PubMed
Interest of metabonomic approach in environmental nephrotoxicants: Application to aristolochic acid exposure.
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Interest of metabonomic approach in environmental nephrotoxicants: Application to aristolochic acid exposure.
Food Chem Toxicol. 2017 Oct;108(Pt A):19-29
Authors: Duquesne M, Declèves AE, De Prez E, Nortier J, Colet JM
PMID: 28694082 [PubMed - indexed for MEDLINE]
Mass Spectrometry Imaging, Laser Capture Microdissection, and LC-MS/MS of the Same Tissue Section.
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Mass Spectrometry Imaging, Laser Capture Microdissection, and LC-MS/MS of the Same Tissue Section.
J Proteome Res. 2017 Aug 04;16(8):2993-3001
Authors: Dilillo M, Pellegrini D, Ait-Belkacem R, de Graaf EL, Caleo M, McDonnell LA
Abstract
Mass spectrometry imaging (MSI) is able to simultaneously record the distributions of hundreds of molecules directly from tissue. Rapid direct tissue analysis is essential for MSI in order to maintain spatial localization and acceptable measurement times. The absence of an explicit analyte separation/purification step means MSI lacks the depth of coverage of LC-MS/MS. In this work, we demonstrate how atmospheric pressure MALDI-MSI enables the same tissue section to be first analyzed by MSI, to identify regions of interest that exhibit distinct molecular signatures, followed by localized proteomics analysis using laser capture microdissection isolation and LC-MS/MS.
PMID: 28648079 [PubMed - indexed for MEDLINE]
Integrative Analysis of Renal Ischemia/Reperfusion Injury and Remote Ischemic Preconditioning in Mice.
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Integrative Analysis of Renal Ischemia/Reperfusion Injury and Remote Ischemic Preconditioning in Mice.
J Proteome Res. 2017 Aug 04;16(8):2877-2886
Authors: Cho K, Min SI, Ahn S, Min SK, Ahn C, Yu KS, Jang IJ, Cho JY, Ha J
Abstract
Remote ischemic preconditioning (RIPC) is a strategy to induce resistance in a target organ against the oxidative stress and injury caused by ischemia and reperfusion (IR). RIPC harnesses the body's endogenous protective capabilities through brief episodes of IR applied in organs remote from the target. Few studies have analyzed this phenomenon in the kidney. Furthermore, the window of protection representing RIPC efficacy has not been fully elucidated. Here, we performed a multiomics study to specify those associated with protective effects of RIPC against the IR injury. A total of 30 mice were divided to four groups: sham, IR only, late RIPC + IR, and early RIPC + IR. We found that IR clearly led to tubular injury, whereas both preconditioning groups exhibited attenuated injury after the insult. In addition, renal IR injury produced changes of the metabolome in kidney, serum, and urine specimens. Furthermore, distinctive mRNA and associated protein expression changes supported potential mechanisms. Our findings revealed that RIPC effectively reduces renal damage after IR and that the potential mechanisms differed between the two time windows of protection. These results may potentially be extended to humans to allow non- or minimally invasive diagnosis of renal IR injury and RIPC efficacy.
PMID: 28627174 [PubMed - indexed for MEDLINE]
Metabolome analysis of effect of aspirin on Drosophila lifespan extension.
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Metabolome analysis of effect of aspirin on Drosophila lifespan extension.
Exp Gerontol. 2017 Sep;95:54-62
Authors: Song C, Zhu C, Wu Q, Qi J, Gao Y, Zhang Z, Gaur U, Yang D, Fan X, Yang M
Abstract
Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin-treated flies. The results identified 404 active metabolites in addition to the extended lifespan and improved healthspan in fly. There were 28 metabolites having significant changes between aspirin-treated group and the control group, out of which 22 compounds were found to have detailed information. These compounds are reported to have important functions in energy metabolism, amino sugar metabolism, and urea metabolism, indicating that aspirin might be playing positive roles in the fly's lifespan and healthspan improvement. Because of the conservation of major longevity pathways and mechanisms in different species, the health benefits of aspirin administration could be extended to other animals and humans as well.
