PubMed
Targeted metabolomics analysis of aromatic amino acids and their gut microbiota-host co-metabolites in rat serum and urine by liquid chromatography with tandem mass spectrometry.
Targeted metabolomics analysis of aromatic amino acids and their gut microbiota-host co-metabolites in rat serum and urine by liquid chromatography with tandem mass spectrometry.
J Sep Sci. 2017 Jun 12;:
Authors: Zeng Y, Luo L, Hou W, Lu B, Gong J, Chen J, Zhang X, Han B, Xie Z, Liao Q
Abstract
Gut microbiota-host co-metabolites are closely related to various diseases. Monitoring dynamic changes of co-metabolites can provide a more comprehensive understanding of pathophysiology. Here, a novel liquid chromatography-tandem mass spectrometry method was performed for the analysis of aromatic amino acids and their gut microbiota-host co-metabolites in rat serum and urine. In the developed method, seven key gut microbiota-host co-metabolites were chromatographically separated on a Kinetex Phenyl-Hexyl column by gradient elution, and the run time was 6 min. Serum and urine were extracted by protein precipitation. This method was linear between 10.20 and 1000.00 ng/mL for phenylalanine and p-cresyl sulfate; 25.60-2500.00 ng/mL for tryptophan; 51.20-5000.00 ng/mL for tyrosine, indole and indoxyl sulfate; and 75.50-7500.00 ng/mL for p-cresol. The linearity, accuracy, precision and recovery of seven analytes were all satisfactory. The method was sufficiently sensitive and robust. It was successfully applied to characterize the alterations of gut microbiota-host co-metabolites in inflammatory disorders. All of these results suggest that the developed method is able to simultaneously monitor aromatic amino acids and their gut microbiota-host co-metabolites. This method will be expected to be a valuable tool for clinical researches and comprehensive studies of the pathophysiological roles. This article is protected by copyright. All rights reserved.
PMID: 28605162 [PubMed - as supplied by publisher]
Phenotyping of gut microbiota: Focus on capillary electrophoresis.
Phenotyping of gut microbiota: Focus on capillary electrophoresis.
Electrophoresis. 2017 Jun 12;:
Authors: Ferrer M, Raczkowska BA, Martínez-Martínez M, Barbas C, Rojo D
Abstract
The analysis of the microbial metabolome is crucial to fully understand the symbiotic relation between humans and microbes. That is why an explosion of metabolomics took place in the area. So far, at least several hundreds of microbial metabolites have been shown to be statistically altered when humans undergo a plethora of commonly faced perturbations. NMR and MS, usually coupled with GC, LC and CE have revealed their identities. CE is a robust analytical platform for the analysis of polar and ionic metabolites that are essential in order to assess the cells' activity. Due to its novelty, only 5 % of the metabolomics studies investigate gut microbiota using CE, even though the metabolites found by CE as being significantly altered in human microbiota represent around 23 % of the total number of metabolites identified by metabolomics tools. Herein, we discuss the advances of metabolomics in the frame of other OMICS techniques for human gut microbiota analysis. Afterwards, we focus on sample treatment, analytical methods and data processing in CE coupled to any detector that have been reported to date in order to enhance metabolite coverage in the art, and to identify metabolite markers that cannot be covered by other platforms but are of key importance for determining microbial activity and human health. This article is protected by copyright. All rights reserved.
PMID: 28605027 [PubMed - as supplied by publisher]
Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions.
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Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions.
Front Cell Infect Microbiol. 2017;7:213
Authors: Papa A, Tsergouli K, Tsioka K, Mirazimi A
Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans by bite of infected ticks or by direct contact with blood or tissues of viremic patients or animals. It causes to humans a severe disease with fatality up to 30%. The current knowledge about the vector-host-CCHFV interactions is very limited due to the high-level containment required for CCHFV studies. Among ticks, Hyalomma spp. are considered the most competent virus vectors. CCHFV evades the tick immune response, and following its replication in the lining of the tick's midgut, it is disseminated by the hemolymph in the salivary glands and reproductive organs. The introduction of salivary gland secretions into the host cells is the major route via which CCHFV enters the host. Following an initial amplification at the site of inoculation, the virus is spread to the target organs. Apoptosis is induced via both intrinsic and extrinsic pathways. Genetic factors and immune status of the host may affect the release of cytokines which play a major role in disease progression and outcome. It is expected that the use of new technology of metabolomics, transcriptomics and proteomics will lead to improved understanding of CCHFV-host interactions and identify potential targets for blocking the CCHFV transmission.
