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; +16 new citations

Fri, 21/12/2018 - 12:10
16 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 2018/12/21PubMed 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

Thu, 20/12/2018 - 18:05
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 2018/12/20PubMed 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, 19/12/2018 - 14:42
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 2018/12/19PubMed 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; +27 new citations

Tue, 18/12/2018 - 14:23
27 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 2018/12/18PubMed 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.

Utility of sheathless capillary electrophoresis-mass spectrometry for metabolic profiling of limited sample amounts.

Mon, 17/12/2018 - 14:07
Related Articles Utility of sheathless capillary electrophoresis-mass spectrometry for metabolic profiling of limited sample amounts. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Dec 06;1105:10-14 Authors: Zhang W, Guled F, Hankemeier T, Ramautar R Abstract Metabolomics studies using a small amount of cells may save time and money, while in some cases (e.g., profiling pathogenic cells in an early-stage tissue), only a small number of cells are accessible for analysis. The analysis of small amounts of biological samples challenges the analytical toolbox used in present-day metabolomics studies, and a significant number of crucial biological questions cannot be properly addressed. To allow metabolic profiling of limited sample amounts, the potential of capillary electrophoresis-mass spectrometry (CE-MS) using a sheathless porous tip interface has been assessed using HepG2 cells in starting amounts of 500 and 10,000 cells as a model system in this work. It is shown that highly efficient and information-rich metabolic profiles for cationic metabolites at low-pH separation conditions could be obtained by sheathless CE-MS using an injection volume of only circa 42 nL, which equals the content/aliquot of circa 0.25 and 5 HepG2 cells, respectively. With as little as the content of 0.25 cell injected, more than 24 cationic metabolites could be identified. A further improvement of sample preparation and/or the injection part is required in order to effectively analyze the compounds of interest in very low sample amounts by sheathless CE-MS. However, the results obtained so far clearly indicate the strong potential of the proposed method for metabolic profiling of limited sample amounts. PMID: 30554093 [PubMed - as supplied by publisher]

The concentration of dissolved organic matter impacts the metabolic response in Daphnia magna exposed to 17α-ethynylestradiol and perfluorooctane sulfonate.

Mon, 17/12/2018 - 14:07
Related Articles The concentration of dissolved organic matter impacts the metabolic response in Daphnia magna exposed to 17α-ethynylestradiol and perfluorooctane sulfonate. Ecotoxicol Environ Saf. 2018 Dec 13;170:468-478 Authors: Kovacevic V, Simpson AJ, Simpson MJ Abstract The pharmaceutical 17α-ethynylestradiol (EE2) and the industrial chemical perfluorooctane sulfonate (PFOS) are organic contaminants frequently detected in freshwater environments. It is hypothesized that hydrophobic organic contaminants can sorb to dissolved organic matter (DOM) and this may reduce the toxicity of these contaminants by reducing the contaminants' bioavailability. To investigate this hypothesis, 1H nuclear magnetic resonance (NMR)-based metabolomics was used to determine how the metabolome of Daphnia magna changes when a range of DOM concentrations are added during EE2 and PFOS exposure experiments. D. magna were exposed for 48 h to sub-lethal concentrations of 1 mg/L EE2 or 30 mg/L PFOS in the presence of 0, 1, 2, 3 and 4 mg dissolved organic carbon (DOC)/L. EE2 exposure resulted in increased amino acids and decreased glucose in D. magna. All DOM concentrations were able to lessen these metabolite disturbances from EE2 exposure, likely due to reductions in the bioavailability of EE2 through interactions with DOM. Exposure to PFOS resulted in decreased amino acids, and the presence of 1 mg DOC/L did not alter this metabolic response. However, PFOS exposure with the higher DOM concentrations resulted in a different pattern of metabolite changes which may be due to combined impacts of PFOS and DOM on the metabolome or due to an increase in PFOS bioavailability and uptake in D. magna. These results suggest that the concentration of DOM influences the sensitive biochemical changes in organisms that occur during acute sub-lethal exposure to organic contaminants. PMID: 30553925 [PubMed - as supplied by publisher]

Addressing the Nutritional Phenotype through Personalized Nutrition for Chronic Disease Prevention and Management.