PMID: 28457986 [PubMed - indexed for MEDLINE]
Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis.
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Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis.
Clin Transl Sci. 2017 Jul;10(4):292-301
Authors: Roda A, Aldini R, Camborata C, Spinozzi S, Franco P, Cont M, D'Errico A, Vasuri F, Degiovanni A, Maroni L, Adorini L
Abstract
Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analog and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to carbon tetrachloride-induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BAs. After administration of OCA (30 mg/kg), we used liquid chromatography-mass spectrometry to measure OCA, its metabolites, and BAs at different timepoints in various organs and fluids. Plasma and hepatic concentrations of OCA and BAs were higher in cirrhotic rats than in controls. OCA and endogenous BAs had similar metabolic pathways in cirrhotic rats, although OCA hepatic and intestinal clearance were lower than in controls. BAs' qualitative and quantitative compositions were not modified by a single administration of OCA. In all the matrices studied, OCA concentrations were significantly lower than those of endogenous BAs, potentially much more cytotoxic.
PMID: 28411380 [PubMed - indexed for MEDLINE]
metabolomics; +46 new citations
46 new pubmed citations were retrieved for your search.
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metabolomics
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Citations may include links to full-text content from PubMed Central and publisher web sites.
metabolomics; +18 new citations
18 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 2018/05/15PubMed 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; +18 new citations
18 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 2018/05/15PubMed 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.
Analyzing omics data by pair-wise feature evaluation with horizontal and vertical comparisons.
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Analyzing omics data by pair-wise feature evaluation with horizontal and vertical comparisons.
J Pharm Biomed Anal. 2018 May 01;157:20-26
Authors: Huang X, Lin X, Zhou L, Su B
Abstract
Feature relationships are complex and may contain important information. k top scoring pairs (k-TSP) studies feature relationships by the horizontal comparison. This study examines feature relationships and proposes vertical and horizontal k-TSP (VH-k-TSP) to identify the discriminative feature pairs by evaluating feature pairs based on the vertical and horizontal comparisons. Complexity is introduced to compute the discriminative abilities of feature pairs by means of these two comparisons. VH-k-TSP was compared with support vector machine-recursive feature elimination, relative simplicity-support vector machine, k-TSP and M-k-TSP on nine public genomics datasets. For multi-class problems, one-to-one method was used. The experiments showed that VH-k-TSP outperformed the four methods in most cases. Then, VH-k-TSP was applied to a metabolomics data of liver disease. An accuracy rate of 88.11 ± 3.30% in discrimination between cirrhosis and hepatocellular carcinoma was obtained by VH-k-TSP, better than 77.39 ± 4.10% and 79.28 ± 3.73% obtained by k-TSP and M-k-TSP, respectively. Hence combining the vertical and horizontal comparisons could define more discriminative feature pairs.
PMID: 29754039 [PubMed - as supplied by publisher]
Nicotinamide phosphoribosyltransferase regulates cocaine reward through Sirtuin 1.
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Nicotinamide phosphoribosyltransferase regulates cocaine reward through Sirtuin 1.
Exp Neurol. 2018 May 10;:
Authors: Kong J, Du C, Jiang L, Jiang W, Deng P, Shao X, Zhang B, Li Y, Zhu R, Zhao Q, Fu D, Gu H, Luo L, Long H, Zhao Y, Cen X
Abstract
Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis in mammals, converts nicotinamide into nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD, a component that is critical for cell energy metabolism and survival. Sirtuin 1 (SIRT1), an NAD-dependent histone deacetylase, plays an important role in mediating memory and synaptic plasticity. Here, we found that NAMPT was significantly upregulated in the ventral tegmental area (VTA) of cocaine-conditioned mice. Intraperitoneal or intra-VTA injection of FK866, a specific inhibitor of NAMPT, significantly attenuated cocaine reward. However, such effects were clearly repressed by intra-VTA expression of NAMPT or supplementation with NMN. Using 1H-nuclear magnetic resonance metabolomic analysis, we found that the content of NAD and NMN were increased in the VTA of cocaine-conditioned mice; moreover, the expression of SIRT1 was also upregulated. Interestingly, the inhibitory effect of FK866 on cocaine reward was significantly weakened in Sirt1 midbrain conditional knockout mice. Our results suggest that NAMPT-mediated NAD biosynthesis may modify cocaine behavioral effects through SIRT1. Moreover, our findings reveal that the interplay between NAD biosynthesis and SIRT1 regulation may comprise a novel regulatory pathway that responds to chronic cocaine stimuli.
