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

Characterization of global metabolic profile of Rhodiola crenulata after oral administration in rat plasma, urine, bile and feces based on UHPLC-FT-ICR MS.

Thu, 09/08/2018 - 14:51
Related Articles Characterization of global metabolic profile of Rhodiola crenulata after oral administration in rat plasma, urine, bile and feces based on UHPLC-FT-ICR MS. J Pharm Biomed Anal. 2018 Feb 05;149:318-328 Authors: Li Y, Zhao Y, Li X, Liu T, Jiang X, Han F Abstract Rhodiola crenulata has been widely used as a health food, antifatigue and antidepressant in China and many other countries for centuries. However, to date the metabolism of it in vivo still remains unclear. In this study, UHPLC-FT-ICR MS was used to analyze the major components and their metabolites in rats after oral administration of Rhodiola crenulata for the first time. A total of 179 constituents, including 37 prototype compounds and 142 metabolites (89 phase I metabolites and 53 phase II metabolites) were tentatively identified. The metabolic pathways included hydroxylation, deglycosylation, dehydrogenation, glucuronidation and sulphate conjugation. In summary, this study showed an insight into the metabolism of Rhodiola crenulata in vivo, which may provide helpful chemical information for better understanding the multiple functions of it. And also, the developed method could be used as a reliable strategy to study the metabolic profile for other traditional chinese medicines. PMID: 29132111 [PubMed - indexed for MEDLINE]

Key Role for the 12-Hydroxy Group in the Negative Ion Fragmentation of Unconjugated C24 Bile Acids.

Thu, 09/08/2018 - 14:51
Related Articles Key Role for the 12-Hydroxy Group in the Negative Ion Fragmentation of Unconjugated C24 Bile Acids. Anal Chem. 2016 07 19;88(14):7041-8 Authors: Lan K, Su M, Xie G, Ferslew BC, Brouwer KL, Rajani C, Liu C, Jia W Abstract Host-gut microbial interactions contribute to human health and disease states and an important manifestation resulting from this cometabolism is a vast diversity of bile acids (BAs). There is increasing interest in using BAs as biomarkers to assess the health status of individuals and, therefore, an increased need for their accurate separation and identification. In this study, the negative ion fragmentation behaviors of C24 BAs were investigated by UPLC-ESI-QTOF-MS. The step-by-step fragmentation analysis revealed a distinct fragmentation mechanism for the unconjugated BAs containing a 12-hydroxyl group. The unconjugated BAs lacking 12-hydroxylation fragmented via dehydration and dehydrogenation. In contrast, the 12-hydroxylated ones, such as deoxycholic acid (DCA) and cholic acid (CA), employed dissociation routes including dehydration, loss of carbon monoxide or carbon dioxide, and dehydrogenation. All fragmentations of the 12-hydroxylated unconjugated BAs, characterized by means of stable isotope labeled standards, were associated with the rotation of the carboxylate side chain and the subsequent rearrangements accompanied by proton transfer between 12-hydroxyl and 24-carboxyl groups. Compared to DCA, CA underwent further cleavages of the steroid skeleton. Accordingly, the effects of stereochemistry on the fragmentation pattern of CA were investigated using its stereoisomers. Based on the knowledge gained from the fragmentation analysis, a novel BA, 3β,7β,12α-trihydroxy-5β-cholanic acid, was identified in the postprandial urine samples of patients with nonalcoholic steatohepatitis. The analyses used in this study may contribute to a better understanding of the chemical diversity of BAs and the molecular basis of human liver diseases that involve BA synthesis, transport, and metabolism. PMID: 27322813 [PubMed - indexed for MEDLINE]

metabolomics; +16 new citations

Wed, 08/08/2018 - 14:33
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 2018/08/08PubMed 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; +18 new citations

Tue, 07/08/2018 - 14:06
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 2018/08/07PubMed 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.

Global omics strategies to investigate the effect of cyclodextrin nanoparticles on MCF-7 breast cancer cells.

