PubMed

19 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 2018/07/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

29 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 2018/07/17PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

29 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 2018/07/17PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Comparison of accuracy and precision between multipoint calibration, single point calibration, and relative quantification for targeted metabolomic analysis. Anal Bioanal Chem. 2018 Jul 13;: Authors: Khamis MM, Klemm N, Adamko DJ, El-Aneed A Abstract Targeted metabolomics requires accurate and precise quantification of candidate biomarkers, often through tandem mass spectrometric (MS/MS) analysis. Differential isotope labeling (DIL) improves mass spectrometric (MS) analysis in metabolomics by derivatizing metabolites with two isotopic forms of the same reagent. Despite its advantages, DIL-liquid chromatographic (LC)-MS/MS can result in substantial increase in workload when fully validated quantitative methods are required. To decrease the workload, we hypothesized that single point calibration or relative quantification could be used as alternative methods. Either approach will result in significant saving in resources and time. To test our hypothesis, six urinary metabolites were selected as model compounds. Urine samples were analyzed using a fully validated multipoint dansyl chloride-DIL-LC-MS/MS method. Samples were reprocessed using single point calibration and relative quantification modes. Our results demonstrated that the performance of single point calibration or relative quantification was inferior, for some metabolites, to multipoint calibration. The lower limit of quantification failed in the quantification of ethanolamine in most of participant samples using single point calibration. In addition, its precision was not acceptable in one participant during serine and ethanolamine quantification. On the other hand, relative quantification resulted in the least accurate data. In fact, none of the data generated from relative quantification for serine was comparable to that obtained from multipoint calibration. Finally, while single point calibration showed an overall acceptable performance for the majority of the model compounds, we cannot extrapolate the findings to other metabolites within the same analytical run. Analysts are advised to assess accuracy and precision for each metabolite in which single point calibration is the intended quantification mean. PMID: 30006724 [PubMed - as supplied by publisher]

Related Articles Dynamics of Plasma Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes - Type 1 Diabetes Prediction and Prevention Study (DIPP). Sci Rep. 2018 Jul 13;8(1):10635 Authors: Lamichhane S, Ahonen L, Dyrlund TS, Kemppainen E, Siljander H, Hyöty H, Ilonen J, Toppari J, Veijola R, Hyötyläinen T, Knip M, Oresic M Abstract Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that distinct lipidomic signatures characterize children who progressed to islet autoimmunity or overt T1D, which may be helpful in the identification of at-risk children before the initiation of autoimmunity. PMID: 30006587 [PubMed - in process]

Related Articles Reactive Metabolite-induced Protein Glutathionylation: a Potentially Novel Mechanism Underlying Acetaminophen Hepatotoxicity. Mol Cell Proteomics. 2018 Jul 13;: Authors: Chan CY, Soh ACK, Kioh DYQ, Li J, Verma C, Koh SK, Beuerman RW, Zhou L, Chan ECY Abstract Although covalent protein binding is established as the pivotal event underpinning acetaminophen (APAP) toxicity, its mechanistic details remain unclear. In this study, we demonstrated that APAP induces widespread protein glutathionylation in a time-, dose- and bioactivation-dependent manner in HepaRG cells. Proteo-metabonomic mapping provided evidence that APAP-induced glutathionylation resulted in functional deficits in energy metabolism, elevations in oxidative stress and cytosolic calcium, as well as mitochondrial dysfunction that correlate strongly with the well-established toxicity features of APAP. We also provide novel evidence that APAP-induced glutathionylation of carnitine O-palmitoyltransferase 1 (CPT1) and voltage-dependent anion-selective channel protein 1 are respectively involved in inhibition of fatty acid β-oxidation and opening of the mitochondrial permeability transition pore. Importantly, we show that the inhibitory effect of CPT1 glutathionylation can be mitigated by PPARα induction, which provides a mechanistic explanation for the prophylactic effect of fibrates, which are PPARα ligands, against APAP toxicity. Finally, we propose that APAP-induced protein glutathionylation likely occurs secondary to covalent binding, which is a previously unknown mechanism of glutathionylation, suggesting that this post-translational modification could be functionally implicated in drug-induced toxicity. PMID: 30006487 [PubMed - as supplied by publisher]

