PubMed

Related Articles The Enchytraeus crypticus stress metabolome - CuO NM case study. Nanotoxicology. 2018 Jun 22;:1-15 Authors: Maria VL, Licha D, Ranninger C, Scott-Fordsmand JJ, Huber CG, Amorim MJB Abstract The stress metabolome provides a thorough insight into the signals and hence mechanisms of response of organisms. This is an excellent tool to advance the understanding of interactions, especially for substances like nanomaterials (NMs), for which there is an urgent need for alternative methods for hazard assessment. The metabolome of Enchytraeus crypticus was studied for the first time. The case study, CuO NM (and CuCl2) covered exposure along a time frame [0-7-14 days (d)] and two reproduction effect concentrations (EC10 and EC50). High-performance liquid chromatography-mass spectrometry based method (HPLC-MS) was used, with reversed phase (RP) separation and mass spectrometric detection in positive and negative modes. Metabolite profiling of Cu materials yielded 155 and 382 metabolite features in positive and negative modes, respectively, showing an expression related with time, material, and ECx. The number of differentially expressed metabolites (DEMs) decreased with exposure time (14 d) for CuO NM, whereas for CuCl2 EC50 it increased. Overall, almost all DEMs are down-regulated for CuO NM and up-regulated for CuCl2 (both modes). Early effects were mainly related to amino acids and later to lysophospholipids (down-regulation). Furthermore, the underlying mechanisms of CuO NM toxicity (e.g. neurotransmission, nucleic acids generation, cellular energy, and immune defense) differ from CuCl2, where later metabolomic responses are mostly linked to the metabolism of lipids and fewer to amino acids. This study reports a large scale metabolome profiling for E. crypticus and identifies potential markers of Cu materials, which can help to align intelligent testing strategies and safer-by-design materials. PMID: 29933707 [PubMed - as supplied by publisher]

Related Articles [Inhibitory effect of Scutellariae Radix on hepatic fibrosis based on urinary metabonomic]. Zhongguo Zhong Yao Za Zhi. 2018 May;43(10):2140-2146 Authors: Chang H, Meng HY, Wang Y, Teng Z, Liu SM Abstract Urinary metabolomics combined with histological progression were utilized to evaluate the therapeutic effect of Scutellariae Radix decoction and baicalin on hepatic fibrosis (HF) and explore their mechanisms, intervention targets and metabolic pathways. HF rat model was established through subcutaneous injection of CCl₄ for 8 weeks. Meanwhile, different doses of Scutellariae Radix decoction and baicalin were administered. Histomorphology of liver tissue was observed and scored by HE and Masson. Urinary metabonomic analysis based on UPLC-Q-TOF-MS was made for the changes of urinary potential biomarkers among different groups at different time points of HF. Finally, it was found that Scutellariae Radix decoction could improve HF by regulating L-tryptophan, 3-methyldioxyindole, 5-hydroxyindoleacetylglycine, kynurenic acid, 4-(2-amino-3-hydroxyphenyl)-2,4-dioxobutanoic acid, methylmalonic acid and L-leucine. However, baicalin could improve HF by regulating L-tryptophan, 3-methyldioxyindole, 5-hydroxyindoleacetylglycine, 4-(2-amino-3-hydroxyphenyl)-2,4-dioxobutanoic acid, kynurenic acid, and methylmalonic acid. These metabolites involved in tryptophan metabolism and valine, leucine and isoleucine degradation pathways. These results indicated that Scutellariae Radix had the multi-target and multi-pathway characteristics in the treatment of HF. Additionally, low-dose Scutellariae Radix decoction and baicalin are showed better efficacies, with no statistically significant difference between them in histomorphology. PMID: 29933684 [PubMed - in process]

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 2018/06/23PubMed 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.

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 2018/06/23PubMed 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 2018/06/22PubMed 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 2018/06/22PubMed 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 2018/06/21PubMed 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.

22 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 2018/06/20PubMed 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.

22 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 2018/06/20PubMed 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.

