Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

metabolomics; +29 new citations

Fri, 22/06/2018 - 02:43
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.

metabolomics; +22 new citations

Wed, 20/06/2018 - 23:10
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.

metabolomics; +22 new citations

Wed, 20/06/2018 - 14:03
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.

Tue, 19/06/2018 - 13:48
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.

Tue, 19/06/2018 - 13:48
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.

Tue, 19/06/2018 - 13:48
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?

Tue, 19/06/2018 - 13:48
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.

Tue, 19/06/2018 - 13:48
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]

Comprehensive relative quantitative metabolomics analysis of lycopodium alkaloids in different tissues of Huperzia serrata.

Tue, 19/06/2018 - 13:48
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]

Short-Term Fasting Reveals Amino Acid Metabolism as a Major Sex-Discriminating Factor in the Liver.

Tue, 19/06/2018 - 13:48
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]

Propagating annotations of molecular networks using in silico fragmentation.

Tue, 19/06/2018 - 13:48
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]

Non-invasively predicting differentiation of pancreatic cancer through comparative serum metabonomic profiling.

Tue, 19/06/2018 - 13:48
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]

Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes.

Tue, 19/06/2018 - 13:48
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]

Tumor vessel disintegration by maximum tolerable PFKFB3 blockade.

Tue, 19/06/2018 - 13:48
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]

Germline BAP1 mutations induce a Warburg effect.

Tue, 19/06/2018 - 13:48
Related Articles Germline BAP1 mutations induce a Warburg effect. Cell Death Differ. 2017 10;24(10):1694-1704 Authors: Bononi A, Yang H, Giorgi C, Patergnani S, Pellegrini L, Su M, Xie G, Signorato V, Pastorino S, Morris P, Sakamoto G, Kuchay S, Gaudino G, Pass HI, Napolitano A, Pinton P, Jia W, Carbone M Abstract Carriers of heterozygous germline BAP1 mutations (BAP1+/-) develop cancer. We studied plasma from 16 BAP1+/- individuals from 2 families carrying different germline BAP1 mutations and 30 BAP1 wild-type (BAP1WT) controls from these same families. Plasma samples were analyzed by liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS), ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-TQ-MS), and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found a clear separation in the metabolic profile between BAP1WT and BAP1+/- individuals. We confirmed the specificity of the data in vitro using 12 cell cultures of primary fibroblasts we derived from skin punch biopsies from 12/46 of these same individuals, 6 BAP1+/- carriers and 6 controls from both families. BAP1+/- fibroblasts displayed increased aerobic glycolysis and lactate secretion, and reduced mitochondrial respiration and ATP production compared with BAP1WT. siRNA-mediated downregulation of BAP1 in primary BAP1WT fibroblasts and in primary human mesothelial cells, led to the same reduced mitochondrial respiration and increased aerobic glycolysis as we detected in primary fibroblasts from carriers of BAP1+/- mutations. The plasma and cell culture results were highly reproducible and were specifically and only linked to BAP1 status and not to gender, age or family, or cell type, and required an intact BAP1 catalytic activity. Accordingly, we were able to build a metabolomic model capable of predicting BAP1 status with 100% accuracy using data from human plasma. Our data provide the first experimental evidence supporting the hypothesis that aerobic glycolysis, also known as the 'Warburg effect', does not necessarily occur as an adaptive process that is consequence of carcinogenesis, but rather that it may also predate malignancy by many years and facilitate carcinogenesis. PMID: 28665402 [PubMed - indexed for MEDLINE]

Comprehensive metabonomic analysis of heart tissue from isoproterenol-induced myocardial infarction rat based on reversed-phase and hydrophilic interaction chromatography coupled to mass spectrometry.