Mon, 17/12/2018 - 14:07
Related Articles Addressing the Nutritional Phenotype through Personalized Nutrition for Chronic Disease Prevention and Management. Prog Cardiovasc Dis. 2018 Dec 13;: Authors: Laddu D, Hauser M Abstract The primary focus of public health recommendations related to the prevention of food-related chronic disease has been on the adoption of healthy dietary patterns; however, implementation has been challenging. There has been increasing recognition that an individual's diet and environment may impact disease susceptibility by affecting the expression of genes involved in critical metabolic pathways. Precision nutrition (PN) has emerged to translate discoveries about diversity in nutrient metabolism between subgroups and the inter-individual variability in the responses to dietary interventions. The overarching goals of PN are to deliver individualized, actionable dietary therapy based on an individual's nutritional phenotype, created from the integration of genetics, metabolic profile, and environmental factors in order to prevent and treat chronic disease. This review addresses the developments of genome- and omic-driven PN and how they have been used to prevent and treat disease, as well as how they might be integrated into broader clinical practice. PMID: 30553801 [PubMed - as supplied by publisher]

Nasal insulin administration does not affect hepatic glucose production at systemic fasting insulin levels.

Sun, 16/12/2018 - 13:48
Related Articles Nasal insulin administration does not affect hepatic glucose production at systemic fasting insulin levels. Diabetes Obes Metab. 2018 Dec 15;: Authors: Plomgaard P, Hansen JS, Ingerslev B, Clemmesen JO, Secher NH, van Hall G, Fritsche A, Weigert C, Lehmann R, Häring HU, Heni M Abstract AIM: Pharmacologic administration of insulin as nasal spray in humans has demonstrated a modulation of endogenous glucose production via the brain when systemic insulin levels are high. Results are conflicting under fasting insulin concentrations. To evaluate effects of brain insulin on endogenous glucose production in fasting humans with focus on hepatic glucose release, we performed a randomized, placebo controlled, blinded, cross-over experiment. MATERIALS AND METHODS: On two separate days, 2 H2 -glucose was infused to nine healthy lean males and blood was sampled from the hepatic vein and a radial artery. On day 1, participants received 160 U human insulin through nasal spray, on day 2 participants received placebo spray together with an intravenous insulin bolus to mimic spill over of nasal insulin to the circulation. Hepatic glucose fluxes and endogenous glucose production were calculated. RESULTS: Plasma insulin concentrations were comparable between study days, and no differences in whole-body endogenous glucose production or hepato-splanchnic glucose turn-over were detected. CONCLUSIONS: Nasal administration of insulin does not influence whole-body or hepatic glucose production in fasting humans. In contrast, pharmacologic delivery of insulin to the brain might modulate insulin effectiveness in glucose-producing tissue when circulating insulin levels are elevated. Therefore, metabolic consequences of brain insulin action appear to dependent on the metabolic prandial status. This article is protected by copyright. All rights reserved. PMID: 30552787 [PubMed - as supplied by publisher]

Sensitivity of physiological and biochemical endpoints in early ontogenetic stages of crops under diclofenac and paracetamol treatments.

Sun, 16/12/2018 - 13:48
Related Articles Sensitivity of physiological and biochemical endpoints in early ontogenetic stages of crops under diclofenac and paracetamol treatments. Environ Sci Pollut Res Int. 2018 Dec 14;: Authors: Zezulka Š, Kummerová M, Babula P, Hájková M, Oravec M Abstract Early stages of ontogenesis determining subsequent growth, development, and productivity of crops can be affected by wastewater and sludge contaminated with pharmaceuticals. Diclofenac (DCF) and paracetamol (PCT; both 0.0001 to 10 mg/L) did not affect seed germination and primary root length of onion, lettuce, pea, and tomato. Conversely, 20-day-old pea and maize plants exhibited decrease in biomass production, leaf area (by approx. 40% in pea and 70% in maize under 10 mg/L DCF), or content of photosynthetic pigments (by 10% and 60% under 10 mg/L PCT). Quantum yields of photosystem II were reduced only in maize (FV/FM and ΦII by more than 40% under 10 mg/L of both pharmaceuticals). Contents of H2O2 and superoxide increased in roots of both species (more than four times under 10 mg/L PCT in pea). Activities of antioxidant enzymes were elevated in pea under DCF treatments, but decreased in maize under both pharmaceuticals. Oxidative injury of root cells expressed as lowered oxidoreductase activity (MTT assay, by 40% in pea and 80% in maize) and increase in malondialdehyde content (by 60% and 100%) together with the membrane integrity disruption (higher Evans Blue accumulation, by 100% in pea and 300% in maize) confirmed higher sensitivity of maize as a C4 monocot plant to both pharmaceuticals. PMID: 30552611 [PubMed - as supplied by publisher]

Editorial and Review: 33rd Asilomar Conference on Mass Spectrometry-Impact of Metabolomics in Translational and Clinical Research.