PMID: 28603698 [PubMed - in process]
Association of amine biomarkers with incident dementia and Alzheimer's disease in the Framingham Study.
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Association of amine biomarkers with incident dementia and Alzheimer's disease in the Framingham Study.
Alzheimers Dement. 2017 Jun 08;:
Authors: Chouraki V, Preis SR, Yang Q, Beiser A, Li S, Larson MG, Weinstein G, Wang TJ, Gerszten RE, Vasan RS, Seshadri S
Abstract
INTRODUCTION: The identification of novel biomarkers associated with Alzheimer's disease (AD) could provide key biological insights and permit targeted preclinical prevention. We investigated circulating metabolites associated with incident dementia and AD using metabolomics.
METHODS: Plasma levels of 217 metabolites were assessed in 2067 dementia-free Framingham Offspring Cohort participants (mean age = 55.9 ± 9.7 years; 52.4% women). We studied their associations with future dementia and AD risk in multivariate Cox models.
RESULTS: Ninety-three participants developed incident dementia (mean follow-up = 15.6 ± 5.2 years). Higher plasma anthranilic acid levels were associated with greater risk of dementia (hazard ratio [HR] = 1.40; 95% confidence interval [CI] = [1.15-1.70]; P = 8.08 × 10(-4)). Glutamic acid (HR = 1.38; 95% CI = [1.11-1.72]), taurine (HR = 0.74; 95% CI = [0.60-0.92]), and hypoxanthine (HR = 0.74; 95% CI = [0.60-0.92]) levels also showed suggestive associations with dementia risk.
DISCUSSION: We identified four biologically plausible, candidate plasma biomarkers for dementia. Association of anthranilic acid implicates the kynurenine pathway, which modulates glutamate excitotoxicity. The associations with hypoxanthine and taurine strengthen evidence that uric acid and taurine may be neuroprotective.
PMID: 28602601 [PubMed - as supplied by publisher]
Enantioselective bioaccumulation following exposure of adult zebrafish (Danio rerio) to epoxiconazole and its effects on metabolomic profile as well as genes expression.
Enantioselective bioaccumulation following exposure of adult zebrafish (Danio rerio) to epoxiconazole and its effects on metabolomic profile as well as genes expression.
Environ Pollut. 2017 Jun 07;229:264-271
Authors: Wang Y, Teng M, Wang D, Yan J, Miao J, Zhou Z, Zhu W
Abstract
Although epoxiconazole is the worldwidely used fungicide, limited information is known about its toxic effects and bioaccumulation behavior in freshwater ecosystems. In this study, zebrafish were exposed to epoxiconazole at concentrations of 100 and 1000 μg L(-1) for 21 d. (1)H NMR-based metabolomics analysis showed that low- and high-dose epoxiconazole exposure resulted in two similar but not identical patterns for the change of endogenous metabolites related to energy, lipid and amino acid metabolism. The expression of genes associated with mitochondrial respiratory chain, ATP synthesis and fatty acid β-oxidation were further measured to explore the reason for the disturbed energy metabolism, finding epoxiconazole had an inhibition effect on the genes expression of the above ways. Significant enantioselectivity was observed with (+)-epoxiconazole enrichment in the bioaccumulation process. These results will be of great importance in understanding the toxic effects induced by epoxiconazole and provide important basis for its comprehensive environmental assessment.
PMID: 28601015 [PubMed - as supplied by publisher]
Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis.
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Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis.
Clin Rheumatol. 2017 Jun 10;:
Authors: Xie X, Li F, Li S, Tian J, Chen JW, Du JF, Mao N, Chen J
Abstract
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressive joint erosion. Tumor necrosis factor (TNF) antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA. However, there continue to be one third of RA patients who have poor or no response to TNF antagonists. Following consideration of the uncertainty of therapeutic effects and the high price of TNF antagonists, it is worthy to predict the treatment responses before anti-TNF therapy. According to the comparisons between the responders and non-responders to TNF antagonists by omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, rheumatologists are eager to find significant biomarkers to predict the effect of TNF antagonists in order to optimize the personalized treatment in RA.
