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

The 1H-NMR-based metabolite profile of acute alcohol consumption: A metabolomics intervention study.

Fri, 11/05/2018 - 15:00
The 1H-NMR-based metabolite profile of acute alcohol consumption: A metabolomics intervention study. PLoS One. 2018;13(5):e0196850 Authors: Irwin C, van Reenen M, Mason S, Mienie LJ, Wevers RA, Westerhuis JA, Reinecke CJ Abstract Metabolomics studies of disease conditions related to chronic alcohol consumption provide compelling evidence of several perturbed metabolic pathways underlying the pathophysiology of alcoholism. The objective of the present study was to utilize proton nuclear magnetic resonance (1H-NMR) spectroscopy metabolomics to study the holistic metabolic consequences of acute alcohol consumption in humans. The experimental design was a cross-over intervention study which included a number of substances to be consumed-alcohol, a nicotinamide adenine dinucleotide (NAD) supplement, and a benzoic acid-containing flavoured water vehicle. The experimental subjects-24 healthy, moderate-drinking young men-each provided six hourly-collected urine samples for analysis. Complete data sets were obtained from 20 of the subjects and used for data generation, analysis and interpretation. The results from the NMR approach produced complex spectral data, which could be resolved sufficiently through the application of a combination of univariate and multivariate methods of statistical analysis. The metabolite profiles resulting from acute alcohol consumption indicated that alcohol-induced NAD+ depletion, and the production of an excessive amount of reducing equivalents, greatly perturbed the hepatocyte redox homeostasis, resulting in essentially three major metabolic disturbances-up-regulated lactic acid metabolism, down-regulated purine catabolism and osmoregulation. Of these, the urinary excretion of the osmolyte sorbitol proved to be novel, and suggests hepatocyte swelling due to ethanol influx following acute alcohol consumption. Time-dependent metabolomics investigations, using designed interventions, provide a way of interpreting the variation induced by the different factors of a designed experiment, thereby also giving methodological significance to this study. The outcomes of this approach have the potential to significantly advance our understanding of the serious impact of the pathophysiological perturbations which arise from the consumption of a single, large dose of alcohol-a simulation of a widespread, and mostly naive, social practice. PMID: 29746531 [PubMed - in process]

Big Data Analytics in Medicine and Healthcare.

Fri, 11/05/2018 - 15:00
Big Data Analytics in Medicine and Healthcare. J Integr Bioinform. 2018 May 10;: Authors: Ristevski B, Chen M Abstract This paper surveys big data with highlighting the big data analytics in medicine and healthcare. Big data characteristics: value, volume, velocity, variety, veracity and variability are described. Big data analytics in medicine and healthcare covers integration and analysis of large amount of complex heterogeneous data such as various - omics data (genomics, epigenomics, transcriptomics, proteomics, metabolomics, interactomics, pharmacogenomics, diseasomics), biomedical data and electronic health records data. We underline the challenging issues about big data privacy and security. Regarding big data characteristics, some directions of using suitable and promising open-source distributed data processing software platform are given. PMID: 29746254 [PubMed - as supplied by publisher]

Molecular insights into the activity and mechanism of cyanide hydratase enzyme associated with cyanide biodegradation by Serratia marcescens.

Fri, 11/05/2018 - 15:00
Related Articles Molecular insights into the activity and mechanism of cyanide hydratase enzyme associated with cyanide biodegradation by Serratia marcescens. Arch Microbiol. 2018 May 09;: Authors: Kushwaha M, Kumar V, Mahajan R, Bhalla TC, Chatterjee S, Akhter Y Abstract The present study provides molecular insights into the activity and mechanism of cyanide hydratase enzyme associated with degradation of cyanide compounds, using Serratia marcescens RL2b as a model organism. Resting cells harvested after 20 h achieved complete degradation of 12 mmol l- 1 cyanide in approximately 10 h. High-performance liquid chromatography analysis of reaction samples revealed formation of formamide as the only end product, which confirmed the presence of cyanide hydratase activity in S. marcescens RL2b. Comparative structural analysis with the other nitrilase family proteins, which was carried out using a sequence of cyanide hydratase from a phylogenetically related strain S. marcescens WW4, also revealed subtle but significant differences in amino acid residues of the substrate-binding pocket and catalytic triad (Cys-Lys-Glu). PMID: 29744557 [PubMed - as supplied by publisher]

Comparative metabolomics and glycolysis enzyme profiling of embryogenic and nonembryogenic grape cells.