Related Articles Integrated Omics: Tools, Advances, and Future Approaches. J Mol Endocrinol. 2018 Jul 13;: Authors: Misra BB, Langefeld CD, Olivier M, Cox LA Abstract With the rapid adoption of high-throughput omic approaches to analyze biological samples such as genomics, transcriptomics, proteomics, and metabolomics, each analysis can generate tera- to peta-byte sized data files on a daily basis. These data file sizes, together with differences in nomenclature among these data types, make the integration of these multi-dimensional omics data into biologically meaningful context challenging. Variously named as integrated omics, multi-omics, poly-omics, trans-omics, pan-omics, or shortened to just 'omics', the challenges include differences in data cleaning, normalization, biomolecule identification, data dimensionality reduction, biological contextualization, statistical validation, data storage and handling, sharing, and data archiving. The ultimate goal is towards the holistic realization of a 'systems biology' understanding of the biological question in hand. Commonly used approaches in these efforts are currently limited by the 3 i's - integration, interpretation, and insights. Post integration, these very large datasets aim to yield unprecedented views of cellular systems at exquisite resolution for transformative insights into processes, events, and diseases through various computational and informatics frameworks. With the continued reduction in costs and processing time for sample analyses, and increasing types of omics datasets generated such as glycomics, lipidomics, microbiomics, and phenomics, an increasing number of scientists in this interdisciplinary domain of bioinformatics face these challenges. We discuss recent approaches, existing tools, and potential caveats in the integration of omics datasets for development of standardized analytical pipelines that could be adopted by the global omics research community. PMID: 30006342 [PubMed - as supplied by publisher]

Related Articles Metabolomic analysis of mammalian cells and human tissue through one-pot two stage derivatizations using sheathless capillary electrophoresis-electrospray ionization-mass spectrometry. J Chromatogr A. 2018 Jul 04;: Authors: Huang T, Armbruster M, Lee R, Hui DS, Edwards JL Abstract Analysis of metabolites is often performed using separations coupled to mass spectrometry which is challenging due to their vast structural heterogeneity and variable charge states. Metabolites are often separated based on their class/functional group which in large part determine their acidity or basicity. This charge state dictates the ionization mode and efficiency of the molecule. To improve the sensitivity and expand the coverage of the mammalian metabolome, multifunctional derivatization with sheathless CE-ESI-MS was undertaken. In this work, amines, hydroxyls and carboxylates were labeled with tertiary amines tags. This derivatization was performed in under 100 min and resulted in high positive charge states for all analytes investigated. Amino acids and organic acids showed average limits of detection of 76 nM with good linearity of 0.96 and 10% RSD for peak area. Applying this metabolomic profiling system to bovine aortic endothelial cells showed changes in 15 metabolites after treatment with high glucose. The sample injection volume on-capillary was <300 cells for quantitative analyses. Targeted metabolites were found in human tissue, which indicates possible application of the system complex metabolome quantitation. PMID: 30005940 [PubMed - as supplied by publisher]

pH plays a role in the mode of action of trimethoprim on Escherichia coli. PLoS One. 2018;13(7):e0200272 Authors: AlRabiah H, Allwood JW, Correa E, Xu Y, Goodacre R Abstract Metabolomics-based approaches were applied to understand interactions of trimethoprim with Escherichia coli K-12 at sub-minimum inhibitory concentrations (MIC≈0.2, 0.03 and 0.003 mg L-1). Trimethoprim inhibits dihydrofolate reductase and thereby is an indirect inhibitor of nucleic acid synthesis. Due to the basicity of trimethoprim, two pH levels (5 and 7) were selected which mimicked healthy urine pH. This also allowed investigation of the effect on bacterial metabolism when trimethoprim exists in different ionization states. UHPLC-MS was employed to detect trimethoprim molecules inside the bacterial cell and this showed that at pH 7 more of the drug was recovered compared to pH 5; this correlated with classical growth curve measurements. FT-IR spectroscopy was used to establish recovery of reproducible phenotypes under all 8 conditions (3 drug levels and control in 2 pH levels) and GC-MS was used to generate global metabolic profiles. In addition to finding direct mode-of-action effects where nucleotides were decreased at pH 7 with increasing trimethoprim levels, off-target pH-related effects were observed for many amino acids. Additionally, stress-related effects were observed where the osmoprotectant trehalose was higher at increased antibiotic levels at pH 7. This correlated with glucose and fructose consumption and increase in pyruvate-related products as well as lactate and alanine. Alanine is a known regulator of sugar metabolism and this increase may be to enhance sugar consumption and thus trehalose production. These results provide a wider view of the action of trimethoprim. Metabolomics indicated alternative metabolism areas to be investigated to further understand the off-target effects of trimethoprim. PMID: 30005078 [PubMed - in process]