PMID: 28600618 [PubMed - as supplied by publisher]
Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG).
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Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG).
Bioorg Med Chem Lett. 2017 May 29;:
Authors: Globisch D, Eubanks LM, Shirey RJ, Pfarr KM, Wanji S, Debrah AY, Hoerauf A, Janda KD
Abstract
The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG's biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development.
PMID: 28600214 [PubMed - as supplied by publisher]
MetabolitePredict: a de-novo human metabolomics prediction system and its applications in rheumatoid arthritis.
Related Articles
MetabolitePredict: a de-novo human metabolomics prediction system and its applications in rheumatoid arthritis.
J Biomed Inform. 2017 Jun 06;:
Authors: Wang Q, Xu R
Abstract
Human metabolomics has great potential in disease mechanism understanding, early diagnosis, and therapy. Existing metabolomics studies are often based on profiling patient biofluids and tissue samples and are difficult owing to the challenges of sample collection and data processing. Here, we report an alternative approach and developed a computation-based prediction system, MetabolitePredict, for disease metabolomics biomarker prediction. We applied MetabolitePredict to identify metabolite biomarkers and metabolite targeting therapies for rheumatoid arthritis (RA), a last-lasting complex disease with multiple genetic and environmental factors involved. MetabolitePredict is a de-novo prediction system. It first constructs a disease-specific genetic profile using genes and pathways data associated with an input disease. It then constructs genetic profiles for a total of 259,170 chemicals/metabolites using known chemical genetics and human metabolomic data. MetabolitePredict prioritizes metabolites for a given disease based on the genetic profile similarities between disease and metabolites. We evaluated MetabolitePredict using 63 known RA-associated metabolites. MetabolitePredict found 24 of the 63 metabolites (recall: 0.38) and ranked them highly (mean ranking: top 4.13%, median ranking: top 1.10%, P-value: 5.08E-19). MetabolitePredict performed better than an existing metabolite prediction system, PROFANCY, in predicting RA-associated metabolites (PROFANCY: recall: 0.31, mean ranking: 20.91%, median ranking: 16.47%, P-value: 3.78E-7). Short-chain fatty acids (SCFAs), the abundant metabolites of gut microbiota in the fermentation of fiber, ranked highly (butyrate, 0.03%; acetate, 0.05%; propionate, 0.38%). Finally, we established MetabolitePredict's potential in novel metabolite targeting for disease treatment: MetabolitePredict ranked highly three known metabolite inhibitors for RA treatments (methotrexate:0.25%; leflunomide: 0.56%; sulfasalazine: 0.92%). MetabolitePredict is a generalizable disease metabolite prediction system. The only required input to the system is a disease name or a set of disease-associated genes. The web-based MetabolitePredict is available at: http://xulab.
CASE: edu/MetabolitePredict.
PMID: 28600026 [PubMed - as supplied by publisher]
Quantification of metabolites in dried blood spots by direct infusion high resolution mass spectrometry.
Related Articles
Quantification of metabolites in dried blood spots by direct infusion high resolution mass spectrometry.
Anal Chim Acta. 2017 Aug 01;979:45-50
Authors: de Sain-van der Velden MGM, van der Ham M, Gerrits J, Prinsen HCMT, Willemsen M, Pras-Raves ML, Jans JJ, Verhoeven-Duif NM
Abstract
Diagnosis and treatment of inborn errors of metabolism (IEM) require the analysis of a variety of metabolites. These compounds are usually quantified by targeted platforms. High resolution mass spectrometry (HRMS) has the potential to detect hundreds to thousands of metabolites simultaneously. A chip-based nanoelectrospray source (chip-based nanoESI) enables the direct infusion of biological samples. Major advantages of this system include high sample throughput, no sample carryover, and low sample consumption. The combination, chip-based nanoESI-HRMS enables untargeted metabolomics of biological samples but its potential for quantification of metabolites has not been reported. We investigated whether chip-based nanoESI-HRMS is suitable for quantification of metabolites in dried blood spots (DBS). After addition of internal standards, metabolites were extracted with methanol. Aliquots of each extract were analysed by chip-based nanoESI-HRMS operating in both positive and negative mode with an m/z window of 70-600 and a resolution of 140,000. Total run time was 4.5 min per sample and a full report could be generated within 40 min. Concentrations of all 21 investigated diagnostic metabolites in DBS as quantified by chip-based nanoESI-HRMS correlated well with those obtained by targeted liquid chromatography-tandem mass spectrometry. We conclude that chip-based nanoESI-HRMS is suitable for quantification.