Fri, 11/05/2018 - 15:00
Related Articles Comparative metabolomics and glycolysis enzyme profiling of embryogenic and nonembryogenic grape cells. FEBS Open Bio. 2018 May;8(5):784-798 Authors: Parrilla J, Gaillard C, Verbeke J, Maucourt M, Aleksandrov RA, Thibault F, Fleurat-Lessard P, Gibon Y, Rolin D, Atanassova R Abstract A novel biological model was created for the comparison of grapevine embryogenic cells (EC) and nonembryogenic cells (NEC) sharing a common genetic background but distinct phenotypes, when cultured on their respective most appropriate media. Cytological characterization, 1H-NMR analysis of intracellular metabolites, and glycolytic enzyme activities provided evidence for the marked metabolic differences between EC and NEC. The EC were characterized by a moderate and organized cell proliferation, coupled with a low flux through glycolysis, high capacity of phosphoenolpyruvate carboxylase and glucokinase, and high oxygen consumption. The NEC displayed strong anarchic growth, and their high rate of glycolysis due to the low energetic efficiency of the fermentative metabolism is confirmed by increased enolase capacity and low oxygen consumption. PMID: 29744293 [PubMed]

Role of biobanks in transplantation.

Fri, 11/05/2018 - 15:00
Related Articles Role of biobanks in transplantation. Ann Med Surg (Lond). 2018 Apr;28:30-33 Authors: Hanif Z, Sufiyan N, Patel M, Akhtar MZ Abstract The establishment of bio-banks together with high throughput technologies, such as genomics, transcriptomics and proteomics has opened new frontiers in biomarker discovery and the development of systems biology approaches to identifying key pathways that could be exploited to improve outcomes of solid organ transplantation. One of the major challenges in organ donation has been the lack of access to large scale well characterised material to facilitate projects that aim to characterise injury to donor organs and identify biomarkers. This may have hampered research in the field of organ donation by not allowing researchers to materials of high quality and lower pre-analytical variability. We describe in this manuscript the need for bio-banks in organ donation, research opportunities and the particular challenges in establishing such an initiative. PMID: 29744049 [PubMed]

Pharmacokinetics of Chinese medicines: strategies and perspectives.

Fri, 11/05/2018 - 15:00
Related Articles Pharmacokinetics of Chinese medicines: strategies and perspectives. Chin Med. 2018;13:24 Authors: Yan R, Yang Y, Chen Y Abstract The modernization and internationalization of Chinese medicines (CMs) are hampered by increasing concerns on the safety and the efficacy. Pharmacokinetic (PK) study is indispensable to establish concentration-activity/toxicity relationship and facilitate target identification and new drug discovery from CMs. To cope with tremendous challenges rooted from chemical complexity of CMs, the classic PK strategies have evolved rapidly from PK study focusing on marker/main drug components to PK-PD correlation study adopting metabolomics approaches to characterize associations between disposition of global drug-related components and host metabolic network shifts. However, the majority of PK studies of CMs have adopted the approaches tailored for western medicines and focused on the systemic exposures of drug-related components, most of which were found to be too low to account for the holistic benefits of CMs. With an area under concentration-time curve- or activity-weighted approach, integral PK attempts to understand the PK-PD relevance with the integrated PK profile of multiple co-existing structural analogs (prototyes/metabolites). Cellular PK-PD complements traditional PK-PD when drug targets localize inside the cells, instead of at the surface of cell membrane or extracellular space. Considering the validated clinical benefits of CMs, reverse pharmacology-based reverse PK strategy was proposed to facilitate target identification and new drug discovery. Recently, gut microbiota have demonstrated multifaceted roles in drug efficacy/toxicity. In traditional oral intake, the presystemic interactions of CMs with gut microbiota seem inevitable, which can contribute to the holistic benefits of CMs through biotransforming CMs components, acting as the peripheral target, and regulating host drug disposition. Hence, we propose a global PK-PD approach which includes the presystemic interaction of CMs with gut microbiota and combines omics with physiologically based pharmacokinetic modeling to offer a comprehensive understanding of the PK-PD relationship of CMs. Moreover, validated clinical benefits of CMs and poor translational potential of animal PK data urge more research efforts in human PK study. PMID: 29743935 [PubMed]

Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro, high resolution NMR (nuclear magnetic resonance) spectroscopy based analysis.

Fri, 11/05/2018 - 15:00
Related Articles Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro, high resolution NMR (nuclear magnetic resonance) spectroscopy based analysis. EXCLI J. 2018;17:257-272 Authors: Srivastava NK, Sharma S, Sharma R, Sinha N, Mandal SK, Sharma D Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA. PMID: 29743863 [PubMed]

NMR-Based Plasma Metabolomics at Set Intervals in Newborn Dairy Calves with Severe Sepsis.

Fri, 11/05/2018 - 15:00
Related Articles NMR-Based Plasma Metabolomics at Set Intervals in Newborn Dairy Calves with Severe Sepsis. Mediators Inflamm. 2018;2018:8016510 Authors: Basoglu A, Sen I, Meoni G, Tenori L, Naseri A Abstract The aim of this first study was to reveal the new potential biomarkers by a metabolomics approach in severe septic calves. Sepsis is a common cause of morbidity and mortality in newborn dairy calves. The main challenges with the use of biomarkers of sepsis in domestic animals are their availability, cost, and time required to obtain a result. Metabolomics may offer the potential to identify biomarkers that define calf sepsis in terms of combined clinical, physiological, and pathobiological abnormalities. To our knowledge, this is the first study presenting an NMR- (nuclear magnetic resonance-) based plasma metabolomics at set intervals in neonatal septic calves. Twenty neonatal dairy calves with severe sepsis and ten healthy calves were used. Hematological and biochemical health profiles were gathered in plasma samples at set intervals. Similarly, NMR spectra were acquired. All diseased animals (except one) died after 72 hours. Clinical and laboratory results were in accordance with those of severe septic animals. Multivariate analysis on NMR plasma spectra proved to be an excellent tool for faster identification of calves with severe sepsis from healthy animals. The NMR-based metabolomic profile may contribute to the better understanding of severe sepsis in newborn calves. PMID: 29743812 [PubMed - in process]

Untargeted metabolomic on urine samples after α-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women.