Sun, 05/08/2018 - 13:09
Global omics strategies to investigate the effect of cyclodextrin nanoparticles on MCF-7 breast cancer cells. Eur J Pharm Sci. 2018 Aug 01;: Authors: Ercan A, Çelebier M, Varan G, Öncül S, Nenni M, Kaplan O, Bilensoy E Abstract Cyclodextrins (CD) are natural macrocyclic oligosaccharides linked by α(1,4) glycosidic bonds. Hydrophobic cavity of CDs are able to incorporate small molecules, ions, macromolecules which makes them excellent delegates for forming nanoparticulate carriers upon chemical modification to render amphiphilicity to CDs. In this study, blank 6OCaproβCD nanoparticle was prepared and administered to MCF-7 breast cancer cells. The effects of these nanoparticles on the cells were investigated in depth through biochemical and proteomic tests following 48 h of incubation. Proteomics studies revealed that apoptosis-related protein levels of hnRNP and CBX1 were increased while HDGF was not affected supporting the idea that 6OCaproβCD nanoparticles prevent cell proliferation. Gene expression studies were generally in correlation with protein levels since gene expression was significantly stimulated while protein levels were lower compared to the control group suggesting that a post-transcriptional modification must have occurred. Furthermore, 6OCaproβCD was observed to not trigger multidrug resistance as proved with RT-PCR that effectuates another exquisite characteristic of 6OCaproβCD nanoparticle as carrier of chemotherapeutic drugs. Metabolomic pathways of CD effect on MCF7 cells were elucidated with HMDB as serine biosynthesis, transmembrane transport of small molecules, metabolism of steroid hormones, estrogen biosynthesis and phospholipid biosynthesis. In conclusion, 6OCaproβCD is a promising nanoparticulate carrier for chemotherapeutic drugs with intrinsic apoptotic effect to be employed in treatment of breast cancer and further studies should be conducted in order to comprehend the exact mechanism of action. PMID: 30076952 [PubMed - as supplied by publisher]

Metabolomics studies on corticosterone-induced PC12 cells: A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism.

Sun, 05/08/2018 - 13:09
Metabolomics studies on corticosterone-induced PC12 cells: A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism. Neurotoxicol Teratol. 2018 Aug 01;: Authors: Tian JS, Liu SB, He XY, Xiang H, Chen JL, Gao Y, Zhou YZ, Qin XM Abstract There are three types of differentiated (un-, poorly- and well-differentiated) PC12 cells, which have been widely used as a model system for depression studies after the administration of corticosterone (CORT). In order to investigate the underlying metabolic profiles of CORT-induced PC12 cells and evaluate the suitable differentiated types of PC12 cells for use in depressive studies, proton nuclear magnetic resonance (1H NMR) metabolomics coupled with network analysis approaches were employed. The results showed that CORT induced metabolic alterations in PC12 cells. There were 8 and 13 common differential metabolites in intracellular and extracellular extracts, respectively, of the three types of differentiated PC12 cells in response to CORT treatment, and the perturbed metabolic pathways were involved in amino acid metabolism, glutathione metabolism, pyruvate metabolism and inositol phosphate metabolism. Eighteen protein targets of depression were identified from the five different metabolic pathways from metabolomics and network analysis among the three types of CORT-induced differentiated PC12 cells, and these proteins were all found in the pathways that were perturbed by CORT treatment of poorly-differentiated PC12 cells. These results may indicate that the metabolism of CORT-induced PC12 cells is similar to the pathogenesis of depression, and poorly-differentiated PC12 cells are the most suitable cells for depressive research among the distinct types of differentiated PC12 cells. Thus, an effective predicative strategy to evaluate the in vitro disease models could be referenced. PMID: 30076895 [PubMed - as supplied by publisher]

Increased Levels of Branched-chain Amino Acid Associated With Increased Risk of Pancreatic Cancer in a Prospective Case-Control Study of a Large Cohort.