Sample treatment optimization for fish stool metabolomics. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jun 07;1092:258-267 Authors: Hano T, Ito M, Ito K, Uchida M Abstract Gut microbiota play an essential role in an organism's health. The fecal metabolite profiling content reflects these microbiota-mediated physiological changes in various organisms, including fish. Therefore, metabolomics analysis of fish feces should provide insight into the dynamics linking physiology and gut microbiota. However, metabolites are often unstable in aquatic environments, making fecal metabolites difficult to examine in fish. In this study, a novel method using gas chromatography-mass spectrometry (GC-MS) was developed and optimized for the preparation of metabolomics samples from the feces of the marine fish, red sea bream (Pagrus major). The preparation methodology was optimized, focusing on rinsing frequency and rinsing solvent. Feces (collected within 4 h of excretion) were rinsed three times with sterilized 2.5% NaCl solution or 3.0% artificial seawater (ASW). Among the 86 metabolites identified in the NaCl-rinsed samples, 57 showed superior recovery to that in ASW-rinsed samples, indicating that NaCl is a better rinsing solvent, particularly for amino acids, organic acids, and fatty acids. To evaluate rinsing frequency, fecal samples were rinsed with NaCl solution 0, 1, 3, or 5 times. The results indicate that three or more rinses enabled robust and stable detection of metabolites encapsulated within the solid fecal residue. Furthermore, these data suggest that rinsing is unnecessary when studying sugars, amino acids, and sterols, again highlighting the need for appropriate rinsing solvent and frequency. This study provides further insight into the use of fecal samples to evaluate and promote fish health during farming and supports the application of this and similar analyses to study the effects of environmental fluctuations and/or contamination. PMID: 29913338 [PubMed - as supplied by publisher]

Serum metabolome profiling revealed potential biomarkers for milk protein yield in dairy cows. J Proteomics. 2018 Jun 15;: Authors: Wu X, Sun H, Xue M, Wang D, Guan LL, Liu J Abstract Milk yield (MY) and milk protein (MP) content are crucial milk performance traits of dairy cows that directly affect the dairy profits. This study first proposed milk protein yield (MPY) by considering MY and MP content together. Forty multiparous cows were selected from the 348 Holstein dairy cows, which fed the same diet under the same management condition, to investigate the serum metabolome profiles and to identify key metabolites associated with MPY. Among them, 20 cows with a higher MPY (MY > 34.5 kg/d and MP > 3.2%. i.e., MPY > 1.11 kg/d) were defined as the HH group, and 20 cows with a lower MPY (MY < 31 kg/d and MP < 2.9%, i.e., MPY < 0.87 kg/d) as the LL group. The GC-TOF/MS and the ultra HPLC-MS/MS platforms were used to identify metabolites and quantify biomarkers, respectively. Orthogonal partial least squares discriminant analysis of serum metabolomes revealed a clear separation between the 2 groups. Thirty-six significantly different metabolites were identified, which mainly involved in valine, leucine and isoleucine biosynthesis and glycine, serine and threonine metabolism. With biomarker analysis and validation, hippuric acid, nicotinamide and pelargonic acid may serve as key metabolites associated with MPY. BIOLOGICAL SIGNIFICANCE: This study reports the application of serum metabolomics to identify biomarkers related to MPY and to reveal the biological pathways affecting milk protein synthesis. Three novel serum biomarkers were discovered to reflect the MPY variation of dairy cows, which may be useful in quality control in dairy cow production and for optimizing industrial production of dairy products. This study confirms that individual physiological and metabolic differences contribute to the variations in MPY and provides directions for further improving the MPY of dairy cows. PMID: 29913267 [PubMed - as supplied by publisher]

