PubMed

Related Articles NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in patients with colorectal cancer. Oncotarget. 2016 Apr 16; Authors: Lin Y, Ma C, Liu C, Wang Z, Yang J, Liu X, Shen Z, Wu R Abstract Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its earlier detection for optimal disease management. A metabolomics based approach provides potential for noninvasive identification of biomarkers of colorectal carcinogenesis, as well as dissection of molecular pathways of pathophysiological conditions. Here, proton nuclear magnetic resonance spectroscopy (1HNMR) -based metabolomic approach was used to profile fecal metabolites of 68 CRC patients (stage I/II=20; stage III=25 and stage IV=23) and 32 healthy controls (HC). Pattern recognition through principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied on 1H-NMR processed data for dimension reduction. OPLS-DA revealed that each stage of CRC could be clearly distinguished from HC based on their metabolomic profiles. Successive analyses identified distinct disturbances to fecal metabolites of CRC patients at various stages, compared with those in cancer free controls, including reduced levels of acetate, butyrate, propionate, glucose, glutamine, and elevated quantities of succinate, proline, alanine, dimethylglycine, valine, glutamate, leucine, isoleucine and lactate. These altered fecal metabolites potentially involved in the disruption of normal bacterial ecology, malabsorption of nutrients, increased glycolysis and glutaminolysis. Our findings revealed that the fecal metabolic profiles of healthy controls can be distinguished from CRC patients, even in the early stage (stage I/II), highlighting the potential utility of NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in CRC patients. PMID: 27107423 [PubMed - as supplied by publisher]

Related Articles Evaluation of the technical variations and the suitability of a hydrophilic interaction liquid chromatography-high resolution mass spectrometry (ZIC-pHILIC-Exactive orbitrap) for clinical urinary metabolomics study. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Apr 13;1022:199-205 Authors: Zhang T, Watson DG Abstract Although many hydrophilic interaction liquid chromatography-high resolution mass spectrometry (HILIC-HRMS) methods have been developed and applied for untargeted metabolite profiling in clinical metabolomics, according to the literature, the suitability of these HILIC-HRMS methods has not been fully evaluated with respect to their performance when they are subjected to statistical analysis. In this study, using a series of human urine samples we investigated the effect of technical variations on multivariate and univariate analysis of the data collected using a previously developed HILIC-HRMS method for untargeted urinary metabolite profiling in clinical metabolomics. The technical variation introduced by sample preparation was more significant than that produced by the HILIC-HRMS method. By using an orthogonal partial least squares (OPLS) model, subtle fold-changes were accurately measured in the urine samples spiked with (13)C and (15)N isotope labelled amino acids at different concentrations. The robustness of this HILIC method was also evaluated by analysing the obtained data from a single urine sample following manipulation of several primary LC parameters. High reproducibility in the chromatographic performance of three ZIC-pHILIC columns with different batch numbers indicated the reliability of the polymer based zwitterionic stationary phase allowing column replacement without compromising the performance of the method. PMID: 27107246 [PubMed - as supplied by publisher]

Related Articles Identification of a polyketide synthase involved in sorbicillin biosynthesis by Penicillium chrysogenum. Appl Environ Microbiol. 2016 Apr 22; Authors: Salo O, Guzmán-Chávez F, Ries MI, Lankhorst PP, Bovenberg RA, Vreeken RJ, Driessen AJ Abstract Secondary metabolism in Penicillium chrysogenum was intensively subjected to classical strain improvement (CSI) resulting industrial strains producing high levels of β-lactams. During this process, the production of yellow pigments including sorbicillinoids was eliminated as part of a strategy to enable the rapid purification of β-lactams. Here we report the identification of the polyketide synthase (PKS) gene essential for sorbicillinoids biosynthesis in P. chrysogenum We demonstrate that the production of polyketide precursors like sorbicillinol and dihydrosorbicillinol as well as their derivatives bisorbicillinoids require the function of a highly reducing PKS encoded by the gene Pc21g05080 (pks13). This gene belongs to the cluster that was mutated and transcriptionally silenced during the strain improvement program. Using an improved β-lactam producing strain, repair of the mutation in pks13 led to the restoration of sorbicillinoids production. This now enable genetic studies on the mechanism of sorbicillinoid biosynthesis in P. chrysogenum and opens new perspectives for pathway engineering. IMPORTANCE: Sorbicillinoids are secondary metabolites with anti-viral, anti-inflammatory and anti-microbial activity produced by filamentous fungi. This study identified the gene cluster responsible for sorbicillinoids formation in Penicillium chrysogenum now allow engineering of this diverse group of compounds. PMID: 27107123 [PubMed - as supplied by publisher]