Sun, 05/08/2018 - 13:09
Increased Levels of Branched-chain Amino Acid Associated With Increased Risk of Pancreatic Cancer in a Prospective Case-Control Study of a Large Cohort. Gastroenterology. 2018 Aug 01;: Authors: Katagiri R, Goto A, Nakagawa T, Nishiumi S, Kobayashi T, Hidaka A, Budhathoki S, Yamaji T, Sawada N, Shimazu T, Inoue M, Iwasaki M, Yoshida M, Tsugane S Abstract BACKGROUND & AIMS: A marker is needed to identify individuals at risk for pancreatic cancer. Increases in branched-chain amino acids (BCAAs) have been associated with pancreatic cancer. We performed a prospective case-control study to study the association between plasma levels of BCAAs and risk of pancreatic cancer in a large cohort. METHODS: We conducted a nested case-control study selected from 30,239 eligible participants, 40-69 years old within the Japan public health center-based prospective study. Over 16.4 years, 170 newly diagnosed pancreatic cancer cases were identified. Each case was matched to 2 controls by age, sex, geographic area, and fasting time at blood collection. The adjusted odds ratios (ORs) and 95% CIs for pancreatic cancer were calculated using conditional logistic regression models with adjustment for potential confounding factors. RESULTS: Increased plasma BCAA levels at baseline were associated with an increased risk of pancreatic cancer. Compared with the lowest quartile of BCAA levels, the OR in the highest quartile was 2.43 (95% CI, 1.21-4.90), and the OR per 1 standard deviation increase in BCAA levels was 1.32 (95% CI, 1.05-1.67). The association was especially strong among cases with blood samples collected 10 years or more before cancer diagnosis (OR per SD, 1.60; 95% CI, 1.10-2.32) compared to those detected less than 10 years before diagnosis (OR per SD, 1.16; 95% CI, 0.86-1.57). CONCLUSIONS: In an analysis of data from the Japan public health center-based prospective study, we found an association between increased plasma level of BCAA and an increased risk of pancreatic cancer-particularly when the increase in BCAAs was observed 10 years or more before diagnosis. These findings add to the growing body of evidence for the association between BCAA levels and pancreatic cancer risk. PMID: 30076838 [PubMed - as supplied by publisher]

Metabolomics in patients with psychosis: A systematic review.

Sun, 05/08/2018 - 13:09
Metabolomics in patients with psychosis: A systematic review. Am J Med Genet B Neuropsychiatr Genet. 2018 Aug 04;: Authors: Li C, Wang A, Wang C, Ramamurthy J, Zhang E, Guadagno E, Trakadis Y Abstract The purpose of this article is to provide a comprehensive review of metabolomics studies for psychosis, as a means of biomarker discovery. Manuscripts were selected for review if they involved discovery of metabolites using high-throughput analysis in human subjects and were published in the last decade. The metabolites identified were searched in Human Metabolome Data Base (HMDB) for a link to psychosis. Metabolites associated with psychosis based on evidence in HMBD were then searched using PubMed to explore the availability of further evidence. Almost all of the studies which underwent full review involved patients with schizophrenia. Ten biomarkers were identified. Six of them were reported in two or more independent metabolomics studies: N-acetyl aspartate, lactate, tryptophan, kynurenine, glutamate, and creatine. Four additional metabolites were encountered in a single metabolomics study but had significant evidence (two supporting articles or more) for a link to psychosis based on PubMed: linoleic acid, D-serine, glutathione, and 3-hydroxybutyrate. The pathways affected are discussed as they may be relevant to the pathophysiology of psychosis, and specifically of schizophrenia, as well as, constitute new drug targets for treatment of related conditions. Based on the biomarkers identified, early diagnosis of schizophrenia and/or monitoring may be possible. PMID: 30076730 [PubMed - as supplied by publisher]

Application of polyethyleneimine-modified attapulgite for the solid-phase extraction of chlorophenols at trace levels in environmental water samples.

