PubMed

Lipidomics to investigate the pharmacologic mechanisms of ginkgo folium in the hyperuricemic rat model. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jun 20;1060:407-415 Authors: Zhang S, Zhuang J, Yue G, Wang Y, Liu M, Zhang B, Du Z, Ma Q Abstract Hyperuricemia caused by purine metabolic abnormalities is reported to have close correlation with lipid metabolic disorders. Ginkgo folium, a frequently-used lipid-lowering medicine, has significant anti-hyperuricemia effects. However, it is poorly known about the interaction between lowering uric acid and regulation of lipid metabolic disorders. In this study, hyperuricemic rat model was induced by orally administration with fructose. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with pattern recognition approaches were used to determine different lipid metabolites in serum of control group, model group, and different doses of ginkgo folium groups. Principal component analysis (PCA) was applied to analyze the MS data to assess the establishment of model, partial least squares-discriminate analysis (PLS-DA) and independent samples T-test were performed to indicate the differences between different groups of rats and to find biomarkers. Metabolomics pathway analysis (MetPA) was introduced to reveal the pharmacologic mechanisms of ginkgo folium. 19 potential biomarkers associated with hyperuricemia were found. After intervened by ginkgo folium, these biomarkers were returning to normal level. Among these biomarkers, 13 lipid biomarkers were significantly reversed. Ginkgo filum can lower uric acid via adjusting back the level of PCs and LPCs, which suggested that its treatment mechanisms may be related to reducing the activity of PLA2. In sum, the lipidomics analysis in the system level have enhanced our understanding to pathogenesis of hyperuricemia and the results suggested that ginkgo folium could alleviate the abnormal metabolic status of hyperuricemia. These results demonstrated a new mechanism for lowering uric acid, which was helpful to the early treatment for hyperuricemia. PMID: 28672255 [PubMed - as supplied by publisher]

Metabolomic Tools to Assess the Chemistry and Bioactivity of Endophytic Aspergillus Strain. Chem Biodivers. 2017 Jul 03;: Authors: Tawfike AF, Tate R, Abbott G, Young L, Viegelmann C, Schumacher M, Diederich M, Edrada-Ebel RA Abstract Endophytic fungi associated with medicinal plants are a potential source of novel chemistry and biology that may find applications as pharmaceutical and agrochemical drugs. In this study, a combination of metabolomics and bioactivity-guided approaches were employed to isolate anticancer secondary metabolites from an endophytic Aspergillus aculeatus. The endophyte was isolated from the Egyptian medicinal plant Terminalia laxiflora and identified using molecular biological methods. Metabolomics and dereplication studies were accomplished by utilizing the MZmine software coupled with the universal Dictionary of Natural Products database. Metabolic profiling, with aid of multivariate data analysis, was performed at different stages of the growth curve to choose the optimised method suitable for up-scaling. The optimised culture method yielded a crude extract abundant with biologically-active secondary metabolites. Crude extracts were fractionated using different high-throughput chromatographic techniques. Purified compounds were identified by HRESI-MS, 1D and 2D-NMR. This study introduced a new method of dereplication utilising both high-resolution mass spectrometry and NMR spectroscopy. The metabolites were putatively identified by applying a chemotaxonomic filter. We also present a short review on the diverse chemistry of terrestrial endophytic strains of Aspergillus, which has become a part of our dereplication work and this will be of wide interest to those working in this field. This article is protected by copyright. All rights reserved. PMID: 28672096 [PubMed - as supplied by publisher]