Sun, 16/12/2018 - 13:48
Related Articles Editorial and Review: 33rd Asilomar Conference on Mass Spectrometry-Impact of Metabolomics in Translational and Clinical Research. J Am Soc Mass Spectrom. 2018 Dec 14;: Authors: Garrett T, Petucci C Abstract PMID: 30552567 [PubMed - as supplied by publisher]

Development and validation of a simple LC-MS/MS method for the simultaneous quantitative determination of trimethylamine-N-oxide and branched chain amino acids in human serum.

Sun, 16/12/2018 - 13:48
Related Articles Development and validation of a simple LC-MS/MS method for the simultaneous quantitative determination of trimethylamine-N-oxide and branched chain amino acids in human serum. Anal Bioanal Chem. 2018 Dec 15;: Authors: Le TT, Shafaei A, Genoni A, Christophersen C, Devine A, Lo J, Wall PL, Boyce MC Abstract Serum branched chain amino acids and trimethylamine-N-oxide are monitored as potential indicators of diabetes and cardiovascular health respectively. A rapid method for their simultaneous determination using liquid chromatography and tandem mass spectrometry is described here. Branched chain amino acids and trimethylamine-N-oxide were quantified based on their specific MS/MS fragments using a selected reaction monitoring approach. A number of columns were tested for their ability to separate the analytes. A C18-PFP column separated the analytes in just 4 minutes, and resulted in excellent peak shape and retention time repeatability, and was therefore chosen as the optimal column. A second column, the Intrada Amino Acid column, was chosen for comparison and validation experiments as it provided an orthogonal separation mechanism. The intra-day and inter-day precision and accuracy were less than 12% for trimethylamine-N-oxide and less than 6% for the branched chain amino acids. Recoveries, where serum was spiked with three different concentrations of the analytes, ranged from 97 to 113%. The LODs and LOQs for trimethylamine-N-oxide were 1 and 6 ng/mL, for leucine and isoleucine were 4 and 8 ng/mL, and for valine were 5 and 15 ng/mL, respectively. The C18-PFP column method was validated using the Intrada Amino Acid column method and percentage agreement for all four analytes was within 10%. Sample preparation was minimal, and use of labelled internal standards accounted for matrix effects. The method was successfully applied to human plasma samples. Graphical abstract ᅟ. PMID: 30552494 [PubMed - as supplied by publisher]

Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism.

Sun, 16/12/2018 - 13:48
Related Articles Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism. Arch Toxicol. 2018 Dec 14;: Authors: Behrends V, Giskeødegård GF, Bravo-Santano N, Letek M, Keun HC Abstract Acetaminophen (APAP) is one of the most commonly used analgesics worldwide, and overdoses are associated with lactic acidosis, hepatocyte toxicity, and acute liver failure due to oxidative stress and mitochondrial dysfunction. Hepatoma cell lines typically lack the CYP450 activity to generate the reactive metabolite of APAP observed in vivo, but are still subject to APAP cytotoxicity. In this study, we employed metabolic profiling and isotope labelling approaches to investigate the metabolic impact of acute exposure to cytotoxic doses of APAP on the widely used HepG2 cell model. We found that APAP exposure leads to limited cellular death and substantial growth inhibition. Metabolically, we observed an up-regulation of glycolysis and lactate production with a concomitant reduction in carbon from glucose entering the pentose-phosphate pathway and the TCA cycle. This was accompanied by a depletion of cellular NADPH and a reduction in the de novo synthesis of fatty acids and the amino acids serine and glycine. These events were not associated with lower reduced glutathione levels and no glutathione conjugates were seen in cell extracts. Co-treatment with a specific inhibitor of the lactate/H+ transporter MCT1, AZD3965, led to increased apoptosis in APAP-treated cells, suggesting that lactate accumulation could be a cause of cell death in this model. In conclusion, we show that APAP toxicity in HepG2 cells is largely independent of oxidative stress, and is linked instead to a decoupling of glycolysis from the TCA cycle, lactic acidosis, reduced NADPH production, and subsequent suppression of the anabolic pathways required for rapid growth. PMID: 30552463 [PubMed - as supplied by publisher]

The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study.

