PubMed

Related Articles Energetics of endurance exercise in young horses determined by nuclear magnetic resonance metabolomics. Front Physiol. 2015;6:198 Authors: Luck MM, Le Moyec L, Barrey E, Triba MN, Bouchemal N, Savarin P, Robert C Abstract Long-term endurance exercise severely affects metabolism in both human and animal athletes resulting in serious risk of metabolic disorders during or after competition. Young horses (up to 6 years old) can compete in races up to 90 km despite limited scientific knowledge of energetic metabolism responses to long distance exercise in these animals. The hypothesis of this study was that there would be a strong effect of endurance exercise on the metabolomic profiles of young horses and that the energetic metabolism response in young horses would be different from that of more experienced horses. Metabolomic profiling is a powerful method that combines Nuclear Magnetic Resonance (NMR) spectrometry with supervised Orthogonal Projection on Latent Structure (OPLS) statistical analysis. (1)H-NMR spectra were obtained from plasma samples drawn from young horses (before and after competition). The spectra obtained before and after the race from the same horse (92 samples) were compared using OPLS. The statistical parameters showed the robustness of the model (R2Y = 0.947, Q2Y = 0.856 and cros-validated ANOVA p < 0.001). For confirmation of the predictive value of the model, a test set of 104 sample spectra were projected by the model, which provided perfect predictions as the area under the receiving-operator curve was 1. The metabolomic profile determined with the OPLS model showed that glycemia after the race was lower than glycemia before the race, despite the involvement of lipid and protein catabolism. An OPLS model was calculated to compare spectra obtained on plasma taken after the race from 6-year-old horses and from experienced horses (cross-validated ANOVA p < 0.001). The comparison of metabolomic profiles in young horses to those from experienced horses showed that experienced horses maintained their glycemia with higher levels of lactate and a decrease of plasma lipids after the race. PMID: 26347654 [PubMed]

Related Articles Seasonal Variations of Metabolome and Tyrosinase Inhibitory Activity of Lespedeza maximowiczii During the Growth Periods. J Agric Food Chem. 2015 Sep 8; Authors: Kim NK, Park HM, Lee J, Ku KM, Lee CH Abstract Lespedeza species are useful for pasture and energy crops and medical plant. We determined the metabolites discriminated from the each growth period (3, 4, 6, 8, 15, and 18 months) after germination in leaves and stems of Lespedeza maximowizii by metabolomics technique. Specifically, levels of sugars and luteolin-dominated derivatives were significantly elevated in samples harvested in November. This maybe related with cold tolerance mechanism against the low temperatures of the winter season. The concentrations of secondary metabolites, isoflavones and flavanones, as well as tyrosinase inhibitory activity were the highest in 6 months samples, which were harvested in September, fall season. The tyrosinase inhibitory activity in leaves was higher than stems irrespective of the growth period. This study suggests that MS-based metabolite profiling could be used as a tool to examine quantitative or qualitative metabolite changes related to seasonal variations, and to understand the correlation between activity and metabolites. PMID: 26345477 [PubMed - as supplied by publisher]

Related Articles [Effect of Psoraleae Fructus and Myristicae Semen in "Ershen pill" on serum metabonomics in spleen-kidney Yang deficiency diarrhea rats before and after processing]. Zhongguo Zhong Yao Za Zhi. 2015 Apr;40(7):1400-3 Authors: Chen ZM, Hu CJ, Xiong R, Cui YY, Zhang M, Pan X, Zhao L Abstract The metabonomics method was used to study the intervention effect of Psoraleae Fructus and Myristicae Semen in "Ershen pill" on the changes in serum endogenous metabolites in spleen-kidney Yang deficiency diarrhea rats before and after processing, screen out differentiated metabolites related to spleen-kidney Yang deficiency diarrhea and explore the metabolic patterns related to spleen-kidney Yang deficiency diarrhea and the processing synergy mechanism of Psoraleae Fructus and Myristicae Semen in "Ershen pill". Efforts were made to detect SOD and MDA of each group, test rat serum metabolic fingerprints in different stages by using GC-MS, analyze by PCA and PLS-DA methods and screen out potential biomarks through VIP and t test. The results revealed that "Ershen pill" could enhance the level of SOD and decrease the level of MDA and identified 10 differentiated metabolites related to spleen-kidney Yang deficiency diarrhea. Compared with the model group, all of metabolites recovered to varying levels after being intervened with "Ershen pill", with the best effect shown in the "Ershen pill" IV group (salt-processed Psoraleae Fructus + bran-roasted Myristicae Semen). It is speculated that that Psoraleae Fructus and Semen Myristicae in "Ershen pill" show a synergistic effect by inhibiting peroxide, improving aglucolipid, amino acids and energy metabolism, with multiple target sites. PMID: 26281569 [PubMed - indexed for MEDLINE]

