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

A low ω-6/ω-3 ratio high-fat diet improves rat metabolism via purine and tryptophan metabolism in intestine tract while reversed by inulin.

Wed, 12/06/2019 - 12:59
A low ω-6/ω-3 ratio high-fat diet improves rat metabolism via purine and tryptophan metabolism in intestine tract while reversed by inulin. J Agric Food Chem. 2019 Jun 11;: Authors: Xiao Y, Li X, Zeng X, Wang H, Mai Q, Cheng Y, Li J, Tang L, Ding H Abstract BACKGROUND: High-fat diet (HFD) is the main cause of metabolic diseases. However, HFD in previous studies consists of much lard, which contains a large amount of omega-6 (ω-6) polyunsaturated fatty acid (PUFA) and low omega-3 (ω-3) PUFA. The role of ω-6/ω-3 ratio of HFD in the development of metabolic diseases remains incompletely discussed. METHODS: Rats were fed with either a low or a high ω-6/ω-3 ratio HFD singly or combined with inulin. Metabolism state was valued and metabolomics of cecal content were detected. RESULTS: HFD with low ω-6/ω-3 ratio promotes the glucose utilization in rats. However, inulin had different effects on metabolism with different diet. Xanthosine and kynurenic acid in cecum were positively related to epididymal white adipose tissues (eWAT) mass. CONCLUSIONS: The present study indicated the beneficial effects of LRD on rat metabolic state. Moreover, xanthosine and kynurenic acid were closely related to the development of metabolic diseases. PMID: 31184122 [PubMed - as supplied by publisher]

A metabolomic signature of treated and drug-naïve patients with Parkinson's disease: a pilot study.

Wed, 12/06/2019 - 12:59
Related Articles A metabolomic signature of treated and drug-naïve patients with Parkinson's disease: a pilot study. Metabolomics. 2019 Jun 10;15(6):90 Authors: Troisi J, Landolfi A, Vitale C, Longo K, Cozzolino A, Squillante M, Savanelli MC, Barone P, Amboni M Abstract INTRODUCTION: About 90% of cases of Parkinson's disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment. OBJECTIVE: The aim of our case-control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment. METHODS: We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression. RESULTS: This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment. CONCLUSION: Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions. PMID: 31183578 [PubMed - in process]

A Single 48 mg Sucralose Sip Unbalances Monocyte Subpopulations and Stimulates Insulin Secretion in Healthy Young Adults.

Wed, 12/06/2019 - 12:59
Related Articles A Single 48 mg Sucralose Sip Unbalances Monocyte Subpopulations and Stimulates Insulin Secretion in Healthy Young Adults. J Immunol Res. 2019;2019:6105059 Authors: Gómez-Arauz AY, Bueno-Hernández N, Palomera LF, Alcántara-Suárez R, De León KL, Méndez-García LA, Carrero-Aguirre M, Manjarrez-Reyna AN, Martínez-Reyes CP, Esquivel-Velázquez M, Ruiz-Barranco A, Baltazar-López N, Islas-Andrade S, Escobedo G, Meléndez G Abstract Sucralose is a noncaloric artificial sweetener that is widely consumed worldwide and has been associated with alteration in glucose and insulin homeostasis. Unbalance in monocyte subpopulations expressing CD11c and CD206 hallmarks metabolic dysfunction but has not yet been studied in response to sucralose. Our goal was to examine the effect of a single sucralose sip on serum insulin and blood glucose and the percentages of classical, intermediate, and nonclassical monocytes in healthy young adults subjected to an oral glucose tolerance test (OGTT). This study was a randomized, placebo-controlled clinical trial. Volunteers randomly received 60 mL water as placebo (n = 20) or 48 mg sucralose dissolved in 60 mL water (n = 25), fifteen minutes prior to an OGTT. Blood samples were individually drawn every 15 minutes for 180 minutes for quantifying glucose and insulin concentrations. Monocyte subsets expressing CD11c and CD206 were measured at -15 and 180 minutes by flow cytometry. As compared to controls, volunteers receiving sucralose exhibited significant increases in serum insulin at 30, 45, and 180 minutes, whereas blood glucose values showed no significant differences. Sucralose consumption caused a significant 7% increase in classical monocytes and 63% decrease in nonclassical monocytes with respect to placebo controls. Pearson's correlation models revealed a strong association of insulin with sucralose-induced monocyte subpopulation unbalance whereas glucose values did not show significant correlations. Sucralose ingestion decreased CD11c expression in all monocyte subsets and reduced CD206 expression in nonclassical monocytes suggesting that sucralose does not only unbalance monocyte subpopulations but also alter their expression pattern of cell surface molecules. This work demonstrates for the first time that a 48 mg sucralose sip increases serum insulin and unbalances monocyte subpopulations expressing CD11c and CD206 in noninsulin-resistant healthy young adults subjected to an OGTT. The apparently innocuous consumption of sucralose should be reexamined in light of these results. PMID: 31183389 [PubMed - in process]