Metabolomics combined with pattern recognition and bioinformatics analysis methods for the development of pharmacodynamic biomarkers on liver fibrosis. Mol Biosyst. 2017 Jul 03;: Authors: Fang J, Wang L, Wang Y, Qiu M, Zhang Y Abstract The major obstacle for the development of targeted therapies is the lack of pharmacodynamic (PD) biomarkers to provide an early readout of biological activities. As the modulation of metabolites may reflect the biological changes occurring in the targets, metabolomics is promising to be an efficient way to explore PD biomarkers. In the present study, a liver fibrosis rat model was established by intraperitoneal injection of CCl4 twice weekly for 6 weeks, the treatment of total aglycone extracts of Scutellaria baicalensis (TAES) was begun 4 weeks after the modeling, and gas chromatography-mass spectrometry (GC-MS) based metabolomics combined with pattern recognition and network analysis were carried out for the research on PD biomarkers of TAES on liver fibrosis. After 2 weeks of treatment, TAES shows positive effects on CCl4-induced liver fibrosis. In the metabolomics study, 63 urinary metabolites contributing to liver fibrosis were identified. Six metabolic pathways significantly enriched in metabolomics data were mapped onto a network to determine global patterns of metabolic alterations in liver fibrosis. By topological analysis, 6 metabolites with high centrality in the metabolic sub-network were selected as potential PD biomarkers. Within 24 h of the final administration, the 6 identified urine metabolic biomarkers with response to time variation of TAES were validated as PD biomarkers. This integrative study presents an attractive strategy to explore PD biomarkers, which may give insight into the actual pharmacological effect of target drugs, and the information from PD biomarkers can be combined with pharmacokinetics to select the optimal dose and a schedule of administration for the drugs. PMID: 28671700 [PubMed - as supplied by publisher]

Extracellular vesicles are independent metabolic units with asparaginase activity. Nat Chem Biol. 2017 Jul 03;: Authors: Iraci N, Gaude E, Leonardi T, Costa ASH, Cossetti C, Peruzzotti-Jametti L, Bernstock JD, Saini HK, Gelati M, Vescovi AL, Bastos C, Faria N, Occhipinti LG, Enright AJ, Frezza C, Pluchino S Abstract Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although it has been shown that cells can traffic metabolic enzymes via EVs, much remains to be elucidated with regard to their intrinsic metabolic activity. Accordingly, herein we assessed the ability of neural stem/progenitor cell (NSC)-derived EVs to consume and produce metabolites. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed by the enzyme asparaginase-like protein 1 (Asrgl1). Critically, we show that Asrgl1 activity is selective for asparagine and is devoid of glutaminase activity. We found that mouse and human NSC EVs traffic Asrgl1. Our results demonstrate, for the first time, that NSC EVs function as independent metabolic units that are able to modify the concentrations of critical nutrients, with the potential to affect the physiology of their microenvironment. PMID: 28671681 [PubMed - as supplied by publisher]

Volatile compounds in blood headspace and nasal breath. J Breath Res. 2017 Jul 03;: Authors: Ross BM, Babgi R Abstract Breath analysis is a form of metabolomics that utilises the identification and quantification of volatile chemicals to provide information about physiological or pathological processes occurring within the body. An inherent assumption of such analyses is that the concentration of the exhaled gases correlates with the concentration of the same gas in the tissue of interest. In this study we have investigated this assumption by quantifying some volatile compounds in peripheral venous blood headspace, and in nasal breath collected in Tedlar bags obtained at the same time from 30 healthy volunteers, prior to analysis by Selected Ion Flow Tube Mass Spectrometry. Some endogenous compounds were significantly correlated between blood headspace and nasal breath such as isoprene (rp = 0.68) and acetone (rp = 0.63), however many, such as propanal (rp = -0.26) and methanol (rp = 0.23), were not. Furthermore, the relative concentrations of volatiles in blood and breath varied markedly between compounds, with some, such as isoprene and acetone having similar concentrations in each, others such as acetic acid, ammonia and methanol being significantly more abundant in breath, and others, such as methanal, being detectable in breath alone. We also observed that breath propanol and acetic acid concentrations were higher in male compared to female participants, and that the blood headspace methanol concentration was negatively correlated to body mass index. No relationship between volatile concentrations and age was observed. Our data suggest that breath concentrations of volatiles do not necessarily give information about the same compound in the blood stream. This was likely due to the upper airway contributing compounds over and above that originating in the circulation. An investigation of the relationship between breath volatile concentrations and that in the tissue(s) of interest should therefore become a routine part of the development process of breath-based biomarkers. PMID: 28671107 [PubMed - as supplied by publisher]