Sun, 05/08/2018 - 13:09
Related Articles Application of polyethyleneimine-modified attapulgite for the solid-phase extraction of chlorophenols at trace levels in environmental water samples. Anal Bioanal Chem. 2018 Aug 04;: Authors: Chai M, Chen Y, Xuan R, Ma J, Jin Z, Wang T, Qiu D, Zhang L, Zhang Y Abstract A polyethyleneimine (PEI)-modified attapulgite was employed as a new adsorbent for solid-phase extraction (SPE) of chlorophenols (CPs) from environmental water samples. Key factors pivotal to extraction efficiency, such as organic additive, pH, salt, sample loading volume, elution volume, and sample loading flow rate, were investigated. The maximum adsorption capacity of CPs reached 38 mg/g, and the adsorption behavior could be described with the Langmuir isotherm model. The developed SPE procedure was then tested on river water samples. Of this cartridge, 0.4 g could be used to treat up to 100 mL of the water sample, with high recoveries achieved. The limit of detection (S/N = 3) and the limit of quantification (S/N = 10) were in range of 0.08-0.56 and 0.27-1.88 ng/mL, respectively. The mean recoveries of CPs spiked in river water samples ranged from 84.4 to 96.8% with relative standard deviations for the intra-day and inter-day less than 6.30%. The developed SPE method exhibited high sensitivity, high selectivity, excellent accuracy, and good repeatability to the analysis of trace CPs in complicated aqueous matrices. Graphical abstract Graphical abstract contains poor quality and small text inside the artwork. Please do not re-use the file that we have rejected or attempt to increase its resolution and re-save. It is originally poor, therefore, increasing the resolution will not solve the quality problem. We suggest that you provide us the original format. We prefer replacement figures containing vector/editable objects rather than embedded images. Preferred file formats are eps, ai, tiff and pdf.The separated figures were attached, which named Graphical abstract. ᅟ. PMID: 30076461 [PubMed - as supplied by publisher]

Effects of low-levels of three hexabromocyclododecane diastereomers on the metabolic profiles of pak choi leaves using high-throughput untargeted metabolomics approach.

Sun, 05/08/2018 - 13:09
Related Articles Effects of low-levels of three hexabromocyclododecane diastereomers on the metabolic profiles of pak choi leaves using high-throughput untargeted metabolomics approach. Environ Pollut. 2018 Jul 28;: Authors: Zhang Y, Guo Q, Tan D, He Z, Wang Y, Liu X Abstract The ecological toxicity of hexabromocyclododecane (HBCD) on animals, including fish and mice, has been reported, but its effects in plants, particularly its toxic mechanism, have rarely been investigated. An untargeted metabolomics approach for comprehensive assessment was selected to study the alterations in the metabolic profiles in pak choi leaves induced by exposure to trace-level amounts of HBCD diastereomers over 30 days. A supervised orthogonal partial least-squares-discriminant analysis (OPLS-DA) was performed to investigate differences between the HBCD and control groups. The discriminating metabolites were identified using public databases. The results indicated that the toxicity of the HBCD diastereomers was ordered as γ-HBCD > α-HBCD > β-HBCD. 13 metabolites were identified as potential biomarkers to discriminate the presence of HBCD toxicity. The lipid, carbohydrate, nucleotide and amino acid metabolic pathways affected were found in accordance with animals and humans, and also HBCD could induce the interference of the secondary metabolite pathways. The system of the stress defences was activated, including signalling pathway, antioxidant defence system, shikimate and phenylpropanoid metabolism. The carbohydrate and amino acid metabolism were disturbed by HBCD intervention, and the lipid, amino acid and secondary metabolite metabolism were regulated for HBCD stress prevention. These results provide insights into the mechanism and degree of HBCD phytotoxicity. PMID: 30076056 [PubMed - as supplied by publisher]

Metabolite profiling of plasma in patients with ossification of the posterior longitudinal ligament.

Sun, 05/08/2018 - 13:09
Related Articles Metabolite profiling of plasma in patients with ossification of the posterior longitudinal ligament. J Orthop Sci. 2018 Jul 31;: Authors: Tsuji T, Matsumoto M, Nakamura M, Miyamoto T, Yagi M, Fujita N, Okada E, Nagoshi N, Tsuji O, Watanabe K Abstract BACKGROUND: Metabolomics is one of the "omics" technologies, and is a comprehensive analysis of small molecule metabolites which include amino acid, nucleotides, carbohydrates and fatty acid. The purpose of the present study was to compare the differences of metabolite profiling between patients with ossification of the posterior longitudinal ligament (OPLL) and control subjects. METHODS: We analyzed plasma metabolites in patients with cervical OPLL (n = 10) and in control subjects (n = 10). Ionic metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) and lipophilic metabolites were analyzed using liquid chromatograph time-of-flight mass spectrometry (LC-TOFMS). RESULTS: A total of 259 metabolites (144 metabolites in CE-TOFMS and 115 metabolites in LC-TOFMS) were detected. Among the 259 metabolites, six metabolites, namely acylcarnitine (AC) (14:0), palmitoylcarnitine, AC (18:2), fatty acid (FA) (24:2), thyroxine, thiaproline were significantly larger in OPLL group, even in analyzes excluding patients with diabetes mellitus and hyperlipidemia. CONCLUSIONS: We examined the metabolite profiling in patients with OPLL for the first time and detected six metabolites showing suggestive association with disease. These results of the present study could lead to new insights into clarifying the molecular pathomechanisms of OPLL. PMID: 30075996 [PubMed - as supplied by publisher]

Serum metabolomic profiling predicts synovial gene expression in rheumatoid arthritis.