Metabolomic Characterization of Human Model of Liver Rejection Identifies Aberrancies Linked to Cyclooxygenase (COX) and Nitric Oxide Synthase (NOS).

Wed, 12/06/2019 - 12:59
Related Articles Metabolomic Characterization of Human Model of Liver Rejection Identifies Aberrancies Linked to Cyclooxygenase (COX) and Nitric Oxide Synthase (NOS). Ann Transplant. 2019 Jun 11;24:341-349 Authors: Skill NJ, Elliott CM, Ceballos B, Saxena R, Pepin R, Bettcher L, Ellensberg M, Raftery D, Malucio MA, Ekser B, Mangus RS, Kubal CA Abstract BACKGROUND Acute liver rejection (ALR), a significant complication of liver transplantation, burdens patients, healthcare payers, and the healthcare providers due to an increase in morbidity, cost, and resources. Despite clinical resolution, ALR is associated with an increased risk of graft loss. A unique protocol of delayed immunosuppression used in our institute provided a model to characterize metabolomic profiles in human ALR. MATERIAL AND METHODS Twenty liver allograft biopsies obtained 48 hours after liver transplantation in the absence of immunosuppression were studied. Hepatic metabolites were quantitated in these biopsies by liquid chromatography and mass spectroscopy (LC/MS). Metabolite profiles were compared among: 1) biopsies with reperfusion injury but no histological evidence of rejection (n=7), 2) biopsies with histological evidence of moderate or severe rejection (n=5), and 3) biopsies with histological evidence of mild rejection (n=8). RESULTS There were 133 metabolites consistently detected by LC/MS and these were prioritized using variable importance to projection (VIP) analysis, comparing moderate or severe rejection vs. no rejection or mild rejection using partial least squares discriminant statistical analysis (PLS-DA). Twenty metabolites were identified as progressively different. Further PLS-DA using these metabolites identified 3 metabolites (linoleic acid, γ-linolenic acid, and citrulline) which are associated with either cyclooxygenase or nitric oxide synthase functionality. CONCLUSIONS Hepatic metabolic aberrancies associated with cyclooxygenase and nitric oxide synthase function occur contemporaneous with ALR. Additional studies are required to better characterize the role of these metabolic pathways to enhance utility of the metabolomics approach in diagnosis and outcomes of ALR. PMID: 31182705 [PubMed - in process]

From intracellular bacteria to differentiated bacteroids: transcriptome and metabolome analysis in Aeschynomene nodules using the Bradyrhizobium sp. ORS285 bclA mutant.

