulant-treated plants were significantly higher at 0.24 mL plant-1 and to a lesser extent at 0.12 and 0.48 mL plant-1, in comparison to 0.06 mL plant-1 and untreated melon plants. A convoluted biochemical response to the biostimulant treatment was highlighted through UHPLC/QTOF-MS metabolomics, in which brassinosteroids and their interaction with other hormones appeared to play a pivotal role. Root metabolic profile was more markedly altered than leaves, following application of the biopolymer-based biostimulant. Brassinosteroids triggered in roots could have been involved in changes of root development observed after biostimulant application. These hormones, once transported to shoots, could have caused an hormonal imbalance. Indeed, the involvement of abscisic acid, cytokinins, and gibberellin related compounds was observed in leaves following root application of the biopolymer-based biostimulant. Nonetheless, the treatment triggered an accumulation of several metabolites involved in defense mechanisms against biotic and abiotic stresses, such as flavonoids, carotenoids, and glucosinolates, thus potentially improving resistance toward plant stresses. PMID: 29692795 [PubMed]

Deciphering hepatocellular carcinoma through metabolomics: from biomarker discovery to therapy evaluation.

Thu, 26/04/2018 - 14:04
Deciphering hepatocellular carcinoma through metabolomics: from biomarker discovery to therapy evaluation. Cancer Manag Res. 2018;10:715-734 Authors: Guo W, Tan HY, Wang N, Wang X, Feng Y Abstract Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer, with increasing prevalence worldwide. The mortality rate of HCC is similar to its incidence rate, which reflects its poor prognosis. At present, the diagnosis of HCC is still mostly dependent on invasive biopsy, imaging methods, and serum α-fetoprotein (AFP) testing. Because of the asymptomatic nature of early HCC, biopsy and imaging methods usually detect HCC at the middle-late stages. AFP has limited sensitivity and specificity, as many other nonmalignant liver diseases can also result in a very high serum level of AFP. Therefore, better biomarkers with higher sensitivity and specificity at earlier stages are greatly needed. Since metabolic reprogramming is an essential hallmark of cancer and the liver is the metabolic hub of living systems, it is useful to investigate HCC from a metabolic perspective. As a noninvasive and nondestructive approach, metabolomics provides holistic information on dynamically metabolic responses of living systems to both endogenous and exogenous factors. Therefore, it would be conducive to apply metabolomics in investigating HCC. In this review, we summarize recent metabolomic studies on HCC cellular, animal, and clinicopathologic models with attention to metabolomics as a biomarker in cancer diagnosis. Recent applications of metabolomics with respect to therapeutic and prognostic evaluation of HCC are also covered, with emphasis on the potential of treatment by drugs from natural products. In the last section, the current challenges and trends of future development of metabolomics on HCC are discussed. Overall, metabolomics provides us with novel insight into the diagnosis, prognosis, and therapeutic evaluation of HCC. PMID: 29692630 [PubMed]

metabolomics; +22 new citations

Wed, 25/04/2018 - 22:44
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 2018/04/25PubMed 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; +26 new citations

Tue, 24/04/2018 - 16:01
26 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 2018/04/24PubMed 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; +26 new citations

Tue, 24/04/2018 - 12:58
26 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 2018/04/24PubMed 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.

NMR-based metabolic toxicity of low-level Hg exposure to earthworms.

Sun, 22/04/2018 - 14:53
Related Articles NMR-based metabolic toxicity of low-level Hg exposure to earthworms. Environ Pollut. 2018 Apr 18;239:428-437 Authors: Tang R, Ding C, Dang F, Ma Y, Wang J, Zhang T, Wang X Abstract Mercury is a globally distributed toxicant to aquatic animals and mammals. However, the potential risks of environmental relevant mercury in terrestrial systems remain largely unclear. The metabolic profiles of the earthworm Eisenia fetida after exposure to soil contaminated with mercury at 0.77 ± 0.09 mg/kg for 2 weeks were investigated using a two-dimensional nuclear magnetic resonance-based (1H-13C NMR) metabolomics approach. The results revealed that traditional endpoints (e.g., mortality and weight loss) did not differ significantly after exposure. Although histological examination showed sub-lethal toxicity in the intestine as a result of soil ingestion, the underlying mechanisms were unclear. Metabolite profiles revealed significant decreases in glutamine and 2-hexyl-5-ethyl-3-furansulfonate in the exposed group and remarkable increases in glycine, alanine, glutamate, scyllo-inositol, t-methylhistidine and myo-inositol. More importantly, metabolic network analysis revealed that low mercury in the soil disrupted osmoregulation, amino acid and energy metabolisms in earthworms. A metabolic net link and schematic diagram of mercury-induced responses were proposed to predict earthworm responses after exposure to mercury at environmental relevant concentrations. These results improved the current understanding of the potential toxicity of low mercury in terrestrial systems. PMID: 29679940 [PubMed - as supplied by publisher]

Mechanisms of the active components from Korean pine nut preventing and treating d-galactose-induced aging rats.

