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

Fine-tuning of SIRT1 expression is essential to protect the liver from cholestatic liver disease.

Thu, 20/09/2018 - 13:16
Fine-tuning of SIRT1 expression is essential to protect the liver from cholestatic liver disease. Hepatology. 2018 Sep 19;: Authors: Blokker BA, Maijo M, Echeandia M, Galduroz M, Patterson AM, Ten A, Philo M, Schungel R, Gutierrez-de Juan V, Halilbasic E, Fuchs C, Le Gall G, Milkiewicz M, Milkiewicz P, Banales JM, Rushbrook SM, Mato JM, Trauner M, Müller M, Martínez-Chantar ML, Varela-Rey M, Beraza N Abstract Cholestasis comprises aetiologically heterogeneous conditions characterized by accumulation of bile acids in the liver that actively contribute to liver damage. Sirtuin 1 (SIRT1) regulates liver regeneration and bile acid metabolism via modulating the farnesoid X receptor (FXR); we here investigate its role in cholestatic liver disease. We determined SIRT1 expression in livers from patients with cholestatic disease, in two experimental models of cholestasis, as well as in human and murine liver cells in response to bile acid loading. SIRT1 overexpressing (SIRToe ) and hepatocyte-specific SIRT1-KO mice (SIRThep-/- ) were subjected to BDL and were fed with 0.1%DDC diet to determine the biological relevance of SIRT1 during cholestasis. The effect of NorUDCA was tested in BDL/SIRToe mice. We found that SIRT1 was highly expressed in livers from cholestatic patients, mice after BDL and Mdr2-/- animals. The detrimental effects of SIRT1 during cholestasis were validated in vivo and in vitro. SIRToe mice showed exacerbated parenchymal injury whereas SIRThep-/- mice evidenced a moderate improvement after BDL and 0.1%DDC feeding. Likewise, hepatocytes isolated from SIRToe mice showed increased apoptosis in response to bile acids, while a significant reduction was observed in SIRThep-/- hepatocytes. Importantly, the decrease, but not complete inhibition of SIRT1 exerted by NorUDCA treatment correlated with pronounced improvement in liver parenchyma in BDL/SIRToe mice. Interestingly, both SIRT1 overexpression and hepatocyte-specific SIRT1 depletion correlated with inhibition of the farnesoid X receptor (FXR), whereas modulation of SIRT1 by NorUDCA associated with restored FXR-signalling. CONCLUSION: SIRT1 expression is increased during human and murine cholestasis. Fine-tuning expression of SIRT1 is essential to protect the liver from cholestatic-liver damage. This article is protected by copyright. All rights reserved. PMID: 30229970 [PubMed - as supplied by publisher]

1H NMR metabolomics identifies underlying inflammatory pathology in osteoarthritis and rheumatoid arthritis synovial joints.

Thu, 20/09/2018 - 13:16
1H NMR metabolomics identifies underlying inflammatory pathology in osteoarthritis and rheumatoid arthritis synovial joints. J Proteome Res. 2018 Sep 19;: Authors: Anderson JR, Chokesuwattanaskul S, Phelan MM, Welting TJ, Lian LY, Peffers MJ, Wright HL Abstract Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age-related, their underlying aetiologies are markedly different. We used 1H Nuclear Magnetic Resonance (NMR) spectroscopy to identify differences in metabolite profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from knee joints of 10 OA and 14 RA patients. 100µL SF was analysed using a 700 MHz Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analysed by Chenomx, Bruker TopSpin and AMIX software. Statistical analysis was undertaken using Metaboanalyst®. 50 metabolites were annotated, including amino acids, saccharides, nucleotides and soluble lipids. Discriminant analysis identified group separation between OA and RA cohorts, with 32 metabolites significantly different between OA and RA SF (False Discovery Rate (FDR)<0.05). Metabolites of glycolysis and the tricarboxylic acid cycle were lower in RA compared to OA; these results concur with higher levels of inflammation, synovial proliferation and hypoxia found in RA compared to OA. Elevated taurine in OA may indicate increased subchondral bone sclerosis. We demonstrate that quantifiable differences in metabolite abundance can be measured in low volumes of SF by 1H NMR spectroscopy, which may be clinically useful to aid diagnosis and improve understanding of disease pathogenesis. PMID: 30229649 [PubMed - as supplied by publisher]

A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation.