Neonatal Meningitis: Overcoming Challenges in Diagnosis, Prognosis, and Treatment with Omics. Front Pediatr. 2017;5:139 Authors: Gordon SM, Srinivasan L, Harris MC Abstract Neonatal meningitis is a devastating condition. Prognosis has not improved in decades, despite the advent of improved antimicrobial therapy and heightened index of suspicion among clinicians caring for affected infants. One in ten infants die from meningitis, and up to half of survivors develop significant lifelong complications, including seizures, impaired hearing and vision, and delayed or arrested development of such basic skills as talking and walking. At present, it is not possible to predict which infants will suffer poor outcomes. Early treatment is critical to promote more favorable outcomes, though diagnosis of meningitis in infants is technically challenging, time-intensive, and invasive. Profound neuronal injury has long been described in the setting of neonatal meningitis, as has elevated levels of many pro- and anti-inflammatory cytokines. Mechanisms of the host immune response that drive clearance of the offending organism and underlie brain injury due to meningitis are not well understood, however. In this review, we will discuss challenges in diagnosis, prognosis, and treatment of neonatal meningitis. We will highlight transcriptomic, proteomic, and metabolomic data that contribute to suggested mechanisms of inflammation and brain injury in this setting with a view toward fruitful areas for future investigation. PMID: 28670576 [PubMed - in process]

Urinary metabolomic analysis of intrahepatic cholestasis of pregnancy based on high performance liquid chromatography/mass spectrometry. Clin Chim Acta. 2017 Jun 29;: Authors: Ma L, Zhang X, Pan F, Cui Y, Yang T, Deng L, Shao Y, Ding M Abstract BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-related liver disease, leads to complications for both mothers and fetuses. Metabolomic approach has been applied to maternal-fetal medicine. The global metabolomic alterations that are specific in ICP as yet have not been investigated. METHODS: Based on high performance liquid chromatography/hybrid quadrupole time-of-flight (HPLC/Q-TOF) mass spectrometry, the untargeted metabolomics was used to analyze the changes of urinary metabolites between ICP group and the control group. RESULTS: One hundred nine variables in positive model and 119 variables in negative model were significantly different (p<0.05) between the ICP group and the control group, with the VIP (variable importance in the project) score>1 by the orthogonal partial least squares discriminant analysis (OPLS-DA). 14 metabolites in positive model and 18 metabolites in negative model were selected and identified based on HMDB (human metabolome database). Most of these metabolites were involved in bile acids biosynthesis and metabolism, hormone metabolism and lipid metabolism. A metabolite panel (MG (22:5), LysoPE (22:5), l-homocysteine sulfonic acid, glycocholic acid and chenodeoxycholic acid 3-sulfate) was contrusted by the binary logistic regression analysis with high diagnostic accuracy for ICP. The area under the receiver operating characteristic curve was 0.988 with the sensitivity of 90.0% and specificity of 93.3%. CONCLUSIONS: Urinary metabolites allow for the discrimination of ICP from the controls by orthogonal partial least squares discriminant analysis. Therefore, these findings may provide deep insights for the etiopathogenesis of ICP. Moreover, the maternal urinary metabolite panel has the potential to be used as non-invasive biomarkers for the diagnosis of ICP. PMID: 28669684 [PubMed - as supplied by publisher]