Sun, 16/12/2018 - 13:48
Related Articles The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study. Eur J Hum Genet. 2018 Dec 14;: Authors: Papuc SM, Abela L, Steindl K, Begemann A, Simmons TL, Schmitt B, Zweier M, Oneda B, Socher E, Crowther LM, Wohlrab G, Gogoll L, Poms M, Seiler M, Papik M, Baldinger R, Baumer A, Asadollahi R, Kroell-Seger J, Schmid R, Iff T, Schmitt-Mechelke T, Otten K, Hackenberg A, Addor MC, Klein A, Azzarello-Burri S, Sticht H, Joset P, Plecko B, Rauch A Abstract Early-onset epileptic encephalopathy (EE) and combined developmental and epileptic encephalopathies (DEE) are clinically and genetically heterogeneous severely devastating conditions. Recent studies emphasized de novo variants as major underlying cause suggesting a generally low-recurrence risk. In order to better understand the full genetic landscape of EE and DEE, we performed high-resolution chromosomal microarray analysis in combination with whole-exome sequencing in 63 deeply phenotyped independent patients. After bioinformatic filtering for rare variants, diagnostic yield was improved for recessive disorders by manual data curation as well as molecular modeling of missense variants and untargeted plasma-metabolomics in selected patients. In total, we yielded a diagnosis in ∼42% of cases with causative copy number variants in 6 patients (∼10%) and causative sequence variants in 16 established disease genes in 20 patients (∼32%), including compound heterozygosity for causative sequence and copy number variants in one patient. In total, 38% of diagnosed cases were caused by recessive genes, of which two cases escaped automatic calling due to one allele occurring de novo. Notably, we found the recessive gene SPATA5 causative in as much as 3% of our cohort, indicating that it may have been underdiagnosed in previous studies. We further support candidacy for neurodevelopmental disorders of four previously described genes (PIK3AP1, GTF3C3, UFC1, and WRAP53), three of which also followed a recessive inheritance pattern. Our results therefore confirm the importance of de novo causative gene variants in EE/DEE, but additionally illustrate the major role of mostly compound heterozygous or hemizygous recessive inheritance and consequently high-recurrence risk. PMID: 30552426 [PubMed - as supplied by publisher]

Comparative metabolomics of scab-resistant and susceptible apple cell cultures in response to scab fungus elicitor treatment.

Sun, 16/12/2018 - 13:48
Related Articles Comparative metabolomics of scab-resistant and susceptible apple cell cultures in response to scab fungus elicitor treatment. Sci Rep. 2018 Dec 14;8(1):17844 Authors: Sarkate A, Saini SS, Teotia D, Gaid M, Mir JI, Roy P, Agrawal PK, Sircar D Abstract Apple scab disease caused by the fungus Venturia inaequalis is a devastating disease that seriously affects quality and yield of apples. In order to understand the mechanisms involved in scab resistance, we performed gas chromatography-mass spectrometry based metabolomics analysis of the cell culture of scab resistant cultivar 'Florina' and scab susceptible cultivar 'Vista Bella' both prior -to and -following treatment with V. inaequalis elicitor (VIE). A total 21 metabolites were identified to be altered significantly in 'Florina' cell cultures upon VIE-treatment. Among 21 metabolites, formation of three new specialized metabolites aucuparin, noraucuparin and eriobofuran were observed only in resistant cultivar 'Florina' after the elicitor treatment. The score plots of principal component analysis (PCA) exhibited clear discrimination between untreated and VIE-treated samples. The alteration in metabolite levels correlated well with the changes in the transcript levels of selected secondary metabolite biosynthesis genes. Aucuparin, noraucuparin and eriobofuran isolated from the 'Florina' cultures showed significant inhibitory effect on the conidial germination of V. inaequalis. The results expand our understanding of the metabolic basis of scab-resistance in apple and therefore are of interest in apple breeding programs to fortify scab resistance potential of commercially grown apple cultivars. PMID: 30552373 [PubMed - in process]

Empagliflozin, an SGLT2 inhibitor, reduced the mortality rate after acute myocardial infarction with modification of cardiac metabolomes and anti-oxidants in diabetic rats.