PMID: 29753648 [PubMed - as supplied by publisher]
Reserve Flux Capacity in the Pentose Phosphate Pathway Enables Escherichia coli's Rapid Response to Oxidative Stress.
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Reserve Flux Capacity in the Pentose Phosphate Pathway Enables Escherichia coli's Rapid Response to Oxidative Stress.
Cell Syst. 2018 May 02;:
Authors: Christodoulou D, Link H, Fuhrer T, Kochanowski K, Gerosa L, Sauer U
Abstract
To counteract oxidative stress and reactive oxygen species (ROS), bacteria evolved various mechanisms, primarily reducing ROS through antioxidant systems that utilize cofactor NADPH. Cells must stabilize NADPH levels by increasing flux through replenishing metabolic pathways like pentose phosphate (PP) pathway. Here, we investigate the mechanism enabling the rapid increase in NADPH supply by exposing Escherichia coli to hydrogen peroxide and quantifying the immediate metabolite dynamics. To systematically infer active regulatory interactions governing this response, we evaluated ensembles of kinetic models of glycolysis and PP pathway, each with different regulation mechanisms. Besides the known inactivation of glyceraldehyde 3-phosphate dehydrogenase by ROS, we reveal the important allosteric inhibition of the first PP pathway enzyme by NADPH. This NADPH feedback inhibition maintains a below maximum-capacity PP pathway flux under non-stress conditions. Relieving this inhibition instantly increases PP pathway flux upon oxidative stress. We demonstrate that reducing cells' capacity to rapidly reroute their flux through the PP pathway increases their oxidative stress sensitivity.
PMID: 29753645 [PubMed - as supplied by publisher]
A network pharmacology-integrated metabolomics strategy for clarifying the difference between effective compounds of raw and processed Farfarae flos by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry.
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A network pharmacology-integrated metabolomics strategy for clarifying the difference between effective compounds of raw and processed Farfarae flos by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry.
J Pharm Biomed Anal. 2018 May 04;156:349-357
Authors: Ding M, Li Z, Yu XA, Zhang D, Li J, Wang H, He J, Gao XM, Chang YX
Abstract
This study aimed to clarify the difference between the effective compounds of raw and processed Farfarae flos using a network pharmacology-integrated metabolomics strategy. First, metabolomics data were obtained by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS). Then, metabolomics analysis was developed to screen for the influential compounds that were different between raw and processed Farfarae flos. Finally, a network pharmacology approach was applied to verify the activity of the screened compounds. As a result, 4 compounds (chlorogenic acid, caffeic acid, rutin and isoquercitrin) were successfully screened, identified, quantified and verified as the most influential effective compounds. They may synergistically inhibit the p38, JNK and ERK-mediated pathways, which would induce the inhibition of the expression of the IFA virus. The results revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful tool for discovering the effective compounds that were responsible for the difference between raw and processed Chinese herbs.
PMID: 29753281 [PubMed - as supplied by publisher]
Identification and efficacy of glycine, serine and threonine metabolism in potentiating kanamycin-mediated killing of Edwardsiella piscicida.
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Identification and efficacy of glycine, serine and threonine metabolism in potentiating kanamycin-mediated killing of Edwardsiella piscicida.