Orthogonal partial least squares/projections to latent structures regression-based metabolomics approach for identification of gene targets for improvement of 1-butanol production in Escherichia coli. J Biosci Bioeng. 2017 Jun 29;: Authors: Nitta K, Laviña WA, Pontrelli S, Liao JC, Putri SP, Fukusaki E Abstract Metabolomics is the comprehensive analysis of metabolites in biological systems that uses multivariate analyses such as principal component analysis (PCA) or partial least squares/projections to latent structures regression (PLSR) to understand the metabolome state and extract important information from biological systems. In this study, orthogonal PLSR (OPLSR) model-based metabolomics approach was applied to 1-butanol producing Escherichia coli to facilitate in strain improvement strategies. Here, metabolite data obtained by liquid chromatography/mass spectrometry (LC/MS) was used to construct an OPLSR model to correlate metabolite changes with 1-butanol production and rationally identify gene targets for strain improvement. Using this approach, acetyl-CoA was determined as the rate-limiting step of the pathway while free CoA was found to be insufficient for 1-butanol production. By resolving the problems addressed by the OPLSR model, higher 1-butanol productivity was achieved. In this study, the usefulness of OPLSR-based metabolomics approach for understanding the whole metabolome state and determining the most relevant metabolites was demonstrated. Moreover, it was able to provide valuable insights for selection of rational gene targets for strain improvement. PMID: 28669528 [PubMed - as supplied by publisher]

Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis. Diabetes Metab. 2017 Jun 29;: Authors: Friedrich N, Skaaby T, Pietzner M, Budde K, Thuesen BH, Nauck M, Linneberg A Abstract AIM: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies of possible subclinical states of disturbed glucose metabolism are limited. Therefore, the aim of this study was to analyze the associations between baseline urinary metabolites and 5-year changes in continuous markers of glucose homoeostasis, including fasting glucose, HbA1c and homoeostasis model assessment of insulin resistance (HOMA-IR) index values. METHODS: Urine metabolites in 3986 participants at both baseline and 5-year follow-up of the population-based Inter99 study were analyzed by (1)H-NMR spectroscopy. Linear regression and analyses of covariance models were used to detect associations between urine metabolites and 5-year changes in markers of glucose homoeostasis. RESULTS: Higher baseline levels of urinary alanine, betaine, N,N-dimethylglycine (DMG), creatinine and trimethylamine were associated with an increase in HbA1c from baseline to follow-up. In contrast, formic acid and trigonelline levels were associated with a decrease in HbA1c over time. Analyses of 5-year changes in fasting glucose and HOMA-IR index showed similar findings, with high baseline levels of lactic acid, beta-d-glucose, creatinine, alanine and 1-methylnicotinamide associated with increases in both parameters. CONCLUSION: Several urine metabolites were found to be associated with detrimental longitudinal changes in biomarkers of glucose homoeostasis. The identified metabolites point to mechanisms involving betaine and coffee metabolism as well as the possible influence of the gut microbiome. PMID: 28669514 [PubMed - as supplied by publisher]

Related Articles Di(2-ethylhexyl)phthalate Alters the Synthesis and β-Oxidation of Fatty Acids and Hinders ATP Supply in Mouse Testes via UPLC-Q-Exactive Orbitrap MS-Based Metabonomics Study. J Agric Food Chem. 2017 Jun 21;65(24):5056-5063 Authors: Shen G, Zhou L, Liu W, Cui Y, Xie W, Chen H, Yu W, Li W, Li H Abstract Di(2-ethylhexyl) phthalate (DEHP) is considered to be an environmental endocrine disruptor at high levels of general exposure. Studies show that DEHP may cause testicular toxicity on human being. In this study, metabonomics techniques were used to identify differential endogenous metabolites, draw the network metabolic pathways, and conduct network analysis, to determine the underlying mechanisms of testicular toxicity induced by DEHP. The results showed that DEHP inhibited synthesis and accelerated β-oxidation of fatty acids and impaired the tricarboxylic acid cycle (TCA cycle) and gluconeogenesis, resulting in lactic acid accumulation and an insufficient ATP supply in the microenvironment of the testis. These alterations led to testicular atrophy and, thus, may be the underlying causes of testicular toxicity. DEHP also inhibited peroxisome proliferator activated receptors in the testis, which may be another potential reason for the testicular atrophy. These findings provided new insights to better understand the mechanisms of testicular toxicity induced by DEHP exposure. PMID: 28609104 [PubMed - indexed for MEDLINE]