Sun, 16/12/2018 - 13:48
Related Articles Empagliflozin, an SGLT2 inhibitor, reduced the mortality rate after acute myocardial infarction with modification of cardiac metabolomes and anti-oxidants in diabetic rats. J Pharmacol Exp Ther. 2018 Dec 14;: Authors: Oshima H, Miki T, Kuno A, Mizuno M, Sato T, Tanno M, Yano T, Nakata K, Kimura Y, Abe K, Ohwada W, Miura T Abstract BACKGROUND: Mechanism by which sodium glucose cotransporter 2 (SGLT2) inhibitors reduce cardiac events in diabetic patients remains unclear. Here we examined effects of an SGLT2 inhibitor on the acute survival rate after myocardial infarction (MI) in an animal model of type 2 diabetes mellitus (DM) and possible involvement of modification of cardiac metabolomes and anti-oxidative proteins. METHODS AND RESULTS: MI was induced in DM rats (OLETF) and control rats (LETO). Treatment with empagliflozin (10 mg/kg/day, 14 days) before MI reduced blood glucose and increased blood and myocardial β-hydroxybutyrate (βOHB) levels in OLETF. Survival rate at 48 hr after MI was significantly lower in OLETF than in LETO (40% vs 84%), and empagliflozin significantly improved the survival rate in OLETF to 70% though sizes of MI were comparable. Patterns of metabolomes and gene expression in the non-infarcted myocardium of OLETF were consistent with increased fatty acid oxidation and decreased glucose oxidation. The patterns were modified by empagliflozin, suggesting both increased glucose oxidation and ketone utilization in OLETF. Empagliflozin prevented reduction of ATP level in the non-infarcted myocardium after MI and significantly increased myocardial levels of Sirt3 and SOD2 in OLETF. Administration of βOHB partially mimicked the effects of empagliflozin in OLETF. CONCLUSIONS: The results suggest that empagliflozin prevents DM-induced increase in post-MI mortality possibly by protective modification of cardiac energy metabolism and anti-oxidant proteins. PMID: 30552292 [PubMed - as supplied by publisher]

New views on the Malpighian tubule from post-genomic technologies.

Sun, 16/12/2018 - 13:48
Related Articles New views on the Malpighian tubule from post-genomic technologies. Curr Opin Insect Sci. 2018 Oct;29:7-11 Authors: Dow JA, Pandit A, Davies SA Abstract Successful insect diversification depends at least in part on the ability to osmoregulate successfully across a broad range of ecological niches. First described in the 17th Century, and Malpighian tubules have been studied physiologically for 70 years. However, our understanding has been revolutionized by the advent of genomics, transcriptomics, proteomics and metabolomics. Such technologies are natural partners with (though do not obligatorily require) model organisms and transgenic technologies. This review describes the recent impact of multi-omic technologies on our understanding or renal function and control in insects. PMID: 30551828 [PubMed - in process]

Omics approaches to study juvenile hormone synthesis.

Sun, 16/12/2018 - 13:48
Related Articles Omics approaches to study juvenile hormone synthesis. Curr Opin Insect Sci. 2018 Oct;29:49-55 Authors: Nouzova M, Rivera-Pérez C, Noriega FG Abstract The juvenile hormones (JHs) are a family of insect acyclic sesquiterpenoids produced by the corpora allata (CA), a pair of endocrine glands connected to the brain. They are involved in the regulation of development, reproduction, behavior, caste determination, diapause, stress response, and numerous polyphenisms. In the post-genomics era, comprehensive analyses using functional 'omics' technologies such as transcriptomics, proteomics and metabolomics have increased our understanding of the activity of the minute CA. This review attempts to summarize some of the 'omics' studies that have contributed to further understand JH synthesis in insects, with an emphasis on our own research on the mosquito Aedes aegypti. PMID: 30551825 [PubMed - in process]

The Metabolome and Osteoarthritis: Possible Contributions to Symptoms and Pathology.

Sun, 16/12/2018 - 13:48
Related Articles The Metabolome and Osteoarthritis: Possible Contributions to Symptoms and Pathology. Metabolites. 2018 Dec 13;8(4): Authors: Rockel JS, Kapoor M Abstract Osteoarthritis (OA) is a progressive, deteriorative disease of articular joints. Although traditionally viewed as a local pathology, biomarker exploration has shown that systemic changes can be observed. These include changes to cytokines, microRNAs, and more recently, metabolites. The metabolome is the set of metabolites within a biological sample and includes circulating amino acids, lipids, and sugar moieties. Recent studies suggest that metabolites in the synovial fluid and blood could be used as biomarkers for OA incidence, prognosis, and response to therapy. However, based on clinical, demographic, and anthropometric factors, the local synovial joint and circulating metabolomes may be patient specific, with select subsets of metabolites contributing to OA disease. This review explores the contribution of the local and systemic metabolite changes to OA, and their potential impact on OA symptoms and disease pathogenesis. PMID: 30551581 [PubMed]

Seasonal Variations in the Metabolome and Bioactivity Profile of Fucus vesiculosus Extracted by an Optimised, Pressurised Liquid Extraction Protocol.

