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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 2017/06/06PubMed 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.

The Athlete Biological Passport: How to Personalize Anti-Doping Testing across an Athlete's Career? Med Sport Sci. 2017;62:107-118 Authors: Robinson N, Sottas PE, Schumacher YO Abstract For decades, drug testing has been the main instrument at the disposal of anti-doping authorities. The availability in the 1980s of substances identical to those produced by the human body, including the "big 3" (erythropoietin, testosterone, and growth hormone), necessitated a new paradigm in anti-doping. The athlete biological passport (ABP) is a new paradigm, complementary to traditional drug testing, based on the personalized monitoring of doping biomarkers. Athletes who abuse doping substances do so to trigger physiological changes that provide performance enhancement. The ABP aims to detect these changes through its 3 hematological, steroidal, and endocrine modules. Any deviation of a biomarker from what is expected in a healthy physiological condition can be attributable to doping or a medical condition, which, interestingly, is also the criterion used to define a banned substance. Recent advances in proteomics and metabolomics offer immense opportunities to enhance the ABP. The ABP shares multiple aspects with the present customization of health care and personalized medicine. PMID: 28578329 [PubMed - in process]

Cross-platform metabolomics investigating the intracellular metabolic alterations of HaCaT cells exposed to phenanthrene. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 May 23;1060:15-21 Authors: Jiang G, Kang H, Yu Y Abstract Phenanthrene (Phe) is one of the most abundant Polycyclic aromatic hydrocarbons (PAHs) contamination from various ambient sources, which has a tremendous impact on public health. However, our knowledge regarding its effects on skin remains limited. In this study, we investigated the metabolite profiling of the human keratinocytes HaCaT cells after Phe exposure to understand the toxic effects of Phe exposure on skin. To obtain a broad picture of metabolome with various hydrophilicity, a cross-platform approach with GC-MS and UHPLC-QTOF-MS has been employed. Data were analyzed by multivariate statistical analysis and samples were separated successfully using supervised PLS-DA models. It was shown that the impacts of Phe exposure on HaCaT cells were both dose-related and time-related. A total of 48 Phe-regulated metabolites were identified and among which 19 were confirmed by reference standards. By pathway analysis, amino acid metabolism, glutathione metabolism and glycerophospholipid metabolism were highlighted as the major metabolic pathways disturbed by Phe. Furthermore, it was found that the mechanisms included a reduced amino pool and a reduced antioxidant status. Overall, these results aid in improving understanding of the dermal toxicology related to Phe, and demonstrate this cross-platform approach is suitable for metabolomics researches on HaCaT cells. PMID: 28578192 [PubMed - as supplied by publisher]

Phenolic profile and fermentation patterns of different commercial gluten-free pasta during in vitro large intestine fermentation. Food Res Int. 2017 Jul;97:78-86 Authors: Rocchetti G, Lucini L, Chiodelli G, Giuberti G, Gallo A, Masoero F, Trevisan M Abstract The fate of phenolic compounds, along with short-chain fatty acids (SCFAs) production kinetics, was evaluated on six different commercial gluten-free (GF) pasta samples varying in ingredient compositions, focussing on the in vitro faecal fermentation after the gastrointestinal digestion. A general reduction of both total phenolics and reducing power was observed in all samples, together with a substantial change in phenolic profile over 24h of faecal fermentation, with differences among GF pasta samples. Flavonoids, hydroxycinnamics and lignans degraded over time, with a concurrent increase in low-molecular-weight phenolic acids (hydroxybenzoic acids), alkylphenols, hydroxybenzoketones and tyrosols. Interestingly, discriminant analysis also identified several alkyl derivatives of resorcinol as markers of the changes in phenolic profile during in vitro fermentation. Furthermore, degradation pathways of phenolics by intestinal microbiota have been proposed. Considering the total SCFAs and butyrate production during the in vitro fermentation, different fermentation kinetics were observed among GF pasta post-hydrolysis residues. PMID: 28578068 [PubMed - in process]