Wed, 12/06/2019 - 12:59
Related Articles From intracellular bacteria to differentiated bacteroids: transcriptome and metabolome analysis in Aeschynomene nodules using the Bradyrhizobium sp. ORS285 bclA mutant. J Bacteriol. 2019 Jun 10;: Authors: Lamouche F, Chaumeret A, Guefrachi I, Barrière Q, Pierre O, Guérard F, Gilard F, Giraud E, Dessaux Y, Gakière B, Timchenko T, Kereszt A, Mergaert P, Alunni B Abstract Soil bacteria called rhizobia trigger the formation of root nodules on legume plants. The rhizobia infect these symbiotic organs and adopt an intracellular lifestyle within the nodule cells where they differentiate into nitrogen-fixing bacteroids. Several legume lineages enforce their symbionts into an extreme cellular differentiation, comprising cell enlargement and genome endoreduplication. The antimicrobial peptide transporter BclA is a major determinant of this process in Bradyrhizobium sp. ORS285, a symbiont of Aeschynomene spp.. In the absence of BclA, the bacteria proceed until the intracellular infection of nodule cells but they cannot differentiate into enlarged polyploid and functional bacteroids. The bclA nodule bacteria constitute thus an intermediate stage between the free-living soil bacteria and the nitrogen-fixing bacteroids. Metabolomics on whole nodules of Aeschynomene afraspera and Aeschynomene indica infected with the wild type or the bclA mutant revealed 47 metabolites that differentially accumulated concomitantly with bacteroid differentiation. Bacterial transcriptome analysis of these nodules demonstrated that the intracellular settling of the rhizobia in the symbiotic nodule cells is accompanied with a first transcriptome switch involving several hundreds of upregulated and downregulated genes and a second switch accompanying the bacteroid differentiation, involving less genes but ones that are expressed to extremely elevated levels. The transcriptomes further suggested a dynamic role for oxygen and redox regulation of gene expression during nodule formation and a non-symbiotic function of BclA. Together, our data uncover the metabolic and gene expression changes that accompany the transition from intracellular bacteria into differentiated nitrogen-fixing bacteroids.ImportanceThe legume-rhizobium symbiosis is a major ecological process fueling the biogeochemical nitrogen cycle with reduced nitrogen. It represents also a promising strategy to cut down the use of chemical nitrogen fertilizers in agriculture, thereby improving its sustainability. This interaction leads to the intracellular accommodation of rhizobia within plant cells of symbiotic organs where they differentiate into nitrogen-fixing bacteroids. In specific legume clades, this differentiation process requires the bacterial transporter BclA to counteract antimicrobial peptides produced by the host. Transcriptome analysis of Bradyrhizobium wild-type and bclA mutant bacteria in culture and in symbiosis with Aeschynomene host plants dissected the bacterial transcriptional response in distinct phases and highlighted functions of the transporter in the free-living stage of the bacterial life cycle. PMID: 31182497 [PubMed - as supplied by publisher]

Associations between usual food intake and fecal sterols and bile acids: results from the KORA FF4 study.

Wed, 12/06/2019 - 12:59
Related Articles Associations between usual food intake and fecal sterols and bile acids: results from the KORA FF4 study. Br J Nutr. 2019 Jun 11;:1-26 Authors: Mitry P, Wawro N, Sharma S, Kriebel J, Artati A, Adamski J, Heier M, Meisinger C, Thorand B, Grallert H, Peters A, Linseisen J Abstract Animal sterols, plant sterols and bile acids in stool samples have been suggested as biomarkers of dietary intake. It is still unknown whether they also reflect long-term habitual dietary intake and can be used in aetiological research. In a subgroup of the KORA FF4 study, habitual dietary intake was estimated based on repeated 24HFL and a FFQ. Stool samples were collected according to a SOP and those meeting the quality criteria were extracted and analysed by means of a metabolomics technique. The present study is based on data from 513 men and 495 women with a mean age of 60 and 58 years, respectively, for which fecal animal and plant sterols and bile acids concentrations and dietary intake data were available. In adjusted regression models, the associations between food intake and log-normalised metabolite concentrations were analysed. Bonferroni correction was used to account for multiple testing. In this population-based sample, associations between habitual dietary intake and fecal concentrations of animal sterols were identified, while the impact of usual diet on bile acids was limited. A habitual diet high in 'fruits' and 'nuts and seeds' is associated with lower animal fecal sterols concentrations, whereas a diet high in 'meat and meat products' is positively related to fecal concentrations of animal sterols. A positive association between glycocholate and fruit consumption was found. Further studies are necessary for evaluation of fecal animal sterols as biomarkers of diet. The findings need to be confirmed in other populations with diverse dietary habits. PMID: 31182174 [PubMed - as supplied by publisher]

Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells.