Related Articles High-resolution magic angle spinning (1)H nuclear magnetic resonance spectroscopy metabolomics of hyperfunctioning parathyroid glands. Surgery. 2016 Apr 20; Authors: Battini S, Imperiale A, Taïeb D, Elbayed K, Cicek AE, Sebag F, Brunaud L, Namer IJ Abstract BACKGROUND: Primary hyperparathyroidism (PHPT) may be related to a single gland disease or multiglandular disease, which requires specific treatments. At present, an operation is the only curative treatment for PHPT. Currently, there are no biomarkers available to identify these 2 entities (single vs. multiple gland disease). The aims of the present study were to compare (1) the tissue metabolomics profiles between PHPT and renal hyperparathyroidism (secondary and tertiary) and (2) single gland disease with multiglandular disease in PHPT using metabolomics analysis. METHODS: The method used was (1)H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy. Forty-three samples from 32 patients suffering from hyperparathyroidism were included in this study. RESULTS: Significant differences in the metabolomics profile were assessed according to PHPT and renal hyperparathyroidism. A bicomponent orthogonal partial least square-discriminant analysis showed a clear distinction between PHPT and renal hyperparathyroidism (R(2)Y = 0.85, Q(2) = 0.63). Interestingly, the model also distinguished single gland disease from multiglandular disease (R(2)Y = 0.96, Q(2) = 0.55). A network analysis was also performed using the Algorithm to Determine Expected Metabolite Level Alterations Using Mutual Information (ADEMA). Single gland disease was accurately predicted by ADEMA and was associated with higher levels of phosphorylcholine, choline, glycerophosphocholine, fumarate, succinate, lactate, glucose, glutamine, and ascorbate compared with multiglandular disease. CONCLUSION: This study shows for the first time that (1)H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy is a reliable and fast technique to distinguish single gland disease from multiglandular disease in patients with PHPT. The potential use of this method as an intraoperative tool requires specific further studies. PMID: 27106795 [PubMed - as supplied by publisher]

Amino acid deprivation promotes intestinal homeostasis through autophagy. Oncotarget. 2016 Apr 19; Authors: Galluzzi L, Kroemer G PMID: 27105494 [PubMed - as supplied by publisher]

Posttranslational modulation of FoxO1 contributes to cardiac remodeling in post-ischemic heart failure. Atherosclerosis. 2016 Apr 7;249:148-156 Authors: Kappel BA, Stöhr R, De Angelis L, Mavilio M, Menghini R, Federici M Abstract OBJECTIVE: Forkhead box protein O1 (FoxO1) plays a key role in energy homeostasis, stress response and autophagy and is dysregulated in diabetes and ischemia. We investigated cardiac FoxO1 expression and posttranstranslational modifications after myocardial infarction (MI) and further tested if active posttranstranslational modulation of FoxO1 can alter cardiac remodeling in postischemic heart failure. METHODS: Non-diabetic and diabetic C57BL/6 mice were subjected to MI by ligation of left anterior descending artery. In selected experiments we combined this model with intramyocardial injection of adenovirus expressing different isoforms of FoxO1. We used Millar catheter, histology, Western blot and metabolomics for further analyses. RESULTS: We show that after MI total cardiac FoxO1 is downregulated and partly recovers after 7 days. This downregulation is accompanied by fundamental posttranslational modifications of FoxO1, particularly acetylation. Adenovirus experiments revealed smaller infarction size and improved heart function in mice expressing a constitutively deacetylated variant of FoxO1 compared to a wild type variant of FoxO1 in both non-diabetic (MI size: -13.4 ± 3.5%; LVDP: +29.1 ± 9.4  mmHg; p < 0.05) and diabetic mice (MI size: -17.6 ± 3.7%; LVDP: +10.9 ± 3.6  mmHg; p < 0.05). Metabolomics analyses showed alterations in metabolites connected to muscle breakdown, collagen/elastin and energy metabolism between the two groups. CONCLUSION: First, our results demonstrate that myocardial ischemia is associated with downregulation and posttranslational modification of cardiac FoxO1. Second, we show in a mouse model of postischemic heart failure that posttranslational modulation of FoxO1 alters heart function involving collagen and protein metabolism. Therefore, posttranslational modifications of FoxO1 could be an option to target remodeling processes in postischemic heart failure. PMID: 27105158 [PubMed - as supplied by publisher]