Phenolic compounds profile and antioxidant properties of six sweet cherry (Prunus avium) cultivars. Food Res Int. 2017 Jul;97:15-26 Authors: Martini S, Conte A, Tagliazucchi D Abstract Sweet cherry (Prunus avium) fruits are a nutritionally important food rich in dietary phenolic compounds. The aim of this study was to investigate the phenolic profile and chemometric discrimination of fruits from six cherry cultivars using a quantitative metabolomics approach, which combine non-targeted mass spectrometry and chemometric analysis. The assessment of the phenolic fingerprint of cherries allowed the tentative identification of 86 compounds. A total of 40 chlorogenic acids were identified in cherry fruit, which pointed out hydroxycinnamic acid derivatives as the main class of phenolics by number of compounds. Among the compounds detected, 40 have been reported for the first time in sweet cherry fruit. Hydroxycinnamic acids are also the quantitatively most represented class of phenolic compounds in the cherry cultivars with the exception of Lapins and Durone della Marca where the most representative class of phenolic compounds were anthocyanins and flavan-3-ols, respectively. This non-targeted approach allowed the tentative identification of the cultivar-compound relationships of these six cherry cultivars. Both anthocyanins and colorless phenolic compounds profile appeared to be cultivar-dependent. In detail, anthocyanins and flavonols patterns have the potential to be used for the determination of a varietal assignment of cherries. PMID: 28578036 [PubMed - in process]

Impact of blood sample collection methods on blood protein profiling studies. Clin Chim Acta. 2017 May 31;: Authors: Ilies M, Iuga CA, Loghin F, Dhople VM, Thiele T, Völker U, Hammer E Abstract Pre-analytical factors have a significant impact on the integrity of blood samples used for qualitative and quantitative protein profiling. Important factors are the type of the blood collection tube and the anticoagulant used. Only a few studies have been performed to assess these variables by comparing only serum and EDTA plasma collection tubes with some target proteins or peptides. In this study, we investigated the protein profile of blood samples collected in serum, EDTA-, heparin-, and citrate plasma tubes. Furthermore, we compared the depletion efficiency of 6 high abundant proteins, the detectable blood protein profile, the variance, and the coverage of the detectable protein sets. The largest differences were found between serum and plasma samples with respect to the peptide number and the occurrence of classical blood proteins. The heparin plasma evidenced a high number of detectable proteins, low global variance and a high similarity to EDTA- and citrate plasma and may therefore be also a useful test tube for blood protein profiling. In addition, a core set of blood proteins were described and the portions and compositions of sampling specific proteins were disclosed. Therefore, pre-analytical issues such as the sample collection method should be considered for protein profiling studies. PMID: 28577959 [PubMed - as supplied by publisher]

Related Articles Metabolomics of mitochondrial disease. Mitochondrion. 2017 May 30;: Authors: Esterhuizen K, van der Westhuizen FH, Louw R Abstract Mitochondrial disease (MD) diagnostics and disease progression investigations have traditionally relied very little on metabolic data, due to a lack of biomarker sensitivity and specificity. The recent drive to find novel, low intervention biomarkers and new therapeutic approaches have revived an interest in what metabolic data can offer, as presented in this timely review. We review how metabolomics has been applied to MD and provide an extensive overview of the reported metabolic perturbations and common mechanistic features that may provide a basis for future research. We conclude by highlighting the substantial potential of metabolomics for future diagnostics and mitochondrial medicine. PMID: 28576558 [PubMed - as supplied by publisher]

