PubMed

SERUM metabolomics of acute lymphoblastic leukaemia and acute myeloid leukaemia for probing biomarker molecules. Hematol Oncol. 2016 Jun 10; Authors: Musharraf SG, Siddiqui AJ, Shamsi T, Naz A Abstract Acute leukaemia (AL) is a critical neoplasm of white blood cells. Diagnosing AL requires bone marrow puncture procedure, which many patients do not consent to for it is invasive. Hence sensitive and specific early diagnostic biomarkers are essential for non-invasive diagnosis, new therapeutics and improving the disease prognosis. To differentiate the metabolic alterations associated with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), we investigated serum of ALL and AML patients in comparison with two controls using gas chromatography coupled with triple quadrupole tandem mass spectrometry and multivariate statistical analysis. Twenty seven out of 1425 metabolites were found differentiative among ALL, AML, aplastic anaemia (APA) patients and healthy control using p-value ≤ 0.001. ALL is the most dissimilar group from other three groups as in hierarchical clustering showed 72.1% dissimilarity. Model generation using PLSDA gave an overall accuracy of 91.9%. This study helps in metabolic fingerprinting of control and disease serum at high significance levels and could be used for early diagnosing of AL. Based on pathways analysis, fatty acid metabolism is deregulated in patients with AL and may represent an underlying metabolic pathway associated with disease progression. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27283238 [PubMed - as supplied by publisher]

(1)H-NMR based metabolomics reveals a pedoclimatic metabolic imprinting in ready to drink carrot juices. J Agric Food Chem. 2016 Jun 9; Authors: Tomassini A, Sciubba F, Di Cocco ME, Capuani G, Delfini M, Aureli W, Miccheli A Abstract Carrots are usually consumed as such or processed into many different products. Carrot juice is a popular beverage consumed throughout the world and is attracting more attention due to its nutritional value, being a natural source of bioactive compounds. Ready-to-drink carrot juices produced in the same factory, were analyzed by 1H Nuclear Magnetic Resonance (NMR) spectroscopy. The juices were obtained from carrots roots of the same cultivar grown in three different geographical areas in Italy. More than 30 metabolites have been identified and quantified and the data were analyzed by univariate ANOVA and multivariate analyses. A geographical-dependent clear clustering was observed and the metabolic profiles were related to the different pedoclimatic conditions. The proposed phytoprofiling approach could be employed on industrial scale in order to evaluate finished products in relation to different sites of supply of the raw material thus improving both the quality and the uniformity of the juices. PMID: 27281439 [PubMed - as supplied by publisher]

Serum-Based Oxylipins Are Associated with Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients. PLoS One. 2016;11(6):e0157035 Authors: Zhang Y, Guallar E, Blasco-Colmenares E, Harms AC, Vreeken RJ, Hankemeier T, Tomaselli GF, Cheng A Abstract INTRODUCTION: Individuals with systolic heart failure are at risk of ventricular arrhythmias and all-cause mortality. Little is known regarding the mechanisms underlying these events. We sought to better understand if oxylipins, a diverse class of lipid metabolites derived from the oxidation of polyunsaturated fatty acids, were associated with these outcomes in recipients of primary prevention implantable cardioverter defibrillators (ICDs). METHODS: Among 479 individuals from the PROSE-ICD study, baseline serum were analyzed and quantitatively profiled for 35 known biologically relevant oxylipin metabolites. Associations with ICD shocks for ventricular arrhythmias and all-cause mortality were evaluated using Cox proportional hazards models. RESULTS: Six oxylipins, 17,18-DiHETE (HR = 0.83, 95% CI 0.70 to 0.99 per SD change in oxylipin level), 19,20-DiHDPA (HR = 0.79, 95% CI 0.63 to 0.98), 5,6-DiHETrE (HR = 0.73, 95% CI 0.58 to 0.91), 8,9-DiHETrE (HR = 0.76, 95% CI 0.62 to 0.95), 9,10-DiHOME (HR = 0.81, 95% CI 0.65 to 1.00), and PGF1α (HR = 1.33, 95% CI 1.04 to 1.71) were associated with the risk of appropriate ICD shock after multivariate adjustment for clinical factors. Additionally, 4 oxylipin-to-precursor ratios, 15S-HEPE / FA (20:5-ω3), 17,18-DiHETE / FA (20:5-ω3), 19,20-DiHDPA / FA (20:5-ω3), and 5S-HEPE / FA (20:5-ω3) were positively associated with the risk of all-cause mortality. CONCLUSION: In a prospective cohort of patients with primary prevention ICDs, we identified several novel oxylipin markers that were associated with appropriate shock and mortality using metabolic profiling techniques. These findings may provide new insight into the potential biologic pathways leading to adverse events in this patient population. PMID: 27281224 [PubMed - as supplied by publisher]