Fri, 11/05/2018 - 15:00
Related Articles Untargeted metabolomic on urine samples after α-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women. Lipids Health Dis. 2018 May 09;17(1):103 Authors: Romo-Hualde A, Huerta AE, González-Navarro CJ, Ramos-López O, Moreno-Aliaga MJ, Martínez JA Abstract BACKGROUND: Eicosapentaenoic acid (EPA) and α-lipoic acid (α-LA) have been investigated for their beneficial effects on obesity and cardiovascular risk factors. In the current research, the goal was to evaluate metabolomic changes following the dietary supplementation of these two lipids, alone or combined in healthy overweight/obese sedentary women following an energy-restricted diet. For this purpose, an untargeted metabolomics approach was conducted on urine samples using liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOF-MS). METHODS: This is a short-term double blind placebo-controlled study with a parallel nutritional design that lasted 10 weeks. Participants were assigned to one of the 4 experimental groups [Control, EPA (1.3 g/d), α-LA (0.3 g/d) and EPA+α-LA (1.3 g/d + 0.3 g/d)]. All intervention groups followed an energy-restricted diet of 30% less than total energy expenditure. Clinically relevant biochemical measurements were analyzed. Urine samples (24 h) were collected at baseline and after 10 weeks. Untargeted metabolomic analysis on urine samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification. RESULTS: Urine samples were scattered in the PCA scores plots in response to the supplementation with α-LA. Totally, 28 putative discriminant metabolites in positive ionization, and 6 in negative ionization were identified among groups clearly differentiated according to the α-LA administration. Remarkably is the presence of an ascorbate intermediate metabolite (one of the isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate) in the groups supplemented with α-LA. This fact might be associated with antioxidant properties of both α-LA and ascorbic acid. Correlations between phenotypical parameters and putative metabolites of provided additional information on whether there is a direct or inverse relationship between them. Especially interesting are the negative correlation between ascorbate intermediate metabolite and asymmetric dimethylarginine (ADMA) and the positive one between superoxide dismutase (SOD) and α-LA supplementation. CONCLUSIONS: This metabolomic approach supports that the beneficial effects of α-LA administration on body weight reduction may be partly explained by the antioxidant properties of this organosulfur carboxylic acid mediated by isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01138774 . PMID: 29743087 [PubMed - in process]

Barrett's oesophagus: Current controversies.

Fri, 11/05/2018 - 15:00
Related Articles Barrett's oesophagus: Current controversies. World J Gastroenterol. 2017 Jul 28;23(28):5051-5067 Authors: Amadi C, Gatenby P Abstract Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett's oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus. PMID: 28811703 [PubMed - indexed for MEDLINE]

Cardioprotective effects and mechanism of Radix Salviae miltiorrhizae and Lignum Dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury.

Fri, 11/05/2018 - 15:00
Related Articles Cardioprotective effects and mechanism of Radix Salviae miltiorrhizae and Lignum Dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury. Mol Med Rep. 2017 Aug;16(2):1759-1770 Authors: Mu F, Duan J, Bian H, Yin Y, Zhu Y, Wei G, Guan Y, Wang Y, Guo C, Wen A, Yang Y, Xi M Abstract Radix Salviae miltiorrhizae (SM) and Lignum Dalbergiae odoriferae (DO) are traditional Chinese medicinal herbs used to treat ischemic heart disease and other cardiovascular diseases; however, to the best of our knowledge, there are currently few studies regarding their effects. The present study aimed to investigate the cardioprotective effects of SM and DO during myocardial ischemia/reperfusion (MI/R) injury in rats, and explore the molecular mechanisms that underlie their actions. In the present study, Sprague‑Dawley rats were pretreated with SM, the aqueous extract of DO (DOA) and the volatile oil of DO (DOO), either as a monotherapy or in combination for 7 days. Subsequently, the rats were subjected to 30 min of ischemia followed by 180 min of reperfusion. Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time‑of‑flight mass spectrometry were used to identify the therapeutic effects of these traditional Chinese medicines. The results revealed that SM, DOA and DOO monotherapies ameliorated cardiac function, and this effect was strengthened further when used in combined therapies. Among the combined treatments, SM + DOO exhibited the greatest potential (P<0.05) to improve electrocardiogram results and heart rate, reduce the heart weight index and myocardial infarct size, and decrease the levels of creatine kinase‑MB and lactate dehydrogenase. In addition, metabonomics‑based findings, including the principal component analysis and partial least squares discriminant analysis score plot of the metabolic state in rat serum, provided confirmation for the aforementioned results, verifying that SM + DOO exerted synergistic therapeutic efficacies to exhibit a greater effect on rats with MI/R injury when compared with the other pretreatment groups. Furthermore, the most effective duration of SM + DOO treatment was 30 min and the least effective duration was 180 min. Treatment with SM + DOO also significantly (P<0.01) reduced the number of terminal deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling‑positive cells, tumor necrosis factor‑α andinterleukin‑6 expression, and malondialdehyde content, and increased the serum and tissue activity of superoxide dismutase. These results indicated that the combined effects of SM + DOO may be more effective compared with the single pretreatments against MI/R injury in rats. This effect may be achieved partly through anti‑apoptotic, antioxidant and anti‑inflammatory activities. Therefore, SM + DOO may be considered an effective and promising novel strategy for the prophylaxis and treatment of ischemic heart disease. PMID: 28656200 [PubMed - indexed for MEDLINE]

Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke.

Fri, 11/05/2018 - 15:00
Related Articles Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke. J Appl Physiol (1985). 2017 Sep 01;123(3):544-557 Authors: Audet GN, Dineen SM, Stewart DA, Plamper ML, Pathmasiri WW, McRitchie SL, Sumner SJ, Leon LR Abstract It has been suggested that medications can increase heat stroke (HS) susceptibility/severity. We investigated whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) increases HS severity in a rodent model. Core temperature (Tc) of male, C57BL/6J mice (n = 45) was monitored continuously, and mice were given a dose of INDO [low dose (LO) 1 mg/kg or high dose (HI) 5 mg/kg in flavored treat] or vehicle (flavored treat) before heating. HS animals were heated to 42.4°C and euthanized at three time points for histological, molecular, and metabolic analysis: onset of HS [maximal core temperature (Tc,Max)], 3 h of recovery [minimal core temperature or hypothermia depth (HYPO)], and 24 h of recovery (24 h). Nonheated (control) animals underwent identical treatment in the absence of heat. INDO (LO or HI) had no effect on physiological indicators of performance (e.g., time to Tc,Max, thermal area, or cooling time) during heating or recovery. HI INDO resulted in 45% mortality rate by 24 h (HI INDO + HS group). The gut showed dramatic increases in gross morphological hemorrhage in HI INDO + HS in both survivors and nonsurvivors. HI INDO + HS survivors had significantly lower red blood cell counts and hematocrit suggesting significant hemorrhage. In the liver, HS induced cell death at HYPO and increased inflammation at Tc,Max, HYPO, and 24 h; however, there was additional effect with INDO + HS group. Furthermore, the metabolic profile of the liver was disturbed by heat, but there was no additive effect of INDO + HS. This suggests that there is an increase in morbidity risk with INDO + HS, likely resulting from significant gut injury.NEW & NOTEWORTHY This paper suggests that in a translational mouse model, NSAIDs may be counterindicated in situations that put an individual at risk of heat injury. We show here that a small, single dose of the NSAID indomethacin before heat stroke has a dramatic and highly damaging effect on the gut, which ultimately leads to increased systemic morbidity. PMID: 28596269 [PubMed - indexed for MEDLINE]

[Plasma metabonomics of Guifu Dihuang Wan in the treatment of yang deficiency].

Fri, 11/05/2018 - 15:00
Related Articles [Plasma metabonomics of Guifu Dihuang Wan in the treatment of yang deficiency]. Nan Fang Yi Ke Da Xue Xue Bao. 2016 Nov 20;36(11):1489-1495 Authors: Xiao Y, Jing Y, Chen JY, Li F, Cheng JR, Bi JL, Luo R, Zhao XS Abstract OBJECTIVE: To assess the effect of Guifu Dihuang Wan (GFDHW) in the treatment of yang deficiency and explore the underlying molecular mechanism. METHODS: Sixty-two participants without diseases were randomized into control group (n=31) and experimental group (n=31) and were given lifestyle intervention additional GFDHW treatment for a month. NMR technology was used for metabonomics analysis. RESULTS: Intervention with GFDHW resulted in significantly decreased conversion scores of yang deficiency in the experimental group compared with the control group (P<0.005). The concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate were increased in the plasma of yang-deficient subjects after lifestyle intervention. GFDHW treatment with lifestyle intervention significantly increased the concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate and also the levels of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol. CONCLUSION: GFDHW treatment improves yang deficiency possibly by increasing the concentrations of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol and promoting energy metabolism of the body. PMID: 27881338 [PubMed - indexed for MEDLINE]

metabolomics; +18 new citations

Thu, 10/05/2018 - 14:42
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 2018/05/10PubMed 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.