Sun, 05/08/2018 - 13:09
Related Articles Serum metabolomic profiling predicts synovial gene expression in rheumatoid arthritis. Arthritis Res Ther. 2018 Aug 03;20(1):164 Authors: Narasimhan R, Coras R, Rosenthal SB, Sweeney SR, Lodi A, Tiziani S, Boyle D, Kavanaugh A, Guma M Abstract BACKGROUND: Metabolomics is an emerging field of biomedical research that may offer a better understanding of the mechanisms of underlying conditions including inflammatory arthritis. Perturbations caused by inflamed synovial tissue can lead to correlated changes in concentrations of certain metabolites in the synovium and thereby function as potential biomarkers in blood. Here, we explore the hypothesis of whether characterization of patients' metabolomic profiles in blood, utilizing 1H-nuclear magnetic resonance (NMR), predicts synovial marker profiling in rheumatoid arthritis (RA). METHODS: Nineteen active, seropositive patients with RA, on concomitant methotrexate, were studied. One of the involved joints was a knee or a wrist appropriate for arthroscopy. A Bruker Avance 700 MHz spectrometer was used to acquire NMR spectra of serum samples. Gene expression in synovial tissue obtained by arthroscopy was analyzed by real-time PCR. Data processing and statistical analysis were performed in Python and SPSS. RESULTS: Analysis of the relationships between each synovial marker-metabolite pair using linear regression and controlling for age and gender revealed significant clustering within the data. We observed an association of serine/glycine/phenylalanine metabolism and aminoacyl-tRNA biosynthesis with lymphoid cell gene signature. Alanine/aspartate/glutamate metabolism and choline-derived metabolites correlated with TNF-α synovial expression. Circulating ketone bodies were associated with gene expression of synovial metalloproteinases. Discriminant analysis identified serum metabolites that classified patients according to their synovial marker levels. CONCLUSION: The relationship between serum metabolite profiles and synovial biomarker profiling suggests that NMR may be a promising tool for predicting specific pathogenic pathways in the inflamed synovium of patients with RA. PMID: 30075744 [PubMed - in process]

Simultaneous determination of ten nonsteroidal anti-inflammatory drugs from drinking water, surface water and wastewater using micro UHPLC-MS/MS with on-line SPE system.

Sat, 04/08/2018 - 12:43
Simultaneous determination of ten nonsteroidal anti-inflammatory drugs from drinking water, surface water and wastewater using micro UHPLC-MS/MS with on-line SPE system. J Pharm Biomed Anal. 2018 Jul 18;160:99-108 Authors: Márta Z, Bobály B, Fekete J, Magda B, Imre T, Szabó PT Abstract A simple, accurate and sensitive micro UHPLC-MS/MS method was developed and validated for the simultaneous determination of 10 nonsteroidal anti-inflammatory drugs (NSAIDs) from different environmental matrices. The micro LC ‒ on-line SPE method described in this study allowed to determine the selected drugs at ultra-trace levels without the most commonly used complex off-line SPE sample preparation procedures. The presented method is capable of reaching satisfactory low LOQ values with analysing the sample directly after being diluted with water. In order to attain high sensitivity, mass spectrometry was carefully optimized for the analysis of the drugs. Fenoprofen, flurbiprofen and naproxen were found to produce CO2 loss during ionization, forming intense [M-H-CO2]- ions instead of [M-H]-. All the other compounds were analyzed through their [M+H]+ and [M-H]- ions. Effect of mobile phase pH on ionization was also studied. Lower pH resulted in higher ion intensities. For this reason, a reversed phase chromatographic separation was applied at pH 3.1 with formic acid at concentration of 0.01%. Matrix effects have been evaluated during validation and sample dilution was optimized focusing on the lowest achievable LOQ values. Analytes were determined from drinking water directly, from surface water and wastewater following dilution with purified water by 2 : 8 (v/v) and 1 : 9 (v/v), respectively. Finally, the method was applied to real sample analysis. PMID: 30075399 [PubMed - as supplied by publisher]