Related Articles Microfluidic Exosome Analysis toward Liquid Biopsy for Cancer. J Lab Autom. 2016 Aug;21(4):599-608 Authors: He M, Zeng Y Abstract Assessment of a tumor's molecular makeup using biofluid samples, known as liquid biopsy, is a prominent research topic in precision medicine for cancer, due to its noninvasive property allowing repeat sampling for monitoring molecular changes of tumors over time. Circulating exosomes recently have been recognized as promising tumor surrogates because they deliver enriched biomarkers, such as proteins, RNAs, and DNA. However, purification and characterization of these exosomes are technically challenging. Microfluidic lab-on-a-chip technology effectively addresses these challenges owing to its inherent advantages in integration and automation of multiple functional modules, enhancing sensing performance, and expediting analysis processes. In this article, we review the state-of-the-art development of microfluidic technologies for exosome isolation and molecular characterization with emphasis on their applications toward liquid biopsy-based analysis of cancer. Finally, we share our perspectives on current challenges and future directions of microfluidic exosome analysis. PMID: 27215792 [PubMed - indexed for MEDLINE]

Experimental design and reporting standards for metabolomics studies of mammalian cell lines. Cell Mol Life Sci. 2017 Jul 01;: Authors: Hayton S, Maker GL, Mullaney I, Trengove RD Abstract Metabolomics is an analytical technique that investigates the small biochemical molecules present within a biological sample isolated from a plant, animal, or cultured cells. It can be an extremely powerful tool in elucidating the specific metabolic changes within a biological system in response to an environmental challenge such as disease, infection, drugs, or toxins. A historically difficult step in the metabolomics pipeline is in data interpretation to a meaningful biological context, for such high-variability biological samples and in untargeted metabolomics studies that are hypothesis-generating by design. One way to achieve stronger biological context of metabolomic data is via the use of cultured cell models, particularly for mammalian biological systems. The benefits of in vitro metabolomics include a much greater control of external variables and no ethical concerns. The current concerns are with inconsistencies in experimental procedures and level of reporting standards between different studies. This review discusses some of these discrepancies between recent studies, such as metabolite extraction and data normalisation. The aim of this review is to highlight the importance of a standardised experimental approach to any cultured cell metabolomics study and suggests an example procedure fully inclusive of information that should be disclosed in regard to the cell type/s used and their culture conditions. Metabolomics of cultured cells has the potential to uncover previously unknown information about cell biology, functions and response mechanisms, and so the accurate biological interpretation of the data produced and its ability to be compared to other studies should be considered vitally important. PMID: 28669031 [PubMed - as supplied by publisher]

Dynamic changes of plasma metabolites in pigs with GalN-induced acute liver failure using GC-MS and UPLC-MS. Biomed Pharmacother. 2017 Jun 29;93:480-489 Authors: Chen E, Lu J, Chen D, Zhu D, Wang Y, Zhang Y, Zhou N, Wang J, Li J, Li L Abstract Metabolomics facilitates investigation of the mechanisms of disease and screening for biomarkers. Here, a gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach was employed to identify plasma biomarkers of acute liver failure (ALF) in pigs. Blood was collected from pigs at 12h intervals during ALF. Hepatic injury was quantified by determining liver function and histopathology. Based on a multivariate data matrix and pattern recognition, two upregulated metabolites, namely, amino acids and conjugated bile acids, and two downregulated metabolites, lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs), were identified. All of these metabolites showed a strong relationship with the extent of liver injury. Amino acids were biomarkers of the severity of liver impairment, conjugated bile acids were predictive of early stage liver damage, and LPCs and PCs were related to the prognosis of liver injury. In conclusion, our results demonstrated the occurrence of marked metabolic disturbances during ALF and that integrated metabolomics analysis facilitates identification of biomarkers of disease. PMID: 28668767 [PubMed - as supplied by publisher]