Related Articles Chloroformate derivatization for tracing the fate of Amino acids in cells and tissues by multiple stable isotope resolved metabolomics (mSIRM). Anal Chim Acta. 2017 Jul 11;976:63-73 Authors: Yang Y, Fan TW, Lane AN, Higashi RM Abstract Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment. Conversely, a single precursor labeled with two (or more) different elemental isotopes can trace the allocation of e.g. C and N atoms through the network. Such dual-label experiments however challenge the resolution of conventional mass spectrometers, which must distinguish the neutron mass differences among different elemental isotopes. This requires ultrahigh resolution Fourier transform mass spectrometry (UHR-FTMS). When combined with direct infusion nano-electrospray ion source (nano-ESI), UHR-FTMS can provide rapid, global, and quantitative analysis of all possible mass isotopologues of metabolites. Unfortunately, very low mass polar metabolites such as amino acids can be difficult to analyze by current models of UHR-FTMS, plus the high salt content present in typical cell or tissue polar extracts may cause unacceptable ion suppression for sources such as nano-ESI. Here we describe a modified method of ethyl chloroformate (ECF) derivatization of amino acids to enable rapid quantitative analysis of stable isotope labeled amino acids using nano-ESI UHR-FTMS. This method showed excellent linearity with quantifiable limits in the low nanomolar range represented in microgram quantities of biological specimens, which results in extracts with total analyte abundances in the low to sub-femtomole range. We have applied this method to profile amino acids and their labeling patterns in (13)C and (2)H doubly labeled PC9 cell extracts, cancerous and non-cancerous tissue extracts from a lung cancer patient and their protein hydrolysates as well as plasma extracts from mice fed with a liquid diet containing (13)C6-glucose (Glc). The multi-element isotopologue distributions provided key insights into amino acid metabolism and intracellular pools in human lung cancer tissues in high detail. The (13)C labeling of Asp and Glu revealed de novo synthesis of these amino acids from (13)C6-Glc via the Krebs cycle, specifically the elevated level of (13)C3-labeled Asp and Glu in cancerous versus non-cancerous lung tissues was consistent with enhanced pyruvate carboxylation. In addition, tracking the fate of double tracers, ((13)C6-Glc + (2)H2-Gly or (13)C6-Glc + (2)H3-Ser) in PC9 cells clearly resolved pools of Ser and Gly synthesized de novo from (13)C6-Glc ((13)C3-Ser and (13)C2-Gly) versus Ser and Gly derived from external sources ((2)H3-Ser, (2)H2-Gly). Moreover the complex (2)H labeling patterns of the latter were results of Ser and Gly exchange through active Ser-Gly one-carbon metabolic pathway in PC9 cells. PMID: 28576319 [PubMed - in process]

Related Articles Automated quantification of metabolites in blood-derived samples by NMR. Anal Chim Acta. 2017 Jul 11;976:52-62 Authors: Verhoeven A, Slagboom E, Wuhrer M, Giera M, Mayboroda OA Abstract NMR is widely applied in the field of metabolomics due to the quantitative nature of the technology and the reproducible data generated. However, because of severe spectral crowding, quantifying individual metabolites in body fluids such as serum and plasma remains a challenge. In this study, a method to automatically annotate and quantify a number of small metabolites in human serum and EDTA plasma is introduced. It combines the superior signal-to-noise ratio of the commonly applied CPMG and NOESY1D pulse sequences with the superior resolution of the 2D JRES experiment to construct a model that extracts the metabolite concentrations directly from the 1D spectra without tedious deconvolution. The performance of the method was assessed by comparing the calculated areas of the various glucose peaks with known clinical values, by comparing several peaks of the same metabolite (extracted versus non-extracted), and by comparing areas obtained from various NMR pulse sequences. Additionally, the models were tested on independent datasets. It was found that for many metabolites peaks could be assigned that show a consistent behavior, indicating a precise quantification. The same method should be applicable to other biofluids with a stable composition and pH, such as CSF fluid, cell extracts, and cell media. PMID: 28576318 [PubMed - in process]

Related Articles Biological determinants of health: Genes, microbes, and metabolism exemplars of nursing science. Nurs Outlook. 2017 Apr 12;: Authors: Ferranti EP, Grossmann R, Starkweather A, Heitkemper M Abstract BACKGROUND: Increasingly, nurse scientists are incorporating "omics" measures (e.g., genomics, transcriptomics, proteomics, and metabolomics) in studies of biologic determinants of health and behavior. The role of omics in nursing science can be conceptualized in several ways: (a) as a portfolio of biological measures (biomarkers) to monitor individual risk, (b) as a set of combined data elements that can generate new knowledge based on large and complex patient data sets, (c) as baseline information that promotes health education and potentially personalized interventions, and (d) as a platform to understand how environmental parameters (e.g., diet) interact with the individual's physiology. PURPOSE: In this article, we provide exemplars of nursing scientists who use omics to better understand specific health conditions. METHODS: We highlight various ongoing nursing research investigations incorporating omics technologies to study chronic pain vulnerability, risk for a pain-related condition, cardiometabolic complications associated with pregnancy, and as biomarkers of response to a dietary intervention. DISCUSSION: Omics technologies add an important dimension to nursing science across many foci of investigation. However, there are also challenges and opportunities for nurse scientists who consider using omics in their research. CONCLUSION: The integration of omics holds promise for increasing the impact of nursing research and practice on population health outcomes. PMID: 28576296 [PubMed - as supplied by publisher]

Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication. Nucleic Acids Res. 2017 May 29;: Authors: Bjørås KØ, Sousa MML, Sharma A, Fonseca DM, Søgaard CK, Bjørås M, Otterlei M Abstract Base lesions in DNA can stall the replication machinery or induce mutations if bypassed. Consequently, lesions must be repaired before replication or in a post-replicative process to maintain genomic stability. Base excision repair (BER) is the main pathway for repair of base lesions and is known to be associated with DNA replication, but how BER is organized during replication is unclear. Here we coupled the iPOND (isolation of proteins on nascent DNA) technique with targeted mass-spectrometry analysis, which enabled us to detect all proteins required for BER on nascent DNA and to monitor their spatiotemporal orchestration at replication forks. We demonstrate that XRCC1 and other BER/single-strand break repair (SSBR) proteins are enriched in replisomes in unstressed cells, supporting a cellular capacity of post-replicative BER/SSBR. Importantly, we identify for the first time the DNA glycosylases MYH, UNG2, MPG, NTH1, NEIL1, 2 and 3 on nascent DNA. Our findings suggest that a broad spectrum of DNA base lesions are recognized and repaired by BER in a post-replicative process. PMID: 28575236 [PubMed - as supplied by publisher]

Targeting oxidative stress improves disease outcomes in a rat model of acquired epilepsy. Brain. 2017 May 30;: Authors: Pauletti A, Terrone G, Shekh-Ahmad T, Salamone A, Ravizza T, Rizzi M, Pastore A, Pascente R, Liang LP, Villa BR, Balosso S, Abramov AY, van Vliet EA, Del Giudice E, Aronica E, Antoine DJ, Patel M, Walker MC, Vezzani A Abstract Epilepsy therapy is based on antiseizure drugs that treat the symptom, seizures, rather than the disease and are ineffective in up to 30% of patients. There are no treatments for modifying the disease-preventing seizure onset, reducing severity or improving prognosis. Among the potential molecular targets for attaining these unmet therapeutic needs, we focused on oxidative stress since it is a pathophysiological process commonly occurring in experimental epileptogenesis and observed in human epilepsy. Using a rat model of acquired epilepsy induced by electrical status epilepticus, we show that oxidative stress occurs in both neurons and astrocytes during epileptogenesis, as assessed by measuring biochemical and histological markers. This evidence was validated in the hippocampus of humans who died following status epilepticus. Oxidative stress was reduced in animals undergoing epileptogenesis by a transient treatment with N-acetylcysteine and sulforaphane, which act to increase glutathione levels through complementary mechanisms. These antioxidant drugs are already used in humans for other therapeutic indications. This drug combination transiently administered for 2 weeks during epileptogenesis inhibited oxidative stress more efficiently than either drug alone. The drug combination significantly delayed the onset of epilepsy, blocked disease progression between 2 and 5 months post-status epilepticus and drastically reduced the frequency of spontaneous seizures measured at 5 months without modifying the average seizure duration or the incidence of epilepsy in animals. Treatment also decreased hippocampal neuron loss and rescued cognitive deficits. Oxidative stress during epileptogenesis was associated with de novo brain and blood generation of disulfide high mobility group box 1 (HMGB1), a neuroinflammatory molecule implicated in seizure mechanisms. Drug-induced reduction of oxidative stress prevented disulfide HMGB1 generation, thus highlighting a potential novel mechanism contributing to therapeutic effects. Our data show that targeting oxidative stress with clinically used drugs for a limited time window starting early after injury significantly improves long-term disease outcomes. This intervention may be considered for patients exposed to potential epileptogenic insults. PMID: 28575153 [PubMed - as supplied by publisher]