Sun, 22/04/2018 - 14:53
Related Articles Mechanisms of the active components from Korean pine nut preventing and treating d-galactose-induced aging rats. Biomed Pharmacother. 2018 Apr 18;103:680-690 Authors: Zhang J, Lin W, Wu R, Liu Y, Zhu K, Ren J, Zhang S, Ling X Abstract Age-related neuronal injury and oxidative damage are the predominant factors for neurodegenerative diseases like Alzheimer's disease (AD). The aim of this study was to explore whether chronic administration of d-galactose (d-gal) can cause neuronal injury and oxidative damage, and to investigate the neuroprotective and antioxidative effects of the active components (UPNO-1) from Korean pine nut (Pinus koraiensis). Two dosing regimens were designed, one for the evaluation of preventive effects in which the rats were simultaneously administrated d-gal and UPNO-1/fishoil for 12 weeks, the other for the evaluation of therapeutic effects in which the rats were given d-gal for 8 weeks before treated with UPNO-1/selegiline for 8 weeks. The experimental results demonstrated that chronic administration of d-gal produced histopathological changes and increased neuronal apoptosis, and decreased significantly the activities of T-AOC, T-SOD and CAT. Additionally, a comprehensive metabolic profiling of d-gal-treated rats was performed for the first time to investigate the metabolic disorders in the hippocampus, cortex and plasma, and a total of 32 annotated metabolites were significantly increased or decreased in the modeled rats. Major disturbed metabolic pathways were fatty acid, glycerolphospholipid and arachidonic acid metabolic pathways. UPNO-1 significantly diminished neuronal apoptosis, ameliorated histopathological findings, and increased the activities of T-SOD and CAT but not T-AOC. Furthermore, UPNO-1 attenuated the decreased plasma levels of 3-oxooctanoic acid, l-tryptophan, 12-hydroxyheptadecanoic acid, lysophosphatidylcholine (16:0) (LPC(16:0)), LPC(18:3) and LPC(18:1) in the modeled rats. These results illustrated the mechanisms of d-gal induced neurotoxicity and oxidative stress and proved the positive effects of UPNO-1 on preventing and treating d-gal-induced-aging rats. PMID: 29679909 [PubMed - as supplied by publisher]

Integrated genomic and metabolomic profiling of ISC1, an emerging Leishmania donovani population in the Indian subcontinent.

Sun, 22/04/2018 - 14:53
Related Articles Integrated genomic and metabolomic profiling of ISC1, an emerging Leishmania donovani population in the Indian subcontinent. Infect Genet Evol. 2018 Apr 18;: Authors: Cuypers B, Berg M, Imamura H, Dumetz F, De Muylder G, Domagalska MA, Rijal S, Bhattarai NR, Maes I, Sanders M, Cotton JA, Meysman P, Laukens K, Dujardin JC Abstract Leishmania donovani is the responsible agent for visceral leishmaniasis (VL) in the Indian subcontinent (ISC). The disease is lethal without treatment and causes 0.2 to 0.4 million cases each year. Recently, reports of VL in Nepalese hilly districts have increased as well as VL cases caused by L. donovani from the ISC1 genetic group, a new and emerging genotype. In this study, we perform for the first time an integrated, untargeted genomics and metabolomics approach to characterize ISC1, in comparison with the Core Group (CG), main population that drove the last outbreak of VL in the ISC. We show that the ISC1 population is very different from the CG, both at genome and metabolome levels. These differences included SNPs, CNV and small indels in genes coding for known virulence factors, immunogens and surface proteins. Both genomic and metabolic approaches highlighted dissimilarities related to membrane lipids, the nucleotide salvage pathway and the urea cycle in ISC1 versus CG. Many of these pathways and molecules are important for the interaction with the host/extracellular environment. Altogether, our data predict major functional differences in ISC1 parasites, including virulence. Therefore, particular attention is required to monitor the fate of this emerging population in the ISC, especially in a post-VL elimination context. PMID: 29679745 [PubMed - as supplied by publisher]

A probiotic modulates the microbiome and immunity in multiple sclerosis.