An integrative investigation of the toxicity of Aconiti kusnezoffii radix and the attenuation effect of its processed drug using a UHPLC-Q-TOF based rat serum and urine metabolomics strategy. J Pharm Biomed Anal. 2017 Jun 21;145:240-247 Authors: Sui Z, Li Q, Zhu L, Wang Z, Lv C, Liu R, Xu H, He B, Li Z, Bi K Abstract Aconiti kusnezoffii radix (AKR), the root of Aconitum kusnezoffii Reichb., is commonly used in the treatment of the rheumatoid arthritis. However, the clinical application is limited due to its potential toxicity. Therefore, to investigate the mechanism of its potential neurotoxicity and nephrotoxicity, a comprehensive metabolomics study combined with serum biochemistry and histopathology measurements was carried out. A UHPLC-Q-TOF mass spectrometry based metabolomics approach was applied to characterize the AKR toxicity, while the toxicity attenuation effects of Aconiti kusnezoffii radix cocta (AKRC) on Wistar rats were also investigated. Two chromatographic techniques involving reversed-phase chromatography and hydrophilic interaction chromatography were combined for the serum and urine detection, which balanced the integrity and selectivity of the two matrices. Principal component analysis was used to determine the groups, and principal component analysis discriminant analysis was carried out to confirm the important variables. Then, the developed integrative toxicity evaluation method was applied to assess the toxicity of AKR and the attenuation effect of AKRC. The highly sensitive and specific toxic biomarkers, which can provide practical bases were identified for the diagnosis of the neurotoxicity and nephrotoxicity induced by AKR. In all, a total of 19 putative biomarkers were characterized, and related metabolic pathways were identified. The study demonstrated that the established metabolomics strategy is a powerful approach for investigating the mechanisms of herbal toxicity and the attenuation effect of a processing method and would provide medical solutions for other toxic herbal medications and further clinical evidence on how AKR improves symptoms of rheumatoid arthritis patients. PMID: 28668652 [PubMed - as supplied by publisher]

GC-MS based metabolomics of CSF and blood serum: Metabolic phenotype for a rat model of cefoperazone-induced disulfiram-like reaction. Biochem Biophys Res Commun. 2017 Jun 28;: Authors: Liu L, Huang C, Bian Y, Miao L Abstract Cefoperazone are most popularly used in the treatment of complicated infections clinically. Concomitant ingestion of ethnaol and cefoperazone may cause a disulfiram-like reaction. However, very little is known about the possible interactions between cefoperazone treatment and an alcohol with regard to the induction of disulfiram-like reaction. Study of the metabolic impact of cotreatment with cefoperazone and alcohol on animals can facilitate the identification of markers relevant to disulfiram-like reaction. In this study, the serum and cerebrospinal fluid (CSF) metabolites from Sprague-Dawley rats were profiled using gas chromatography mass spectrometry. Serum levels of valine, leucine, glycine, palmitelaidic acid, and 2-hydroxyisobutyrate in combination application group were significantly higher than those in the control; while alanine and pyruvate deceased in cotreatment group. Most TCA intermediates, glutamate and aspartate had lower CSF level in combination application group, except citrate. In addition, most carbohydrates, ethylmalonate and N-acetylaspartate had higher level compared with control group. These results highlight concomitant ingestion of alcohol and cefoperazone generated disulfiram-like reaction by way of disrupting normal metabolic pathway. Cefoperazone magnifes ethanol-induced impairment of TCA cycle and aspartate metabolism, thereby affects energy metabolism and neural transmission. PMID: 28668395 [PubMed - as supplied by publisher]