Wed, 12/06/2019 - 12:59
Related Articles Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells. Cancers (Basel). 2019 Jun 09;11(6): Authors: Melzer C, Rehn V, Yang Y, Bähre H, von der Ohe J, Hass R Abstract MSC-derived exosomes display, among others, an efficient biocompatibility and a reduced intrinsic immunogenicity, representing a valuable vehicle for drug delivery in a tumor-therapeutic approach. Following treatment of several human mesenchymal stroma/stem-like cell (MSC) populations with sub-lethal concentrations of taxol for 24 h, exosomes were isolated and applied to different human cancer populations including A549 lung cancer, SK-OV-3 ovarian cancer, and MDA-hyb1 breast cancer cells. While MSC control exosomes revealed little if any growth inhibition on the tumor cells, exposure to taxol-loaded MSC-derived exosomes was associated with 80-90% cytotoxicity. A similar application of taxol-loaded exosomes from HuVEC displayed much fewer effects. Quantification by LC-MS/MS analysis demonstrated a 7.6-fold reduced taxol concentration in MSC exosomes when compared to equivalent cytotoxic in vitro effects achieved with taxol substances, indicating a specific and more efficient tumor-targeting property. Consequently, MSC-derived taxol exosomes were tested in vivo. Highly metastatic MDA-hyb1 breast tumors were induced in NODscid mice, and systemic intravenous application of MSC-derived taxol exosomes revealed a more than 60% reduction of subcutaneous primary tumors. Moreover, the amount of distant organ metastases observed at least in lung, liver, spleen, and kidney was reduced by 50% with MSC taxol exosomes, similar to the effects observed with taxol, although the concentration of taxol in exosomes was about 1000-fold reduced. Together, these findings in different cancer cell populations and in vivo provide promising future perspectives for drug-loaded MSC-derived exosomes in efficiently targeting primary tumors and metastases by reducing side effects. PMID: 31181850 [PubMed]

Snail-Overexpression Induces Epithelial-mesenchymal Transition and Metabolic Reprogramming in Human Pancreatic Ductal Adenocarcinoma and Non-tumorigenic Ductal Cells.

Wed, 12/06/2019 - 12:59
Related Articles Snail-Overexpression Induces Epithelial-mesenchymal Transition and Metabolic Reprogramming in Human Pancreatic Ductal Adenocarcinoma and Non-tumorigenic Ductal Cells. J Clin Med. 2019 Jun 08;8(6): Authors: Liu M, Hancock SE, Sultani G, Wilkins BP, Ding E, Osborne B, Quek LE, Turner N Abstract The zinc finger transcription factor Snail is a known effector of epithelial-to-mesenchymal transition (EMT), a process that underlies the enhanced invasiveness and chemoresistance of common to cancerous cells. Induction of Snail-driven EMT has also been shown to drive a range of pro-survival metabolic adaptations in different cancers. In the present study, we sought to determine the specific role that Snail has in driving EMT and adaptive metabolic programming in pancreatic ductal adenocarcinoma (PDAC) by overexpressing Snail in a PDAC cell line, Panc1, and in immortalized, non-tumorigenic human pancreatic ductal epithelial (HPDE) cells. Snail overexpression was able to induce EMT in both pancreatic cell lines through suppression of epithelial markers and upregulation of mesenchymal markers alongside changes in cell morphology and enhanced migratory capacity. Snail-overexpressed pancreatic cells additionally displayed increased glucose uptake and lactate production with concomitant reduction in oxidative metabolism measurements. Snail overexpression reduced maximal respiration in both Panc1 and HPDE cells, with further reductions seen in ATP production, spare respiratory capacity and non-mitochondrial respiration in Snail overexpressing Panc1 cells. Accordingly, lower expression of mitochondrial electron transport chain proteins was observed with Snail overexpression, particularly within Panc1 cells. Modelling of 13C metabolite flux within both cell lines revealed decreased carbon flux from glucose in the TCA cycle in snai1-overexpressing Panc1 cells only. This work further highlights the role that Snail plays in EMT and demonstrates its specific effects on metabolic reprogramming of glucose metabolism in PDAC. PMID: 31181802 [PubMed]

Characterization of Bulk Phosphatidylcholine Compositions in Human Plasma Using Side-Chain Resolving Lipidomics.