Related Articles A New View of Vitiligo: Looking at Normal-Appearing Skin. J Invest Dermatol. 2015 Jul;135(7):1713-4 Authors: Picardo M, Bastonini E Abstract Debate over the pathogenesis of vitiligo is still ongoing among scientists, with several hypotheses currently under consideration. The study by Wagner et al. in this issue focuses on the role of E-cadherin-mediated cell adhesion in vitiliginous epidermis under oxidative and mechanical stress. Their work highlights how alterations in cell-cell adhesion across nonlesional melanocyte membranes in patients with vitiligo argue for primary intrinsic defects in the melanocytes. PMID: 26066890 [PubMed - indexed for MEDLINE]

Related Articles Normalization to specific gravity prior to analysis improves information recovery from high resolution mass spectrometry metabolomic profiles of human urine. Anal Chem. 2014 Nov 4;86(21):10925-31 Authors: Edmands WM, Ferrari P, Scalbert A Abstract Extraction of meaningful biological information from urinary metabolomic profiles obtained by liquid-chromatography coupled to mass spectrometry (MS) necessitates the control of unwanted sources of variability associated with large differences in urine sample concentrations. Different methods of normalization either before analysis (preacquisition normalization) through dilution of urine samples to the lowest specific gravity measured by refractometry, or after analysis (postacquisition normalization) to urine volume, specific gravity and median fold change are compared for their capacity to recover lead metabolites for a potential future use as dietary biomarkers. Twenty-four urine samples of 19 subjects from the European Prospective Investigation into Cancer and nutrition (EPIC) cohort were selected based on their high and low/nonconsumption of six polyphenol-rich foods as assessed with a 24 h dietary recall. MS features selected on the basis of minimum discriminant selection criteria were related to each dietary item by means of orthogonal partial least-squares discriminant analysis models. Normalization methods ranked in the following decreasing order when comparing the number of total discriminant MS features recovered to that obtained in the absence of normalization: preacquisition normalization to specific gravity (4.2-fold), postacquisition normalization to specific gravity (2.3-fold), postacquisition median fold change normalization (1.8-fold increase), postacquisition normalization to urinary volume (0.79-fold). A preventative preacquisition normalization based on urine specific gravity was found to be superior to all curative postacquisition normalization methods tested for discovery of MS features discriminant of dietary intake in these urinary metabolomic datasets. PMID: 25285402 [PubMed - indexed for MEDLINE]