Toward Precision Nutrition: Commercial Infant Formulas and Human Milk Compared for Stereospecific Distribution of Fatty Acids Using Metabolomics. OMICS. 2018 Jul;22(7):484-492 Authors: Lopes TIB, Cañedo MC, Oliveira FMP, Alcantara GB Abstract Precision nutrition and nutrimetabolomics are emerging omics technology applications in public health. In this context, the infant formula (IF) is a manufactured foodstuff that aims to match the composition of human milk (HM), especially the lipid profile. The IF manufacturers have achieved relative success in matching the predominant fatty acid (FAs) profiles, but the stereospecific structures of the triacylglycerides in HM require deeper analyses with system sciences. We employed NMR-based metabolomics to compare the lipid profiles of 12 commercial IF samples and 10 HM samples. Additionally, vegetables, fish, and microalgae oil as raw materials in IFs were also investigated to understand the lipid profile of IFs. We found that IF has significantly less saturated fatty acids (SFA), higher unsaturated FAs, and similar polyunsaturated fatty acid (PUFA) content, compared with HM. However, the main difference was the stereospecific distribution of FAs: HM samples were associated with a high content of SFAs in the sn-2 position (26.03% ± 2.93%) and PUFAs in the sn-1,3 position (15.35% ± 3.94%). The IF had the opposite distribution, with SFAs esterified mainly in the sn-1,3 position (33.07 ± 4.93%) and PUFAs in the sn-2 position (9.57% ± 7.05%). Consequently, the hydrolysis of HM results in SFA mainly as sn-2-monoacylglycerides, which are well absorbed. In contrast, the hydrolysis of the IF provided SFA, mainly as free FAs, which tend to bind calcium and form insoluble calcium soaps in the intestine. Taken together, these observations can inform optimal design of infant formulas with a view to precision nutrition. PMID: 30004842 [PubMed - in process]

Ingestion of an Inulin-Enriched Pork Sausage Product Positively Modulates the Gut Microbiome and Metabolome of Healthy Rats. Mol Nutr Food Res. 2018 Jul 13;:e1800608 Authors: Thøgersen R, Castro-Mejía JL, Sundekilde UK, Hansen LH, Hansen AK, Nielsen DS, Bertram HC Abstract SCOPE: Processed meat intake is associated with a potential increased colorectal cancer (CRC) risk. In contrast, dietary fiber consumption has been found to lower CRC risk, possibly via mechanisms involving the gut microbiota (GM) and its metabolites. This study investigated the effect of inulin enrichment of a common pork sausage product on GM composition and activity in healthy rats. METHODS AND RESULTS: Thirty Sprague-Dawley rats were fed a diet based on either an inulin-enriched sausauge (n = 12), a corresponding control sausage without enrichment (n = 12) or a standard chow diet (n = 6) during a four-week intervention. NMR-based metabolomics analyses were conducted on fecal and plasma samples, and GM composition was determined using 16S rRNA gene amplicon sequencing. Pronounced effects of diets on GM composition and activity were found. Rats fed the inulin-enriched sausages had increased levels of short chain fatty acids (SCFAs) in the fecal and plasma metabolome and increased fecal levels of Bifidobacterium spp. as compared to rats fed sausages without enrichment. CONCLUSION: Inulin enrichment of a meat product resembles general effects seen upon dietary fiber consumption and corroborates that healthier processed meats can be developed through strategic inclusion of dietary fiber ingredients. This article is protected by copyright. All rights reserved. PMID: 30004630 [PubMed - as supplied by publisher]