Tue, 19/06/2018 - 13:48
Related Articles Comprehensive metabonomic analysis of heart tissue from isoproterenol-induced myocardial infarction rat based on reversed-phase and hydrophilic interaction chromatography coupled to mass spectrometry. J Sep Sci. 2017 May;40(10):2198-2206 Authors: Sun L, Liu J, Sun M, Lin L, Miao L, Ge Z, Yang B Abstract We aim to describe the metabonomic characteristics of myocardial infarction rats. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was utilized to develop a metabonomic method of the heart homogenates of myocardial infarction rats. Hydrophilic interaction chromatography allows the analysis of high polar metabolites, providing complementary information to reversed-phase liquid chromatography. We combined reversed phase and hydrophilic interaction chromatographic separations to analyze 18 samples, ten from myocardial infarction rat hearts and eight from normal rat hearts. A total of 16 potential biomarkers in rat heart tissue were screened out, primarily related to oxidative stress, nitric oxide damage, taurine, and hypotaurine metabolism and sphingolipid metabolism. This research showed that a comprehensive metabonomic study is a useful tool to reveal the underlying mechanism of myocardial infarction. PMID: 28371309 [PubMed - indexed for MEDLINE]

High-throughput ultra high performance liquid chromatography combined with mass spectrometry approach for the rapid analysis and characterization of multiple constituents of the fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms.

Tue, 19/06/2018 - 13:48
Related Articles High-throughput ultra high performance liquid chromatography combined with mass spectrometry approach for the rapid analysis and characterization of multiple constituents of the fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms. J Sep Sci. 2017 May;40(10):2178-2187 Authors: Han Y, Zhang A, Sun H, Zhang Y, Meng X, Yan G, Liu L, Wang X Abstract Acanthopanax senticosus (Rupr. et Maxim.) Harms, a traditional Chinese medicine, has been widely used to improve the function of skeleton, heart, spleen and kidney. This fruit is rich in nutrients, but the chemical constituents of Acanthopanax senticosus fruit are still unclear. A rapid method based on ultra high performance liquid chromatography with time-of-flight mass spectrometry was developed for the compound analysis of Acanthopanax senticosus fruit in vitro and in vivo. In this study, the Acanthopanax senticosus fruit could significantly increase the weight of immune organs, promote the proliferation of lymphatic T cells, regulate the lymphatic B cell function, and decrease the ability of natural killer cells. A total of 104 compounds of Acanthopanax senticosus fruit including lignans, flavones, triterpenoidsaponins, phenolic acids, and other constituents were identified. Among them, seven chemical compounds were reported for the first time in the Acanthopanax senticosus fruit. Compared with the serum sample of blank and dosed samples, 24 prototype compositions were characterized. The results of our experiment could be helpful to understand the complex compounds of Acanthopanax senticosus fruit in vitro and in vivo for further pharmacological activity studies. PMID: 28371133 [PubMed - indexed for MEDLINE]

What about the herb? A new metabolomics approach for synthetic cannabinoid drug testing.

Mon, 18/06/2018 - 13:12
Related Articles What about the herb? A new metabolomics approach for synthetic cannabinoid drug testing. Anal Bioanal Chem. 2018 Jun 16;: Authors: Bijlsma L, Gil-Solsona R, Hernández F, Sancho JV Abstract Synthetic cannabinoids (SCs) are consumed as legal alternative to cannabis and often allow passing drug-screening tests. Their rapid transience on the drug scene, combined with their mostly unknown metabolic profiles, creates a scenario with constantly moving analytical targets, making their monitoring and identification challenging. The development of fast screening strategies for SCs, not directly focused on their chemical structure, as an alternative to the commonly applied target acquisition methods, would be highly appreciated in forensic and public health laboratories. An innovative untargeted metabolomics approach, focused on herbal components commonly used for 'spice' products, was applied. Saliva samples of healthy volunteers were collected at pre-dose and after smoking herbal components and analysed by high-resolution mass spectrometry. The data obtained, combined with appropriate statistical analysis, allowed to highlight and elucidate two markers (scopoletin and N,N-bis(2-hydroxyethyl)dodecylamine), which ratio permitted to differentiate herbal smokers from non-smokers. The proposed strategy will allow discriminating potential positives, on the basis of the analysis of two markers identified in the herbal blends. This work is presented as a step forward in SC drug testing, promoting a smart first-line screening approach, which will allow reducing the number of samples to be further investigated by more sophisticated HRMS methods. Graphical abstract The development of an alternative, generic screening methods of synthetic cannabinoids, not directly based on the chemical structure, in order to provide fast response on its potential consumption. PMID: 29909458 [PubMed - as supplied by publisher]

Thrombospondin-1 interactions regulate eicosanoid metabolism and signaling in cancer-related inflammation.