1H NMR metabolomics of plasma unveils liver dysfunction in dengue patients. J Virol. 2016 Jun 8; Authors: El-Bacha T, Struchiner CJ, Cordeiro MT, Almeida FC, de Azevedo Marques ET, Da Poian AT Abstract Dengue, due to its global burden, is the most important arthropod-born flavivirus disease and early detection lowers fatality rates to below 1%. Since the metabolic resources crucial for viral replication are provided by host cells, detecting changes in the metabolic profile associated with disease pathogenesis could help identifying markers of prognostic and diagnostic importance. We applied (1)H NMR exploratory metabolomics to study longitudinal changes in plasma metabolites in a cohort in Recife, Brazil. To gain statistical power, we used innovative paired multivariate analyzes to discriminate individuals with dengue fever (DF; mild) and dengue hemorrhagic fever (DHF; severe) presenting primary and secondary infection and subjects with non-specific infection (ND). Our results showed that a decrease in plasma LDL and VLDL discriminated dengue-infected from ND subjects and also those subjects with severe infection presented an even decrease in lipoproteins concentration when compared to subjects with mild infection. These results add to the ongoing discussion that manipulation of lipid metabolism is crucial for DENV replication and infection. In addition, a decrease in plasma glutamine was characteristic of DENV infection and disease severity and an increase in plasma acetate discriminated subjects with DF and DHF from ND-subjects. Several other metabolites showed to be altered in DENV infection and the implications of these alterations are discussed. We hypothesize that these changes in plasma metabolome are suggestive of liver dysfunction and could provide insights into the underlying molecular mechanisms of dengue pathogenesis and could help discriminating individuals at risk to develop severe infection and to predict disease outcome. IMPORTANCE: Dengue virus infection, due to its global burden, is the most important mosquito-born viral disease. There is no specific treatment for dengue disease and early detection lowers fatality rates to below 1%. In this study we observed the effects of dengue virus infection on the profile of small molecules in the blood of patients with mild and severe infection. Variations in the profile of these small molecules reflect the replication of dengue virus in different tissues and the extent of tissue damage during infection. The results of this study showed that the molecules that changed the most were VLDL and LDL lipoproteins and amino acids. We proposed that these changes reflect liver dysfunction and also that they can be used to discriminate subjects with mild and severe dengue infection. PMID: 27279613 [PubMed - as supplied by publisher]

Screening of Indian Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes): A UPC2-SQD-MS Approach. Int J Med Mushrooms. 2016;18(2):177-89 Authors: Bhardwaj A, Srivastava M, Pal M, Sharma YK, Bhattacharya S, Tulsawani R, Sugadev R, Misra K Abstract Oriental medicinal mushroom Ganoderma lucidum has been widely used for the promotion of health and longevity owing to its various bioactive constituents. Therefore, comprehending metabolomics of different G. lucidum parts could be of paramount importance for investigating their pharmacological properties. Ultra-performance convergence chromatography (UPC2) along with mass spectrometry (MS) is an emerging technique that has not yet been applied for metabolite profiling of G. lucidum. This study has been undertaken to establish metabolomics of the aqueous extracts of mycelium (GLM), fruiting body (GLF), and their mixture (GLMF) using ultra-performance convergence chromatography single quadrupole mass spectrometry (UPC2-SQD-MS). Aqueous extracts of G. lucidum prepared using an accelerated solvent extraction technique have been characterized for their mycochemical activities in terms of total flavonoid content, 1,1-diphenyl-2-picryl-hydrazyl scavenging activity, and ferric ion reducing antioxidant power. The UPC2-SQD-MS technique has been used for the first time for metabolite profiling of G. lucidum on a Princeton Diol column (4.6 × 250 mm; 5 µm) using supercritical CO2 (solvent) and 20 mM ammonium acetate in methanol (co-solvent). In the present study, UPC2-SQD-MS was found to be a rapid, efficient, and high-throughput analytical technique, whose coupling to principal component analysis (PCA) and phytochemical evaluation could be used as a powerful tool for elucidating metabolite diversity between mycelium and fruiting body of G. lucidum. PCA showed a clear distinction in the metabolite compositions of the samples. Mycochemical studies revealed that overall GLF possessed better antioxidant properties among the aqueous extracts of G. lucidum. PMID: 27279539 [PubMed - in process]

Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis. J Clin Lab Anal. 2016 Jun 9; Authors: Hu Z, Zhu Z, Cao Y, Wang L, Sun X, Dong J, Fang Z, Fang Y, Xu X, Gao P, Hongzhi S Abstract Cerebral infarction (CI) and intracerebral hemorrhage are lethal cerebrovascular diseases, sometimes sharing similar clinical manifestations but with distinct therapeutic strategies. Delayed treatment usually resulted in poor prognosis. A timely diagnosis report is highly warranted especially in emergency. One hundred twenty-nine CI patients, 73 intracerebral hemorrhage (ICH) patients, and 98 controls were enrolled in this study. A direct injection mass spectrometry metabolomics approach was adopted using dried blood spot samples. This targeted metabolomics analysis focused on absolute quantitation of 23 amino acids, 26 carnitine/carnitine esters, and 22 calculated ratios parameters. Compared to the normal control group, CI and ICH showed distinct metabolite changes, respectively. For stroke differentiation, Tyr, C5-OH/C0, Cit, Asn, Pro, Val, Arg/Orn, Leu, and Val/Phe were elevated in the CI group. On the contrary, C5:1, Phe/Tyr, (C0 + C2 + C3 + C16 + C18:1)/Cit, and Met/Leu were of lower levels in the CI group. Using regression model based on some of the above-mentioned parameters, 79.07% of stroke patients from a new set could be definitely confirmed. This study proved the targeted metabolomics analysis was a promising tool for rapid and timely stroke differentiation. PMID: 27278546 [PubMed - as supplied by publisher]

Chemical composition and anti-inflammatory activity of the leaves of Byrsonima verbascifolia. J Nat Med. 2016 Jun 8; Authors: Saldanha AA, do Carmo LF, do Nascimento SB, de Matos NA, de Carvalho Veloso C, Castro AH, De Vos RC, Klein A, de Siqueira JM, Carollo CA, do Nascimento TV, Toffoli-Kadri MC, Soares AC Abstract An ethnopharmacological survey indicates that the genus Byrsonima has some medicinal species that are commonly found in the Brazilian Cerrado and has been used as an anti-inflammatory and for gastroduodenal disorders. The aim of this study was to evaluate the anti-inflammatory and antioxidant activity along with qualitative chemical characterization of the methanolic extract of the leaves of Byrsonima verbascifolia (BvME) obtained by exhaustive percolation. The data from the chemical analyses by liquid chromatography-mass spectrometry led to tentative identification of 42 compounds belonging to proanthocyanidins, galloyl quinic acid derivatives, flavonoids, and triterpene glycoside derivatives. BvME contain flavonoids and show an antioxidative activity. The methanolic extract administered intraperitoneally at doses of 50, 100, or 300 mg/kg showed a significant reduction in paw edema and modulated the neutrophil influx in a mouse model. Furthermore, the anti-edematogenic activity of the extract provided in smaller doses (12.5 and 25 mg/kg) was also demonstrated in a mouse paw edema model. The extract inhibited NO production by macrophages induced by lipopolysaccharide. We presume that the anti-inflammatory effects of BvME are due to a combination of compounds present in B. verbascifolia, including catechins (procyanidins), flavonoids, and triterpene glycosides and that these anti-inflammatory actions should be mediated, at least partly, through the inhibition of NO production. This study supports and validates the ethnopharmacological uses of B. verbascifolia as an anti-inflammatory. PMID: 27278224 [PubMed - as supplied by publisher]

41 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 2016/06/09PubMed comprises more than 24 million 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.