Wed, 12/06/2019 - 12:59
Related Articles Characterization of Bulk Phosphatidylcholine Compositions in Human Plasma Using Side-Chain Resolving Lipidomics. Metabolites. 2019 Jun 08;9(6): Authors: Quell JD, Römisch-Margl W, Haid M, Krumsiek J, Skurk T, Halama A, Stephan N, Adamski J, Hauner H, Mook-Kanamori D, Mohney RP, Daniel H, Suhre K, Kastenmüller G Abstract Kit-based assays, such as AbsoluteIDQTM p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally-relevant information on the detailed fatty acid side-chain compositions as only the total number of carbon atoms and double bonds is identified by the kit. To enable more substantiated interpretations, we characterized these PC sums using the side-chain resolving LipidyzerTM platform, analyzing 223 samples in parallel to the AbsoluteIDQTM. Combining these datasets, we estimated the quantitative composition of PC sums and subsequently tested their replication in an independent cohort. We identified major constituents of 28 PC sums, revealing also various unexpected compositions. As an example, PC 16:0_22:5 accounted for more than 50% of the PC sum with in total 38 carbon atoms and 5 double bonds (PC aa 38:5). For 13 PC sums, we found relatively high abundances of odd-chain fatty acids. In conclusion, our study provides insights in PC compositions in human plasma, facilitating interpretation of existing epidemiological data sets and potentially enabling imputation of PC compositions for future meta-analyses of lipidomics data. PMID: 31181753 [PubMed]

metabolomics; +18 new citations

Tue, 11/06/2019 - 15:46
18 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 2019/06/11PubMed 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; +18 new citations

Tue, 11/06/2019 - 12:44
18 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 2019/06/11PubMed 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 of the alimurgic plants Taraxacum officinale, Papaver rhoeas and Urtica dioica by combined NMR and GC-MS analysis.

Mon, 10/06/2019 - 12:36
Metabolomics of the alimurgic plants Taraxacum officinale, Papaver rhoeas and Urtica dioica by combined NMR and GC-MS analysis. Phytochem Anal. 2019 Jun 09;: Authors: Grauso L, Emrick S, Bonanomi G, Lanzotti V Abstract INTRODUCTION: The phytoalimurgic plants, common dandelion (Taraxacum officinale), corn poppy (Papaver rhoeas) and stinging nettle (Urtica dioica) are a source of nutraceuticals. OBJECTIVES: To apply a combined metabolomic fingerprinting approach by nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) to common dandelion, corn poppy and stinging nettles to obtain simultaneous identification and quantitation of the major classes of organic compounds. METHODOLOGY: The whole plants collected in the Cilento National Park were dried and then extracted to obtain non-polar and polar organic extracts. GC-MS was used for non-polar extracts while 1 H-NMR spectroscopy was used for polar extracts. In both cases, simultaneous identification and quantification of the bioactive metabolites was obtained. RESULTS: Non-polar organic extracts of all plants were mainly composed of palmitic, stearic and oleic acids. The two pentacyclic triterpenols α- and β-amyrin were detected in nettle extract. The analysis of polar organic extracts allowed to detect and quantify organic acids and sugars as main metabolites along with amino acids, caffeoyl derivatives, flavonoids, and nucleotides. In particular, corn poppy leaves contained a huge amount of glyceric acid (55.7% of the total extract). Stinging nettles, instead, exhibited a large amount of choline (19.5%). CONCLUSION: Metabolomic approach coupling GC-MS with NMR spectroscopy allowed to provide a detailed metabolite profile of three alimurgic plants, common dandelion, corn poppy and stinging nettle, from both a qualitative and quantitative point of view. PMID: 31177603 [PubMed - as supplied by publisher]

UPLC-QTOF/MS-based metabolomics reveals the mechanism of chronic unpredictable mild stress-induced hypertension in rats.