The use of metabolomic quantitative trait locus mapping and osmotic adjustment traits for the improvement of crop yields under environmental stresses. Semin Cell Dev Biol. 2017 Jun 28;: Authors: Adbelrahman M, Burritt DJ, Tran LP Abstract The sustainable production of food to feed an increasing world population is a major challenge for plant scientists, especially due to the unpredictable and dynamic nature of global climatic conditions. Heat waves, drought, increased soil salinity, unseasonal cold and flooding are all becoming more common climate-related causes of stress for crop plants, and are already affecting yields and the geographical distributions of optimal growing regions for many crops. Therefore, the development and application of multi-faceted strategies, including sustainable agricultural practices and the development and cultivation of intraspecific hybrids containing genetic traits associated with abiotic stress tolerance from wild relatives, will either alone or together be essential to sustainably grow high-yielding crops under increasingly stressful environmental conditions. The development of abiotic stress-resilient crops requires an in-depth knowledge of plant development and of the biological processes that enable plants to survive in stressful environments, and this knowledge can be obtained from "omic" studies, such as bioinformatics, genomics, transcriptomics, proteomics and metabolomics. The plant metabolome can provide a snapshot of the physiological and biochemical status of a plant cell under normal or stressful conditions, and thus it is closely related to the plant phenotypes. Analysis of the metabolomes of plants growing under stressful conditions can be used to identify stress resistance-associated metabolites, or biomarkers, which can then be used by plant breeders as selective markers to help identify the phenotypes, resulted from the complex interactions between genotype and environment, associated with stress-tolerant crop plants. Osmotic adjustment is an important metabolic adaptation mechanism which helps plants survive abiotic stress and can support higher crop yield under stressful environmental conditions. This review highlights the recent advances in our understanding of the functions of abiotic stress-responsive metabolites, with an emphasis on the use of metabolomic quantitative trait locus mapping and osmotic adjustment agronomic traits, for the improvement of crop yields under environmental stresses. PMID: 28668354 [PubMed - as supplied by publisher]

Unravelling HIV-1 Latency, One Cell at a Time. Trends Microbiol. 2017 Jun 28;: Authors: Kok YL, Ciuffi A, Metzner KJ Abstract A single virus is capable of infecting and replicating in a single cell. Recent advances across single-cell omics technologies - genomics, epigenomics, transcriptomics, epitranscriptomics, proteomics, and metabolomics - will offer unprecedented opportunities to gain more insights into the various aspects of the life cycle of viruses and their impact on the host cell. Here, using the human immunodeficiency virus type 1 (HIV-1) as an example, we summarize the current knowledge and the future potential of single-cell omics in the investigation of an important aspect of the life cycle of HIV-1 that represents a major hurdle in achieving viral eradication, HIV-1 latency. PMID: 28668335 [PubMed - as supplied by publisher]

Valproic acid alters the content and function of the cell-free DNA released by hepatocellular carcinoma (HepG2) cells in vitro. Biochimie. 2017 Jun 28;: Authors: Aucamp J, Van Dyk HC, Bronkhorst AJ, Pretorius PJ Abstract BACKGROUND: It has long been believed that cell-free DNA (cfDNA) actively released into circulation can serve as intercellular messengers, and their involvement in processes such as the bystander effect strongly support this. However, this intercellular messaging function of cfDNA may have clinical implications that have not yet been considered. METHODS: CfDNA was isolated from the growth medium of HepG2 cells treated with valproic acid (VPA). This cfDNA was then administered to untreated cells and cellular metabolic activity was measured. RESULTS: VPA altered the characteristics of cfDNA released by treated HepG2 cells in vitro. When administered to untreated cells, the cfDNA from cells treated with VPA resulted in the dose-dependent induction of glycolytic activity within 36 min of administration, but little to no alterations in oxidative phosphorylation. The glycolytic activity lasted for 4-6 h, whereas changes in subsequent cfDNA release and characteristics were found to remain persistent after two 24 h treatments. Fragmented genomic DNA from VPA-treated cells did not induce the effects observed for cfDNA obtained VPA-treated cells. CONCLUSIONS: It is possible for cfDNA to, under in vitro conditions, transfer pharmaceutically-induced effects to untreated recipient cells. Further investigation regarding this occurrence under in vivo conditions is, therefore, strongly encouraged. GENERAL SIGNIFICANCE: The intercellular messaging functions of cfDNA present in donated biological fluids has potential clinical implications that require urgent attention. These implications may, however, also have potential as new forms of treatment that can circumvent pharmacological barriers. PMID: 28668269 [PubMed - as supplied by publisher]