J Proteomics. 2018 May 09;:
Authors: Ye JZ, Lin XM, Cheng ZX, Su YB, Li WX, Ali FM, Zheng J, Peng B
Abstract
We previously showed that glucose potentiated kanamycin to kill multidrug-resistant Edwardsiella piscicida through activation of the TCA cycle. However, whether other regulatory mechanism is involved requires further investigation. By quantitative proteomics technology, iTRAQ, we systematically mapped the altered proteins in the presence of glucose and identified 94 differentially expressed proteins. The analysis of the altered proteins by pathways, amino acid biosynthesis and metabolism were enriched. And the most significantly altered eight amino acids tyrosine, phenylalanine, valine, leucine, isoleucine, glycine, serine and threonine were investigated for their potentiation of kanamycin to kill EIB202, where glycine, serine and threonine showed the strongest efficacy than the others. The combinations of glycine and serine or glucose with glycine, serine or threonine had the best effects. Moreover, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and succinate dehydrogenase activities were increased as well as the proton motive force (PMF) and intracellular kanamycin. Finally, inhibitors that disrupt PMF production abolished the potentiation. These results shed light on the mechanism of how glucose promoting the amino acids biosynthesis and metabolism to potentiate kanamycin to kill antibiotic-resistant bacteria. More importantly, our results suggested that adjusting amino acid biosynthesis and metabolism might be a strategy to become phenotypic resistance to antibiotics in bacteria.
SIGNIFICANCE: Tackling antibiotic resistance is an emerging issue in current years. Despite the efforts made toward developing new antibiotics, the progress is still lagged behind expectation. Novel strategies are required. The use of metabolite to revert antibiotic resistant is highly appreciated in recent years due to the less toxicity, more economic and high efficacy. As a continued study of our previous report on glucose potentiating kanamycin to kill antibiotic-resistant bacteria. The current study further expands the previous discovery on the mechanism of how glucose potentiate this effect. This result provides more basis on the action of glucose in reverting antibiotic resistance. And more importantly, we may derive more metabolites other than glucose to manage antibiotic resistance.
PMID: 29753025 [PubMed - as supplied by publisher]
Metabolomic Analysis of Overactive Bladder in Male Patients: Identification of Potential Metabolite Biomarkers.
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Metabolomic Analysis of Overactive Bladder in Male Patients: Identification of Potential Metabolite Biomarkers.
Urology. 2018 May 09;:
Authors: Shimura H, Mitsui T, Kira S, Ihara T, Sawada N, Nakagomi H, Miyamoto T, Tsuchiya S, Kanda M, Takeda M
Abstract
OBJECTIVES: To identify metabolites that are associated with an overactive bladder (OAB) using metabolomics.
PATIENTS AND METHODS: A total of 58 males without apparent neurological disease completed 24-hr bladder diaries of their micturition behavior and International Prostate Symptom Score (IPSS) for the assessment of micturition behavior and lower urinary tract symptoms. Urgency was defined as an IPSS urgency score of ≥2 (OAB group), and patients with IPSS urgency scores of ≤1 belonged to the control group. A comprehensive study of plasma metabolites was also conducted using capillary electrophoresis time-of-flight mass spectrometry. Metabolite levels were compared between the control and OAB groups using the Mann-Whitney U test. Potential metabolite biomarkers were selected using multivariate logistic regression analysis.
RESULTS: Of the 58 subjects, the control and OAB groups consisted of 32 and 26 males, respectively. Nocturnal urinary volume, 24-hr micturition frequency, nocturnal micturition frequency, and the nocturia index were significantly higher in the OAB group. Metabolomic analysis revealed 60 metabolites in the subjects' plasma. The levels of 11 metabolites differed between and the control and OAB groups. Multivariate analysis showed that an increased glutamate level and reduced arginine, glutamine, and inosine monophosphate levels are significantly associated with OAB in males. Reduced levels of asparagine and hydroxyproline could also be associated with OAB.
CONCLUSIONS: Urgency is associated with abnormal metabolism. Analyses of amino acid profiles might aid the search for new treatment targets for OAB.
PMID: 29752971 [PubMed - as supplied by publisher]
Metabolomic comparison between wild Ophiocordyceps Sinensis and artificial cultured Cordyceps militaris.
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Metabolomic comparison between wild Ophiocordyceps Sinensis and artificial cultured Cordyceps militaris.