Epoxide Value-A Novel Marker for the Quality Assessment of Food Lipids.

Wed, 09/05/2018 - 14:15
Related Articles Epoxide Value-A Novel Marker for the Quality Assessment of Food Lipids. J Agric Food Chem. 2018 May 08;: Authors: Grüneis V, Pignitter M PMID: 29738241 [PubMed - as supplied by publisher]

Lipidomics reveal Aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate(ANIT)-induced intrahepatic cholestasis.

Wed, 09/05/2018 - 14:15
Related Articles Lipidomics reveal Aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate(ANIT)-induced intrahepatic cholestasis. Xenobiotica. 2018 May 08;:1-33 Authors: Wang BL, Zhang CW, Wang L, Tang KL, Tanaka N, Gonzalez FJ, Xu Y, Fang ZZ Abstract 1. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was employ to elucidate new mechanism of alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. 2. Multiple lipid components significantly increased in ANIT-induced intrahepatic cholestasis, including PC 16:0, 20:4, PC 16:0, 22:6, PC 16:0, 18:2, LPC 18:2, PC 18:2, LPC 18:1, PC 18:1, 14:0, SM 18:1, 16:0, oleoylcarnitine, and palmitoylcarnitine. This alteration of lipid profile was induced by the changed expression of genes choline kinase (Chk) a, sphingomyelin phosphodiesterase (SMPD) and stearoyl-coenzyme A desaturase 1 (SCD1). 3. Knockout of Aryl hydrocarbon receptor (Ahr) in mice can significantly reverse alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis, as indicated by lowered ALT, AST and ALP activity, and liver histology. Aryl hydrocarbon receptor (Ahr) knockout significantly reversed alpha-naphthyl isothiocyanate (ANIT)-induced lipid metabolism alteration through regulating the expression of Chka. 4. In conclusion, this study demonstrated ANIT-induced lipid metabolism disruption might be the potential pathogenesis of ANIT-induced intrahepatic cholestasis in mice. PMID: 29737914 [PubMed - as supplied by publisher]

Metabolomics research on potential role for 9-cis-Retinoic acid in breast cancer progression.

Wed, 09/05/2018 - 14:15
Related Articles Metabolomics research on potential role for 9-cis-Retinoic acid in breast cancer progression. Cancer Sci. 2018 May 08;: Authors: Wu J, Yang R, Zhang L, Li Y, Liu B, Kang H, Fan Z, Tian Y, Liu S, Li T Abstract Deciphering the molecular networks that discriminate organ-confined breast cancer from metastatic breast cancer may lead to the identification of critical biomarkers for breast cancer invasion and aggressiveness. Here metabolomics, a global study of metabolites, has been applied to explore the metabolic alterations that characterize breast cancer progression. We profiled a total of 693 metabolites across 87 serum samples related to breast cancer (46 clinically localized and 41 metastatic breast cancer) and 49 normal samples. These unbiased metabolomic profiles were able to distinguish normal individuals, clinically localized and metastatic breast cancer patients. 9-cis-Retinoic acid, an isomer of all-trans retinoic acid, was identified as a differential metabolite that significantly decreased during breast cancer progression to metastasis, and its levels were also reduced in urine samples from biopsy positive breast cancer patients relative to biopsy negative individuals and in invasive breast cancer cells relative to benign MCF-10A cells. The addition of exogenous 9-cis-Retinoic acid to MDA-MB-231 cells and knock-down of aldehyde dehydrogenase 1 family member A1, an regulatory enzyme for 9-cis-Retinoic acid, remarkably impaired cell invasion and migration, presumably through preventing the key regulator cofilin from activation and inhibiting MMP2 and MMP9 expression. Taken together, our study revealed the potential inhibitory role for 9-cis-Retinoic acid in breast cancer progression by attenuating cell invasion and migration. This article is protected by copyright. All rights reserved. PMID: 29737597 [PubMed - as supplied by publisher]