Thu, 20/09/2018 - 13:16
Related Articles A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation. Int J Legal Med. 2018 Sep 18;: Authors: Rousseau G, Chao de la Barca JM, Rougé-Maillart C, Teresiński G, Jousset N, Dieu X, Chabrun F, Prunier-Mirabeau D, Simard G, Reynier P, Palmiere C Abstract INTRODUCTION: Hypothermia is a potentially lethal condition whose postmortem diagnosis is often complex to perform due to the absence of pathognomonic lesions and biomarkers. Our first study of human serum and urinary metabolome in hypothermia fatalities sought novel biomarkers with better diagnostic performances than those already existing. MATERIAL AND METHOD: Thirty-two cases of hypothermia deaths and 16 cases excluding known antemortem exposure to cold or postmortem elements suggesting hypothermia were selected. A targeted metabolomic study allowing the detection and quantitation of 188 metabolites was performed on collected serum and urine using direct flow injection (FIA) and liquid chromatography (LC) separation, both coupled to tandem mass spectrometry (MS/MS). Amino acid quantification was also carried on using an in-house LC-MS/MS method in order to replicate the results obtained with the metabolomic study. RESULTS: A discriminant metabolic signature allowing a clear separation between hypothermia and control groups was obtained in the serum. This signature was characterized by increased arginase activity and fatty acid unsaturation along with decreased levels of tryptophan in hypothermia fatalities compared to controls. By contrast, no discriminant metabolic signature separating hypothermia from control fatalities was found in urines. DISCUSSION: The serum metabolic signature of hypothermia fatalities herein observed pointed toward metabolic adaptations that likely aimed at heat production enhancement, endothelial function, and cell membrane fluidity preservation. Novel biomarkers potentially useful in a hypothermia diagnosis were also identified. PMID: 30229331 [PubMed - as supplied by publisher]

TumGrowth: An open-access web tool for the statistical analysis of tumor growth curves.

Thu, 20/09/2018 - 13:16
Related Articles TumGrowth: An open-access web tool for the statistical analysis of tumor growth curves. Oncoimmunology. 2018;7(9):e1462431 Authors: Enot DP, Vacchelli E, Jacquelot N, Zitvogel L, Kroemer G Abstract The analysis of tumor growth curves is standard practice in experimental oncology including tumor immunology. In experimental oncology, cancer cells are inoculated into rodents (mostly mice) and their growth is monitored by measuring tumor diameter, surface or volume over time as a function of distinct treatments. Then, different groups of tumors/treatments are compared among each other for their evolution and possible responses to treatment. The R package TumGrowth has been created as a software tool allowing to carry out a series of statistical comparisons across or between groups of tumor growth curves obtained in a standard laboratory, for experimenters with limited knowledge in statistics. TumGrowth is freely available online at https://kroemerlab.shinyapps.io/TumGrowth/ and can be downloaded into any computer. It offers an exhaustive panoply of tools to visualize and analyze complex data sets including longitudinal, cross-sectional and time-to-endpoint measurements. PMID: 30228932 [PubMed]

Development of a novel UHPLC-MS/MS-based platform to quantify amines, amino acids and methylarginines for applications in human disease phenotyping.

Thu, 20/09/2018 - 13:16
Related Articles Development of a novel UHPLC-MS/MS-based platform to quantify amines, amino acids and methylarginines for applications in human disease phenotyping. Sci Rep. 2018 Sep 18;8(1):13987 Authors: Ahmetaj-Shala B, Olanipekun M, Tesfai A, MacCallum N, Kirkby NS, Quinlan GJ, Shih CC, Kawai R, Mumby S, Paul-Clark M, Want EJ, Mitchell JA Abstract Amine quantification is an important strategy in patient stratification and personalised medicine. This is because amines, including amino acids and methylarginines impact on many homeostatic processes. One important pathway regulated by amine levels is nitric oxide synthase (NOS). NOS is regulated by levels of (i) the substrate, arginine, (ii) amino acids which cycle with arginine and (iii) methylarginine inhibitors of NOS. However, biomarker research in this area is hindered by the lack of a unified analytical platform. Thus, the development of a common metabolomics platform, where a wide range of amino acids and methylarginines can be measured constitutes an important unmet need. Here we report a novel high-throughput ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) platform where ≈40 amine analytes, including arginine and methylarginines can be detected and quantified on a molar basis, in a single sample of human plasma. To validate the platform and to generate biomarkers, human plasma from a well-defined cohort of patients before and after coronary artery bypass surgery, who developed systemic inflammatory response syndrome (SIRS), were analysed. Bypass surgery with SIRS significantly altered 26 amine analytes, including arginine and ADMA. Consequently, pathway analysis revealed significant changes in a range of pathways including those associated with NOS. PMID: 30228360 [PubMed - in process]

Pan-cancer transcriptional signatures predictive of oncogenic mutations reveal that Fbw7 regulates cancer cell oxidative metabolism.