Bioaccumulation and metabolomics responses in oysters Crassostrea hongkongensis impacted by different levels of metal pollution. Environ Pollut. 2016 Jun 1;216:156-165 Authors: Cao C, Wang WX Abstract Jiulong River Estuary, located in southern China, was heavily contaminated by metal pollution. In this study, the estuarine oysters Crassostrea hongkongensis were transplanted to two sites with similar hydrological conditions but different levels of metal pollution in Jiulong River Estuary over a six-month period. We characterized the time-series change of metal bioaccumulation and final metabolomics responses of oysters. Following transplantation, all metals (Cd, Cu, Cr, Ni, Pb, and Zn) in the oyster digestive glands had elevated concentrations over time. By the end of six-month exposure, Cu, Zn and Cd were the main metals significantly differentiating the two sites. Using (1)H NMR metabolite approach, we further demonstrated the disturbance in osmotic regulation, energy metabolism, and glycerophospholipid metabolism induced by metal contaminations. Six months later, the oysters transplanted in the two sites showed a similar metabolite variation pattern when compared with the initial oysters regardless of different metal levels in the tissues. Interestingly, by comparing the oysters from two sites, the more severely polluted oysters accumulated significantly higher amounts of osmolytes (betaine and homarine) and lower energy storage compounds (glycogen) than the less polluted oysters; these changes could be the potential biomarkers for different levels of metal pollution. Our study demonstrated the complexity of biological effects under field conditions, and NMR metabolomics provides an important approach to detect sensitive variation of oyster inner status. PMID: 27262129 [PubMed - as supplied by publisher]

Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target. Asian Pac J Trop Med. 2016 Jun;9(6):525-534 Authors: Krungkrai SR, Krungkrai J Abstract Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria. PMID: 27262062 [PubMed - as supplied by publisher]

Establishment of local searching methods for orbitrap-based high throughput metabolomics analysis. Talanta. 2016 Aug 15;156-157:163-71 Authors: Tang H, Wang X, Xu L, Ran X, Li X, Chen L, Zhao X, Deng H, Liu X Abstract Our method aims to establish local endogenous metabolite databases economically without purchasing chemical standards, giving strong bases for following orbitrap based high throughput untargeted metabolomics analysis. A new approach here is introduced to construct metabolite databases on the base of biological sample analysis and mathematic extrapolation. Building local metabolite databases traditionally requires expensive chemical standards, which is barely affordable for most research labs. As a result, most labs working on metabolomics analysis have to refer public libraries, which is time consuming and limited for high throughput analysis. Using this strategy, a high throughput orbitrap based metabolomics platform can be established at almost no cost within a couple of months. It enables to facilitate the application of high throughput metabolomics analysis to identify disease-related biomarkers or investigate biological functions using orbitrap. PMID: 27260449 [PubMed - in process]

Genetic transformation of rare Verbascum eriophorum Godr. plants and metabolic alterations revealed by NMR-based metabolomics. Biotechnol Lett. 2016 Jun 3; Authors: Marchev A, Yordanova Z, Alipieva K, Zahmanov G, Rusinova-Videva S, Kapchina-Toteva V, Simova S, Popova M, Georgiev MI Abstract OBJECTIVES: To develop a protocol to transform Verbascum eriophorum and to study the metabolic differences between mother plants and hairy root culture by applying NMR and processing the datasets with chemometric tools. RESULTS: Verbascum eriophorum is a rare species with restricted distribution, which is poorly studied. Agrobacterium rhizogenes-mediated genetic transformation of V. eriophorum and hairy root culture induction are reported for the first time. To determine metabolic alterations, V. eriophorum mother plants and relevant hairy root culture were subjected to comprehensive metabolomic analyses, using NMR (1D and 2D). Metabolomics data, processed using chemometric tools (and principal component analysis in particular) allowed exploration of V. eriophorum metabolome and have enabled identification of verbascoside (by means of 2D-TOCSY NMR) as the most abundant compound in hairy root culture. CONCLUSION: Metabolomics data contribute to the elucidation of metabolic alterations after T-DNA transfer to the host V. eriophorum genome and the development of hairy root culture for sustainable bioproduction of high value verbascoside. PMID: 27259724 [PubMed - as supplied by publisher]