Insights into the impact of silver nanoparticles on human keratinocytes metabolism through NMR metabolomics. Arch Biochem Biophys. 2015 Sep 3; Authors: Carrola J, Bastos V, Ferreira de Oliveira JM, Oliveira H, Santos C, Gil AM, Duarte IF Abstract Due to their antimicrobial properties, silver nanoparticles (AgNPs) are increasingly incorporated into consumer goods and medical products. Their potential toxicity to human cells is however a major concern, and there is a need for improved understanding of their effects on cell metabolism and function. Here, Nuclear Magnetic Resonance (NMR) metabolomics was used to investigate the metabolic profile of human epidermis keratinocytes (HaCaT cell line) exposed for 48h to 30 nm citrate-stabilized spherical AgNPs (10 and 40 μg/mL). Intracellular aqueous extracts, organic extracts and extracellular culture medium were analysed to provide an integrated view of the cellular metabolic response. The specific metabolite variations, highlighted through multivariate analysis and confirmed by spectral integration, suggested that HaCaT cells exposed to AgNPs displayed upregulated glutathione-based antioxidant protection, increased glutaminolysis, downregulated tricarboxylic acid (TCA) cycle activity, energy depletion and cell membrane modification. Importantly, most metabolic changes were apparent in cells exposed to a concentration of AgNPs which did not affect cell viability at significant levels, thus underlying the sensitivity of NMR metabolomics to detect early biochemical events, even in the absence of a clear cytotoxic response. It can be concluded that NMR metabolomics is an important new tool in the field of in vitro nanotoxicology. PMID: 26344855 [PubMed - as supplied by publisher]

Metabolomic approach for improving ethanol stress tolerance in Saccharomyces cerevisiae. J Biosci Bioeng. 2015 Sep 3; Authors: Ohta E, Nakayama Y, Mukai Y, Bamba T, Fukusaki E Abstract The budding yeast Saccharomyces cerevisiae is widely used for brewing and ethanol production. The ethanol sensitivity of yeast cells is still a serious problem during ethanol fermentation, and a variety of genetic approaches (e.g., random mutant screening under selective pressure of ethanol) have been developed to improve ethanol tolerance. In this study, we developed a strategy for improving ethanol tolerance of yeast cells based on metabolomics as a high-resolution quantitative phenotypic analysis. We performed gas chromatography-mass spectrometry analysis to identify and quantify 36 compounds on 14 mutant strains including knockout strains for transcription factor and metabolic enzyme genes. A strong relation between metabolome of these mutants and their ethanol tolerance was observed. Data mining of the metabolomic analysis showed that several compounds (such as trehalose, valine, inositol and proline) contributed highly to ethanol tolerance. Our approach successfully detected well-known ethanol stress related metabolites such as trehalose and proline thus, to further prove our strategy, we focused on valine and inositol as the most promising target metabolites in our study. Our results show that simultaneous deletion of LEU4 and LEU9 (leading to accumulation of valine) or INM1 and INM2 (leading to reduction of inositol) significantly enhanced ethanol tolerance. This study shows the potential of the metabolomic approach to identify target genes for strain improvement of S. cerevisiae with higher ethanol tolerance. PMID: 26344121 [PubMed - as supplied by publisher]

Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis. Cell Metab. 2015 Sep 2; Authors: Gray LR, Sultana MR, Rauckhorst AJ, Oonthonpan L, Tompkins SC, Sharma A, Fu X, Miao R, Pewa AD, Brown KS, Lane EE, Dohlman A, Zepeda-Orozco D, Xie J, Rutter J, Norris AW, Cox JE, Burgess SC, Potthoff MJ, Taylor EB Abstract Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D. PMID: 26344103 [PubMed - as supplied by publisher]

Metabolomic profiling in inner ear fluid by gas chromatography/mass spectrometry in guinea pig cochlea. Neurosci Lett. 2015 Sep 3; Authors: Fujita T, Yamashita D, Irino Y, Kitamoto J, Fukuda Y, Inokuchi G, Hasegawa S, Otsuki N, Yoshida M, Nibu KI Abstract The composition and homeostasis of inner ear fluids are important in hearing function. The purpose of this study was to perform metabolomic analysis of the inner ear fluid in guinea pig cochlea, which has not been previously reported in literature, using gas chromatography/mass spectrometry (GC/MS). Seventy-seven kinds of metabolites were detected in the inner ear fluid. Six metabolites, ascorbic acid, fructose, galactosamine, inositol, pyruvate + oxaloacetic acid, and meso-erythritol, were significantly more abundant, and nine metabolites, phosphate, valine, glycine, glycerol, ornithine, glucose, citric acid + isocitric acid, mannose, and trans-4-hydroxy-L-proline, were less abundant in the inner ear fluid than in plasma. The levels of ten metabolites, 3-hydroxy-butyrate, glycerol, fumaric acid, galactosamine, pyruvate + oxaloacetic acid, phosphate, meso-erythritol, citric acid + isocitric acid, mannose, and inositol, in the inner ear fluid significantly changed after loud noise exposure. These observations may help to elucidate various clinical conditions of sensorineural hearing loss, including noise-induced hearing loss. PMID: 26343935 [PubMed - as supplied by publisher]