Sun, 16/12/2018 - 13:48
Related Articles Seasonal Variations in the Metabolome and Bioactivity Profile of Fucus vesiculosus Extracted by an Optimised, Pressurised Liquid Extraction Protocol. Mar Drugs. 2018 Dec 13;16(12): Authors: Heavisides E, Rouger C, Reichel AF, Ulrich C, Wenzel-Storjohann A, Sebens S, Tasdemir D Abstract The metabolism of seaweeds depends on environmental parameters, the availability of nutrients, and biotic/abiotic stresses; therefore, their chemical composition fluctuates throughout the year. This study investigated seasonal variations in the metabolome of the Baltic Sea brown alga Fucus vesiculosus and its potential relation to the bioactivity profile. By using a definitive screening design (DSD) combined with pressurised liquid extraction (PLE), an optimised protocol was developed to extract algal biomass monthly for a full calendar year. An untargeted metabolomics approach using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MSn)-based molecular networking and manual dereplication was employed. The extracts were simultaneously screened for their in vitro antimicrobial, anticancer/apoptotic, and free radical scavenging activities. 44 compounds were putatively dereplicated in the metabolome. Many compounds were found to vary with the sampling month; phlorotannin total ion count (TIC) was highest in summer, whilst chlorophylls, lipids, and carotenoids peaked in winter and spring. The greatest radical scavenging and apoptotic activities against pancreas cancer cells observed in the summer months were attributed to high phlorotannin TIC. Methicillin-resistant Staphylococcus aureus (MRSA) inhibitory activity was produced year-round without a clear seasonal trend. This is the first study applying DSD-based optimised PLE extraction combined with a metabolome analysis of F. vesiculosus for the identification of seasonal variations in both metabolome and bioactivity. PMID: 30551573 [PubMed - in process]

Mechanisms of bergenin treatment on chronic bronchitis analyzed by liquid chromatography-tandem mass spectrometry based on metabolomics.

Sun, 16/12/2018 - 13:48
Related Articles Mechanisms of bergenin treatment on chronic bronchitis analyzed by liquid chromatography-tandem mass spectrometry based on metabolomics. Biomed Pharmacother. 2019 Jan;109:2270-2277 Authors: Zhang C, Zhao B, Zhang C, Qiu M, Ma S, Jin X, Shao Y, Wang M, Wang X Abstract With increasing air pollution, chronic bronchitis (CB) has become a major public health problem worldwide. Previous studies have shown beneficial effects of Bergenin (Ber) on chronic bronchitis. To facilitate understanding of the pathogenesis underlying CB as well as to elucidate the Ber therapeutic mechanism, it is crucial to confirm the rational biomarkers of CB and its treatment. This study aimed to investigate the preventive chronic bronchitis mechanism of Ber by applying a serum metabolomics strategy. In this study, 18 Sprague-Dawley rats were randomly divided into three groups,with six rats in each group. Rats from the CB and Ber groups were exposed to tobacco smoke for 1 hd-1 (1 h per day) for 28 days. Ber was administered orally to Ber rats 3 h after exposure every day, and the others were administered water. According to the morphometric analysis of the airway epithelium and the count of white blood cells in the bronchoalveolar lavage fluid, Ber suppressed the infiltration of inflammatory cells, inhibited the secretion of mucus, and reduced white blood cells in bronchoalveolar lavage fluid. The metabolic profiles of sera were analyzed by multivariate statistical analyses, including PCA, PLS-DA and OPLS-DA models, and revealed that the levels of thirteen metabolites were significantly changed and identified as potential biomarkers in the CB group and Ber group. The results suggested that the therapeutic mechanism of Ber may be related to the regulation of dysfunctions in glycerophospholipid, tryptophan, arginine and proline metabolism induced by CB, and changes in arachidonic acid metabolism. PMID: 30551484 [PubMed - in process]

Pages