Metabolic profiling of the traditional Chinese medicine formulation Yu Ping Feng San for the identification of constituents relevant for effects on expression of TNF-α, IFN-γ, IL-1β and IL-4 in U937 cells. J Pharm Biomed Anal. 2017 Jun 15;145:219-229 Authors: Stefanie N, Marlene M, Huiqin Z, Yong L, Xiaojuan H, Danping F, Aiping L, Kate Y, Giorgis I, Rudolf B Abstract Yu Ping Feng San (YPFS) is a classical TCM formulation which has been traditionally used for treatment of immune system related diseases such as chronic bronchitis, allergic rhinitis and asthma. The formula is a mixture of Radix Saposhnikoviae (Fangfeng), Radix Astragali (Huangqi), and Rhizoma Atractylodis macrocephalae (Baizhu). TLC- and LC-DAD-ESI-MS/MS methods have been developed for the analysis of the metabolic profiles of the single herbs and of the formula. Decoctions and ASE extracts were analyzed in order to trace components of the individual herbs in YPFS. Nine constituents of Radix Saposhnikoviae, ten constituents of Radix Astragali and five constituents of Rhizoma Atractylodis macrocephalae have been assigned in the chemical profiles of the formula, which now allow the standardisation of YPFS. The pharmacological testing showed that all extracts significantly inhibited expression of TNF-α, IFN-γ, and IL-1β in U937 cells, while the inhibition of IL-4 was consistently low. Compared to conventional analyses which are focused on a limited set of compounds, metabolomics approaches, together with novel data processing tools, enable a more holistic comparison of the herbal extracts. In order to identify the constituents which are relevant for the immunomodulatory effects of the formula, metabolomics studies (PCA, OPLS-DA) have been performed using UPLC/QTOF MS data. PMID: 28667937 [PubMed - as supplied by publisher]

Metabolomics analysis of TiO2 nanoparticles induced toxicological effects on rice (Oryza sativa L.). Environ Pollut. 2017 Jun 28;230:302-310 Authors: Wu B, Zhu L, Le XC Abstract The wide occurrence and high environmental concentration of titanium dioxide nanoparticles (nano-TiO2) have raised concerns about their potential toxic effects on crops. In this study, we employed a GC-MS-based metabolomic approach to investigate the potential toxicity of nano-TiO2 on hydroponically-cultured rice (Oryza sativa L.) after exposed to 0, 100, 250 or 500 mg/L of nano-TiO2 for fourteen days. Results showed that the biomass of rice was significantly decreased and the antioxidant defense system was significantly disturbed after exposure to nano-TiO2. One hundred and five identified metabolites showed significant difference compared to the control, among which the concentrations of glucose-6-phosphate, glucose-1-phosphate, succinic and isocitric acid were increased most, while the concentrations of sucrose, isomaltulose, and glyoxylic acid were decreased most. Basic energy-generating ways including tricarboxylic acid cycle and the pentose phosphate pathway, were elevated significantly while the carbohydrate synthesis metabolism including starch and sucrose metabolism, and glyoxylate and dicarboxylate metabolism were inhibited. However, the biosynthetic formation of most of the identified fatty acids, amino acids and secondary metabolites which correlated to crop quality, were increased. The results suggest that the metabolism of rice plants is distinctly disturbed after exposure to nano-TiO2, and nano-TiO2 would have a mixed effect on the yield and quality of rice. PMID: 28667911 [PubMed - as supplied by publisher]