PMID: 28599708 [PubMed - in process]
metabolomics; +17 new citations
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 2017/06/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
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The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice.
The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice.
PLoS One. 2017;12(6):e0178426
Authors: Bian X, Chi L, Gao B, Tu P, Ru H, Lu K
Abstract
Artificial sweeteners have been widely used in the modern diet, and their observed effects on human health have been inconsistent, with both beneficial and adverse outcomes reported. Obesity and type 2 diabetes have dramatically increased in the U.S. and other countries over the last two decades. Numerous studies have indicated an important role of the gut microbiome in body weight control and glucose metabolism and regulation. Interestingly, the artificial sweetener saccharin could alter gut microbiota and induce glucose intolerance, raising questions about the contribution of artificial sweeteners to the global epidemic of obesity and diabetes. Acesulfame-potassium (Ace-K), a FDA-approved artificial sweetener, is commonly used, but its toxicity data reported to date are considered inadequate. In particular, the functional impact of Ace-K on the gut microbiome is largely unknown. In this study, we explored the effects of Ace-K on the gut microbiome and the changes in fecal metabolic profiles using 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. We found that Ace-K consumption perturbed the gut microbiome of CD-1 mice after a 4-week treatment. The observed body weight gain, shifts in the gut bacterial community composition, enrichment of functional bacterial genes related to energy metabolism, and fecal metabolomic changes were highly gender-specific, with differential effects observed for males and females. In particular, ace-K increased body weight gain of male but not female mice. Collectively, our results may provide a novel understanding of the interaction between artificial sweeteners and the gut microbiome, as well as the potential role of this interaction in the development of obesity and the associated chronic inflammation.
PMID: 28594855 [PubMed - in process]
Metabolomics analysis of rice responses to salinity stress revealed elevation of serotonin, and gentisic acid levels in leaves of tolerant varieties.
Metabolomics analysis of rice responses to salinity stress revealed elevation of serotonin, and gentisic acid levels in leaves of tolerant varieties.
Plant Signal Behav. 2017 Jun 08;:0
Authors: Gupta P, De B
Abstract
A GC-MS based analytical approach was undertaken in order to understand the metabolomic responses of seedlings of two salt sensitive (Sujala and MTU 7029) and two tolerant varieties (Bhutnath, and Nonabokra) of indica rice (Oryza sativa L.) to NaCl induced stress. The four varieties responded differently to NaCl treatment with respect to the conserved primary metabolites (sugars, polyols, amino acids, organic acids and certain purine derivatives) of the leaf of rice seedlings. However, there were significant differences in salt induced production of chorismic acid derivatives. Serotonin level was increased in both the salt tolerant varieties in response to NaCl induced stress. In both the salt tolerant varieties, increased production of the signalling molecule gentisic acid in response to NaCl treatment was noticed. Salt tolerant varieties also produced increased level of ferulic acid and vanillic acid. In the salt sensitive varieties, cinnamic acid derivatives, 4-hydroxycinnamic acid (in Sujala) and 4-hydroxybenzoic acid (in MTU 7029), were elevated in the leaves. So increased production of the two signalling molecules serotonin and gentisic acid may be considered as two important biomarker compounds produced in tolerant varieties contributing towards NaCl tolerance..
PMID: 28594277 [PubMed - as supplied by publisher]
Novel serum metabolomics-based approach by gas chromatography/triple quadrupole mass spectrometry for detection of human skin cancers: Candidate biomarkers.
Related Articles
Novel serum metabolomics-based approach by gas chromatography/triple quadrupole mass spectrometry for detection of human skin cancers: Candidate biomarkers.