Development of a Data-Independent Targeted Metabolomics Method for Relative Quantification Using Liquid Chromatography Coupled with Tandem Mass Spectrometry. Anal Chem. 2017 Jun 02;: Authors: Chen Y, Zhou Z, Yang W, Bi N, Xu J, He J, Zhang R, Wang L, Abliz Z Abstract Quantitative metabolomics approaches can significantly improve the repeatability and reliability of metabolomics investi-gations but face critical technical challenges, owing to the vast number of unknown endogenous metabolites and the lack of authentic standards. The present study contributes to the development of a novel method known as "data-independent tar-geted quantitative metabolomics," (DITQM) which was used to investigate the label-free quantitative metabolomics of mul-tiple known and unknown metabolites in biofluid samples. This approach initially involved the acquisition of MS/MS data for all metabolites in biosamples using a sequentially stepped targeted MS/MS (sst-MS/MS) method, in which multiple prod-uct ion scans were performed by selecting all ions in the targeted mass ranges as the precursor ions. Subsequently, scheduled multiple reaction monitoring (MRM) by LC-MS/MS of the metabolome was established for 1,658 characteristic ion pairs of 1,324 metabolites. For sensitive and accurate quantification of these metabolites, mixed calibration curves were generated using sequentially diluted standard reference plasma samples using established MRM methods. Relative concentrations of all metabolites in each sample were calculated without using individual authentic standards. To evaluate the reliability and applicability of this new method, the performance of DITQM was validated by comparison to absolute quantification of twelve acylcarnitines using authentic standards and traditional metabolomics analysis for lung cancer. The results proved that the DITQM protocol is more reliable and can significantly improve clustering effects and repeatability in biomarker discovery. In this study, we established a novel methodology to standardize and quantify large-scale metabolome, providing a new choice for metabolomics research and its clinical applications. PMID: 28574715 [PubMed - as supplied by publisher]

A Novel Anti-Hepatitis C Virus and Antiproliferative Agent Alters Metabolic Networks in HepG2 and Hep3B Cells. Metabolites. 2017 Jun 02;7(2): Authors: Keogh A, Şenkardeş S, Idle JR, Küçükgüzel ŞG, Beyoğlu D Abstract A series of novel diflunisal hydrazide-hydrazones has been reported together with their anti-hepatitis C virus and antiproliferative activities in a number of human hepatoma cell lines. However, the mechanisms underlying the efficacy of these agents remain unclear. It was chosen to investigate the lead diflunisal hydrazide-hydrazone, 2',4'-difluoro-4-hydroxy-N'- [(pyridin-2-yl)methylidene]biphenyl-3-carbohydrazide (compound 3b), in two cultured human hepatoma cell lines-HepG2 and Hep3B-using a metabolomic protocol aimed at uncovering any effects of this agent on cellular metabolism. One sub-therapeutic concentration (2.5 μM) and one close to the IC50 for antimitotic effect (10 μM), after 72 h in cell culture, were chosen for both compound 3b and its inactive parent compound diflusinal as a control. A GCMS-based metabolomic investigation was performed on cell lysates after culture for 24 h. The intracellular levels of a total of 42 metabolites were found to be statistically significantly altered in either HepG2 or Hep3B cells, only eight of which were affected in both cell lines. It was concluded that compound 3b affected the following pathways-purine and pyrimidine catabolism, the glutathione cycle, and energy metabolism through glycolysis and the pentose phosphate pathway. Although the metabolomic findings occurred after 24 h in culture, significant cytotoxicity of compound 3b to both HepG2 and Hep3B cells at 10 μM were reported not to occur until 72 h in culture. These observations show that metabolomics can provide mechanistic insights into the efficacy of novel drug candidates prior to the appearance of their pharmacological effect. PMID: 28574427 [PubMed - in process]

Related Articles Maximal clique method for the automated analysis of NMR TOCSY spectra of complex mixtures. J Biomol NMR. 2017 Jun 01;: Authors: Li DW, Wang C, Brüschweiler R Abstract Characterization of the chemical components of complex mixtures in solution is important in many areas of biochemistry and chemical biology, including metabolomics. The use of 2D NMR total correlation spectroscopy (TOCSY) experiments has proven very useful for the identification of known metabolites as well as for the characterization of metabolites that are unknown by taking advantage of the good resolution and high sensitivity of this homonuclear experiment. Due to the complexity of the resulting spectra, automation is critical to facilitate and speed-up their analysis and enable high-throughput applications. To better meet these emerging needs, an automated spin-system identification algorithm of TOCSY spectra is introduced that represents the cross-peaks and their connectivities as a mathematical graph, for which all subgraphs are determined that are maximal cliques. Each maximal clique can be assigned to an individual spin system thereby providing a robust deconvolution of the original spectrum for the easy extraction of critical spin system information. The approach is demonstrated for a complex metabolite mixture consisting of 20 compounds and for E. coli cell lysate. PMID: 28573376 [PubMed - as supplied by publisher]