Thu, 20/09/2018 - 13:16
Related Articles Pan-cancer transcriptional signatures predictive of oncogenic mutations reveal that Fbw7 regulates cancer cell oxidative metabolism. Proc Natl Acad Sci U S A. 2018 05 22;115(21):5462-5467 Authors: Davis RJ, Gönen M, Margineantu DH, Handeli S, Swanger J, Hoellerbauer P, Paddison PJ, Gu H, Raftery D, Grim JE, Hockenbery DM, Margolin AA, Clurman BE Abstract The Fbw7 (F-box/WD repeat-containing protein 7) ubiquitin ligase targets multiple oncoproteins for degradation and is commonly mutated in cancers. Like other pleiotropic tumor suppressors, Fbw7's complex biology has impeded our understanding of how Fbw7 mutations promote tumorigenesis and hindered the development of targeted therapies. To address these needs, we employed a transfer learning approach to derive gene-expression signatures from The Cancer Gene Atlas datasets that predict Fbw7 mutational status across tumor types and identified the pathways enriched within these signatures. Genes involved in mitochondrial function were highly enriched in pan-cancer signatures that predict Fbw7 mutations. Studies in isogenic colorectal cancer cell lines that differed in Fbw7 mutational status confirmed that Fbw7 mutations increase mitochondrial gene expression. Surprisingly, Fbw7 mutations shifted cellular metabolism toward oxidative phosphorylation and caused context-specific metabolic vulnerabilities. Our approach revealed unexpected metabolic reprogramming and possible therapeutic targets in Fbw7-mutant cancers and provides a framework to study other complex, oncogenic mutations. PMID: 29735700 [PubMed - indexed for MEDLINE]

Urinary Metabolomic Profiling in Chronic Hepatitis B Viral Infection Using Gas Chromatography/Mass Spectrometry

Thu, 20/09/2018 - 13:16
Related Articles Urinary Metabolomic Profiling in Chronic Hepatitis B Viral Infection Using Gas Chromatography/Mass Spectrometry Asian Pac J Cancer Prev. 2018 Mar 27;19(3):741-748 Authors: Dittharot K, Jittorntam P, Wilairat P, Sobhonslidsuk A Abstract Background: Chronic hepatitis B (CHB) can lead to cirrhosis and hepatocellular carcinoma. The metabolomic profiling has been shown to be associated with pathogenic mechanisms in many medical conditions including CHB. The purpose of this study was to investigate the urine metabolomic profiles in CHB patients by gas chromatography/mass spectrometry (GC/MS). Methods: Urine samples were collected from CHB patients (n = 20) and normal control subjects (n = 20). Metabolite profiles were assessed using GC/MS in conjunction with multivariate statistical analysis, in order to identify biomarker metabolites. Pathway analysis was performed by MetaboAnalyst 3.0 and KEGG database.Results: Twelve out of 377 metabolites were shown to be significantly different between the CHB and normal control groups (p < 0.05). These include palmitic acid, stearic acid, oleic acid, benzoic acid, butanoic acid, cholesterol, glycine, 3-heptanone, 4-heptanone, hexanal, 1-tetradecanol and naphthalene. Multivariate statistical analysis constructed using these expressed metabolites showed CHB patients can be discriminated from healthy controls with high sensitivity (95%) and specificity (85%). All the metabolic perturbations in this disease are associated with pathways of fatty acid, amino acid, bile acid and gut microbial metabolism. Conclusion: CHB patients have a specific urinary metabolomic profile. The abnormalities of fatty acid, amino acid, bile acid, and gut microbial metabolism lead to the development of disease progression. GC/MS-based assay is a promising tool for the metabolomic study in CHB. PMID: 29582629 [PubMed - indexed for MEDLINE]

Glutathione S-transferase genes and the risk of type 2 diabetes mellitus: Role of sexual dimorphism, gene-gene and gene-smoking interactions in disease susceptibility.