Metabolomics and Lipidomics Approaches in the Science of Probiotics: A Review. J Med Food. 2018 Jul 13;: Authors: Chung HJ, Sim JH, Min TS, Choi HK Abstract The intestinal microflora plays important roles in the health of the host, such as nutrient processing and the modulation of intestinal immune responses. The constituents of the diet greatly affect the composition of the microbiota and its metabolites. The human intestinal microbiota is made up of around 100 trillion microbial cells encompassing at least 300 species. Consuming probiotics may lead to changes in the intestinal microflora that influence host health. Metabolomics is a powerful tool for revealing metabolic changes in biofluids, tissues, and organs of hosts induced by the consumption of probiotics, and lipidomics in particular is a technical approach that focuses on the analysis of lipids in various cells and biofluids. Metabolomics and lipidomics have been used to investigate intracellular and extracellular metabolites as well as for the nontargeted profiling and fingerprinting of metabolites. Based on metabolomics and lipidomics investigations, we reviewed the effects of consuming probiotics on metabolic profiles in controlled intestinal environments. We also discuss the associations between metabolic changes and human diseases after consuming probiotics in uncontrolled intestinal environments. In addition, we review the metabolic changes that take place within the food matrix during probiotic fermentation. PMID: 30004273 [PubMed - as supplied by publisher]

Related Articles Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity- A prospective exploratory pilot study. Diabetes Metab Res Rev. 2018 Jul 13;:e3045 Authors: Wijayatunga NN, Sams VG, Dawson JA, Mancini ML, Mancini GJ, Moustaid-Moussa N Abstract AIM: Bariatric surgery induces significant weight loss, increases insulin sensitivity and reduces mortality, but the underlying mechanisms are not clear. It was hypothesized that Roux-en-Y gastric bypass (RYGB) surgery improves metabolic profile along with weight loss. The objective of this study was to evaluate changes in serum metabolites and fatty acids (FA) at two weeks and six months after RYGB. MATERIALS AND METHODS: Serum samples were collected pre-surgery, at 2 weeks and 6 months post-surgery from twenty patients undergoing RYGB surgery. Serum non-esterified free FA (NEFA) were measured. Serum metabolites and fatty acids were measured using Nuclear Magnetic Resonance (NMR) spectroscopy and improved direct fatty acid methyl ester (FAME) synthesis and the gas chromatography/mass spectrometry (GC/MS) method, respectively, in subjects who completed follow up at 6 months (n=8). RESULTS: Mean (standard deviation; SD) percent total weight loss was 6.70% (1.7) and 26.95% (7.37) at 2 weeks (n=15) and 6 months (n=8) post-surgery, respectively. NEFA were significantly reduced at 6 months post-surgery (p=0.001, n=8). Serum branched chain amino acids, 2-aminobutyrate, butyrate, 2-hydroxybutyrate, 3-hydroxybutyrate, acetone, 2-methylglutarate and 2-oxoisocaproate were significantly reduced, while serum alanine, glycine, pyruvate, and taurine were significantly elevated at six months post-surgery compared to pre-surgery (n=8, p<0.05). Also, serum FA C10:0, C13:0, C14:0, C15:0 and C18:0 increased significantly (n=8, p<0.05) by 6 months post-surgery. CONCLUSIONS: Changes in serum metabolites and fatty acids at 6 months post-RYGB surgery in this pilot study with limited number of participants are suggestive of metabolic improvement; larger studies are warranted for confirmation. PMID: 30003682 [PubMed - as supplied by publisher]

Related Articles High-throughput optimization of the chemically defined synthetic medium for the production of erythromycin A. Bioprocess Biosyst Eng. 2018 Jul 13;: Authors: Hong M, Liao J, Chu J Abstract Erythromycin A is an important antibiotic. A chemically defined synthetic medium for erythromycin production was systematically optimized in this study. A high-throughput method was employed to reduce the number of components and optimize the concentration of each component. After two round single composition deletion experiment, only 19 components were remained in the medium, and then the concentration of each component was optimized through PB experiment. The optimal medium from the PB experiment was further optimized according to the nitrogen and phosphate metabolic consumption in 5 L bioreactor. It was observed that among the 8 amino acids concluded in the media, 4 amino acids were first consumed, when they are almost depleted, the other 4 amino acids were initiated their consumption afterwards in 5 L bioreactor. The decrease of phosphate concentration would increase qglc and qery. However, when phosphate concentration was too low, the production of erythromycin was hindered. The positive correlation between intracellular metabolite pools and Yery/glc indicated that low phosphate concentration in the medium can promote cell metabolism especially secondary metabolism during the stationary phase; however, if it was too low (5 mmol/L), the cell metabolism and secondary metabolism would both slow down. The erythromycin titer in the optimized medium (medium V) reached 1380 mg/L, which was 17 times higher than the previously used synthetic medium in our lab. The optimized medium can facilitate the metabolomics study or metabolic flux analysis of the erythromycin fermentation process, which laid a solid foundation for further study of erythromycin fermentation process. PMID: 30003380 [PubMed - as supplied by publisher]