Related Articles Exposure Marker Discovery of Phthalates Using Mass Spectrometry. Mass Spectrom (Tokyo). 2017;6(Spec Iss):S0062 Authors: Hsu JY, Shih CL, Liao PC Abstract Phthalates are chemicals widely used in industry and the consequences on human health caused by exposure to these agents are of significant interest currently. The urinary metabolites of phthalates can be measured and used as exposure markers for the assessment of the actual internal contamination of phthalates coming from different sources and absorbed by various ways. The purpose of this paper is to review the markers for exposure and risk assessment of phthalates such as di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP), benzylbutyl phthalate (BBP), di-(2-ethylhexyl)phthalate (DEHP), di-(2-propylheptyl)phthalate (DPHP), di-iso-nonyl phthalate (DINP), di-n-octyl phthalate (DnOP) and di-iso-decyl phthalate (DIDP), and introduction of the analytical approach of three metabolomics data processing approaches that can be used for chemical exposure marker discovery in urine with high-resolution mass spectrometry (HRMS) data. PMID: 28573083 [PubMed - in process]

Related Articles Erythrocyte Purinergic Signaling Components Underlie Hypoxia Adaptation. J Appl Physiol (1985). 2017 Jun 01;:jap.00155.2017 Authors: Sun K, Liu H, Song A, Manalo JM, D'Alessandro A, Hansen KC, Kellems RE, Eltzschig HK, Blackburn MR, Roach RC, Xia Y Abstract Erythrocytes are vital to human adaptation under hypoxic conditions because of their abundance in number and irreplaceable function of delivering oxygen (O2). However, although multiple large-scale altitude studies investigating the overall coordination of the human body for hypoxia adaptation have been conducted, detailed research with a focus on erythrocytes was missing due to lack of proper techniques. The recently maturing metabolomics profiling technology appears to be the answer to this limitation. Metabolomics profiling provides unbiased high-throughput screening data that reveal the overall metabolic status of erythrocytes. Recent studies have exploited this new technology and provided novel insight into erythrocyte physiology and pathology. In particular, a series of studies focusing on erythrocyte purinergic signaling have reported that adenosine signaling, coupled with 5' AMP-activated protein kinase (AMPK) and the production of erythrocyte-enriched bioactive signaling lipid sphingosine 1-phosphate, regulate erythrocyte glucose metabolism for more O2 delivery. Moreover, an adenosine-dependent "Erythrocyte Hypoxic Memory" was discovered which provides an explanation for fast acclimation upon re-ascent. These findings not only shed new light on our understanding of erythrocyte function and hypoxia adaptation but also offer a myriad of novel therapeutic possibilities to counteract various hypoxic conditions. PMID: 28572494 [PubMed - as supplied by publisher]

Related Articles Advantages and Limitations of Current Biomarker Research: From Experimental Research to Clinical Application. Curr Pharm Biotechnol. 2017 May 31;: Authors: Kim SH, Weiß C, Hoffmann U, Borggrefe M Abstract BACKGROUND: Biomarkers are indispensable tools for screening, diagnosis, and prognosis in cardiovascular diseases and their clinical application increases steadily. As cardiovascular diseases include various pathophysiological processes, no single biomarker, even natriuretic peptides, can be regarded as ideal fulfilling all necessary criteria for a comprehensive diagnostic or prognostic assessment revealing optimal clinical application. Hence, the multi-marker approaches using different biomarkers reflecting different pathophysiologies were highlighted recently. Advances in biomedical technologies expanded the spectrum of novel blood-derived biomarkers, such as micro-RNA (miRNA) or "omics"-data potentially providing a more advanced knowledge about pathogenesis of cardiovascular disease. CONCLUSION: This review describes the advantages and limitations of blood circulating biomarkers with regard to proteins, metabolomics and transcriptional level both within single as well as multi-marker strategies. Moreover, their usefulness is focused on clinical decision-making in cardiovascular diseases. PMID: 28571562 [PubMed - as supplied by publisher]