Thu, 20/09/2018 - 13:16
Related Articles Glutathione S-transferase genes and the risk of type 2 diabetes mellitus: Role of sexual dimorphism, gene-gene and gene-smoking interactions in disease susceptibility. J Diabetes. 2018 May;10(5):398-407 Authors: Azarova I, Bushueva O, Konoplya A, Polonikov A Abstract BACKGROUND: Compromised defense against reactive oxygen species (ROS) is considered important in the pathogenesis of type 2 diabetes mellitus (T2DM); therefore, genes encoding antioxidant defense enzymes may contribute to disease susceptibility. This study investigated whether polymorphisms in genes encoding glutathione S-transferase M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) jointly contribute to the risk of T2DM. METHODS: In all, 1120 unrelated Russian subjects (600 T2DM patients, 520 age- and sex-matched healthy subjects), were recruited to the study. Genotyping was performed by multiplex polymerase chain reaction (PCR; del/del polymorphisms of GSTM1 and GSTT1) and TaqMan-based PCR (polymorphisms I105V and A114V of GSTP1). Plasma ROS and glutathione levels in study subjects were analyzed by fluorometric and colorimetric assays, respectively. RESULTS: Genotype del/del GSTT1 was significantly associated with the risk of T2DM (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.17-2.21, P = 0.003). Gender-stratified analysis showed that the deletion genotypes of GSTM1 (OR 1.99, 95% CI 1.30-3.05; P = 0.0002, Q = 0.016) and GSTT1 (OR 2.23, 95% CI 1.22-4.09; P = 0.008, Q = 0.0216), as well as genotype 114A/V of GSTP1 (OR 2.85, 95% CI 1.44-5.62; P = 0.005, Q = 0.02) were associated with an increased risk of T2DM exclusively in males. Three genotype combinations (i.e. GSTM1+ × GSTT1+, GSTM1+ × GSTP1 114A/A and GSTT1+ × GSTP1 114A/A) showed significant associations with a decreased risk of T2DM in males. CONCLUSIONS: This study demonstrates, for the first time, that genes encoding glutathione S-transferases jointly contribute to the risk of T2DM, and that their effects on disease susceptibility are gender specific. PMID: 29111615 [PubMed - indexed for MEDLINE]

metabolomics; +17 new citations

Wed, 19/09/2018 - 15:54
17 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 2018/09/19PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +17 new citations

Wed, 19/09/2018 - 12:47
17 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 2018/09/19PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +18 new citations

Tue, 18/09/2018 - 15:21
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 2018/09/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +18 new citations

Tue, 18/09/2018 - 12:20
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 2018/09/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

From 1H NMR-based non-targeted to LC-MS-based targeted metabolomics strategy for in-depth chemome comparisons among four Cistanche species.

Mon, 17/09/2018 - 12:07
From 1H NMR-based non-targeted to LC-MS-based targeted metabolomics strategy for in-depth chemome comparisons among four Cistanche species. J Pharm Biomed Anal. 2018 Sep 06;162:16-27 Authors: Liu W, Song Q, Cao Y, Xie N, Li Z, Jiang Y, Zheng J, Tu P, Song Y, Li J Abstract The great orthogonality between 1H NMR spectroscopy and LC-MS implies that their deployments in series could offer an opportunity to gain the qualified molecular markers via comparative metabolomics, and an attempt was made here to propose an integrated strategy namely "from 1H NMR-based non-targeted to LC-MS-based targeted metabolomics". In-depth chemome comparisons of Cistanche plants, such as C. deserticola, C. salsa, C. tubulosa, and C. sinensis, that possess dramatic economic and ecological benefits for the arid regions in the northwest China attributing to their dramatic medicinal and edible values, were employed to verify the applicability. 1H NMR-based non-targeted matabolomics acted as the survey experiment to find those signals offering decisive contributions towards the species discrimination, and the signals were translated to a set of putative identities, eighteen ones in total, through matching with authentic compounds and referring to some accessible databases. Afterwards, an advanced LC-MS platform assembling reversed phase liquid chromatography, hydrophilic interaction liquid chromatography, and tailored multiple reaction monitoring, was introduced to simultaneously quantify those eighteen potential markers in a single analytical run, because those candidates exhibited great polarity span as well as wide content range. Significant species differences occurred amongst their chemome patterns. Echinacoside, acteoside, betaine, mannitol, 6-deoxycatalpol, sucrose, and 8-epi-loganic acid were disclosed as the markers enabling the discrimination of those four species. The findings offered an alternative tool to differentiate Cistanche plants. More importantly, the strategy namely "from 1H NMR-based non-targeted to LC-MS-based targeted metabolomics" facilitates the pursuit of molecular markers among analogue plants, and thereby provides a promising choice for in-depth chemome comparison. PMID: 30219595 [PubMed - as supplied by publisher]

Metabolomics analysis of oral mucosa reveals profile perturbation in reticular oral lichen planus.