Mon, 18/06/2018 - 13:12
Related Articles Thrombospondin-1 interactions regulate eicosanoid metabolism and signaling in cancer-related inflammation. Cancer Metastasis Rev. 2018 Jun 16;: Authors: Ramirez MU, Stirling ER, Emenaker NJ, Roberts DD, Soto-Pantoja DR Abstract The metabolism of arachidonic acid and other polyunsaturated fatty acids produces eicosanoids, a family of biologically active lipids that are implicated in homeostasis and in several pathologies that involve inflammation. Inflammatory processes mediated by eicosanoids promote carcinogenesis by exerting direct effects on cancer cells and by affecting the tumor microenvironment. Therefore, understanding how eicosanoids mediate cancer progression may lead to better approaches and chemopreventive strategies for the treatment of cancer. The matricellular protein thrombospondin-1 is involved in processes that profoundly regulate inflammatory pathways that contribute to carcinogenesis and metastatic spread. This review focuses on interactions of thrombospondin-1 and eicosanoids in the microenvironment that promote carcinogenesis and how the microenvironment can be targeted for cancer prevention to increase curative responses of cancer patients. PMID: 29909440 [PubMed - as supplied by publisher]

The multilevel antibiotic-induced perturbations to biological systems: Early-life exposure induces long-lasting damages to muscle structure and mitochondrial metabolism in flies.

Mon, 18/06/2018 - 13:12
Related Articles The multilevel antibiotic-induced perturbations to biological systems: Early-life exposure induces long-lasting damages to muscle structure and mitochondrial metabolism in flies. Environ Pollut. 2018 Jun 07;241:821-833 Authors: Renault D, Yousef H, Mohamed AA Abstract Antibiotics have been increasingly used over the past decades for human medicine, food-animal agriculture, aquaculture, and plant production. A significant part of the active molecules of antibiotics can be released into the environment, in turn affecting ecosystem functioning and biogeochemical processes. At lower organizational scales, these substances affect bacterial symbionts of insects, with negative consequences on growth and development of juveniles, and population dynamics. Yet, the multiple alterations of cellular physiology and metabolic processes have remained insufficiently explored in insects. We evaluated the effects of five antibiotics with different mode of action, i.e. ampicillin, cefradine, chloramphenicol, cycloheximide, and tetracycline, on the survival and ultrastructural organization of the flight muscles of newly emerged blow flies Chrysomya albiceps. Then, we examined the effects of different concentrations of antibiotics on mitochondrial protein content, efficiency of oxidative phosphorylation, and activity of transaminases (Glutamate oxaloacetate transaminase and glutamate pyruvate transaminase) and described the cellular metabolic perturbations of flies treated with antibiotics. All antibiotics affected the survival of the insects and decreased the total mitochondrial protein content in a dose-dependent manner. Ultrastructural organization of flight muscles in treated flies differs dramatically compared to the control groups and severe pathological damages/structures disorganization of mitochondria appeared. The activities of mitochondrial transaminases significantly increased with increased antibiotic concentrations. The oxidation rate of pyruvate + proline from isolated mitochondria of the flight muscles of 1-day-old flies was significantly reduced at high doses of antibiotics. In parallel, the level of several metabolites, including TCA cycle intermediates, was reduced in antibiotics-treated flies. Overall, antibiotics provoked a system-wide alteration of the structure and physiology of flight muscles of the blow fly Ch. albiceps, and may have fitness consequences at the organism level. Environmental antibiotic pollution is likely to have unwanted cascading ecological effects of insect population dynamics and community structure. PMID: 29909308 [PubMed - as supplied by publisher]

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