Precision Medicine for psychopharmacology: a general introduction. Expert Rev Neurother. 2016 Apr 22; Authors: Shin C, Han C, Pae CU, Patkar AA Abstract INTRODUCTION: Precision medicine is an emerging medical model that can provide accurate diagnoses and tailored therapeutic strategies for patients based on data pertaining to genes, microbiomes, environment, family history and lifestyle. Areas covered: Here, we provide basic information about precision medicine and newly introduced concepts, such as the precision medicine ecosystem and big data processing, and omics technologies including pharmacogenomics, pharamacometabolomics, pharmacoproteomics, pharmacoepigenomics, connectomics and exposomics. The authors review the current state of omics in psychiatry and the future direction of psychopharmacology as it moves towards precision medicine. Expert Commentary: Advances in precision medicine have been facilitated by achievements in multiple fields, including large-scale biological databases, powerful methods for characterizing patients (such as genomics, proteomics, metabolomics, diverse cellular assays, and even social networks and mobile health technologies), and computer-based tools for analyzing large amounts of data. PMID: 27104961 [PubMed - as supplied by publisher]

A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters. Molecules. 2016;21(4) Authors: Peter DM, Vögeli B, Cortina NS, Erb TJ Abstract Coenzyme A (CoA) is a ubiquitous cofactor present in every known organism. The thioesters of CoA are core intermediates in many metabolic processes, such as the citric acid cycle, fatty acid biosynthesis and secondary metabolism, including polyketide biosynthesis. Synthesis of CoA-thioesters is vital for the study of CoA-dependent enzymes and pathways, but also as standards for metabolomics studies. In this work we systematically tested five chemo-enzymatic methods for the synthesis of the three most abundant acyl-CoA thioester classes in biology; saturated acyl-CoAs, α,β-unsaturated acyl-CoAs (i.e., enoyl-CoA derivatives), and α-carboxylated acyl-CoAs (i.e., malonyl-CoA derivatives). Additionally we report on the substrate promiscuity of three newly described acyl-CoA dehydrogenases that allow the simple conversion of acyl-CoAs into enoyl-CoAs. With these five methods, we synthesized 26 different CoA-thioesters with a yield of 40% or higher. The CoA esters produced range from short- to long-chain, include branched and α,β-unsaturated representatives as well as other functional groups. Based on our results we provide a general guideline to the optimal synthesis method of a given CoA-thioester in respect to its functional group(s) and the commercial availability of the precursor molecule. The proposed synthetic routes can be performed in small scale and do not require special chemical equipment, making them convenient also for biological laboratories. PMID: 27104508 [PubMed - as supplied by publisher]