Biomed Chromatogr. 2018 May 11;:e4279
Authors: Chen L, Liu Y, Guo Q, Zheng Q, Zhang W
Abstract
In this study, a systematic research on the metabolome differences between wild Ophiocordyceps sinensis (O. sinensis) and artificial cultured Cordyceps militaris (C. militaris) was conducted using liquid chromatography-mass spectrometry. Principal components analysis (PCA) and Orthogonal projection on latent structure-discriminant analysis (OPLS-DA) results showed that C. militaris grown on solid rice medium (R-CM) and C. militaris grown on tussah pupa (T-CM) evidently separated and individually separated from wild O. sinensis, indicating the metabolome difference among wild O. sinensis, R-CM and T-CM. The metabolome differences between R-CM and T-CM indicated that C. militaris could accommodate to culture medium by different metabolic regulation. Hierarchical clustering analysis (HCA) was further performed to cluster the differential metabolites and samples based on their metabolic similarity. The higher content of amino acids (pyroglutamic acid, glutamic acid, histidine, phenylalanine and arginine), unsaturated fatty acid (linolenic acid and linoleic acid), peptides, mannitol, adenosine and succinoadenosine in O. sinensis make it as an excellent choice as traditional Chinese medicine for invigoration or nutritional supplementation. Similar compositions with O. sinensis and easy cultivation make artificial cultured C. militaris possible as alternatives as O. sinensis.
PMID: 29752731 [PubMed - as supplied by publisher]
NMR metabolomic study of blood plasma in ischemic and ischemically preconditioned rats: an increased level of ketone bodies and decreased content of glycolytic products 24 h after global cerebral ischemia.
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NMR metabolomic study of blood plasma in ischemic and ischemically preconditioned rats: an increased level of ketone bodies and decreased content of glycolytic products 24 h after global cerebral ischemia.
J Physiol Biochem. 2018 May 11;:
Authors: Baranovicova E, Grendar M, Kalenska D, Tomascova A, Cierny D, Lehotsky J
Abstract
Cardiac arrest is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia at global level is essential for the prevention and ischemic patient's treatment. In this study, we used a global cerebral ischemia induced by four-vessel occlusion as an established animal model for ischemic stroke to investigate metabolic changes after 24 h reperfusion, when transitions occur due to the onset of delayed neuronal death. We also focused on the endogenous phenomenon known as ischemic tolerance by the pre-ischemic treatment. The experiments were carried out on blood plasma samples as easily available and metabolically reflecting the overall changes in injured organism. Our results imply that disturbed glycolysis pathway, as a consequence of ischemic injury, leads to the increased level of ketone bodies (acetone, acetoacetate and β-hydroxybutyrate) along with increased utilization of triacylglycerols in plasma of ischemic and ischemically preconditioned rats. Complementary to, a decreased level of glycolytic intermediates (lactate, pyruvate, acetate) with increased level of glucose was found in ischemic and preconditioned animals. The protective effect of ischemic preconditioning on metabolome recovery was demonstrated by significantly increased level of creatine compared to ischemic, non-preconditioned rats. We also document that acetoacetate, pyruvate, lactate, and leucine have the best discriminatory power between ischemic and control plasma. Conclusively, our results provide evidence that NMR spectra analysis can identify specific group of metabolites present in plasma with the capability for discrimination between individual groups of animals. In addition, an excellent feasibility for the statistical discrimination among ischemic, preconditioned, and control rats can be applied regardless of native or deproteinated plasma and also regardless of noesy or cpmg NMR acquisition.
PMID: 29752707 [PubMed - as supplied by publisher]
Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models.
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Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models.
Chin J Integr Med. 2018 May;24(5):390-398
Authors: Liu L, Wang LP, He S, Ma Y
Abstract
Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of IgE antibodies by B cells and a decrease of the interferon-γ/interleukin-4 (Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine (CM) research on the mechanisms and effificacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the PubMed and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specifific immunoglobulin E, inflflammatory cell infifiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.
PMID: 29752613 [PubMed - in process]
TG2 regulates the heat-shock response by the post-translational modification of HSF1.
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TG2 regulates the heat-shock response by the post-translational modification of HSF1.