Related Articles The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research. Nat Prod Rep. 2018 Jul 13;: Authors: McAlpine JB, Chen SN, Kutateladze A, MacMillan JB, Appendino G, Barison A, Beniddir MA, Biavatti MW, Bluml S, Boufridi A, Butler MS, Capon RJ, Choi YH, Coppage D, Crews P, Crimmins MT, Csete M, Dewapriya P, Egan JM, Garson MJ, Genta-Jouve G, Gerwick WH, Gross H, Harper MK, Hermanto P, Hook JM, Hunter L, Jeannerat D, Ji NY, Johnson TA, Kingston DGI, Koshino H, Lee HW, Lewin G, Li J, Linington RG, Liu M, McPhail KL, Molinski TF, Moore BS, Nam JW, Neupane RP, Niemitz M, Nuzillard JM, Oberlies NH, Ocampos FMM, Pan G, Quinn RJ, Reddy DS, Renault JH, Rivera-Chávez J, Robien W, Saunders CM, Schmidt TJ, Seger C, Shen B, Steinbeck C, Stuppner H, Sturm S, Taglialatela-Scafati O, Tantillo DJ, Verpoorte R, Wang BG, Williams CM, Williams PG, Wist J, Yue JM, Zhang C, Xu Z, Simmler C, Lankin DC, Bisson J, Pauli GF Abstract Covering: up to 2018With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields. PMID: 30003207 [PubMed - as supplied by publisher]

Related Articles Iterative cycle of widely targeted metabolic profiling for the improvement of 1-butanol titer and productivity in Synechococcus elongatus. Biotechnol Biofuels. 2018;11:188 Authors: Fathima AM, Chuang D, Laviña WA, Liao J, Putri SP, Fukusaki E Abstract Background: Metabolomics is the comprehensive study of metabolites that can demonstrate the downstream effects of gene and protein regulation, arguably representing the closest correlation with phenotypic features. Hence, metabolomics-driven approach offers an effective way to facilitate strain improvement. Previously, targeted metabolomics on the 1-butanol-producing cyanobacterial strain Synechococcus elongatus BUOHSE has revealed the reduction step from butanoyl-CoA to butanal, catalyzed by CoA-acylating propionaldehyde dehydrogenase (PduP), as a rate-limiting step in the CoA-dependent pathway. Moreover, an increase in acetyl-CoA synthesis rate was also observed in this strain, by which the increased rate of release of CoA from butanoyl-CoA was used to enhance formation of acetyl-CoA to feed into the pathway. Results: In the present study, a new strain (DC7) with an improved activity of PduP enzyme, was constructed using BUOHSE as the background strain. DC7 showed a 33% increase in 1-butanol production compared to BUOHSE. For a deeper understanding of the metabolic state of DC7, widely targeted metabolomics approach using ion-pair reversed-phase LC/MS was performed. Results showed a decreased level of butanoyl-CoA and an increased level of acetyl-CoA in DC7 compared to BUOHSE. This served as an indication that the previous bottleneck has been solved and free CoA regeneration increased upon the improvement of the PduP enzyme. In order to utilize the enhanced levels of acetyl-CoA in DC7 for 1-butanol production, overexpression of acetyl-CoA carboxylase (ACCase) in DC7 was performed by inserting the gene encoding an ACCase subunit from Yarrowia lipolytica into the aldA site. The resulting strain, named DC11, was able to reach a production titer of 418.7 mg/L in 6 days, compared to DC7 that approached a similar titer in 12 days. A maximum productivity of 117 mg/L/day was achieved between days 4 and 5 in DC11. Conclusions: In this study, the iterative cycle of genetic modification based on insights from metabolomics successfully resulted in the highest reported 1-butanol productivity for engineered Synechococcus elongatus PCC 7942. PMID: 30002728 [PubMed]