Translational and emerging clinical applications of metabolomics in cardiovascular disease diagnosis and treatment. Eur J Prev Cardiol. 2016 Apr 21; Authors: Dona AC, Coffey S, Figtree G Abstract Numerous molecular screening strategies have recently been developed to measure the chemical diversity of a population's biofluids with the ultimate aim to provide clinicians, medical scientists and epidemiologists with a clearer picture of the presence and severity of cardiovascular disease; prognosis; and response to treatment. Current cardiology practice integrates clinical history and examination with state-of-the-art imaging, invasive measures, and electrical interrogation. Biomarkers in common clinical use are relatively limited to troponin and brain natriuretic peptide, dependent on damage to heart muscle, or myocyte 'stretch' respectively. Although they have been recently applied to risk stratification in asymptomatic individuals at higher risk, the development of markers capable of detecting earlier phases of disease development would facilitate targeted strategies to prevent pathological complications in the general community. Metabolomics is the systematic study of small molecules in biological fluids. Profiling strategies aim to comprehensively measure and quantify such biomarkers in a fast, cost-effective and clinically informative manner. Techniques tend to be applied in an unbiased fashion, with advanced statistical methods allowing for identification of signature profiles in particular cohorts. In this manner, metabolomics has the potential to identify new pathophysiological pathways, and thus therapeutic targets, as well as assist in improved risk-stratification and personalized cardiovascular medicine. The latter has great potential in the primary and secondary cardiovascular disease prevention settings, integrating known and as yet unidentified host and environmental factors. The current review discusses applications of metabolomic techniques relevant to both the research and the clinical cardiologist. PMID: 27103630 [PubMed - as supplied by publisher]

Metabolic changes may precede proteostatic dysfunction in a Drosophila model of amyloid beta peptide toxicity. Neurobiol Aging. 2016 May;41:39-52 Authors: Ott S, Vishnivetskaya A, Malmendal A, Crowther DC Abstract Amyloid beta (Aβ) peptide aggregation is linked to the initiation of Alzheimer's disease; accordingly, aggregation-prone isoforms of Aβ, expressed in the brain, shorten the lifespan of Drosophila melanogaster. However, the lethal effects of Aβ are not apparent until after day 15. We used shibire(TS) flies that exhibit a temperature-sensitive paralysis phenotype as a reporter of proteostatic robustness. In this model, we found that increasing age but not Aβ expression lowered the flies' permissive temperature, suggesting that Aβ did not exert its lethal effects by proteostatic disruption. Instead, we observed that chemical challenges, in particular oxidative stressors, discriminated clearly between young (robust) and old (sensitive) flies. Using nuclear magnetic resonance spectroscopy in combination with multivariate analysis, we compared water-soluble metabolite profiles at various ages in flies expressing Aβ in their brains. We observed 2 genotype-linked metabolomic signals, the first reported the presence of any Aβ isoform and the second the effects of the lethal Arctic Aβ. Lethality was specifically associated with signs of oxidative respiration dysfunction and oxidative stress. PMID: 27103517 [PubMed - in process]

Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses. Sci Rep. 2016;6:24828 Authors: Aho V, Ollila HM, Kronholm E, Bondia-Pons I, Soininen P, Kangas AJ, Hilvo M, Seppälä I, Kettunen J, Oikonen M, Raitoharju E, Hyötyläinen T, Kähönen M, Viikari JS, Härmä M, Sallinen M, Olkkonen VM, Alenius H, Jauhiainen M, Paunio T, Lehtimäki T, Salomaa V, Orešič M, Raitakari OT, Ala-Korpela M, Porkka-Heiskanen T Abstract Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases. PMID: 27102866 [PubMed - in process]

Dietary proanthocyanidins boost hepatic NAD(+) metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats. Sci Rep. 2016;6:24977 Authors: Aragonès G, Suárez M, Ardid-Ruiz A, Vinaixa M, Rodríguez MA, Correig X, Arola L, Bladé C Abstract Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD(+)) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD(+) precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD(+). Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD(+) availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD(+) levels. PMID: 27102823 [PubMed - in process]