Pilot assessment of probiotics for pregnant women in Rwanda. PLoS One. 2018;13(6):e0195081 Authors: McMillan A, Rulisa S, Gloor GB, Macklaim JM, Sumarah M, Reid G Abstract BACKGROUND: While the global market for probiotics is soon to reach in excess of US$50 billion, the continent of Africa has been largely ignored, despite these products having the ability to reduce the burden of disease and death. TRIAL DESIGN: The present randomised, blinded, placebo-controlled clinical trial was undertaken in Rwanda, a country devoid of well-documented probiotics. The primary outcome aim was to examine receptivity and compliance for orally administered probiotic capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 in pregnant women and assess any initial side effects or changes to the vaginal microbiome. METHODS: Pregnant women between the ages of 18 and 55 were recruited from the Nyamata District Hospital in Rwanda and randomly assigned to receive probiotic or placebo capsules for one month. Clinicians were blinded to the treatments. RESULTS: The drop-out rate was 21%, with 13 of 18 women in the placebo group and 17 of 20 in the probiotic group completing the study. Only 13 women returned for birthing and additional sample collection. No side effects of either treatment group were reported. Microbiota and metabolomics data showed similar findings to those reported in the literature, with low bacterial diversity and Lactobacillus dominance associated with a healthy vagina, and birthing associated with high diversity. Despite the small sample size and lack of changes in the microbiota, women in the placebo arm were significantly more likely to give birth pre-term. CONCLUSION: Overall women were receptive to the probiotic concept, but the lack of information on such products and logistical and economical challenges pose problems for wider population engagement. TRIAL REGISTRATION: ClinicalTrials.gov NCT02150655. PMID: 29912913 [PubMed - in process]

Antibiotic and Modulation of Microbiota: A New Paradigm? J Clin Gastroenterol. 2018 Jun 16;: Authors: Rizzatti G, Ianiro G, Gasbarrini A Abstract Recently new insights on gut microbiota have revolutionized many concepts of the modern medicine. The alteration of microbiota, which is called dysbiosis, has been associated with an expanding list of diseases and conditions. The development of next-generation sequencing techniques allowed comprehensive analysis of gut microbiota composition without the limitations of classic culture methods. Furthermore, introduction of functional techniques such as metabolomics and proteomics allowed for integrated analysis thus obtaining more robust insights on microbiota functions in health and disease. These tools allow to address the role of factors able to modify the gut microbiota, the so called "microbiota influencers." These data are useful to explain the physiopathology of several disease and thus to identify new potential therapeutic targets. Among microbiota influencers, many studies focused on the impact of antibiotic administration on the gut microbiota, because of their widespread use. Notably, beside the known beneficial effect of antibiotic in treating infectious diseases, these drugs have shown detrimental effects on gut microbiota which, in turn, might have long-term consequences on the host. Finally, therapeutic modulation of gut microbiota, by means of selected antibiotics with eubiotic effects, probiotics and with fecal microbiota transplantation seems of great interest as it might be able to prevent or even revert antibiotic-induced dysbiosis. PMID: 29912755 [PubMed - as supplied by publisher]

Dietary supplemental Kluyveromyces marxianus alters the serum metabolite profile in broiler chickens. Food Funct. 2018 Jun 18;: Authors: Wang W, Li Z, Gan L, Fan H, Guo Y Abstract Metabolomics is used to evaluate the bioavailability of food components, as well as to validate the metabolic changes associated with food consumption. This study was conducted to investigate the effects of the dietary supplement Kluyveromyces marxianus on the serum metabolite profile in broiler chickens. A total of 240 1-d-old broilers were divided into 2 groups with 8 replicates. Birds were fed basal diets without or with K. marxianus supplementation (5 × 1010 CFU kg-1 of diet). Serum samples were collected on d 21 and were analyzed by high-performance liquid chromatography with quadrupole time-of flight/mass spectrometry. The results showed that supplemental K. marxianus altered the concentrations of a variety of metabolites in the serum. Thereinto, a total of 39 metabolites were identified at higher (P < 0.05) concentrations while 21 metabolites were identified at lower (P < 0.05) concentrations in the treatment group as compared with the control. These metabolites were primarily involved with the regulation of amino acids and carbohydrate metabolism. Further metabolic pathway analysis revealed that glutamine and glutamate metabolism was the most relevant and critical pathway identified from these two groups. The activated pathway may partially interpret the beneficial effects of K. marxianus. Overall, the present research could promote our understanding of the probiotic action of K. marxianus and provide new insight into the design and application of K. marxianus-containing functional foods. PMID: 29912245 [PubMed - as supplied by publisher]