Subversion of anticancer immunosurveillance by radiotherapy. Nat Immunol. 2015 Sep 7; Authors: Zitvogel L, Kroemer G PMID: 26343538 [PubMed - as supplied by publisher]

A metabolomic perspective of griseofulvin-inducedliver injury in mice. Biochem Pharmacol. 2015 Sep 4; Authors: Liu K, Yan J, Sachar M, Zhang X, Guan M, Xie W, Ma X Abstract Griseofulvin (GSF) causes hepatic porphyria in mice, which mimics the liver injury associated with erythropoietic protoporphyria (EPP) in humans. The current study investigated the biochemical basis of GSF-induced liver injury in mice using a metabolimic approach. GSF treatment in mice resulted in significant accumulations of protoporphyrin IX (PPIX), N-methyl PPIX, bile acids, and glutathione (GSH) in the liver. Metabolomic analysis also revealed bioactivation pathways of GSF that contributed to the formation of GSF-PPIX, GSF-GSH and GSF-proline adducts. GSF-PPIX is the precursor of N-methyl PPIX. A six-fold increase of N-methyl PPIX was observed in the liver of mice after GSF treatment. N-methyl PPIX strongly inhibits ferrochelatase, the enzyme that converts PPIX to heme, and leads to PPIX accumulation. Excessive PPIX in the liver results in bile duct blockage and disturbs bile acid homeostasis. The accumulation of GSH in the liver was likely due to Nrf2-mediated upregulation of GSH synthesis. In summary, this study provides the biochemical basis of GSF-induced liver injury that can be used to understand the pathophysiology of EPP-associated liver injury in humans. PMID: 26343413 [PubMed - as supplied by publisher]

Related Articles Comparison of blood plasma sample preparation methods for combined LC-MS lipidomics and metabolomics. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Aug 28;1002:260-266 Authors: Patterson RE, Ducrocq AJ, McDougall DJ, Garrett TJ, Yost RA Abstract The goal of this research was to find the most comprehensive lipid extraction of blood plasma, while also providing adequate aqueous preparation for metabolite analysis. Comparisons have been made previously of the Folch, Bligh-Dyer, and Matyash lipid extractions; furthermore, this paper provides an additional comparison of a phospholipid removal plate for analysis. This plate was used for lipid extraction rather than its intended use in lipid removal for polar analysis, and it proves to be robust for targeted lipid analysis. Folch and Matyash provided reproducible recovery over a range of lipid classes, however the Matyash aqueous layer compared well to a typical methanol preparation for polar metabolite analysis. Thus, the Matyash method is the best choice for an untargeted biphasic extraction for metabolomics and lipidomics in blood plasma. PMID: 26343017 [PubMed - as supplied by publisher]

Related Articles Recent developments in sample preparation and data pre-treatment in metabonomics research. Arch Biochem Biophys. 2015 Sep 2; Authors: Li N, Song YP, Tang H, Wang Y Abstract Metabonomics is a powerful approach for biomarker discovery and an effective tool for pinpointing endpoint metabolic effects of external stimuli, such as pathogens and disease development. Due to its wide applications, metabonomics is required to deal with various biological samples of different properties. Hence sample preparation and corresponding data pre-treatment become important factors in ensuring validity of an investigation. In this review, we summarize some recent developments in metabonomics sample preparation and data-pretreatment procedures. PMID: 26342458 [PubMed - as supplied by publisher]