Mon, 10/06/2019 - 12:36
UPLC-QTOF/MS-based metabolomics reveals the mechanism of chronic unpredictable mild stress-induced hypertension in rats. Biomed Chromatogr. 2019 Jun 08;:e4619 Authors: Wu Q, Xia DM, Lan F, Wang YK, Tan X, Sun JC, Wang WZ, Wang R, Peng XD, Liu M Abstract Hypertension is a common chronic disease, and it is the strongest risk factor for cardiovascular diseases. Recently, the number of patients with hypertension-related complications has increased significantly, adding a heavy burden to the public health system. It is known that chronic stress plays an important role in the pathogenesis of cardiovascular diseases such as hypertension and stroke. However, the impact of hypertension on the dysfunctions induced by chronic stress remains poorly understood. In this study, using LC-MS-based metabolomics, we established a chronic stress model to demonstrate the mechanisms of stress-induced hypertension. We found that 30 metabolites in chronically stressed rats were changed; of these metabolites, 7 had been upregulated, and 23 had been downregulated, including amino acids, phospholipids, carnitines and fatty acids, many of which are involved in amino acid metabolism, cell membrane injury, ATP supply and inflammation. These metabolites are engaged in dysregulated pathways and will provide a targeted approach to study the mechanism of stress-induced hypertension. PMID: 31177559 [PubMed - as supplied by publisher]

Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague-Dawley Rats But Aflibercept Affects Serum and Urine Metabolic Profiles.

Mon, 10/06/2019 - 12:36
Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague-Dawley Rats But Aflibercept Affects Serum and Urine Metabolic Profiles. Transl Oncol. 2019 Jun 06;12(8):1122-1130 Authors: Forsgård RA, Marrachelli VG, Lindén J, Frias R, Collado MC, Korpela R, Monleon D, Spillmann T, Österlund P Abstract Gastrointestinal toxicity is a frequently observed adverse event during cancer treatment with traditional chemotherapeutics. Currently, traditional chemotherapeutics are often combined with targeted biologic agents. These biologics, however, possess a distinct toxicity profile, and they may also exacerbate the adverse effects of traditional chemotherapeutics. In this study, we aimed to characterize the gastrointestinal and metabolic changes after a 2-week treatment period with aflibercept, an antiangiogenic VEGFR decoy, and with erlotinib, a tyrosine-kinase inhibitor. Male rats were treated either with aflibercept or erlotinib for 2 weeks. During the 2-week treatment period, the animals in the aflibercept group received two subcutaneous doses of 25 mg/kg aflibercept. The erlotinib group got 10 mg/kg of erlotinib by oral gavage every other day. The control groups were treated similarly but received either saline injections or oral gavage of water. Intestinal toxicity was assessed by measuring intestinal permeability and by histological analyses of intestinal tissues. Metabolic changes were measured with 1H nuclear magnetic resonance in serum and urine. Neither aflibercept nor erlotinib induced changes in intestinal permeability or intestinal tissue morphology. However, aflibercept treatment resulted in stunted body weight gain and altered choline, amino acid, and lipid metabolism. Two-week treatment with aflibercept or erlotinib alone does not induce observable changes in gastrointestinal morphology and function. However, observed aflibercept-treatment related metabolic changes suggest alterations in intestinal microbiota, nutrient intake, and adipose tissue function. The metabolic changes are also interesting in respect to the systemic effects of aflibercept and their possible associations with adverse events caused by aflibercept administration. PMID: 31176994 [PubMed - as supplied by publisher]

Metabolomics, stunting and neurodevelopment.

Mon, 10/06/2019 - 12:36
Metabolomics, stunting and neurodevelopment. EBioMedicine. 2019 Jun 05;: Authors: van den Heuvel M PMID: 31176679 [PubMed - as supplied by publisher]

Mortality, growth and metabolic responses by 1H-NMR-based metabolomics of earthworms to sodium selenite exposure in soils.