A rapid classification and identification method applied to analysis of glycosides in Bupleuri radix and Liquorice by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Sat, 04/08/2018 - 12:43
A rapid classification and identification method applied to analysis of glycosides in Bupleuri radix and Liquorice by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. J Sep Sci. 2018 Aug 03;: Authors: Shan L, Yang N, Zhao Y, Sheng X, Yang S, Li Y Abstract Bupleuri radix and liquorice are commonly used as a hepatoprotectants. Their main effective ingredients are triterpenoid saponins. It is known that the saponins in liquorice and Bupleuri radix not only promote the metabolism of sugar and lipids but also have anti-inflammatory functions and hepatoprotective effect. However, the complexity of these compounds results in difficulty in studying their pharmacodynamics and mechanism. In this study, glycosides were the main components identified and were selected as the main research object. First, the mass spectrometry information of the main chemical components in liquorice and Bupleuri radix were collected from the literature. The characteristic fragments and neutral losses were summarized according to typical cleavage methods. Second, the samples were analysed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology, and characteristic fragment filters and neutral loss filters were successfully applied to screen 18 saponins from BR and 23 saponins and 9 flavonoid glycosides from liquorice. Rapid classification and identification of the main components in Bupleuri radix and liquorice were finally achieved. This method promoted the development of chemical components in Bupleuri radix and liquorice, and provided a new way for screening, classifying and identifying target components in complex samples of metabolomics and pharmacokinetics. This article is protected by copyright. All rights reserved. PMID: 30074686 [PubMed - as supplied by publisher]

Solid-phase extraction of drugs with cuttlebone powder as a sorbent.

Sat, 04/08/2018 - 12:43
Solid-phase extraction of drugs with cuttlebone powder as a sorbent. J Sep Sci. 2018 Aug 03;: Authors: Khazri H, Ghorbel-Abid I, Debrauwer L, Kalfat R, Trabelsi-Ayadi M Abstract We investigated cuttlefish bone powder for the solid-phase extraction of naproxen, ibuprofen and carbamazepine. The basic principles controlling the extraction are presented to aid in the choice of the nature and quantity of the extracting phase according to the sample matrix and the solute properties, based on the mechanisms of phase retention. Their retention mechanism is based on hydrogen bonding and electrostatic interactions. The results show a significant recovery rate for the three drugs, selectivity and low cost. The method has successfully reduced the amount of tested pharmaceuticals with recoveries higher than 87% at pH 4. This article is protected by copyright. All rights reserved. PMID: 30074301 [PubMed - as supplied by publisher]

Plasma profiling of amino acids distinguishes acute gout from asymptomatic hyperuricemia.

Sat, 04/08/2018 - 12:43
Related Articles Plasma profiling of amino acids distinguishes acute gout from asymptomatic hyperuricemia. Amino Acids. 2018 Aug 02;: Authors: Luo Y, Wang L, Liu XY, Chen X, Song YX, Li XH, Jiang C, Peng A, Liu JY Abstract Gout and hyperuricemia are highly prevalent metabolic diseases caused by high level of uric acid. Amino acids (AAs) involve in various biochemical processes including the biosynthesis of uric acid. However, the role of AAs in discriminating gout from hyperuricemia remains unknown. Here, we report that the plasma AAs profile can distinguish acute gout (AG) from asymptomatic hyperuricemia (AHU). We established an LC-MS/MS-based method to measure the plasma AAs without derivatization for the AG and AHU patients, and healthy controls. We found that the plasma profiling of AAs separated the AG patients from AHU patients and controls visually in both principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) models. In addition, L-isoleucine, L-lysine, and L-alanine were suggested as the key mediators to distinguish the AG patients from AHU and control groups based on the S-plot analysis and variable importance in the projection values in the OPLS-DA models, volcano plot, and the receiver operating characteristic curves. In addition, the saturation of monosodium urate in the AA solutions at physiologically mimic status supported the changes in plasma AAs facilitating the precipitation of monosodium urate. This study suggests that L-isoleucine, L-lysine, and L-alanine could be the potential markers to distinguish the AG from AHU when the patients have similar blood levels of uric acid, providing new strategies for the prevention, treatment, and management of acute gout. PMID: 30073607 [PubMed - as supplied by publisher]

Serum Metabonomics Analysis of Liver Failure Treated by Nonbioartificial Liver Support Systems.