EMBO Rep. 2018 May 11;:
Authors: Rossin F, Villella VR, D'Eletto M, Farrace MG, Esposito S, Ferrari E, Monzani R, Occhigrossi L, Pagliarini V, Sette C, Cozza G, Barlev NA, Falasca L, Fimia GM, Kroemer G, Raia V, Maiuri L, Piacentini M
Abstract
Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter. We show that the inhibition of TG2 restores the unbalance in HSF1-HSP70 pathway in cystic fibrosis (CF), a human disorder characterized by deregulation of proteostasis. The absence of TG2 leads to an increase of about 40% in CFTR function in a new experimental CF mouse model lacking TG2. Altogether, these results indicate that TG2 plays a key role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat-shock response.
PMID: 29752334 [PubMed - as supplied by publisher]
Mass Spectrometric Identification of Urinary Biomarkers of Pulmonary Tuberculosis.
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Mass Spectrometric Identification of Urinary Biomarkers of Pulmonary Tuberculosis.
EBioMedicine. 2018 Apr 22;:
Authors: Isa F, Collins S, Lee MH, Decome D, Dorvil N, Joseph P, Smith L, Salerno S, Wells MT, Fischer S, Bean JM, Pape JW, Johnson WD, Fitzgerald DW, Rhee KY
Abstract
BACKGROUND: Tuberculosis (TB) is the leading infectious cause of death worldwide. A major barrier to control of the pandemic is a lack of clinical biomarkers with the ability to distinguish active TB from healthy and sick controls and potential for development into point-of-care diagnostics.
METHODS: We conducted a prospective case control study to identify candidate urine-based diagnostic biomarkers of active pulmonary TB (discovery cohort) and obtained a separate blinded "validation" cohort of confirmed cases of active pulmonary TB and controls with non-tuberculous pulmonary disease for validation. Clean-catch urine samples were collected and analyzed using high performance liquid chromatography-coupled time-of-flight mass spectrometry.
RESULTS: We discovered ten molecules from the discovery cohort with receiver-operator characteristic (ROC) area-under-the-curve (AUC) values >85%. These 10 molecules also significantly decreased after 60 days of treatment in a subset of 20 participants followed over time. Of these, a specific combination of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine exhibited ROC AUCs >80% in a blinded validation cohort of participants with active TB and non-tuberculous pulmonary disease.
CONCLUSION: Urinary levels of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine distinguished patients with tuberculosis from healthy controls and patients with non-tuberculous pulmonary diseases, providing a potential noninvasive biosignature of active TB.
FUNDING: This study was funded by Weill Cornell Medicine, the National Institute of Allergy and Infectious Diseases, the Clinical and Translational Science Center at Weill Cornell, the NIH Fogarty International Center grants, and the NIH Tuberculosis Research Unit (Tri-I TBRU).
PMID: 29752217 [PubMed - as supplied by publisher]
Blood biomarkers in Alzheimer's disease.
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Blood biomarkers in Alzheimer's disease.
Neurologia. 2018 May 08;:
Authors: Altuna-Azkargorta M, Mendioroz-Iriarte M
Abstract
INTRODUCTION: The early diagnosis of Alzheimer's disease (AD) via the use of biomarkers could facilitate the implementation and monitoring of early therapeutic interventions with the potential capacity to significantly modify the course of the disease.
DEVELOPMENT: Classic cerebrospinal fluid biomarkers and approved structural and functional neuroimaging have a limited clinical application given their invasive nature and/or high cost. The identification of more accessible and less costly biomarkers, such as blood biomarkers, would facilitate application in clinical practice. We present a literature review of the main blood biochemical biomarkers with potential use for diagnosing Alzheimer's disease.
CONCLUSIONS: Blood biomarkers are cost and time effective with regard to cerebrospinal fluid biomarkers. However, the immediate applicability of blood biochemical biomarkers in clinical practice is not very likely. The main limitations come from the difficulties in measuring and standardising thresholds between different laboratories and in failures to replicate results. Among all the molecules studied, apoptosis and neurodegeneration biomarkers and the biomarker panels obtained through omics approaches, such as isolated or combined metabolomics, offer the most promising results.
PMID: 29752036 [PubMed - as supplied by publisher]