Related Articles A Pilot Study on Characteristics of Metabolomics and Lipidomics according to Sasang Constitution. Evid Based Complement Alternat Med. 2018;2018:9214960 Authors: Kim MJ, Lee DH, Ahn J, Ha TY, Jang YJ, Do E, Jung CH Abstract Although classification of an individual's Sasang constitution is a key step in the prescription of traditional Korean medicine, the classifying process is complex and not objective. Identification of metabolic-based biomarkers could allow the development of a reliable and sensitive classification technique and even therapeutic management. Our pilot study investigated whether metabolites in plasma are characteristic of Sasang constitutions. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolic analysis was conducted against 15 Soyangin (SY), 15 Taeeumin (TE), and 18 Soeumin (SE) individuals, as classified according to the Questionnaire for Sasang Constitution Classification II (QSCC II) and specialist diagnosis. Metabolomics data showed that the TE group was significantly separated from the SY and SE groups. Nine canonical pathways related to constitution; phenylalanine metabolism, aminoacyl-tRNA, tyrosine, and tryptophan biosynthesis were activated in the TE group as compared with the other groups. Similar to the results of the metabolomics analysis, the TE group was also significantly separated from the other two groups by lipidomic analysis. On the other hand, the intensity of lipid metabolites was higher in the SY group than in the other groups. Our findings suggest that the combined analysis of metabolomics and lipidomics can provide useful information for characteristics of Sasang constitutions. PMID: 30002718 [PubMed]

Related Articles Mass Spectrometry Based Imaging of Labile Glucosides in Plants. Front Plant Sci. 2018;9:892 Authors: Bøgeskov Schmidt F, Heskes AM, Thinagaran D, Lindberg Møller B, Jørgensen K, Boughton BA Abstract Mass spectrometry based imaging is a powerful tool to investigate the spatial distribution of a broad range of metabolites across a variety of sample types. The recent developments in instrumentation and computing capabilities have increased the mass range, sensitivity and resolution and rendered sample preparation the limiting step for further improvements. Sample preparation involves sectioning and mounting followed by selection and application of matrix. In plant tissues, labile small molecules and specialized metabolites are subject to degradation upon mechanical disruption of plant tissues. In this study, the benefits of cryo-sectioning, stabilization of fragile tissues and optimal application of the matrix to improve the results from MALDI mass spectrometry imaging (MSI) is investigated with hydroxynitrile glucosides as the main experimental system. Denatured albumin proved an excellent agent for stabilizing fragile tissues such as Lotus japonicus leaves. In stem cross sections of Manihot esculenta, maintaining the samples frozen throughout the sectioning process and preparation of the samples by freeze drying enhanced the obtained signal intensity by twofold to fourfold. Deposition of the matrix by sublimation improved the spatial information obtained compared to spray. The imaging demonstrated that the cyanogenic glucosides (CNglcs) were localized in the vascular tissues in old stems of M. esculenta and in the periderm and vascular tissues of tubers. In MALDI mass spectrometry, the imaged compounds are solely identified by their m/z ratio. L. japonicus MG20 and the mutant cyd1 that is devoid of hydroxynitrile glucosides were used as negative controls to verify the assignment of the observed masses to linamarin, lotaustralin, and linamarin acid. PMID: 30002667 [PubMed]