Related Articles Evolutionary Adaptation of the Essential tRNA Methyltransferase TrmD to the Signaling Molecule 3',5'-cAMP in Bacteria. J Biol Chem. 2017 Jan 06;292(1):313-327 Authors: Zhang Y, Agrebi R, Bellows LE, Collet JF, Kaever V, Gründling A Abstract The nucleotide signaling molecule 3',5'-cyclic adenosine monophosphate (3',5'-cAMP) plays important physiological roles, ranging from carbon catabolite repression in bacteria to mediating the action of hormones in higher eukaryotes, including human. However, it remains unclear whether 3',5'-cAMP is universally present in the Firmicutes group of bacteria. We hypothesized that searching for proteins that bind 3',5'-cAMP might provide new insight into this question. Accordingly, we performed a genome-wide screen and identified the essential Staphylococcus aureus tRNA m(1)G37 methyltransferase enzyme TrmD, which is conserved in all three domains of life as a tight 3',5'-cAMP-binding protein. TrmD enzymes are known to use S-adenosyl-l-methionine (AdoMet) as substrate; we have shown that 3',5'-cAMP binds competitively with AdoMet to the S. aureus TrmD protein, indicating an overlapping binding site. However, the physiological relevance of this discovery remained unclear, as we were unable to identify a functional adenylate cyclase in S. aureus and only detected 2',3'-cAMP but not 3',5'-cAMP in cellular extracts. Interestingly, TrmD proteins from Escherichia coli and Mycobacterium tuberculosis, organisms known to synthesize 3',5'-cAMP, did not bind this signaling nucleotide. Comparative bioinformatics, mutagenesis, and biochemical analyses revealed that the highly conserved Tyr-86 residue in E. coli TrmD is essential to discriminate between 3',5'-cAMP and the native substrate AdoMet. Combined with a phylogenetic analysis, these results suggest that amino acids in the substrate binding pocket of TrmD underwent an adaptive evolution to accommodate the emergence of adenylate cyclases and thus the signaling molecule 3',5'-cAMP. Altogether this further indicates that S. aureus does not produce 3',5'-cAMP, which would otherwise competitively inhibit an essential enzyme. PMID: 27881678 [PubMed - indexed for MEDLINE]

Related Articles Characterisation of plasmalemmal shedding of vesicles induced by the cholesterol/sphingomyelin binding protein, ostreolysin A-mCherry. Biochim Biophys Acta. 2016 11;1858(11):2882-2893 Authors: Skočaj M, Yu Y, Grundner M, Resnik N, Bedina Zavec A, Leonardi A, Križaj I, Guella G, Maček P, Kreft ME, Frangež R, Veranič P, Sepčić K Abstract Ostreolysin A (OlyA) is a 15-kDa protein that binds selectively to cholesterol/sphingomyelin membrane nanodomains. This binding induces the production of extracellular vesicles (EVs) that comprise both microvesicles with diameters between 100nm and 1μm, and larger vesicles of around 10-μm diameter in Madin-Darby canine kidney cells. In this study, we show that vesiculation of these cells by the fluorescent fusion protein OlyA-mCherry is not affected by temperature, is not mediated via intracellular Ca(2+) signalling, and does not compromise cell viability and ultrastructure. Seventy-one proteins that are mostly of cytosolic and nuclear origin were detected in these shed EVs using mass spectroscopy. In the cells and EVs, 218 and 84 lipid species were identified, respectively, and the EVs were significantly enriched in lysophosphatidylcholines and cholesterol. Our collected data suggest that OlyA-mCherry binding to cholesterol/sphingomyelin membrane nanodomains induces specific lipid sorting into discrete patches, which promotes plasmalemmal blebbing and EV shedding from the cells. We hypothesize that these effects are accounted for by changes of local membrane curvature upon the OlyA-mCherry-plasmalemma interaction. We suggest that the shed EVs are a potentially interesting model for biophysical and biochemical studies of cell membranes, and larger vesicles could represent tools for non-invasive sampling of cytosolic proteins from cells and thus metabolic fingerprinting. PMID: 27591807 [PubMed - indexed for MEDLINE]