Related Articles A metabolomic approach to dry eye disorders. The role of oral supplements with antioxidants and omega 3 fatty acids. Mol Vis. 2015;21:555-67 Authors: Galbis-Estrada C, Pinazo-Durán MD, Martínez-Castillo S, Morales JM, Monleón D, Zanon-Moreno V Abstract PURPOSE: We used nuclear magnetic resonance spectroscopy of hydrogen-1 nuclei ((1)H NMR S) to analyze the metabolic profile of reflex tears from patients with dry eye disorders. METHODS: We performed a prospective case-control study involving 90 participants: 55 patients diagnosed with dry eye syndrome (DESG) and 35 healthy subjects (control group, CG). From the DESG, two subgroups were formed: mild DES (n=22) and moderate DES (n=33). Participants were prescribed an oral nutraceutic supplementation containing antioxidants and essential polyunsaturated fatty acids to be taken as three capsules per day for 3 months. Reflex tears (20-30 µl) were collected from the tear meniscus of both eyes of each subject with a microglass pipette. Nuclear magnetic resonance (NMR) spectra were acquired with a standard one-dimensional pulse sequence with water suppression; 256 free induction decays were collected into 64,000 data points with 14 ppm spectral width. RESULTS: Basal tears showed a differential metabolomic profile between groups. Almost 50 metabolites were identified by H cholesterol, N-acetylglucosamine, glutamate, amino-n-butyrate, choline, glucose, and formate were detected before supplementation and choline/acetylcholine after supplementation. The metabolic profile of the tears was statistically different between groups, as well as before and after supplementation. CONCLUSIONS: Our data indicate that DES induces changes in the tear metabolic profile that can be modified with appropriate oral supplementation with antioxidants and essential polyunsaturated fatty acids. PMID: 25999682 [PubMed - indexed for MEDLINE]

Related Articles A Preliminary Investigation of NSCL/P Plasma and Urine in Guizhou Province in China Using NMR-Based Metabonomics. Cleft Palate Craniofac J. 2013 Sep;50(5):603-9 Authors: Lei HG, Hong L, Kun SJ, Hai YX, Dong WY, Ke Z, Ping X, Hao C Abstract Objective : To assess the feasibility of metabonomics in clinical studies. This is a pilot study introducing nuclear magnetic resonance (NMR)-based metabonomics to elucidate and compare the metabolism of patients with nonsyndromic cleft lip and/or palate (NSCL/P) and children without orofacial clefts. Methods : High-resolution (1)H NMR spectroscopy was performed on plasma and urine samples obtained from NSCL/P and healthy children. The (1)H NMR spectra were further analyzed with principal component analysis. Results : Compared to the control group, the level of low-molecular-weight metabolites in plasma such as asparagine was higher in NSCL/P patients, while arginine, lysine, acetate, lactate, proline, glutamine, pyruvate, creatinine, choline, and β-glucose were lower. The carnitine, citrate, and formate excretion in urine appeared to be higher in the healthy children, while the NSCL/P group excreted higher concentrations of aspartic acid and phenylalanine in urine. Conclusion : The present study clearly demonstrated the great potential of NMR-based metabonomics in elucidating NSCL/P plasma metabolism and the possible application of this technology in clinical diagnosis and screening. PMID: 22612714 [PubMed - indexed for MEDLINE]

Related Articles LC/MS-based metabolomics strategy to assess the amelioration effects of ginseng total saponins on memory deficiency induced by simulated microgravity. J Pharm Biomed Anal. 2016 Apr 1;125:329-338 Authors: Feng L, Yue XF, Chen YX, Liu XM, Wang LS, Cao FR, Wang Q, Liao YH, Pan RL, Chang Q Abstract Microgravity-induced memory deficiency seriously affects learning and memory ability of the astronaut during spaceflight, with few effective countermeasures. Panax ginseng C. A. Mey. has been used as a nootropic herb for thousands of years in Asian countries. Saponins are recognized as its major active components. Previous studies have shown that ginseng saponins offer protection against memory deficits caused by various factors. Nevertheless, the underlying mechanisms of their nootropic effects are still largely unknown. In this study, we evaluated the memory-improving effects of ginseng total saponins (GTS) on simulated microgravity hindlimb-unloaded rats using a metabolomics approach. After being exposed to a 7-days hindlimb unloading (HU), variations of plasmatic and hippocampal metabolic profiles of rats with and without GTS intervention were examined by a liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics method. Subsequently, 8 hippocampal neurotransmitters were determined using a LC-MS/MS method. Finally, a LC-MS/MS based targeted metabolomics was performed to validate biomarkers found in the untargeted analysis. Besides, to support the metabolomics results, passive avoidance (PA) test, Nissl staining, and plasmatic corticosterone (CORT) levels determination were performed. The results showed that HU could lead to variations of 7 neurotransmitters and significantly different plasmatic and hippocampal metabolic profiles. GTS could restore most of the imbalanced neurotransmitters, especially glutamic acid and acetylcholine, and correct the levels of various disturbed learning and memory relevant biomarkers such as asparagine, phenylalanine, tyrosine, tryptophan, and choline. In addition, GTS could markedly ameliorate HU-induced memory deficiency, protect hippocampal neurons from damage, and down-regulate elevated CORT levels. In conclusion, GTS exhibits memory-improving effects mainly through regulating the metabolism of amino acids, neurotransmitters, choline, kynurenine, and sphingolipids. The findings of this study not only can deepen our understanding of the underlying molecular mechanisms of MG-induced memory disorders, but also provide scientific evidence for choosing ginseng as a countermeasure against MG-induced memory deficiency. PMID: 27100700 [PubMed - as supplied by publisher]