Sun, 22/04/2018 - 14:53
Related Articles A probiotic modulates the microbiome and immunity in multiple sclerosis. Ann Neurol. 2018 Apr 20;: Authors: Tankou SK, Regev K, Healy BC, Tjon E, Laghi L, Cox LM, Kivisäkk P, Pierre IV, Lokhande H, Gandhi R, Cook S, Glanz B, Stankiewicz J, Weiner HL Abstract OBJECTIVE: Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: MS patients (N=9) and controls (N=13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium and Streptococcus twice daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy. Frozen peripheral blood mononuclear cells (PBMCs) were used for immune cell profiling. Stool samples were used for 16S rRNA profiling and metabolomics. RESULTS: Probiotic administration increased the abundance of several taxa known to be depleted in MS such as Lactobacillus. We found that probiotic use decreased the abundance of taxa previously associated with dysbiosis in MS including Akkermansia and Blautia. Predictive metagenomic analysis revealed a decrease in the abundance of several KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathways associated with altered gut microbiota function in MS patients such as methane metabolism following probiotic supplementation. At the immune level, probiotic administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of inflammatory monocytes, decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes as well as decreased HLA-DR MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA-DQA1 in controls. Probiotic induced increased in the abundance of Lactobacillus and Bifidobacterium were associated with decreased expression of MS risk allele HLA.DPB1 in controls. INTERPRETATION: Our results suggest that probiotic could have a synergistic effect with current MS therapies. This article is protected by copyright. All rights reserved. PMID: 29679417 [PubMed - as supplied by publisher]

Longitudinal urinary metabolomic profiling reveals metabolites for asthma development in early childhood.

Sun, 22/04/2018 - 14:53
Related Articles Longitudinal urinary metabolomic profiling reveals metabolites for asthma development in early childhood. Pediatr Allergy Immunol. 2018 Apr 21;: Authors: Chiu CY, Lin G, Cheng ML, Chiang MH, Tsai MH, Su KW, Hua MC, Liao SL, Lai SH, Yao TC, Yeh KW, Huang JL Abstract BACKGROUND: Several metabolites and altered metabolic pathways have been reported to be associated with asthma. However, longitudinal analysis of the dynamics of metabolites contributing to the development of asthma has not yet been fully clarified. METHODS: We sought to identify the metabolic mechanisms underlying asthma development in early childhood. Thirty children with asthma and paired healthy controls from a prospective birth cohort were enrolled. Time-series analysis of urinary metabolites collected at ages 1, 2, 3, and 4 years were assessed using 1 H-nuclear magnetic resonance (NMR) spectroscopy coupled with partial least-squares discriminant analysis (PLS-DA). Metabolites identified were studied in relation to changes over time in a linear mixed model for repeated measures. RESULTS: A total of 172 urine samples collected from the enrolled children were analyzed. Urinary metabolomics identified four metabolites significantly associated with childhood asthma development, with longitudinal analysis. Among them, dimethylamine, a metabolite produced by intestinal bacteria, appeared to shift from higher to lower level during asthma development. A persistent lower level of 1-methylnicotinamide and allantoin was found in children with asthma, with a peak difference at age 3 years (P = 0.032 and P = 0.021 respectively). Furthermore, a significant inverse correlation was found between allantoin and house dust mite sensitization (Spearman's r = -0.297 P = 0.035). CONCLUSIONS: Longitudinal urinary metabolomic profiling provides a link of microbe-environment interactions in the development of childhood asthma. 1-Methylnicotinamide and allantoin may participate in allergic reactions in response to allergen exposure, potentially serving as specific biomarkers for asthma. This article is protected by copyright. All rights reserved. PMID: 29679407 [PubMed - as supplied by publisher]

LC-MS/MS-Based Metabolome Analysis of Biochemical Pathways Altered by Food Limitation in Larvae of Ivory Shell, Babylonia areolata.