Related Articles Comprehensive relative quantitative metabolomics analysis of lycopodium alkaloids in different tissues of Huperzia serrata. Synth Syst Biotechnol. 2018 Mar;3(1):44-55 Authors: Wu S, Fan Z, Xiao Y Abstract Qian ceng Ta, the whole plant of Huperzia serrata, is an important landscape and medicinal herbs and contains abundant bioactive lycopodium alkaloids. Although the structures of more than 100 lycopodium alkaloids in Huperzia serrata have been isolated and identified, the content and distribution of these alkaloids in different tissues are still unclear. In current study, an ultra-performance liquid chromatography-mass spectrometry based comprehensive metabolomics strategy was developed, including the extraction, separation, identification, and statistical analysis. The results showed that different types lycopodium alkaloids could be separated at different time-windows, which was helpful for further metabolite identification. Peak4388 and peak3954 were metabolite biomarkers for the different tissues according to the principle component analysis and partial least squares-discriminant analysis model. A computational tool based in-house database was also built up and used for putative identification. Of the 2354 true peaks after four-step filtration, 118 peaks were putatively identified as lycopodium alkaloids by using in-house database, and four of which was identified by authentic standards. Alternatively, another computational software was used to predict the fragmentation pattern, to dereplicate the structure of identified peaks, and identified the peak3585 to N-methylhuperzine A. The integration of both computational tools could be used for more metabolites identification. PMID: 29911198 [PubMed]

Related Articles Short-Term Fasting Reveals Amino Acid Metabolism as a Major Sex-Discriminating Factor in the Liver. Cell Metab. 2018 Jun 06;: Authors: Della Torre S, Mitro N, Meda C, Lolli F, Pedretti S, Barcella M, Ottobrini L, Metzger D, Caruso D, Maggi A Abstract Sex impacts on liver physiology with severe consequences for energy metabolism and response to xenobiotic, hepatic, and extra-hepatic diseases. The comprehension of the biology subtending sex-related hepatic differences is therefore very relevant in the medical, pharmacological, and dietary perspective. The extensive application of metabolomics paired to transcriptomics here shows that, in the case of short-term fasting, the decision to maintain lipid synthesis using amino acids (aa) as a source of fuel is the key discriminant for the hepatic metabolism of male and female mice. Pharmacological and genetic interventions indicate that the hepatic estrogen receptor (ERα) has a key role in this sex-related strategy that is primed around birth by the aromatase-dependent conversion of testosterone into estradiol. This energy partition strategy, possibly the result of an evolutionary pressure enabling mammals to tailor their reproductive capacities to nutritional status, is most important to direct future sex-specific dietary and medical interventions. PMID: 29909969 [PubMed - as supplied by publisher]

Related Articles Propagating annotations of molecular networks using in silico fragmentation. PLoS Comput Biol. 2018 04;14(4):e1006089 Authors: da Silva RR, Wang M, Nothias LF, van der Hooft JJJ, Caraballo-Rodríguez AM, Fox E, Balunas MJ, Klassen JL, Lopes NP, Dorrestein PC Abstract The annotation of small molecules is one of the most challenging and important steps in untargeted mass spectrometry analysis, as most of our biological interpretations rely on structural annotations. Molecular networking has emerged as a structured way to organize and mine data from untargeted tandem mass spectrometry (MS/MS) experiments and has been widely applied to propagate annotations. However, propagation is done through manual inspection of MS/MS spectra connected in the spectral networks and is only possible when a reference library spectrum is available. One of the alternative approaches used to annotate an unknown fragmentation mass spectrum is through the use of in silico predictions. One of the challenges of in silico annotation is the uncertainty around the correct structure among the predicted candidate lists. Here we show how molecular networking can be used to improve the accuracy of in silico predictions through propagation of structural annotations, even when there is no match to a MS/MS spectrum in spectral libraries. This is accomplished through creating a network consensus of re-ranked structural candidates using the molecular network topology and structural similarity to improve in silico annotations. The Network Annotation Propagation (NAP) tool is accessible through the GNPS web-platform https://gnps.ucsd.edu/ProteoSAFe/static/gnps-theoretical.jsp. PMID: 29668671 [PubMed - indexed for MEDLINE]