Sat, 04/08/2018 - 12:43
Related Articles Serum Metabonomics Analysis of Liver Failure Treated by Nonbioartificial Liver Support Systems. Can J Gastroenterol Hepatol. 2018;2018:2586052 Authors: Wu C, Zhu Y, Yu M Abstract Objective: To analyze the small molecular metabolic compounds of nonbioartificial liver for treatment of hepatic failure and make further efforts to study the clinical efficacy, mechanism of action, and pathogenesis of hepatic failure. Methods: 52 patients who met the standard of artificial liver treatment for liver failure were enrolled; these patients included 6 cases of acute liver failure (11.54%), 3 cases of subacute liver failure (5.77%), acute-on-chronic liver failure in 10 cases (19.23%), and 33 cases of chronic liver failure (63.46%). Treatment modes included plasma exchange in 34 patients (65.38%), bilirubin adsorption in 9 patients (17.31%), and hemofiltration in 9 patients (17.31%). The clinical efficacy of artificial liver was assessed by monitoring the effects in the near future. Significant changes in metabolic compounds of liver failure in the treatment before and after artificial liver were screened by using Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). Related metabolic pathways were analyzed by MetaboAnalyst. Results: After artificial liver treatment, the liver function and coagulation function of liver failure patients were significantly improved (P < 0.01), the Meld score was lower than that before treatment, and the difference was statistically significant (P < 0.05). Serum metabolomics identified 29 small metabolic compounds and 12 metabolic pathways with variable projection importance (VIP) greater than 1 before and after artificial liver treatment. There were 11 metabolic compounds of VIP over 1 and 7 metabolic pathways in the different modes of artificial liver treatment for chronic liver failure. Among them, bile acid metabolism, fatty acid metabolism, and amino acid metabolism are the main sources. Conclusion: Artificial liver treatment can effectively improve liver function and blood coagulation function and Meld score, clinical symptoms and signs in patients with liver failure; the curative effect of artificial liver was verified, which reflected the clinical value of artificial liver in the treatment of liver failure. Artificial liver treatment of liver failure on fatty acids and primary bile acid synthesis pathway was the most significant. The difference of fatty acid, primary bile acid synthesis pathway, and phenylalanine metabolic pathway in different artificial liver patterns of chronic liver failure was the most significant. This provides a new basis for understanding the mechanism of hepatic failure and the mechanism of liver failure by artificial liver treatment. PMID: 30073154 [PubMed - in process]

Metabolomics Responses of Pearl Oysters (Pinctada fucata martensii) Fed a Formulated Diet Indoors and Cultured With Natural Diet Outdoors.

Sat, 04/08/2018 - 12:43
Related Articles Metabolomics Responses of Pearl Oysters (Pinctada fucata martensii) Fed a Formulated Diet Indoors and Cultured With Natural Diet Outdoors. Front Physiol. 2018;9:944 Authors: Yang C, Hao R, Du X, Deng Y, Sun R, Wang Q Abstract Natural disasters and environmental pollution are the main problems in traditional offshore cultivation. While culturing pearl oysters through industrial farming can avoid these problems, food availability in this case is limited. This study compares the metabolomics responses of pearl oysters, Pinctada fucata martensii, fed a formulated diet indoors with those of oysters cultured with natural diet outdoors by using a gas chromatography time-of-flight mass spectrometry (GC-TOF/MS)-based metabolomics approach. The animals were divided into two groups as follows: the experimental group (EG) was fed a formulated diet indoors and the control group (CG) was cultured with natural diet outdoors. After 45 days of feeding, the survival rate of EG was significantly higher than that of CG. The absolute growth rate (AGR) of the total weight of EG did not significantly differ from that of CG, but the AGRs of the shell length, shell height, and shell width of CG were significantly higher than those of EG. EG showed significantly higher amylase activities than CG, and the hexokinase and glucose-6-phosphate isomerase concentrations of the former were significantly lower than those of the latter. Metabolomics revealed 125 metabolites via mass spectrum matching with a spectral similarity value > 700 in the hepatopancreas, and 48 metabolites were considered to be significantly different between groups (VIP > 1 and P < 0.05). Pathway analysis results indicated that these significantly different metabolites were involved in 34 pathways. Further integrated key metabolic pathway analysis showed that, compared with CG, EG had lower capabilities for cysteine and methionine metabolism, sulfur metabolism, and starch and sucrose metabolism. This study demonstrated that the formulated diet could be an excellent substitute for natural diet; however, its nutrients were insufficient. Effective strategies should be developed to enhance the utilization of formulated diets. PMID: 30072917 [PubMed]