Related Articles Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human. PLoS One. 2016;11(4):e0153970 Authors: Zanotto-Filho A, Dashnamoorthy R, Loranc E, de Souza LH, Moreira JC, Suresh U, Chen Y, Bishop AJ Abstract Alkylating agents are a key component of cancer chemotherapy. Several cellular mechanisms are known to be important for its survival, particularly DNA repair and xenobiotic detoxification, yet genomic screens indicate that additional cellular components may be involved. Elucidating these components has value in either identifying key processes that can be modulated to improve chemotherapeutic efficacy or may be altered in some cancers to confer chemoresistance. We therefore set out to reevaluate our prior Drosophila RNAi screening data by comparison to gene expression arrays in order to determine if we could identify any novel processes in alkylation damage survival. We noted a consistent conservation of alkylation survival pathways across platforms and species when the analysis was conducted on a pathway/process level rather than at an individual gene level. Better results were obtained when combining gene lists from two datasets (RNAi screen plus microarray) prior to analysis. In addition to previously identified DNA damage responses (p53 signaling and Nucleotide Excision Repair), DNA-mRNA-protein metabolism (transcription/translation) and proteasome machinery, we also noted a highly conserved cross-species requirement for NRF2, glutathione (GSH)-mediated drug detoxification and Endoplasmic Reticulum stress (ER stress)/Unfolded Protein Responses (UPR) in cells exposed to alkylation. The requirement for GSH, NRF2 and UPR in alkylation survival was validated by metabolomics, protein studies and functional cell assays. From this we conclude that RNAi/gene expression fusion is a valid strategy to rapidly identify key processes that may be extendable to other contexts beyond damage survival. PMID: 27100653 [PubMed - as supplied by publisher]

Related Articles Childhood obesity: a systems medicine approach. Front Biosci (Landmark Ed). 2016;21:1061-1075 Authors: Stone WL, Schetzina K, Stuart C Abstract Childhood obesity and its sequelae are a major public health problem in both the USA and globally. This review will focus on a systems medicine approach to obesity. Systems medicine is an integrative approach utilizing the vast amount of data garnered from "omics" technology and integrating these data with conventional pathophysiology as well as diverse environmental factors such as diet, exercise, community dynamics and the intestinal microbiome. Omics technology includes genomics, epigenomics, metagenomics, metabolomics and proteomics. In addition to unraveling etiology, the goals of a systems medicine approach are to provide actionable and evidenced-based clinical approaches. In the case of childhood obesity, an additional goal is characterizing measureable risk factors/biomarkers for obesity at the earliest possible age and devising age-appropriate optimal intervention strategies. It is also important to establish the age at which interventions could be critical. As discussed below, it is possible that some of the pathophysiological and epigenetic changes resulting from childhood obesity could become more irreversible the longer the obesity remains untreated. PMID: 27100491 [PubMed - as supplied by publisher]