J Dermatol. 2017 Jun 08;:
Authors: Fukumoto T, Nishiumi S, Fujiwara S, Yoshida M, Nishigori C
Abstract
Skin cancer incidence rates are continuing to rise; however, if detected at an early stage, they can be cured with minimally invasive treatment. Therefore, the identification of novel and robust biomarkers for the early detection of skin cancer is required to improve the quality of life of the patient after treatment. In the present study, we aimed to identify novel biomarkers of skin cancers. We carried out serum metabolomics using gas chromatography/triple quadrupole mass spectrometry for two types of skin cancer: squamous cell carcinoma and melanoma. The changes in the expression of metabolites compared with healthy volunteers were analyzed by principal component analysis. Among all 118 metabolites, 27 in patients with squamous cell carcinoma and 33 in patients with melanoma showed significant changes in comparison with healthy volunteers. Principal component analysis showed that both skin cancer groups could be distinguished from the healthy volunteers group. We further investigated the specific metabolites most useful for these distinctions. In the squamous cell carcinoma group, these metabolites were glycerol, 4-hydroxybenzoic acid, sebacic acid, fucose and suberic acid. In the melanoma group, these metabolites were glutamic acid, sebacic acid, suberic acid, 4-hydroxybenzoic acid and phenylalanine. The present study identified several metabolites that were distinct for certain skin cancer types, which could potentially be used as diagnostic biomarkers leading to novel clinical management strategies.
PMID: 28593747 [PubMed - as supplied by publisher]
Second generation multiple reaction monitoring assays for enhanced detection of ultra-low abundance Mycobacterium tuberculosis peptides in human serum.
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Second generation multiple reaction monitoring assays for enhanced detection of ultra-low abundance Mycobacterium tuberculosis peptides in human serum.
Clin Proteomics. 2017;14:21
Authors: Mehaffy C, Dobos KM, Nahid P, Kruh-Garcia NA
Abstract
BACKGROUND: Mycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), the number one cause of death due to an infectious disease. TB diagnosis is performed by microscopy, culture or PCR amplification of bacterial DNA, all of which require patient sputum or the biopsy of infected tissue. Detection of mycobacterial products in serum, as biomarkers of diagnosis or disease status would provide an improvement over current methods. Due to the low-abundance of mycobacterial products in serum, we have explored exosome enrichment to improve sensitivity. Mtb resides intracellularly where its secreted proteins have been shown to be packaged into host exosomes and released into the bloodstream. Exosomes can be readily purified assuring an enrichment of mycobacterial analytes from the complex mix of host serum proteins.
METHODS: Multiple reaction monitoring assays were optimized for the enhanced detection of 41 Mtb peptides in exosomes purified from the serum of individuals with TB. Exosomes isolated from the serum of healthy individuals was used to create and validate a unique data analysis algorithm and identify filters to reduce the rate of false positives, attributed to host m/z interference. The final optimized method was tested in 40 exosome samples from TB positive patients.
RESULTS: Our enhanced methods provide limit of detection and quantification averaging in the low femtomolar range for detection of mycobacterial products in serum. At least one mycobacterial peptide was identified in 92.5% of the TB positive patients. Four peptides from the Mtb proteins, Cfp2, Mpt32, Mpt64 and BfrB, show normalized total peak areas significantly higher in individuals with active TB as compared to healthy controls; three of the peptides from these proteins have not previously been associated with serum exosomes from individuals with active TB disease. Some of the detected peptides were significantly associated with specific geographical locations, highlighting potential markers that can be linked to the Mtb strains circulating within each given region.
CONCLUSIONS: An enhanced MRM method to detect ultra-low abundance Mtb peptides in human serum exosomes is demonstrated, highlighting the potential of this methodology for TB diagnostic biomarker development.
PMID: 28592925 [PubMed - in process]
Lower affinity of isradipine for L-type Ca(2+) channels during substantia nigra dopamine neuron-like activity: implications for neuroprotection in Parkinson's disease.
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Lower affinity of isradipine for L-type Ca(2+) channels during substantia nigra dopamine neuron-like activity: implications for neuroprotection in Parkinson's disease.