Sun, 09/06/2019 - 15:23
Mortality, growth and metabolic responses by 1H-NMR-based metabolomics of earthworms to sodium selenite exposure in soils. Ecotoxicol Environ Saf. 2019 Jun 04;181:69-77 Authors: Shao X, He J, Liang R, Lu Y, Shi Y, Wang Y, Zheng X, Zhang S, Wang T Abstract The rapid development of selenium-enriched agriculture leads to the accumulation of selenium in the soil, which has an adverse impact on terrestrial ecosystems. In the present study, the mortality, growth inhibition rate and metabolism of earthworms were examined to investigate the toxicological effects of sodium selenite (Na2SeO3) on earthworms (Eisenia fetida) after exposuring for 14 days (d). We used 1H-NMR-based metabolomics to identify sensitive biomarkers and explored the metabolic responses of earthworms exposed to Na2SeO3. The mortality and growth inhibition rate of earthworms exposed to 70 and 90 mg/kg Na2SeO3 were significantly higher than the rate of control group. The LC50 (the median lethal concentration) of Na2SeO3 was 57.4 mg/kg in this artificial soil test of E. fetida exposed to Na2SeO3 for 14 d. However, there was no significant differences when earthworms were exposed to different concentrations of Na2SeO3. The selected metabolic markers were ATP, lactic acid, leucine, alanine, valine, glycine, glutamic acid, lysine, α-glucose and betaine. Na2SeO3 affected the metabolic level of earthworms, as the percentage of metabolic markers in the earthworm changes when exposed to different concentrations of Na2SeO3. The metabolic disturbances were greater with increasing concentrations of Na2SeO3. The differential metabolic markers were significantly changed when exposed to Na2SeO3 comparing to those in the control group, affecting the tricarboxylic acid cycle process and breaking the metabolic balance. This study showed that Na2SeO3 had toxic effect on the growth and development of earthworms. In addition, this study provided a biochemical insights for the development of selenium-enriched agriculture. PMID: 31176249 [PubMed - as supplied by publisher]

Extreme, but not moderate climate scenarios, impart sublethal effects on polyps of the Irukandji jellyfish, Carukia barnesi.

Sun, 09/06/2019 - 15:23
Extreme, but not moderate climate scenarios, impart sublethal effects on polyps of the Irukandji jellyfish, Carukia barnesi. Sci Total Environ. 2019 May 30;685:471-479 Authors: Boco SR, Pitt KA, Melvin SD Abstract Ocean acidification and warming, fueled by excess atmospheric carbon dioxide, can impose stress on marine organisms. Most studies testing the effects of climate change on marine organisms, however, use extreme climate projection scenarios, despite moderate projections scenarios being most likely to occur. Here, we examined the interactive effects of warming and acidification on reproduction, respiration, mobility and metabolic composition of polyps of the Irukandji jellyfish, Carukia barnesi, to determine the responses of a cubozoan jellyfish to moderate and extreme climate scenarios in Queensland, Australia. The experiment consisted two orthogonal factors: temperature (current 25 °C and future 28 °C) and pH (current (8.0) moderate (7.9) and extreme (7.7)). All polyps survived in the experiment but fewer polyps were produced in the pH 7.7 treatment compared to pH 7.9 and pH 8.0. Respiration rates were elevated in the lowest pH treatment throughout most of the experiment and polyps were approximately half as mobile in this treatment compared to pH 7.9 and pH 8.0, regardless of temperature. We identified metabolites occurring at significantly lower relative abundance in the lowest pH (i.e. glutamate, acetate, betaine, methylguanidine, lysine, sarcosine, glycine) and elevated temperature (i.e. proline, trigonelline, creatinine, mannose, acetate, betaine, methylguanidine, lysine, sarcosine) treatments. Glycine was the only metabolite exhibiting an interactive effect between pH and temperature. Our results suggest that C. barnesi polyps are unaffected by the most optimistic climate scenario and may tolerate even extreme climate conditions to some extent. PMID: 31176232 [PubMed - as supplied by publisher]

Comparing the disrupting effects of short-, medium- and long-chain chlorinated Paraffins on cell viability and metabolism.