Related Articles Compartmentation of metabolites in regulating epigenome of cancer. Mol Med. 2016 Apr 14;22 Authors: Zhao Z, Wang L, Di LJ Abstract Covalent modification of DNA and histones are important epigenetic events and the genome wide reshaping of epigenetic markers is common in cancer. The epigenetic markers are produced by enzymatic reactions and some of these reactions require the presence of metabolites as cofactors (termed Epigenetic Enzyme Required Metabolites, EERMs). Recent studies found that the abundance of these EERMs correlates with epigenetic enzymes activity. Also, the subcellular compartmentation, especially the nuclear localization of these EERMs may play a role in regulating the activities of epigenetic enzymes. Moreover, gene specific recruitment of enzymes which produce the EERMs in the proximity of the epigenetic modification events accompanying the gene expression regulation, were proposed. Therefore, it is of importance to summarize these findings of the EERMs in regulating the epigenetic modifications at both DNA and histone levels, and to understand how EERMs contribute to cancer development by addressing their global versus local distribution. PMID: 27258652 [PubMed - as supplied by publisher]

Related Articles Development of Database Assisted Structure Identification (DASI) Methods for Nontargeted Metabolomics. Metabolites. 2016;6(2) Authors: Menikarachchi LC, Dubey R, Hill DW, Brush DN, Grant DF Abstract Metabolite structure identification remains a significant challenge in nontargeted metabolomics research. One commonly used strategy relies on searching biochemical databases using exact mass. However, this approach fails when the database does not contain the unknown metabolite (i.e., for unknown-unknowns). For these cases, constrained structure generation with combinatorial structure generators provides a potential option. Here we evaluated structure generation constraints based on the specification of: (1) substructures required (i.e., seed structures); (2) substructures not allowed; and (3) filters to remove incorrect structures. Our approach (database assisted structure identification, DASI) used predictive models in MolFind to find candidate structures with chemical and physical properties similar to the unknown. These candidates were then used for seed structure generation using eight different structure generation algorithms. One algorithm was able to generate correct seed structures for 21/39 test compounds. Eleven of these seed structures were large enough to constrain the combinatorial structure generator to fewer than 100,000 structures. In 35/39 cases, at least one algorithm was able to generate a correct seed structure. The DASI method has several limitations and will require further experimental validation and optimization. At present, it seems most useful for identifying the structure of unknown-unknowns with molecular weights <200 Da. PMID: 27258318 [PubMed - as supplied by publisher]

Related Articles Plant Metabolomics: An Indispensable System Biology Tool for Plant Science. Int J Mol Sci. 2016;17(6) Authors: Hong J, Yang L, Zhang D, Shi J Abstract As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality. PMID: 27258266 [PubMed - as supplied by publisher]

Related Articles Application of Two-Dimensional Nuclear Magnetic Resonance for Signal Enhancement by Spectral Integration Using a Large Dataset of Metabolic Mixtures. Anal Chem. 2016 Jun 3; Authors: Misawa T, Wei F, Kikuchi J Abstract Nuclear magnetic resonance (NMR) spectroscopy has tremendous advantages of minimal sample preparation and inter-convertibility of data among different institutions; thus, large datasets are frequently acquired in metabolomics studies. Pre-viously, we used a novel analytical strategy, named signal enhancement by spectral integration (SENSI), to overcome the low signal to noise ratio (S/N ratio) problem in (13)C NMR by integration of hundreds of spectra without additional measure-ments. In this letter, the development of a SENSI 2D method and application to >1000 2D JRES NMR spectra are described. Remarkably, the obtained SENSI 2D spectrum had an approximate 14-fold increase in the S/N ratio and 80-250 additional peaks without any additional measurements. These results suggest that SENSI 2D is a useful method for assigning weak signals and that the use of coefficient of variation values can support the assignment information and extraction of features from the population characteristics among large datasets. PMID: 27257670 [PubMed - as supplied by publisher]