metabolomics; +37 new citations

Tue, 08/05/2018 - 22:42
37 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 2018/05/08PubMed 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 and Isotope Tracing.

Mon, 07/05/2018 - 22:26
Related Articles Metabolomics and Isotope Tracing. Cell. 2018 May 03;173(4):822-837 Authors: Jang C, Chen L, Rabinowitz JD Abstract Great strides have been made over the past decade toward comprehensive study of metabolism. Mass spectrometry (MS) has played a central role by enabling measurement of many metabolites simultaneously. Tracking metabolite labeling from stable isotope tracers can in addition reveal pathway activities. Here, we describe the basics of metabolite measurement by MS, including sample preparation, metabolomic analysis, and data interpretation. In addition, drawing on examples of successful experiments, we highlight the ways in which metabolomics and isotope tracing can illuminate biology. PMID: 29727671 [PubMed - in process]

TD/GC-MS analysis of volatile markers emitted from mono- and co-cultures of Enterobacter cloacae and Pseudomonas aeruginosa in artificial sputum.

Mon, 07/05/2018 - 22:26
Related Articles TD/GC-MS analysis of volatile markers emitted from mono- and co-cultures of Enterobacter cloacae and Pseudomonas aeruginosa in artificial sputum. Metabolomics. 2018;14(5):66 Authors: Lawal O, Knobel H, Weda H, Nijsen TME, Goodacre R, Fowler SJ, BreathDx consortium Abstract Introduction: Infections such as ventilator-associated pneumonia (VAP) can be caused by one or more pathogens. Current methods for identifying these pathogenic microbes often require invasive sampling, and can be time consuming, due to the requirement for prolonged cultural enrichment along with selective and differential plating steps. This results in delays in diagnosis which in such critically ill patients can have potentially life-threatening consequences. Therefore, a non-invasive and timely diagnostic method is required. Detection of microbial volatile organic compounds (VOCs) in exhaled breath is proposed as an alternative method for identifying these pathogens and may distinguish between mono- and poly-microbial infections. Objectives: To investigate volatile metabolites that discriminate between bacterial mono- and co-cultures. Methods: VAP-associated pathogens Enterobacter cloacae and Pseudomonas aeruginosa were cultured individually and together in artificial sputum medium for 24 h and their headspace was analysed for potential discriminatory VOCs by thermal desorption gas chromatography-mass spectrometry. Results: Of the 70 VOCs putatively identified, 23 were found to significantly increase during bacterial culture (i.e. likely to be released during metabolism) and 13 decreased (i.e. likely consumed during metabolism). The other VOCs showed no transformation (similar concentrations observed as in the medium). Bacteria-specific VOCs including 2-methyl-1-propanol, 2-phenylethanol, and 3-methyl-1-butanol were observed in the headspace of axenic cultures of E. cloacae, and methyl 2-ethylhexanoate in the headspace of P. aeruginosa cultures which is novel to this investigation. Previously reported VOCs 1-undecene and pyrrole were also detected. The metabolites 2-methylbutyl acetate and methyl 2-methylbutyrate, which are reported to exhibit antimicrobial activity, were elevated in co-culture only. Conclusion: The observed VOCs were able to differentiate axenic and co-cultures. Validation of these markers in exhaled breath specimens could prove useful for timely pathogen identification and infection type diagnosis. PMID: 29725275 [PubMed]

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