Related Articles Non-invasively predicting differentiation of pancreatic cancer through comparative serum metabonomic profiling. BMC Cancer. 2017 Nov 02;17(1):708 Authors: Wen S, Zhan B, Feng J, Hu W, Lin X, Bai J, Huang H Abstract BACKGROUND: The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy. METHODS: By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using 1H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight. RESULTS: An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation. CONCLUSION: The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively. PMID: 29096620 [PubMed - indexed for MEDLINE]

Related Articles Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes. EBioMedicine. 2017 Oct;24:257-266 Authors: Qin XY, Hara M, Arner E, Kawaguchi Y, Inoue I, Tatsukawa H, Furutani Y, Nagatsuma K, Matsuura T, Wei F, Kikuchi J, Sone H, Daub C, Kawaji H, Lassmann T, Itoh M, Suzuki H, Carninci P, Hayashizaki Y, FANTOM consortium, Kokudo N, Forrest ARR, Kojima S Abstract The acute phase protein orosomucoid-1 (Orm1) is mainly expressed by hepatocytes (HPCs) under stress conditions. However, its specific function is not fully understood. Here, we report a role of Orm1 as an executer of HPC proliferation. Increases in serum levels of Orm1 were observed in patients after surgical resection for liver cancer and in mice undergone partial hepatectomy (PH). Transcriptome study showed that Orm1 became the most abundant in HPCs isolated from regenerating mouse liver tissues after PH. Both in vitro and in vivo siRNA-induced knockdown of Orm1 suppressed proliferation of mouse regenerating HPCs and human hepatic cells. Microarray analysis in regenerating mouse livers revealed that the signaling pathways controlling chromatin replication, especially the minichromosome maintenance protein complex genes were uniformly down-regulated following Orm1 knockdown. These data suggest that Orm1 is induced in response to hepatic injury and executes liver regeneration by activating cell cycle progression in HPCs. PMID: 28927749 [PubMed - indexed for MEDLINE]

Related Articles Tumor vessel disintegration by maximum tolerable PFKFB3 blockade. Angiogenesis. 2017 Nov;20(4):599-613 Authors: Conradi LC, Brajic A, Cantelmo AR, Bouché A, Kalucka J, Pircher A, Brüning U, Teuwen LA, Vinckier S, Ghesquière B, Dewerchin M, Carmeliet P Abstract Blockade of the glycolytic activator PFKFB3 in cancer cells (using a maximum tolerable dose of 70 mg/kg of the PFKFB3 blocker 3PO) inhibits tumor growth in preclinical models and is currently being tested as a novel anticancer treatment in phase I clinical trials. However, a detailed preclinical analysis of the effects of such maximum tolerable dose of a PFKFB3 blocker on the tumor vasculature is lacking, even though tumor endothelial cells are hyper-glycolytic. We report here that a high dose of 3PO (70 mg/kg), which inhibits cancer cell proliferation and reduces primary tumor growth, causes tumor vessel disintegration, suppresses endothelial cell growth for protracted periods, (model-dependently) aggravates tumor hypoxia, and compromises vascular barrier integrity, thereby rendering tumor vessels more leaky and facilitating cancer cell intravasation and dissemination. These findings contrast to the effects of a low dose of 3PO (25 mg/kg), which induces tumor vessel normalization, characterized by vascular barrier tightening and maturation, but reduces cancer cell intravasation and metastasis. Our findings highlight the importance of adequately dosing a glycolytic inhibitor for anticancer treatment. PMID: 28875379 [PubMed - indexed for MEDLINE]