Related Articles Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring. Anal Bioanal Chem. 2015 Sep 5; Authors: Zhu J, Djukovic D, Deng L, Gu H, Himmati F, Abu Zaid M, Chiorean EG, Raftery D Abstract Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and a major cause of human morbidity and mortality. In addition to early detection, close monitoring of disease progression in CRC can be critical for patient prognosis and treatment decisions. Efforts have been made to develop new methods for improved early detection and patient monitoring; however, research focused on CRC surveillance for treatment response and disease recurrence using metabolomics has yet to be reported. In this proof of concept study, we applied a targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolic profiling approach focused on sequential metabolite ratio analysis of serial serum samples to monitor disease progression from 20 CRC patients. The use of serial samples reduces patient to patient metabolic variability. A partial least squares-discriminant analysis (PLS-DA) model using a panel of five metabolites (succinate, N2, N2-dimethylguanosine, adenine, citraconic acid, and 1-methylguanosine) was established, and excellent model performance (sensitivity = 0.83, specificity = 0.94, area under the receiver operator characteristic curve (AUROC) = 0.91 was obtained, which is superior to the traditional CRC monitoring marker carcinoembryonic antigen (sensitivity = 0.75, specificity = 0.76, AUROC = 0.80). Monte Carlo cross validation was applied, and the robustness of our model was clearly observed by the separation of true classification models from the random permutation models. Our results suggest the potential utility of metabolic profiling for CRC disease monitoring. PMID: 26342311 [PubMed - as supplied by publisher]

Related Articles Metabolic Characterization of Asthenozoospermia Using Nontargeted Seminal Plasma Metabolomics. Clin Chim Acta. 2015 Sep 2; Authors: Zhang X, Diao R, Zhu X, Li Z, Cai Z Abstract BACKGROUND: Asthenozoospermia (AS) is a common cause of male infertility. Due to the limitation of routine semen analysis, metabolic alterations associated with the disease are unclear. We applied a metabolic profiling strategy as a surrogate method to accurately assess and provide new insights into the etiologies of asthenozoospermia. METHODS: Seminal plasma samples from patients diagnosis with asthenozoospermia (n = 33) and healthy subjects (n = 30) were investigated using a nontargeted metabolomics approach based on proton nuclear magnetic resonance ((1)H NMR) spectroscopy. The spectral data were then subjected to multivariate and univariate analysis to identify metabolites that were correlated with asthenozoospermia. The disturbed metabolic pathways which the biomarkers were involved in were analyzed. RESULTS: Nineteen metabolites including up-regulation or down-regulation of several amino acids, changes in lipids metabolism, phospholipids (choline) metabolism, cholesterol metabolism, nucleoside metabolism, the Krebs cycle and energy metabolism were identified and associated with asthenozoospermia. In particular, the elevation of oxysterols such as 5α-cholesterol and 7-ketocholesterol in seminal plasma of patients with asthenozoospermia was an important finding, indicating the important role of oxidative stress in the mechanism of asthenozoospermia. CONCLUSIONS: The excellent performance of this metabolomics approach offer a highly novel means of etiological diagnosis of asthenozoospermia. PMID: 26342261 [PubMed - as supplied by publisher]