Effects of Different Pollens on Primary Metabolism and Lignin Biosynthesis in Pear.

Sat, 04/08/2018 - 12:43
Related Articles Effects of Different Pollens on Primary Metabolism and Lignin Biosynthesis in Pear. Int J Mol Sci. 2018 Aug 02;19(8): Authors: Li S, Su X, Abdullah M, Sun Y, Li G, Cheng X, Lin Y, Cai Y, Jin Q Abstract To investigate the effect of pollination on the fruit quality of 'Dangshan Su' pear, 'Dangshan Su' was fertilized by the pollen of 'Wonhwang' (Pyrus pyrifolia Nakai.) (DW) and 'Jingbaili' (Pyrus ussuriensis Maxim.) (DJ). The analysis of primary metabolites was achieved through untargeted metabolomics, and the quantitative analysis of intermediate metabolites of lignin synthesis was undertaken using targeted metabolomics. The untargeted metabolomics analysis was performed via gas chromatography-mass spectrometry (GC-MS). The targeted metabolomics analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) under the multiple reaction monitoring (MRM) mode. The results showed that the metabolite content was significantly different between DW and DJ. Compared with that in DJ, the sugar and amino acid content in DW was higher and the fatty acid content was lower at 47 days after pollination (DAPs), and the sugar, amino acid, and fatty acid content in DW was lower at 63 DAPs. The intermediate metabolites of lignin synthesis were analyzed using the orthogonal partial least squares discriminant analysis (OPLS-DA) model, and the differential metabolites at 47 DAPs were p-coumaric acid, ferulic acid, sinapaldehyde, coniferyl alcohol, and sinapyl alcohol. The differential significant metabolite at 63 DAPs was p-coumaric acid. At 47 DAPs and 63 DAPs, the p-coumaric acid level was significantly different, and the p-coumaric acid content was positively correlated with lignin synthesis. The pollination pollen affects the quality of 'Dangshan Su' pear fruit through regulation of the sugar, amino acid, and fatty acid content; at the same time, regulating the levels of intermediate metabolites of lignin synthesis, especially the p-coumaric acid content, to affect lignin synthesis ultimately affects the stone cell content and improves the quality of the pears. PMID: 30072670 [PubMed - in process]

Metabolic oscillations on the circadian time scale in Drosophila cells lacking clock genes.

Sat, 04/08/2018 - 12:43
Related Articles Metabolic oscillations on the circadian time scale in Drosophila cells lacking clock genes. Mol Syst Biol. 2018 Aug 02;14(8):e8376 Authors: Rey G, Milev NB, Valekunja UK, Ch R, Ray S, Silva Dos Santos M, Nagy AD, Antrobus R, MacRae JI, Reddy AB Abstract Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 h. Current models propose that transcriptional feedback loops are the primary mechanism for the generation of circadian oscillations. Within this framework, Drosophila S2 cells are regarded as "non-rhythmic" cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery that Drosophila S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products, and in particular metabolic enzymes, are rhythmically expressed in a 24-h cycle. Metabolomics analyses extended these findings and demonstrate that central carbon metabolism and amino acid metabolism are core metabolic pathways driven by protein rhythms. We thus demonstrate that 24-h metabolic oscillations, coupled to gene and protein cycles, take place in nucleated cells without the contribution of any known circadian regulators. These results therefore suggest a reconsideration of existing models of the clockwork in Drosophila and other eukaryotic systems. PMID: 30072421 [PubMed - in process]

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