PubMed

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]

Related Articles 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]

Related Articles 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]

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]

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]

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]

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.

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.

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]