Sun, 09/06/2019 - 15:23
Comparing the disrupting effects of short-, medium- and long-chain chlorinated Paraffins on cell viability and metabolism. Sci Total Environ. 2019 May 30;685:297-307 Authors: Ren X, Geng N, Zhang H, Wang F, Gong Y, Song X, Luo Y, Zhang B, Chen J Abstract With the phasing out of short-chain chlorinated paraffins (SCCPs), the production and emissions of medium- and long-chain chlorinated paraffins (MCCPs and LCCPs) are expected to increase. In this study, cell viability assay and pseudotargeted metabolomics approach were adopted to define and compare the toxic effects induced by SCCPs, MCCPs and LCCPs. The dose response curves indicated that three CP mixtures with comparable chlorine contents produced similar inhibitory effects on cell viability. At exposure concentration of 100 μg/L, three CP mixtures all induced significant increases in levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and a significant reduction in level of adenosine triphosphate production (ATP), and produced similar impact intensities on overall metabolism. A stronger perturbation in phospholipid and fatty acid metabolism was observed in all CP exposure groups. In comparison with SCCPs and MCCPs, LCCPs produced a stronger suppressive effect on amino acid transport across cell membrane and induced an opposite effect on purine metabolism. Furthermore, the toxicity mechanism and possible health risks of the three types of CPs were discussed. MCCPs shared the most similar cytotoxicity and metabolic perturbation with SCCPs, suggesting that there should be concern about using MCCPs as alternatives to SCCPs. PMID: 31176216 [PubMed - as supplied by publisher]

Lactulose: patient- and dose-dependent prebiotic properties in humans.

Sun, 09/06/2019 - 15:23
Lactulose: patient- and dose-dependent prebiotic properties in humans. Anaerobe. 2019 Jun 05;: Authors: Jakub R, Jacek M W Abstract Lactulose is a disaccharide used in clinical practice since 1957 and has since been tested in the treatment of many human disorders, including chronic constipation, hepatic encephalopathy, and chronic kidney disease. Its mode of action is based on the lactulose fermentation by intestinal microbiota. Based on in silico, in vitro and in vivo studies we comprehensively review here the impact of lactulose on human gut/fecal and vaginal microbiota composition and both fecal and blood metabolomes. However, both in vitro and in vivo studies summarized in this review have revealed that the effects of lactulose on human microbiota composition are both patient- and dose-dependent. This highlights the need of heterogeneity indication in clinical trials. PMID: 31176002 [PubMed - as supplied by publisher]

Whole-genome sequence of Arthrinium phaeospermum, a globally distributed pathogenic fungus.

Sun, 09/06/2019 - 15:23
Whole-genome sequence of Arthrinium phaeospermum, a globally distributed pathogenic fungus. Genomics. 2019 Jun 05;: Authors: Li S, Tang Y, Fang X, Qiao T, Han S, Zhu T Abstract Arthrinium phaeospermum (Corda) M.B. Ellis is a globally distributed pathogenic fungus with a wide host range; its hosts include not only plants, but also humans and animals. This study aimed to develop genomic resources for A. phaeospermum to provide solid data and a theoretical basis for further studies of its pathogenesis, transcriptomics, proteomics, metabolomics and RNA genomics. The genome was obtained from the mycelia of the strain AP-Z13 using a combination of analyses with the high-throughput Illumina HiSeq 4000 system and PacBio RSII LongRead sequencing platform. Functional annotation was performed by BLASTing protein sequences against those in different publicly available databases to obtain their corresponding annotations. The genome is 48.45 Mb in size, with an N90 scaffold size of 1,931,147 bp, and encodes 19,836 putative predicted genes. This is the first report of the genome-scale assembly and annotation for A. phaeospermum, the first species in the genus Arthrinium to be subjected to whole genome sequencing. PMID: 31175977 [PubMed - as supplied by publisher]

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