Sun, 16/09/2018 - 14:56
Related Articles Metabolomics analysis of oral mucosa reveals profile perturbation in reticular oral lichen planus. Clin Chim Acta. 2018 Sep 12;: Authors: Yang XY, Li XZ, Zhang SN Abstract BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory mucosal disorder and potentially oral premalignant lesion affecting the stratified squamous epithelia. In OLP, reticular type is the most common clinical form of the disease. However, little is known about it. Metabolomics analysis may help to investigate the disease pathogenesis and to improve clinical treatment. METHODS: Liquid chromatography (LC)-mass spectrometry (MS) system, XCMS software, SIMCA software, and OSI / SMMS software were integrated to identify differentially expressed metabolites for the pathways and pathology analysis. RESULTS: Totally, 21 modulated metabolites were identified, whose dysregulations affected 30 metabolic pathways. Through an impact-value screen (impact-value>0.1), 8 pathways were selected as the significantly dysregulated pathways. Pathological network showed that these metabolites participated in 5 pathological processes, that is, inflammatory lesion, DNA damage and repair disorder, apoptosis process, oxidative stress injury, and abnormal energy expenditure. CONCLUSION: The study revealed the metabolic perturbation of oral mucosa in reticular OLP, which may provide an important reference for the understanding of the pathogenesis of the disease and the discovery of therapeutic targets. PMID: 30218656 [PubMed - as supplied by publisher]

Intracellular Metabolic Changes of Rhodococcus sp. LH During the Biodegradation of Diesel Oil.

Sun, 16/09/2018 - 14:56
Related Articles Intracellular Metabolic Changes of Rhodococcus sp. LH During the Biodegradation of Diesel Oil. Mar Biotechnol (NY). 2018 Sep 14;: Authors: Chen Z, Zheng Z, Wang FL, Niu YP, Miao JL, Li H Abstract In recent years, some marine microbes have been used to degrade diesel oil. However, the exact mechanisms underlying the biodegradation are still poorly understood. In this study, a hypothermophilous marine strain, which can degrade diesel oil in cold seawater was isolated from Antarctic floe-ice and identified and named as Rhodococcus sp. LH. To clarify the biodegradation mechanisms, a gas chromatography-mass spectrometry (GC-MS)-based metabolomics strategy was performed to determine the diesel biodegradation process-associated intracellular biochemical changes in Rhodococcus sp. LH cells. With the aid of partial least squares-discriminant analysis (PLS-DA), 17 differential metabolites with variable importance in the projection (VIP) value greater than 1 were identified. Results indicated that the biodegradation of diesel oil by Rhodococcus sp. LH was affected by many different factors. Rhodococcus sp. LH could degrade diesel oil through terminal or sub-terminal oxidation reactions, and might also possess the ability to degrade aromatic hydrocarbons. In addition, some surfactants, especially fatty acids, which were secreted by Rhodococcus into medium could also assist the strain in dispersing and absorbing diesel oil. Lack of nitrogen in the seawater would lead to nitrogen starvation, thereby restraining the amino acid circulation in Rhodococcus sp. LH. Moreover, nitrogen starvation could also promote the conversation of relative excess carbon source to storage materials, such as 1-monolinoleoylglycerol. These results would provide a comprehensive understanding about the complex mechanisms of diesel oil biodegradation by Rhodococcus sp. LH at the systematic level. PMID: 30218327 [PubMed - as supplied by publisher]

Skeletal muscle metabolomics and blood biochemistry analysis reveal metabolic changes associated with dietary amino acid supplementation in dairy calves.