Serum metabolomics research of the anti-hypertensive effects of Tengfu Jiangya tablet on spontaneously hypertensive rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Aug 28;1002:210-217 Authors: Jiang H, Shen Z, Chu Y, Li Y, Li J, Wang X, Yang W, Zhang X, Ju J, Xu J, Yang C Abstract A HPLC/TOF-MS-based metabolomic study was conducted to investigate the holistic therapeutic effects of Tengfu Jiangya Tablet (TJT) on spontaneously hypertensive rats (SHRs). The SHRs were divided into valsartan (VST) group, TJT group and model group, in addition, the Wistar-Kyoto rats (WKY) were taken as normal control. Serum samples were separated and identified by HPLC/TOF-MS, while the obtained data was further processed by partial least-squares discriminant analysis (PLS-DA). A clear cluster among the four groups was observed, and we identified thirteen biomarkers involved involved in sphingolipid metabolism (sphinganine, lysosphingomyelin, ceramide), glycerophospholipid metabolism (phosphatidylcholines, phosphatidylethanolamine, lysophosphatidylcholines), arginine and proline metabolism (l-proline, citrulline), tryptophan metabolism (xanthuiulrenic acid, l-kynurenine, l-tryptophan), arachidonic acid metabolism(leukotriene D4), and linoleic acid metabolism (gamma-linolenic acid). Altered metabolic pathways involved in impaired NO production, inflammation and vascular smooth muscle cells (VSMCs) apoptosis and proliferation, which suggesting the possible pathological state in SHRs. TJT as well as VST altered the metabolic state, suggesting a possible anti-hypertension role by improving NO production, and an extra cardiovascular protection role possibly by amelioration of inflammatory state and vascular remodeling. PMID: 26342163 [PubMed - as supplied by publisher]

Bioinformatics tools for the analysis of NMR metabolomics studies focused on the identification of clinically relevant biomarkers. Brief Bioinform. 2015 Sep 4; Authors: Puchades-Carrasco L, Palomino-Schätzlein M, Pérez-Rambla C, Pineda-Lucena A Abstract Metabolomics, a systems biology approach focused on the global study of the metabolome, offers a tremendous potential in the analysis of clinical samples. Among other applications, metabolomics enables mapping of biochemical alterations involved in the pathogenesis of diseases, and offers the opportunity to noninvasively identify diagnostic, prognostic and predictive biomarkers that could translate into early therapeutic interventions. Particularly, metabolomics by Nuclear Magnetic Resonance (NMR) has the ability to simultaneously detect and structurally characterize an abundance of metabolic components, even when their identities are unknown. Analysis of the data generated using this experimental approach requires the application of statistical and bioinformatics tools for the correct interpretation of the results. This review focuses on the different steps involved in the metabolomics characterization of biofluids for clinical applications, ranging from the design of the study to the biological interpretation of the results. Particular emphasis is devoted to the specific procedures required for the processing and interpretation of NMR data with a focus on the identification of clinically relevant biomarkers. PMID: 26342127 [PubMed - as supplied by publisher]

Plasma metabolomics profiling for the prediction of cytomegalovirus DNAemia and analysis of virus-host interaction in allogeneic stem cell transplant recipients. J Gen Virol. 2015 Sep 3; Authors: Monleón D, Giménez E, Muñoz-Cobo B, Morales JM, Solano C, Amat P, Navarro D Abstract Metabolomics analysis of biofluids is being increasingly recognized as a useful tool for the diagnosis and management of a number of infectious diseases. Here we showed that plasma metabolomics profiling by untargeted 1H nuclear magnetic resonance may allow the anticipation of the occurrence of CMV DNAemia in allogeneic stem cell transplant (Allo-SCT). For this purpose, key discriminatory metabolites were total glutathione, taurine, methylamine, trimethylamine N-oxide and lactate, all of which were upregulated in patients eventually developing CMV DNAemia. The overall classification accuracy (predictability) of the projection to latent structure discriminant analysis (PLS-DA) model in cross-validation technical replicates was 73%. Increased levels of alanine, lactate and total fatty acids, and a shift in the fatty acid profile towards unsaturated species were observed in patients with detectable CMV DNA in plasma. The classification accuracy of this PLS-DA model in cross-validation technical replicates was 81%. Plasma metabolomics profiling may prove useful for identifying patients at highest risk for CMV DNAemia thus allowing early inception of antiviral therapy. PMID: 26341195 [PubMed - as supplied by publisher]

[Development of new vaccines]. Enferm Infecc Microbiol Clin. 2015 Sep 1; Authors: González-Romo F, Picazo JJ Abstract Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. PMID: 26341041 [PubMed - as supplied by publisher]

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