Related Articles ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling. Science. 2016 Jun 3;352(6290):1221-5 Authors: Wright RH, Lioutas A, Le Dily F, Soronellas D, Pohl A, Bonet J, Nacht AS, Samino S, Font-Mateu J, Vicent GP, Wierer M, Trabado MA, Schelhorn C, Carolis C, Macias MJ, Yanes O, Oliva B, Beato M Abstract Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming enzymes. It remains unclear how the ATP demands of such processes are met in response to rapid stimuli. We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP-ribose) to ADP-ribose. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. The nuclear source of ATP is essential for hormone-induced chromatin remodeling, transcriptional regulation, and cell proliferation. PMID: 27257257 [PubMed - in process]

Related Articles Identification of Rare Variants in Metabolites of the Carnitine Pathway by Whole Genome Sequencing Analysis. Genet Epidemiol. 2016 Jun 3; Authors: Yazdani A, Yazdani A, Liu X, Boerwinkle E Abstract We use whole genome sequence data and rare variant analysis methods to investigate a subset of the human serum metabolome, including 16 carnitine-related metabolites that are important components of mammalian energy metabolism. Medium pass sequence data consisting of 12,820,347 rare variants and serum metabolomics data were available on 1,456 individuals. By applying a penalization method, we identified two genes FGF8 and MDGA2 with significant effects on lysine and cis-4-decenoylcarnitine, respectively, using Δ-AIC and likelihood ratio test statistics. Single variant analyses in these regions did not identify a single low-frequency variant (minor allele count > 3) responsible for the underlying signal. The results demonstrate the utility of whole genome sequence and innovative analyses for identifying candidate regions influencing complex phenotypes. PMID: 27256581 [PubMed - as supplied by publisher]

Related Articles Autophagy in acute brain injury. Nat Rev Neurosci. 2016 Jun 3; Authors: Galluzzi L, Pedro JM, Blomgren K, Kroemer G Abstract Autophagy is an evolutionarily ancient mechanism that ensures the lysosomal degradation of old, supernumerary or ectopic cytoplasmic entities. Most eukaryotic cells, including neurons, rely on proficient autophagic responses for the maintenance of homeostasis in response to stress. Accordingly, autophagy mediates neuroprotective effects following some forms of acute brain damage, including methamphetamine intoxication, spinal cord injury and subarachnoid haemorrhage. In some other circumstances, however, the autophagic machinery precipitates a peculiar form of cell death (known as autosis) that contributes to the aetiology of other types of acute brain damage, such as neonatal asphyxia. Here, we dissect the context-specific impact of autophagy on non-infectious acute brain injury, emphasizing the possible therapeutic application of pharmacological activators and inhibitors of this catabolic process for neuroprotection. PMID: 27256553 [PubMed - as supplied by publisher]

Related Articles Metabolic profiling of potential lung cancer biomarkers using bronchoalveolar lavage fluid and the integrated direct infusion/ gas chromatography mass spectrometry platform. J Proteomics. 2016 May 30; Authors: Callejón-Leblic B, García-Barrera T, Grávalos-Guzmán J, Pereira-Vega A, Gómez-Ariza JL Abstract Lung cancer is one of the ten most common causes of death worldwide, so that the search for early diagnosis biomarkers is a very challenging task. Bronchoalveolar lavage fluid (BALF) provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomics techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. BIOLOGICAL SIGNIFICANCE: The search for early diagnosis of lung cancer is a very challenging task because of the high mortality associated to this disease and its critical linkage to the initiation of treatment. Bronchoalveolar lavage fluid provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Since BALF is in close interaction with lung tissue it is a more representative sample of lung status than other peripheral biofluids as blood or urine studied in previous works. Therefore, this study represents an innovative contribution in this topic that complement previous investigations about lung cancer, opening up new possibilities for understanding the pathogenesis of this disease and the use of efficient biomarkers. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomic techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically sifnificant differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. PMID: 27255828 [PubMed - as supplied by publisher]