J Neurosci. 2017 Jun 07;:
Authors: Ortner NJ, Bock G, Dougalis A, Kharitonova M, Duda J, Hess S, Tuluc P, Pomberger T, Stefanova N, Pitterl F, Ciossek T, Oberacher H, Draheim HJ, Kloppenburg P, Liss B, Striessnig J
Abstract
Ca(2+)-influx through L-type Ca(2+)-channels (LTCCs) is associated with activity-related stressful oscillations of Ca(2+)-levels within dopaminergic (DA) neurons in the substantia nigra (SN), which may contribute to their selective degeneration in Parkinson's disease (PD). LTCC blockers were neuroprotective in mouse neurotoxin models of PD and isradipine is currently undergoing testing in a phase-III clinical trial in early PD. We report no evidence for neuroprotection by in vivo pretreatment with therapeutically relevant isradipine plasma levels, or Cav1.3 LTCC -deficiency in 6-OHDA treated male mice. To explain this finding, we investigated the pharmacological properties of human LTCCs during SN DA-like and arterial smooth muscle (aSM)-like activity patterns using whole-cell patch-clamp recordings in HEK293-cells (Cav1.2 α1-subunit, long and short Cav1.3 α1-subunit splice-variants; β3/α2δ1). During SN DA-like pacemaking, only Cav1.3 variants conducted Ca(2+)-current (ICa) at subthreshold potentials between action potentials. SN DA-like burst activity increased integrated ICa during (Cav1.2+Cav1.3) and after (Cav1.3) the burst. Isradipine inhibition was splice-variant and isoform-dependent, with a 5 to 11-fold lower sensitivity to Cav1.3 variants during SN DA-like pacemaking compared to Cav1.2 during aSM-like activity. Supratherapeutic isradipine concentrations reduced the pacemaker precision of adult mouse SN DA neurons but did not affect their somatic Ca(2+)-oscillations. Our data predicts that Cav1.2 and Cav1.3 splice-variants contribute differentially to Ca(2+)-load in SN DA neurons, with prominent Cav1.3-mediated ICa between action potentials and after bursts. The failure of therapeutically relevant isradipine levels to protect SN DA neurons can be explained by weaker state-dependent inhibition of SN DA LTCCs as compared to aSM Cav1.2.SIGNIFICANCE STATEMENTThe high vulnerability of dopamine (DA) neurons in the substantia nigra (SN) to neurodegenerative stressors causes Parkinson's disease (PD). Ca(2+)-influx through voltage-gated L-type Ca(2+)-channels (LTCCs), in particular Cav1.3, appears to contribute to this vulnerability, and the LTCC inhibitor isradipine is currently being tested as a neuroprotective agent for PD in a phase-III clinical trial. However, in our study isradipine plasma concentrations approved for therapy were not neuroprotective in a PD mouse model. We provide an explanation for this observation by demonstrating that during SN DA-like neuronal activity LTCCs are less sensitive to isradipine than Cav1.2 LTCCs in resistance blood vessels (mediating dose-limiting vasodilating effects) and even at supratherapeutic concentrations isradipine fails to reduce somatic Ca(2+)-oscillations of SN DA neurons.TH - tyrosine hydroxylase; UV-LMD - UV-laser-microdissection; V0.5 - voltage of half-maximal activation; Vmax - voltage of maximal activation; VTA - ventral tegmental area.
PMID: 28592699 [PubMed - as supplied by publisher]
Exploring Cancer Metabolism using Stable Isotope Resolved Metabolomics (SIRM).
Related Articles
Exploring Cancer Metabolism using Stable Isotope Resolved Metabolomics (SIRM).
J Biol Chem. 2017 Jun 07;:
Authors: Bruntz RC, Lane AN, Higashi RM, Fan TW
Abstract
Metabolic reprogramming is a hallmark of cancer. The changes in metabolism are adaptive to permit proliferation, survival and eventually metastasis in a harsh environment. Stable Isotope Resolved Metabolomics (SIRM) is an approach that uses advanced approaches of NMR and mass spectrometry to analyze the fate of individual atoms from stable isotope-enriched precursors to products to deduce metabolic pathways and networks. The approach can be applied to a wide range of biological systems including human subjects. This review focuses on the applications of SIRM to cancer metabolism and its use in understanding drug actions.
PMID: 28592486 [PubMed - as supplied by publisher]
[Gas chromatography-mass spectrometry based urinary metabolomics in very low birth weight premature infants].
Related Articles
[Gas chromatography-mass spectrometry based urinary metabolomics in very low birth weight premature infants].