Related Articles Proteomics and Metabolomics Analyses to Elucidate the Desulfurization Pathway of Chelatococcus sp. PLoS One. 2016;11(4):e0153547 Authors: Bordoloi NK, Bhagowati P, Chaudhuri MK, Mukherjee AK Abstract Desulfurization of dibenzothiophene (DBT) and alkylated DBT derivatives present in transport fuel through specific cleavage of carbon-sulfur (C-S) bonds by a newly isolated bacterium Chelatococcus sp. is reported for the first time. Gas chromatography-mass spectrometry (GC-MS) analysis of the products of DBT degradation by Chelatococcus sp. showed the transient formation of 2-hydroxybiphenyl (2-HBP) which was subsequently converted to 2-methoxybiphenyl (2-MBP) by methylation at the hydroxyl group of 2-HBP. The relative ratio of 2-HBP and 2-MBP formed after 96 h of bacterial growth was determined at 4:1 suggesting partial conversion of 2-HBP or rapid degradation of 2-MBP. Nevertheless, the enzyme involved in this conversion process remains to be identified. This production of 2-MBP rather than 2-HBP from DBT desulfurization has a significant metabolic advantage for enhancing the growth and sulfur utilization from DBT by Chelatococcus sp. and it also reduces the environmental pollution by 2-HBP. Furthermore, desulfurization of DBT derivatives such as 4-M-DBT and 4, 6-DM-DBT by Chelatococcus sp. resulted in formation of 2-hydroxy-3-methyl-biphenyl and 2-hydroxy -3, 3/- dimethyl-biphenyl, respectively as end product. The GC and X-ray fluorescence studies revealed that Chelatococcus sp. after 24 h of treatment at 37°C reduced the total sulfur content of diesel fuel by 12% by per gram resting cells, without compromising the quality of fuel. The LC-MS/MS analysis of tryptic digested intracellular proteins of Chelatococcus sp. when grown in DBT demonstrated the biosynthesis of 4S pathway desulfurizing enzymes viz. monoxygenases (DszC, DszA), desulfinase (DszB), and an NADH-dependent flavin reductase (DszD). Besides, several other intracellular proteins of Chelatococcus sp. having diverse biological functions were also identified by LC-MS/MS analysis. Many of these enzymes are directly involved with desulfurization process whereas the other enzymes/proteins support growth of bacteria at an expense of DBT. These combined results suggest that Chelatococcus sp. prefers sulfur-specific extended 4S pathway for deep-desulphurization which may have an advantage for its intended future application as a promising biodesulfurizing agent. PMID: 27100386 [PubMed - as supplied by publisher]

Related Articles Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring. Kidney Blood Press Res. 2016 Apr 22;41(3):250-257 Authors: Li J, Lu YP, Reichetzeder C, Kalk P, Kleuser B, Adamski J, Hocher B Abstract BACKGROUND/AIMS: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. METHODS: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. RESULTS: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. CONCLUSIONS: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age. PMID: 27100327 [PubMed - as supplied by publisher]

Related Articles The biochemical origins of the surface-enhanced Raman spectra of bacteria: a metabolomics profiling by SERS. Anal Bioanal Chem. 2016 Apr 21; Authors: Premasiri WR, Lee JC, Sauer-Budge A, Théberge R, Costello CE, Ziegler LD Abstract The dominant molecular species contributing to the surface-enhanced Raman spectroscopy (SERS) spectra of bacteria excited at 785 nm are the metabolites of purine degradation: adenine, hypoxanthine, xanthine, guanine, uric acid, and adenosine monophosphate. These molecules result from the starvation response of the bacterial cells in pure water washes following enrichment from nutrient-rich environments. Vibrational shifts due to isotopic labeling, bacterial SERS spectral fitting, SERS and mass spectrometry analysis of bacterial supernatant, SERS spectra of defined bacterial mutants, and the enzymatic substrate dependence of SERS spectra are used to identify these molecular components. The absence or presence of different degradation/salvage enzymes in the known purine metabolism pathways of these organisms plays a central role in determining the bacterial specificity of these purine-base SERS signatures. These results provide the biochemical basis for the development of SERS as a rapid bacterial diagnostic and illustrate how SERS can be applied more generally for metabolic profiling as a probe of cellular activity. Graphical Abstract Bacterial typing by metabolites released under stress. PMID: 27100230 [PubMed - as supplied by publisher]