Related Articles Screening of Combinatorial Quality Markers for Natural Products by Metabolomics Coupled With Chemometrics. A Case Study on Pollen Typhae. Front Pharmacol. 2018;9:691 Authors: Ding M, Jiang Y, Yu X, Zhang D, Li J, Wang H, Shen J, Gao XM, Chang YX Abstract Natural products, especially for traditional Chinese medicines (TCMs), are of great importance to cure diseases. Yet it was hard to screen the influential quality markers for monitoring the quality. A simple and comprehensive strategy was developed and validated to screen for the combinatorial quality markers for precise quality evaluation and discrimination of natural products. In this study, Pollen Typhae (PT) and it's processed products carbonized PT were selected as the representative case. Firstly, metabolomics data of 49 batches crude PT and carbonized PT was obtained by ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Then, metabolomics approaches were performed to screen for the potential markers that lead to the quality difference. Finally, chemometric methods were used to validate the accuracy of combinatorial quality markers. Thus, 42 compounds were identified from PT, 5 markers (isorhamnetin-3-O-(2G-α-L-rhamnosyl)-rutinoside, isorhamnetin-3-O-neohesperidoside, astragalin, kaempferol and umbelliferone) were successfully screened, identified, quantified and regarded as combinatorial quality markers for precise quality evaluation of crude and carbonized PT. It was demonstrated that the established comprehensively strategy provide an efficient tool for precise quality evaluation of natural products from the whole. PMID: 30002628 [PubMed]

Related Articles Pazopanib plus cetuximab in recurrent or metastatic head and neck squamous cell carcinoma: an open-label, phase 1b and expansion study. Lancet Oncol. 2018 Jul 09;: Authors: Adkins D, Mehan P, Ley J, Siegel MJ, Siegel BA, Dehdashti F, Jiang X, Salama NN, Trinkaus K, Oppelt P Abstract BACKGROUND: Angiogenesis is a hallmark of head and neck squamous cell carcinoma (HNSCC), and a mechanism of resistance to EGFR inhibition. We investigated the safety and potential activity of pazopanib, an angiogenesis inhibitor, plus cetuximab, an EGFR inhibitor, in patients with recurrent or metastatic HNSCC. METHODS: We did an open-label, single-centre, dose-escalation phase 1b trial using a standard 3 + 3 design, followed by an expansion cohort phase. Eligible participants were patients with histologically or cytologically confirmed recurrent or metastatic HNSCC, aged at least 18 years, had measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and an Eastern Cooperative Oncology Group performance status of 0-1. During dose escalation, pazopanib oral suspension was administered daily in 8-week cycles at doses of 200 mg/day, 400 mg/day, 600 mg/day, or 800 mg/day, with cetuximab given intravenously once per week (400 mg/m2 first dose and 250 mg/m2 in consecutive cycles). The primary endpoint was to determine the maximum tolerated dose or recommended phase 2 dose of pazopanib in combination with cetuximab. Analyses were done per protocol. This trial is registered with ClinicalTrials.gov, number NCT01716416, and it is ongoing but closed to accrual. FINDINGS: Between June 5, 2013, and April 4, 2017, we enrolled 22 patients into the phase 1b, dose-escalation phase of the trial. A maximum tolerated dose of pazopanib in combination with cetuximab was not reached. Single dose-limiting toxic events (all grade 3) during dose escalation occurred with pazopanib 400 mg/day (neutropenia with infection), 600 mg/day (proteinuria), and 800 mg/day (fatigue). The established recommended phase 2 dose for the combination was 800 mg/day of pazopanib during cycles of 8 weeks each, plus cetuximab 400 mg/m2 on day 1 of cycle 1, then cetuximab 250 mg/m2 weekly. A further nine patients were enrolled into the expansion cohort and treated with the established recommended phase 2 dose. The most common (grade 3-4) adverse events for all patients were hypertension (ten [32%] of 31), lymphocyte count decrease (seven [23%]), and dysphagia (seven [23%]). There were no treatment-related deaths. 11 (35%; 95% CI 19·2-54·6) of 31 patients achieved an overall response, as assessed by the investigator; two (6%) had a complete response and nine (29%) a partial response. Tumour responses were also observed in six (55%) of 11 patients with platinum-naive and cetuximab-naive disease, three (25%) of 12 patients with cetuximab-resistant disease, and five (28%) of 18 patients with platinum-resistant disease. INTERPRETATION: Pazopanib oral suspension at a dose of 800 mg/day was feasible to administer in combination with standard weekly cetuximab for patients with recurrent or metastatic HNSCC. Encouraging preliminary antitumour activity was observed with this combination therapy and warrants further validation in randomised trials. FUNDING: GlaxoSmithKline and Novartis. PMID: 30001987 [PubMed - as supplied by publisher]