Sun, 16/09/2018 - 14:56
Related Articles Skeletal muscle metabolomics and blood biochemistry analysis reveal metabolic changes associated with dietary amino acid supplementation in dairy calves. Sci Rep. 2018 Sep 14;8(1):13850 Authors: Yu K, Matzapetakis M, Valent D, Saco Y, De Almeida AM, Terré M, Bassols A Abstract The effects of different amino acid (AA) supplementations of milk protein-based milk replacers in pre-ruminant calves from 3 days to 7 weeks of age were studied. Animals were divided into 4 groups: Ctrl) Control group fed with milk protein-based milk replacer without supplementation; GP) supplementation with 0.1% glycine and 0.3% proline; FY) supplementation with 0.2% phenylalanine and 0.2% tyrosine; MKT) supplementation with 0.62% lysine, 0.22% methionine and 0.61% threonine. For statistical analysis, t-test was used to compare AA-supplemented animals to the Ctrl group. At week 7, body weight and average daily gain (ADG) were measured and blood samples and skeletal muscle biopsies were taken. Blood biochemistry analytes related to energy metabolism were determined and it was shown that MKT group had higher serum creatinine and higher plasma concentration of three supplemented AAs as well as arginine compared with the Ctrl group. GP group had similar glycine/proline plasma concentration compared with the other groups while in FY group only plasma phenylalanine concentration was higher compared with Control. Although the AA supplementations in the GP and FY groups did not affect average daily gain and metabolic health profile from serum, the metabolome analysis from skeletal muscle biopsy revealed several differences between the GP-FY groups and the Ctrl-MKT groups, suggesting a metabolic adaptation especially in GP and FY groups. PMID: 30218007 [PubMed - in process]

Metabolic profiling of hypoxia/reoxygenation injury in H9c2 cells reveals the accumulation of phytosphingosine and the vital role of Dan-Shen in Xin-Ke-Shu.

Sun, 16/09/2018 - 14:56
Related Articles Metabolic profiling of hypoxia/reoxygenation injury in H9c2 cells reveals the accumulation of phytosphingosine and the vital role of Dan-Shen in Xin-Ke-Shu. Phytomedicine. 2018 Oct 01;49:83-94 Authors: Sun L, Jia H, Ma L, Yu M, Yang Y, Liu Y, Zhang H, Zou Z Abstract BACKGROUND: Xin-Ke-Shu (XKS), a patent medicine consisting of five commonly used traditional Chinese herbs, is used for the treatment of coronary heart diseases. A previous study showed that XKS has protective effects for ameliorating myocardial ischemia/reperfusion (I/R) injury. PURPOSE: This study was aimed to deeply understand the mechanisms and compatible principle of XKS against hypoxia/reoxygenation (H/R) injury and the contribution of each single herb to the efficacy of XKS. METHODS: An H/R model in H9c2 cardiomyocytes was applied to mimic I/R injury observed in vivo. The cell viability, the levels of LDH, MDA, SOD, and apoptosis were determined to evaluate the cardioprotection of XKS and its subtracted formula (knocked out one herb) in H/R injury. Cell metabolomics, combined with western blot analysis, was performed to uncover the inert molecular mechanism of XKS against H/R injury. RESULTS: Significant protective effects of XKS against oxidative stress and apoptosis induced by H/R injury were found in the pharmacodynamic evaluation. Moreover, the metabolic profile deviation of the H/R group from the control group was mainly ascribed to thirteen metabolites involved in four aberrant pathways, in which sphingolipid metabolism was revealed as the most relevant pathway involved in H/R injury (impact > 0.1). Notably, the accumulation of phytosphingosine (VIP = 5.84) was considered the most likely characteristic in H/R injury, which is well known to promote the opening of the mitochondrial permeability transition pore (mPTP) and activate cell apoptosis. Furthermore, XKS ameliorated all the abnormalities of the metabolic network in response to H/R injury. In agreement with this, a western blot analysis showed that XKS markedly regulated the over-expression of CaMK II and cleaved caspase-3. However, the subtracted formula showed no significant difference in comparison with the XKS group on protecting H/R injury except for QDS (subtracted Dan-Shen from XKS). CONCLUSION: The roots of Salvia miltiorrhiza Bge. (Dan-Shen) play an important role in the regulation of Ca2+ overloading, oxidative stress and apoptosis in H/R injury. Our study enabled information from holistic cell metabolomics to be used for mechanism and compatibility rule elucidations of TCMs. PMID: 30217265 [PubMed - in process]

metabolomics; +21 new citations

Sat, 15/09/2018 - 14:10
21 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 2018/09/15PubMed 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; +23 new citations

Fri, 14/09/2018 - 16:41
23 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 2018/09/14PubMed 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; +23 new citations

Fri, 14/09/2018 - 13:35
23 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 2018/09/14PubMed 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.

Pages