Zhonghua Er Ke Za Zhi. 2017 Jun 02;55(6):434-438
Authors: Li ST, Huang XL, Wu SG, Ma YM, Shi CC, Xiao X, Hao H
Abstract
Objective: To investigate the urinary metabolic spectrum and pathways in very low birth weight (VLBW) premature infants. Method: A prospective case-control study was conducted to collect and compare the data of VLBW premature infants and full term infants from the Sixth Affiliated Hospital of Sun Yet-Sen University in 2014. Within 24 hours after birth, urine specimens in each group were collected. Metabolites of urine samples including amino acid, fatty acid and organic acid were detected using the urease pre-processing and gas chromatography mass spectrometry (GC-MS) technology. Using the orthogonal partial least squares discriminant analysis (OPLS-DA), the biomarkers and differences between the two groups were found. The online metabolic pathway website was explored and multivariable analysis was conducted to investigate the valuable pathways and biomarkers related to the prematurity. Result: A total of 20 VLBW premature infants were enrolled, among whom 11 were male, 9 were female; and 20 full term infants were enrolled, among whom 9 were male, 11 were female. The urinary metabolites were established and compared between the VLBW premature and term infants. The investigation showed that the following nine pathways were enriched: amino-acyl-tRNA biosynthesis(P=0.000), lysine degradation(P=0.007), fatty acid biosynthesis(P=0.008), pyrimidine metabolism(P=0.014), pantothenate and CoA biosynthesis(P=0.022), valine, leucine and isoleucine biosynthesis(P=0.022), lysine biosynthesis(P=0.031), glycerolipid metabolism(P=0.046), and valine, leucine and isoleucine degradation(P=0.031). Almost all the metabolites decreased except for the glyceric acid exhibiting a higher content in the VLBW premature infant. 12 potential biomarkers were explored with the most significant covariance and correlation, within which stearic acid, palmiticacid, myristic acid, β-amino-isobutyric acid, and uric acid were lower, while myo-inositol, mannitol, glycine, glucose1, glucose2, glyceric acid and N-acetyl-tyrosine were higher in the VLBW premature group compared with the control group. Conclusion: There is a significant difference between the VLBW premature infants and full-term infants in the metabolic state and pathways. The urease pre-processing and GC-MS technology followed by the OPLS-DA and multivariable analysis to investigate VLBW premature infants' urinary metabolites is a valuable method to evaluate the patients' metabolism.
PMID: 28592011 [PubMed - in process]
Plasma Metabonomic Profiling of Diabetic Retinopathy.
Related Articles
Plasma Metabonomic Profiling of Diabetic Retinopathy.
Diabetes. 2016 Apr;65(4):1099-108
Authors: Chen L, Cheng CY, Choi H, Ikram MK, Sabanayagam C, Tan GS, Tian D, Zhang L, Venkatesan G, Tai ES, Wang JJ, Mitchell P, Cheung CM, Beuerman RW, Zhou L, Chan EC, Wong TY
Abstract
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults. Patients with diabetes often develop DR despite appropriate control of systemic risk factors, suggesting the involvement of other pathogenic factors. We hypothesize that the plasma metabolic signature of DR is distinct and resolvable from that of diabetes alone. A nested population-based case-control metabonomic study was first performed on 40 DR cases and 40 control subjects with diabetes using gas chromatography-mass spectrometry. Eleven metabolites were found to be correlated with DR, and the majority were robust when adjusted for metabolic risk factors and confounding kidney disease. The metabolite markers 2-deoxyribonic acid; 3,4-dihydroxybutyric acid; erythritol; gluconic acid; and ribose were validated in an independent sample set with 40 DR cases, 40 control subjects with diabetes, and 40 individuals without diabetes. DR cases and control subjects with diabetes were matched by HbA1c in the validation set. Activation of the pentose phosphate pathway was identified from the list of DR metabolite markers. The identification of novel metabolite markers for DR provides insights into potential new pathogenic pathways for this microvascular complication and holds translational value in DR risk stratification and the development of new therapeutic measures.
PMID: 26822086 [PubMed - indexed for MEDLINE]
metabolomics; +17 new citations
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 2017/06/08PubMed 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; +20 new citations
20 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 2017/06/07PubMed 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.