Sun, 22/04/2018 - 14:53
Related Articles LC-MS/MS-Based Metabolome Analysis of Biochemical Pathways Altered by Food Limitation in Larvae of Ivory Shell, Babylonia areolata. Mar Biotechnol (NY). 2018 Apr 20;: Authors: Fu J, Shen M, Shen Y, Lü W, Huang M, Luo X, Yu J, Ke C, You W Abstract Ivory shell, Babylonia areolata, is one of the commercially important mariculture species in China and South East Asia. Survival varies in the artificial hatching and larval rearing of B. areolata. Food deprivation may be involved in rearing mortality, and so, a better understanding of how larvae respond and adjust to starvation is needed. In this study, the metabolite profiles of newly hatched larvae with yolk (I), larvae with yolk exhaustion (II), larvae suffering 24 h starvation after yolk exhaustion (III), and larvae fed with exogenous nutrients after yolk exhaustion (IV) were analyzed by LC-MS/MS. Principal component and cluster analyses revealed differential abundance of metabolite profiles across groups. When compared to metabolite levels of the I group, significantly up-regulated metabolites included polyunsaturated fatty acids, phospholipids, nucleotide, amino acids, and their derivatives were found in the II group, indicating that organisms relied predominantly on glycerophospolipid metabolism and protein-based catabolism for energy production during this stage. During starvation after yolk exhaustion, the levels of all energy related metabolites were significantly reduced, but an increase in products of purine and pyrimidine metabolism indicated an insufficient energy supply and an increase in cellular disintegration. Larvae fed exogenous nutrients can have significantly improved metabolism compared to starved larvae. These findings suggest that metabolomics, using LC-MS/MS, can be used to assess the physiological status and food-affected metabolic changes affecting B. areolata larvae. PMID: 29679249 [PubMed - as supplied by publisher]

A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence.

Sun, 22/04/2018 - 14:53
Related Articles A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence. Geroscience. 2018 Apr 20;: Authors: Lewis KN, Rubinstein ND, Buffenstein R Abstract Mouse-sized naked mole-rats (Heterocephalus glaber), unlike other mammals, do not conform to Gompertzian laws of age-related mortality; adults show no age-related change in mortality risk. Moreover, we observe negligible hallmarks of aging with well-maintained physiological and molecular functions, commonly altered with age in other species. We questioned whether naked mole-rats, living an order of magnitude longer than laboratory mice, exhibit different plasma metabolite profiles, which could then highlight novel mechanisms or targets involved in disease and longevity. Using a comprehensive, unbiased metabolomics screen, we observe striking inter-species differences in amino acid, peptide, and lipid metabolites. Low circulating levels of specific amino acids, particularly those linked to the methionine pathway, resemble those observed during the fasting period at late torpor in hibernating ground squirrels and those seen in longer-lived methionine-restricted rats. These data also concur with metabolome reports on long-lived mutant mice, including the Ames dwarf mice and calorically restricted mice, as well as fruit flies, and even show similarities to circulating metabolite differences observed in young human adults when compared to older humans. During evolution, some of these beneficial nutrient/stress response pathways may have been positively selected in the naked mole-rat. These observations suggest that interventions that modify the aging metabolomic profile to a more youthful one may enable people to lead healthier and longer lives. PMID: 29679203 [PubMed - as supplied by publisher]

Thromboxane A2 facilitates IL-17A production from Vγ4+ γδ T cells and promotes psoriatic dermatitis in mice.

Sun, 22/04/2018 - 14:53
Related Articles Thromboxane A2 facilitates IL-17A production from Vγ4+ γδ T cells and promotes psoriatic dermatitis in mice. J Allergy Clin Immunol. 2018 Apr 17;: Authors: Ueharaguchi Y, Honda T, Kusuba N, Hanakawa S, Adachi A, Sawada Y, Otsuka A, Kitoh A, Dainichi T, Egawa G, Nakashima C, Nakajima S, Murata T, Ono S, Arita M, Narumiya S, Miyachi Y, Kabashima K Abstract Thromboxane A2-TP signaling facilitates IL-17A production from dermal Vγ4+ γδ T cells and promotes psoriatic dermatitis in mice. Regulation of TP activation may become a novel therapeutic target for psoriasis. PMID: 29678752 [PubMed - as supplied by publisher]

Severity of Allergic Rhinitis Assessed by Urine Metabolomic Profiling: Proof of Concept.

Sun, 22/04/2018 - 14:53
Related Articles Severity of Allergic Rhinitis Assessed by Urine Metabolomic Profiling: Proof of Concept. J Allergy Clin Immunol. 2018 Apr 17;: Authors: Adamko DJ, Khamis MM, Steacy LM, Regush S, Bryce R, Ellis AK Abstract Patients with chronic airway diseases tend to become "accustomed" to their impairments and fail to recognize the significance of their symptoms. We suggest that a metabolomic approach could become a diagnostic/monitoring solution in clinical trials or in a typical doctor's office. PMID: 29678748 [PubMed - as supplied by publisher]

Pages